Active Research

CeTIR at UTHealth Houston is actively engaged in research, clinical trials, and training programs to improve trauma care and drive innovation in the field. Below are the center’s ongoing research initiatives.

Led by CeTIR:

• A Video Conversation Aid to Improve Shared Decision-Making for Life-Sustaining Care after Injury in Older Adults

  A Video Conversation Aid to Improve Shared Decision-Making for Life-Sustaining Care after Injury in Older Adults
  PI – Thaddeus Puzio, MD
  UTHealth Houston Learning Healthcare Grant
  The proposed study will evaluate the effectiveness and acceptability of a video conversation aid to enhance communication between trauma care providers and patient surrogate decision makers. We hypothesize that this tool will increase the concordance between care received and patient preferences. The results of this study will provide preliminary data for a larger multicenter trial. Guided by an experienced and knowledgeable mentoring and advisory team, this project will allow me to gain skills and expertise in implementing evidence-based practices, using mixed-methods, and conducting patient-centered geriatric research.
  Aim 1: Perform baseline assessment of discussions utilized to establish goals for life-sustaining care in older adults admitted after injury Aim 2: Utilize a multidisciplinary team to create an educational code status primer video targeting injured older adults and their surrogates Aim 3: Determine the factors that influence intervention-related healthcare preferences and the effect of a video-based conversation aid

• An Assessment of Green Plasma: The Potential Hemostatic Superiority of a Currently Discarded Blood Product

  An Assessment of Green Plasma: The Potential Hemostatic Superiority of a Currently Discarded Blood Product
  PI – Bryan Cotton, MD
  Supporting Agency – TRC4 – Trauma Research & Combat Casualty Care Collaborative
  Our long-term goal is to determine whether green plasma should be actively re-introduced into the medical community for transfusion as a safe and functionally non-inferior (and potentially superior) product.
  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.

• Antithrombin to Improve Thromboprophylaxis and Reduce the Incidence of Trauma-Related Venous Thromboembolism (TRAIT) RCT

  Antithrombin to Improve Thromboprophylaxis and Reduce the Incidence of Trauma-Related Venous Thromboembolism (TRAIT) RCT
  PI – Bryan Cotton, MD
  Co-Investigator – Erin Fox, PhD; Charles Wade, PhD; David Meyer, MD
  Supporting Agency – Grifols Shared Services North American, Inc.
  NCT # – NCT05794165
  Thromboembolic complications are a serious threat to recovery in surviving trauma patients, affecting 2-20% of this population. Despite prophylactic treatment with enoxaparin, these rates of venous thromboembolism (VTE) have persisted and are associated with aggressive interventions, increased lengths of hospital and ICU stay, and recurrent thrombotic disease. The data from this trial could redefine VTE prophylaxis protocols for trauma patients and have a significant impact of the burden of VTE in this population. The overall goal of this project is to perform a multicenter, randomized trial to determine if early administration of antithrombin will improve responsiveness to low molecular weight heparin prophylaxis and reduce the incidence of venous thromboembolism in hospitalized and recovering trauma patients. Aim 1: Determine the efficacy of Thrombate administration for reducing the 14-day VTE incidence among severely injured trauma patients. Aim 2: Determine the efficacy of Thrombate administration for improving responsiveness to enoxaparin and reducing time to achieve a target anti-FXa among severely injured trauma patients. Aim 3: Assess the incidence of other thrombotic complications, bleeding events and evaluate lengths of hospital stay, antithrombin activity levels, endothelial markers and inflammatory markers between randomization arms.

• Assessment of the Relationship between Statins, Microvascular Dysregulation, and Venous Thromboembolism in Severely Injured Trauma Patients

  Assessment of the Relationship between Statins, Microvascular Dysregulation, and Venous Thromboembolism in Severely Injured Trauma Patients
  PI – Gabrielle Hatton, MD
  Supporting Agency – TRC4 – Trauma Research & Combat Casualty Care Collaborative
  This study will evaluate the role of stains in treating trauma/combat casualty-induced injuries, specifically related to hemorrhage and vascular dysfunction, with the ultimate goal of including them in a multimodal VTE chemoprophylaxis strategy.
  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.

• Freeze Dried Mechanotransduced MSC Derived Exosomes for Neurological Injury

  Freeze Dried Mechanotransduced MSC Derived Exosomes for Neurological Injury
  PI – Charles Cox, MD
  Supporting Agency – TRC4 – Trauma Research & Combat Casualty Care Collaborative
  We propose to manufacture and validate EVs derived from MSCs that have undergone shear stress mechanotransduction in a novel bioreactor to down regulate the inflammatory response to TBI. Further, these will be freeze-dried for use in rural and military environments.
  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.

• Hemodynamic Management Following Acute Traumatic Spinal Cord Injury: A Pilot Randomized, Controlled Trial

  Hemodynamic Management Following Acute Traumatic Spinal Cord Injury: A Pilot Randomized, Controlled Trial
  PI – David Meyer, MD
  Supporting Agency – TRC4 – Trauma Research & Combat Casualty Care Collaborative
  NCT # – NCT06451133
  We propose to perform a randomized, controlled trial comparing the effectiveness of goal-directed therapy targeting MAP ≥85 mmHg or SCPP ≥65 mmHg compared to usual care (MAP ≥65 mmHg) with strict avoidance of hypotension for the first 5 days following SCI. The primary outcome is degree of neurologic impairment at 12 months as measured by the American Spinal Injury Association (ASIA) motor score and the Spinal Cord Independence Measure (SCIM).
  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.

• Identifying SUR1/TRPM4 Polymorphisms to Reduce Contusion Expansion after Traumatic Brain Injury: Clinical Trial Planning Grant

  Identifying SUR1/TRPM4 Polymorphisms to Reduce Contusion Expansion after Traumatic Brain Injury: Clinical Trial Planning Grant
  PI – Charles Cox, MD
  Supporting Agency – TRC4 – Trauma Research & Combat Casualty Care Collaborative
  A critical mode of failure in clinical trials for TBI is related to heterogeneity of the population in terms of type of injury, and now we have insight into genetic variation that is impactful. To design an impactful clinical trial, both must be considered to be important. We propose using BOTH a contusion endophenotype AND developing the infrastructure for rapid SNP genotyping to allow determination of the population most likely to respond to SUR1/TRPM4 inhibition. Genetic determination of therapeutic responders for personalized TBI treatment is not currently available and would alter the treatment paradigm for TBI, preferentially benefiting populations with historically worse outcomes after trauma. The failure mode of the previous trials utilizing this strategy is due to a relatively small number of patients with the genetic variants most responsive to treatment. Identifying those SNPs will then allow a rapid determination strategy to allow personalized medicine approaches to treating severe TBI. Further, we will utilize advanced imaging to confirm the biologic activity of the treatment after TBI in reducing cerebral edema using quantitative DT-MRI.
  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.

• Impact of Health Literacy on Infections (Health LIT) Study

  Impact of Health Literacy on Infections (Health LIT) Study
  PI – Krislynn Mueck, MD
  Supporting Agency – Surgical Infection Society
  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.

• Long-term outcomes for the randomized, controlled trial of hemodynamic management following acute traumatic spinal cord injury

  Long-term outcomes for the randomized, controlled trial of hemodynamic management following acute traumatic spinal cord injury
  PI – David Meyer, MD
  Supporting Agency – Mission Connect
  The trial will compare the effectiveness of goal-directed therapy targeting MAP ?85 mmHg or SCPP ?65 mmHg to normal hemodynamics (MAP ?65 mmHg with strict avoidance of hypotension) for the first 5 days following SCI. The primary outcome is the degree of neurologic impairment at 6 weeks as measured by the American Spinal Injury Association (ASIA) International Standards for Neurological Classification of Spinal Cord Injury (ISNCSC) motor score and the Spinal Cord Independence Measure (SCIM) III. However, functional neurologic outcomes following acute traumatic SCI continue to evolve over the course of the first year, and outcome measurements prior to 12 months from injury may offer an incomplete picture of the potential benefit or harm of a particular treatment. To this end, we are seeking funding from Mission Connect to support the collection of functional outcomes (ASIA motor score and SCIM III) at 6- and 12-months following injury to be able to accurately assess the benefits and harms of each treatment strategy.
  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) at 6 weeks, 6 months, and 12 months following injury. Aim 2: Determine the effect of MAP or SCPP goal on non-neurologic adverse events following SCI at 6 weeks, 6 months, and 12 months following injury.

• Pediatric Prospective Observational Vascular Injury Trial (Pedi PROOVIT)

  Pediatric Prospective Observational Vascular Injury Trial (Pedi PROOVIT)
  PI – Natalie Drucker, MD
  Supporting Agency – TRC4 – Trauma Research & Combat Casualty Care Collaborative
  The objective of this proposal is to improve understanding of pediatric major vascular injuries by establishing a prospective pediatric multicenter vascular injury registry. We will then review the database to compare management and outcomes in pediatric major vascular injuries to provide evidence-based interventions to improve outcomes and standard of care for children with vascular injuries.
  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.

• Plasma Regulators of Fibrinolysis in Severely Injured Patients at Risk for VTE: A CLOTT-2 Study

  Plasma Regulators of Fibrinolysis in Severely Injured Patients at Risk for VTE: A CLOTT-2 Study
  PI – Charles Cox, MD
  Supporting Agency – Grifols
  The primary objective of our proposed study is to identify circulating regulatory proteins that suppress fibrinolysis in severely injured patients during their early Intensive Care Unit stay rendering them at risk for VTE. Specifically, we plan to assess regulators of fibrinolysis in the plasma samples of CLOTT-2 patients to determine potential therapeutic targets to mitigate tPA resistance and thereby reduce the risk for VTE in severely injured patients requiring SICU care. This study will set the stage for future prospective clinical investigations of therapeutic interventions aimed at reducing post-traumatic VTE by targeting the specific proteins identified in this pre-clinical study that are associated with fibrinolytic failure. In turn, this would be a completely novel approach to prevention of VTE events.

• Postdoctoral Training Program in Trauma and Hemorrhagic Shock

  Postdoctoral Training Program in Trauma and Hemorrhagic Shock
  PI – Charles Cox, MD
  Supporting Agency – National Institute of General Medical Sciences
  Ruth L. Kirschstein National Research Service Award (NSRA) Institutional Research Training Grant - 2T32GM008792
  The long-term objective of this trauma research training program is to provide multidisciplinary research training for post doctorates in trauma to develop future independent investigators who will use these skills in research-intensive and research-related careers that increase understanding of the mechanisms of traumatic injury and inform clinical practice. To accomplish these objectives, our program selects fellows each calendar year for 2-year positions within the structured program. The program recruits postdoctoral candidates who are interested in pursuing an academic career in trauma-related research. At the end of the 2 years of training, the goal is that each fellow is able to 1) critically analyze available published data; 2) formulate a focused hypothesis; 3) design and perform necessary experiments to test the hypothesis; 4) analyze and interpret results to draw appropriate conclusions and potentially modify experimental strategies; 5) effectively present the results of their research both orally and in writing; and 6) prepare a competitive research proposal. T32 Fellowship Program

• Prevention of Trauma-related Infections through an Embedded Clinical Trials (PROTECT) Network

  Prevention of Trauma-related Infections through an Embedded Clinical Trials (PROTECT) Network
  PI – Lillian Kao, MD
  Supporting Agency – Surgical Infection Society
  The proposed project will build the infrastructure for a national learning trauma care system optimally designed for continuous improvement and innovation focused on infection. The project will create reusable templates for research contracts and data use agreements for future trauma trials and build on existing participation in TQIP and the National Trauma Data Bank. The goal is to embed high-quality pragmatic clinical trials with routine trauma care.
  Aim 1: Compare the effectiveness of 2 prophylactic antibiotic regimens, ertapenem and cefazolin with metronidazole, in preventing OS-SSI after emergency trauma laparotomy within Aim 2: Validate a Bayesian OS-SSI risk calculator using TQIP standardized variables.

• Stem Cells for the Prevention of Inflammatory Complications of Severely Injured Trauma Patients - MATRICS-1

  Stem Cells for the Prevention of Inflammatory Complications of Severely Injured Trauma Patients - MATRICS-1
  PI – Charles Cox, MD
  Co-Investigators – Erin Fox, PhD; Laura Moore, MD; Charles Wade, PhD
  Supporting Agency –Medical Technology Enterprise Consortium (MTEC)
  NCT # – NCT04533464
  The objective of this trial is to evaluate the safety and efficacy of MultiStem for the treatment of severely injured trauma patients suffering hemorrhagic shock for the prevention and early treatment of inflammatory complications. This trial will improve knowledge and techniques to treat ischemia-reperfusion injury. The investigational intervention is feasible early after injury, potentially even in remote operating environment scenarios. If the MultiStem cells decrease the incidence of inflammatory complications, transport of treated casualties from remote locations will be logistically simpler and safer, and mortality of these patients would be expected to decrease.
  Aim 1: Compare the incidence, severity and duration of acute kidney injury (AKI) in multiply injured, post-hemorrhage patients administered MultiStem with patients administered placebo. Aim 2: Compare the incidence of inflammatory complications in multiply injured, post-hemorrhage patients administered MultiStem with patients administered placebo. Aim 3: Compare all-cause mortality at 30 days in multiply injured, post-hemorrhage patients administered MultiStem with patients administered placebo. Aim 4: Determine the inflammatory profiles associated with incidence of AKI, other inflammatory complications and mortality.

• The Impact of Rapid Infuser Use on Fibrinogen Levels, Fibrinogen Function, and Hemostatic Potential of Cryoprecipitate Products

  The Impact of Rapid Infuser Use on Fibrinogen Levels, Fibrinogen Function, and Hemostatic Potential of Cryoprecipitate Products
  PI – Bryan Cotton, MD
  Supporting Agency – Cerus Corporation
  The proposed research would examine the impact of various transfusion delivery methods, including rapid infusers, on the hemostatic potential and overall clotting factor activity of cryoprecipitate products. If we are able to demonstrate rapid infuser non-inferiority (and potential superiority) of hemostatic potential and capacity to maintain functional clotting factors of cryoprecipitate during a massive transfusion scenario, this would simplify the delivery of these products with other competing products being transfused (whole blood, RBCs, plasma). This would likely accelerate earlier delivery of cryoprecipitate products as they could be delivered through a rapid infuser and through a single access line.

• Trauma-induced coagulopathy and the blood-brain barrier: Impact of resuscitation

  Trauma-induced coagulopathy and the blood-brain barrier: Impact of resuscitation
  PI – Charles Cox, MD
  Co-Investigators – Erin Fox, PhD; Charles Wade, PhD; Brijesh Gill, MD
  Supporting Agency – Department of Defense
  Hemorrhagic shock (HS) amplifies and exacerbates bleeding and barrier dysfunction after traumatic brain injury (TBI). Endothelial failure, more broadly, failure of the neurovascular unit that comprises the blood-brain barrier (BBB), has severe physiological consequences. Further, trauma-induced fibrinolysis that develops in 25% of HS patients is linked to endotheliopathy through the release of coagulation enzymes and byproducts into systemic circulation (via crosstalk mechanisms) that can disrupt homeostasis in distant organs/vascular beds.
  We seek to understand these interactions with a multi-platform strategy using patient samples from trauma-induced fibrinolysis phenotypes (delayed clot initiation/polymerization; reduced clot strength; platelet dysfunction [PD]; hyperfibrinolysis) and unique in vitro assays: (1) a novel platelet contractility assay; (2) a neurovascular unit, circulating-microfluidic BBB model capable of measuring physiological pressures/flows; (3) an HS/TBI animal model; and (4) advanced magnetic resonance imaging (MRI) protocols of patients to quantitate cytotoxic and vasogenic edema. We further seek to identify transfusion practices that not only reverse fibrinolysis but also attenuate pathological mechanisms that subsequently promote hemorrhagic expansion and edema in the neurovasculature
  The following 4 projects comprise our Focused Program Award addressing Focus Area 2 (Prevent and Assess) and subarea 2a, "Identification and validation of biomarkers or other objective markers for diagnosis, prognosis, or monitoring of …TBI" and Focus Area 3 (Treat) and subarea 3a, "Interventions that promote sustained functional recovery, including interventions administered acutely, during the post-acute phase, or during the chronic phase of injury."
  Project 1: The goals are to define the role of fibrin(ogen) degradation products (FDPs) in mediating disruption of the BBB through their interaction with vascular and circulating blood cells and identify therapeutic targets for inhibiting FDP release and cellular interactions. We hypothesize that FDPs drive disruption of the BBB and that attenuation of FDP release and blocking of FDP-endothelial cell (EC) interactions will mitigate BBB disruption and cerebral edema following TBI+HS. The overall approach is to quantify FDPs in polytrauma patient plasma and correlate with clinical BBB metrics; identify novel EC receptors for FDPs; and determine the effects of inhibiting FDP release and blocking FDP-EC interactions on BBB disruption.
  Project 2: The goal is to define the mechanism by which HS and/or fibrinolysis exacerbate cerebral edema after severe TBI using our novel, high-throughput, physiologically relevant BBB model to test variables that can only be inferred in vivo or are impractical to test in a multimodal manner. We propose to determine the influence of increasing injury severity/complexity on BBB permeability; characterize the fibrinolytic phenotype that worsens TBI via the PAR1-MMP9-SUR1-TRPM4 signaling axis; and determine the contribution of upregulation and/or SUR1-TRPM4 channel activation mechanisms to HS amplification of BBB permeability. Our approach will allow us to optimize therapeutic approaches for TBI patients using data derived from the proposed experiments.
  Project 3: The goal is to define platelet dysfunction in the setting of TBI +/- HS. Four potential contributory mechanisms will be explored: activation, aggregation, and contraction phenotypes in each patient cohort; metabolic crisis and/or RNA degradation as etiology of dysfunction; and impact of FDPs on platelet dysfunction. Understanding platelet dysfunction in the setting of TBI +/- HS +/- hyperfibrinolysis will provide insight into resuscitation strategies, potential druggable targets, and early clinical risk stratification by comparison of samples taken on patient arrival and after resuscitation is completed.
  Project 4: The goal is to longitudinally quantify and compare acute/subacute vasogenic cerebral edema due to BBB disruption across TBI patients with and without HS and relate these metrics back to corresponding fibrinolytic and phenotypes ascertained in Projects 1 and 2. The impact will be to quantify BBB permeability 4 and cerebral edema and correlate this with blood-based biomarkers. These data will provide a translational link to the pathophysiology of how HS amplifies cerebral edema after TBI. This Project implements a multimodal, transdisciplinary approach to investigate longitudinal relationships between blood-based markers of fibrinolysis, blood-based markers of cerebral edema (CE), and physiologic measures of CE. This Project will provide clinically relevant imaging data that link to mechanisms and biomarkers that are measurable with standard techniques. Aim 1a. Quantify release of FDPs in patients with TBI+/-HS and correlate with transfusions and clinical outcomes Aim 1b. Define the impact and critical dose thresholds of FDPs for inducing hyperpermeability using an in vitro BBB model Aim 1c. Examine EC signaling events induced by FDP exposure that result in endothelial activation and hyperpermeability Aim 1d. Identify novel therapeutic targets to limit FDP-endothelial interactions Aim 1e. Determine the effectiveness of inhibiting FDP release and/or FDP-EC interactions on BBB disruption Aim 2a. Determine the influence of increasing injury severity/complexity on BBB permeability Aim 2b. Characterize the fibrinolytic phenotype that worsens TBI via the PAR1-MMP-9-SUR1-TRPM4 signaling axis Aim 2c. Determine the contribution of upregulation and/or SUR1-TRPM4 channel activation mechanisms to HS amplification of BBB permeability Aim 3b. Determine the relative contribution of metabolic crisis vs. mRNA degradation as the etiology of platelet contractile dysfunction Aim 3c. Investigation of GPVI-fibrin interface in platelet dysfunction and hyperfibrinolysis Aim 4a. Determine the relationship between changes in extent and subtype of CE (acutely with CT and subacutely with MRI) with quantitative assays of blood-based concentrations of FDPs and potential biomarkers of CE Aim 4b. Determine the relationship between quantitative measures of BBB permeability (Ktrans; 3T DCE-MRI) with blood-based concentrations of SUR1, TRPM4, AQP4, and FDPs Aim 4c. Determine the relationship between quantitative BBB permeability measures and volume of vasogenic CE

Led By Other Sites:

• Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID Trial)

  Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID Trial)
  Site PI – Lillian Kao, MD
  Supporting Agency – University of Washington
  The Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID) study aims to test if, from a patient’s perspective, partial colectomy is better than medical management for the treatment of quality of life (QoL)-limiting diverticulitis. We hypothesize that partial colectomy will be better than medical management with respect to patient-reported and patient-centered outcomes. A large-scale pragmatic, randomized trial is expected to result in better understanding of the best management of a common gastrointestinal, QoL-limiting condition in patients nationwide. Understanding which patient subgroups benefit from partial colectomy and which patient subgroups benefit from best medical management will improve patient choice and support a shift from practice variations dependent on provider preferences or precedent to clinical care that corresponds to selecting the right treatment for the right patient at the right time.
  Aim 1: Compare patient-reported outcomes (e.g., quality of life, work productivity, decisional regret) in patients with QoL-limiting diverticulitis randomized to elective colectomy vs. best medical management. Aim 2: Compare clinical outcomes (e.g., rates of serious adverse events, number of subsequent episodes of diverticulitis) between patients with QoL-limiting diverticulitis randomized to elective colectomy vs. best medical management. Aim 3: Compare healthcare utilization between patients with QoL-limiting diverticulitis randomized to elective colectomy vs. best medical management.

• Identifying miRNA Signatures of Opioid Misuse Risk in Trauma Patients

  Identifying miRNA Signatures of Opioid Misuse Risk in Trauma Patients
  Co-Investigator – John Harvin, MD
  Supporting Agency – Wellcome Leap
  To assess associations between opioid demand and clinically/biologically relevant outcomes measures. To assess if miRNA signatures at discharge predict a patient’s likelihood to exhibit continued opioid use at more than 90 days post-discharge.

• iRemedyACT: Identification and Remediation of Delays to Definitive Care of Critically Injured Patients in the Texas Trauma System (Remedy) with Advances in AI to Improve Care for Trauma (ACT)

  iRemedyACT: Identification and Remediation of Delays to Definitive Care of Critically Injured Patients in the Texas Trauma System (Remedy) with Advances in AI to Improve Care for Trauma (ACT)
  PI – Lillian Kao, MD
  Co-Investigator – Erin Fox, PhD
  Supporting Agency - TRC4 – Trauma Research & Combat Casualty Care Collaborative
  Delayed access to definitive care in critically injured patients is associated with worse outcomes, including increased morbidity and mortality. To address this gap within the Texas trauma system, we propose iRemedyACT to provide novel and valuable datasets upon which to develop (1) public health policy, (2) injury prevention initiatives, (3) trauma care interventions / evidence-based guidelines, (4) trauma system development / improvement activities and (5) targets for future research and development strategies. In conjunction with database development, the iRemedyACT initiative introduces ACT (Advances in AI to Improve Care for Trauma), a broadly-accessible artificial intelligence (AI) tools and training infrastructure in the field of trauma and trauma care. ACT will accelerate both interpretation of the data we collect for the Texas Trauma System as well as empower all researchers and clinicians in trauma to utilize novel approaches in AI to address hypotheses and decision-making of their interest.
  Aim 1: Develop data-sharing and database infrastructure for a multi-institutional network of trauma centers within the University of Texas System in order to create and sustain a capability to acquire and analyze composite outcomes of trauma patients across the state of Texas. Aim 2: Design and deploy data analyses and visualizations in order to (1) determine the impact of delays in access to definitive care in critically injured patients, (2) identify factors associated with delays and (3) quantify the public health impact of delays in care and predict benefits from specific actions to minimize delays. Aim 3: Build a user-friendly artificial intelligence and machine learning (AI/ML) platform and training program (ACT) in order to empower researchers and clinicians to harness AI/ML in interpreting (1) the new University of Texas System trauma database and (2) data from their research and/or clinical practice.

• LITES Task Order 7: Type O Whole Blood and Assessment of Age During Prehospital Resuscitation Trial (TOWAR)

  Microvascular Barrier Biomarkers to Predict ICP Therapeutic Intensity After Severe TBI
  PI - Charles Cox, MD
  Co-Investigators – Erin Fox, PhD; Charles Wade, PhD
  Supporting Agency – US Army Medical Research & Material Command (W81XWH18SBAA1)
  NCT # – NCT04684719
  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.

• Massive Transfusion in Children (MATIC-2)
  
  

  Massive Transfusion in Children (MATIC-2)
  PI – Charles Cox, MD
  Supporting Agency - Biomedical Advanced Research Development Authority (BARDA)
  NCT # – NCT06070350
  The Massive Transfusion in Children-2 (MATIC-2) trial will examine the effectiveness, safety and mechanisms between multiple resuscitation practices in children with life-threatening bleeding from traumatic injury. The interventions in the trial will include blood component therapy with red cells, plasma and platelet units compared to low titer group O whole blood, and tranexamic acid compared to placebo. These interventions have been chosen for this randomized controlled trial due to laboratory, animal, and human data that suggests the use of low titer group O whole blood and tranexamic acid have the potential to improve survival in children with life-threatening bleeding. The trial will also thoroughly explore the mechanisms of trauma induced blood failure and the biologic consequences of each of the interventions studied in this trial with the innovative use of a multi-omics platform (proteomics, lipidomics, and metabolomics).
  More Information (English): https://www.uab.edu/medicine/cis/matic-2-the-university-of-texas-health-science-center-at-houston-uthealth-houston More Information (Spanish): https://www.uab.edu/medicine/cis/matic-2-the-university-of-texas-health-science-center-at-houston-uthealth-houston/matic-2-the-university-of-texas-health-science-center-at-houston-uthealth-houston-spanish

• Novel ‘Short Wave Assessment Tool in Texas’ (SWATT) to Enhance Burn Tissue Viability Assessment

  Novel ‘Short Wave Assessment Tool in Texas’ (SWATT) to Enhance Burn Tissue Viability Assessment
  PI – John Harvin, MD
  Supporting Agency – TRC4 – Trauma Research & Combat Casualty Care Collaborative
  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.

• Project TRUST - Trauma Recovery Using Support from Trauma-Informed-Care Approach

  Project TRUST – Trauma Recovery Using Support from Trauma-Informed-Care Approach
  PI – Stephanie Martinez-Ugarte, MD
  Co-Investigator – Natalie Drucker, MD
  Supporting Agency – TRC4 – Trauma Research & Combat Casualty Care Collaborative
  Our project aims to provide a structured approach to implement TIC and screening for mental health illnesses after physical trauma in all Level I Trauma Centers (adult and pediatric) across the UT system. Our team of social worker and educator will travel to each participating site to ensure standardized implementation of the TIC curriculum and mental health screening. We plan to collect baseline mental health screening scores on patients and health care workers at each institution prior to full initiation of TIC and mental health screening. A validated PTSD / Depression checklist will be used for screening over the continuum of the project period of 18 months. Benefit to Cost Ratio will be calculated by reviewing readmission rates, compliance to scheduled follow-up after discharge, and post-injury quality of life scores before and after implementation at UT System affiliated ACS Verified Trauma Centers.

• Treatment Individualized Appendicitis Decision Making Implementation Program - TRIAD

  Treatment Individualized Appendicitis Decision Making Implementation Program – TRIAD
  PI – Lillian Kao, MD
  Supporting Agency – University of Washington
  Accumulating evidence for the safety and efficacy of non-operative management of appendicitis with antibiotics means that patients now have a preference-sensitive decision for how to treat appendicitis. The goal of this study is to understand how patients are making this treatment decision and their opinions and satisfaction with the type of information and support they are receiving in making this decision. This information will be used to inform the design of decision-support interventions to help patients improve their ability to make an informed decision in line with their preferences and values.

• Vitamin C in Thermal injury: The VICToRY Trial

  Vitamin C in Thermal injury: The VICToRY Trial
  PI – John Harvin, MD
  Supporting Agency – Queen’s University at Kingston
  NCT # – NCT04138394
  The objective of this pilot trial is to demonstrate feasibility and safety of a high-dose intravenous vitamin C administration in 180 severely burned patients. Furthermore, this study´s purpose is a) to gain first information about the safety and pharmacokinetics of high dose intravenous vitamin C in this patient population, b) determine possible endpoints for a definitive study, and c) to evaluate the oxidation-reduction potential as a new biomarker for oxidative stress. If feasibility is demonstrated in the pilot, a larger phase II/III component will be conducted and aimed at lowering morbidity and mortality and reducing health care costs in an otherwise very devastating and disabling injury worldwide. However, before proceeding to such a large trial, we propose to conduct a smaller pilot trial aimed at assessing the feasibility and fidelity of implementation of the larger trial protocol. We hypothesize that the inexpensive therapeutic strategy tested in this randomized controlled trial will be feasible to conduct with high fidelity of implementation. This trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirements.