Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children.

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083).

Low molecular weight heparin decreases pro-coagulant activity in clinical MSC products.

Background Aims: Mesenchymal stromal cells (MSCs) are multipotent adult cells that can be isolated from tissues including bone marrow [MSC(BM)], adipose [MSC(AT)] and umbilical cord [MSC(CT)]. Previous studies have linked expression of tissue factor (TF) on MSC surfaces to a procoagulant effect. Venous thromboembolism (VTE), immediate blood-mediated inflammatory reaction (IBMIR) and microvascular thrombosis remain a risk with intravascular MSC therapy.

Design and Development of a Clot Burst Pressure Device to Investigate Resuscitation Strategies.

Introduction: A reduction in clot strength is a hallmark feature of trauma-induced coagulopathy. A better understanding of clot integrity can optimize resuscitation strategies. We designed a device to gauge clot strength by pressurizing fluids over a formed clot and measuring the pressure needed to dislodge the clot.

Citrate Phosphate Dextrose Alters Coagulation Dynamics Ex Vivo.

Introduction: Citrate-phosphate-dextrose (CPD) is the most common anticoagulant for blood product storage in the United States. It was developed to prolong shelf life, though there is little research regarding its impact on function following transfusion. We used flow cytometry (FC), thromboelastography (TEG), and a clot contraction assay called the zFlex platform to measure platelet activation and global clot formation in blood samples anticoagulated with either CPD or in a standard blue top citrate (BTC) tube.

Impact of Transfused Citrate on Pathophysiology in Massive Transfusion.

Unlabelled: This narrative review article seeks to highlight the effects of citrate on physiology during massive transfusion of the bleeding patient.

Data Sources: A limited library of curated articles was created using search terms including "citrate intoxication," "citrate massive transfusion," "citrate pharmacokinetics," "hypocalcemia of trauma," "citrate phosphate dextrose," and "hypocalcemia in massive transfusion." Review articles, as well as prospective and retrospective studies were selected based on their relevance for inclusion in this review.

PLATELET FUNCTION IN TRAUMA: IS CURRENT TECHNOLOGY IN FUNCTION TESTING MISSING THE MARK IN INJURED PATIENTS?

Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. After injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure one or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events.

Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing Mechanotransduction.

Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing leads to heightened immune regulation cell-to-cell interaction and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation.

Microelectromechanical System Measurement of Platelet Contraction: Direct Interrogation of Myosin Light Chain Phosphorylation.

Myosin Light Chain (MLC) regulates platelet contraction through its phosphorylation by Myosin Light Chain Kinase (MLCK) or dephosphorylation by Myosin Light Chain Phosphatase (MLCP). The correlation between platelet contraction force and levels of MLC phosphorylation is unknown. We investigate the relationship between platelet contraction force and MLC phosphorylation using a novel microelectromechanical (MEMS) based clot contraction sensor (CCS).

Bone marrow stromal cell therapy improves survival after radiation injury but does not restore endogenous hematopoiesis.

The only available option to treat radiation-induced hematopoietic syndrome is allogeneic hematopoietic cell transplantation, a therapy unavailable to many patients undergoing treatment for malignancy, which would also be infeasible in a radiological disaster. Stromal cells serve as critical components of the hematopoietic stem cell niche and are thought to protect hematopoietic cells under stress. Prior studies that have transplanted mesenchymal stromal cells (MSCs) without co-administration of a hematopoietic graft have shown underwhelming rescue of endogenous hematopoiesis and have delivered the cells within 24 h of radiation exposure.

Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury.

The immune system plays critical roles in promoting tissue repair during recovery from neurotrauma but is also responsible for unchecked inflammation that causes neuronal cell death, systemic stress, and lethal immunodepression. Understanding the immune response to neurotrauma is an urgent priority, yet current models of traumatic brain injury (TBI) inadequately recapitulate the human immune response. Here, we report the first description of a humanized model of TBI and show that TBI places significant stress on the bone marrow.

Procoagulant in vitro effects of clinical cellular therapeutics in a severely injured trauma population.

Clinical trials in trauma populations are exploring the use of clinical cellular therapeutics (CCTs) like human mesenchymal stromal cells (MSC) and mononuclear cells (MNC). Recent studies demonstrate a procoagulant effect of these CCTs related to their expression of tissue factor (TF). We sought to examine this relationship in blood from severely injured trauma patients and identify methods to reverse this procoagulant effect.

A Novel Platelet Function Assay for Trauma.

Background: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients.

Clinical Cellular Therapeutics Accelerate Clot Formation.

Clinical cellular therapeutics (CCTs) have shown preliminary efficacy in reducing inflammation after trauma, preserving cardiac function after myocardial infarction, and improving functional recovery after stroke. However, most clinically available cell lines express tissue factor (TF) which stimulates coagulation. We sought to define the degree of procoagulant activity of CCTs as related to TF expression.

Platelet biomechanics, platelet bioenergetics, and applications to clinical practice and translational research.

The purpose of this review is to explore the relationship between platelet bioenergetics and biomechanics and how this relationship affects the clinical interpretation of platelet function devices. Recent experimental and technological advances highlight platelet bioenergetics and biomechanics as alternative avenues for collecting clinically relevant data. Platelet bioenergetics drive energy production for key biomechanical processes like adhesion, spreading, aggregation, and contraction.

A Useful Device to Measure Kinetics of Platelet Contraction.

Platelet contraction provides a minimally invasive source for physiologic information. In this article, we describe a device that directly measures the kinetics of platelet contraction. Whole blood is injected between acrylic plates and an adherent clot forms.

Management of blunt cerebrovascular injury (BCVI) in the multisystem injury patient with contraindications to immediate anti-thrombotic therapy.

Introduction: Practice management guidelines for screening and treatment of patients with blunt cerebrovascular injury (BCVI) have been associated with a decreased risk of ischemic stroke.

Treatment: of patients with BCVI and multisystem injuries that delays immediate antithrombotic therapy remains controversial. The purpose of this study was to determine the timing of BCVI treatment initiation, the incidence of stroke, and bleeding complications as a result of antithrombotic therapy in patients with isolated BCVI in comparison to those with BCVI complicated by multisystem injuries.

3D Printed Surgical Instruments: The Design and Fabrication Process.

Background: 3D printing is an additive manufacturing process allowing the creation of solid objects directly from a digital file. We believe recent advances in additive manufacturing may be applicable to surgical instrument design. This study investigates the feasibility, design and fabrication process of usable 3D printed surgical instruments.

Early surgical intervention for blunt bowel injury: the Bowel Injury Prediction Score (BIPS).

Background: Computed tomography (CT) scan of the abdomen has been used for 30 years to evaluate the stable blunt trauma patient. However, the early diagnosis of blunt hollow viscus injury (BHVI) remains a challenge. Delayed diagnosis and intervention of BHVI lead to significant morbidity and mortality.

Aligned PVDF-TrFE nanofibers with high-density PVDF nanofibers and PVDF core–shell structures for endovascular pressure sensing.

Nanostructures of polyvinyledenedifluoride-tetrafluoroethylene (PVDF-TrFE), a semicrystalline polymer with high piezoelectricity, results in significant enhancement of crystallinity and better device performance as sensors, actuators, and energy harvesters. Using electrospinning of PVDF to manufacture nanofibers, we demonstrate a new method to pattern high-density, highly aligned nanofibers. To further boost the charge transfer from such a bundle of nanofibers, we fabricated novel core-shell structures.

Evaluation of noninvasive hemoglobin measurements in trauma patients.

Background: Reliable, accurate, noninvasive, and continuous determination of hemoglobin would be an important advance in the care of trauma patients. The aim of this study was to evaluate the utility of the Masimo Radical 7 device in severely injured trauma patients.

Methods: Highest level trauma activation patients were enrolled over a 1-year period.