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Background and Objectives: Blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have recently been Food and Drug Administration approved as predictors of intracranial lesions on CT after mild traumatic brain injury (mTBI). However, most cases with mTBI are CT negative, and no biomarkers are approved to assist diagnosis in these individuals. In this study, we aimed to determine the optimal combination of blood biomarkers to assist mTBI diagnosis in otherwise healthy adults younger than 50 years presenting to an emergency department within 6 hours of injury. To further understand the utility of biomarkers, we assessed how biological sex, presence or absence of loss of consciousness and/or post-traumatic amnesia (LOC/PTA), and delayed presentation affected classification performance., Methods: Blood samples, symptom questionnaires, and cognitive tests were prospectively conducted for participants with mTBI recruited from The Alfred Hospital Level 1 Emergency & Trauma Center and uninjured controls. Follow-up testing was conducted at 7 days. Simoa quantified plasma GFAP, UCH-L1, tau, neurofilament light chain (NfL), interleukin (IL)-6, and IL-1β. Area under the receiver operating characteristic (AUC) analysis assessed classification accuracy for diagnosed mTBI, and logistic regression models identified optimal biomarker combinations., Results: Plasma IL-6 (AUC 0.91, 95% CI 0.86-0.96), GFAP (AUC 0.85, 95% CI 0.78-0.93), and UCH-L1 (AUC 0.79, 95% CI 0.70-0.88) best differentiated mTBI (n = 74) from controls (n = 44) acutely (<6 hours), with NfL (AUC 0.81, 95% CI 0.72-0.90) the only marker to have such utility subacutely (7 days). Biomarker performance was similar between sexes and for participants with and without LOC/PTA, with the exception at 7 days, where GFAP and IL-6 retained some utility in female participants (GFAP: AUC 0.71, 95% CI 0.55-0.88; IL-6: AUC 0.71, 95% CI 0.55-0.87) and in those with LOC/PTA (GFAP: AUC 0.73, 95% CI 0.59-0.86; IL-6: AUC 0.71, 95% CI 0.57-0.84). Acute IL-6 ( R 2 = 0.50, 95% CI 0.34-0.64) outperformed GFAP and UCH-L1 combined ( R 2 = 0.35, 95% CI 0.17-0.50), with the best acute model featuring GFAP and IL-6 ( R 2 = 0.54, 95% CI 0.34-0.68)., Discussion: These findings indicate that adding IL-6 to a panel of brain-specific proteins such as GFAP and UCH-L1 might assist in the acute diagnosis of mTBI in adults younger than 50 years. Multiple markers had high classification accuracy in participants without LOC/PTA. When compared with the best-performing acute markers, subacute measures of plasma NfL resulted in minimal reduction in classification accuracy. Future studies will investigate the optimal time frame over which plasma IL-6 might assist diagnostic decisions and how extracranial trauma affects utility., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The diagnosis of mild traumatic brain injury (mTBI) and early identification of patients who have persistent symptoms remains challenging. Symptoms are variably reported, and tests for cognitive impairment require specific expertise. The aim of this study was to assess the ability of plasma micro-ribonucleic acid (miRNA) biomarkers to distinguish between patients with mTBI and healthy controls. A secondary aim was to assess whether miRNA biomarker levels on the day of injury could predict persistent symptoms on day 7. Injured patients presented to an adult, tertiary referral hospital emergency department and were diagnosed with isolated mTBI (n = 75). Venous blood samples were collected within 6 h of injury. Symptom severity was assessed using the Rivermead Post-Concussion Symptom Questionnaire (RPQ) on the day of injury and at 7 days post-injury. The comparator group (n = 44) were healthy controls without any injury, who had bloods sampled and symptom severity assessed at the same time-point. Patients after mTBI reported higher symptom severity and had worse cognitive performance than the control group. Plasma miR423-3p levels were significantly higher among mTBI patients acutely post-injury compared to healthy controls and provided moderate discriminative ability (AUROC 0.67; 95 %CI: 0.57-0.77). None of the assessed miRNA biomarkers predicted persistent symptoms at 7 days. Plasma miR423-3p levels measured within 6 h of injury can discriminate for mTBI compared to healthy controls, with potential utility for screening after head injury or as an adjunct to the diagnosis of mTBI. Acute plasma miRNA levels did not predict patients who reported persistent symptoms at 7 days., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed., Objective: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion., Methods: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression., Results: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations., Conclusion: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Abstract Best practice guidelines have advanced severe traumatic brain injury (TBI) care; however, there is little that currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the S eattle I nternational severe traumatic B rain I njury C onsensus C onference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, and acceptability of neurological outcomes, as well as putative means of improving decisions that might limit care. A total of 97.6% of the 42 SIBICC panelists completed the survey. Responses to most questions were highly variable. Overall, panelists reported infrequent use of prognostic calculators, and observed variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a "nihilism guard." More than 50% of panelists felt that if it was certain to be permanent, a vegetative state or lower severe disability would justify a withdrawal of care decision, whereas 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, on average a 64-69% chance of a poor outcome was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes that might prompt consideration of care withdrawal; however, imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care-limiting decisions.

Background: The aim of this study was to test whether participation in an alcohol risk reduction program known as Prevent Alcohol and Risk-Related Trauma in Youth (P.A.R.T.Y.) is effective in reducing the prevalence of risky drinking at 12 months' post-intervention in a sample of Royal Australian Navy (RAN) trainees., Methods: A non-blinded randomized controlled trial of 952 RAN trainees comparing two forms of P.A.R.T.Y. plus RAN annual alcohol and other drug awareness training with annual alcohol and other drugs awareness training only (Control). Participants were screened at baseline and at 12-month follow-up using the Alcohol Use Disorders Identification Test (AUDIT). Participants were randomized to one of three arms: (1) in-hospital P.A.R.T.Y program, (2) on-base P.A.R.T.Y. program, or (3) control.The primary outcome measure was the percentage of participants reporting an AUDIT score of 8 or above at 12 months in each group. A secondary outcome considered was reports of alcohol-related incidents in the 12-month follow-up., Results: There was no difference in the risk of reporting an AUDIT score of 8 or above in either the in-hospital (Relative Risk (RR) 0.96, 95% CI: 0.75-1.23; P = .75) or on-base (RR 1.11, 95% CI: 0.89-1.369; P = 0.35) intervention groups, compared to the control group. Compared to the on-base group, there was no difference in the risk of reporting an AUDIT score of 8 or above in the in-hospital group (RR 1.16, 95% CI: 0.90-1.48; P = .24). The rate of reporting an alcohol-related incident was not different for the in-hospital (Hazard Ratio (HR) 0.60, 95% CI: 0.27-1.33; P = .21) or on-base (HR 0.50, 95% CI: 0.21-1.16; P = .11) intervention groups when compared to the control group., Conclusion: Participation in either an on-base or an in-hospital P.A.R.T.Y. program did not affect the proportion of naval trainee participants screening positive for risky drinking on the AUDIT., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To investigate beliefs and factors associated with padded headgear (HG) use in junior (<13 years) and youth (≥13 years) Australian football., Design: Online survey., Setting: Junior and youth athletes in Australia., Participants: Australian football players aged U8 to U18., Assessment of Variables: Survey questions regarding demographics, HG use, concussion history, beliefs about HG, and risk-taking propensity., Main Outcome Measures: Rates of padded HG use, and beliefs associated with HG use., Results: A total of 735 players (including 190, 25.9% female) representing 206 clubs participated. Headgear was worn by 315 players (42.9%; 95% CI: 39.3-46.4). Most (59.5%) HG users wore it for games only and wore it voluntarily (59.7%), as opposed to being mandated to do so. Junior players were more likely than youth players to agree to feeling safer ( P < 0.001) and being able to play harder while wearing HG ( P < 0.001). Median responses were "disagree" on preferring to risk an injury than wear HG, and on experienced players not needing to wear HG. Beliefs did not differ between males and females. Headgear use was associated with players belonging to a club where HG was mandated for other age groups (OR 16.10; 95% CI: 7.71-33.62, P < 0.001), youth players (OR 2.79; 95% CI: 1.93-3.93, P < 0.001), and female players (OR 1.57; 95% CI: 1.07-2.30, P = 0.019)., Conclusions: Club HG culture, older age and being female were prominent variables associated with voluntary HG use. Players reported believing that HG offers protection. The rate of voluntary and mandated HG use identified is at odds with current scientific evidence that does not support HG as effective concussion prevention., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Given the neurotrauma that soldiers might face during wars, a byproduct of such devastating neurosurgical conditions can be novel data, which can act as a catalyst for potentially paradigm-shifting research. We aimed to identify the impact of major U.S. military campaigns on military neurosurgery literature across defined time periods., Methods: A comprehensive Elsevier's Scopus database search was performed to capture all published and indexed studies from 1915 to 2021 relevant to military neurosurgery. A discrete set of validated informetric metadata parameters were extracted and analyzed using productivity analysis, citation analysis, keyword analysis, text mining, content analysis, and collaboration network mapping., Results: Our search yielded 2216 documents. Annual scientific production since 1915 grew at a compounded rate of 6.1% per year, with the most significant increases during U.S. military campaigns (coefficient = 42.9, P < 0.001) and following the introduction of the Department of Defense Trauma Registry in 2007 (coefficient = 114.5; P < 0.001). Each war had a direct influence on military neurosurgery literature growth (P < 0.05), with the most prominent following the Afghanistan war. The journals with the most publications on military neurosurgery were Military Medicine (n = 168) and Journal of Head Trauma. The topmost cited author was Hoge et al. (N = 2083), while the topmost cited country was the United States (N = 1098)., Conclusions: Since World War II, the military has contributed significant historical developments to neurosurgery, the most prominent being after the Iraq and Afghanistan wars and the introduction of the Department of Defense Trauma Registry., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Although it is often assumed that preinjury anticoagulant (AC) or antiplatelet (AP) use is associated with poorer outcomes among those with acute subdural hematoma (aSDH), previous studies have had varied results. This study examines the impact of preinjury AC and AP therapy on aSDH thickness, 30-day mortality, and extended Glasgow Outcome Scale at 6 months in elderly patients (aged ≥65)., Methods: A level 1 trauma center registry was interrogated to identify consecutive elderly patients who presented with moderate or severe traumatic brain injury (TBI) and associated traumatic aSDH between the first of January 2013 and the first of January 2018. Relevant demographic, clinical, and radiological data were retrieved from institutional medical records. The 3 primary outcome measures were aSDH thickness on initial computed tomography scan, 30-day mortality, and unfavorable outcome at 6 months (extended Glasgow Outcome Scale)., Results: One hundred thirty-two elderly patients were admitted with moderate or severe TBI and traumatic aSDH. The mean (±SD) age was 78.39 (±7.87) years, and a majority of patients (59.8%, n = 79) were male. There was a statistically significant difference in mean aSDH thickness, but there were no significant differences in 30-day mortality (P = 0.732) and unfavorable outcome between the AP, AC, combined AP and AC, and no antithrombotic exposure groups (P = 0.342)., Conclusions: Further studies with larger sample sizes are necessary to confirm these observations, but our findings do not support the preconceived notion in clinical practice that antithrombotic use is associated with poor outcomes in elderly patients with moderate or severe TBI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The advent of the COVID-19 pandemic with its extreme pressure on resources and intensive care beds has prompted many healthcare providers to consider more fully the potentially futile nature of some treatments and how resources might be better managed. This is especially relevant in the context of neurosurgery which is highly resource dependent in terms of technology, funding, and manpower and it may be difficult to balance fair, equitable and sustainable resource allocation, especially in circumstances where those healthcare resources become limited or completely exhausted. Indeed, it may be necessary to consider limiting the availability of certain neurosurgical services or perhaps reconsider the utility or otherwise of performing procedures that commit very restricted resources, such as intensive care beds, to patients who are arguably receiving limited long-term benefit. In these circumstances, the decision-making paradigm is challenging and there are several ethically disparate viewpoints that need to be reconciled. These include but are not limited to, Futility, Utilitarianism and the Rule of rescue.

Giovanni Andrea Dalla Croce was a Venetian physician who lived in the 16th century and was famous for his treatment of wounds, which was surprisingly modern. He was the military surgeon of the Venetian Republic's naval fleet. In 1537, he published the Chirurgiae universalis opus absolutum (The absolute work on universal surgery) in Latin, then expanded and translated into vernacular Italian and published in 1574 with the title Cirugia universale e perfetta di tutte le parti pertinenti all'ottimo chirurgo (Universal and perfect surgery of all the parts necessary for the optimal surgeon). This monumental work was a comprehensive handbook of surgery, medicine, and the treatment of many kinds of wounds with techniques to be used on the battlefield. It is also notable for the inclusion of illustrations of various weapons and projectiles, for the most comprehensive description and illustrations of surgical instruments at that time, and for the first illustrations of a surgeon performing trephination of the skull in an operating room. Dalla Croce also considered the writings of his surgical forebears in formulating his own ideas. Dalla Croce was a leader of traumatology, a universal surgeon who exemplified the erudite Renaissance man, and left a tremendous legacy to military surgery of the 16th century and beyond.

Penetrating traumatic brain injury (pTBI) affects civilian and military populations resulting in significant morbidity, mortality, and healthcare costs. No up-to-date and evidence-based guidelines exist to assist modern medical and surgical management of these complex injuries. A preliminary literature search revealed a need for updated guidelines, supported by the Brain Trauma Foundation. Methodologists experienced in TBI guidelines were recruited to support project development alongside two cochairs and a diverse steering committee. An expert multi-disciplinary workgroup was established and vetted to inform key clinical questions, to perform an evidence review and the development of recommendations relevant to pTBI. The methodological approach for the project was finalized. The development of up-to-date evidence- and consensus-based clinical care guidelines and algorithms for pTBI will provide critical guidance to care providers in the pre-hospital and emergent, medical, and surgical settings., Competing Interests: No competing financial interests exist., (© Gregory W.J. Hawryluk et al., 2022; Published by Mary Ann Liebert, Inc.)

The wide-spread use of an initial 'Glasgow Coma Scale (GCS) 8 or less' to define and dichotomise 'severe' from 'mild' or 'moderate' traumatic brain injury (TBI) is an out-dated research heuristic that has become an epidemiological convenience transfixing clinical care. Triaging based on GCS can delay the care of patients who have rapidly evolving injuries. Sole reliance on the initial GCS can therefore provide a false sense of security to caregivers and fail to provide timely care for patients presenting with GCS greater than 8. Nearly 50 years after the development of the GCS - and the resultant misplaced clinical and statistical definitions - TBI remains a heterogeneous entity, in which 'best practice' and 'prognoses' are poorly stratified by GCS alone. There is an urgent need for a paradigm shift towards more effective initial assessment of TBI., (© 2022 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Evidence from recent trials evaluating efficacy of antifibrinolytic agents in the context of traumatic brain injury may lead to changes in the management of patients with traumatic brain injury. Tranexamic acid (TXA) reduces the proteolytic action of plasmin on fibrin clots, resulting in an inhibition of fibrinolysis and stabilisation of established blood clots. There has been significant interest in use of the drug as a therapeutic agent in the context of severe haemorrhage; however, considerable controversies regarding its efficacy remain. A number of trials have demonstrated a small but significant decrease in mortality following its administration, but the results have been somewhat inconsistent and may not be generalisable. The results of the CRASH-3 trial were that there was no statistical difference in the number of traumatic brain injury related deaths (18.5% with TXA and 19.8% with placebo; relative risk [RR] 0·94; 95% confidence interval [CI] 0·86-1·02). Nonetheless, there was a subgroup of patients for whom TXA appeared to provide benefit, and this was in patients with mild and moderate injury (with a Glasgow Coma Score > 8). This is potentially a very important finding that may have huge potential implications; however, we believe it does not currently provide indisputable evidence to support the administration of TXA to all patients with TBI. Further work is required to better define the subset of patients who may benefit as well as to evaluate the long-term functional benefit in order to determine which types of severe traumatic brain injury patients would derive more benefits than harms from TXA., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Objectives: To assess whether padded headgear was associated with incidence of suspected sports-related concussion, non-sports-related concussion head injury, and injuries to other body regions in junior Australian football., Design: Prospective cohort injury surveillance., Methods: There were 400 junior players (42.5% female) enrolled across two seasons. Suspected sports-related concussion was defined by detection of observable signs on the field and medical assessment or missed match(es) due to suspected sports-related concussion. Non-sports-related concussion head injury and injuries to other body regions were defined as those that received medical assessment or resulted in a missed match., Results: There were 20 teams monitored over 258 matches. 204 players (2484 player hours) wore mandated headgear throughout the season and 196 (2246 player hours) did not. The incidence rate of suspected sports-related concussion was 3.17 (95% confidence interval: 3.04-3.30) per 1000 player-hours and no differences were observed between males and females (risk ratio 1.11; 95% confidence interval: 0.40-3.06). Headgear use was not associated with suspected sports-related concussion (risk ratio 1.09; 95% confidence interval: 0.41-2.97), non-sports-related concussion head injury (risk ratio 0.27; 95% confidence interval: 0.06-1.31), or injuries to other body regions (risk ratio 1.41; 95% confidence interval: 0.79-2.53)., Conclusions: Headgear use was not associated with reduced risk of suspected sports-related concussion, non-sports-related concussion head injury or injuries to other body regions. There was no difference in the rate of suspected sports-related concussion in female compared to male players, however, rates of non-sports-related concussion head injury and injuries to other body regions were higher in male players., (Copyright © 2021 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Video surveillance and detection of players with visible signs of concussion by experienced medical staff facilitates rapid on-field screening of suspected concussion in professional sports. This method, however has not been validated in community sports where video footage is unavailable. This study aimed to explore the utility of visible signs of concussion to identify players with decrements in performance on concussion screening measures. In this observational prospective cohort study, personnel with basic training observed live matches across a season (60 matches) of community male and female Australian football for signs of concussion outlined in the community-based Head Injury Assessment form (HIAf). Players identified to have positive signs of concussion (CoSign+) following an impact were compared with players without signs (CoSign-). Outcome measures, the Sport Concussion Assessment Tool (SCAT3) and Cogstate, were administered at baseline and post-match. CoSign+ ( n  = 22) and CoSign- ( n  = 61) groups were similar with respect to age, sex, education, baseline mood, and medical history. CoSign+ players exhibited worse orientation, concentration, and recall, and slower reaction time in attention and working memory tasks. Comparing individual change from baseline to post-match assessment revealed 100% (95% confidence interval [CI]: 84-100%) of CoSign+ players demonstrated clinically significant deficits on SCAT3 or Cogstate tasks, compared with 59% (95% CI: 46-71%) of CoSign- players. All CoSign+ players observed to have a blank/vacant look demonstrated clinically significant decline on the Standardized Assessment of Concussion (SAC). Detection of visible signs of concussion represents a rapid, real-time method for screening players suspected of concussion in community sports where video technology and medical personnel are rarely present. Consistent with community guidelines, it is recommended that all CoSign+ players be immediately removed from play for further concussion screening.

Micro riboneucleic acids (miRNAs) may be transcribed after brain injury and be detectable in plasma. This study aimed to assess the discriminative ability of seven miRNAs in plasma to differentiate between patients with mild traumatic brain injury (mTBI) and healthy controls. Changes in miRNA levels over 28 days were compared to changes in self-reported symptom profile. This was a prospective cohort study with longitudinal measurements of miRNA levels and symptom self-report. The Rivermead Post-Concussion Symptom Questionnaire (RPQ) was used to determine symptom severity. Mean normalised expression ratios (NER) of miRNAs at day 0 between mTBI and healthy controls were compared. An analysis of response profiles compared the response over time of miRNA species with RPQ symptom severity. miRNA levels of subjects who were defined to have "recovered" on Day 7 and 28 were compared to "non-recovered" subjects. There were 28 mTBI patients and 30 healthy controls included for analysis. Symptom severity was significantly higher on the day of injury among mTBI subjects (p < 0.001), and miRNA 32-5p levels were also higher (p = 0.009). Change of miRNA levels were similar to RPQ change at Day 7, but significantly different at Day 28. Differences were observed among miRNA levels of recovered subjects. This study demonstrated differences in miRNA levels among mTBI subjects compared to healthy controls and different miRNA levels among those who had recovered compared to those reporting symptoms. The change in profiles of miRNAs was different to symptom severity, suggesting that the two measures reflect different aspects of brain injury and recovery., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mr. Edmond Sorich is the director of Glia Diagnostics. Glia Diagnostics holds an exclusive IP licence agreement associated with miRNA listed in this manuscript. It did not contribute to any funding related to the study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Neurosurgeons commonly encounter futility of care decisions in their practice. Are these decisions being made with adequate consideration? What is the preparation of neurosurgical trainees for making these decisions? The advent of the COVID-19 pandemic with its extreme pressure on resources and, in particular, intensive care unit beds, has prompted many health care providers including neurosurgeons to consider more fully the potentially futile nature of some treatments and how we might better manage limited resources for the future. We review the concept of futility in neurosurgery and suggest potential solutions to the multiple challenges that arise., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: There has been immense interest and debate regarding the effectiveness of antibiotic treatment for chronic low back pain. Two randomised controlled trials have examined the efficacy of antibiotics for chronic low back pain with disc herniation and Modic changes, but have reported conflicting results. The aim of this double-blind, randomised, placebo-controlled trial is to determine the efficacy of antibiotic treatment in a broader patient subgroup of chronic low back pain with disc herniation and investigate whether the presence of Modic changes predicts response to antibiotic therapy., Methods: One hundred and seventy individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics; advertising in national, community and social media; and posting of flyers in community locations. They will be randomly allocated to receive either amoxicillin-clavulanate (500 mg/125 mg) twice per day for 90 days or placebo. The primary outcome measure of pain intensity will be assessed using the Low Back Pain Rating scale and a 100-mm visual analogue scale at 12 months. Secondary measures of self-reported low back disability and work absence and hindrance will also be examined, and an economic analysis will be conducted. Intention-to-treat analyses will be performed., Discussion: There is uncertainty about whether antibiotic treatment is effective for chronic low back pain and, if effective, which patient subgroup is most likely to respond. We will conduct a clinical trial to investigate the efficacy of antibiotics compared with placebo in individuals with chronic low back pain and a disc herniation. Our findings will provide high-quality evidence to assist in answering these questions., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12615000958583 . Registered on 11 September 2015., (© 2021. The Author(s).)

Objective: The aim of this manuscript is to compare characteristics, management, and outcomes of patients with severe Traumatic Brain Injury (TBI) between Australia, the United Kingdom (UK) and Europe., Methods: We enrolled patients with severe TBI in Victoria, Australia (OzENTER-TBI), in the UK and Europe (CENTER-TBI) from 2015 to 2017. Main outcome measures were mortality and unfavourable outcome (Glasgow Outcome Scale Extended <5) 6 months after injury. Expected outcomes were compared according to the IMPACT-CT prognostic model, with observed to expected (O/E) ratios and 95% confidence intervals., Results: We included 107 patients from Australia, 171 from UK, and 596 from Europe. Compared to the UK and Europe, patients in Australia were younger (median 32 vs 44 vs 44 years), a larger proportion had secondary brain insults including hypotension (30% vs 17% vs 21%) and a larger proportion received ICP monitoring (75% vs 74% vs 58%). Hospital length of stay was shorter in Australia than in the UK (median: 17 vs 23 vs 16 days), and a higher proportion of patients were discharged to a rehabilitation unit in Australia than in the UK and Europe (64% vs 26% vs 28%). Mortality overall was lower than expected (27% vs 35%, O/E ratio 0.77 [95% CI: 0.64 - 0.87]. O/E ratios were comparable between regions for mortality in Australia 0.86 [95% CI: 0.49-1.23] vs UK 0.82 [0.51-1.15] vs Europe 0.76 [0.60-0.87]). Unfavourable outcome rates overall were in line with historic expectations (O/E ratio 1.32 [0.96-1.68] vs 1.13 [0.84-1.42] vs 0.96 [0.85-1.09])., Conclusions: There are major differences in case-mix between Australia, UK, and Europe; Australian patients are younger and have a higher rate of secondary brain insults. Despite some differences in management and discharge policies, mortality was less than expected overall, and did not differ between regions. Functional outcomes were similar between regions, but worse than expected, emphasizing the need to improve treatment for patients with severe TBI., Competing Interests: Declaration of Competing Interest AIRM declares consulting fees from PresSura Neuro, Integra Life Sciences, and NeuroTrauma Sciences. DKM reports grants from the UK National Institute for Health Research, during the conduct of the study; grants, personal fees, and non-financial support from GlaxoSmithKline; personal fees from Neurotrauma Sciences, Lantmaanen AB, Pressura, and Pfizer, outside of the submitted work. ES reports personal fees from Springer, during the conduct of the study. DJC is an Australian NHMRC Practitioner Fellow and reports grants from the NHMRC and consulting fees to Monash University from PresSura Neuro. All other authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of all clinical, pathological, radiological, and surgical aspects of this important neoplasm to inform future management strategies., Methods: A systematic review and meta-analysis of MEDLINE, EMBASE, Cochrane, and Google Scholar databases adherent to PRISMA guidelines was conducted., Results: Of the 1145 articles initially retrieved, 24 studies encompassing 890 cases were included. The authors identified 3 retrospective cohort studies and 21 case series, but no controlled trials. Mean age at presentation was 46.7 ± 18.1 years with a male predominance (70.2%). Common sites of tumor origin were the lateral ventricle (44.5%) and fourth ventricle (43.1%). Cumulative postoperative mortality and morbidity rates were 3.4% and 24.3% respectively. Meta-analysis revealed that male sex (HR 3.15, 95% CI 1.39-7.14, p = 0.006) was associated with poorer 5-year overall mortality rates. All-cause mortality rates were similar when performing subgroup meta-analyses for age (HR 0.50, 95% CI 0.03-7.36, p = 0.61), smaller subependymoma size (HR 1.51, 95% CI 0.78-2.92, p = 0.22), gross-total resection (HR 0.65, 95% CI 0.35-1.23, p = 0.18), and receipt of postoperative radiation therapy (HR 0.88, 95% CI 0.27-2.88, p = 0.84). Postoperative Karnofsky Performance Index scores improved by a mean difference of 1.62 ± 12.14 points (p = 0.42). The pooled overall 5-year survival rate was 89.2%, while the cumulative recurrence rate was 1.3% over a median follow-up ranging from 15.3 to 120.0 months. The pure subependymoma histopathological subtype was most prevalent (85.6%), followed by the mixed subependymoma-ependymoma tumor variant (13.7%)., Conclusions: Surgical extirpation without postoperative radiotherapy results in excellent postoperative survival and functional outcomes in the treatment of intracranial subependymomas. Aggressive tumor behavior should prompt histological reevaluation for a mixed subependymoma-ependymoma subtype. Further high-quality controlled trials are still required to investigate this rare tumor.

To investigate cerebral autoregulatory status in patients with severe traumatic brain injury (TBI), guidelines now suggest active manipulation of mean arterial pressure (MAP). There is a paucity of data, however, describing the effect on intracranial pressure (ICP) when MAP is raised. Consecutive patients with TBI requiring ICP monitoring were enrolled from November 2019 to April 2020. The MAP and ICP were recorded continuously, and clinical annotations were made whenever intravenous vasopressors were commenced or adjusted to defend cerebral perfusion pressure (CPP) targets. A significant change in MAP burden was defined as MAP >100min.mm Hg over 15 min. The primary outcome was the change in ICP burden over the same 15-min period. Bedside and clinical parameters were then compared between these groups. Twenty-eight patients were enrolled, providing 212 clinical events, of which 60 were deemed significant. Over the first 15 min, 65% were associated with a net negative ICP burden. A greater reduction in ICP burden was observed with events occurring in patients without a history of hypotension at scene ( p  = 0.016), after three days post-injury ( p  = 0.0018), and where the pressure-reactivity index (PRx) was <0.25 ( p  = 0.0005) or the ICP amplitude to CPP correlation coefficient (RAC) was <-0.10 ( p  = 0.0036) at the initiation of vasopressor changes. The ICP burden in the first 15 min was highly correlated with the next 15-min period. In patients with severe TBI requiring ICP monitoring, increasing MAP to pursue a CPP target was followed by a net negative ICP burden in approximately two-thirds of events. These data suggest a MAP challenge may be a useful adjunct in managing intracranial hypertension.

Introduction: Harmful or risky-single occasion drinking (RSOD) alcohol use in the military is a significant problem. However, most studies of interventions have focused on veterans, representing a missed opportunity for intervention with active military personnel. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework, the aim of this systematic review was to analyse and synthesise the evidence related to workplace-based interventions for reducing alcohol use in active-duty military personnel., Methods: Four electronic databases and reference lists of relevant articles were searched from database inception until 20 January 2020. This review focused on experimental and quasi-experimental studies of active-duty military personnel. Data extraction and methodological quality assessment were independently performed by two reviewers using a standardised checklist. A third reviewer was used to arbitrate the disputed studies for final selection., Results: The search yielded seven studies from an initial 1582 records identified. A range of interventions were used in these studies (four randomised controlled trials, two non-randomised trials and one before and after cohort study), including web-based approaches, telephone-delivered interventions and individual and group-based face-to-face interventions. Seven studies found decreased drinking, measured using a range of outcomes, following the intervention. However, this was not sustained in the longer term in any of the studies., Conclusions: The low methodological rigour of most studies limited the capacity to demonstrate the efficacy of the interventions studied. Given the importance of reducing harmful or RSOD use of alcohol in the military, future studies would benefit from improved methodological rigour including ensuring adequate study power, randomisation, selection of validated outcome measures, including measures other than consumption (eg, attitudinal measures), and longer-term follow-up. There is also a need to develop methods that ensure participant loss to follow-up is minimised., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Exposure to repeated concussive traumatic brain injury (TBI) and to blast-induced TBI has been associated with the potential development of the neurodegenerative condition known as chronic traumatic encephalopathy (CTE). CTE is characterized by the accumulation of hyperphosphorylated tau protein, with the resultant tau tangles thought to initiate the cognitive and behavioral manifestations that appear as the condition progresses. However, the mechanisms linking concussive and blast TBI with tau hyperphosphorylation are unknown. Here we show that single moderate TBI, repeated concussive TBI and blast-induced mild TBI all result in hyperphosphorylation of tau via a substance P mediated mechanism. Post-injury administration of a substance P, NK1 receptor antagonist attenuated the injury-induced phosphorylation of tau by modulating the activity of several key kinases including Akt, ERK1/2 and JNK, and was associated with improvement in neurological outcome. We also demonstrate that inhibition of the TRPV1 mechanoreceptor, which is linked to substance P release, attenuated injury-associated tau hyperphosphorylation, but only when it was administered prior to injury. Our results demonstrate that TBI-mediated stimulation of brain mechanoreceptors is associated with substance P release and consequent tau hyperphosphorylation, with administration of an NK1 receptor antagonist attenuating tau phosphorylation and associated neurological deficits. NK1 antagonists may thus represent a pharmacological approach to attenuate the potential development of CTE following concussive and blast TBI.

This study aimed to evaluate the utility of the 11-variable modified Frailty Index (mFI) in prognosticating elderly patients with traumatic acute subdural hematomas (aSDHs). A state-service level 1 trauma center registry was interrogated to investigate consecutive patients ≥65 years of age presenting with traumatic aSDH, with or without major extracranial injury, between January 2013 and December 2017. mFI on admission, demographics, and admission details, including Glasgow Coma Scale (GCS) and pupillary status and radiological findings, were retrospectively retrieved from institutional records. Clinical outcome data were retrieved from medical records and the Victorian State Trauma Registry (VSTR). Outcome measures were 1) 30-day mortality and 2) 6-month unfavorable outcome, defined by the Extended Glasgow Outcome Scale (GOS-E). Five hundred twenty-nine consecutive cases were identified from the registry. Demographic data included: 1) age (median; interquartile range) = 80.46; 74.17-85.89; 2) mFI (mean ± standard deviation) = 1.96 ± 1.42 of 11 variables. Four hundred sixteen cases (79%) had complete outcome data. As mFI increased from 0/11 variables to ≥5/11 variables (≥0.45), 30-day mortality risk increased from 17.72% to 39.29% ( p  = 0.023) and 6-month unfavorable outcome risk increased from 40.51% to 96.43% ( p  < 0.001). Multi-variate analysis showed that greater mFI score of ≥3/11 variables (≥0.27) suggested a significantly higher risk of 30-day mortality ( p  = 0.009) and unfavorable outcome ( p  < 0.001). We conclude that increasing frailty, as measured by the mFI, was associated with significantly higher risk of 30-day mortality and 6-month unfavorable outcome in elderly patients presenting with aSDH to a level 1 neurotrauma center. Assessment of mFI in elderly patients with aSDH may be a useful determinant of outcome for this rapidly growing population.

Objective: Cortical vision prostheses aim to restore visual percepts to those who have lost sight by delivering electrical stimulation to the visual cortex. These devices need to be implanted intracranially using subdural or intracortical microelectrodes, and should preferably dispense with the need of transcranial wiring. The risks of cortical tissue injury from mechanical trauma, material biocompatibility, heat generation, electrical stimulation and long-term immune responses need to be evaluated. In this paper, we investigate the biological response to a wireless cortical vision prosthesis (Gennaris array), by characterizing the histological changes that occur following chronic electrical stimulation., Approach: Ten arrays (7 active, 3 passive) were implanted in three sheep using a pneumatic insertor. Each device consisted of a wireless receiver and Application Specific Integrated Circuit encased in a ceramic box, and could deliver electrical stimulation through one of 43 electrodes., Main Results: Stimulation was delivered through seven of these devices for up to 3 months and each device was treated as independent for further analysis. Cumulatively, over 2700 h of stimulation were achieved without any observable adverse health effects. Histology showed that the devices and implantation procedure were well tolerated by the brain with a similar tissue response to the more common Utah arrays. However, voltage transients across the stimulating electrodes were not measured so exact charge injection could not be verified., Significance: This work represents one of the first long-term tests of a fully implantable cortical vision prosthesis. The results indicate that long-term stimulation through wireless arrays can be achieved without induction of widespread tissue damage.

Objective: To explore the potential utility of head acceleration event (HAE) measurements to augment identification of players for further concussion screening in non-helmeted contact sport., Design: Prospective observational pilot study., Participants: 210 (118 female) professional Australian football players in 2017 season., Methods: Players wore the X-Patch® accelerometer for one match each with data collected across 14 matches. Players with HAEs above thresholds associated with concussion, 95 g (males) or 85.5 g (females), were compared to players identified to have suspected concussion by club personnel during the inspected matches. Video review of matches was undertaken by a physician blinded to HAEs to identify players with concussive signs., Results: Among 26 players (50% female) with HAEs above threshold, two players were screened for concussion. Of the remaining 24 players, nine were not visible on video at the HAE time, six sustained verifiable head impacts, and nine sustained verifiable body impacts with no head impacts. Among 184 players with HAEs below threshold, five players were screened., Conclusion: Players were identified to have head impacts and suspected concussion in the absence of HAEs above threshold. Use of X-Patch® was not sufficiently reliable for identifying players for further concussion screening in professional Australian football. Video review of head impacts remains essential in concussion screening., Competing Interests: Declaration of competing interest The X2 Biosystems X-Patch© devices were purchased on a commercial basis, and no author has any financial interest in the product or distribution of the product., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place., Methods: Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting., Results: We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms., Conclusions: These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference.

Background: Exposure to head acceleration events (HAEs) has been associated with player sex, player position, and player experience in North American football, ice hockey, and lacrosse. Little is known of these factors in professional Australian football. Video analysis allows HAE verification and characterization of important determinants of injury., Purpose: To characterize verified HAEs in the nonhelmeted contact sport of professional Australian football and investigate the association of sex, player position, and player experience with HAE frequency and magnitude., Study Design: Descriptive epidemiology study., Methods: Professional Australian football players wore a nonhelmeted accelerometer for 1 match, with data collected across 14 matches. HAEs with peak linear accelerations (PLAs) ≥30 g were verified with match video. Verified HAEs were summarized by frequency and median PLA and compared between the sexes, player position, and player experience. Characterization of match-related situations of verified HAEs was conducted, and the head impact rate per skill execution was calculated., Results: 92 male and 118 female players were recruited during the 2017 season. Male players sustained more HAEs (median, 1; IQR, 0-2) than female players (median, 0; IQR, 0-1; P = .007) during a match. The maximum PLAs incurred during a match were significantly higher in male players (median, 61.8 g ; IQR, 40.5-87.1) compared with female players (median, 44.5 g ; IQR, 33.6-74.8; P = .032). Neither player position nor experience was associated with HAE frequency. Of all verified HAEs, 52% (n = 110) occurred when neither team had possession of the football, and 46% (n = 98) were caused by contact from another player attempting to gain possession of the football. A subset of HAEs (n = 12; 5.7%) resulted in players seeking medical aid and/or being removed from the match (median PLA, 58.8 g ; IQR, 34.0-89.0), with 2 (male) players diagnosed with concussion after direct head impacts and associated PLAs of 62 g and 75 g , respectively. In the setting of catching (marking) the football, female players exhibited twice the head impact rate (16 per 100 marking contests) than male players (8 per 100 marking contests)., Conclusion: Playing situations in which players have limited control of the football are a common cause of impacts. Male players sustained a greater exposure to HAEs compared with female players. Female players, however, sustained higher exposure to HAEs than male players during certain skill executions, possibly reflecting differences in skill development. These findings can therefore inform match and skill development in the emerging professional women's competition of Australian football.

Functional outcomes at 12 months were a secondary outcome of the randomized DECRA trial of early decompressive craniectomy for severe diffuse traumatic brain injury (TBI) and refractory intracranial hypertension. In the DECRA trial, patients were randomly allocated 1:1 to either early decompressive craniectomy or intensive medical therapies (standard care). We conducted planned secondary analyses of the DECRA trial outcomes at 6 and 12 months, including all 155 patients. We measured functional outcome using the Glasgow Outcome Scale-Extended (GOS-E). We used ordered logistic regression, and dichotomized the GOS-E using logistic regression, to assess outcomes in patients overall and in survivors. We adjusted analyses for injury severity using the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. At 12 months, the odds ratio (OR) for worse functional outcomes in the craniectomy group (OR 1.68; 95% confidence interval [CI]: 0.96-2.93; p  = 0.07) was no longer significant. Unfavorable functional outcomes after craniectomy were 11% higher (59% compared with 48%), but were not significantly different from standard care (OR 1.58; 95% CI: 0.84-2.99; p  = 0.16). Among survivors after craniectomy, there were fewer good (OR 0.33; 95% CI: 0.12-0.91; p  = 0.03) and more vegetative (OR 5.12; 95% CI: 1.04-25.2; p  = 0.04) outcomes. Similar outcomes in survivors were found at 6 months after injury. Vegetative (OR 5.85; 95% CI: 1.21-28.30; p  = 0.03) and severely disabled outcomes (OR 2.49; 95% CI: 1.21-5.11; p  = 0.01) were increased. Twelve months after severe diffuse TBI and early refractory intracranial hypertension, decompressive craniectomy did not improve outcomes and increased vegetative survivors.

Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients. Objectives: To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates. Methods: This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI. Functional status was assessed with Glasgow Outcome Scale Extended (GOSE) 6, 12, and 24 months after injury. Cohort subgroups were defined by admission to an ICU. Features associated with functional outcome were assessed from the ICU subgroup. Measurements and Main Results: The study included 540 older adults who had been hospitalized with severe TBI over the 10-year period; 428 (79%) patients died in hospital, and 456 (84%) died 6 months after injury. There were 277 patients who had not been admitted to an ICU; at 6 months, 268 (97%) had died, 8 (3%) were dependent (GOSE 2-4), and 1 (0.4%) was functionally independent (GOSE 5-8). There were 263 patients who had been admitted to an ICU; at 6 months, 188 (73%) had died, 39 (15%) were dependent, and 32 (12%) were functionally independent. These proportions did not change over longer follow-up. The only clinical features associated with a lower rate of functional independence were Injury Severity Score ≥25 (adjusted odds ratio, 0.24 [95% confidence interval, 0.09-0.67]; P  = 0.007) and older age groups ( P  = 0.017). Conclusions: Severe TBI in older adults is a condition with very high mortality, and few recover to functional independence.

Trauma/stroke centres optimise acute 24/7/365 surgical/critical care in high-income countries (HICs). Concepts from low-income and middle-income countries (LMICs) offer additional cost-effective healthcare strategies for limited-resource settings when combined with the trauma/stroke centre concept. Mass casualty centres (MCCs) integrate resources for both routine and emergency care-from prevention to acute care to rehabilitation. Integration of the various healthcare systems-governmental, non-governmental and military-is key to avoid both duplication and gaps. With input from LMIC and HIC personnel of various backgrounds-trauma and subspecialty surgery, nursing, information technology and telemedicine, and healthcare administration-creative solutions to the challenges of expanding care (both daily and disaster) are developed. MCCs are evolving initially in Chile and Pakistan. Technologies for cost-effective healthcare in LMICs include smartphone apps (enhance prehospital care) to electronic data collection and analysis (quality improvement) to telemedicine and drones/robots (support of remote regions and resource optimisation during both daily care and disasters) to resilient, mobile medical/surgical facilities (eg, battery-operated CT scanners). The co-ordination of personnel (within LMICs, and between LMICs and HICs) and the integration of cost-effective advanced technology are features of MCCs. Providing quality, cost-effective care 24/7/365 to the 5 billion who lack it presently makes MCCs an appealing means to achieve the healthcare-related United Nations Sustainable Development Goals for 2030., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Epidemiological studies suggest a relationship between posttraumatic stress disorder (PTSD) and dementia., Objective: This study assessed whether Alzheimer's disease (AD) imaging biomarkers were elevated in Vietnam veterans with PTSD., Methods: The study compared cognition, amyloid-β, tau, regional brain metabolism and volumes, and the effect of APOE in 83 veterans with and without PTSD defined by the Clinician-Administered PTSD Scale., Results: The PTSD group had significantly lower education, predicted premorbid IQ, total intracranial volume, and Montreal Cognitive Assessment score compared with the controls. There was no difference between the two groups in the imaging or genetic biomarkers for AD., Conclusion: Our findings do not support an association between AD pathology and PTSD of up to 50 years duration. Measures to assess cognitive reserve, a factor that may delay the onset of dementia, were lower in the PTSD group compared with the controls and this may account for the previously observed higher incidence of dementia with PTSD.

Paulus of Aegina (625-690 ad) was the last of the prolific Byzantine physicians. His works consolidated and extended the knowledge of his predecessors, with pioneering efforts to improve the surgical management of spinal injuries. In this article, we review the literature to present an overview of the remarkable evolution of spine surgery throughout classical antiquity. In particular, we discuss the contributions of Paulus to this corpus and explore his classic 7-book anthology, Epitomoe Medicae Libri Septem (Medical Compendium in Seven Books). In reviewing Paulus' legacy, we show the significant milestones in the early development of anatomic and functional knowledge of the spine., (Copyright © 2019 Elsevier Inc. All rights reserved.)

It has been well-documented recently that 5 billion people globally lack surgical care. Also well-documented is the need to improve mass casualty disaster response. Many of the United Nations (UN) Sustainable Development Goals (SDGs) for 2030-healthcare and economic milestones-require significant improvement in global surgical care, particularly in low-income and middle-income countries. Trauma/stroke centres evolved in high-income countries with evidence that 24/7/365 surgical and critical care markedly improved morbidity and mortality for trauma and stroke and for cardiovascular events, difficult childbirth, acute abdomen. Duplication of emergency services, especially civilian and military, often results in suboptimal, expensive care. By combining all healthcare resources within the ongoing healthcare system, more efficient care for both individual emergencies and mass casualty situations can be achieved. We describe progress in establishing mass casualty centres in Chile and Pakistan. In both locations, planning among the stakeholders (primarily civilian and military) indicates the feasibility of such integrated surgical and emergency care. We also review other programmes and initiatives to provide integrated mass casualty disaster response. Integrated mass casualty centres are a feasible means to improve both day-to-day surgical care and mass casualty disaster response. The humanitarian aspect of mass casualty disasters facilitates integration among stakeholders-from local healthcare systems to military resources to international healthcare organisations. The benefits of mass casualty centres-both healthcare and economic-can facilitate achieving the 2030 UN SDGs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based., Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations., Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination., Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.

Facial nerve identification and preservation is a critical step in the resection of vestibular schwannoma. The use of intraoperative neurostimulation to positively identify the facial nerve along its entire course is essential to prevent injury. To our knowledge, this is the first reported case of a bifid facial nerve with a dual origin at the brainstem, which we observed during resection of vestibular schwannoma via the translabyrinthine approach. Both roots were visualized to join as one facial nerve trunk outside the brainstem in the cisternal segment of the facial nerve, and both trunks demonstrated positive signal with neurostimulation. This case highlights an important anatomic variation and also the importance of correct identification of facial nerve anatomy during resection of vestibular schwannoma and other pathologies within the cerebellopontine angle., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Traumatic brain injury has been called the "signature injury" of the wars in Iraq and Afghanistan, and the management of severe and penetrating brain injury has evolved considerably based on the experiences of military neurosurgeons. Current guidelines recommend that decompressive hemicraniectomy be performed with large, frontotemporoparietal bone flaps, but practice patterns vary markedly. The following case is illustrative of potential clinical courses, complications, and efforts to salvage inadequately-sized decompressive craniectomies performed for combat-related severe and penetrating brain injury. The authors follow this with a review of the current literature pertaining to decompressive craniectomy, and finally provide their recommendations for some of the technical nuances of performing decompressive hemicraniectomy after severe or penetrating brain injury., (© Association of Military Surgeons of the United States 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Alcohol Use Disorders Identification Test (AUDIT) is widely used for monitoring harmful alcohol consumption among high-risk populations. A number of short versions of AUDIT have been developed for use in time-constrained settings. In military populations, a range of AUDIT variations have been used, but the optimal combination of AUDIT items has not been determined., Methods: A total of 952 participants (80% male), recruited as part of a wider study, completed the AUDIT-10. We systematically assessed all possible combinations of three or four AUDIT items and established AUDIT variations using the following statistics: Cronbach's alpha (internal consistency), variance explained (R 2 ) and Pearson's correlation coefficient (concurrent validity)., Results: Median AUDIT-10 score was 7 for males and 6 for females, and 380 (40%) participants were classified as having a score indicative of harmful or hazardous alcohol use (≥8) according to WHO classifications.A novel four-item AUDIT variation (3, 4, 8 and 9) performed consistently higher than established variations across statistical measures; it explained 85% of variance in AUDIT-10, had a Pearson's correlation of 0.92 and Cronbach's alpha was 0.63. The FAST, an established shortened AUDIT variant, together with several other four-item novel variants of AUDIT-10 performed similarly. The AUDIT-C performed consistently low on all measures, but with a satisfactory level of internal consistency (75%)., Conclusion: Shortened AUDIT variations may be suitable alternatives to the full AUDIT for screening hazardous alcohol consumption in military populations. Four-item AUDIT variations focused on short-term risky drinking and its consequences performed better than three item versions., Trial Registration Number: ACTRN12614001332617., Competing Interests: Declarations of competing interest: JW, BG, AB and JVR declare that they have no competing interests. PD has received an untied educational grant from Reckitt Benckinser and an investigator-driven grant from Gilead Sciences for work unrelated to this paper., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The nomenclature of the 12 cranial nerves as we know it today was developed over a series of anatomic findings by some of history's most famous anatomists from Galen to Von Soemmerring. In this paper, we review the literature to present an overview of the remarkable historical journey that brought our forefathers to trace the pathway of individual cranial nerves from origin to destination. In particular, we discuss the evolution of the naming of the cranial nerves and highlight relevant eponymous descriptions. We also include some poignant illustrations of cranial nerves by ancient anatomists that set the scene to their discoveries. In reviewing this legacy, we summarize the important product of centuries of discoveries and investigations and the limitations of cranial nerve classification systems., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Neurosurgical residents are finding it more difficult to obtain experience as the primary operator in aneurysm surgery. The present study aimed to replicate patient-derived cranial anatomy, pathology and human tissue properties relevant to cerebral aneurysm intervention through 3D printing and 3D print-driven casting techniques. The final simulator was designed to provide accurate simulation of a human head with a middle cerebral artery (MCA) aneurysm., Methods: This study utilized living human and cadaver-derived medical imaging data including CT angiography and MRI scans. Computer-aided design (CAD) models and pre-existing computational 3D models were also incorporated in the development of the simulator. The design was based on including anatomical components vital to the surgery of MCA aneurysms while focusing on reproducibility, adaptability and functionality of the simulator. Various methods of 3D printing were utilized for the direct development of anatomical replicas and moulds for casting components that optimized the bio-mimicry and mechanical properties of human tissues. Synthetic materials including various types of silicone and ballistics gelatin were cast in these moulds. A novel technique utilizing water-soluble wax and silicone was used to establish hollow patient-derived cerebrovascular models., Results: A patient-derived 3D aneurysm model was constructed for a MCA aneurysm. Multiple cerebral aneurysm models, patient-derived and CAD, were replicated as hollow high-fidelity models. The final assembled simulator integrated six anatomical components relevant to the treatment of cerebral aneurysms of the Circle of Willis in the left cerebral hemisphere. These included models of the cerebral vasculature, cranial nerves, brain, meninges, skull and skin. The cerebral circulation was modeled through the patient-derived vasculature within the brain model. Linear and volumetric measurements of specific physical modular components were repeated, averaged and compared to the original 3D meshes generated from the medical imaging data. Calculation of the concordance correlation coefficient (ρ c : 90.2%-99.0%) and percentage difference (≤0.4%) confirmed the accuracy of the models., Conclusions: A multi-disciplinary approach involving 3D printing and casting techniques was used to successfully construct a multi-component cerebral aneurysm surgery simulator. Further study is planned to demonstrate the educational value of the proposed simulator for neurosurgery residents.

Objectives: To assess the utility and functionality of the X-Patch ® as a measurement tool to study head impact exposure in Australian Football. Accuracy, precision, reliability and validity were examined., Designs: Laboratory tests and prospective observational study., Methods: Laboratory tests on X-Patch ® were undertaken using an instrumented Hybrid III head and neck and linear impactor. Differences between X-Patch ® and reference data were analysed. Australian Football players wore the X-Patch ® devices and games were video-recorded. Video recordings were analysed qualitatively for head impact events and these were correlated with X-Patch ® head acceleration events. Wearability of the X-Patch ® was assessed using the Comfort Rating Scale for Wearable Computers., Results: Laboratory head impacts, performed at multiple impact sites and velocities, identified significant correlations between headform-measured and device-measured kinematic parameters (p<0.05 for all). On average, the X-Patch ® -recorded peak linear acceleration (PLA) was 17% greater than the reference PLA, 28% less for peak rotational acceleration (PRA) and 101% greater for the Head Injury Criterion (HIC). For video analysis, 118 head acceleration events (HAE) were included with PLA ≥30g across 53 players. Video recordings of X-Patch ® -measured HAEs (PLA ≥30g) determined that 31.4% were direct head impacts, 9.3% were indirect impacts, 44.1% were unknown or unclear and 15.3% were neither direct nor indirect head impacts. The X-Patch ® system was deemed wearable by 95-100% of respondents., Conclusions: This study reinforces evidence that use of the current X-Patch ® devices should be limited to research only and in conjunction with video analysis., (Copyright © 2019 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Background: Two randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach., Methods: The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries., Results: The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval., Conclusions: In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.

Objective: The aim of the present review was to describe the evolution of the damage control concept in neurotrauma, including the surgical technique and medical postoperative care, from the lessons learned from civilian and military neurosurgeons who have applied the concept regularly in practice at military hospitals and civilian institutions in areas with limited resources., Methods: The present narrative review was based on the experience of a group of neurosurgeons who participated in the development of the concept from their practice working in military theaters and low-resources settings with an important burden of blunt and penetrating cranial neurotrauma., Results: Damage control surgery in neurotrauma has been described as a sequential therapeutic strategy that supports physiological restoration before anatomical repair in patients with critical injuries. The application of the concept has evolved since the early definitions in 1998. Current strategies have been supported by military neurosurgery experience, and the concept has been applied in civilian settings with limited resources., Conclusion: Damage control in neurotrauma is a therapeutic option for severe traumatic brain injury management in austere environments. To apply the concept while using an appropriate approach, lessons must be learned from experienced neurosurgeons who use this technique regularly., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Implantable neural stimulating and recording devices have the potential to restore capabilities such as vision or motor control to disabled patients, improving quality of life. Implants with a large number of stimulating electrodes typically utilize implanted batteries and/or subcutaneous wiring to deal with their high-power consumption and high data throughput needed to address all electrodes with low latency. The use of batteries places severe limitations on the implant's size, usable duty cycle, device longevity while subcutaneous wiring increases the risk of infection and mechanical damage due to device movement., Approach: To overcome these limitations, we have designed and implemented a system that supports up to 473 implanted stimulating microelectrodes, all wirelessly powered and individually controlled by micropower application specific integrated circuits (ASICs)., Main Results: Each ASIC controls 43 electrodes and draws 3.18 mW of power when stimulating through 24 channels. We measured the linearity of the digital-to-analog convertors (DACs) to be 0.21 LSB (integrated non-linearity) and the variability in timing of stimulation pulses across ASICs to be 172 ns., Significance: This work demonstrates the feasibility of a new low power ASIC designed to be implanted in the visual cortex of humans. The fully implantable device will greatly reduce the risks of infection and damage due to mechanical issues.

The Internet comprises a decentralized global system that serves humanity's collective effort to generate, process, and store data, most of which is handled by the rapidly expanding cloud. A stable, secure, real-time system may allow for interfacing the cloud with the human brain. One promising strategy for enabling such a system, denoted here as a "human brain/cloud interface" ("B/CI"), would be based on technologies referred to here as "neuralnanorobotics." Future neuralnanorobotics technologies are anticipated to facilitate accurate diagnoses and eventual cures for the ∼400 conditions that affect the human brain. Neuralnanorobotics may also enable a B/CI with controlled connectivity between neural activity and external data storage and processing, via the direct monitoring of the brain's ∼86 × 10 9 neurons and ∼2 × 10 14 synapses. Subsequent to navigating the human vasculature, three species of neuralnanorobots (endoneurobots, gliabots, and synaptobots) could traverse the blood-brain barrier (BBB), enter the brain parenchyma, ingress into individual human brain cells, and autoposition themselves at the axon initial segments of neurons (endoneurobots), within glial cells (gliabots), and in intimate proximity to synapses (synaptobots). They would then wirelessly transmit up to ∼6 × 10 16 bits per second of synaptically processed and encoded human-brain electrical information via auxiliary nanorobotic fiber optics (30 cm 3 ) with the capacity to handle up to 10 18 bits/sec and provide rapid data transfer to a cloud based supercomputer for real-time brain-state monitoring and data extraction. A neuralnanorobotically enabled human B/CI might serve as a personalized conduit, allowing persons to obtain direct, instantaneous access to virtually any facet of cumulative human knowledge. Other anticipated applications include myriad opportunities to improve education, intelligence, entertainment, traveling, and other interactive experiences. A specialized application might be the capacity to engage in fully immersive experiential/sensory experiences, including what is referred to here as "transparent shadowing" (TS). Through TS, individuals might experience episodic segments of the lives of other willing participants (locally or remote) to, hopefully, encourage and inspire improved understanding and tolerance among all members of the human family.