Primary Mechanism Of Injury Research Articles

The Role of Temporal Lobectomy as a Part of Surgical Resuscitation in Patients with Severe Traumatic Brain Injury.

Background:Traumatic brain injuries (TBIs) are serious morbidity and mortality risk for especially in the young population. Primary and secondary injury mechanisms may cause cerebral edema and intracranial hypertension. The target point of the TBI treatment is lowering the intracranial pressure medically or surgically if indicated.Methods:The files of the patients with severe brain injury admitted between January 2015 and December 2017 were reviewed retrospectively. Patients who underwent decompression surgery due to severe brain injury ([The Glasgow Coma Scale [GCS] score] <8) and additional temporal lobectomy were included in the study group.Results:Ten patients were included in the study during the 3 years. All the patients were suffering from blunt severe TBI. Traumatic etiology was vehicle traffic accident in six cases, nonvehicle traffic accident in two cases, and falling from height in two cases. All the cases suffered from blunt trauma. The admission GCS of the patients was 4–7 (mean = 5.5). Right-sided decompression surgery and lobectomy were performed for seven patients and left-sided in three cases. The postoperational survival was 60%. All the survivors were functionally independent with mild cognitive disturbances.Conclusion:Temporal lobectomy might be added to the surgery to apply all the interventions available in combat with progressively increasing intracerebral pressure as a part of surgical resuscitation.

Investigational RNAi Therapeutic Targeting C5 Is Efficacious in Pre-clinical Models of Myasthenia Gravis

Complement-mediated damage to the neuromuscular junction (NMJ) is a key mechanism of pathology in myasthenia gravis (MG), and therapeutics inhibiting complement have shown evidence of efficacy in the treatment of MG. In this study, we describe the development of a subcutaneously administered N-acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) targeting the C5 component of complement that silences C5 expression in the liver (ALN-CC5). Treatment of wild-type rodents with ALN-CC5 resulted in robust and durable suppression of liver C5 expression. Dose-dependent serum C5 suppression was observed in non-human primates, with a lowering of serum C5 of up to 97.5% and the concomitant inhibition of serum complement activity. C5 silencing was efficacious in ameliorating disease symptoms in two standard rat models of MG, demonstrating the key role of circulating C5 in pathology at the NMJ. Improvement in disease activity scores and NMJ pathology was observed at intermediate levels of complement activity inhibition, suggesting that complete ablation of complement activity may not be required for efficacy in MG. The pre-clinical studies of ALN-CC5 and efficacy of C5 silencing in rat models of MG support further clinical development of ALN-CC5 as a potential therapeutic for the treatment of MG and other complement-mediated disorders.

Acute Spinal Cord Injury: A Systematic Review Investigating miRNA Families Involved.

Acute traumatic spinal cord injury (SCI) involves primary and secondary injury mechanisms. The primary mechanism is related to the initial traumatic damage caused by the damaging impact and this damage is irreversible. Secondary mechanisms, which begin as early as a few minutes after the initial trauma, include processes such as spinal cord ischemia, cellular excitotoxicity, ionic dysregulation, and free radical-mediated peroxidation. SCI is featured by different forms of injury, investigating the pathology and degree of clinical diagnosis and treatment strategies, the animal models that have allowed us to better understand this entity and, finally, the role of new diagnostic and prognostic tools such as miRNA could improve our ability to manage this pathological entity. Autopsy could benefit from improvements in miRNA research: the specificity and sensitivity of miRNAs could help physicians in determining the cause of death, besides the time of death.

Mass Properties Comparison of Dismounted and Ground-Mounted Head-Supported Mass Configurations to Existing Performance and Acute Injury Risk Guidelines.

In order to limit the aviator's exposure to potentially unsafe helmet configurations, the U.S. Army Aeromedical Research Laboratory (USAARL) developed the USAARL Head-supported mass (HSM) Performance Curve and Acute Injury Risk Curve as guidelines for Army aviation HSM. These Curves remain the only established guidelines for Army HSM, but have limited applicability outside of the aviation environment. Helmet developers and program managers have requested guidelines be developed for the dismounted, ground-mounted, and airborne operating environments that consider currently fielded and proposed HSM configurations. The aim of this project was to measure mass properties (mass and center of mass offset) of currently fielded and proposed HSM configurations and compare them against the existing USAARL HSM Curve guidelines. Mass properties were collected for 71 unique dismounted and ground-mounted HSM configurations. None of the 71 HSM configurations met the Acute Injury Risk Curve recommendations, and only 11 of the 71 configurations met Performance Curve recommendations. While some helmets fell within acceptable limits, the addition of night vision goggles and protective masks pushed all configurations outside of the recommended guidelines. Future guidelines will need to be expanded to consider the operating environment, movement techniques, and primary mechanism of injury.

A Prospective Analysis of Patients With Anterior Versus Posterior Shoulder Instability: A Matched Cohort Examination and Surgical Outcome Analysis of 200 Patients

Background: Anterior and posterior shoulder instabilities are entirely different entities. The presenting complaints and symptoms vastly differ between patients with these 2 conditions, and a clear understanding of these differences can help guide effective treatment. Purpose: To compare a matched cohort of patients with anterior and posterior instability to clearly outline the differences in the initial presenting history and overall outcomes after arthroscopic stabilization. Study Design: Cohort study; Level of evidence, 2. Methods: Consecutive patients with either anterior or posterior glenohumeral instability were prospectively enrolled; patients were excluded if they had more than 10% anterior or posterior glenoid bone loss, multidirectional instability, neurologic injury, or prior surgery. Patients were assigned to anterior or posterior shoulder instability groups based on the history and clinical examination documenting the primary direction of instability, with imaging findings to confirm a labral tear associated with the specific direction of instability. Preoperative demographic data, injury history, and overall clinical outcome scores (American Shoulder and Elbow Surgeons [ASES], Single Assessment Numeric Evaluation [SANE], and Western Ontario Shoulder Index [WOSI]) were assessed and compared statistically between the 2 cohorts. Patients were indicated for surgery if they elected to proceed with surgical management or did not respond to a course of nonoperative management. Results: The study included 103 patients who underwent anterior stabilization (mean age, 23.5 years; range, 18-36 years) and 97 patients who underwent posterior stabilization (mean age, 24.5 years; range, 18-36 years). The mean follow-up was 39.7 months (range, 24-65 months), and there were no age or sex differences between the groups. No patients were lost to follow-up. The primary mechanism of injury in the anterior cohort was a formal dislocation event (82.5% [85/103], of which 46% [39/85] required reduction by a medical provider), followed by shoulder subluxation (12%, 12/103), and “other” (6%, 6/103; no forceful injury). No primary identifiable mechanism of injury was found in the posterior cohort for 78% (75/97) of patients; lifting and pressing (11%, 11/97) and contact injuries (10% [all football blocking], 10/97) were the common mechanisms that initiated symptoms. Only 10 patients (10.3%) in the posterior cohort sustained a dislocation. The most common complaints for patients with anterior instability were joint instability (80%) and pain with activities (32%). In the posterior cohort, the most common complaint was pain (90.7%); only 13.4% in this cohort reported instability as the primary complaint. Clinical outcomes after arthroscopic stabilization were significantly improved in both groups, but the anterior cohort had significantly better outcomes in all scores measured: ASES (preoperative: anterior 58.0, posterior 60.0; postoperative: anterior 94.2 vs posterior 87.7, P < .005), SANE (preoperative: anterior 50.0, posterior 60.0; postoperative: anterior 92.9 vs posterior 84.9, P < .005), and WOSI (preoperative: anterior 55.95, posterior 60.95; postoperative: anterior 92% of normal vs posterior 84%, P < .005). Conclusion: This study outlines clear distinctions between anterior and posterior shoulder instability in terms of presentation and clinical findings. Patients with anterior instability present primarily with an identifiable mechanism of injury and complaints of instability, whereas most patients with classic posterior instability have no identifiable mechanism of injury and their primary symptom is pain. Anterior instability outcomes in this matched cohort were superior in all domains versus posterior instability after arthroscopic stabilization, which further highlights the differences between anterior and posterior instability.

Modulation of parietal cytokine and chemokine gene profiles by mesenchymal stem cell as a basis for neurotrauma recovery

Following traumatic brain injury (TBI), primary mechanical injury to the brain may cause blood-brain-barrier damage followed by secondary injury, ultimately culminating in cell death. We aimed to test whether one injection of mesenchymal stem cells (MSC) derived from the human umbilical cord can modulate brain cytokine and chemokine gene profiles and attenuate neurological injury in rats with TBI. One-day post-TBI, the injured rats were treated with one injection of MSC (4×106/rat, i.v.). Three days later, immediately after assessment of neurobehavioral function, animals were sacrificed for analysis of neurological injury (evidenced by both brain contusion volume and neurological deficits) and parietal genes encoding 84 cytokines and chemokines in the injured brain by qPCR methods. Three days post-TBI, rats displayed both neurological injury and upgrade of 11 parietal genes in the ipsilateral brain. One set of 8 parietal genes (e.g., chemokine [C-X-C motif] ligand 12, platelet factor 4, interleukin-7, chemokine [C-C motif] ligand (CCL)19, CCL 22, secreted phosphoprotein 1, pro-platelet basic protein 1, and CCL 2) differentially upgraded by TBI was related to pro-inflammatory and/or neurodegenerative processes. Another set of 3 parietal genes up-graded by TBI (e.g., glucose-6-phosphate isomerase, bone morphogenetic protein (BMP) 2, and BMP 4) was related to anti-inflammatory/neuroregenerative events. Administration of MSC attenuated neurological injury, down-regulated these 8 parietal pro-inflammatory genes, and up-regulated these 3 parietal anti-inflammatory genes in the rats with TBI. Our data suggest that modulation of parietal cytokines and chemokines gene profiles by MSC as a basis for neurotrauma recovery.

Bone Bruises Associated with Anterior Cruciate Ligament Injury as Indicators of Injury Mechanism: A Systematic Review.

Anterior cruciate ligament (ACL) injury is one of the most common injuries in sports, and the injury mechanisms are not completely clear. Bone bruises seen on magnetic resonance imaging (MRI) following ACL injuries may provide significant information for determining ACL injury mechanisms. The aim was to determine ACL injury mechanisms through an evaluation of locations of bone bruises associated with ACL injury. A search for related articles in PubMed and the EBSCO Sport Database was performed using selected search strings from inception to August 6, 2018. Original studies with specified bone bruise locations identified using MRI technology were reviewed. A total of 12 studies with 589 patients were selected for review. A total of 471 bone bruises in the lateral tibial plateau were reported. Of these bone bruises, 409 (87%) occurred in the posterior section. A total of 242 bone bruises in the medial tibial plateau were reported. Of these bone bruises, 208 (86%) occurred in the posterior section. A total of 266 bone bruises in the lateral femoral condyle were reported. Of these bone bruises, 65 (25%) and 184 (69%) occurred in the anterior and central sections, respectively. A total of 105 bone bruises in the medial femoral condyle were reported. Of these bone bruises, 49 (47%) and 41 (39%) occurred in the anterior and central sections, respectively. Bone bruise location patterns indicate that tibial anterior translation relative to the femur was a primary injury mechanism in the majority of ACL injuries selected in this review, and that the maximal knee valgus apparently occurred after tibial anterior translation sufficient to injure the ACL. Bone bruise location patterns also indicate knee hyper-extension as another mechanism of non-contact ACL injury.

Circular RNA Expression Alteration and Bioinformatics Analysis in Rats After Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is mostly caused by trauma. As primary mechanical injury is unavoidable in SCI, a focus on the pathophysiology and underlying molecular mechanisms of SCI-induced secondary injury is necessary to develop promising treatments for SCI patients. Circular RNAs (circRNAs) are associated with various diseases. Nevertheless, studies to date have not yet determined the functional roles of circRNAs in traumatic SCI. We examined circRNA expression profiles in the contused spinal cords of rats using microarray and quantitative reverse transcription-PCR (qRT-PCR) then predict their potential roles in post-SCI pathophysiology with bioinformatics. We found a total of 1676 differentially expressed circRNAs (fold change ≥ 2.0; P < 0.05) in spinal cord 3 days after contusion using circRNA microarray; 1261 circRNAs were significantly downregulated, whereas the remaining 415 were significantly upregulated. Then, five selected circRNAs, namely, rno_circRNA_005342, rno_circRNA_015513, rno_circRNA_002948, rno_circRNA_006096, and rno_circRNA_013017 were all significantly downregulated in the SCI group after verification by qRT-PCR, demonstrating a similar expression pattern in both microarray and PCR data. The next section of the study was concerned with the prediction of circRNA/miRNA/mRNA interactions using bioinformatics analysis. In the final part of the study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses indicated carbohydrate metabolic process was one of the most significant enrichments and meaningful terms after GO analysis, and the top two signaling pathways affected by the circRNAs-miRNAs axes were the AMP-activated protein kinase signaling pathway and the peroxisome related pathway. In summary, this study showed an altered circRNA expression pattern that may be involved in physiological and pathological processes in rats after traumatic SCI, providing deep insights into numerous possibilities for SCI treatment targets by regulating circRNAs.

Neuroimaging of the component white matter connections and structures within the cerebellar-frontal pathway in posterior fossa tumor survivors.

IntroductionIn posterior fossa tumor survivors, lower white matter integrity (WMI) in the right cerebellar-left frontal pathway has been well documented and appears to be related to proximity to the cerebellum, radiation treatment, as well as time since treatment in both cranial radiation and surgery-only treatment groups. The current study investigated theories of transneural degeneration following cerebellar tumor resection that may underlie or relate to reductions in WMI and regional brain volumes using correlations. We hypothesized a positive relationship between the volume of the right cerebellum and known white matter output pathways, as well as with the volume of structures that receive cerebellar projections along the pathway.MethodsAdult survivors of childhood brain tumors were recruited (n = 29; age, M = 22 years, SD = 5; 45% female). Age- and gender-matched controls were also included (n = 29). Participants completed 3 T diffusion-weighted and T1 MPRAGE MRI scans. Brain structure volume relative to intracranial vault served as regional volumetric measures. Fractional anisotropy (FA) and radial diffusivity (RD) served as WMI measures. In the survivor group, partial correlations between WMI and regional volume included controlling for disease severity.ResultsIn posterior fossa tumor survivors, the volumes of the cerebellum, thalamus, and frontal lobe were correlated with WMI of the thalamic-frontal segment of the cerebellar-frontal pathway (r = 0.41–0.49, p < .05). Cerebellar atrophy was correlated with reduced WMI in the cerebellar-rubral segment (FA, r = −0.32 p > .05; RD, r = 0.53, p < .01). In the no-radiation survivor group, the regional volume of each structure along the pathway was associated with WMI in the cerebellar-rubral segment. In the radiation survivor group, significant correlations were found between the regional brain volume of each structure and the thalamic-frontal segment of the pathway.DiscussionThe results of this multimodal neuroimaging study provide correlational evidence that the mechanism of injury subsequent to brain tumor treatment may be different depending on type of treatment(s). Without radiation, the primary mechanism of injury is cerebellar tumor growth, resection, and hydrocephalus. Therefore, the most proximal connection to that injury (cerebellar-rubral pathway) was correlated with reductions in volume along the pathway. In contrast, the survivor group treated with radiation may have had possible radiation-induced demyelination of the thalamic-frontal portion of the pathway, based on a strong correlation with volume loss in the cerebellum, red nucleus, thalamus, and frontal lobe.

Burden and profile of spinal pathology at a major tertiary hospital in the Western Cape, South Africa

Background: Spinal pathology in the Western Cape is managed at three tertiary level hospitals, including Tygerberg Hospital. The Tygerberg Hospital Orthopaedic Spinal Unit is responsible for the management of spinal pathology for the 3.4 million people in the hospital’s catchment area. However, the unit’s overall burden of disease and associated resource use is currently unclear. Aim: The first aim was to investigate the overall burden and clinical profile of spinal pathology presenting to the Tygerberg Hospital Spinal Unit over a one-year period. The second aim was to determine resource use associated with spine pathology admissions. Methods: Overall burden was investigated by performing a retrospective review of all patients admitted to the Spine Unit between 1 October 2016 and 30 September 2017. Demographic and clinical data was collected, and patients were assigned to one of five spinal pathology sub-groups. Resource use was determined by length of hospital stay, waiting times, advanced imaging and theatre usage. Results: Overall burden comprised 349 individual patients and 376 admissions, including readmissions. Trauma (51%) and infection (24%) accounted for the majority of admitted pathology with degenerative (10%), deformity (7%) and malignancy (7%) representing fewer admissions. Motor vehicle accidents were the primary mechanism of injury, accounting for 48% of spine trauma. Tuberculosis was the causative organism in 87% of spinal infections with 44% HIV co-infection. Hospital resource use was considerable with 92% of spine patients requiring advanced imaging, a median operating time of 3 h 36 min and a median hospital stay of 19 days. Infection and malignancy sub-groups had the longest waiting times for advanced imaging and theatre with a median wait of 14–16 days, accounting for approximately 62% of the typical total hospital stay. Conclusions: The Spine Unit experienced a substantial patient burden requiring significant hospital resources. Reduced in-patient waiting times and upskilling of orthopaedic services at secondary hospitals represent key areas for health system strengthening. However, multi-sectoral strategies would be required to effectively address our high burden of largely preventable spinal pathology. Level of evidence: Level 4

Detection of Drug-Induced Cholestasis Potential in Sandwich-Cultured Human Hepatocytes.

Drug-induced cholestasis poses a major hurdle for the pharmaceutical industry as it is one the primary mechanisms of drug-induced liver injury. Hence, detection of drug-induced cholestasis during the early stages of drug development is of utmost importance. The most commonly used in vitro models rely on the extent of inhibition of bile salt export pump-mediated taurocholic acid transport, thereby assuming that drug-induced cholestasis mechanisms are merely restricted to the interaction with this sole hepatic transporter. Sandwich-cultured human hepatocytes represent a more holistic in vitro tool to investigate drug-induced cholestasis as they preserve all relevant disposition pathways and cellular functions involved in bile acid homeostasis. We developed and validated a sandwich-cultured human hepatocytes-based in vitro assay which is able to identify compounds causing cholestasis by altering bile acid disposition. The in vitro cholestatic potential is expressed by calculating a drug-induced cholestasis index value, which reflects the relative residual urea formation of sandwich-cultured human hepatocytes co-incubated with bile acids and test compound as compared to sandwich-cultured human hepatocytes treated with test compound alone. In addition, a safety margin can be calculated to determine the in vivo risk for cholestasis based on the determination of the drug-induced cholestasis index at various concentrations and the peak plasma concentration of the drug candidate. This chapter outlines the various steps involved in performing our sandwich-cultured human hepatocytes-based in vitro assay.

Epidemiology of Equestrian Accidents: a Literature Review

Purpose: This manuscript aimed to present a review of the literature pertaining to horse riding and other horse-related injuries. Method: A review of the literature was performed, searching for appropriate terms with regards to horse accidents, horse riding injuries and protective clothing for the horse riding context. The literature review search returned 151 relevant full-text articles, with 71 of these detailing the overall injury epidemiology of horse-related accidents. Most of these studies were conducted in the USA and used a retrospective review of hospital data methodology. Results: Of the 71 articles investigated, 60 suggested that those most frequently involved in horse-related accidents are young females and 97% of papers investigating injury mechanisms found the most commonly involved was a fall from horseback. It was suggested in multiple studies that these injury events mostly occurred in warm weather conditions, when the horse behaved in an unexpected manner. Injury type and location varied by the primary mechanism of injury; but frequently involved body regions were the head and upper extremities, and the most common injuries observed were fractures and soft tissue injuries. Neurological trauma was reported by all relevant studies to be the most frequent cause of fatality. Conclusion: Some improvements in horse-related accident numbers and outcomes have been observed with the development and introduction of protective devices such as helmets and vests. Yet despite the benefits of helmet and vest usage, there is evidence to suggest helmets do not perform as well as they could. Further work could investigate improvements in safety measures and risk factors associated with fatalities.

Clinical relevance between anatomic features of sustentaculum tali and intra-articular calcaneal fractures

The calcaneus is the most commonly fractured tarsal bone, calcaneal fracture comprises 2% of all fractures, the primary mechanism of injury involves a high energy axial load. To get a better outcome, the literature review recommends the use of Open Reduction and Internal Fixation (ORIF) for this kind of injury. Sustentaculum tali is a triangular projection from the medial surface of the calcaneus, it possesses strong trabecular structure and thick cortex, and it's thought to remain tightly bound to the talus by ligaments and muscle tendons nearby, that's why it′s often used as a constant fragment to which other fracture fragments are reduced to restore congruity of the subtalar joint. Hence, it's important to understand the anatomic features of sustentaculum tali. In this article, we describes the anatomic measurements of the sustentaculum tali including the size, angle and soft tissue nearby, and described the correlation between these anatomic features and intra-articular calcaneal fractures. We are hoping that we can provide theoretical reference to the clinical treatment of calcaneal fractures. Key words: Calcaneus; Anatomy; Intra-articular fractures; Surgical procedures, operative

Diffusion tensor imaging shows mechanism-specific differences in injury pattern and progression in rat models of acute spinal cord injury

We investigate the ability of diffusion tensor imaging (DTI) to distinguish between three experimental rat models of spinal cord injury mechanism – contusion, dislocation, and distraction. Ex vivo DTI scans were performed on cord specimens that were preserved at different time points of the acute injury (3 hr, 24 hr, and 7 days post-injury) across all three injury mechanisms. White matter was classified as abnormal if their DTI metric was substantially different from regional values measured from a set of uninjured controls, thus allowing generation of binary “white matter damage maps” which categorizes each pixel in the DTI image as “normal” or “damaged”. Damage classification was most robust using thresholds in the longitudinal diffusivity, which supports previous studies that show that longitudinal diffusivity is the most robust DTI metric in depicting damage in SCI. Furthermore, the spatial damage patterns from all subjects in the same group were consolidated into a "damage occurrence ratio map", which illustrates an average damage shape that characterizes the injury mechanism. Our analysis has yielded a dataset which highlights the differences in injury pattern due to the initial mode of mechanical injury. For example, contusion produced an initial injury that emanated radially outward from the central canal, with subsequent damage along the caudal corticospinal tract and rostral gracile fasciculus; dislocation injuries showed a high level of involvement in the lateral and ventral white matter which became less apparent by 7 days post-injury, and distraction injuries were found to be less focal and more distributed rostrocaudally. This work represents a first step in adopting the use of the primary injury mechanism as a clinical prognostic factor in SCI, which may help to inform the trialing of existing neuroprotective treatment candidates, the development of new therapies as well as personalize the management of SCI for the individual patient.

Neuroinflammation and blood-brain barrier disruption following traumatic brain injury: Pathophysiology and potential therapeutic targets.

Traumatic Brain Injury (TBI) is the most frequent cause of death and disability in young adults and children in the developed world, occurring in over 1.7 million persons and resulting in 50,000 deaths in the United States alone. The Centers for Disease Control and Prevention estimate that between 3.2 and 5.3 million persons in the United States live with a TBI-related disability, including several neurocognitive disorders and functional limitations. Following the primary mechanical injury in TBI, literature suggests the presence of a delayed secondary injury involving a variety of neuroinflammatory changes. In the hours to days following a TBI, several signaling molecules and metabolic derangements result in disruption of the blood-brain barrier, leading to an extravasation of immune cells and cerebral edema. The primary, sudden injury in TBI occurs as a direct result of impact and therefore cannot be treated, but the timeline and pathophysiology of the delayed, secondary injury allows for a window of possible therapeutic options. The goal of this review is to discuss the pathophysiology of the primary and delayed injury in TBI as well as present several preclinical studies that identify molecular targets in the potential treatment of TBI. Additionally, certain recent clinical trials are briefly discussed to demonstrate the current state of TBI investigation.

Intermittent Treadmill Running Induces Kinematic Compensations to Maintain Soccer Kick Foot Speed Despite No Change in Knee Extensor Strength.

Kicking is a fundamental skill and a primary noncontact mechanism of injury in soccer, with injury incidence increasing during the latter stages of match-play. Ten male professional soccer players completed a 90-minute treadmill protocol based on the velocity profile of soccer match-play. Preexercise, and at 15-minute intervals, players completed a maximal velocity kick subjected to kinematic analysis at 200Hz. Preexercise, and at the end of each half, players also completed isokinetic concentric knee extensor repetitions at 180°·s-1, 300°·s-1, and 60°·s-1. Kicking foot speed was maintained at ∼19m·s-1, with no main effect for exercise duration. In relation to proximal-distal sequencing during the kicking action, there was a significant increase in the duration (but not magnitude) of thigh rotation, with a compensatory decrease in the duration (but not magnitude) of shank rotation during the latter stages of the exercise protocol. In relation to long-axis rotation, pelvic orientation at ball contact was maintained at ∼6°, representing a total pelvic rotation in the order of ∼15° during the kicking action. Peak knee extensor torque at all speeds was also maintained throughout the protocol, such that kinematic modifications are not attributable to a decline in knee extensor strength.

Risk of Infection and Sepsis in Pediatric Patients with Traumatic Brain Injury Admitted to Hospital Following Major Trauma

Head injury accounts for 29% of all traumatic deaths in children. Sepsis is significantly associated with an increased risk of mortality in adult traumatic brain injury patients. In the pediatric population, this relationship is not well understood. The objective of this study was to compare the proportion of pediatric traumatic brain injury (TBI) patients and trauma patients without brain injury (NTBI) who developed sepsis or any infection during their index hospital admission. We performed a retrospective study of all trauma patients <18 years of age, admitted to trauma centres in Alberta, Canada from January 1, 2003 to December 31, 2012. Patients who died within 24 hrs of trauma (n = 147) and those with burns as the primary mechanism of injury (n = 53) were excluded. Hospital admission data for the remaining 2556 patients was analyzed. 1727 TBI patients and 829 NTBI patients were included. TBI was associated with lower odds of developing sepsis (OR 0.32 95% CI 0.14–0.77 p = 0.011). TBI was not found to be independently associated with developing any infectious complication after adjusting for confounding by Injury Severity Score (OR 1.25 95% CI 0.90–1.74 p = 0.180). These relationships warrant further study.

The cysteine-rich whey protein supplement, Immunocal®, preserves brain glutathione and improves cognitive, motor, and histopathological indices of traumatic brain injury in a mouse model of controlled cortical impact

Traumatic brain injury (TBI) is a major public health problem estimated to affect nearly 1.7 million people in the United States annually. Due to the often debilitating effects of TBI, novel preventative agents are highly desirable for at risk populations. Here, we tested a whey protein supplement, Immunocal®, for its potential to enhance resilience to TBI. Immunocal® is a non-denatured whey protein preparation which has been shown to act as a cysteine delivery system to increase levels of the essential antioxidant glutathione (GSH). Twice daily oral supplementation of CD1 mice with Immunocal® for 28 days prior to receiving a moderate TBI prevented an ~ 25% reduction in brain GSH/GSSG observed in untreated TBI mice. Immunocal® had no significant effect on the primary mechanical injury induced by TBI, as assessed by MRI, changes in Tau phosphorylation, and righting reflex time or apnea. However, pre-injury supplementation with Immunocal® resulted in statistically significant improvements in motor function (beam walk and rotarod) and cognitive function (Barnes maze). We also observed a significant preservation of corpus callosum width (axonal myelination), a significant decrease in degenerating neurons, a reduction in Iba1 (microglial marker), decreased lipid peroxidation, and preservation of brain-derived neurotrophic factor (BDNF) in the brains of Immunocal®-pretreated mice compared to untreated TBI mice. Taken together, these data indicate that pre-injury supplementation with Immunocal® significantly enhances the resilience to TBI induced by a moderate closed head injury in mice. We conclude that Immunocal® may hold significant promise as a preventative agent for TBI, particularly in certain high risk populations such as athletes and military personnel.

Temporal and Spatial Effects of Blast Overpressure on Blood-Brain Barrier Permeability in Traumatic Brain Injury

Blast-induced traumatic brain injury (bTBI) is a “signature wound” in soldiers during training and in combat and has also become a major cause of morbidity in civilians due to increased insurgency. This work examines the role of blood-brain barrier (BBB) disruption as a result of both primary biomechanical and secondary biochemical injury mechanisms in bTBI. Extravasation of sodium fluorescein (NaF) and Evans blue (EB) tracers were used to demonstrate that compromise of the BBB occurs immediately following shock loading, increases in intensity up to 4 hours and returns back to normal in 24 hours. This BBB compromise occurs in multiple regions of the brain in the anterior-posterior direction of the shock wave, with maximum extravasation seen in the frontal cortex. Compromise of the BBB is confirmed by (a) extravasation of tracers into the brain, (b) quantification of tight-junction proteins (TJPs) in the brain and the blood, and (c) tracking specific blood-borne molecules into the brain and brain-specific proteins into the blood. Taken together, this work demonstrates that the BBB compromise occurs as a part of initial biomechanical loading and is a function of increasing blast overpressures.

Practice Current: When do you order ancillary tests to determine brain death?

Brain death has been accepted as a legal definition of death in most countries, but practices for determining brain death vary widely. One source of variation is in the use of ancillary tests to assist in the diagnosis of brain death. Through case-based discussions with 3 experts from 3 continents, this article discusses selected aspects of brain death, with a focus on the use of ancillary tests. In particular, we explore the following questions: Are ancillary tests necessary, or is the clinical examination sufficient? What ancillary tests are preferred, and under which circumstances? Are ancillary tests required when the primary mechanism of injury is brainstem injury? Should the family's wishes play a role in the need for ancillary tests? The same case-based questions were posed to the rest of our readership in an online survey, the preliminary results of which are also presented.