Alun Ackery

An in vitro model of neurotrauma in organotypic spinal cord cultures from adult mice

Cellular degeneration after spinal cord injury (SCI) involves numerous pathways. It is essential to use appropriate experimental models in order to understand the complex processes, which evolve after the initial trauma. The purpose of this study was to develop and assess an in vitro model of neurotrauma using organotypic slice culture of adult mice spinal cord. This model will facilitate the investigation of primary and secondary mechanisms of cell death that occurs after SCI. We modified previously described methods for generating organotypic cultures of murine spinal cord. The viability of organotypic cultures was assessed by observing the outgrowth of neurites and by using a mitochondria dependent dye for live cells (tetrazolium dye; MTT). The morphological integrity of cultures was examined histologically by hematoxylin and eosin (H&E) staining for general morphology and with luxol fast blue (LFB) for myelin. Neuronal and glial (GFAP; CNPase) markers were used to identify neurons, astrocytes and oligodendroglia, respectively. Primary injury was achieved by using a weight drop (0.2 g) model of injury. Cell death after primary injury was attenuated by pre-treatment with two known neuroprotective agents: the AMPA/KA blocker CNQX and methylprednisolone. The nuclear markers Propidium iodide and Sytox-green, as well as the TUNEL (in situ terminal deoxytransferase-mediated dUTP nick end labeling) technique, were used as a quantitative indicators of cell death at 24, 48 and 72 h post-injury using a confocal microscope and image analysis software. This novel in vitro model of SCI is easy to reproduce, will facilitate the examination of post-trauma cell death mechanisms and the neuroprotective effects of pharmacological agents and aid in the study of transgenic murine models.

Transcranial Doppler monitoring in subarachnoid hemorrhage: a critical tool in critical care.

Purpose: To review the literature regarding the use of transcranial Doppler ultrasonography (TCD) for monitoring cerebral vasospasm following subarachnoid hemorrhage (SAH).Source: We searched Medline (1980 to August 2007) and Embase (1980 to August 2007) and reviewed all relevant manuscripts regarding TCD and SAH.Principal findings: Currently, the gold standard for vasospasm diagnosis is cerebral angiography, replaceable by computed tomography angiography, only when angiography is not available. Obviously, it is not feasible to perform such investigation as frequently as bedside clinical assessment. Repeated clinical assessments of a patient’s neurological status carry the problem of detecting the clinical signs and symptoms of vasospasm, which occur only after vasospasm has already manifested its deleterious effects on the cerebral parenchyma. Transcranial Doppler ultrasonography is a relatively new, non-invasive tool, allowing for bedside monitoring to determine flow velocities indicative of changes in vascular calibre. Transcranial Doppler ultrasonography can be useful pre-, intra- and post-operatively, while helping to recognize the development of cerebral vasospasm before the onset of its clinical effects.Conclusion: Vasospasm following SAH is a very important source of morbidity and mortality. Too often, the first sign is a neurologic deficit, which may be too late to reverse. Transcranial Doppler ultrasonography assists in the clinical decision-making regarding further diagnostic evaluation and therapeutic interventions. When performed in isolation, the contribution of TCD to improving patient outcome has not been established. Nevertheless, TCD has become a regularly employed tool in neurocritical care and perioperative settings.RésuméObjectif: Passer en revue la littérature concernant l’utilisation de l’échographie Doppler transcrânienne (TCD) pour surveiller un vasospasme cérébral survenu à la suite d’une hémorragie sous-arachnoïdienne (SAH).Source: Nous avons effectué des recherches sur Medline (1980 à août 2007) et Embase (1980 à août 2007) et révisé tous les manuscrits pertinents concernant la TCD et la SAH.Constatations principales: À l’heure actuelle, l’angiographie est l’étalon or pour diagnostiquer un vasospasme. Celle-ci peut être remplacée par l’angiographie par tomodensitométrie seulement lorsqu’une angiographie n’est pas disponible. Il est évident qu’il n’est pas possible d’effectuer de telles recherches aussi fréquemment que les évaluations cliniques au chevet du malade. Des évaluations cliniques répétées de l’état neurologique d’un patient donné ont pour objectif primaire la détection des signes et symptômes cliniques du vasospasme, lesquels ne surviennent qu’après que le vasospasme a manifesté ses effets nuisibles sur le parenchyme cérébral. L’échographie Doppler transcrânienne est un outil relativement nouveau et non invasif qui permet un monitorage au chevet du patient afin de déterminer les vitesses du débit qui indiquent les changements dans le calibre vasculaire. L’échographie Doppler transcrânienne peut être utile avant, pendant et après l’opération tout en constituant un outil précieux pour identifier le développement d’un vasospasme cérébral avant que ses effets cliniques ne se manifestent.Conclusion: Le vasospasme à la suite d’une SAH est une cause majeure de morbidité et de mortalité. Trop souvent, le premier signe visible d’un vasospasme est un déficit neurologique, et il pourrait être trop tard déjà pour qu’il soit réversible. L’échographie Doppler transcrânienne est un outil qui assiste la prise de décision clinique concernant une évaluation diagnostique approfondie et des interventions thérapeutiques. Il n’a pas été démontré que la TCD, utilisée seule, améliore le suivi des patients. Cependant, la TCD est devenue un outil régulièrement employé dans des contextes de soins intensifs neurologiques et périopératoires.

Concussion in hockey: compliance with return to play advice and follow-up status.

OBJECTIVES To determine the compliance rate among hockey players with concussion or other head injuries who were advised by a physician about return to play. To assess compliance of hockey players with return to play advice and to assess the incidence of long-term post-concussion symptoms. METHODS A retrospective chart review, telephone questionnaire and follow-up analysis of income, level of education and professional aspirations. The study examined 40 hockey players with concussion or other head injury treated at a neurosurgical ambulatory clinic, who had initial visits between 1995 and 2003, and had been seen at least two years prior to completing the questionnaire. RESULTS There was a 58% (23 of 40) participation rate in the study. Fifteen (65%) of the 23 participants were advised to never return to play, and 5 (33%) were non-compliant and returned to play. Four (80%) of the five noncompliant players continued to suffer from post concussion symptoms. Overall, 15 (65%) of the 23 players participating in the study continued to suffer post concussion symptoms at least two years after the clinic visit. CONCLUSIONS Five (33%) of 15 hockey players advised to never return to play were non-compliant and returned to play, and four continued to suffer from post concussion symptoms two or more years later. After repeated concussions, 65% of hockey players had long-term sequelae that prevented return to play and produced long-term post-concussion symptoms.

“Is there a doctor on board?”: Practical recommendations for managing in-flight medical emergencies

KEY POINTS Hearing the call go out for a doctor at 36 000 feet can be anxiety-provoking for any physician. If health professionals offer their expertise, they may have to manage an unfamiliar clinical scenario, in a foreign and limited environment, without knowledge of the available resources.

Tranexamic acid for trauma-related hemorrhage

Uncontrolled hemorrhage causes 30%–45% of all trauma-related deaths. The Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial, an international, multicentre randomized controlled trial of tranexamic acid in trauma-related hemorrhage, randomized trauma patients

The Anticoagulated trauma patient in the age of the direct oral anticoagulants: a Canadian perspective

BackgroundThe anticoagulated trauma patient presents a particular challenge to the critical care physician. Our understanding of these patients is defined and extrapolated by experience with patients on warfarin pre-injury. Today, many patients who would have been on warfarin are now prescribed the Direct Oral Anticoagulants (DOACs) a class of anticoagulants with entirely different mechanisms of action, effects on routine coagulation assays and approach to reversal.MethodsTrauma registry data from Toronto’s (Ontario, Canada) two Level 1 trauma centres were used to identify patients on oral anticoagulation pre-injury from June 1, 2014 to June 1, 2015. The trauma registry and medical records were reviewed and used to extract demographic and clinical data.ResultsWe found 81 patients were on oral anticoagulants pre-injury representing 3.2% of the total trauma population and 33% of the orally anticoagulated patients were prescribed a DOAC prior to presentation. Comparison between the DOAC and warfarin groups showed similar age, mechanisms of injury, indications for anticoagulation, injury severity score and rate of intracranial hemorrhage. Patients on DOACs had higher initial mean hemoglobin vs warfarin (131 vs 120) and lower serum creatinine (94.8 vs 129.5). The percentage of patients receiving a blood transfusion in the trauma bay and total in-hospital transfusion was similar between the two groups however patients on DOACs were more likely to receive tranexamic acid vs patients on warfarin (32.1% vs 9.1%) and less likely to receive prothrombin concentrates (18.5% vs 60%). Patients on DOACs were found to have higher survival to discharge (92%) vs patients on warfarin (72%).ConclusionPatients on DOACs pre-injury now represent a significant proportion of the anticoagulated trauma population. Although they share demographic and clinical similarities with patients on warfarin, patients on DOACs may have improved outcomes despite lack of established drug reversal protocols and challenging interpretation of coagulation assays.Level of Evidence: III; Study Type: Retrospective Review.

Direct oral anticoagulants and the bleeding patient.

Rivaroxaban, apixaban and dabigatran are now commonly used as alternatives to vitamin K antagonist therapy (e.g., warfarin) for patients with atrial fibrillation, and for the treatment and prevention of venous thromboembolism. Dabigatran is a direct thrombin inhibitor, whereas apixaban and

Reducing lifelong disability from sports injuries in children

See also research article by Emery and colleagues on page [1249][1] and at [www.cmaj.ca/lookup/doi/10.1503/cmaj.101540][2]. Canadians admire their professional athletes, especially if they overcome adversity and continue to play while injured. These athletes are often role models for children and

Traumatic brain injuries in mixed martial arts: A systematic review:

Introduction Mixed martial arts is an emerging combat sport that is gaining popularity worldwide. We systematically reviewed the literature regarding the prevalence, severity and risk factors of head injuries sustained in mixed martial arts activities. Methods We conducted a comprehensive systematic review of Ovid MEDLINE, Embase, PsycINFO, EBM Reviews, CINAHL, SPORTDiscus, and Web of Science from 1990 to 2016 for studies of any design that reported associations of acute or chronic head injuries in persons participating in mixed martial arts activities. Results The initial database search yielded a total 472 citations, including 264 unique citations after duplications were removed. A total of 18 articles, primarily of observational data, showed ‘technical knockouts’ and ‘knockouts’ are prevalent in this sport (range: 28.3–46.2% of all matches) with other studies showing the lifetime average of 6.2 technical knockouts or knockouts in a career. Studies used inconsistent reporting methods for concussion, and no information regarding long-term follow-up was available. Conclusion Mixed martial arts fighting may be associated with repetitive head injuries and potential long-term neurological consequences; however, data on this topic are poor. Larger studies and stringent medical oversight are needed to improve the management and understanding of mixed martial arts head injuries, with implementation of harm reduction strategies and/or rule modifications to prevent long-term neurological sequelae. Systematic Review Registration: PROSPERO – CRD42014010019.

Can a single primary care paramedic configuration safely transport low-acuity patients in air ambulances?

OBJECTIVE To determine if utilizing a single paramedic crew configuration is safe for transporting low acuity patients requiring only a primary care paramedic (PCP) level of care in Air Ambulances. METHODS We studied single-PCP transports of low acuity patients done by contract air ambulance carriers, organized by Ornge (Ontarios Air Ambulance Service) for one year. We only included interfacility transports. We excluded all scene calls, and all Code 4 (emergent) calls. Our primary outcome was clinical deterioration during transport. We then asked a panel to analyze each case of deterioration to determine if a dual-PCP configuration might have reasonably prevented the deterioration or have better treated the deterioration, compared to a single-PCP configuration. RESULTS In one year, contract carriers moved 3264 patients, who met inclusion criteria. 85% were from Northern Ontario. There were 21 cases of medical deterioration (0.6%±0.26%). Paper charts were found for 20 of these cases. Most were self-limited cases of pain or nausea. A small number of cases (n=5) were cardiorespiratory decompensation. There was 100% consensus amongst the panel that all cases of clinical deterioration were not related to team size. There was also 100% consensus that a dual-PCP team would not have been better able to deal with the deterioration, compared to a single-PCP crew. CONCLUSIONS We found that using a single-PCP configuration for transporting low acuity patients is safe. This finding is particularly important for rural areas where air ambulance is the only means for accessibility to care and where staffing issues are magnified.