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Background: Experimental work suggested that resuscitative Endovascular Balloon Occlusion of the aorta (REBOA) preserves cerebral circulation in animal models of traumatic brain injury. No clinical work has evaluated the role of REBOA in the presence of associated severe traumatic brain injury (TBI). We investigated the impacts of REBOA on neurological and survival outcomes., Methods: Propensity-score matched study, using the American College of Surgeons Trauma Quality Improvement Program database. Patients with severe TBI patients (Abbreviated Injury Scale ≥3) receiving REBOA within 4 ​h from arrival were matched with similar patients not receiving REBOA. Neurological matching included head AIS, pupils, and midline shift. Clinical outcomes were compared between the two groups., Results: 434 REBOA patients were matched with 859 patients without REBOA. Patients in the REBOA group had higher rates of in-hospital mortality (63.6 ​% vs 44.2 ​%, p ​< ​0.001), severe sepsis (4.4 ​% vs 2.2 ​%, p ​= ​0.029), acute kidney injury (10.1 ​% vs 6.6 ​%, p ​= ​0.029), and withdrawal of life support (25.4 ​% vs 19.6 ​%, p ​= ​0.020) despite of lower craniectomy/craniotomy rate (7.1 ​% vs 12.7 ​%, p ​< ​0.002)., Conclusion: In patients with severe TBI, REBOA use is associated with an increased risk of in-hospital mortality, AKI, and infectious complications., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest related to this manuscript. The only assistance from generative artificial intelligence technology is grammar check to ensure the clarity and fluency of the manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients with type O blood may have an increased risk of hemorrhagic complications because of lower baseline levels of von Willebrand factor and factor VIII, but the transition to a mortality difference in trauma is less clear. We hypothesized that type O trauma patients will have differential proteomic and metabolomic signatures in response to trauma beyond von Willebrand factor and factor VIII alone., Methods: Patients meeting the highest level of trauma activation criteria were prospectively enrolled. Blood samples were collected upon arrival to the emergency department. Proteomic and metabolomic (multiomics) analyses of these samples were performed using liquid chromatography-mass spectrometry. Demographic, clinical, and multiomics data were compared between patients with type O blood versus all other patients., Results: There were 288 patients with multiomics data; 146 (51%) had type O blood. Demographics, injury patterns, and initial vital signs and laboratory measurements were not different between groups. Type O patients had increased lengths of stay (7 vs. 6 days, p = 0.041) and a trend toward decreased mortality secondary to traumatic brain injury compared with other causes (traumatic brain injury, 44.4% vs. 87.5%; p = 0.055). Type O patients had decreased levels of mannose-binding lectin and mannose-binding lectin-associated serine proteases 1 and 2, which are required for the initiation of the lectin pathway of complement activation. Type O patients also had metabolite differences signifying energy metabolism and mitochondrial dysfunction., Conclusion: Blood type O patients have a unique multiomics signature, including decreased levels of proteins required to activate the lectin complement pathway. This may lead to overall decreased levels of complement activation and decreased systemic inflammation in the acute phase, possibly leading to a survival advantage, especially in traumatic brain injury. However, this may later impair healing. Future work will need to confirm these associations, and animal studies are needed to test therapeutic targets., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Level-I and level-II trauma centers are required to offer equivalent resources since "The Orange Book." This study evaluates differences between level-I and level-II management of solid organ injury (SOI) with traumatic brain injury (TBI)., Methods: We conducted a retrospective review of the National Trauma Data Banks from 2013 to 2021 of adult (≥18 years), blunt trauma patients with both TBI and SOI treated at level-I or level-II trauma centers., Results: 48,479 TBI and SOI patients were identified, 32,611 (67.3%) at level-I centers. Unadjusted incidence of laparotomy was higher at level I (14.5% vs 11.7%, P < 0.001), and angiography rates were similar (3.3% vs 3.4%, P 0.717). Sub-group analysis of stable patients (SBP ≥100) showed an increase in nonoperative management at level II (87.3% vs 88.7%, P < 0.001) and decrease in laparotomy (9.9% vs 8.3%, P < 0.001). On logistic regression (LR), severe TBI, high-grade SOI, and level I trauma status were predictors of laparotomy. Logistic regression showed mild/moderate TBI with high-grade SOI and level II were associated with use of angiography. Unadjusted mortality rates were slightly different (14.8% vs 13.4%, P < 0.001), but there was no association with trauma level on LR., Discussion: Nonoperative management was seen more at level-II centers with laparotomy at level I. Subgroup analysis showed no difference in mortality in trauma levels. Matched patients for level I and II showed no statistical difference in management. Patients were treated similarly at both levels with similar outcomes and mortality., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Traumatic brain injuries (TBIs) are one of the leading causes of death or long-term disability around the world. As a result of improvements in supportive care, patients are surviving more severe insults with more pronounced dependency on their families, hospitals, and long-term care facilities. The introduction of brain tissue oxygenation (PbtO2) monitoring aims to recognize episodes of reduced cerebral perfusion with and without associated increased intracranial pressure (ICP)., Aim: The aim of this review is to determine the impact of PbtO2 on the Glasgow Outcome Scale/Glasgow Outcome Scale Extended (GOS/GOSE) in patients with moderate to severe TBI., Study Design: Systematic review with narrative and meta-analysis. All original research in which adult patients undergoing PbtO2 were compared with a control group of traditional ICP/cerebral perfusion pressure (CPP) monitoring. Both randomized controlled trials and observational studies were included in this review., Methods: Databases were searched in September 2022. The primary outcome of the review was the impact of PbtO2 monitoring on GOS/GOSE, while secondary outcomes were mortality and length of stay (LOS) in the intensive care unit (ICU)., Results: Seven studies with a combined number of 770 patients were included in the review. These patients were adults ≥16 years of age. Only two of the studies included found a statistically significant association between PbtO2 monitoring and improved long-term neurological outcomes in patients with TBI (p = .01, p < .01). A meta-analysis of the secondary outcomes identified an associated reduction of mortality in favour of the group treated with PbtO2 monitoring (p < .0001). Results from studies examining LOS in ICU have demonstrated an associated increase of LOS in ICU in patients treated with PbtO2-guided therapy., Conclusion: From the studies included in this review, only two found a statistically significant association between PbtO2 monitoring and long-term outcomes. It is unclear whether PbtO2 goal-directed therapy has a positive impact on the long-term neurological functions and mortality of patients suffering from TBI. A multicentre randomized controlled trial may provide further evidence, but not necessarily conclusive., Relevance to Clinical Practice: Further research is warranted to determine the efficacy of the introduction of this new monitoring system to guide local policy change., (© 2023 British Association of Critical Care Nurses.)

Traumatic brain injury (TBI) is a common problem in elderly individuals, with significant morbidity and mortality. The elderly Traumatic Brain Injury (eTBI) score, a novel tool for predicting outcomes in elderly patients with TBI, has shown promising results in previous studies. This study aimed to validate the eTBI score in a larger cohort of elderly patients with TBI in the Middle East. We conducted a retrospective study on 337 TBI patients with a mean age of 73.04 ± 8.73, admitted to a tertiary care hospital between March 2021 and November 2022. Within 30 days of admission, the patients' conditions, including mortality and entering a vegetative state, were evaluated. The study population was split into three groups based on eTBI score: low, medium, and high risk; then patients were divided into two subgroups based on their Glasgow Outcome Scale (GOS ≤ 2, GOS > 2) in 30 days from hospital admission. Poor outcomes (mortality and entering a vegetative state) occurred in 24.3% of the study population. Within 30 days of hospital admission, 88% of low-risk patients experienced some degree of improvement, while 100% of high-risk patients died or fell into a vegetative state. In the medium-risk group, there was a significant correlation between unresponsive pupil (P = 0.006), initial GCS score (P = 0.003), need for a ventilator device (P = 0.015), need for surgical treatment (P = 0.031) and poor outcomes. Despite having a low sensitivity (21% vs. 57%), the eTBI score performed well in terms of accuracy (81% vs. 88%), specificity (100 vs. 98%), positive predictive value (100% vs. 90%), and negative predictive value (80% vs. 88%) for both eTBI ≤ 0 and eTBI ≤ 3 thresholds. The eTBI score is a reliable tool for predicting outcomes in elderly patients with TBI. This scoring system has a positive predictive value of 100% in the eTBI ≤ 0 group, which shows that 100% of the patients who are predicted by the eTBI score to have a poor outcome will indeed have a poor outcome. Patients in the high-risk group should be closely monitored and provided with intensive care, while those in the low-risk group can be reassured about their prognosis. The eTBI score can also be used in conjunction with other clinical factors to inform treatment decisions for patients in the medium-risk group., (© 2024. The Author(s).)

Background and Objectives: Administrative data are invaluable for assessing outcomes at the population level. However, there are few validated patient-centered outcome measures that capture morbidity following traumatic brain injury (TBI) using these data. We sought to characterize and validate days at home (DAH) as a measure to quantify population-level outcomes after moderate to severe TBI. We additionally assessed the earliest feasible outcome assessment period for patients with TBI using this outcome measure., Methods: This multicenter retrospective cohort study used linked health administrative data sources to identify adults with moderate to severe TBI presenting to trauma centers in Ontario, Canada, between 2009 and 2021. DAH at 180 days (DAH 180 days ) reflects the total number of days spent alive and at home excluding the days spent institutionalized across care settings. Construct validity was determined using hierarchical quantile regression to assess the associations between clinical and injury covariates with DAH 180 days . Predictive validity was assessed using Spearman rank correlation. We estimated minimally important difference (MID) in DAH 180 days to aid with outcome measure interpretability., Results: There were 6,340 patients who met inclusion criteria. Median DAH 180 days was 70 days (interquartile range 0-144). Mortality occurred in 2,162 (34.1%) patients within 90 days following injury. Patients in the lower DAH 180 days group were more commonly older (absolute standardized difference [ASD] = 0.68) with higher preinjury health resource utilization (ASD = 0.36) and greater injury severity (ASD = 0.81). Increased baseline health resource utilization (-10.1 days, 95% CI -17.4 to -2.8, p = 0.0041), older age (-4.6 days, 95% CI -5.7 to -3.4, p < 0.001), higher cranial injury severity (-84.6 days, 95% CI -98.3 to -71.0, p < 0.001), and major extracranial injuries (-14.2 days, 95% CI -19.5 to -8.93, p < 0.001) were significantly associated with fewer DAH 180 days . DAH 180 days was positively correlated with DAH at up to 3 years ( r = 0.91, 95% CI 0.90-0.92) and negatively correlated with direct health care expenditure ( r s = -0.89, 95% CI -0.88 to -0.90). The average MID estimated from anchor-based and distribution-based methods was 18 days., Discussion: We validate DAH 180 days as a potentially useful outcome measure with construct, predictive, and face validity in a population with moderate to severe TBI. Given the intensity of acute care requirements for patients with TBI, our work highlights DAH 180 days as a feasible and sufficiently responsive outcome measure.

Patients with traumatic brain injury (TBI) frequently exhibit concomitant immunosuppression. In this study, we evaluated the predictive values of soluble programmed death-1 (sPD-1) and soluble programmed death ligand-1 (sPD-L1) in patients with severe TBI. Peripheral blood sPD-1 and sPD-L1 levels were measured within 48 h of patient admission. A total of 20 healthy volunteers and 82 patients were enrolled in this study. The levels of sPD-1 and sPD-L1 were upregulated in patients with severe TBI (P < 0.001). They were significantly increased in the post-TBI severe pneumonia group and among non-survivors (P < 0.001). The area under the curves (AUCs) for sPD-1 and sPD-L1 levels to predict severe pneumonia were 0.714 and 0.696, respectively, and the AUCs to predict mortality were 0.758 and 0.735. The levels of sPD-1 and sPD-L1 are correlated with the GCS scores at admission, APACHE II scores, length of MV, and time elapsed to mortality. The levels of sPD-1 and sPD-L1 emerged as independent predictive factors for severe pneumonia and mortality. This study demonstrates that upregulation of sPD-1 and sPD-L1 in severe TBI patients is significantly associated with severe pneumonia and mortality, suggesting their potential as predictive biomarkers for these outcomes., (© 2024. The Author(s).)

Background: Although the optimization of brain oxygenation is thought to improve the prognosis, the effect of brain tissue oxygen pressure (PbtO2) for patients with severe traumatic brain injury (STBI) remains controversial. Therefore, the present study aimed to determine whether adding PbtO2 to intracranial pressure (ICP) monitoring improves clinical outcomes for patients with STBI., Methods: PubMed, Embase, Scopus and Cochrane Library were searched for eligible trials from their respective inception through April 10th, 2024. We included clinical trials contrasting the combined monitoring of PbtO 2 and ICP versus isolated ICP monitoring among patients with STBI. The primary outcome was favorable neurological outcome at 6 months, and secondary outcomes including the in-hospital mortality, long-term mortality, length of stay in intensive care unit (ICU) and hospital., Results: A total of 16 studies (four randomized studies and 12 cohort studies) were included in the meta-analysis. Compared with isolated ICP monitoring, the combined monitoring was associated with a higher favorable neurological outcome rate at 6 months (RR 1.33, 95% CI [1.17-1.51], P  < 0.0001, I 2 = 0%), reduced long-term mortality (RR 0.72, 95% CI [0.59-0.87], P  = 0.0008, I 2 = 2%). No significant difference was identified in the in-hospital mortality (RR 0.81, 95% CI 0.66 to 1.01, P  = 0.06, I 2 = 32%), length of stay in ICU (MD 2.10, 95% CI [-0.37-4.56], P  = 0.10, I 2 = 78%) and hospital (MD 1.07, 95% CI [-2.54-4.67], P  = 0.56, I 2 = 49%) between two groups. However, the pooled results of randomized studies did not show beneficial effect of combined monitoring in favorable neurological outcome and long-term mortality., Conclusions: Currently, there is limited evidence to prove that the combined PbtO2 and ICP monitoring may contribute to improved neurological outcome and long-term mortality for patients with STBI. However, the benefit of combined monitoring should be further validated in more randomized studies., Competing Interests: The authors declare there are no competing interests., (©2024 Zhang et al.)

Background: Globally, 64-74 million individuals around the world are estimated to sustain traumatic brain injury every year. Moderate and severe traumatic brain injury can lead to a lifetime physical, cognitive, emotional, and behavioral changes. There were limited studies conducted in Ethiopia regarding to traumatic brain injury mortality., Methods: An institutional based retrospective cohort study was conducted on 429 randomly selected traumatic brain injury patients aged 18 to 64 years who were admitted to East Amhara Comprehensive Specialized Hospitals from January 1, 2016 to December 31, 2021. Kobo toolbox was applied for data collection and exported to Stata version 17 for data processing and analysis. To estimate death free time, a Kaplan Meier failure curve was used. The Cox proportional hazards regression model was used at the 5% level of significance to determine effect of predictor variables on time to death., Result: A total of 429 traumatic brain injury patients aged 18 to 64 years were included with response rate of 91.3% and 145(33.8%) were dead. Open injuries (AHR = 0.25; 95% CI: 0.18-0.36), co-existing injuries (AHR = 0.40; 95% CI: 0.24-0.66), ICU admission (AHR = 0.42; 95% CI: 0.29-0.60), arrival within 4-24 h (AHR = 3.48; 95% CI: 2.01-6.03), arrival after 24 h (AHR = 6.69; 95% CI: 3.49-12.28), subdural hematoma (AHR = 2.72; 95% CI: 1.77-4.19), serum albumin < 3.5 g/dL (AHR = 0.66; 95% CI: 0.49-0.94), moderate (AHR = 0.56; 95% CI: 0.21-0.89), and mild traumatic brain injury (AHR = 0.43; 95% CI: 0.29-0.56) were predictors of traumatic brain injury mortality., Conclusion: The finding of this study showed that the mortality was 1/3rd of the total patients. Open injuries, co-existing injuries, ICU admission, arrival time (4-24 h and > 24 h), subdural hematoma, serum albumin < 3.5 g/dL and severity of traumatic brain injury (mild and moderate) were predictors of traumatic brain mortality. Therefore, working on these factors to reduce the morality of traumatic brain injury patients is very important., (© 2024. The Author(s).)

Traumatic brain injury (TBI) is a leading cause of death and disability globally as well as in Bangladesh; its incidences are growing with an increasing number of high-speed motor vehicles, more movement of the public and mechanization in industry. The aim of the study was to analyze the causes, risk factors and treatment outcomes of traumatic brain injuries in victims reported to emergency and casualty departments following intensive care with or without surgical intervention in a tertiary care hospital. This prospective type of observational study was conducted at the Neurosurgery ward of Rangpur Medical College Hospital, Bangladesh from March 2022 to February 2024. A total of 360 head injury patients with TBI were assessed with gender, age, cause, and type of trauma, Glasgow Coma Scale on admission, associated other injuries, time lapsed from trauma to hospitalization and care given. A total of 360 Cases (n=360) of TBI, male 273(n=273) and female 87(n=87) were included most common group was 16-30 years (45%) and Males (75.83%) victims were more than female (24.16%). Frequency percentage cause is RTA 190(52.7%) and intra-cranial injury (42.77%), Intra and extra-cranial injury 206(57.22%), pathophysiological cause (n=360), SDH 122(33.88%), EDH (28.33%), concussion (15.83%), cerebral contusion (14.16%), diffuse axonal injury (05%) and subarachnoid haemorrhage (2.77%). Traumatic brain injury was common among young adult males and RTA was the leading cause. Many factors influence the better outcome of TBI with reduced mortality and morbidity including the patient's age, the injury's severity, the time between TBI and the start of definitive treatment associated with other major injuries and facilities available for resuscitative care.

Introduction: The management of traumatic brain injury (TBI) requires significant health-care resources. The modified Brain Injury Guidelines (mBIG) stratifies TBI patients by severity to help guide disposition and management. We sought to analyze the outcomes of TBI patients managed in a non-intensive care unit (ICU) setting after stratifying them using the mBIG criteria., Methods: A retrospective single-center study was performed on all adult patients who sustained blunt TBI from 2021 to 2022 and were managed in a non-ICU setting. Primary outcome was unplanned upgrade to the ICU. Secondary outcomes were need for neurosurgical intervention, unplanned intubation, mortality, and hospital length of stay. Patients were divided into cohorts of mBIG 1 & 2 versus mBIG 3., Results: Of the 274 patients managed in a non-ICU setting, 119 (43.4%) met mBIG 3 criteria. The majority (76.5%) were managed in a step-down level of care. Nine patients required upgrade to the ICU, with only two upgraded for acute progression of their intracranial hemorrhage. Eight patients in mBIG 3 cohort required neurosurgical interventions, with only two related to progression of their intracranial hemorrhage and both over 24 h after admission. The remaining six patients had planned delayed neurosurgical intervention. Unplanned intubation occurred in three patients with only one related to a delayed progression of their TBI. Longer hospitalization and decreased survival were noted in mBIG 3 group. No differences in 30-d readmissions, stroke, venous thromboembolism events or seizures were found between the two groups., Conclusions: Select patients with severe TBI may be considered for admission to step-down units with frequent neurologic exams in lieu of ICU level of care., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Recent evidence links the prognosis of traumatic brain injury (TBI) to various factors, including baseline clinical characteristics, TBI specifics, and neuroimaging outcomes. This study focuses on identifying risk factors for short-term survival in severe traumatic brain injury (sTBI) cases and developing a prognostic model., Methods: Analyzing 430 acute sTBI patients from January 2018 to December 2023 at the 904th Hospital's Neurosurgery Department, this retrospective case-control study separated patients into survival outcomes: 288 deceased and 142 survivors. It evaluated baseline, clinical, hematological, and radiological data to identify risk and protective factors through univariate and Lasso regression. A multivariate model was then formulated to pinpoint independent prognostic factors, assessing their relationships via Spearman's correlation. The model's accuracy was gauged using the Receiver Operating Characteristic (ROC) curve, with additional statistical analyses for quantitative factors and model effectiveness. Internal validation employed ROC, calibration curves, Decision Curve Analysis (DCA), and Clinical Impact Curves (CIC) to assess model discrimination, utility, and accuracy. The International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) and Corticosteroid Randomization After Significant Head injury (CRASH) models were also compared through multivariate regression., Results: Factors like unilateral and bilateral pupillary non-reactivity at admission, the derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), D-dimer to fibrinogen ratio (DFR), infratentorial hematoma, and Helsinki CT score were identified as independent risk factors (OR > 1), whereas serum albumin emerged as a protective factor (OR < 1). The model showed superior predictive performance with an AUC of 0.955 and surpassed both IMPACT and CRASH models in predictive accuracy. Internal validation confirmed the model's high discriminative capability, clinical relevance, and effectiveness., Conclusions: Short-term survival in sTBI is significantly influenced by factors such as pupillary response, dNLR, PLR, DFR, serum albumin levels, infratentorial hematoma occurrence, and Helsinki CT scores at admission. The developed nomogram accurately predicts sTBI outcomes, offering significant clinical utility., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Trauma patients are at increased risk for venous thromboembolism events (VTEs). The decision of when to initiate VTE chemoprophylaxis (VTEP) and with what agent remains controversial in patients with severe traumatic brain injury (TBI)., Methods: This comparative effectiveness study evaluated the impact of timing and agent for VTEP on outcomes for patients with severe TBI (Abbreviated Injury Scale head score of 3, 4, or 5). Data were collected at 35 Level 1 and 2 trauma centers from January 1, 2017, to June 1, 2022. Patients were placed into analysis cohorts: no VTEP, low-molecular-weight heparin (LMWH) ≤48 hours, LMWH >48 hours, heparin ≤48 hours, and heparin >48 hours. Propensity score matching accounting for patient factors and injury characteristics was used with logistic regression modeling to evaluate in-hospital mortality, VTEs, and discharge disposition. Neurosurgical intervention after initiation of VTEP was used to evaluate extension of intracranial hemorrhage., Results: Of 12,879 patients, 32% had no VTEP, 36% had LMWH, and 32% had heparin. Overall mortality was 8.3% and lowest among patients receiving LMWH ≤48 hours (4.1%). Venous thromboembolism event rates were lower with use of LMWH (1.6% vs. 4.5%; odds ratio, 2.98; 95% confidence interval, 1.40-6.34; p = 0.005) without increasing mortality or neurosurgical interventions. Venous thromboembolism event rates were lower with early prophylaxis (2.0% vs. 3.5%; odds ratio, 1.76; 95% confidence interval, 1.15-2.71; p = 0.01) without increasing mortality ( p = 1.0). Early VTEP was associated with more nonfatal intracranial operations ( p < 0.001). However, patients undergoing neurosurgical intervention after VTEP initiation had no difference in rates of mortality, withdrawal of care, or unfavorable discharge disposition ( p = 0.7, p = 0.1, p = 0.5)., Conclusion: In patients with severe TBI, LMWH usage was associated with lower VTE incidence without increasing mortality or neurosurgical interventions. Initiation of VTEP ≤48 hours decreased VTE incidence and increased nonfatal neurosurgical interventions without affecting mortality. Low-molecular-weight heparin is the preferred VTEP agent for severe TBI, and initiation ≤48 hours should be considered in relation to these risks and benefits., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Antiplatelet agents (AAs) may increase the risk of intracranial hemorrhage (ICH). It is unclear whether reversal of antiplatelet effects (REV = desmopressin acetate [DDAVP] + Platelets) decreases ICH progression. The goal of the study was to determine whether REV was associated with decreased progression of ICH on repeat brain computed tomography (CT) scan., Methods: This is a clustered study (November 2019 to March 2022) at two regionally distinct trauma centers (TCs) with differing standards of practice in patients with ICH, one reversal with DDAVP + Platelets (REV+) and the other no reversal with DDAVP + Platelets (REV-). Using electronic and manual chart review, data were collected on inpatients aged ≥ 18 y on preinjury AAs with CT proven ICH (abbreviated injury scale head ≥ 2) and no other abbreviated injury scale > 2 injuries, who had at least one repeat CT scan within 120 h of admission. ICH progression on repeat brain CT scan, mortality, and resource utilization were compared via univariate analysis (α = 0.05)., Results: One hundred fourteen patients were enrolled: 72 REV+ at the first TC and 42 REV- at the second TC. REV+ group had fewer White patients and a lower proportion on preinjury aspirin but were otherwise similar. ICH progression rate was 24/72 (33.3%) for REV+ and 11/42 (26.2%) for REV- (P = 0.43). Isolated subarachnoid hemorrhage was the most common lesion, followed by isolated subdural hemorrhage. No patients required cranial surgery. All-cause mortality (expired + hospice) was 5/72 (6.9%) and 1/42 (2.4%), respectively (P = 0.29)., Conclusions: In this study of patients on preinjury AAs, REV was not associated with decreased ICH progression, lower mortality, or less resource utilization. These findings should be confirmed in a larger, prospective study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The main focus of traumatic brain injury (TBI) management is prevention of secondary injury. Therapeutic hypothermia (TH), the induction of a targeted low core body temperature, has been explored as a potential neuroprotectant in TBI. The aim of this article is to synthesize the available clinical data comparing the use of TH with the use of normothermia in TBI., Methods: A systematic search was conducted through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized clinical trials including one or more outcome of interest associated with TH use in TBI. Independent reviewers evaluated quality of the studies and extracted data on patients with TBI undergoing TH treatment compared with those undergoing normothermia treatment. Pooled estimates, confidence intervals (CIs), and risk ratios (RRs) or odds ratios were calculated for all outcomes., Results: A total of 3,909 patients from 32 studies were eligible for analysis. Pooled analysis revealed a significant benefit of TH on mortality and functional outcome (RR 0.81, 95% CI 0.68-0.96, I 2  = 41%; and RR 0.77; 95% CI 0.67-0.88, I 2  = 68%, respectively). However, subgroup analysis based on risk of bias showed that only studies with a high risk of bias maintained this benefit. When divided by cooling method, reduced poor functional outcome was seen in the systemic surface cooling and cranial cooling groups (RR 0.68, 95% CI 0.59-0.79, I 2  = 35%; and RR 0.44, 95% CI 0.29-0.67, I 2  = 0%), and no difference was seen for the systemic intravenous or gastric cooling group. Reduced mortality was only seen in the systemic surface cooling group (RR 0.63, 95% CI 0.53-0.75, I 2  = 0%,); however, this group had mostly high risk of bias studies. TH had an increased rate of pneumonia (RR 1.24, 95% CI 1.10-1.40, I 2  = 32%), coagulation abnormalities (RR 1.63, 95% CI 1.09-2.44, I 2  = 55%), and cardiac arrhythmias (RR 1.78, 95% CI 1.05-3.01, I 2  = 21%). Once separated by low and high risk of bias, we saw no difference in these complications in the groups with low risk of bias. Overall quality of the evidence was moderate for mortality, functional outcome, and pneumonia and was low for coagulation abnormalities and cardiac arrhythmias., Conclusions: With the addition of several recent randomized clinical trials and a thorough quality assessment, we have provided an updated systematic review and meta-analysis that concludes that TH does not show any benefit over normothermia in terms of mortality and functional outcome., (© 2024. Crown.)

Introduction: Traumatic brain injury (TBI) is a leading cause of death and disability, often resulting in prolonged coma and disordered consciousness. There are currently gaps in understanding the factors affecting rehabilitation location and outcome after TBI., Objective: To identify the impact of demographics, comorbidities, and complications on discharge disposition in adults with prolonged coma following TBI., Design: Retrospective cohort study., Setting: Tertiary care hospitals and trauma centers in the United States., Participants: Patients 18 years of age or older with TBI and prolonged coma during the years 2008 to 2015., Intervention: Not applicable., Main Outcome Measures: Demographics, clinical injury data, comorbidities, and complications were collected, and odds ratios (ORs) and descriptive analysis were calculated for mortality, long-term rehabilitation, and home discharge without services., Results: A total of 6929 patients with TBI and prolonged coma were included in the final analysis; 3318 (47.9%) were discharged to rehabilitation facilities, 1859 (26.8%) died, and 1752 (25.3%) were discharged home. Older patients and those with higher injury severity scores had significantly higher ORs for mortality and rehab discharge. A total of 58.3% of patients presented with at least one comorbidity. Non-White ethnicities and self-pay/uninsured patients were significantly less likely to be discharged to a rehab facility. Furthermore, comorbidities including congestive heart failure (CHF) and diabetes were associated with a significantly increased OR for mortality and rehab discharge compared to home discharge without services., Conclusions: Comorbidities, age, and injury severity were the most significant risk factors for increased mortality and acute rehab discharge. Maximizing the treatment of comorbidities including CHF and diabetes has the potential to decrease mortality and adverse outcomes following TBI with prolonged coma., (© 2024 American Academy of Physical Medicine and Rehabilitation.)

Purpose: This study examined the research on older adults with a moderate to severe traumatic brain injury (TBI), with a focus on mortality and discharge disposition., Method: Systematic searches were conducted in MEDLINE, CINAHL, EMBASE and PsycINFO for studies up to April 2022 in accordance with PRISMA guidelines., Results: 64 studies, published from 1992 to 2022, met the inclusion criteria. Mortality was higher for older adults ≥60 years old than for their younger counterparts; with a dramatic increase for those ≥80 yr, with rates as high as 93 %. Similar findings were reported regarding mortality in intensive care, surgical mortality, and mortality post-hospital discharge; with an 80 % rate at 1-year post-discharge. Up to 68.4 % of older adults were discharged home; when compared to younger adults, those ≥65 years were less likely to be discharged home (50-51 %), compared to those <64 years (77 %). Older adults were also more likely to be discharged to long-term care (up to 31.6 %), skilled nursing facilities (up to 46.1 %), inpatient rehabilitation (up to 26.9 %), and palliative or hospice care (up to 58 %)., Conclusion: Given their vulnerability, optimizing outcomes for older adults with moderate-severe TBI across the healthcare continuum is critical., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To explore mortality risk factors and to construct an online nomogram for predicting in-hospital mortality in traumatic brain injury (TBI) patients receiving invasive mechanical ventilation (IMV) in intensive care unit (ICU)., Methods: We retrospectively analyzed TBI patients on IMV in ICU from Medical Information Mart for Intensive Care IV database and 2 hospitals. Least absolute shrinkage and selection operation regression and multiple logistic regression were used to detect predictors of in-hospital mortality and to construct an online nomogram. The predictive performance of nomogram was evaluated using area under the receiver operating characteristic curves (AUC), calibration curves, decision curve analysis, and clinical impact curves., Results: Five hundred ten from Medical Information Mart for Intensive Care IV database were enrolled for nomogram construction (80%, n = 408) and internal validation (20%, n = 102). One hundred eighty-five from 2 hospitals were enrolled for external validation. Least absolute shrinkage and selection operation-logistic regression revealed predictors of in-hospital mortality among TBI patients on IMV in ICU included Glasgow Coma Scale (GCS) after ICU admission, Acute Physiology Score III (APS III) after ICU admission, neutrophil and lymphocyte ratio after IMV, blood urea nitrogen after IMV, arterial serum lactate after IMV, and in-hospital tracheotomy. The AUC, calibration curves, decision curve analysis, and clinical impact curves indicated the nomogram had good discrimination, calibration, clinical benefit, and applicability. The multimodel comparisons revealed the nomogram had higher AUC than GCS, APS III, and Simplified Acute Physiology Score II., Conclusions: We constructed and validated an online nomogram based on routinely recorded factors at admission to ICU and at the beginning of IMV to target prediction of in-hospital mortality among TBI patients on IMV in ICU., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In the prehospital tranexamic acid (TXA) for traumatic brain injury (TBI) trial, TXA administered within 2 hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT)., Methods: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial ( ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale score < 13) and systolic blood pressure ≥ 90 mm Hg within 2 hours of injury to a 2-g out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-g out-of-hospital TXA bolus/1-g in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) ≤ 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors., Results: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-g TXA bolus group (17%) compared with the other two groups (1-g bolus/1-g infusion 26%, placebo 27%). The estimated adjusted difference between the 2-g bolus and placebo groups was -8·5 percentage points (95% confidence interval [CI], -15.9 to -1.0) and between the 2-g bolus and 1-g bolus/1-g infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). Disability Rating Scale at 6 months was lower in the 2-g TXA bolus group than the 1-g bolus/1-g infusion (estimated difference - 2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups., Conclusion: A 2-g out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing., Level of Evidence: Therapeutic/Care Management; Level II., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), the lymphocyte-monocyte ratio (LMR), the neutrophil-monocyte ratio (NMR) and the systemic immune inflammation index (SII) are associated with clinical outcomes in oncological diseases, cardiovascular diseases, infectious / inflammatory diseases, endocrinological, pulmonary and brain injuries. Here, we investigate its association with hospital mortality in patients with severe traumatic brain injury., Methods: We retrospectively reviewed clinical data from patients with severe traumatic brain injury (sTBI) who were treated in our department between January 2015 and December 2020. NLR, PLR, NMR, LMR and SII data were collected between admission and day 3, as well as other indicators related. The relationship between hematological ratios and in-hospital mortality were analyzed., Results: A total of 96 patients were included in study, hospital mortality was 40.6% (N.=39). The levels of NLR on admission (D0), NLR day 1 (D1), NLR day 2 (D2), NLR day 3 (D3), NMR day 1 (D1) and NMR day (2) remained significantly higher in patients with death intra-hospital (P=0.030; P=0.038; P=0.016; P=0.048; P=0.046 and P=0.001, respectively). Multivariate logistic analysis showed that higher NLR values at admission and day 2 NMR were associated with in-hospital mortality (OR=1.120, P=0.037; and OR=1.307, P=0.004, respectively). Analysis of the recipient operating characteristic (ROC) curve showed that the NLR on admission had a sensitivity of 59.0% and a specificity of 66.7% (area under the curve 0.630, P=0.031, Youden's Index 0.26) and the NMR of day 2 had a sensitivity of 67.7% and a specificity of 70.4% (area under the curve 0.719, P=0.001, Youden's index 0.38) to predict mortality intra-hospital based on the best threshold., Conclusions: Our analysis indicates that higher NLR levels on admission and day 2 NMR are independent predictors of in-hospital mortality in patients with sTBI.

Purpose: Mortality is often assessed during ICU stay and early after, but rarely at later stage. We aimed to compare the long-term mortality between TBI and ICH patients., Materials and Methods: From an observational cohort, we studied 580 TBI patients and 435 ICH patients, admitted from January 2013 to February 2021 in 3 ICUs and alive at 7-days post-ICU discharge. We performed a Lasso-penalized Cox survival analysis., Results: We estimated 7-year survival rates at 72.8% (95%CI from 67.3% to 78.7%) for ICH patients and at 84.9% (95%CI from 80.9% to 89.1%) for TBI patients: ICH patients presenting a higher mortality risk than TBI patients. Additionally, we identified variables associated with higher mortality risk (age, ICU length of stay, tracheostomy, low GCS, absence of intracranial pressure monitoring). We also observed anisocoria related with the mortality risk in the early stage after ICU stay., Conclusions: In this ICU survivor population with a prolonged follow-up, we highlight an acute risk of death after ICU stay, which seems to last longer in ICH patients. Several variables characteristic of disease severity appeared associated with long-term mortality, raising the hypothesis that the most severe patients deserve closer follow-up after ICU stay., (Copyright © 2024. Published by Elsevier Inc.)

Among patients with severe traumatic brain injury (TBI), there is high prognostic uncertainty but growing evidence that recovery of independence is possible. Nevertheless, families are often asked to make decisions about withdrawal of life-sustaining treatment (WLST) within days of injury. The range of potential outcomes for patients who died after WLST (WLST+) is unknown, posing a challenge for prognostic modeling and clinical counseling. We investigated the potential for survival and recovery of independence after acute TBI in patients who died after WLST. We used Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data and propensity score matching to pair participants with WLST+ to those with a similar probability of WLST (based on demographic and clinical characteristics), but for whom life-sustaining treatment was not withdrawn (WLST-). To optimize matching, we divided the WLST- cohort into tiers (Tier 1 = 0-11%, Tier 2 = 11-27%, Tier 3 = 27-70% WLST propensity). We estimated the level of recovery that could be expected in WLST+ participants by evaluating 3-, 6-, and 12-month Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale outcomes in matched WLST- participants. Of 90 WLST+ participants (80% male, mean [standard deviation; SD] age = 59.2 [17.9] years, median [IQR] days to WLST = 5.4 [2.2, 11.7]), 80 could be matched to WLST- participants. Of 56 WLST- participants who were followed at 6 months, 31 (55%) died. Among survivors in the overall sample and survivors in Tiers 1 and 2, more than 30% recovered at least partial independence (GOSE ≥4). In Tier 3, recovery to GOSE ≥4 occurred at 12 months, but not 6 months, post-injury. These results suggest a substantial proportion of patients with TBI and WLST may have survived and achieved at least partial independence. However, death or severe disability is a common outcome when the probability of WLST is high. While further validation is needed, our findings support a more cautious clinical approach to WLST and more complete reporting on WLST in TBI studies.

Objectives: We sought to evaluate the effectiveness of any antiseizure medication on the incidence of early post-traumatic seizures among adult patients with traumatic brain injury., Data Sources: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, and LILACS were searched from inception to October 2023., Study Selection: We included randomized trials of adult patients with traumatic brain injury evaluating any antiseizure medication compared with either placebo or another agent., Data Extraction: Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Our main outcome of interest was the occurrence of early seizures (i.e., within 7 d); secondary outcomes included late-seizures and all-cause mortality., Data Synthesis: Bayesian network meta-analyses were used to derive risk ratios (RRs) alongside 95% credible intervals (CrIs). We used Grading of Recommendations Assessment, Development, and Evaluation methodology to rate the certainty in our findings. Overall, ten individual randomized controlled trials (1851 participants) were included. Compared with placebo, phenytoin (RR, 0.28; 95% CrI, 0.13-0.57; moderate certainty) and levetiracetam (RR, 0.20; 95% CrI, 0.07-0.60; moderate certainty) were associated with a reduction in the risk of early seizures. Carbamazepine may be associated with a reduced risk of early seizures, but the evidence is very uncertain (RR, 0.41; 95% CrI, 0.12-1.27; very low certainty). Valproic acid may result in little to no difference in the risk of early seizures, but the evidence is very uncertain (RR, 0.97; 95% CrI, 0.16-9.00; very low certainty). The evidence is very uncertain about the impact of any antiseizure medication on the risk of late seizures or all-cause mortality at longest reported follow-up time., Conclusions: Phenytoin or levetiracetam reduce the risk of early seizures among adult patients with traumatic brain injury. Further research is needed to evaluate required duration of therapy and long-term safety profiles., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Traumatic brain injury (TBI) is the leading cause of traumatic death worldwide and is a public health problem associated with high mortality and morbidity rates, with a significant socioeconomic burden. The diagnosis of brain injury may be difficult in some cases or may leave diagnostic doubts, especially in mild trauma with insignificant pathological brain changes or in cases where instrumental tests are negative. Therefore, in recent years, an important area of research has been directed towards the study of new biomarkers, such as micro-RNAs (miRNAs), which can assist clinicians in the diagnosis, staging, and prognostic evaluation of TBI, as well as forensic pathologists in the assessment of TBI and in the estimation of additional relevant data, such as survival time. The aim of this study is to investigate the expression profiles (down- and upregulation) of a panel of miRNAs in subjects deceased with TBI in order to assess, verify, and define the role played by non-coding RNA molecules in the different pathophysiological mechanisms of brain damage. This study also aims to correlate the detected expression profiles with survival time, defined as the time elapsed between the traumatic event and death, and with the severity of the trauma. This study was conducted on 40 cases of subjects deceased with TBI (study group) and 10 cases of subjects deceased suddenly from non-traumatic causes (control group). The study group was stratified according to the survival time and the severity of the trauma. The selection of miRNAs to be examined was based on a thorough literature review. Analyses were performed on formalin-fixed, paraffin-embedded (FFPE) brain tissue samples, with a first step of total RNA extraction and a second step of quantification of the selected miRNAs of interest. This study showed higher expression levels in cases compared to controls for miR-16, miR-21, miR-130a, and miR-155. In contrast, lower expression levels were found in cases compared to controls for miR-23a-3p. There were no statistically significant differences in the expression levels between cases and controls for miR-19a. In cases with short survival, the expression levels of miR-16-5p and miR-21-5p were significantly higher. In cases with long survival, miR-21-5p was significantly lower. The expression levels of miR-130a were significantly higher in TBI cases with short and middle survival. In relation to TBI severity, miR-16-5p and miR-21-5p expression levels were significantly higher in the critical-fatal TBI subgroup. Conclusions: This study provides evidence for the potential of the investigated miRNAs as predictive biomarkers to discriminate between TBI cases and controls. These miRNAs could improve the postmortem diagnosis of TBI and also offer the possibility to define the survival time and the severity of the trauma. The analysis of miRNAs could become a key tool in forensic investigations, providing more precise and detailed information on the nature and extent of TBI and helping to define the circumstances of death.

Platelet inhibition correlates with severity of traumatic brain injury and may be associated with mortality. Adenosine diphosphate participates in platelet aggregation via the activation of the ADP receptors, P2Y1 and P2Y12. Prior work suggests this ADP pathway is significant in managing patients with head injuries. This study aimed to measure the influence of ADP inhibition on outcomes after a traumatic brain injury (TBI), as measured by thromboelastography with platelet mapping (TEG-PM). Outcomes were defined as (a) hospital length of stay; (b) ICU length of stay, (c) mortality, and (d) progression of hemorrhage on CT. The resulting cohort was split into quartiles to compare the effect of increasingly inhibited ADP values on the identified outcomes. Comparisons of 2 groups of patients were also conducted, one defined by ADP inhibition less than or equal to 60% and the other group by ADP inhibition of greater than 60%. 98 patients were included in final analysis, with 72.4% having ADP inhibition less than 60%. These patients were significantly older and had lower global injury severity scores (ISSs), although their head-specific ISS was equivalent. Compared to the group with ADP inhibition over 60%, there was no significant difference in mortality, hospital or ICU length of stay, or progression of lesion on CT. Patients with ADP less than 60% inhibited had smaller ISS and higher GCS, indicating they were less injured than those with greater ADP inhibition, consistent with prior literature. The equivalent ICU and hospital length of stay and mortality suggests that ADP inhibition plays a smaller role in outcomes. Additional study with a larger sample size and guideline-based assessments is necessary to further define the impact of ADP inhibition and to determine the role of platelet transfusion in this population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: With a sustained increase in the proportion of elderly trauma patients, geriatric traumatic brain injury (TBI) is a significant source of morbidity, mortality and resource utilization. The aim of our study was to assess the predictors of mortality in geriatric TBI patients who underwent craniotomy., Methods: We performed a 4-year analysis of ACS-TQIP database (2016-2019) and included all geriatric trauma patients (≥65y) with isolated severe TBI who underwent craniotomy. We calculated 11- point modified frailty index (mFI) for patients. Our primary and secondary outcomes were mortality and unfavorable outcome, respectively. Multivariate regression analysis was performed to identify the predictors of outcomes. Patients with mFI ≥ 0.25 were defined as Frail, whereas patient with mFI of 0.08 or higher (<0.25) were identified as pre-frail; Non-frail patients were identified as mFI of <0.08., Results: We analyzed data from 20,303 patients. The mortality rate was 17.7 % (3,587 patients). Having ≥ 2 concomitant types of intra-cranial hemorrhage (OR = 2.251, p < 0.001), and pre-hospital anticoagulant use (OR = 1.306, p < 0.001) increased the risks of mortality. Frailty, as a continuous variable, was not considered as a risk factor for mortality (p = 0.058) but after categorization, it was shown that compared to non-frails, patients with pre-frailty (OR = 1.946, p = 0.011) and frailty (OR = 1.786, p = 0.026) had increased risks of mortality. Higher mFI (OR = 4.841), age (OR = 1.034), ISS (OR = 1.052), having ≥ 2 concomitant types of intra-cranial hemorrhage (OR = 1.758), and use of anticoagulants (OR = 1.117) were significant risk factors for unfavorable outcomes (p < 0.001, for all)., Conclusions: Having more than two types of intra-cranial hemorrhage and pre-hospital anticoagulant use were significant risk factors for mortality. The study's findings also suggest that frailty may not be a sufficient predictor of mortality after craniotomy in geriatric patients with TBI. However, frailty still affects the discharge disposition and favorable outcome., Level of Evidence: Level III retrospective study., Competing Interests: Declaration of competing interest There are no conflict of interest and no financial funding., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Fever has been shown to be associated with poor outcomes in patients with traumatic brain injury. Earlier studies have used peak daily temperature to derive the burden of fever. The association between hospital mortality and fever burden calculated as the area under the temperature-time curve for the entire duration of intensive care unit (ICU) stay has not been studied before., Objectives: The objective of this study was to investigate the association between the burden of fever and hospital mortality in patients with isolated traumatic brain injury admitted to the ICU., Methods: We conducted this retrospective cohort study using an electronic database in a tertiary ICU in Sydney. We included all adult patients admitted to the ICU with isolated traumatic brain injury over 3 years from 1 July 2017 to 30 June 2020. We collected data on demographics, clinical characteristics, and interventions for all patients. We defined the burden of fever as an area under the temperature-time curve above 37 °C. The primary outcome was hospital mortality. We used multivariable logistic regression to determine the association between burden of fever and hospital mortality. We assessed the importance of the burden of fever in a predictive model using machine-learning methods (Bagging and Random Forest)., Results: A total of 88 patients (76% males, mean age: 54 ± 23 years, mean Acute Physiology and Chronic Health Evaluation [APACHE] II score: 15 ± 7) were included in the study, and 18 (20.5%) of the 88 patients died in hospital. Compared to survivors, the nonsurvivors had lower mean Glasgow Coma Scale (GCS) score at the scene, higher mean APACHE II and III scores, and higher rates of intracranial pressure monitoring, surgery, mechanical ventilation, use of vasopressors, and cooling. On multivariable logistic regression, age (odds ratio: 1.05, 95% confidence interval: 1.02-1.09, p = 0.01) was found to be an independent predictor of hospital mortality. A higher GCS score at the scene (odds ratio: 0.81, 95% confidence interval: 0.66-0.98, p = 0.03) was associated with survival. The burden of fever was not associated with hospital mortality. The top three important variables in the predictive model were APACHE III, GCS score at scene, and age., Conclusion: The burden of fever was not an independent predictor of hospital mortality. The results of this study need to be confirmed in a large multicenter study., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Traumatic Brain Injury (TBI) presents a broad spectrum of clinical presentations and outcomes due to its inherent heterogeneity, leading to diverse recovery trajectories and varied therapeutic responses. While many studies have delved into TBI phenotyping for distinct patient populations, identifying TBI phenotypes that consistently generalize across various settings and populations remains a critical research gap. Our research addresses this by employing multivariate time-series clustering to unveil TBI's dynamic intricates. Utilizing a self-supervised learning-based approach to clustering multivariate time-Series data with missing values (SLAC-Time), we analyzed both the research-centric TRACK-TBI and the real-world MIMIC-IV datasets. Remarkably, the optimal hyperparameters of SLAC-Time and the ideal number of clusters remained consistent across these datasets, underscoring SLAC-Time's stability across heterogeneous datasets. Our analysis revealed three generalizable TBI phenotypes (α, β, and γ), each exhibiting distinct non-temporal features during emergency department visits, and temporal feature profiles throughout ICU stays. Specifically, phenotype α represents mild TBI with a remarkably consistent clinical presentation. In contrast, phenotype β signifies severe TBI with diverse clinical manifestations, and phenotype γ represents a moderate TBI profile in terms of severity and clinical diversity. Age is a significant determinant of TBI outcomes, with older cohorts recording higher mortality rates. Importantly, while certain features varied by age, the core characteristics of TBI manifestations tied to each phenotype remain consistent across diverse populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Many patients suffering from isolated severe traumatic brain injury (sTBI) receive blood transfusion on hospital arrival due to hypotension. We hypothesized that increasing blood transfusions in isolated sTBI patients would be associated with an increase in mortality., Methods: We performed a trauma quality improvement program (TQIP) (2017-2019) and single-center (2013-2021) database review filtering for patients with isolated sTBI (Abbreviated Injury Scale head ≥3 and all other areas ≤2). Age, initial Glasgow Coma Score (GCS), Injury Severity Score (ISS), initial systolic blood pressure (SBP), mechanism (blunt/penetrating), packed red blood cells (pRBCs) and fresh frozen plasma (FFP) transfusion volume (units) within the first 4 h, FFP/pRBC ratio (4h), and in-hospital mortality were obtained from the TQIP Public User Files., Results: In the TQIP database, 9257 patients had isolated sTBI and received pRBC transfusion within the first 4 h. The mortality rate within this group was 47.3%. The increase in mortality associated with the first unit of pRBCs was 20%, then increasing approximately 4% per unit transfused to a maximum mortality of 74% for 11 or more units. When adjusted for age, initial GCS, ISS, initial SBP, and mechanism, pRBC volume (1.09 [1.08-1.10], FFP volume (1.08 [1.07-1.09]), and FFP/pRBC ratio (1.18 [1.08-1.28]) were associated with in-hospital mortality. Our single-center study yielded 138 patients with isolated sTBI who received pRBC transfusion. These patients experienced a 60.1% in-hospital mortality rate. Logistic regression corrected for age, initial GCS, ISS, initial SBP, and mechanism demonstrated no significant association between pRBC transfusion volume (1.14 [0.81-1.61]), FFP transfusion volume (1.29 [0.91-1.82]), or FFP/pRBC ratio (6.42 [0.25-164.89]) and in-hospital mortality., Conclusions: Patients suffering from isolated sTBI have a higher rate of mortality with increasing amount of pRBC or FFP transfusion within the first 4 h of arrival., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Controlling elevated intracranial pressure following brain injury with hyperosmolar agents is one of the mainstay treatments in traumatic brain injury patients. In this study, we compared the effects of hypertonic saline (HS) and mannitol in reducing increased intracranial pressure., Methods: A total of 637 patients from 15 studies were included in our meta-analysis. The primary outcomes were mortality, the length of stay in the hospital and ICU, and the Glasgow Outcome Scale at follow-up., Results: The mortality in the mannitol group was not statistically different compared to the HS group (RR = 1.55; 95% CI = [0.98, 2.47], p  = 0.06). The length of stay in the ICU was significantly shorter in the HS group (MD = 1.18, 95% CI = [0.44, 1.92], p  < 0.01). In terms of favorable neurological outcomes, there was no significant difference between the two agents (RR = 0.92, 95% CI = [0.11, 7.96], p  = 0.94). The duration of the effect was shorter in the mannitol group than in the HS group (MD = -0.67, 95% CI = [-1.00, -0.33], p  < 0.01)., Discussion: The results showed that HS and mannitol had similar effects in reducing ICP. Although the HS was associated with a longer duration of effect and shorter ICU stay, other secondary outcomes including mortality rate and favorable neurological outcomes were similar between the two drugs. In conclusion, considering the condition of each patient individually, HS could be a reasonable option than mannitol to reduce ICP in TBI patients.

Objective: This study aimed to investigate the effects of traumatic brain injury (TBI) on employment status, household income, and the development of new disabilities among survivors, as well as its correlation with mortality rates over a 2-year period., Methods: In this nationwide population-based cohort study, we screened all patients admitted to the intensive care unit (ICU) because of TBI between January 1, 2010, and December 31, 2018, in South Korea. Among them, patients who were alive for > 1 year were considered TBI survivors. Changes in unemployment, decreased household income, and newly acquired disabilities were evaluated one year after the date of ICU admission due to TBI., Results: In total, 78,420 TBI survivors were included in this study. Among them, 5.4 %, 22.5 %, and 8.6 % of the TBI survivors experienced unemployment, decreased household income, and newly acquired disabilities within one year after the date of ICU admission, respectively. A longer ICU stay, comorbidities, hospital admission through the emergency room, increased total cost of hospitalization, and mechanical ventilatory support were associated with unemployment, decreased household income, and newly acquired disabilities. Among the three factors, the newly acquired disability was associated with a 27 % increase in 2-year all-cause mortality (hazard ratio: 1.27, 95 % confidence interval: 1.17-1.39; P < 0.001), while unemployment and decreased household income were not significantly associated (P = 0.371 and P = 0.105, respectively)., Conclusions: A significant number of individuals in South Korea who survived TBI faced challenges such as unemployment, reduced household income, and the acquisition of new disabilities within a year of being admitted to the ICU. In addition, the study found that individuals who developed a new disability after TBI had a higher risk of mortality within two years., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: There is limited evidence that beta-blockers may provide benefit for patients with moderate-severe traumatic brain injury (TBI) during the acute injury period. Larger studies on utilization patterns and impact on outcomes in clinical practice are lacking., Objective: The present study uses a large, national hospital claims-based dataset to examine early beta-blocker utilization patterns and its association with clinical outcomes among critically ill patients with moderate-severe TBI., Methods: We conducted a retrospective cohort study of the administrative claims Premier Healthcare Database of adults (≥17 years) with moderate-severe TBI admitted to the intensive care unit (ICU) from 2016 to 2020. The exposure was receipt of a beta-blocker during day 1 or 2 of ICU stay (BB + ). The primary outcome was hospital mortality, and secondary outcomes were: hospital length of stay (LOS), ICU LOS, discharge to home, and vasopressor utilization. In a sensitivity analysis, we explored the association of beta-blocker class (cardioselective and noncardioselective) with hospital mortality. We used propensity weighting methods to address possible confounding by treatment indication., Results: A total of 109 665 participants met inclusion criteria and 39% (n = 42 489) were exposed to beta-blockers during the first 2 days of hospitalization. Of those, 42% received cardioselective only, 43% received noncardioselective only, and 14% received both. After adjustment, there was no association with hospital mortality in the BB + group compared to the BB - group (adjusted odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94, 1.04). The BB + group had longer hospital stays, lower chance of discharged home, and lower risk of vasopressor utilization, although these difference were clinically small. Beta-blocker class was not associated with hospital mortality., Conclusion: In this retrospective cohort study, we found variation in use of beta-blockers and early exposure was not associated with hospital mortality. Further research is necessary to understand the optimal type, dose, and timing of beta-blockers for this population., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Isolated traumatic spinal cord injury (t-SCI) and traumatic brain injury (TBI) represent significant public health concerns, resulting in long-term disabilities and necessitating sophisticated care, particularly when occurring concurrently. The impact of these combined injuries, while crucial in trauma management, on clinical, socioeconomic, and health care outcomes is largely unknown. To address this gap, our secondary retrospective cohort study used data from the Japan Trauma Data Bank, covering patients enrolled over a 13-year period (2006-2018), to elucidate the effects of concurrent t-SCI and TBI on in-hospital mortality. Data on patient demographics, injury characteristics, treatment modalities, and outcomes were analyzed. Multivariate logistic regression analysis was performed to examine prognostic variables associated with in-hospital mortality, including interaction terms between t-SCI severity and TBI presence. This study included 91,983 patients with neurotrauma, with a median age of 62 years (69.7% men). Among the patients, 9,018 (9.8%) died in the hospital. Concomitant t-SCI and TBI occurred in 2,954 (3.2%) patients. t-SCI only occurred in 9,590 (10.4%) patients, whereas TBI only occurred in the majority of these cases (79,439, 86.4%). Multivariate logistic regression analysis revealed age; sex; total number of comorbidities; systolic blood pressure at presentation; Glasgow coma scale score at presentation; and Abbreviated Injury Scale (AIS) scores for head, face, chest, abdomen, cervical-SCI, thoracic-SCI, and lumbar-SCI as significant independent factors for in-hospital mortality. The odds ratio of cervical-SCI × head AIS as an interaction term was 0.85 (95% confidence interval: 0.77-0.95), indicating a negative interaction. In conclusion, we identified 12 factors associated with in-hospital mortality in patients with t-SCI. In addition, the negative interaction between cervical t-SCI and TBI suggests that the presence of t-SCI in patients with TBI may be underestimated. This study highlights the importance of early recognition and comprehensive management of these complex trauma conditions while considering the possibility of concomitant t-SCI in patients with TBI.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children. Head computed tomography (CT) is frequently utilized for evaluating trauma-related characteristics, selecting treatment options, and monitoring complications in the early stages. This study assessed the relationship between cranial CT findings and early and late neurological outcomes in pediatric TBI patients admitted to the pediatric intensive care unit (PICU). The study included children aged 1 month to 18 years who were admitted to the PICU due to TBI between 2014 and 2020. Sociodemographic data, clinical characteristics, and cranial CT findings were analyzed. Patients were categorized based on their Glasgow Coma Scale (GCS) score. Of the 129 patients, 83 (64%) were male, and 46 (36%) were female, with a mean age of 6.8 years. Falls (n = 51, 39.5%) and in-vehicle traffic accidents (n = 35, 27.1%) were the most common trauma types observed. Normal brain imaging findings were found in 62.7% of the patients, while 37.3% exhibited intracranial pathology. Hemorrhage was the most frequent CT finding. Severe TBI (n = 26, p = 0.032) and mortality (n = 9, p = 0.017) were more prevalent in traffic accidents. The overall mortality rate in the study population was 10.1%. In children with TBI, cranial CT imaging serves as an essential initial method for patients with neurological manifestations. Particularly, a GCS score of ≤ 8, multiple hemorrhages, diffuse cerebral edema, and intraventricular bleeding are associated with sequelae and mortality., (© 2024. The Author(s).)

Emergency medical diseases (EMDs) are the leading cause of death worldwide. A time-to-death analysis is needed to accurately identify the risks and describe the pattern of an EMD because the mortality rate can peak early and then decline. Dose-ranging Phase II clinical trials are essential for developing new therapies for EMDs. However, most dose-finding trials do not analyze mortality as a time-to-event endpoint. We propose three Bayesian dose-response time-to-event models for a secondary mortality analysis of a clinical trial: a two-group (active treatment vs control) model, a three-parameter sigmoid EMAX model, and a hierarchical EMAX model. The study also incorporates one specific active treatment as an active comparator in constructing three new models. We evaluated the performance of these six models and a very popular independent model using simulated data motivated by a randomized Phase II clinical trial focused on identifying the most effective hyperbaric oxygen dose to achieve favorable functional outcomes in patients with severe traumatic brain injury. The results show that the three-group, EMAX, and EMAX model with an active comparator produce the smallest averaged mean squared errors and smallest mean absolute biases. We provide a new approach for time-to-event analysis in early-phase dose-ranging clinical trials for EMDs. The EMAX model with an active comparator can provide valuable insights into the mortality analysis of new EMDs or other conditions that have changing risks over time. The restricted mean survival time, a function of the model's hazards, is recommended for displaying treatment effects for EMD research., (© 2024 John Wiley & Sons Ltd.)

Background and Objectives: To analyze the ability of prehospital lactate levels to predict 2-day in-hospital mortality in patients with traumatic brain injury (TBI), severe TBI (Glasgow Coma Scale (GCS) ≤ 8 points), and mild or moderate TBI (GCS ≥ 9 points). Second, 90-day mortality was also explored., Methods: This was a prospective, multicenter, emergency medical services (EMSs) delivery, ambulance-based, derivation-validation cohort study developed in 5 tertiary hospitals (Spain), from November 1, 2019, to July 31, 2022. Patients were recruited from among all phone requests for emergency assistance among adults who were later evacuated to referral hospitals with acute TBI. The exclusion criteria were minors, pregnancy, trauma patients without TBI, delayed presentations, patients were discharged in situ, participants with cardiac arrest, and unavailability to obtain a blood sample. The primary outcome was all-cause 2-day in-hospital mortality and 90-day mortality in patients with moderate or mild TBI compared with patients with severe TBI. Clinical and analytical parameters (lactate and glucose) were collected. The discriminative power (area under the receiver operating characteristic curve [AUC]) and calibration curve were calculated for 2 geographically separated cohorts., Results: A total of 509 patients were ultimately included. The median age was 58 years (interquartile range: 43-75), and 167 patients were female (32.8%). The primary outcome occurred in 9 (2.2%) of 415 patients with moderate or mild TBI and in 42 (44.7%) of 94 patients with severe TBI. The predictive capacity of the lactate concentration was globally validated in our cohort, for which the AUC was 0.874 (95% CI 0.805-0.942) for the validation cohort. The ability of the GCS score to predict lactate concentration was greater in patients with a GCS score ≥9 points, with an AUC of 0.925 (95% CI 0.808-1.000) and a negative predictive value of 99.09 (95% CI 98.55-99.64) in the validation cohort., Conclusion: Our results show the benefit of using lactate in all patients with TBI, particularly in those with a GCS ≥9 points. Routine incorporation of lactate in the screening of patients with TBI could presumably reduce mortality and deterioration rates because of quicker and better identification of patients at risk.

Pre-hospital end-tidal carbon dioxide (E t CO 2 ) monitoring and arterial to end-tidal carbon dioxide gradient (P a-Et CO 2 ) have been associated with mortality in patients with traumatic brain injury. Our study aimed to analyze the association between alveolar E t CO 2 or P a-Et CO 2 and mortality in patients admitted in intensive care unit (ICU) with neurological injuries. In our retrospective analysis from using large de-identified ICU databases (MIMIC-III and -IV and eICU databases), we included 2872 ICU patients with neurological injuries, identified according to the International Classification of Diseases (ICD-9 and -10), who underwent E t CO 2 monitoring. We performed logistic regression and extended Cox regression to assess the association between mortality and candidate covariates, including E t CO 2 and P a-Et CO 2 . In-hospital mortality was 26% (n = 747). In univariate analysis, both the P a-Et CO 2 gradient and E t CO 2 levels during the first 24 h were significantly associated with mortality (for a 1 mmHg increase: OR = 1.03 [CI 95 1.016-1.035] and OR = 0.94 [CI 95 0.923-0.953]; p < 0.001). The association remained significant in multivariate analysis. The time-varying evolution of EtCO 2 was independently associated with mortality (for a 1 mmHg increase: HR = 0.976 [CI 95 0.966-0.985]; p < 0.001). The time-varying P a-Et CO 2 gradient was associated with mortality only in univariate analysis. In neurocritical patients, lower E t CO 2 levels at admission and throughout the ICU stay were independently associated with mortality and should be avoided., (© 2024. The Author(s).)

Receptor-interacting protein kinase-3 (RIP-3) is a key component for inducing necroptosis following acute brain injury. Purpose of this study is to unveil whether serum RIP-3 levels are related to severity and clinical outcomes after human severe traumatic brain injury (sTBI). In this two-center prospective cohort study, serum RIP-3 levels were detected in 127 healthy controls coupled with 127 sTBI patients. The prognostic indicators encompassed posttraumatic 180-day mortality, overall survival and poor prognosis (defined as extended Glasgow outcome scale scores of 1-4). The prognosis associations were verified via multivariate analysis. There was a significant incremental serum RIP-3 levels in patients with sTBI, relative to the controls. RIP-3 levels of patients were independently correlated with Rotterdam Computed Tomography (CT) scores and Glasgow coma scale (GCS) scores, as well as were independently predictive of mortality, overall survival and poor prognosis. Mortality and poor prognosis were effectively predicted by serum RIP-3 levels under the receiver operating characteristic curve. Linear relationships between RIP-3 levels and their risks were verified. Mortality and poor prognosis models of serum RIP-3 levels combined with GCS and Rotterdam CT scores displayed efficient predictive abilities. The two models were graphically represented, which were of clinical stability and value by employing the calibration and decision curves. Increased serum RIP-3 levels after sTBI are closely linked to heightened trauma severity and poor prognosis, signifying that serum RIP-3 may be an encouraging biomarker for evaluating severity and predicting clinical outcome of sTBI., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Preliminary evidence demonstrates that visit-to-visit systolic blood pressure (SBP) variability is a prognostic factor of TBI. However, literature regarding the impact of initial blood pressure management on the outcomes of TBI patients is limited. We aimed to further validate the clinical significance of BPV on the prognostic outcomes of patients with TBI., Methods: We performed the analysis by using individual patient-level data acquired from the eICU-CRD, which collected 200,859 ICU admissions of 139,367 patients in 2014 and 2015 from 208 US hospitals. Adult patients with traumatic intraparenchymal hemorrhage or contusion were included. The primary outcome was in-hospital mortality and the secondary outcome was discharge-home rate. Blood pressure variability (BPV) was calculated according to standard criteria: at least six measurements were taken in the first 24 h (hyperacute group) and 36 over days 2-7 (acute group). We estimated the associations between BPV and outcomes with logistic and proportional odds regression models. The key parameter for BPV was standard deviation (SD) of SBP, categorized into quintiles. We also calculated the average real variability (ARV), as well as maximum, minimum, and mean SBP for comparison in our analysis., Results: We studied 1486 patients in the hyperacute group and 857 in the acute group. SD of SBP had a significant association with the in-hospital mortality for both the hyperacute group (highest quintile adjusted OR 2.28 95% CI 1.18-4.42; p trend <0.001) and the acute group (highest quintile adjusted OR 2.17, 95% CI 1.08-4.36; p trend <0.001). The strongest predictors of primary outcome were SD of SBP in the hyperacute phase and minimum SBP in the acute phase. Associations were similar for the discharge-home rate (for the hyperacute group, highest quintile adjusted OR 0.58, 95% CI 0.37-0.89; p trend <0.001; for the acute group OR 0.55, 95% CI 0.32-0.95; p trend <0.001)., Conclusion: Systolic BPV seems to predict a poor outcome in patients with TBI. The benefits of early treatment to maintain appropriate SBP level might be enhanced by smooth and sustained control., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Objective: Epilepsy is associated with significant mortality risk. There is limited research examining how traumatic brain injury (TBI) timing affects mortality in relation to the onset of epilepsy. We aimed to assess the temporal relationship between epilepsy and TBI regarding mortality in a cohort of post-9/11 veterans., Methods: This retrospective cohort study included veterans who received health care in the Defense Health Agency and the Veterans Health Administration between 2000 and 2019. For those diagnosed with epilepsy, the index date was the date of first antiseizure medication or first seizure; we simulated the index date for those without epilepsy. We created the study groups by the index date and first documented TBI: (1) controls (no TBI, no epilepsy), (2) TBI only, (3) epilepsy only, (4) TBI before epilepsy, (5) TBI within 6 months after epilepsy, and (6) TBI >6 months after epilepsy. Kaplan-Meier estimates of all-cause mortality were calculated, and log-rank tests were used to compare unadjusted cumulative mortality rates among groups compared to controls. Cox proportional hazard models were used to compute hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: Among 938 890 veterans, 27 436 (2.92%) met epilepsy criteria, and 264 890 (28.22%) had a TBI diagnosis. Mortality was higher for veterans with epilepsy than controls (6.26% vs. 1.12%; p < .01). Veterans with TBI diagnosed ≤6 months after epilepsy had the highest mortality hazard (HR = 5.02, 95% CI = 4.21-5.99) compared to controls, followed by those with TBI before epilepsy (HR = 4.25, 95% CI = 3.89-4.58), epilepsy only (HR = 4.00, 95% CI = 3.67-4.36), and TBI >6 months after epilepsy (HR = 2.49, 95% CI = 2.17-2.85). These differences were significant across groups., Significance: TBI timing relative to epilepsy affects time to mortality; TBI within 6 months after epilepsy or before epilepsy diagnosis was associated with earlier time to death compared to those with epilepsy only or TBI >6 months after epilepsy., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Traumatic brain injury (TBI) is an expensive and common public health problem. Management of TBI oftentimes includes sedation to facilitate mechanical ventilation (MV) for airway protection. Dexmedetomidine has emerged as a potential candidate for improved patient outcomes when used for early sedation after TBI due to its potential modulation of autonomic dysfunction. We examined early sedation patterns, as well as the association of dexmedetomidine exposure with clinical and functional outcomes among mechanically ventilated patients with moderate-severe TBI (msTBI) in the United States., Methods: We conducted a retrospective cohort study using data from the Premier dataset and identified a cohort of critically ill adult patients with msTBI who required MV from January 2016 to June 2020. msTBI was defined by head-neck abbreviated injury scale (AIS) values of 3 (serious), 4 (severe), and 5 (critical). We described early continuous sedative utilization patterns. Using propensity-matched models, we examined the association of early dexmedetomidine exposure (within 2 days of intensive care unit [ICU] admission) with the primary outcome of hospital mortality and the following secondary outcomes: hospital length of stay (LOS), days on MV, vasopressor use after the first 2 days of admission, hemodialysis (HD) after the first 2 days of admission, hospital costs, and discharge disposition. All medications, treatments, and procedures were identified using date-stamped hospital charge codes., Results: The study population included 19,751 subjects who required MV within 2 days of ICU admission. The patients were majority male and white. From 2016 to 2020, the annual percent utilization of dexmedetomidine increased from 4.05% to 8.60%. After propensity score matching, early dexmedetomidine exposure was associated with reduced odds of hospital mortality (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.47-0.74; P < .0001), increased risk for liberation from MV (hazard ratio [HR], 1.20; 95% CI, 1.09-1.33; P = .0003), and reduced LOS (HR, 1.11; 95% CI, 1.01-1.22; P = .033). Exposure to early dexmedetomidine was not associated with odds of HD (OR, 1.14; 95% CI, 0.73-1.78; P = .56), vasopressor utilization (OR, 1.10; 95% CI, 0.78-1.55; P = .60), or increased hospital costs (relative cost ratio, 1.98; 95% CI, 0.93-1.03; P = .66)., Conclusions: Dexmedetomidine is being utilized increasingly as a sedative for mechanically ventilated patients with msTBI. Early dexmedetomidine exposure may lead to improved patient outcomes in this population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

The role of inflammatory cytokines in children with moderate to severe TBI (m-sTBI) is still incompletely understood. We aimed to investigate the associations between early plasma expression profiles of inflammatory cytokines and clinical outcomes in children with m-sTBI. We prospectively recruited children admitted to the intensive care unit (ICU) of a tertiary pediatric hospital due to m-sTBI from November 2022 to May 2023. Plasma interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α concentrations were detected by flow cytometry on admission and on days 5 to 7. The primary outcome was in-hospital mortality. The secondary outcome was the 6-month functional outcome assessed by the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score, dichotomized as favorable (1-4) or unfavorable (5-8). Fifty patients and 20 healthy controls were enrolled. Baseline IL-6, IL-8 and IL-10 levels were significantly higher in TBI patients than in healthy controls. Twelve patients died in the hospital. Compared with survivors, nonsurvivors had significantly increased baseline IL-6 and IL-8 levels. Baseline IL-5, IL-6 and IL-8 levels were also significantly greater in children with unfavorable versus favorable outcomes. The area under the receiver operating characteristic curve (AUC) of the IL-6 and IL-8 levels and motor Glasgow Coma Scale (GCS) score for predicting in-hospital mortality was 0.706, 0.754, and 0.776, respectively. Baseline IL-1β, IL-2, IL-4, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α and TNF-α levels were not associated with in-hospital mortality or an unfavorable 6-month outcome. On days 5 to 7, the IL-6 and IL-8 levels were significantly decreased in survivors but increased in nonsurvivors compared to their respective baselines., Conclusion: After m-sTBI, the plasma profiles of inflammatory cytokines are markedly altered in children. The trends of IL-6 and IL-8 expression vary among m-sTBI children with different outcomes. Elevated plasma IL-6 and IL-8 levels are related to in-hospital mortality and unfavorable 6-month outcomes., Trial Registration: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022., What Is Known: • Inflammation is an important secondary physiological response to TBI., What Is New: • The plasma profiles of inflammatory cytokines are markedly altered in children with m-sTBI. Elevated IL-6 and IL-8 levels are related to mortality and unfavorable outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Importance: Occurrence of mydriasis during the prehospital management of traumatic brain injury (TBI) may suggest severe intracranial hypertension (ICH) subsequent to brain herniation. The initiation of hyperosmolar therapy to reduce ICH and brain herniation is recommended. Whether mannitol or hypertonic saline solution (HSS) should be preferred is unknown., Objectives: The objective of this study is to assess whether HSS, compared with mannitol, is associated with improved survival in adult trauma patients with TBI and mydriasis., Design/setting and Participants: A retrospective observational cohort study using the French Traumabase national registry to compare the ICU mortality of patients receiving either HSS or mannitol. Patients aged 16 years or older with moderate to severe TBI who presented with mydriasis during prehospital management were included., Outcome Measures and Analysis: We performed propensity score matching on a priori selected variables [i.e. age, sex and initial Coma Glasgow Scale (GCS)] with a ratio of 1 : 3 to ensure comparability between the two groups. The primary outcome was ICU mortality. The secondary outcomes were regression of pupillary abnormality during prehospital management, pulsatility index and diastolic velocity on transcranial Doppler within 24 h after TBI, early ICU mortality (within 48 h), ICU and hospital length of stay., Results: Of 31 579 patients recorded in the registry between 2011 and 2021, 1417 presented with prehospital mydriasis and were included: 1172 (82.7%) received mannitol and 245 (17.3%) received HSS. After propensity score matching, 720 in the mannitol group matched 240 patients in the HSS group. Median age was 41 years [interquartile ranges (IQR) 26-60], 1058 were men (73%) and median GCS was 4 (IQR 3-6). No significant difference was observed in terms of characteristics and prehospital management between the two groups. ICU mortality was lower in the HSS group (45%) than in the mannitol group (54%) after matching [odds ratio (OR) 0.68 (0.5-0.9), P  = 0.014]. No differences were identified between the groups in terms of secondary outcomes., Conclusion: In this propensity-matched observational study, the prehospital osmotherapy with HSS in TBI patients with prehospital mydriasis was associated with a lower ICU mortality compared to osmotherapy with mannitol., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although concomitant traumatic brain injury (TBI) is not infrequently associated with spinal cord injury (SCI), there is relatively scarce information about the effects of concomitant TBI on outcomes after SCI., Objective: To assess the impact of concomitant mild-to-moderate TBI on survival, and neurological and functional outcomes within the first year after acute traumatic SCI., Design: Retrospective cohort study., Setting: Acute spine trauma centers in the United States., Participants: This study includes all individuals who were enrolled into the Third National Spinal Cord Injury Study (NASCIS-3). The study population was classified into SCI + TBI group and SCI-alone group. TBI was defined as a Glasgow Coma Scale score <15 on admission., Intervention: Not applicable., Main Outcome Measures: Both groups were compared regarding their survival and neurological outcomes (ie, NASCIS motor, sensory and pain scores) and functional outcome (ie, Functional Independence Measure score) within the first year following SCI. Data analyses were adjusted for major potential confounders., Results: There were 413 individuals in the SCI-alone group and 86 individuals in the SCI + TBI group (17.2%). Both groups were comparable regarding gender distribution (p = .621). However, the SCI + TBI group was older (p < .001), had a higher proportion of complete (p = .006) and cervical SCI (p = .003), and had a higher blood alcohol level (p < .001) than the SCI-alone group. The SCI + TBI group did not significantly differ from the SCI-alone group regarding survival within the first year after SCI (p = .768). Among the survivors, concomitant mild-to-moderate TBI did not significantly affect neurological and functional outcomes at 1 year after SCI in the multiple regression analyses after adjusting for major potential confounders., Conclusions: The results of this study suggest that concomitant mild-to-moderate TBI did not have a significant impact on survival, neurological recovery, and functional outcomes at 1 year after SCI, even though there were some epidemiological differences between SCI-alone and SCI + TBI groups., (© 2023 American Academy of Physical Medicine and Rehabilitation.)

Background: Traumatic brain injury (TBI) among elderly individuals poses a significant global health concern due to the increasing ageing population., Methods: We searched PubMed, Cochrane Library, and Embase from database inception to Feb 1, 2024. Studies performed in inpatient settings reporting in-hospital mortality of elderly people (≥60 years) with TBI and/or identifying risk factors predictive of such outcomes, were included. Data were extracted from published reports, in-hospital mortality as our main outcome was synthesized in the form of rates, and risk factors predicting in-hospital mortality was synthesized in the form of odds ratios. Subgroup analyses, meta-regression and dose-response meta-analysis were used in our analyses., Findings: We included 105 studies covering 2217,964 patients from 30 countries/regions. The overall in-hospital mortality of elderly patients with TBI was 16 % (95 % CI 15 %-17 %) from 70 studies. In-hospital mortality was 5 % (95 % CI, 3 %-7 %), 18 % (95 % CI, 12 %-24 %), 65 % (95 % CI, 59 %-70 %) for mild, moderate and severe subgroups from 10, 7, and 23 studies, respectively. A decrease in in-hospital mortality over years was observed in overall (1981-2022) and in severe (1986-2022) elderly patients with TBI. Older age 1.69 (95 % CI, 1.58-1.82, P < 0.001), male gender 1.34 (95 % CI, 1.25-1.42, P < 0.001), clinical conditions including traffic-related cause of injury 1.22 (95 % CI, 1.02-1.45, P = 0.029), GCS moderate (GCS 9-12 compared to GCS 13-15) 4.33 (95 % CI, 3.13-5.99, P < 0.001), GCS severe (GCS 3-8 compared to GCS 13-15) 23.09 (95 % CI, 13.80-38.63, P < 0.001), abnormal pupillary light reflex 3.22 (95 % CI, 2.09-4.96, P < 0.001), hypotension after injury 2.88 (95 % CI, 1.06-7.81, P = 0.038), polytrauma 2.31 (95 % CI, 2.03-2.62, P < 0.001), surgical intervention 2.21 (95 % CI, 1.22-4.01, P = 0.009), pre-injury health conditions including pre-injury comorbidity 1.52 (95 % CI, 1.24-1.86, P = 0.0020), and pre-injury anti-thrombotic therapy 1.51 (95 % CI, 1.23-1.84, P < 0.001) were related to higher in-hospital mortality in elderly patients with TBI. Subgroup analyses according to multiple types of anti-thrombotic drugs with at least two included studies showed that anticoagulant therapy 1.70 (95 % CI, 1.04-2.76, P = 0.032), Warfarin 2.26 (95 % CI, 2.05-2.51, P < 0.001), DOACs 1.99 (95 % CI, 1.43-2.76, P < 0.001) were related to elevated mortality. Dose-response meta-analysis of age found an odds ratio of 1.029 (95 % CI, 1.024-1.034, P < 0.001) for every 1-year increase in age on in-hospital mortality., Conclusions: In the field of elderly patients with TBI, the overall in-hospital mortality and its temporal-spatial feature, the subgroup in-hospital mortalities according to injury severity, and dose-response meta-analysis of age were firstly comprehensively summarized. Substantial key risk factors, including the ones previously not elucidated, were identified. Our study is thus of help in underlining the importance of treating elderly TBI, providing useful information for healthcare providers, and initiating future management guidelines. This work underscores the necessity of integrating elderly TBI treatment and management into broader health strategies to address the challenges posed by the aging global population., Review Registration: PROSPERO CRD42022323231., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Unexpected ICU admissions are a key quality metric in trauma care. The purpose of this study is to identify the most common causes of unplanned ICU admissions among trauma patients at an ACS-verified level 1 trauma center., Methods: A retrospective review was conducted of all trauma patients with unplanned admission to the ICU at a level 1 trauma center between 2019 and 2021. Unplanned ICU admissions were categorized into (1) "bounce-backs," patients previously admitted to the ICU and (2) "upgrades," patients who had not previously been cared for in the ICU., Results: Of 300 unexpected ICU transfers, bounce-backs accounted for 69% and upgrades 31%. The most common injuries were traumatic brain injuries (40%) and rib fractures (41.3%). In-hospital mortality rate was 10% and did not significantly differ between bounce-backs and upgrades (12 vs 5%, P = .92). Respiratory distress was the most common cause of transfer (41.1%), followed by neurologic (29.6%) and cardiovascular decline (21.2%). Patients were on average 928 mL fluid positive 72 hours prior to transfer (t > 0, P < .0001), and 295 mL fluid positive in the 24 hours prior to transfer (t > 0, P .0003). Patients transferred for respiratory distress were no more fluid over-balanced than those transferred for other reasons., Conclusion: We found a large percent of unplanned transfers occurring within 48 hours of admission or transfer out of the ICU suggesting under-triage as a leading cause of bounce-backs and upgrades. Respiratory distress was the leading cause of transfer. These findings highlight opportunities for targeted interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ronald Sing: Philips Medical.