Age dictates brain functional connectivity and axonal integrity following repetitive mild traumatic brain injuries in mice.

Traumatic brain injuries (TBIs) present a major public health challenge, demanding an in-depth understanding of age-specific symptoms and risk factors. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following TBIs. Repetitive mild TBIs (rmTBIs) compound these issues, resulting in cumulative and long-term brain damage in the brain. In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI). Our hypothesis is that the effects of rmTBI are worsened in aged animals, with this group showing more pronounced alterations in brain connectivity and white matter structure. Utilizing the CHIMERA model, we conducted rmTBIs or sham (control) procedures on young (2.5-3 months old) and aged (22-month-old) male and female mice to model high risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposing effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean, radial, axial diffusivity, fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Neuroinflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in injured aged animals compared to sham aged. These findings offer insight into the interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBIs.

QEEG indices in traumatic brain injury - insights from the CAPTAIN RTMS trial.

This secondary analysis of the CAPTAIN-RTMS trial data focused on the significance of quantitative electroencephalography (qEEG) indices as indicators of recovery in patients with traumatic brain injury (TBI). By focusing on the delta alpha ratio (DAR), delta theta/alpha beta ratio (DTABR), and theta beta ratio (TBR), this study explored the shifts in brainwave activity as a response to an integrative treatment regimen of repetitive transcranial magnetic stimulation (rTMS) combined with the neurotrophic agent Cerebrolysin. Findings revealed significant increases in DAR and DTABR, suggesting changes in neurophysiological dynamics after treatment. However, variations in TBR were inconclusive in providing clear electrophysiological insights. These results indicate that further research is necessary to describe and understand the underlying mechanisms of brain recovery and to develop refined treatment frameworks for patients with TBI.

Validation of Acuros for total body irradiation at extended distance.

PURPOSE: Standardized and accurately reported doses are essential in conventional total body irradiation (TBI), especially lung doses. This study evaluates the accuracy of the Acuros algorithm in predicting doses for extended-distance TBI. METHODS: Measurements and calculations were done with both 6 and 18 MV. Tissue Maximum Ratio (TMR), output and off axis ratios (OAR) were measured at 200 and 500 cm source to detector distance and compared to Acuros calculated values. Two end-to-end tests were carried out, one with an in-house phantom (solid water and Styrofoam) with inserted ion chambers and the other was with the Imaging and Radiation Oncology Core (IROC) TBI anthropomorphic phantom equipped with TLDs. The end-to-end test was done for 6 and 18 MV both with and without lung blocks. The source to midplane distance for both phantoms were at 518 and 508 cm respectively. Lung blocks were placed at the phantom surface and a beam spoiler was positioned 30 cm from the surface of the phantoms as per our clinical set up. RESULTS: The agreement between measured and calculated TMR, output and off axis ratios for both 6 and 18 MV were within 2%. Ion chamber measurements in both the Styrofoam and solid water for both energies carried out with and without lung blocks were within 2% of calculated values. TLD measured doses for both 6 and 18 MV in the IROC phantom were within 5% of calculated doses which is within the uncertainty of the TLD measurement. CONCLUSIONS: The results indicate that the clinical beam model for Acuros 16.1 commissioned at standard clinical distances is capable of calculating doses accurately at extended distances up to 500 cm.

Neuroprotective Mechanism of MOTS-c in TBI Mice: Insights from Integrated Transcriptomic and Metabolomic Analyses.

Background: Traumatic brain injury (TBI) is a condition characterized by structural and physiological disruptions in brain function caused by external forces. However, as the highly complex and heterogenous nature of TBI, effective treatments are currently lacking. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown notable antinociceptive and anti-inflammatory effects, yet its detailed neuroprotective effects and mode of action remain incompletely understood. This study investigated the neuroprotective effects and the underlying mechanisms of MOTS-c. Methods: Adult male C57BL/6 mice were randomly divided into three groups: control (CON) group, MOTS-c group and TBI group. Enzyme-linked immunosorbent assay (ELISA) kit method was used to measure the expression levels of MOTS-c in different groups. Behavioral tests were conducted to assess the effects of MOTS-c. Then, transcriptomics and metabolomics were performed to search Differentially Expressed Genes (DEGs) and Differentially Expressed Metabolites (DEMs), respectively. Moreover, the integrated transcriptomics and metabolomics analysis were employed using R packages and online Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: ELISA kit method showed that TBI resulted in a decrease in the expression of MOTS-c. and peripheral administration of MOTS-c could enter the brain tissue after TBI. Behavioral tests revealed that MOTS-c improved memory, learning, and motor function impairments in TBI mice. Additionally, transcriptomic analysis screened 159 differentially expressed genes. Metabolomic analysis identified 491 metabolites with significant differences. Integrated analysis found 14 KEGG pathways, primarily related to metabolic pathways. Besides, several signaling pathways were enriched, including neuroactive ligand-receptor interaction and retrograde endocannabinoid signaling. Conclusion: TBI reduced the expression of MOTS-c. MOTS-c reduced inflammatory responses, molecular damage, and cell death by down-regulating macrophage migration inhibitory factor (MIF) expression and activating the retrograde endocannabinoid signaling pathway. In addition, MOTS-c alleviated the response to hypoxic stress and enhanced lipid ß-oxidation to provide energy for the body following TBI. Overall, our study offered new insights into the neuroprotective mechanisms of MOTS-c in TBI mice.

Associations Between Intracranial Pressure Extremes and Continuous Metrics of Cerebrovascular Pressure Reactivity in Acute Traumatic Neural Injury: A Scoping Review.

Cerebrovascular pressure reactivity plays a key role in maintaining constant cerebral blood flow. Unfortunately, this mechanism is often impaired in acute traumatic neural injury states, exposing the already injured brain to further pressure-passive insults. While there has been much work on the association between impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) and worse long-term outcomes, there is yet to be a comprehensive review on the association between cerebrovascular pressure reactivity and intracranial pressure (ICP) extremes. Therefore, we conducted a systematic review of the literature for all studies presenting a quantifiable statistical association between a continuous measure of cerebrovascular pressure reactivity and ICP in a human TBI cohort. The methodology described in the Cochrane Handbook for Systematic Reviews was used. BIOSIS, Cochrane Library, EMBASE, Global Health, MEDLINE, and SCOPUS were all searched from their inceptions to March of 2023 for relevant articles. Full-length original works with a sample size of ≥10 patients with moderate/severe TBI were included in this review. Data were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 16 articles were included in this review. Studies varied in population characteristics and statistical tests used. Five studies looked at transcranial Doppler-based indices and 13 looked at ICP-based indices. All but two studies were able to present a statistically significant association between cerebrovascular pressure reactivity and ICP. Based on the findings of this review, impaired reactivity seems to be associated with elevated ICP and reduced ICP waveform complexity. This relationship may allow for the calculation of patient-specific ICP thresholds, past which cerebrovascular reactivity becomes persistently deranged. However, further work is required to better understand this relationship and improve algorithmic derivation of such individualized ICP thresholds.

Diagnostic utility of Brain Injury Guidelines (BIG): systematic review and meta-analysis for prediction of neurosurgical intervention in traumatic brain injury.

BACKGROUND: The Brain Injury Guidelines (BIG) categorize the severity of Traumatic Brain Injury (TBI). The efficacy of BIG in predicting radiological deterioration and the necessity for neurosurgical intervention remains uncertain, as there is a lack of examination of pooled data from current literature despite validation in numerous single and multi-institutional studies. The aim of this study was to analyze existing studies to determine the diagnostic accuracy of BIG scoring criteria. METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPEROID CRD42021277542). Three databases were searched, and articles published from 2000 to October 2022 were included (last search date: 25 November 2022). Pooled sensitivity and specificity were calculated using random effects meta-analysis. RESULTS: Of the 1130 articles identified, 13 were included in the analysis (9032 patients - 1433 BIG1, 2136 BIG2 & 3189 BIG3). A total of 2274 patients were not classified under either group. Pooled sensitivity for predicting neurosurgical intervention was 1.00 (95%CI:1.00-1.00), and 0.98 for radiological deterioration (95% CI: 0.927-0.996). The specificity in predicting radiological deterioration was 0.18 (95% CI: 0.16-0.21) and 0.05 for neurosurgical intervention (95% CI 0.05-0.05). CONCLUSIONS: The BIG score is highly sensitive at excluding TBI cases that do not require neurosurgical intervention; however, BIG-2 and BIG-3 might not be useful for ruling in TBI patients who require neurosurgical intervention.

Who is seeking information about traumatic brain injury? Characterizing online course participants.

Accessible, up-to-date information on traumatic brain injury (TBI) can be challenging to find and is needed to address TBI knowledge gaps and improve outcomes for people who experience a TBI. The Understanding TBI Massive Open Online Course (TBI MOOC) was developed to increase TBI knowledge across a diverse global audience. We sought to characterize the TBI MOOC participant cohort, to understand the reach of the course among this target audience. Examining the characteristics of TBI MOOC enrollees showed that participants came from a wide range of demographic backgrounds, had a variety of TBI experiences and had multiple reasons for enrolling in the MOOC. The majority of course participants shared some characteristics with other groups of health information seekers. Four distinct demographic profiles were identified among TBI MOOC participants (education seekers, TBI-aware participants, TBI care providers and retirees) using a novel approach combining chi-squared tests and network modularity. Participants assigned to the TBI-aware and retiree profiles were most likely to complete all modules of the MOOC, and the TBI-aware profile was more highly represented in more recent iterations of the MOOC. Together, these data indicate that the TBI MOOC provided information to a wide range of people, and particularly engaged participants with personal or family experience of TBI. However, engagement with this course was minimal among some hard-to-reach populations, including men and people with low levels of education, indicating that additional strategies are needed to ensure equity in health promotion.

Concussions in ice hockey: mixed methods study including assessment of concussions on games missed and cap hit among National Hockey League players, systematic review, and concussion protocol analysis.

OBJECTIVE: Concussions can occur at any level of ice hockey. Incidence estimates of concussions in ice hockey vary, and optimal prevention strategies and return-to-play (RTP) considerations have remained in evolution. The authors performed a mixed-methods study with the aim of elucidating the landscape of concussion in ice hockey and catalyzing initiatives to standardize preventative mechanisms and RTP considerations. METHODS: The authors performed a five-part mixed-methods study that includes: 1) an analysis of the impact of concussions on games missed and income for National Hockey League (NHL) players using a publicly available database, 2) a systematic review of the incidence of concussion in ice hockey, 3) a systematic review of preventative strategies, 4) a systematic review of RTP, and 5) a policy review of documents from major governing bodies related to concussions in sports with a focus on ice hockey. The PubMed, Embase, and Scopus databases were used for the systematic reviews and focused on any level of hockey. RESULTS: In the NHL, 689 players had 1054 concussions from the 2000-2001 to 2022-2023 seasons. A concussion led to a mean of 13.77 ± 19.23 (range 1-82) games missed during the same season. After cap hit per game data became available in 2008-2009, players missed 10,024 games due to 668 concussions (mean 15.13 ± 3.81 per concussion, range 8.81-22.60 per concussion), with a cap hit per game missed of $35,880.85 ± $25,010.48 (range $5792.68-$134,146.30). The total cap hit of all missed games was $385,960,790.00, equating to $577,635.91 per concussion and $25,724,052.70 per NHL season. On systematic review, the incidence of concussions was 0.54-1.18 per 1000 athlete-exposures. Prevention mechanisms involved education, behavioral and cognitive interventions, protective equipment, biomechanical studies, and policy/rule changes. Rules prohibiting body checking in youth players were most effective. Determination of RTP was variable. Concussion protocols from both North American governing bodies and two leagues mandated that a player suspected of having a concussion be removed from play and undergo a six-step RTP strategy. The 6th International Conference on Concussion in Sport recommended the use of mouthguards for children and adolescents and disallowing body checking for all children and most levels of adolescents. CONCLUSIONS: Concussions in ice hockey lead to substantial missed time from play. The authors strongly encourage all hockey leagues to adopt and adhere to age-appropriate rules to limit hits to the head, increase compliance in wearing protective equipment, and utilize high-quality concussion protocols.

Total body irradiation: A transition from a Co-60 treatment unit to an IMRT lateral-field extended-SAD technique.

PURPOSE: The purpose of this work was to detail our center's experience in transitioning from a Co-60 treatment technique to an intensity modulated radiation therapy (IMRT) based lateral-field extended source-to-axis distance (e-SAD) technique for total body irradiation (TBI). MATERIALS AND METHODS: An existing beam model in RayStation v.10A was validated for the use of e-SAD TBI treatments. Data were acquired with an Elekta Synergy linear accelerator (LINAC) at an extended source-to-surface distance of 365 cm with an 18 MV beam. Beam model validation measurements included percentage depth dose (PDD), profile data, surface dose, build-up region and transmission measurements. End-to-end testing was carried out using an anthropomorphic phantom. Treatments were performed in a supine position in a whole-body Vac-Lok at an e-SAD of 400 cm with a beam spoiler 10 cm from the couch. Planning was achieved using IMRT, where multi-leaf collimators were used to modulate the beam and shield the organs at risk. Beam's eye view projection images were used for in-room patient positioning and in-vivo dosimetry was performed for every treatment. RESULTS: The percent difference between the measured and calculated PDD and profiles was less than 2% at all locations. Surface dose was 83.8% of the maximum dose with the beam spoiler at a 10 cm distance from the phantom. The largest percent difference between the treatment planning system (TPS) and measured data within the anthropomorphic phantom was approximately 2%. In-vivo dosimetry measurements yielded results within the 5% institutional threshold. CONCLUSION: In 2022, 17 patients were successfully treated using the new IMRT-based lateral-field e-SAD TBI technique. The resulting clinical plans respected the institutional standard. The commissioning process, as well as the treatment planning and delivery aspects were described in this work with the intention of supporting other clinics in implementing this treatment method.

A retrospective chart review to assess the impact of alpha-guided transcranial magnetic stimulation on symptoms of PTSD and depression in active-duty special operations service members.

Introduction: Special Operations Forces service members (SOF) are regularly exposed to traumatic and concussive events, increasing the prevalence of symptoms of post-traumatic stress disorder (PTSD) and depression, shortening potential years of service. Methods: This retrospective chart review presents preliminary data on a Human Performance Optimization (HPO) program that provided an average of 30 sessions of individualized alpha frequency repetitive transcranial magnetic stimulation (α-rTMS) to active-duty SOF as to reduce symptoms of PTSD and depression following traumatic brain injury. Scores from the PTSD Checklist for DSM-5, PROMIS Depression short form and Perceived Deficits Questionnaire (PDQ) were reviewed. Results: Significant reductions were noted after the HPO program in all clinical scales with an average 37% decrease in PCL-5 (p<.01), 11.3% reduction in PROMIS depression T-scores (p<.01), and 45.5% reduction in PDQ scales by session 30 (p<.01), with side effects matching those commonly reported in rTMS. Importantly, the average PCL-5 score decreased from 42.9 to 27 by end of the treatment program, which is below the clinical threshold of 33 for presence of PTSD. For those with depression symptoms scores greater than cut off clinical thresholds at baseline, 46% resolved following treatment. Conclusion: This data provides preliminary support for safe application of α-rTMS for symptom reduction in active-duty special operations military personnel.

Testosterone and neurobehavioral outcomes in special operations forces military with multiple mild traumatic brain injury.

BACKGROUND: U.S. Special Operations Forces (SOF) are at increased risk of multiple mild traumatic brain injury (mmTBI). Testosterone was prescribed for several participants in a VA program designed to address sequelae of mmTBI for SOF. OBJECTIVE: To determine testosterone prevalence in the Palo Alto VA Intensive Evaluation and Treatment Program (IETP) and observe for association between testosterone and neurobehavioral outcomes. METHODS: A retrospective cohort study included patients in the Palo Alto VA IETP. Sociodemographic data, testosterone blood levels, and neurobehavioral outcomes were collected from medical records. RESULTS: 55 IETP participants were included: six were testosterone users; the rest were classified as non-users. Testosterone use in this population is 11%, higher than reported national averages in the U.S. Of the 6 testosterone users, 2 (33%) had a formal diagnosis of hypogonadism prior to initiation of testosterone. Neurobehavioral outcome scores between testosterone users and non-users failed to show statistically significant differences, except for the PROMIS pain score, which was higher in the testosterone user population. CONCLUSION: The current study did not find an association between mmTBI, testosterone use, or testosterone level and neurobehavioral outcomes. This study highlights a need to further examine the relationship between hypogonadism, mmTBI, SOF culture around testosterone, and the effects of testosterone use in this population.

Derivation of the Quebec Brain Injury Categories for complicated mild traumatic brain injuries.

OBJECTIVE: Approximately 10% of patients with mild traumatic brain injury (TBI) present with intracranial bleeding, and only 3.5% eventually require neurosurgical intervention, which often necessitates interhospital transfer. Better guidelines and recommendations are needed to manage complicated mild TBI in the emergency department (ED). The main objective of this study was to derive a clinical decision rule, the Quebec Brain Injury Categories (QueBIC), to predict the risk of adverse outcomes for complicated mild TBI in the ED. The secondary objective was to compare the QueBIC's performance with those of other existing guidelines. METHODS: The authors conducted a retrospective multicenter cohort study in 3 level I trauma centers. Consecutive patients with complicated mild TBI (Glasgow Coma Scale [GCS] score 13-15) who were aged ≥ 16 years were included. The primary outcome was a combination of neurosurgical intervention, mild TBI-related death, and clinical deterioration. Statistical analyses included set covering machine analyses. RESULTS: In total, 477 patients were included in the study. The mean age was 62.9 years, and 68.1% were male. The algorithm classified patients into three risk categories (low, moderate, and high risk). The high-risk group (128 patients) (subdural hemorrhage [SDH] width > 7 mm or any midline shift) presented a sensitivity of 84% (95% CI 71%-93%) and a specificity of 80% (95% CI 76%-84%) to detect neurosurgical intervention and mild TBI-related death, leaving 8 undetected cases. Patients in the moderate-risk group (169 patients) had at least 1 variable: SDH width > 4 mm, initial GCS score ≤ 14, > 1 intraparenchymal hemorrhage, or intraparenchymal hemorrhage width > 4 mm. The combined QueBIC high- and moderate-risk category had a sensitivity of 100% (95% CI 63%-100%) and a specificity of 53% (95% CI 47%-58%) to detect mild TBI-related death or neurosurgical intervention. The sensitivity and specificity values for clinical deterioration when no death or neurosurgical intervention occurred were 81% (95% CI 64%-93%) and 44% (95% CI 39%-49%), respectively. The remaining 180 patients (37.7%) did not meet any high-risk or moderate-risk criteria and were considered low risk. None had neurosurgical intervention or mild TBI-related death. Only 6 (3.3%) low-risk patients showed clinical deterioration. CONCLUSIONS: QueBIC is a safe and effective tool to guide the management of patients presenting to the ED with complicated mild TBI. It accurately identifies patients at low risk for specialized neurotrauma or neurosurgical care. Further validation is required before its use in EDs.

Bezafibrate protects blood-brain barrier (BBB) integrity against traumatic brain injury mediated by AMPK.

Bezafibrate (BEZ) has displayed a wide range of neuroprotective effects in different types of neurological diseases. However, its pharmacological function in traumatic brain injury (TBI) is still unknown. In the current study, a TBI model was constructed in mice to examine the potential beneficial roles of BEZ. After TBI, mice were daily dieted with BEZ or vehicle solution. The motor function, learning and memory, brain edema, vascular inflammatory factors, the integrity of the blood-brain barrier (BBB), and the expression of the tight junction zona occludens 1 (ZO-1) were assessed. The findings demonstrate that after TBI, BEZ treatment significantly promoted the recovery of motor function and cognitive function deficits. Moreover, BEZ attenuated brain edema by reducing the levels of brain water content. We also found that administration of BEZ alleviated cerebral vascular pro-inflammation by suppressing the expression of ICAM-1, VCAM-1, and E-selectin. Notably, BEZ improved the impaired BBB integrity in TBI mice by restoring the expression of the tight junction (TJ) protein ZO-1. Further in vitro experiments show that treatment with BEZ prevented the aggravation of endothelial permeability and restored the reduction of trans-epithelial electrical resistance (TEER) as well as the expression of ZO-1 in TBI-exposed brain bEnd.3 cells. Mechanistically, we prove that the protective effects of BEZ are mediated by AMPK. Based on these findings, we conclude that BEZ improves TBI-induced BBB injury and it might be considered for the treatment or management of TBI.

Experimental Modeling of Cranial Injury and Defect Reconstruction Using Superconstructive Polymers (PEEK).

Experimental model of resection craniotomy with subsequent reconstruction of the defect with a polymer implant enables comprehensive assessment of functional and ultrastructural changes during replacement of the damaged tissue. Reconstruction of a skull defect was accompanied by transient motor disturbance in the acute period and did not cause functional disorders and neurological deficits in a delayed period. Histological examination of osteal and brain tissue revealed no pathological reactions that could be associated with the response to the chemical components of the implant.

Logic "AND Gate Circuit" Based Mussel Inspired Polydopamine Nanocomposite as Bioactive Antioxidant for Management of Oxidative Stress and Neurogenesis in Traumatic Brain Injury.

In the intricate landscape of Traumatic Brain Injury (TBI), the management of TBI remains a challenging task due to the extremely complex pathophysiological conditions and excessive release of reactive oxygen species (ROS) at the injury site and the limited regenerative capacities of the central nervous system (CNS). Existing pharmaceutical interventions are limited in their ability to efficiently cross the blood-brain barrier (BBB) and expeditiously target areas of brain inflammation. In response to these challenges herein, we designed novel mussel inspired polydopamine (PDA)-coated mesoporous silica nanoparticles (PDA-AMSNs) with excellent antioxidative ability to deliver a new potential therapeutic GSK-3ß inhibitor lead small molecule abbreviated as Neuro Chemical Modulator (NCM) at the TBI site using a neuroprotective peptide hydrogel (PANAP). PDA-AMSNs loaded with NCM (i.e., PDA-AMSN-D) into the matrix of PANAP were injected into the damaged area in an in vivo cryogenic brain injury model (CBI). This approach is specifically built while keeping the logic AND gate circuit as the primary focus. Where NCM and PDA-AMSNs act as two input signals and neurological functional recovery as a single output. Therapeutically, PDA-AMSN-D significantly decreased infarct volume, enhanced neurogenesis, rejuvenated BBB senescence, and accelerated neurological function recovery in a CBI.

Can We Actually Predict Long-Term Patient Satisfaction After Traumatic Brain Injury?

INTRODUCTION: The Traumatic Brain Injury - Patient Reported Outcome (TBI-PRO) model was previously derived to predict long-term patient satisfaction as assessed by the Quality of Life After Brain Injury (QOLIBRI) score. The aim of this study is to externally and prospectively validate the TBI-PRO model to predict long-term patient-reported outcomes and to derive a new model using a larger dataset of older adults with TBI. METHODS: Patients admitted to a Level I trauma center with TBI were prospectively followed for 1 y after injury. Outcomes predicted by the TBI-PRO model based on admission findings were compared to actual QOLIBRI scores reported by patients at 3,6, and 12 mo. When deriving a new model, Collaborative European NeuroTrauma Effectiveness Research in TBI and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury databases were used to identify older adults (≥50 y) with TBI from 2014 to 2018. Bayesian additive regression trees were used to identify predictive admission covariates. The coefficient of determination was used to identify the fitness of the model. RESULTS: For prospective validation, a total of 140 patients were assessed at 3 mo, with follow-up from 69 patients at 6 mo and 13 patients at 12 mo postinjury. The area under receiver operating curve of the TBI-PRO model for predicting favorable outcomes at 3, 6, and 12 mo were 0.65, 0.57, and 0.62, respectively. When attempting to derive a novel predictive model, a total of 1521 patients (80%) was used in the derivation dataset while 384 (20%) were used in the validation dataset. A past medical history of heart conditions, initial hospital length of stay, admission systolic blood pressure, age, number of reactive pupils on admission, and the need for craniectomy were most predictive of long-term QOLIBRI-Overall Scale. The coefficient of determination for the validation model including only the most predictive variables were 0.28, 0.19, and 0.27 at 3, 6, and 12 mo, respectively. CONCLUSIONS: In the present study, the prospective validation of a previously derived TBI-PRO model failed to accurately predict a long-term patient reported outcome measures in TBI. Additionally, the derivation of a novel model in older adults using a larger database showed poor accuracy in predicting long-term health-related quality of life. This study demonstrates limitations to current targeted approaches in TBI care. This study provides a framework for future studies and more targeted datasets looking to assess long-term quality of life based upon early hospital variables and can serve as a starting point for future predictive analysis.

Characteristics of the Structural Connectivity in Patients with Brain Injury and Chronic Health Symptoms: A Pilot Study.

Diffusion properties from diffusion tensor imaging (DTI) are exquisitely sensitive to white matter abnormalities incurred during traumatic brain injury (TBI), especially for those patients with chronic post-TBI symptoms such as headaches, dizziness, fatigue, etc. The evaluation of structural and functional connectivity using DTI has become a promising method for identifying subtle alterations in brain connectivity associated with TBI that are otherwise not visible with conventional imaging. This study assessed whether TBI patients with (n = 17) or without (n = 16) chronic symptoms (TBIcs/TBIncs) exhibit any changes in structural connectivity (SC) and mean fractional anisotropy (mFA) of intra- and inter-hemispheric connections when compared to a control group (CG) (n = 13). Reductions in SC and mFA were observed for TBIcs compared to CG, but not for TBIncs. More connections were found to have mFA reductions than SC reductions. On the whole, SC is dominated by ipsilateral connections for all the groups after the comparison of contralateral and ipsilateral connections. More contra-ipsi reductions of mFA were found for TBIcs than TBIncs compared to CG. These findings suggest that TBI patients with chronic symptoms not only demonstrate decreased global and regional mFA but also reduced structural network connectivity.

Effect of erythropoietin on SOFA score, Glasgow Coma Scale and mortality in traumatic brain injury patients: a randomized-double-blind controlled trial.

Background: Recent studies suggest that erythropoietin has an anti-inflammatory effect on the central nervous system. The authors aimed to investigate the effect of erythropoietin on Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA) scores, and the mortality rate of traumatic brain injury (TBI) patients. Methods: Sixty-eight patients with available inclusion criteria were randomly allocated to the control or intervention groups. In the intervention group, erythropoietin (4000 units) was administrated on days 1, 3, and 5. In the control group, normal saline on the same days was used. The primary outcomes were the GCS and SOFA score changes during the intervention. The secondary outcomes were the ventilation period during the first 2 weeks and the 3-month mortality rate. Results: Erythropoietin administration significantly affected SOFA score over time (P=0.008), but no significant effect on the GCS, and duration of ventilation between the two groups was observed. Finally, erythropoietin had no significant effect on the three-month mortality (23.5% vs. 38.2% in the erythropoietin and control group, respectively). However, the mortality rate in the intervention group was lower than in the control group. Conclusion: Our finding showed that erythropoietin administration in TBI may improve SOFA score. Therefore, erythropoietin may have beneficial effects on early morbidity and clinical improvement in TBI patients.

Development and validation of an electronic health record-based algorithm for identifying TBI in the VA: A VA Million Veteran Program study.

The purpose of this study was to develop and validate an algorithm for identifying Veterans with a history of traumatic brain injury (TBI) in the Veterans Affairs (VA) electronic health record using VA Million Veteran Program (MVP) data. Manual chart review (n = 200) was first used to establish 'gold standard' diagnosis labels for TBI ('Yes TBI' vs. 'No TBI'). To develop our algorithm, we used PheCAP, a semi-supervised pipeline that relied on the chart review diagnosis labels to train and create a prediction model for TBI. Cross-validation was used to train and evaluate the proposed algorithm, 'TBI-PheCAP.' TBI-PheCAP performance was compared to existing TBI algorithms and phenotyping methods, and the final algorithm was run on all MVP participants (n = 702,740) to assign a predicted probability for TBI and a binary classification status choosing specificity = 90%. The TBI-PheCAP algorithm had an area under the receiver operating characteristic curve of 0.92, sensitivity of 84%, and positive predictive value (PPV) of 98% at specificity = 90%. TBI-PheCAP generally performed better than other classification methods, with equivalent or higher sensitivity and PPV than existing rules-based TBI algorithms and MVP TBI-related survey data. Given its strong classification metrics, the TBI-PheCAP algorithm is recommended for use in future population-based TBI research.

Letter to the editor: Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis.

The meta-analysis by Shen et al. in Neurosurgical Review highlights the benefits of brain tissue oxygen partial pressure (PbtO2) monitoring in reducing mortality and intracranial pressure in severe traumatic brain injury (TBI) patients. However, it also associates PbtO2 monitoring with prolonged hospital stays. Future research should focus on standardizing PbtO2 protocols, integrating with advanced neuroimaging, exploring long-term outcomes, evaluating combination therapies, and conducting cost-benefit analyses. Addressing these areas could further enhance the clinical application and efficacy of PbtO2 monitoring in improving patient outcomes.