Loss of microglial Arid1a exacerbates microglial scar formation via elevated CCL5 after traumatic brain injury.

Traumatic brain injury (TBI) is an acquired insult to the brain caused by an external mechanical force, potentially resulting in temporary or permanent impairment. Microglia, the resident immune cells of the central nervous system, are activated in response to TBI, participating in tissue repair process. However, the underlying epigenetic mechanisms in microglia during TBI remain poorly understood. ARID1A (AT-Rich Interaction Domain 1 A), a pivotal subunit of the multi-protein SWI/SNF chromatin remodeling complex, has received little attention in microglia, especially in the context of brain injury. In this study, we generated a Arid1a cKO mouse line to investigate the potential roles of ARID1A in microglia in response to TBI. We found that glial scar formation was exacerbated due to increased microglial migration and a heightened inflammatory response in Arid1a cKO mice following TBI. Mechanistically, loss of ARID1A led to an up-regulation of the chemokine CCL5 in microglia upon the injury, while the CCL5-neutralizing antibody reduced migration and inflammatory response of LPS-stimulated Arid1a cKO microglia. Importantly, administration of auraptene (AUR), an inhibitor of CCL5, repressed the microglial migration and inflammatory response, as well as the glial scar formation after TBI. These findings suggest that ARID1A is critical for microglial response to injury and that AUR has a therapeutic potential for the treatment of TBI.

Volumetric modulated arc therapy total body irradiation improves toxicity outcomes compared to 2D total body irradiation.

Introduction: Volumetric modulated arc therapy (VMAT) total body irradiation (TBI) allows for greater organ sparing with improved target coverage compared to 2D-TBI. However, there is limited evidence of whether improved organ sparing translates to decreases in toxicities and how its toxicities compare to those of the 2D technique. We aimed to compare differences in toxicities among patients treated with TBI utilizing VMAT and 2D techniques. Methods/materials: A matched-pair single-institution retrospective analysis of 200 patients treated with TBI from 2014 to 2023 was performed. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and compared using log-rank tests. Differences in characteristics and toxicities between the VMAT and 2D cohorts were compared using Fisher's exact test. Results: Of the 200 patients analyzed, 100 underwent VMAT-TBI, and 100 underwent 2D-TBI. The median age for VMAT-TBI and 2D-TBI patients was 13.7 years and 16.2 years, respectively (p = 0.25). In each cohort, 53 patients were treated with myeloablative regimens (8-13.76 Gy), and 47 were treated with non-myeloablative regimens (2-4 Gy). For the entire VMAT-TBI cohort, lung Dmean, kidney Dmean, and lens Dmax were spared to 60.6% ± 5.0%, 71.0% ± 8.5%, and 90.1% ± 3.5% of prescription, respectively. For the non-myeloablative VMAT-TBI cohort, testis/ovary Dmax, brain, and thyroid Dmean were spared to 33.4% ± 7.3%, 75.4% ± 7.0%, and 76.1% ± 10.5%, respectively. For 2D-TBI, lungs were spared using partial-transmission lung blocks for myeloablative regimens. The VMAT-TBI cohort experienced significantly lower rates of any grade of pneumonitis (2% vs. 12%), nephrotoxicity (7% vs. 34%), nausea (68% vs. 81%), skin (16% vs. 35%), and graft versus host disease (GVHD) (42% vs. 62%) compared to 2D-TBI patients. For myeloablative regimen patients, rates of pneumonitis (0% vs. 17%) and nephrotoxicity (9% vs. 36%) were significantly lower with VMAT-TBI versus 2D-TBI (p < 0.01). Median follow-up was 14.3 months, and neither median OS nor PFS for the entire cohort was reached. In the VMAT versus 2D-TBI cohort, the 1-year OS was 86.0% versus 83.0% (p = 0.26), and the 1-year PFS was 86.6% and 80.0% (p = 0.36), respectively. Conclusion: Normal tissue sparing with VMAT-TBI compared to the 2D-TBI translated to significantly lower rates of pneumonitis, renal toxicity, nausea, skin toxicity, and GVHD in patients, while maintaining excellent disease control.

Mild and Severe Blood Alcohol Concentration Effects on Trauma and Traumatic Brain Injury Outcomes.

INTRODUCTION: Reported outcomes for trauma patients (TPs) with elevated blood alcohol concentration (BAC) have been mixed. Previous studies suggest that positive BAC might lead to lower venous thromboembolism (VTE) rates and mortality. This study expands upon these findings by examining the association of various levels of BAC, with additional emphasis on traumatic brain injury (TBI) patients. We hypothesize that both mild and severe-BAC levels in TPs are associated with decreased risk of VTE and mortality. METHODS: A retrospective review of the 2017 Trauma Quality Improvement Program was performed on adults (≥18 y old) screened for BAC on admission. Patients deceased on arrival and positive for drugs were excluded. We compared three groups: no-BAC, mild-BAC (0-70 mg/dL), and-severe BAC (>80 mg/dL) for associated risk of VTE and mortality. RESULTS: From 203,535 tested patients, 118,427 (58.2%) had no-BAC, 19,813 (9.7%) had mild-BAC, and 65,295 (32.1%) had severe-BAC. The associated risk of VTE was lower for mild-BAC (odds ratios [OR] 0.69, 0.58-0.82, P < 0.001) and severe-BAC (OR 0.80, 0.72-0.89, P < 0.001). This persisted in TBI patients, with mild-BAC (OR 0.67, 0.51-0.89, P = 0.006) and severe-BAC (OR 0.75, 0.64-0.89, P < 0.001) groups exhibiting lower associated VTE risk. However, the associated mortality risk was lower only in severe-BAC patients (OR 0.90, 0.83-0.97, P = 0.009). CONCLUSIONS: A positive BAC is linked to a reduced associated risk of VTE in TPs, including those with TBI. Notably, only the severe-BAC group demonstrated a lower associated risk of mortality. This merits future research including identification of basic science pathways that may be targeted to improve outcomes.

Global traumatic brain injury intracranial pressure: from monitoring to surgical decision.

Traumatic brain injury (TBI) is a significant global public health issue, heavily impacting human health, especially in low-and middle-income areas. Despite numerous guidelines and consensus statements, TBI fatality rates remain high. The pathogenesis of severe TBI is closely linked to rising intracranial pressure (ICP). Elevated intracranial pressure can lead to cerebral herniation, resulting in respiratory and circulatory collapse, and ultimately, death. Managing intracranial pressure (ICP) is crucial in neuro-intensive care. Timely diagnosis and precise treatment of elevated ICP are essential. ICP monitoring provides real-time insights into a patient's condition, offering invaluable guidance for comprehensive management. ICP monitoring and standardization can effectively reduce secondary nerve damage, lowering morbidity and mortality rates. Accurately assessing and using true ICP values to manage TBI patients still depends on doctors' clinical experience. This review discusses: (a) Epidemiological disparities of traumatic brain injuries across countries with different income levels worldwide; (b) The significance and function of ICP monitoring; (c) Current status and challenges of ICP monitoring; (d) The impact of decompressive craniectomy on reducing intracranial pressure; and (e) Management of TBI in diverse income countries. We suggest a thorough evaluation of ICP monitoring, head CT findings, and GCS scores before deciding on decompressive craniectomy. Personalized treatment should be emphasized to assess the need for surgical decompression in TBI patients, offering crucial insights for clinical decision-making.

Vinpocetine Ameliorates Neuronal Injury After Cold-Induced Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI), also known as intracranial injury, is a common condition with the highest incidence rate among neurodegenerative disorders and poses a significant public health burden. Various methods are used in the treatment of TBI, but the effects of cold-induced traumatic brain injury have not been thoroughly studied. In this context, vinpocetine (VPN), derived from Vinca minor, exhibits notable anti-inflammatory and antioxidant properties. VPN is known for its neuroprotective role and is generally utilized for treating various neurodegenerative disorders. However, the function of VPN after cold-induced TBI needs to be studied in more detail. This study aims to investigate the neuroprotective effects of VPN at varying doses (5 mg/kg or 10 mg/kg) after cold-induced TBI. C57BL/6 mice were sacrificed 2 or 28 days after cold-induced TBI. Results indicate that VPN administration significantly reduces brain infarct volume, brain swelling, blood-brain barrier disruption, and DNA fragmentation in a dose-dependent manner. Additionally, VPN enhances neuronal survival in the ipsilesional cortex. In the long term, VPN treatment (5 mg/kg/day or 10 mg/kg/day, initiated 48 h post-TBI) improved locomotor activity, cell proliferation, neurogenesis, and decreased whole brain atrophy, specifically motor cortex atrophy. We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the underlying mechanisms to profile proteins and signaling pathways influenced by prolonged VPN treatment post-TBI. Notably, we found that 192 different proteins were significantly altered by VPN treatment, which is a matter of further investigation for the development of therapeutic targets. Our study has shown that VPN may have a neuroprotective role in cold-induced TBI.

Gastrointestinal bleeding following traumatic brain injury: A clinical study on predisposing factors and outcomes.

Background: Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide. Stress ulcers are common in critically ill patients and can lead to life-threatening gastrointestinal bleeding (GIB). This study investigates the impact of predisposing factors on GIB and outcomes of TBI patients. Methods: This retrospective cohort study included TBI patients admitted between February 2019 and November 2021. Patients' demographic information and clinical characteristics were collected and divided into Post-TBI GIB and No-GIB groups. During clinical follow-up, the Glasgow Outcome Score (GOS) and mortality were assessed. The correlation between predisposing factors and GIB was investigated. Results: Out of 164 eligible patients, 66.5% were males, and the mean age was 31.38 ± 13.44 years. There was a higher rate of severe TBIs (p<0.001), intra-axial lesions (P=0.014), hypotension at admission (p<0.001), and concurrent coagulopathies (p<0.001) in the Post-TBI GIB group compared to the No-GIB group. In contrast, the Glasgow Coma Scale (GCS) level upon admission and discharge (p<0.001) and serum hemoglobin level at admission (p<0.001) were lower in the Post-TBI GIB group than in the other group. Moreover, primary GCS (P=0.017) and hypotension at admission (P=0.009), spinal injury (P=0.028), and intra-axial brain injury (P=0.018) were independently associated with GIB in TBI patients. Conclusion: Primary GCS and hypotension at admission, spinal injury, and intra-axial brain injury are independent predictors for GIB in TBI patients. The presence of GIB in TBI patients is associated with worse neurological outcomes as assessed by GOS at approximately 18 months.

Racial and Ethnic Differences in Traumatic Brain Injury Outcomes From 2009 to 2023: Protocol for a Systematic Review.

BACKGROUND: In 2009, Gary and colleagues reviewed prior research examining racial and ethnic differences in outcomes after traumatic brain injury (TBI). Over the past 15 years, advances in research and changes in the demographic composition of the United States warrant a comprehensive understanding of racial and ethnic disparities after TBI. OBJECTIVE: A systematic review will be conducted to examine racial and ethnic differences in TBI outcomes from 2009 to 2023. METHODS: Preliminary searches and study screening processes will identify relevant English-language articles published from January 2009 to December 2023 using the CINAHL, Gale OneFile, PsycINFO (Ovid), and PubMed electronic databases. Relevant articles will include quantitative or mixed method approaches, involve individuals with TBI or their caregivers, and compare 2 or more groups by race or ethnicity on post-TBI outcomes. Quality will be assessed using the Newcastle-Ottawa Scale. This systematic review protocol was developed following PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. Results will be summarized, and a subgroup analysis may be conducted based on demographics (eg, age, gender, or sex). RESULTS: We have already identified abstracts using the search strategy for all 4 of the included electronic databases. We recently updated the search and will begin abstract screening of the additional abstracts identified from the last search completed in January 2024. This systematic review is anticipated to be completed by fall 2024, and its findings will be disseminated to the scientific community, persons with TBI, caregivers, and the lay audience. CONCLUSIONS: This systematic review will advance our understanding regarding outcome disparities among minoritized individuals with TBI, examine progress over the past 15 years in minimizing barriers encountered by these racial and ethnic groups, and provide professionals with a roadmap illustrating existing gaps in rehabilitation care, making way for further development and implementation of evidence-based interventions to improve health equity in TBI outcomes. TRIAL REGISTRATION: PROSPERO CRD42023394529; https://tinyurl.com/53mtcz9b. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/58763.

Nigella sativa extract abrogates traumatic brain injury-induced memory impairment in adult mice.

Background: Traumatic brain injury (TBI) is an increasing widespread cause of disability and mortality, typically leading to dementia and memory impairment. Objective: This study aims to investigate the neuroprotective potential of Nigella sativa extract against TBI induced memory impairment in adult albino mice. Methods: Adult male mice were divided into four groups randomly: Control, Nigella sativa extract alone, TBI alone and TBI plus Nigella sativa extract. TBI induction was carried out in mice using a weight dropping method then Nigella sativa extract (10 mg/kg) was administered intraperitoneally for two weeks. Morris water maze and Y-maze tests were used to measure memory improvement ability and Western blot technique was used to analyse the neuroinflammatory and synaptic protein markers. Results: Nigella sativa extract significantly decreased phosphorylated c-Jun N-terminal kinase (p-JNK), Tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) proteins to reduce TBI-induced neuroinflammation accompanied by the restoration of both pre- and post-synaptic protein expression in adult mice model. Furthermore, Nigella sativa extract enhanced both short and long-term spatial memory against TBI in adult mice model. Conclusion: Nigella sativa extract abrogated neuroinflammation mediated memory impairment in TBI mice model. Further research is needed to determine Nigella sativa extract ingredients detail completely and to understand its mechanisms of neuroprotection in reducing memory impairments associated with traumatic brain injury and other neurodegenerative diseases.

Superior survival after unrelated allogeneic stem cell transplantation with low-dose ATG compared to low-dose TBI in myeloablative fludarabine/busulfan-based regimen for MDS on behalf of the adult MDS Working Group of the JSTCT.

The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-year overall survival (OS) rates were 39.9, 64.8, and 43.7 %; 3-year non-relapse mortality (NRM) were 32.1, 22.1, and 27.1%; and 3-year relapse incidences were 34.7, 21.2, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27-0.95; P=0.032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36;95% CI, 0.13-1.06; P=0.063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27-0.99, P=0.049) and NRM (HR 0.034, 95% CI 0.11-0.92, P=0.034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors.

Comparative analysis of meningeal transcriptomes in birds: Potential pathways of resilience to repeated impacts.

The meninges and associated vasculature (MAV) play a crucial role in maintaining cerebral integrity and homeostasis. Recent advances in transcriptomic analysis have illuminated the significance of the MAV in understanding the complex physiological interactions at the interface between the skull and the brain after exposure to mechanical stress. To investigate how physiological responses may confer resilience against repetitive mechanical stress, we performed the first transcriptomic analysis of avian MAV tissues using the Downy Woodpecker (Dryobates pubescens) and Tufted Titmouse (Baeolophus bicolor) as the comparison species. Our findings reveal divergences in gene expression profiles related to immune response, cellular stress management, and protein translation machinery. The male woodpeckers exhibit a tailored immune modulation strategy that potentially dampens neuroinflammation while preserving protective immunity. Overrepresented genes involved in cellular stress responses suggest enhanced mechanisms for mitigating damage and promoting repair. Additionally, the enrichment of translation-associated pathways hints at increased capacity for protein turnover and cellular remodeling vital for recovery. Our study not only fills a critical gap in avian neurobiology but also lays the groundwork for research in comparative neuroprotection.

Sex-dependent temporal changes in astrocyte-vessel interactions following diffuse traumatic brain injury in rats.

Traumatic brain injury (TBI) is associated with diffuse axonal injury (DAI), a primary pathology linked to progressive neurodegeneration and neuroinflammation, including chronic astrogliosis, which influences long-term post-TBI recovery and morbidity. Sex-based differences in blood-brain barrier (BBB) permeability increases the risk of accelerated brain aging and early-onset neurodegeneration. However, few studies have evaluated chronic time course of astrocytic responses around cerebrovascular in the context of aging after TBI and sex dependence. We observed increased glial fibrillary acidic protein (GFAP)-labeled accessory processes branching near and connecting with GFAP-ensheathed cortical vessels, suggesting a critical nuance in astrocyte-vessel interactions after TBI. To quantify this observation, male and female Sprague Dawley rats (∼3 months old, n = 5-6/group) underwent either sham surgery or midline fluid percussion injury. Using immunohistochemical analysis, we quantified GFAP-labeled astrocyte primary and accessory processes that contacted GFAP-ensheathed vessels in the somatosensory barrel cortex at 7, 56, and 168 days post-injury (DPI). TBI significantly increased GFAP-positive primary processes at 7 DPI (P < 0.01) in both sexes. At 56 DPI, these vessel-process interactions remained significantly increased exclusively in males (P < 0.05). At 168 DPI, both sexes showed a significant reduction in vessel-process interactions compared to 7 DPI (P < 0.05); however, a modest but significant injury effect reemerged in females (P < 0.05). A similar sex-dependent pattern in the number of accessory processes provides novel evidence of long-term temporal changes in astrocyte-vessel interactions. TBI-induced changes in astrocyte-vessel interactions may indicate chronic BBB vulnerability and processes responsible for early onset vascular and neurodegenerative pathology.

Exposure to Adverse Childhood Experiences Predicts Increased Neurobehavioral Symptom Reporting in Adults with Mild Traumatic Brain Injury.

The objective of this study was to understand whether exposure to adverse childhood experiences (ACEs) before 18 years of age predicts increased neurobehavioral symptom reporting in adults presenting for treatment secondary to persistent symptoms after mild traumatic brain injury (mTBI). This cross-sectional study identified 78 individuals with mTBI from 2014 to 2018 presenting for treatment to an outpatient multidisciplinary rehabilitation clinic. Neurobehavioral symptom inventory (NSI-22) scores were collected on admission, and ACEs for each patient were abstracted by medical record review. A linear regression model was used to assess if an individual who experienced at least one ACE before age 18 resulted in significantly different neurobehavioral scores compared with those not reporting any history of an ACE before age 18. Participants who reported at least one ACE before age 18 had significantly increased NSI-22 scores on admission to the rehabilitation clinic compared with patients without history of ACEs (mean difference 10.1, p = 0.011), adjusted for age and gender. For individuals presenting for treatment after mTBI, a history of ACEs before age 18 was associated with increased neurobehavioral symptoms.

Applications of machine learning in pediatric traumatic brain injury (pTBI): a systematic review of the literature.

OBJECTIVE: Pediatric traumatic brain injury (pTBI) is a heterogeneous condition requiring the development of clinical decision rules (CDRs) for the optimal management of these patients. Machine learning (ML) is a novel artificial intelligence (AI) predictive tool with various applications in modern neurosurgery, including the creation of CDRs for patients with pTBI. In the present study, we summarized the current literature on the applications of ML in pTBI. METHODS: A systematic review was conducted following the PRISMA guidelines. The literature search included PubMed/MEDLINE, SCOPUS, and ScienceDirect databases. We included observational or experimental studies focusing on the applications of ML in patients with pTBI under 18 years of age. RESULTS: A total of 18 articles were included in our systematic review. Of these articles, 16 were retrospective cohorts, 1 was a prospective cohort, and 1 was a case-control study. Of these articles, ten concerned ML applications in predicting the outcome of pTBI patients, while 8 reported applications of ML in predicting the need for CT scans. Artificial Neuronal Network (ANN) and Random Forest (RF) were the most commonly utilized models for the creation of predictive algorithms. The accuracy of the ML algorithms to predict the need for CT scan in pTBI cases ranged from 0.790 to 0.999, and the Area Under Curve (AUC) ranged from 0.411 (95%CI: 0.354-0.468) to 0.980 (95%CI: 0.950-1.00). The model with the maximum accuracy to predict the need for CT scan was a Deep ANN model, while the model with the maximum AUC was Ensemble Learning. The model with the maximum accuracy to predict the outcome (favorable vs. unfavorable) of patients with TBI was a support vector machine (SVM) model with 94.0% accuracy, whereas the model with the highest AUC was an ANN model with an AUC of 0.991. CONCLUSION: In the present systematic review, conventional and novel ML models were utilized to either predict the presence of intracranial trauma or the prognosis of children with pTBI. However, most of the reported ML algorithms have not been externally validated and are pending further research.

Cognitive Rehabilitation for Adults with a History of Traumatic Brain Injury.

Cognitive rehabilitation following traumatic brain injury (TBI) involves a targeted, individualized approach to address deficits in attention, memory, executive functions, and/or other cognitive domains. This overview highlights the importance of thorough assessment to inform cognitive rehabilitation, a multidimensional approach, and current best practices in intervention strategies. It provides exemplar compensatory strategies for each cognitive domain. In addition to broad clinical practice guidelines, it also addresses unique considerations that may be warranted in some subgroups with TBI. Finally, outcome measurement is summarized.

Neuropathological mRNA Expression Changes after Single Mild Traumatic Brain Injury in Pigs.

Traumatic brain injury (TBI) is a public health concern, with an estimated 42 million cases globally every year. The majority of TBIs are mild TBIs, also known as concussion, and result from the application of mechanical forces on the head. Most patients make a complete recovery and mortality is rare; therefore, studies investigating cellular changes after mild TBI in a clinical setting are limited. To address this constraint, our group utilized a pig model of closed-head rotational acceleration-induced TBI, which recreated the biomechanical loading parameters associated with concussion on a large gyrencephalic brain similar to humans. While our previous research has focused on immunohistochemical characterization of neuropathology, the current study utilized transcriptomic assays to evaluate an array of TBI-induced neurodegenerative analytes. Pigs subjected to mild TBI were survived for 3 days post-injury (DPI) (n = 3), 30 DPI (n = 3), or 1 year post-injury (YPI) (n = 3) and compared to animals undergoing a sham procedure (n = 8). RNA was isolated from whole coronal sections of fixed tissue and multiplexed on a Nanostring neuropathology panel. Differential expression analysis revealed 11 differentially expressed genes at 3 DPI versus sham, including downregulation of the synaptotagmin calcium sensor gene (SYT1), upregulation of the neurofibromin gene (NF1), and upregulation of the Alzheimer's disease-associated receptor gene (SORL1). There were no differentially expressed genes at 30 DPI or 1 YPI compared to shams. Additionally, high-magnitude undirected global significance scores (GSS) were detected at 3 DPI for chromatin modification and autophagy gene sets, and at 30 DPI for cytokine gene sets, while many dysregulated gene sets were highlighted by directed GSSs out to 1 YPI. This study adds to a growing body of literature on transcriptomic changes in a clinically relevant large animal model of closed-head TBI, which highlights potential therapeutic targets following mild TBI.

Assessing the Predictive Utility of the C-Reactive Protein-to-Lymphocyte Ratio for Mortality in Isolated Traumatic Brain Injury: A Single-Center Retrospective Analysis.

Introduction: Early identification of high-risk traumatic brain injury (TBI) patients is crucial for optimizing treatment strategies and improving outcomes. The C-reactive protein-to-lymphocyte ratio (CLR) reflects systemic immunology and inflammation function and serves as a new biomarker for patient stratification. This study aimed to assess the predictive value of the CLR for mortality in patients with isolated moderate to severe TBI. Methods: A retrospective analysis of trauma registry data from 2009 to 2022 was conducted, including 1641 adult patients with isolated moderate to severe TBI. Patient demographics, the CLR, injury characteristics, and outcomes were compared between deceased and surviving patients. Univariate and multivariate analyses were performed to identify mortality risk factors. The optimal CLR cut-off value for predicting mortality was determined using receiver operating characteristic (ROC) curve analysis. Results: The CLR was significantly higher in deceased patients compared to survivors (60.1 vs. 33.9, p < 0.001). The optimal CLR cut-off value for predicting mortality was 54.5, with a sensitivity of 0.328 and a specificity of 0.812. The area under the ROC curve was 0.566, indicating poor discriminative ability. In the multivariate analysis, the CLR was not a significant independent predictor of mortality (OR 1.03, p = 0.051). After propensity score matching to attenuate the difference in baseline characteristics, including sex, age, comorbidities, conscious level, and injury severity, the high-CLR group (CLR ≥ 54.5) did not have significantly higher mortality compared to the low-CLR group (CLR < 54.5). Conclusion: While the CLR was associated with mortality in TBI patients, it demonstrated poor discriminative ability as a standalone predictor. The association between a high CLR and worse outcomes may be primarily due to other baseline patient and injury characteristics, rather than the CLR itself.

Evaluating the Benefits of Ventriculostomy Compared to Intracranial Pressure Monitoring for Severe Pediatric Traumatic Brain Injury.

BACKGROUND: In this study, we compared outcomes between intracranial pressure monitoring (ICP) only versus ventriculostomy (VT) using a nationwide database of pediatric trauma patients. METHODS: Pediatric patients (<18 years) with severe blunt TBI who underwent ICP monitoring with or without VT were identified from the 2017-2021 ACS Trauma Quality Programs. We excluded patients who experienced death or craniotomy/craniectomy within 48 h. The primary outcome was discharge disposition. Secondary outcomes were subsequent intracranial surgery, length of stay (LOS), and infectious complications. Competing risks survival analysis was used to evaluate the multivariable association between ICP vs. VT and outcomes. RESULTS: Of 1719 eligible patients, 65.9% were male and 54.1% had VT. Between the ICP and VT groups, there were no differences in mean age (11.4 vs. 11.0 years, p = 0.145), injury severity score (30.9 vs. 30.9, p = 0.937), or median GCS (3 vs. 3, p = 0.120). Multivariable analysis showed a robust association between VT and discharge home (compared to rehabilitation center; sHR 0.85, 95% CI 0.74-0.97, p = 0.017). VT use was not associated with increased mortality compared to ICP (p = 0.342). Finally, VT patients had longer median LOS (20.5 vs. 18.0 days, p < 0.001) but there was no difference in subsequent craniotomy/craniectomy (8.6 vs. 6.5%, p = 0.096) or infectious complications (1.2 vs. 0.9%, p = 0.549). CONCLUSION: VT was associated with greater discharge to home. Although VT patients had a greater LOS, the risk for other secondary outcomes did not vary, suggesting that VT may have benefits for the treatment of severe TBI with respect to discharge disposition. LEVEL OF EVIDENCE: III.

Comparable Results Between 8 and 12 Gray TBI in Combination With Fludarabine and Post-Transplant Cyclophosphamide in MRD-Negative but Not in MRD-Positive Acute Lymphoblastic Leukemia Patients Transplanted in First Complete Remission.

BACKGROUND: The optimal TBI dose for ALL patients undergoing allogeneic SCT is still not clearly defined. METHODS: Single-center retrospective analysis of high-risk ALL patients in CR1 treated with 8 Gy (n = 22) or 12 Gy (n = 50) TBI in combination with fludarabine and PTCy. Median patient age in the 8 Gy TBI cohort was 63 (37-79) and 37 (18-56) in the 12 Gy TBI cohort and median follow-up time was 21 months (range 1-92). RESULTS: OS and LFS at 2 years after 8 Gy were 65% and 55% versus 74% and 74% after 12 Gy (p = 0.3 and p = 0.2, respectively). CIR and NRM at 2 years were 27% and 14% after 8 Gy versus 4% and 20% after 12 Gy (p = 0.004 and p = 0.4, respectively). MRD-positive (+) patients (n = 26) receiving 12 Gy (n = 19) showed better OS (p = 0.01), LFS (p = 0.009), GRFS, lower CIR (p = 0.02), and similar NRM than did MRD+ patients receiving 8 Gy (n = 7). MRD-negative (-) patients (n = 38) receiving 12 Gy (n = 27) had similar OS, LFS, GRFS, lower CIR, and higher NRM (p = 0.04) than did MRD- patients receiving 8 Gy (n = 11). CONCLUSION: Our study demonstrates that 8 Gy TBI in comparison to 12 Gy TBI results in low NRM but a high relapse rate with similar OS, LFS, and GRFS. In MRD+ high-risk ALL patients, allogeneic SCT with 12 Gy TBI leads to improved OS, LFS, GRFS, and a low relapse rate. Prospective studies comparing the different treatment regimens with larger MRD patient cohorts are needed to confirm this data.

External lumbar drainage for the management of refractory intracranial hypertension in pediatric severe traumatic brain injury: a retrospective single-center case series.

OBJECTIVE: Guidelines for the management of pediatric severe traumatic brain injury (TBI) recommend external ventricular drainage for CSF drainage as a first-tier treatment in the intracranial pressure (ICP) pathway. However, ventriculostomy in children can sometimes be challenging because of the small size of the lateral ventricles. External lumbar drainage (ELD) may be a useful alternative; therefore, the authors analyzed the outcome of a cohort of pediatric patients who underwent ELD to manage intracranial hypertension (ICH). METHODS: This study retrospectively enrolled pediatric patients with ICH following severe TBI who underwent ELD. Radiological and clinical severity scores (Marshall classification, Rotterdam score, Injury Severity Score, and Pediatric Trauma Score) were noted. ICP and cerebral perfusion pressure (CPP) curves were analyzed 12 hours before and after the procedure. Any change in medical therapy was recorded, as well as the total volume and duration of drainage. Cerebellar tonsillar position according to the McRae line was noted before and after ELD. Glasgow Outcome Scale-Extended score at follow-up was also noted. RESULTS: Thirty patients were included, with a mean age of 8 ± 4.4 years, and a median admission Glasgow Coma Scale score of 7 ± 4 (range 3-13). ELD was performed after a median delay of 1 day (range 0-7 days), mean drainage volume/day was 296 ± 129 ml, and median duration of drainage was 7 ± 5 (range 2-12) days. Forty-three percent of the patients underwent ELD as a part of the first-tier therapy. ICP decreased after ELD (mean difference 13.4 ± 6.2 mm Hg, p < 0.001), whereas CPP increased (mean difference 10.6 ± 6.4 mm Hg, p < 0.001). Fifty-three percent of the cohort did not need any further second-tier therapy after ELD. The study found 1 case of drain revision and 3 cases of cerebellar tonsil herniation. CONCLUSIONS: These preliminary data suggest ELD is a valuable option to treat ICH in severely head-injured children, limiting the use of second-tier treatments. This pilot study should lay the foundation for a multicenter prospective trial.