Intravenous Versus Intraosseous Use of Tranexamic Acid in Patients With Traumatic Brain Injury.

INTRODUCTION: Tranexamic acid (TXA) is an antifibrinolytic drug that has been demonstrated to reduce head injury-related mortality when given within 2 h of injury in patients with traumatic brain injury and intracranial hemorrhage. It is usually administered via intravenous (IV) access, which can be difficult to obtain in prehospital and austere settings. Intraosseous (IO) access is fast and offers an alternative when IV access proves challenging; however, TXA administration via IO access has never been studied in humans. We sought to determine if the total drug exposure of TXA given in the prehospital setting in patients with moderate or severe brain injury differs based on route of administration. METHODS: We performed a retrospective analysis of prospectively collected data from the prehospital TXA for traumatic brain injury trial (NCT01990768). Participants who received TXA via IO administration were compared to those who received TXA via IV administration and stratified by renal function category based on the Kidney Disease Improving Global Outcomes criteria. The area under the plasma drug concentration-time curve (AUC) was calculated using the trapezoidal rule (Phoenix WinNonlin 8.3, Certara, Princeton NJ) to obtain total drug exposure. The inverse variance method was used to combine observations within strata and calculate mean differences. RESULTS: Of the 966 participants enrolled in the trial, 345 participants received a 2-g TXA prehospital bolus (11 IO, 334 IV); 312 participants received a 1-g TXA prehospital bolus followed by a 1-g TXA infusion in-hospital over 8 h (13 IO, 299 IV). After exclusion because of missing data and extreme estimated AUC, 233 IV and eight IO participants in the 2-g bolus arm and 152 IV and eight IO participants in the 1-g bolus 1-g infusion arm remained. Participants did not differ by age, sex, race, ethnicity, body mass index, serum creatinine, estimated glomerular filtration rate, or clot lysis at 30 min on thromboelastography. No difference in the mean AUCs were observed between IV and IO for either the 2-g bolus group (-2.6 µ g/mL/h [IO] compared to IV, 95% confidence interval: -28.4 to 23.3 µ g/mL/h) or the 1-g bolus/1-g infusion group (-13.0 µ g/mL/h [IO] compared to IV, 95% confidence interval: -236.2 to 210.3 µ g/mL/h). CONCLUSIONS: These preliminary data suggest that the administration of TXA via IO and IV routes may result in similar total drug exposure. Further studies incorporating larger numbers with clinical outcomes are needed to confirm this finding.

Clinician-Prioritized Measures to Use in a Remote Concussion Assessment: Delphi Study.

BACKGROUND: There is little guidance available, and no uniform assessment battery is used in either in-person or remote evaluations of people who are experiencing persistent physical symptoms post concussion. Selecting the most appropriate measures for both in-person and remote physical assessments is challenging because of the lack of expert consensus and guidance. OBJECTIVE: This study used expert consensus processes to identify clinical measures currently used to assess 5 physical domains affected by concussion (neurological examination, cervical spine, vestibular, oculomotor, or effort) and determine the feasibility of applying the identified measures virtually. METHODS: The Delphi approach was used. In the first round, experienced clinicians were surveyed regarding using measures in concussion assessment. In the second round, clinicians reviewed information regarding the psychometric properties of all measures identified in the first round by at least 15% (9/58) of participants. In the second round, experts rank-ordered the measures from most relevant to least relevant based on their clinical experience and documented psychometric properties. A working group of 4 expert clinicians then determined the feasibility of virtually administering the final set of measures. RESULTS: In total, 59 clinicians completed survey round 1 listing all measures they used to assess the physical domains affected by a concussion. The frequency counts of the 146 different measures identified were determined. Further, 33 clinicians completed the second-round survey and rank-ordered 22 measures that met the 15% cutoff criterion retained from round 1. Measures ranked first were coordination, range of motion, vestibular ocular motor screening, and smooth pursuits. These measures were feasible to administer virtually by the working group members; however, modifications for remote administration were recommended, such as adjusting the measurement method. CONCLUSIONS: Clinicians ranked assessment of coordination (finger-to-nose test and rapid alternating movement test), cervical spine range of motion, vestibular ocular motor screening, and smooth pursuits as the most relevant measures under their respective domains. Based on expert opinion, these clinical measures are considered feasible to administer for concussion physical examinations in the remote context, with modifications; however, the psychometric properties have yet to be explored. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/40446.

A Systematic Review of the Relationship Between Traumatic Brain Injury and Disruptions in Heart Rate Variability.

Autonomic nervous system dysfunction is increasingly recognized as a common sequela of traumatic brain injury (TBI). Heart rate variability (HRV) is a specific measure of autonomic nervous system functioning that can be used to measure beat-to-beat changes in heart rate following TBI. The objective of this systematic review was to determine the state of the literature on HRV dysfunction following TBI, assess the level of support for HRV dysfunction following TBI, and determine if HRV dysfunction predicts mortality and the severity and subsequent recovery of TBI symptoms. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two raters coded each article and provided quality ratings with discrepancies resolved by consensus. Eighty-nine papers met the inclusion criteria. Findings indicated that TBI of any severity is associated with decreased (i.e., worse) HRV; the severity of TBI appears to moderate the relationship between HRV and recovery; decreased HRV following TBI predicts mortality beyond age; HRV disturbances may persist beyond return-to-play and symptom resolution following mild TBI. Overall, current literature suggests HRV is decreased following TBI and may be a good indicator of physiological change and predictor of important outcomes including mortality and symptom improvement following TBI.

Neural response to monetary incentives in acquired adolescent depression after mild traumatic brain injury: Stage 2 Registered Report.

Depression is a common consequence of traumatic brain injury. Separately, spontaneous depression-arising without brain injury-has been linked to abnormal responses in motivational neural circuitry to the anticipation or receipt of rewards. It is unknown if post-injury and spontaneously occurring depression share similar phenotypic profiles. This issue is compounded by the fact that nearly all examinations of these psychiatric sequelae are post hoc: there are rarely any prospective assessments of mood and neural functioning before and after a brain injury. In this Stage 2 Registered Report, we used the Adolescent Brain Cognitive Development Consortium dataset to examine if a disruption in functional neural responses to rewards is present in patients with depression after a mild traumatic brain injury. Notably, this study provides an unparalleled opportunity to examine the trajectory of neuropsychiatric symptoms longitudinally within-subjects. This allowed us to isolate mild traumatic brain injury-specific variance independent from pre-existing functioning. Here, we focus on a case-control comparison between 43 youth who experienced a mild traumatic brain injury between MRI visits, and 43 well-matched controls. Contrary to pre-registered predictions (https://osf.io/h5uba/), there was no statistically credible increase in depression in mild traumatic brain injury cases relative to controls. Mild traumatic brain injury was associated with subtle changes in motivational neural circuit recruitment during the anticipation of incentives on the Monetary Incentive Delay paradigm. Specifically, changes in neural recruitment appeared to reflect a failure to deactivate 'task-negative' brain regions (ventromedial prefrontal cortex), alongside blunted recruitment of 'task-positive' regions (anterior cingulate, anterior insula and caudate), during the anticipation of reward and loss in adolescents following mild brain injuries. Critically, these changes in brain activity were not correlated with depressive symptoms at either visit or depression change scores before and after the brain injury. Increased time since injury was associated with a recovery of cognitive functioning-driven primarily by processing speed differences-but depression did not scale with time since injury. These cognitive changes were also uncorrelated with neural changes after mild traumatic brain injury. This report provides evidence that acquired depression may not be observed as commonly after a mild traumatic brain injury in late childhood and early adolescence, relative to findings in adult cases. Several reasons for these differing findings are considered, including sampling enrichment in retrospective cohort studies, under-reporting of depressive symptoms in parent-report data, and neuroprotective factors in childhood and adolescence.

Normative Neuroimaging Library: Designing a Comprehensive and Demographically Diverse Dataset of Healthy Controls to Support Traumatic Brain Injury Diagnostic and Therapeutic Development.

The past decade has seen impressive advances in neuroimaging, moving from qualitative to quantitative outputs. Available techniques now allow for the inference of microscopic changes occurring in white and gray matter, along with alterations in physiology and function. These existing and emerging techniques hold the potential of providing unprecedented capabilities in achieving a diagnosis and predicting outcomes for traumatic brain injury (TBI) and a variety of other neurological diseases. To see this promise move from the research lab into clinical care, an understanding is needed of what normal data look like for all age ranges, sex, and other demographic and socioeconomic categories. Clinicians can only use the results of imaging scans to support their decision-making if they know how the results for their patient compare with a normative standard. This potential for utilizing magnetic resonance imaging (MRI) in TBI diagnosis motivated the American College of Radiology and Cohen Veterans Bioscience to create a reference database of healthy individuals with neuroimaging, demographic data, and characterization of psychological functioning and neurocognitive data that will serve as a normative resource for clinicians and researchers for development of diagnostics and therapeutics for TBI and other brain disorders. The goal of this article is to introduce the large, well-curated Normative Neuroimaging Library (NNL) to the research community. NNL consists of data collected from ∼1900 healthy participants. The highlights of NNL are (1) data are collected across a diverse population, including civilians, veterans, and active-duty service members with an age range (18-64 years) not well represented in existing datasets; (2) comprehensive structural and functional neuroimaging acquisition with state-of-the-art sequences (including structural, diffusion, and functional MRI; raw scanner data are preserved, allowing higher quality data to be derived in the future; standardized imaging acquisition protocols across sites reflect sequences and parameters often recommended for use with various neurological and psychiatric conditions, including TBI, post-traumatic stress disorder, stroke, neurodegenerative disorders, and neoplastic disease); and (3) the collection of comprehensive demographic details, medical history, and a broad structured clinical assessment, including cognition and psychological scales, relevant to multiple neurological conditions with functional sequelae. Thus, NNL provides a demographically diverse population of healthy individuals who can serve as a comparison group for brain injury study and clinical samples, providing a strong foundation for precision medicine. Use cases include the creation of imaging-derived phenotypes (IDPs), derivation of reference ranges of imaging measures, and use of IDPs as training samples for artificial intelligence-based biomarker development and for normative modeling to help identify injury-induced changes as outliers for precision diagnosis and targeted therapeutic development. On its release, NNL is poised to support the use of advanced imaging in clinician decision support tools, the validation of imaging biomarkers, and the investigation of brain-behavior anomalies, moving the field toward precision medicine.

Mild Blast Exposure Dysregulates Metabolic Pathways and Correlation Networking as Evident from LC-MS-Based Plasma Profiling.

Blast-induced trauma is emerging as a serious threat due to its wide pathophysiology where not only the brain but also a spectrum of organs is being affected. In the present study, we aim to identify the plasma-based metabolic dysregulations along with the associated temporal changes at 5-6 h, day 1 and day 7 post-injury in a preclinical animal model for blast exposure, through liquid chromatography-mass spectrometry (LC-MS). Using significantly advanced metabolomic and statistical bioinformatic platforms, we were able to elucidate better and unravel the complex networks of blast-induced neurotrauma (BINT) and its interlinked systemic effects. Significant changes were evident at 5-6 h with maximal changes at day 1. Temporal analysis also depicted progressive changes which continued till day 7. Significant associations of metabolic markers belonging to the class of amino acids, energy-related molecules, lipids, vitamin, hormone, phenolic acid, keto and histidine derivatives, nucleic acid molecules, uremic toxins, and uronic acids were observed. Also, the present study is the first of its kind where comprehensive, detailed pathway dysregulations of amino acid metabolism and biosynthesis, perturbed nucleotides, lipid peroxidation, and nucleic acid damage followed by correlation networking and multiomics networking were explored on preclinical animal models exposed to mild blast trauma. In addition, markers for systemic changes (renal dysfunction) were also observed. Global pathway predictions of unannotated peaks also presented important insights into BINT pathophysiology. Conclusively, the present study depicts important findings that might help underpin the biological mechanisms of blast-induced brain or systemic trauma.

Neuroimmune and Neuroinflammation Response for Traumatic Brain Injury.

Traumatic brain injury (TBI) is one of the major diseases leading to mortality and disability, causing a serious disease burden on individuals' ordinary lives as well as socioeconomics. In primary injury, neuroimmune and neuroinflammation are both responsible for the TBI. Besides, extensive and sustained injury induced by neuroimmune and neuroinflammation also prolongs the course and worsens prognosis of TBI. Therefore, this review aims to explore the role of neuroimmune, neuroinflammation and factors associated them in TBI as well as the therapies for TBI. Thus, we conducted by searching PubMed, Scopus, and Web of Science databases for articles published between 2010 and 2023. Keywords included "traumatic brain injury," "neuroimmune response," "neuroinflammation," "astrocytes," "microglia," and "NLRP3." Articles were selected based on relevance and quality of evidence. On this basis, we provide the cellular and molecular mechanisms of TBI-induced both neuroimmune and neuroinflammation response, as well as the different factors affecting them, are introduced based on physiology of TBI, which supply a clear overview in TBI-induced chain-reacting, for a better understanding of TBI and to offer more thoughts on the future therapies for TBI.

Chronic glial activation and behavioral alterations induced by acute/subacute pioglitazone treatment in a mouse model of traumatic brain injury.

Traumatic brain injury (TBI) is a disabling neurotraumatic condition and the leading cause of injury-related deaths and disability in the United States. Attenuation of neuroinflammation early after TBI is considered an important treatment target; however, while these inflammatory responses can induce secondary brain injury, they are also involved in the repair of the nervous system. Pioglitazone, which activates peroxisome proliferator-activated receptor gamma, has been shown to decrease inflammation acutely after TBI, but the long-term consequences of its use remain unknown. For this reason, the impacts of treatment with pioglitazone during the acute/subacute phase (30 min after injury and each subsequent 24 h for 5 days) after TBI were interrogated during the chronic phase (30- and 274-days post-injury (DPI)) in mice using the controlled cortical impact model of experimental TBI. Acute/subacute pioglitazone treatment after TBI results in long-term deleterious consequences, including disruption of tau homeostasis, chronic glial cell activation, neuronal pathology, and worsened injury severity particularly at 274 DPI, with male mice being more susceptible than female mice. Further, male pioglitazone-treated TBI mice exhibited increased dominant and offensive-like behavior while having a decreased non-social exploring behavior at 274 DPI. After TBI, both sexes exhibited glial activation at 30 DPI when treated with pioglitazone; however, while injury severity was increased in females it was not impacted in male mice. This work reveals that although pioglitazone has been shown to lead to attenuated TBI outcomes acutely, sex-based differences, timing and long-term consequences of treatment with glitazones must be considered and further studied prior to their clinical use for TBI therapy.

Novel application of latent class analysis to outcome assessment in traumatic brain injury with multiple injury subtypes or poly-TBI.

OBJECTIVE: The aim of this study was to stratify poly-traumatic brain injury (poly-TBI) patterns into discrete classes and to determine the association of these classes with mortality and withdrawal of life-sustaining treatment (WLST). METHODS: The authors performed a single-center retrospective review of their institutional trauma registry from 2018 to 2020 to identify patients with traumatic brain injury (TBI). Patients were included if they had moderate to severe TBI, defined as Glasgow Coma Scale score ≤ 12 and Abbreviated Injury Scale (AIS) head score ≥ 3, and the presence of more than one TBI subtype. TBI subtypes were defined as subdural hemorrhage (SDH), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and epidural hemorrhage (EDH). Latent class analysis was used to identify patient classes based on TBI subtypes and Rotterdam CT (RCT) scores. The authors then evaluated class membership in relation to categorical outcomes of in-hospital mortality and WLST by using Lanza et al.'s method. RESULTS: A total of 125 patients met inclusion criteria for poly-TBI. Latent class analysis yielded 3 poly-TBI classes: class 1-mixed; class 2-SDH/SAH; and class 3-EDH/SAH. Class 1-mixed had a higher likelihood of SDH, SAH, and ICH, and a lower likelihood of EDH. Class 2-SDH/SAH had a higher likelihood of only SDH and SAH. Class 3-EDH/SAH had a higher likelihood of EDH and SAH, and a lower likelihood of SDH and ICH. Class 1-mixed was relatively more likely to have an RCT score of 2. Class 2-SDH/SAH was relatively more likely to have an RCT score of 2, 3, and 4. Class 3-EDH/SAH had a higher likelihood of an RCT score of 3, 4, and 5. Class 1-mixed had significantly lower mortality (χ2 = 7.968; p = 0.005) and less WLST (χ2 = 4.618; p = 0.032) than Class 2-SDH/SAH. Class 2-SDH/SAH had the highest probability of death (0.612), followed by class 3-EDH/SAH (0.385) and class 1-mixed (0.277). Similarly, class 2-SDH/SAH had the highest WLST probability (0.498), followed by class 3-EDH/SAH (0.615) and class 1-mixed (0.238). CONCLUSIONS: Distinct poly-TBI classes were associated with increased in-hospital mortality and WLST. Further research with larger datasets will allow for more comprehensive poly-TBI class definitions and outcomes analysis.

Probiotics in Traumatic Brain Injury: New Insights into Mechanisms and Future Perspectives.

Traumatic brain injury (TBI) is a serious global public health issue, recognized as a chronic and progressive disease that can affect multiple organs, including the gastrointestinal (GI) tract. Research shows that there is a specific link between the GI tract and the central nervous system, termed the gut-brain axis, which consists of bidirectional exchange between these two. Several preclinical and clinical studies have demonstrated intestinal barrier dysfunction, intestinal inflammation and gut dysbiosis in patients with TBI. It is proven that probiotics can modulate the inflammatory process and modify gut microbiota. Numerous animal studies and human clinical trials have proven the effectiveness of selected bacterial strains as an adjuvant treatment in reducing inflammation, infection rates and time spent in intensive care of hospitalized patients suffering from brain injury. Thus, this review summarizes the current evidence regarding the beneficial effects of probiotic administration in patients suffering from TBI-related complications. This review will help identify novel therapeutic strategies in the future as probiotics have an extensive history of apparently safe use.

Effects of preinjury oral anticoagulants on the outcomes of traumatic brain injury in elderly patients: a systematic review and meta-analysis.

BACKGROUND: With the increasing cases of TBI cases in the elderly population taking anticoagulants for comorbidities, there is a need to better understand the safety of new anticoagulants and how to manage anticoagulated TBI patients. METHODS: A meta-analysis using a random-effect model was conducted to compare the effect of preinjury use of DOACs and VKAs on the outcomes following TBI. RESULTS: From 1951 studies, 49 studies with a total sample size of 15,180 met our inclusion criteria. Our meta-analysis showed no difference between preinjury use of DOACs or VKAs on ICH progression, in-hospital delayed ICH, delayed ICH at follow-up, and in-hospital mortality, but using DOACs was associated with a lower risk of immediate ICH (OR = 0.58; 95% CI = [0.42; 0.79]; p < 0.01) and neurosurgical interventions (OR = 0.59; 95% CI = [0.42; 0.82]; p < 0.01) compared to VKAs. Moreover, patients on DOACs experienced shorter length of stay in the hospital than those on VKAs (OR = -0.42; 95% CI = [-0.78; -0.07]; p = 0.02). CONCLUSION: We found a lower risk of immediate ICH and surgical interventions as well as a shorter hospital stay in patients receiving DOACs compared to VKA users before the head injury.

Prehospital care for traumatic brain injuries: A review of U.S. state emergency medical services protocols.

Traumatic brain injury (TBIs) necessitates a rapid and comprehensive medical response to minimize secondary brain injury and reduce mortality. Emergency medical services (EMS) clinicians serve a critical role in the management of prehospital TBI, responding during an initial phase of care with significant impact on patient outcomes. We used versions two and three of the Brain Trauma Foundation (BTF) Prehospital Guidelines for the Management of Traumatic Brain Injury and the NASEMSO National Model Clinical Guidelines to determine key elements for a TBI prehospital protocol and included common factors across sources such as recommendations concerning patient monitoring, hypoxia, hypotension, hyperventilation, cerebral herniation, airway management, hyperosmolar therapy, and transport destination. We then conducted a cross-sectional evaluation of publicly available statewide EMS clinical protocols in the US to determine the degree of alignment with national guidelines. We calculated descriptive statistics for each factor in the state protocols. Despite adoption of some evidence-based recommendations for a standard approach to the prehospital management of patients with TBI, we found significant variability in statewide EMS treatment protocols for management of severe TBI, especially in the recommended frequency of patient reassessment and for the management of suspected herniation. Most statewide protocols provided guidance regarding oxygenation, ventilation, and blood pressure management that aligned with evidence-based guidelines. While most protocols did address management of oxygenation and ventilation, one in four protocols had no specific guidance for managing hypoxia and only 31% of protocols recommended avoiding hyperventilation. For the management of suspected cerebral herniation, over half of statewide protocols recommended hyperventilation, whereas only 31% explicitly advised against hyperventilation regardless of TBI severity. Interestingly, 94% of protocols do not mention the use of hyperosmolar therapy for TBI patients, neither recommending use or avoidance of hyperosmolar therapy. In conclusion, we found inconsistent adoption of national recommendations in available statewide protocols for prehospital TBI management. We identified significant gaps and variation in statewide protocols regarding patient monitoring and reassessment, as well as in several key areas of severe TBI management.

Symptomatic Recovery from Concussion in Military Service Members with and Without Associated Bodily Injuries.

Research has found that service members (SMs) with mild traumatic brain injury (mTBI) and co-occurring bodily injuries endorse lower chronic postconcussive symptom severity than SMs with mTBI and no bodily injuries. Investigations were conducted with primarily post-9/11 war-era SMs with blast injuries. The current study explores these findings in a cohort of more heterogeneous and recently evaluated military SM. Possible reasons suggested for the earlier findings include SMs with bodily injuries report fewer postconcussive symptoms due to (1) focusing attention on extra-cranial injuries and associated pain; (2) receiving more interpersonal and medical support, lowering distress; (3) using analgesics such as morphine or opioids; or (4) experiencing delayed postconcussive symptoms. The current investigation evaluates each of these hypothesized reasons for the earlier findings and the generalizability of the findings to a more recent sample. Data were extracted from 165 SMs in a TBI repository at a U.S. military medical center. All participants reported a history of an mTBI, confirmed by a clinical interview to meet Veterans Affairs and Department of Defense criteria. Other bodily injuries received at the time of the mTBI were documented with the Abbreviated Injury Scale (AIS). Multiple regression models evaluated the ability of the four hypothesized mechanisms to predict postconcussive symptom severity, measured by the Neurobehavioral Symptom Inventory. SMs with bodily injuries (n = 48) reported nonsignificantly lower postconcussive symptoms than SMs with no bodily injuries (n = 117). The level of subjective pain was a determinant of postconcussive symptom severity among SMs with a history of mTBI, with or without associated bodily injuries. Social support was a weaker negative predictor of postconcussive symptoms among SMs with no associated bodily injuries.

The death of a neurotrauma trial lessons learned from the prematurely halted randomized evaluation of surgery in elderly with traumatic acute subdural hematoma (RESET-ASDH) trial.

Introduction: Acute subdural hematoma (ASDH) due to traumatic brain injury (TBI) constitutes an increasing global health problem, especially in the elderly population. Treatment decisions on surgical versus conservative management pose a neurosurgical dilemma. Large practice variation exists between countries, hospitals, and individual neurosurgeons, illustrating the presence of 'clinical equipoise'. The RESET-ASDH trial aimed to address this dilemma but was terminated prematurely due to insufficient patient recruitment. Research question: What factors may have contributed to the premature discontinuation of the RESET-ASDH trial? Materials and methods: The RESET-ASDH was a multicenter randomized controlled trial (RCT) comparing functional outcome at 1 year after early surgery or an initial conservative treatment in elderly patients (≥65 years) with a traumatic ASDH. Logs of registry data, medical-ethical approval timelines and COVID-19 related research documents were analyzed. Furthermore, non-structured interviews with involved clinical research personnel were conducted. Results: The concept of clinical equipoise was broadly misinterpreted by neurosurgeons as individual uncertainty, hampering patient recruitment. Also, the elderly target population complicated the inclusion process as elderly and their informal caregivers were hesitant to participate in our acute surgical trial. Moreover, the COVID-19 pandemic added additional hurdles like delayed medical-ethical approval, a decline in eligible patients and repeated trial halts during the peaks of the pandemic. Discussion and conclusion: The premature termination of the RESET-ASDH study may have been related to the trial's methodology and target population with an additional impact of COVID-19. Future acute neurosurgical trials in elderly may consider these challenges to prevent premature trial termination.

An observational cohort study of alcohol use and cognitive difficulties among post-9/11 veterans with and without TBI and PTSD.

BACKGROUND: Traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and alcohol use are highly prevalent among military Veterans and independently associated with cognitive difficulties; less is known about the combined effects. This study aimed to investigate the association between alcohol use patterns and cognitive diagnoses in Veterans with TBI and/or PTSD. METHODS: Using electronic health record data,193,663 Veterans were classified into three alcohol use trajectory groups (consistently low, initially high transitioning to low, initially moderate transitioning to high) based on self-reported Alcohol Use Disorders Identification Test-C (AUDIT-C) scores. Cox proportional hazards models were used to examine the association between alcohol use patterns, TBI, PTSD, and the risk of cognitive diagnosis, while adjusting for demographic factors and comorbidities. RESULTS: Veterans with initially high transitioning to low (HR = 1.21, 95 % CI: 1.11-1.31) and initially moderate transitioning to high (HR = 1.42, 95 % CI: 1.33-1.51) alcohol use patterns had a significantly greater risk of cognitive diagnosis compared to those with consistently low alcohol use when accounting for TBI, PTSD, and comorbidities. TBI (HR = 5.40, 95 % CI: 5.06-5.76) and PTSD (HR = 2.42, 95 % CI: 2.25-2.61) were also independently associated with an elevated risk of cognitive diagnosis. CONCLUSIONS: Findings suggest that Higher levels of alcohol consumption, even if decreasing over time, may confer an increased risk of cognitive diagnosis for Veterans with TBI and/or PTSD. Long-term alcohol use patterns should be considered in clinical assessments and interventions to identify individuals at greater risk for experiencing cognitive difficulties.

Decompressive Craniectomy: From Ancient Practices to Modern Neurosurgery.

Decompressive craniectomy (DC) is a neurosurgical strategy that expels a parcel of the cranium to relieve pressure on a swollen or herniating brain. This review article explores the history of DC, from its ancient roots in trepanning to its contemporary applications. It then examines the mechanisms by which DC reduces intracranial pressure (ICP) and improves cerebral blood flow. The article highlights the efficacy of DC in treating patients with severe traumatic brain injury (TBI), stroke, and other conditions that cause increased ICP. However, it also acknowledges the potential complications of DC, such as infection and bleeding. The ethical considerations surrounding DC are explored in detail, particularly the challenging decision-making process for patients who are unable to give consent. A specific focus is given to the use of DC in pediatric patients, where the developing brain is especially vulnerable to pressure changes.

Incorporating intensity modulated total body irradiation into a Children's Oncology Group trial: Rationale, techniques, and safeguards.

Historically, total body irradiation (TBI) has been delivered using static, parallel opposed photon beams (2D-TBI). Recently, centers have increasingly used intensity-modulated radiation therapy (IMRT) techniques for TBI. Relative to 2D-TBI, IMRT can reduce doses to critical organs (i.e., lungs and kidneys) while delivering myeloablative doses to the rest of the body, so it may decrease the risk of toxicity while maintaining oncologic outcomes. Despite these potential benefits, delivering TBI using IMRT introduces new challenges in treatment planning and delivery. We describe the extensive experience with IMRT-based TBI at Stanford University and City of Hope Cancer Center. These groups, and others, have reported favorable clinical outcomes and have developed methods to optimize treatment planning and delivery. A critical next step is to evaluate the broader adoption of this approach. Therefore, IMRT-based TBI will be incorporated into a prospective, multi-institutional Children's Oncology Group study with careful procedures and safeguards in place.

Unveiling the performance of the prehospital Rapid Emergency Medicine Score (pREMS): How the predictive score impacts in-hospital outcomes in traumatic brain injury (TBI): A retrospective observational cohort study.

INTRODUCTION: This study aimed to evaluate the predictive accuracy of the prehospital rapid emergency medicine score (pREMS) for predicting the outcomes of hospitalized patients with traumatic brain injury (TBI) who died, were discharged, were admitted to the intensive care unit (ICU), or were admitted to the operating room (OR) within 72 h. METHODS: A retrospective cohort analysis was performed on a sample of 513 TBI patients admitted to the emergency department (ED) of Besat Hospital in 2023. Only patients of both sexes aged 18 years or older who were not pregnant and had adequate documentation of vital signs were included in the analysis. Patients who died during transport and patients who were transferred from other hospitals were excluded. The predictive power of the pREMS for each outcome was assessed by calculating the sensitivity and specificity curves and by analyzing the area under the receiver operating characteristic curve (AUROC). RESULTS: The mean pREMS scores for hospital discharge, death, ICU admission and OR admission were 11.97 ± 3.84, 6.32 ± 3.15, 8.24 ± 5.17 and 9.88 ± 2.02, respectively. pREMS accurately predicted hospital discharge and death (AOR = 1.62, P < 0.001) but was not a good predictor of ICU or OR admission (AOR = 1.085, P = 0.603). The AUROCs for the ability of the pREMS to predict outcomes in hospitalized TBI patients were 0.618 (optimal cutoff point = 7) for ICU admission and OR and 0.877 (optimal cutoff point = 9.5) for hospital discharge and death at 72 h. CONCLUSION: The results indicate that the pREMS, a new preclinical trauma score for traumatic brain injury, is a useful tool for prehospital risk stratification (RST) in TBI patients. The pREMS showed good discriminatory power for predicting in-hospital mortality within 72 h in patients with traumatic brain injury.

Early Tracheostomy versus Late Tracheostomy in Patients with Moderate-to-Severe Traumatic Brain Injury.

Objective The aim of this article was to study the impact of early versus late tracheostomy on clinical outcomes of moderate-to-severe traumatic brain injury (TBI). Materials and Methods A retrospective cross-sectional study was conducted in the Neurosurgery Department, Mayo Hospital, Lahore, in which a sample size of 50 cases was calculated over a period of 6 months from January 1, 2022, to June 30, 2022. The included cases were patients who suffered from moderate-to-severe TBI, isolated TBI, needed elective ventilation, required intensive care unit (ICU) admission during their hospital stay, and were between the ages of 18 and 65 years. All the rest were excluded. A structured proforma was used by the physician to collect data after the informed consent of the patient. The results were computed and analyzed statistically using Statistical Package for Social Sciences , version 26. Results The median age of patients was 40 (interquartile [IQ] range 34) years and were predominantly male (72%). The most common mode of injury was road traffic accidents (58%). The median Glasgow Coma Scale (GCS) score at arrival was 8 (IQ range 6) and the most common pupillary light reflex at presentation was bilaterally equally responsive to light (68%). Neurologic deficits were mostly absent or cannot be assessed on presentation (86%) and in 38% of the cases multiple findings were noted on computed tomography (CT) scan while among single findings seen on CT scan, subdural hematoma was the most common (22%). Multiple regression analysis was done through two separate models using age, gender, mode of injury, presenting GCS score, number of CT-scan findings, number of days after endotracheal intubation after which tracheostomy was done, and the timing of tracheostomy (early vs. late) as predictors, and a significant relationship was noted between the timing of tracheostomy (early vs. late) and GCS at discharge ( p = 0.001) as well as extended Glasgow Outcome Score (GOS) at discharge ( p = 0.013). Conclusion This study suggests that moderate-to-severe TBIs are most common in middle-aged males and mostly involve road traffic accidents. In most cases, multiple CT-scan findings are seen as compared with a single predominant finding. In such patients, early tracheostomy is superior to late tracheostomy as it results in significantly better GCS and GOS scores at discharge as well as a decreased duration of mechanical ventilation and ICU stay.