Concussion in facial trauma patients: a retrospective analysis of 100 patients from a UK major trauma centre.

Concussion is a common and potentially debilitating condition. Research has shown that one-third of patients admitted with facial trauma have concurrent concussion. This study aimed to investigate the burden and management of concussion in patients presenting with acute facial trauma, and to identify potential risk factors within this population. A retrospective observational study was conducted at a UK major trauma centre between 1 January 2019 and 1 February2020. One hundred randomly selected patients who attended the acute clinic responsible for managing facial trauma were identified. No parametric data were included. The Mann-Whitney test was used to detect differences for continuous data, the X2 test for categorical data. Clinical significance was defined as p < 0.05. Forty of 100 patients (40%) had evidence of concussion, of which only 4/40 (10%) had evidence that head injury advice had been given. There was no statistically significant difference between the non-concussed and concussed groups for age (p = 0.145), gender (p = 0.921), mechanism of injury (p = 0.158), or location of facial injury (p = 0.451). Clinical features of concussion were found in 40% of patients suffering from facial injury. Despite this, we found that head injury advice was rarely given. In addition, we identified no risk factors for concussion within this population, highlighting the need to screen all patients who present with facial injury. To improve the identification and management of concussion in these patients, future work should focus on the development of simple screening tools for use in clinic, and the signposting of patients to existing written and online concussion resources.

Cerebrospinal Fluid Diversion for Refractory Intracranial Hypertension in Traumatic Brain Injury: A Single Center Experience.

BACKGROUND: Diversion of cerebrospinal fluid (CSF) is a common neurosurgical procedure for control of intracranial pressure (ICP) in the acute phase after traumatic brain injury (TBI), where medical management is insufficient. CSF can be drained via an external ventricular drain (EVD) or, in selected patients, via a lumbar (external lumbar drain [ELD]) drainage catheter. Considerable variability exists in neurosurgical practice on their use. METHODS: A retrospective service evaluation was completed for patients receiving CSF diversion for ICP control after TBI, from April 2015 to August 2021. Patients were included whom fulfilled local criteria deeming them suitable for either ELD/EVD. Data were extracted from patient notes, including ICP values pre/postdrain insertion and safety data including infection or clinically/radiologically diagnosed tonsillar herniation. RESULTS: Forty-one patients were retrospectively identified (ELD = 30 and EVD = 11). All patients had parenchymal ICP monitoring. Both modalities affected statistically significant decreases in ICP, with relative reductions at 1, 6, and 24 hour pre/postdrainage (at 24-hour ELD P < 0.0001, EVD P < 0.01). Similar rates of ICP control failure, blockage and leak occurred in both groups. A greater proportion of patients with EVD were treated for CSF infection than with ELD. One event of clinical tonsillar herniation is reported, which may have been in part attributable to ELD overdrainage, but which did not result in adverse outcome. CONCLUSIONS: The data presented demonstrate that EVD and ELD can be successful in ICP control after TBI, with ELD limited to carefully selected patients with strict drainage protocols. The findings support prospective study to formally determine the relative risk-benefit profiles of CSF drainage modalities in TBI.

External Lumbar Drainage for Refractory Intracranial Hypertension in Traumatic Brain Injury: A Systematic Review.

Considerable variation exists in the clinical practice of cerebrospinal fluid diversion for medically refractory intracranial hypertension in patients with acute traumatic brain injury (TBI), which is achievable via lumbar or ventricular drainage. This systematic review sought to compile the available evidence for the efficacy and safety of the use of lumbar drains for intracranial pressure (ICP) control. A systematic review of the literature was performed with the search and data extraction performed by two reviewers independently in duplicate. Nine independent studies were identified, enrolling 230 patients, 159 with TBI. Efficacy for ICP control was observed across all studies, with immediate and sustained effect, reducing medical therapy requirements. Lumbar drainage with medical therapy appears effective when used alone and as an adjunct to ventricular drainage. Safety reporting varied in quality. Clinical or radiological incidents of cerebral herniation (with an unclear relationship to lumbar drainage) were observed in 14/230 patients resulting in one incident of morbidity without adverse patient outcome. The available data is generally poor in quality and volume, but supportive of the efficacy of lumbar drainage for ICP control. Few reports of adverse outcomes are suggestive of, but are insufficient to confirm, the safety of use in the appropriate patient and clinical setting. Further large prospective observational studies are required to generate sufficient support of an acceptable safety profile.

Concussion in the UK: a contemporary narrative review.

Concussion has been receiving an increasing amount of media exposure following several high-profile professional sports controversies and multimillion-dollar lawsuits. The potential life-changing sequalae of concussion and the rare, but devasting, second impact syndrome have also gained much attention. Despite this, our knowledge of the pathological processes involved is limited and often extrapolated from research into more severe brain injuries. As there is no objective diagnostic test for concussion. Relying on history and examination only, the diagnosis of concussion has become the rate-limiting step in widening research into the disease. Clinical study protocols therefore frequently exclude the most vulnerable groups of patients such as those with existing cognitive impairment, concurrent intoxication, mental health issues or learning difficulties. This up-to-date narrative review aims to summarize our current concussion knowledge and provides an insight into promising avenues for future research.

Concussion in Non-athletes: Assessment of Cognition and Symptomatology (CONTACTS) study protocol - an exploratory cohort study investigating the utility of sports concussion assessment tools and salivary microRNAs to diagnose concussion in NHS patients.

INTRODUCTION: Concussion is a complex pathophysiological process with a wide range of non-specific signs and symptoms. There are currently no objective diagnostic tests to identify concussion, and diagnosis relies solely on history and examination. Recent research has identified a unique panel of microRNAs (miRNAs) that distinguish between concussed and non-concussed rugby players. This study aims to assess the diagnostic utility of salivary miRNAs in concussion for a sample of UK National Health Service patients and whether well-established sports-related concussion (SRC) assessment tools may be translated into the emergency department (ED). METHODS AND ANALYSIS: Concussion in Non-athletes: Assessment of Cognition and Symptomatology is a single-centre, prospective, two-phase cohort study. The concussed cohort will consist of participants with maxillofacial trauma and concurrent concussion. The control cohort will consist of participants with isolated limb trauma and no evidence of concussion. Participants will be recruited in the ED and saliva samples will be taken to identify the presence of miRNAs. The SRC assessments being investigated include the Sports Concussion Assessment Test, Fifth Edition (SCAT5), the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and the ImPACT Quick. Follow-up will be at 24-48 hours in-hospital and remotely via telephone and email at 14 days and 6 months. ETHICS AND DISSEMINATION: Ethical approval was granted in February 2021 by the West Midlands Coventry & Warwickshire Research Ethics Committee (ref 20/WM/0299). The investigators intend to submit their study findings for publication in peer-reviewed journals and to disseminate study findings via presentation at academic meetings. The results will also form part of a doctorate thesis, registered at the University of Birmingham.

Cerebrospinal Fluid Diversion for Refractory Intracranial Hypertension: A United Kingdom and Ireland Survey on Practice Variation.

Introduction Diversion of cerebrospinal fluid (CSF) in a traumatic brain injury (TBI) is an established means for achieving control of intracranial pressure (ICP), aimed at improving intracranial homeostasis. The literature and anecdotal reports suggest a variation in practice between neurosurgical centres internationally, with current guidelines advocating ventricular drainage over lumbar drainage. We sought to establish the current neurosurgical practice in the United Kingdom regarding the methods of ICP control in TBI. Methods A 20-point survey was distributed electronically to British and Irish neurosurgeons after ratification by the Society of British Neurological Surgeons. Questions were directed at the clinician's opinion and experience of lumbar drain usage in patients with TBI: frequency, rationale, and experience of complications. Questions on lumbar drain usage in neurovascular patients were asked for practice comparison. Results Thirty-six responses from 21 neurosurgical centres were returned. Twenty-three per cent (23%) of responders reported using lumbar drains for refractory ICP in TBI patients: six units use lumbar drains and 15 do not. Three units showed partial usage, with mixed "yes/no" responses between consultants. Concerns of tonsillar herniation and familiarity with EVD were commonly given reasons against the usage of lumbar drains. Fifty-six per cent (56%) reported use in neurovascular patients. Conclusion This contemporary practice survey demonstrates mixed practice across the UK and within some centres. Responses and survey feedback demonstrate that the use of lumbar drains in TBI is a polarising topic. The variety of practice between and within neurosurgical units supports consideration of the prospective study of CSF diversion methods for control of refractory ICP in patients with TBI.

A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its Profile in Trauma: ADaPT.

INTRODUCTION: The improvements in short-term outcome after severe trauma achieved through early resuscitation and acute care can be offset over the following weeks by an acute systemic inflammatory response with immuneparesis leading to infection, multiorgan dysfunction/multiorgan failure (MOF) and death. Serum levels of the androgen precursor dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, steroids with immune-enhancing activity, are low after traumatic injury at a time when patients are catabolic and immunosuppressed. Addressing this deficit and restoring the DHEA(S) ratio to cortisol may provide a range of physiological benefits, including immune modulatory effects. OBJECTIVE: Our primary objective is to establish a dose suitable for DHEA supplementation in patients after acute trauma to raise circulating DHEA levels to at least 15 nmol/L. Secondary objectives are to assess if DHEA supplementation has any effect on neutrophil function, metabolic and cytokine profiles and which route of administration (oral vs sublingual) is more effective in restoring circulating levels of DHEA, DHEAS and downstream androgens. METHODS AND ANALYSIS: A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its profile in trauma, with a planned recruitment between April 2019 and July 2021, that will investigate DHEA supplementation and its effect on serum DHEA, DHEAS and downstream androgens in trauma. A maximum of 270 patients will receive sublingual or oral DHEA at 50, 100 or 200 mg daily over 3 days. Females aged ≥50 years with neck of femur fracture and male and female major trauma patients, aged 16-50 years with an injury severity score ≥16, will be recruited. ETHICS AND DISSEMINATION: This protocol was approved by the West Midlands - Coventry and Warwickshire Research Ethics Committee (Reference 18/WM/0102) on 8 June 2018. Results will be disseminated via peer-reviewed publications and presented at national and international conferences. TRIAL REGISTRATION: This trial is registered with the European Medicines Agency (EudraCT: 2016-004250-15) and ISRCTN (12961998). It has also been adopted on the National Institute of Health Research portfolio (CPMS ID:38158). TRIAL PROGRESSION: The study recruited its first patient on 2 April 2019 and held its first data monitoring committee on 8 November 2019. DHEA dosing has increased to 100 mg in both male cohorts and remains on 50 mg in across all female groups.

Comparison of outcomes of neurosurgical operations performed before and during the COVID-19 pandemic: a matched cohort study.

OBJECTIVE: To determine how the first wave of the COVID-19 pandemic affected outcomes for all operatively managed neurosurgical patients, not only those positive for SARS-CoV-2. DESIGN: Matched cohort (pairwise method). SETTING: A single tertiary neurosurgical referral centre at a large UK Major Trauma Centre. PARTICIPANTS: During the first COVID-19 wave, 231 neurosurgical cases were performed. These cases were matched to cases from 2019. Cases were matched for age (±10 years), primary pathology and surgical procedure. Cases were excluded from analysis if either the age could not be matched to within 10 years, or the primary pathology or procedure was too unique. After exclusions, 191 cases were included in final analysis. OUTCOME MEASURES: Primary outcomes were 30-day mortality and postoperative pulmonary complications. Secondary outcomes included Glasgow Outcome Score (GOS) on discharge, length of stay (LoS), operative and anaesthetic times and grade of primary surgeon. An exploratory outcome was the SARS-CoV-2 status of patients. RESULTS: There was no significant difference between the pandemic and matched cohorts in 30-day mortality, pulmonary complications, discharge GOS, LoS, operative or anaesthetic times. There was a significant difference in the variation of grade of primary surgeon. Only 2.2% (n=5) of patients had a SARS-CoV-2 positive swab. CONCLUSION: During the first UK wave of the COVID-19 pandemic, the mortality, morbidity and functional outcomes of operatively managed neurosurgical patients at University Hospitals Birmingham were not significantly affected compared with normal practice. The grade of primary surgeon was significantly more senior and adds to the growing body of evidence that demonstrates how the pandemic has negatively impacted UK surgical training. Mixing COVID-19 positive, unknown and negative cases did not significantly impact on outcomes and indicates that further research is required to support the implementation of evidence-based surgical pathways, such as COVID-light sites, throughout the next stage of the pandemic.

Depiction of personal protective equipment in popular war films.

Background. Personal protective equipment (PPE) is worn by military personnel to protect from combat trauma. War films may not represent PPE accurately, even when considered realistic. There is a risk that the subtle influence of films may subvert the understanding of PPE amongst military personnel and civilians. Methods. An observational study compared the depiction of PPE within popular war films to real-life. Films were included if they depicted land-based warfare. Depiction of helmets, body armour, eye protection, gloves, combat boots and hearing protection was compared to benchmarks. Trends in PPE over time were analysed using linear regression. Results. There were 73 combat scenes viewed from 16 films. Combat boots were the most depicted (72 scenes; 99%); hearing protection was the least (two scenes; 3%). There were statistically significant differences in PPE adherence between real life and films for all items of PPE (p < 0.05), except for combat boots (p = 0.621). There were improvements over time for all PPE except for hearing protection. Conclusions. PPE adherence in modern war films is poor, but has improved over time. There is a hypothetical risk that this has a negative impact on perceptions by both civilians and military personnel.

Evaluation of nationwide referral pathways, investigation and treatment of suspected cauda equina syndrome in the United Kingdom.

Purpose: Cauda equina syndrome (CES) is a spinal emergency with clinical symptoms and signs that have low diagnostic accuracy. National guidelines in the United Kingdom (UK) state that all patients should undergo an MRI prior to referral to specialist spinal units and surgery should be performed at the earliest opportunity. We aimed to evaluate the current practice of investigating and treating suspected CES in the UK. Materials and Methods: A retrospective, multicentre observational study of the investigation and management of patients with suspected CES was conducted across the UK, including all patients referred to a spinal unit over 6 months between 1st October 2016 and 31st March 2017. Results: A total of 28 UK spinal units submitted data on 4441 referrals. Over half of referrals were made without any previous imaging (n = 2572, 57.9%). Of all referrals, 695 underwent surgical decompression (15.6%). The majority of referrals were made out-of-hours (n = 2229/3517, 63.4%). Patient location and pre-referral imaging were not associated with time intervals from symptom onset or presentation to decompression. Patients investigated outside of the spinal unit experienced longer time intervals from referral to undergoing the MRI scan. Conclusions: This is the largest known study of the investigation and management of suspected CES. We found that the majority of referrals were made without adequate investigations. Most patients were referred out-of-hours and many were transferred for an MRI without subsequently requiring surgery. Adherence to guidelines would reduce the number of referrals to spinal services by 72% and reduce the number of patient transfers by 79%.

Investigation into repetitive concussion in sport (RECOS): study protocol of a prospective, exploratory, observational cohort study.

INTRODUCTION: Sport-related concussion management remains a diagnostic dilemma to clinicians in all strata of care, coaching staff and players alike. The lack of objective diagnostic and prognostic biomarkers and over-reliance on subjective clinical assessments carries a significant health risk of undiagnosed concussive episodes and early return to play before full recovery increasing the risk of sustaining additional concussion, and leading to long-term sequelae and/or unfavourable outcome. OBJECTIVE: To identify a set of parameters (neuroimaging with neurophysiological, biological and neuropsychological tests) that may support pitch-side and outpatient clinical decision-making in order to objectively diagnose concussion, determine the severity of injury, guide a safe return to play and identify the potential predictors of the long-term sequelae of concussion. METHODS AND ANALYSIS: An exploratory, observational, prospective, cohort study recruiting between 2017 and 2020. The participants will have a baseline preseason screening (brain imaging, neuropsychological assessments, serum, urine and saliva sampling). If a screened player later suffers a concussion and/or multiple concussions then he/she will be assessed again with the same protocol within 72 hours, and their baseline data will be used as internal control as well as normative data. Inferential statistical analysis will be performed to determine correlations between biological, imaging techniques and neuropsychological assessments. ETHICS AND DISSEMINATION: This study was approved by the East of England-Essex Research Ethics Committee on 22 September 2017-REC 17/EE/0275; IRAS 216703. The results of this study will be presented at national and international conferences and submitted for publication in peer reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN16974791; Pre-results.

Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase.

The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.

Post-traumatic stress disorder in UK civilians with traumatic brain injury: an observational study of TBI clinic attendees to estimate PTSD prevalence and its relationship with radiological markers of brain injury severity.

OBJECTIVES: To estimate the prevalence of post-traumatic stress disorder (PTSD) in a large civilian population with traumatic brain injury (TBI), and to assess whether brain injury severity is correlated with PTSD symptoms. DESIGN: Observational, cross-sectional study. SETTING AND PARTICIPANTS: Outpatient clinic in a major UK trauma centre and secondary care hospital. Estimates of PTSD prevalence are based on 171 sampled individuals attending TBI clinic within an 18-month period. Analysis of the relationship between TBI severity and PTSD was performed on the subset of 127 patients for whom injury severity data were also available. METHODS: Civilian TBI clinic attendees completed validated self-report questionnaires assessing PTSD (PTSD Checklist Civilian Version (PCL-C)) and other psychiatric symptoms. From this, the prevalence of PTSD was estimated in our cohort. Postresuscitation Glasgow Coma Score and Marshall grade on CT brain scan were recorded as indicators of brain injury severity. A hierarchical regression explored whether TBI severity may predict PTSD scores. RESULTS: A high prevalence of PTSD was estimated (21% with PCL-C score >50). Higher Marshall grading displayed a slight negative correlation with PTSD symptoms. This statistically significant relationship persisted after confounding factors such as depression and postconcussion symptoms were controlled for. CONCLUSIONS: PTSD and TBI frequently coexist, share antecedents and overlap in their resultant symptoms. This complexity has given rise to conflicting hypotheses about relationships between the two. This research reveals that PTSD is common in civilians with TBI (adding to evidence drawn from military populations). The analysis indicated that more severe brain injury may exert a slight protective influence against the development of PTSD-potentially by disrupting implicit access to traumatic memories, or via overlapping neuropsychiatric symptoms that impede diagnosis. The association suggests that further research is warranted to explore the reuse of routine clinical and neuroimaging data-investigating its potential to predict risk of psychiatric morbidity.

Post-traumatic stress disorder and self-reported outcomes after traumatic brain injury in victims of assault.

INTRODUCTION: Assault is the third most common cause of traumatic brain injury (TBI), after falls and road traffic collisions. TBI can lead to multiple long-term physical, cognitive and emotional sequelae, including post-traumatic stress disorder (PTSD). Intentional violence may further compound the psychological trauma of the event, in a way that conventional outcome measures, like the Glasgow Outcome Scale (GOS), fail to capture. This study aims to examine the influence of assault on self-reported outcomes, including quality of life and symptoms of PTSD. METHODS: Questionnaire were completed by 256 patients attending a TBI clinic, including Quality of Life after Brain Injury (QOLIBRI) and PTSD checklist (PCL-C). Medical records provided demographics, clinical data and aetiology of injury. Subjective outcomes were compared between assault and other causes. RESULTS: Of 202 patients analysed, 21% sustained TBI from assault. There was no difference in severity of injuries between assault and non-assault groups. No relationship was found between self-reported outcomes and TBI severity or GOS. The assault group scored worse in all self-reported questionnaires, with statistically significant differences for measures of PTSD and post-concussion symptoms. However, using threshold scores, the prevalence of PTSD in assaulted patients was not higher than non-assault. After adjusting for age, ethnicity and the presence of extra-cranial trauma, assault did not have a significant effect on questionnaire scores. Exploratory analysis showed that assault and road traffic accidents were associated with significantly worse outcomes compared to falls. CONCLUSION: Quality of life is significantly related to functional and psychological outcomes after TBI. Assaulted patients suffer from worse self-reported outcomes than other patients, but these differences were insignificant when adjusted for demographic factors. Intentionality behind the traumatic event is likely more important than cause alone. Differences in quality of life and other self-reported outcomes are not reflected by the Glasgow Outcome Scale. This information is useful in arranging earlier and targeted review and support.

Study of Concussion in Rugby Union through MicroRNAs (SCRUM): a study protocol of a prospective, observational cohort study.

INTRODUCTION: The diagnosis of mild traumatic brain injury or sports-related concussion is a challenge for all clinicians, players, coaches and parents involved in contact sports. Currently, there is no validated objective biomarker available to assess the presence or severity of concussion in sport, and so it is necessary to rely on subjective measures like self-reporting of symptoms which depend on the cooperation of the athlete. There is a significant health risk associated with repetitive injury if the diagnosis is missed, and so there is great value in an objective biomarker to assist diagnostic and prognostic decisions. OBJECTIVE: To establish a panel of non-invasive MicroRNA biomarkers in urine and saliva for the rapid diagnosis of sports-related concussion and investigate the kinetics and clinical utility of these biomarkers in assisting diagnostic, prognostic and return-to-play decisions. METHODS AND ANALYSIS: Observational, prospective, multicentre cohort study recruiting between the 2017-2018 and 2018-2019 Rugby Union seasons. Professional rugby players in the two highest tiers of senior professional domestic rugby competition in England will be recruited prospectively to the study. During the season, three groups will be identified: athletes entering the World Rugby Head Injury Assessment (HIA) protocol, uninjured control athletes and control athletes with musculoskeletal injuries. Saliva and urine will be collected from these athletes at multiple timepoints, coinciding with key times in the HIA protocol and return-to-play process. ETHICS AND DISSEMINATION: Ethics approval has been obtained. The compiled and analysed results will be presented at national and international conferences concerning the care of patients with traumatic brain injury. Results will also be submitted for peer review and publication in the subject journals/literature.

Author Correction: Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Non-battle injury among repatriated UK armed forces since cessation of combat operations: a prospective observational study.

AIM: To describe the mechanisms, burden of injury, inpatient management and rehabilitation requirements of wounded military personnel at the UK Role 4 (R4) facility within the first 12 months following cessation of combat operations in Afghanistan. METHODS: All aeromedical evacuations were recorded prospectively between October 2014 and October 2015. Demographic, logistical and clinical data were derived manually from referring medical unit and patient movement requests in addition to host nation and R4 medical records. RESULTS: Ninety-five patients were repatriated to R4 following traumatic injury: 98.9% (n=94) were male, and median age was 27 years (IQR 25-36 years). The most common mechanisms of injury (MOIs) were sports 26.3% (n=25), falls <2 m 11.6% (n=11) and road traffic collisions 9.8% (n=9). The most common anatomical regions of injury were isolated lower limb 24.1% (n=22), isolated hand 20.0% (n=19) and polytrauma 14.7% (n=14). Median Injury Severity Score was 4 (IQR 4-9), mean 8 (range 1-41). Eleven patients (11.6%) were discharged to rehabilitation units, of whom 7 (63.6%) required neurorehabilitation. CONCLUSION: Although service personnel sustain civilian-type injuries, the specific rehabilitation goals and shift in the acute rehabilitation requirements for military personnel must be considered in the absence of enduring combat operations. It is notable that permanent medical downgrading secondary to trauma still occurs outside of warfare. The colocation of civilian major trauma services and R4 has ensured a mutually beneficial partnership that contributes to institutional memory and improves the coordination of patient pathways. The importance of relevant resource allocation, training, support and logistical considerations remain, even during the current scale of military activity overseas.

Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury.

Traumatic brain injury (TBI) is set to become the leading cause of neurological disability across all age groups. Currently, no reliable biomarkers exist to help diagnose the severity of TBI to identify patients who are at risk of developing secondary injuries. Thus, the discovery of reliable biomarkers for the management of TBI would improve clinical interventions. Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins. Using the Proseek Multiplex Inflammation assay, we measured in patients that had suffered mild TBI (n = 10) or severe TBI (n = 10) with extra-cranial injury or extracranial injury only (EC) (n = 10), 92 inflammation-associated proteins in serum obtained: <1 hr (within 1-hour), 4-12 hr and 48-72 hr post injury. Changes were compared to healthy volunteers (HV). Our results identified CST5, AXIN1 and TRAIL as novel early biomarkers of TBI. CST5 identified patients with severe TBI from all other cohorts and importantly was able to do so within the first hour of injury. AXIN1 and TRAIL were able to discriminate between TBI and HV at <1 hr. We conclude that CST5, AXIN1 and TRAIL are worthy of further study in the context of a pre-hospital or pitch-side test to detect brain injury.

Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study.

BACKGROUND: Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS). METHODS AND FINDINGS: The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18-90 years, 75 males) with a mean injury severity score (ISS) of 24 (range 9-66), from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17-60 minutes). Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16BRIGHT CD62LDIM neutrophils (82.07 x 106/l ± 18.94 control versus 1,092 x 106/l ± 165 trauma, p < 0.0005) and CD14+HLA-DRlow/- monocytes (34.96 x 106/l ± 4.48 control versus 95.72 x 106/l ± 8.0 trauma, p < 0.05) and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT) cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function. CONCLUSIONS: Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune alterations consistent with both activation and suppression evident within 1 hour of injury. The relationship of these changes, especially in NKT cell numbers, to patient outcomes such as MODS warrants further investigation.

An adapted Clavien-Dindo scoring system in trauma as a clinically meaningful nonmortality endpoint.

BACKGROUND: There is no consensus on reporting nonmortality trauma complications in a graded manner. The Clavien-Dindo scale of complications was originally for elective surgery and requires adaptation to provide meaningful data for trauma patients. In particular, the original score does not account for those treated without surgery. We report an adapted Clavien-Dindo in trauma (ACDiT) scale and apply it to patients managed operatively and nonoperatively. METHODS: A combined prospective and retrospective international multicenter observational study was undertaken to apply the ACDiT scale to 484 trauma patients at three university teaching hospitals (Birmingham, England (n = 303); Houston, Texas (n = 113); and Glasgow, Scotland (n = 68)). These included both intensive care unit (ICU) and non-ICU-managed patients. The Clavien-Dindo scoring system was adapted for trauma patients based on consensus amongst an international collaboration of trauma specialists at these sites. Data included whether initial patients were managed operatively or nonoperatively. Complication grades were compared with hospital-free and ICU-free days as other outcome measures of patient morbidity. RESULTS: Two hundred seventeen (44.8%) of 484 patients experienced complications, of whom 61 (28.1%) of 217 died (grade V). The remainder consisted of grades I (n = 20), II (n = 60), III (n = 24), and IV (n = 52). There was a strong association between higher ACDiT grade category and lower number of hospital-free and ICU-free days (p < 0.01). Eighty-eight patients with complications did not require surgery, validating the score's usefulness in patients managed nonoperatively. CONCLUSION: The ACDiT scale can be used to grade the severity of posttrauma complications in patients managed both operatively and nonoperatively. It provides clinically meaningful data for morbidity and mortality meetings and other quality improvement exercises. LEVEL OF EVIDENCE: Prognostic, level IV.