Platelet Contribution and Endothelial Activation and Stress Index-Potential Mortality Predictors in Traumatic Brain Injury.

Coagulopathy and traumatic brain injury (TBI) are complexly intertwined. In isolated TBI, coagulopathy may contribute to hemorrhagic lesion development, progression, or recurrence, as it may lead to a particular pattern of coagulopathy called TBI-induced coagulopathy (TBI-IC). We performed a retrospective and descriptive evaluation of 63 patients admitted to the Emergency Clinical Hospital Bucharest with the diagnosis of moderate/severe brain injury. In addition to demographic data, all included patients had a complete paraclinical evaluation that included rotational thromboelastometric (ROTEM) blood-clot analysis. The platelet component (PLTEM) and the endotheliopathy activation and stress index score (EASIX) were calculated. These parameters were presented comparatively according to survival at 30 days and helped define the two study groups: survivors and non-survivors at 30 days. The contribution of platelets to clot strength is derived from maximum clot elasticity (MCE) and maximum clot firmness (MCF). MCE is defined as (MCF × 100)/(100 - MCF), and PLTEM is defined as EXTEM MCE-FIBTEM MCE. EASIX is a novel biomarker recently studied in TBI patients, calculated according to the following formula: lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelets (109 cells/L). Regarding the demographic data, there were no significant differences between the survivors and non-survivors. All ROTEM parameters related to clot amplitude (A5, A10, A20, MCF in EXTEM and FIBTEM channels) were higher in the group of patients who survived. Also, PLTEM was decreased in the group of deceased patients (89.71 ± 22.86 vs. 132.3 ± 16.56 p < 0.0001). The cut-off point determined with the ROC curve is 114.10, with a sensitivity of 94.74% and a specificity of 93.18%, for the detection of the negative prognosis (death at 30 days). The EASIX score was significantly higher in the patients who survived the traumatic event, with a median difference value of 1.15 (p < 0.0001). The ROC analysis of this biomarker highlights a cut-off point of 2.12, with a sensitivity of 88.64% and a specificity of 94.74% (AUC = 0.95, p < 0.0001), for the prediction of mortality. The comparative analysis of the two studied markers was performed using the Cox proportional hazard ratio and highlighted the greater influence that PLTEM has on survival time (b value = -0.05, p < 0.0001) compared to EASIX (b value = 0.49, p = 0.0026). The present retrospective study indicates the potential of the TBI-IC reflecting parameters PLTEM and EASIX as markers of mortality prognosis. Larger prospective studies are needed to confirm their combined prognostic value and use in decision-making and reduction in the burden of disease by adequate allocation of resources in a personalized and timely manner.

Risk factors and outcomes associated with systolic dysfunction following traumatic brain injury.

Systolic dysfunction has been observed following isolated moderate-severe traumatic brain injury (Ims-TBI). However, early risk factors for the development of systolic dysfunction after Ims-TBI and their impact on the prognosis of patients with Ims-TBI have not been thoroughly investigated. A prospective observational study among patients aged 16 to 65 years without cardiac comorbidities who sustained Ims-TBI (Glasgow Coma Scale [GCS] score ≤12) was conducted. Systolic dysfunction was defined as left ventricular ejection fraction <50% or apparent regional wall motion abnormality assessed by transthoracic echocardiography within 24 hours after admission. The primary endpoint was the incidence of systolic dysfunction after Ims-TBI. The secondary endpoint was survival on discharge. Clinical data and outcomes were assessed within 24 hours after admission or during hospitalization. About 23 of 123 patients (18.7%) developed systolic dysfunction after Ims-TBI. Higher admission heart rate (odds ratios [ORs]: 1.05, 95% confidence interval [CI]: 1.02-1.08; P = .002), lower admission GCS score (OR: 0.77, 95% CI: 0.61-0.96; P = .022), and higher admission serum high-sensitivity cardiac troponin T (Hs-cTnT) (OR: 1.14, 95% CI: 1.06-1.22; P < .001) were independently associated with systolic dysfunction among patients with Ims-TBI. A combination of heart rate, GCS score, and serum Hs-cTnT level on admission improved the predictive performance for systolic dysfunction (area under curve = 0.85). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality of patients with systolic dysfunction was higher than that of patients with normal systolic function (P < .05). Lower GCS (OR: 0.66, 95% CI: 0.45-0.82; P = .001), lower admission oxygen saturation (OR: 0.82, 95% CI: 0.69-0.98; P = .025), and the development of systolic dysfunction (OR: 4.85, 95% CI: 1.36-17.22; P = .015) were independent risk factors for in-hospital mortality in patients with Ims-TBI. Heart rate, GCS, and serum Hs-cTnT level on admission were independent early risk factors for systolic dysfunction in patients with Ims-TBI. The combination of these 3 parameters can better predict the occurrence of systolic dysfunction.

Single-centre real-life observational study on mortality and outcomes: decompressive craniectomy and brain death in traumatic brain injury, haemorrhage, and other cerebral diseases.

BACKGROUND: Decompressive hemicraniectomy (DHC) is used after severe brain damages with elevated, refractory intracranial pressure (ICP). In a non age-restricted population, mortality rates and long-term outcomes following DHC are still unclear. This study's objectives were to examine both, as well as to identify predictors of unfavourable outcomes. METHODS: We undertook a retrospective observational analysis of patients aged 18 years and older who underwent DHC at the University Hospital of Bonn between 2018 and 2020, due to traumatic brain injury (TBI), haemorrhage, tumours or infections. Patient outcomes were assessed by conducting telephone interviews, utilising questionnaires for modified Rankin Scale (mRS) and extended Glasgow Outcome scale (GOSE). We evaluated the health-related quality of life using the EuroQol (EQ-5D-5L) scale. RESULTS: A total of 144 patients with a median age of 58.5 years (range: 18 to 85 years) were evaluated. The mortality rate was 67%, with patients passing away at a median of 6.0 days (IQR [1.9-37.6]) after DHC. Favourable outcomes, as assessed by the mRS and GOSE were observed in 10.4% and 6.3% of patients, respectively. Cox regression analysis revealed a 2.0% increase in the mortality risk for every year of age (HR = 1.017; 95% CI [1.01-1.03]; p = 0.004). Uni- and bilateral fixed pupils were associated with a 1.72 (95% CI [1.03-2.87]; p = 0.037) and 3.97 (95% CI [2.44-6.46]; p < 0.001) times higher mortality risk, respectively. ROC-analysis demonstrated that age and pupillary reactivity predicted 6-month mortality with an AUC of 0.77 (95% CI [0.69-0.84]). The only parameter significantly associated with a better quality of life was younger age. CONCLUSIONS: Following DHC, mortality remains substantial, and favourable outcomes occur rarely. Particularly in elderly patients and in the presence of clinical signs of herniation, mortality rates are notably elevated. Hence, the indication for DHC should be set critically.

Machine learning-based prediction of clinical outcomes after traumatic brain injury: Hidden information of early physiological time series.

AIMS: To assess the predictive value of early-stage physiological time-series (PTS) data and non-interrogative electronic health record (EHR) signals, collected within 24 h of ICU admission, for traumatic brain injury (TBI) patient outcomes. METHODS: Using data from TBI patients in the multi-center eICU database, we focused on in-hospital mortality, neurological status based on the Glasgow Coma Score (mGCS) motor subscore at discharge, and prolonged ICU stay (PLOS). Three machine learning (ML) models were developed, utilizing EHR features, PTS signals collected 24 h after ICU admission, and their combination. External validation was performed using the MIMIC III dataset, and interpretability was enhanced using the Shapley Additive Explanations (SHAP) algorithm. RESULTS: The analysis included 1085 TBI patients. Compared to individual models and existing scoring systems, the combination of EHR and PTS features demonstrated comparable or even superior performance in predicting in-hospital mortality (AUROC = 0.878), neurological outcomes (AUROC = 0.877), and PLOS (AUROC = 0.835). The model's performance was validated in the MIMIC III dataset, and SHAP algorithms identified six key intervention points for EHR features related to prognostic outcomes. Moreover, the EHR results (All AUROC >0.8) were translated into online tools for clinical use. CONCLUSION: Our study highlights the importance of early-stage PTS signals in predicting TBI patient outcomes. The integration of interpretable algorithms and simplified prediction tools can support treatment decision-making, contributing to the development of accurate prediction models and timely clinical intervention.

Prognostic value of systemic immune-inflammation index, neutrophil-lymphocyte ratio, and thrombocyte-lymphocyte ratio in critically ill patients with moderate to severe traumatic brain injury.

Traumatic brain injury (TBI) is a significant health problem with a high mortality rate. Inflammatory markers can predict the prognosis of TBI where neuroinflammation is essential. In this study, the prognostic value of the systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) at admission in patients with critical TBI was investigated. Patients with moderately severe TBI in the intensive care unit (ICU) of a tertiary center between June 2020 and June 2022 were retrospectively reviewed. Patients were classified into survivor and mortality groups. The predictive performance of SII, PLR, and NLR levels calculated from blood results at admission and 28-day mortality and patient outcomes were analyzed. One hundred sixty-one patients were included in this study. The median age of the entire population was 41 (18-90) years, and 80.7% (n = 130) of the patients were male. Falls (42.2%) and traffic accidents (40.4%) were the most common causes of TBI. The most common primary diagnoses in patients with TBI were acute subdural hematoma (30.4%) and subarachnoid hemorrhage (26.1%). The SII and NLR levels were significantly higher in the mortality group, and PLR levels were significantly lower (P = .004, P < .001, P < .001, respectively). In multivariate regression analysis, SII and PLR were independent predictors of mortality (P = .031 and P < .001, respectively). In the receiver operating characteristics (ROC) curve analysis, the cutoff value for SII was ≥ 2951, and the area under the curve (AUC) was 0.662 (95% CI, 0.540-0.784). The cutoff value for NLR was ≥ 9.85, AUC was 0.717 (95% CI, 0.600-0.834), and the cutoff value for PLR was ≤ 130.4, AUC was 0.871 (95% CI, 0.796-0.947). 28-day mortality was 21.1%. Neuroinflammation is essential in patients with critical TBI, and inflammatory markers SII, NLR, and PLR have prognostic importance. SII and PLR are independent predictors of mortality. Early detection of those with a poor prognosis in critically ill TBI patients and planning aggressive treatments may contribute to reducing mortality.

Traumatic brain injury in elderly population: A global systematic review and meta-analysis of in-hospital mortality and risk factors among 2.22 million individuals.

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.

Haemoglobin values, transfusion practices, and long-term outcomes in critically ill patients with traumatic brain injury: a secondary analysis of CENTER-TBI.

Haemoglobin (Hb) thresholds and red blood cells (RBC) transfusion strategies in traumatic brain injury (TBI) are controversial. Our objective was to assess the association of Hb values with long-term outcomes in critically ill TBI patients. We conducted a secondary analysis of CENTER-TBI, a large multicentre, prospective, observational study of European TBI patients. All patients admitted to the Intensive Care Unit (ICU) with available haemoglobin data on admission and during the first week were included. During the first seven days, daily lowest haemoglobin values were considered either a continous variable or categorised as < 7.5 g/dL, between 7.5-9.5 and > 9.5 g/dL. Anaemia was defined as haemoglobin value < 9.5 g/dL. Transfusion practices were described as "restrictive" or "liberal" based on haemoglobin values before transfusion (e.g. < 7.5 g/dL or 7.5-9.5 g/dL). Our primary outcome was the Glasgow outcome scale extended (GOSE) at six months, defined as being unfavourable when < 5. Of 1590 included, 1231 had haemoglobin values available on admission. A mean Injury Severity Score (ISS) of 33 (SD 16), isolated TBI in 502 (40.7%) and a mean Hb value at ICU admission of 12.6 (SD 2.2) g/dL was observed. 121 (9.8%) patients had Hb < 9.5 g/dL, of whom 15 (1.2%) had Hb < 7.5 g/dL. 292 (18.4%) received at least one RBC transfusion with a median haemoglobin value before transfusion of 8.4 (IQR 7.7-8.5) g/dL. Considerable heterogeneity regarding threshold transfusion was observed among centres. In the multivariable logistic regression analysis, the increase of haemoglobin value was independently associated with the decrease in the occurrence of unfavourable neurological outcomes (OR 0.78; 95% CI 0.70-0.87). Congruous results were observed in patients with the lowest haemoglobin values within the first 7 days < 7.5 g/dL (OR 2.09; 95% CI 1.15-3.81) and those between 7.5 and 9.5 g/dL (OR 1.61; 95% CI 1.07-2.42) compared to haemoglobin values > 9.5 g/dL. Results were consistent when considering mortality at 6 months as an outcome. The increase of hemoglobin value was associated with the decrease of mortality (OR 0.88; 95% CI 0.76-1.00); haemoglobin values less than 7.5 g/dL was associated with an increase of mortality (OR 3.21; 95% CI 1.59-6.49). Anaemia was independently associated with long-term unfavourable neurological outcomes and mortality in critically ill TBI patients.Trial registration: CENTER-TBI is registered at ClinicalTrials.gov, NCT02210221, last update 2022-11-07.

Admission levels of serum biomarkers have additive and cumulative prognostic value in traumatic brain injury.

Elevated levels of CNS-derived serum proteins are associated with poor outcome in traumatic brain injury (TBI), but the value of adding acute serum biomarker levels to common clinical outcome predictors lacks evaluation. We analyzed admission serum samples for Total-Tau (T-Tau), Neurofilament light chain (Nfl), Glial fibrillary acidic protein (GFAP), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in a cohort of 396 trauma patients including 240 patients with TBI. We assessed the independent association of biomarkers with 1-year mortality and 6-12 months Glasgow Outcome Scale Extended (GOSE) score, as well as the additive and cumulative value of biomarkers on Glasgow Coma Scale (GCS) and Marshall Score for outcome prediction. Nfl and T-Tau levels were independently associated with outcome (OR: Nfl = 1.65, p = 0.01; T-Tau = 1.99, p < 0.01). Nfl or T-Tau improved outcome prediction by GCS (Wald Chi, Nfl = 6.8-8.8, p < 0.01; T-Tau 7.2-11.3, p < 0.01) and the Marshall score (Wald Chi, Nfl = 16.2-17.5, p < 0.01; T-Tau 8.7-12.4, p < 0.01). Adding T-Tau atop Nfl further improved outcome prediction in majority of tested models (Wald Chi range 3.8-9.4, p ≤ 0.05). Our data suggest that acute levels of serum biomarkers are independently associated with outcome after TBI and add outcome predictive value to commonly used clinical scores.

Patients suffering traumatic brain injury: patient characteristics, prehospital triage, primary referral and mortality - A population-based follow-up study.

BACKGROUND: Traumatic brain injury (TBI) is a potential high-risk condition, but appropriate care pathways, including prehospital triage and primary referral to a specialised neurosurgical centre, can improve neurological outcome and survival. The care pathway starts with layman triage, wherein the patient or bystander decides whether to contact a general practitioner (GP) or emergency services (1-1-2 call) as an entryway into the health care system. The GP or 112-health care professional then decides on the level of urgency and dispatches emergency medical services (EMS) when needed. Finally, a decision is made regarding referral of the TBI patient to a specialised neurotrauma centre or a local hospital. Recent studies have shown that injuries are generally more severe in patients entering the health care system through EMS (112-calls) than through GPs; however, no information exists on whether mortality and morbidity outcomes differ depending on the referral choice. The aim of this study was to examine triage pathways, including the method of entry into the health care system, as well as patient characteristics and place of primary referral, to determine the associated 30-day and 1-year mortality rates in TBI patients with confirmed intracranial lesions. METHODS: This retrospective observational population-based follow-up study was conducted in the Central Denmark Region from 1 February 2017 to 31 January 2019. We included all adult patients who contacted hospitals and were ascribed a predefined TBI ICD-10 diagnosis code in the Danish National Patient Register. The obtained TBI cohort was merged with prehospital data from the Prehospital Emergency Medical Services, Central Denmark Region, and vital status from the Danish Civil Registration System. Binary logistic regression analysis of mortality was conducted. In all patients with TBI (including concussions), the primary outcome was primary referral to a specialised centre based on mode of entry ('GP/HCP', '112-call' or 'Unreferred') into the health care system. In the subgroup of patients with confirmed intracranial lesions, the secondary outcomes were the relative risk of death at day 30 and 1 year based on the place of primary referral. RESULTS: Of 5,257 first TBI hospital contacts of adult patients included in the cohort, 1,430 (27.2%) entered the health care system via 1-1-2 emergency medical calls. TBI patients triaged by 112-calls were more likely to receive the highest level of emergency response (15.6% vs. 50.3%; p < 0.001) and second-tier resources and were more frequently referred directly to a specialised centre than were patients entering through GPs or other health care personnel. In the subgroup of 1188/5257 (22.4%) patients with confirmed intracranial lesions, we found no difference in the risk ratio of 30 day (RR 1.04 (95%CI 0.65-1.63)) or 1 year (RR 0.96 (95%CI 0.72-1.25)) all-cause mortality between patients primarily referred to a regional hospital or to a specialised centre when adjusting for age, sex, comorbidities, antiplatelet/anticoagulant treatment and type of intracranial lesions. CONCLUSION: TBI patients mainly enter the health system by contact with GPs or other health care professionals. However, patients entering through 112-calls are more frequently triaged directly to specialised centres. We were unable to demonstrate any significant difference in the adjusted 30-day and 1-year mortality based on e primary referral to a specialised centre. The inability to demonstrate an effect on mortality based on primary referral to a specialised centre may reflect a lack of clinical data in the registries used. Considerable differences may exist in nondocumented baseline characteristics (i.e., GCS, blood pressure and injury severity) between the groups and may limit conclusions about differences in mortality. Further research providing high-quality evidence on the effect of primary referral is needed to secure early neurosurgical interventions in TBI patients.

Improved mortality analysis in early-phase dose-ranging clinical trials for emergency medical diseases using Bayesian time-to-event models with active comparators.

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.

Multicenter Cohort Study to Evaluate the Relationship between Radiological Findings and Disability in Moderate and Severe Head Injury Patients.

This was a multicenter cohort study to evaluate the relationship between radiological findings and disability in moderate and severe head injury patients. The study places were the Neurosurgery department of Sylhet M A G Osmani Medical College Hospital, Sylhet Women's Medical College Hospital (SWMCH) and King Faisal Hospital (KFH), Taif, KSA. Sample size was 104 and the study period was 36 months (July 2021 to December 2022). On the basis of radiological findings the participants were divided into three arms. The different arms were diffused traumatic brain injury (arm-1), focal traumatic brain injury (arm-2) and both (diffused and traumatic) types traumatic brain injury (arm-3). Outcome was assessed by modified Rankin Score (mRS). Mean age was significantly higher in female. Overall mean age was 40.28 year. Highest number was in the below 20-year age group followed by the 41-50-year age group. Lowest number of participants was in the above 60-year group. Improved group was significantly higher than 'not improved' and the 'died' group (p<0.00001). Improved participants were significantly higher in the arm-1 and arm-2. Mortality was significantly higher (p<0.00001) in the arm-3 group.

EASIX is an effective marker in predicting mortality of traumatic brain injury patients.

BACKGROUND: The Endothelial Activation and Stress Index (EASIX) is a novel marker of endothelial injury and correlates with survival of various patients. The endothelial dysfunction plays an important role on the pathophysiological process of traumatic brain injury (TBI). This study was designed to explore the prognostic value of EASIX on TBI patients. METHODS: 358 TBI patients hospitalized in the West China hospital between October 2018 and October 2022 were enrolled for this study. The EASIX was calculated based on the formula: lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelets (109 cells/L). The univariate and multivariate logistic regression with forward method was performed to explore the association between EASIX and mortality. A prognostic model was developed combining significant risk factors in the multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to compare the predictive accuracy of the EASIX and the developed model. RESULTS: The 30-day mortality of enrolled 358 TBI patients was 51.1%. Non-survivors had higher EASIX than survivors (p < 0.001). The multivariate logistic regression confirmed seven risk factors for mortality of TBI including injury mechanism (p = 0.010), GCS (p < 0.001), glucose (p < 0.001), EASIX (p = 0.017), subdural hematoma (p = 0.012), coagulopathy (p = 0.001). The AUC of EASIX, SOFA, GCS was 0.747, 0.748 and 0.774, respectively. The AUC of developed predictive model was 0.874 with the sensitivity of 0.913 and specificity of 0.686. CONCLUSIONS: The EASIX is a reliable marker for predicting mortality of TBI patients. The predictive model incorporating EASIX is helpful for clinicians to evaluate the mortality risk of TBI patients.

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

To assess whether monitoring brain tissue oxygen partial pressure (PbtO2) or employing intracranial pressure (ICP)/cerebral perfusion pressure (CCP)-guided management improves patient outcomes, including mortality, hospital length of stay (LOS), mean daily ICP and mean daily CCP during the intensive care unit(ICU)stay. We searched the Web of Science, EMBASE, PubMed, Cochrane Library, and MEDLINE databases until December 12, 2023. Prospective randomized controlled and cohort studies were included. A meta-analysis was performed for the primary outcome measure, mortality, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eleven studies with a total of 37,492 patients were included. The mortality in the group with PbtO2 was 29.0% (odds ratio: 0.73;95% confidence interval [CI]:0.56-0.96; P = 0.03; I = 55%), demonstrating a significant benefit. The overall hospital LOS was longer in the PbtO2 group than that in the ICP/CPP group (mean difference:2.03; 95% CI:1.03-3.02; P<0.0001; I = 39%). The mean daily ICP in the PbtO2 monitoring group was lower than that in the ICP/CPP group (mean difference:-1.93; 95% CI: -3.61 to -0.24; P = 0.03; I = 41%). Moreover, PbtO2 monitoring did not improve the mean daily CPP (mean difference:2.43; 95%CI: -1.39 to 6.25;P = 0.21; I = 56%).Compared with ICP/CPP monitoring, PbtO2 monitoring reduced the mortality and the mean daily ICP in patients with severe traumatic brain injury; however, no significant effect was noted on the mean daily CPP. In contrast, ICP/CPP monitoring alone was associated with a short hospital stay.

Utility of serum chemokine-like factor 1 as a biomarker of severity and prognosis after severe traumatic brain injury: A prospective observational study.

BACKGROUND: Chemokine-like factor 1 (CKLF1) may be involved in the inflammatory response and secondary brain injury after severe traumatic brain injury (sTBI). We determined serum CKLF1 levels of sTBI patients to further investigate the correlation of CKLF1 levels with disease severity, functional prognosis, and 180-day mortality of sTBI. METHODS: Serum CKLF1 levels were measured at admission in 119 sTBI patients and at entry into study in 119 healthy controls. Serum CKLF levels of 50 patients were also quantified at days 1-3, 5, and 7 after admission. Glasgow coma scale (GCS) scores and Rotterdam computerized tomography (CT) classification were utilized to assess disease severity. Extended Glasgow outcome scale (GOSE) scores were recorded to evaluate function prognosis at 180 days after sTBI. Relations of serum CKLF1 levels to 180-day poor prognosis (GOSE scores of 1-4) and 180-day mortality were analyzed using univariate analysis, followed by multivariate analysis. Receiver-operating characteristic (ROC) curve was built to investigate prognostic predictive capability. RESULTS: Serum CKLF1 levels of sTBI patients increased at admission, peaked at day 2, and then gradually decreased; they were significantly higher during the 7 days after sTBI than in healthy controls. Differences of areas under ROC curve (areas under the curve [AUCs]) were not significant among the six time points. Multivariate analysis showed that serum CKLF1 levels were independently correlated with GCS scores, Rotterdam CT classification, and GOSE scores. Serum CKLF1 levels were significantly higher in non-survivors than in survivors and in poor prognosis patients than in good prognosis patients. Serum CKLF1 levels independently predicted 180-day poor prognosis and 180-day mortality, and had high 180-day prognosis and mortality predictive abilities, and their AUCs were similar to those of GCS scores and Rotterdam CT classification. Combination model containing serum CKLF1, GCS scores, and Rotterdam CT classification performed more efficiently than any of them alone in predicting mortality and poor prognosis. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. CONCLUSION: Serum CKLF1 levels are significantly associated with disease severity, poor 180-day prognosis, and 180-day mortality in sTBI patients. Hence, complement CKLF1 may serve as a potential prognostic biomarker of sTBI.

Comparison of mannitol and hypertonic saline solution for the treatment of suspected brain herniation during prehospital management of traumatic brain injury patients.

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.

Impact of Early Microparticle Release during Isolated Severe Traumatic Brain Injury: Correlation with Coagulopathy and Mortality.

BACKGROUND: Microparticles (MPs) have been implicated in thrombosis and endothelial dysfunction. Their involvement in early coagulopathy and in worsening of outcomes in isolated severe traumatic brain injury (sTBI) patients remains ill defined. OBJECTIVE: We sought to quantify the circulatory MP subtypes derived from platelets (PMPs; CD42), endothelial cells (EMPs; CD62E), and those bearing tissue factor (TFMP; CD142) and analyze their correlation with early coagulopathy, thrombin generation, and in-hospital mortality. MATERIALS AND METHODS: Prospective screening of sTBI patients was done. Blood samples were collected before blood and fluid transfusion. MP enumeration and characterization were performed using flow cytometry, and thrombin-antithrombin complex (TAT) levels were determined using enzyme-linked immunosorbent assay (ELISA). Circulating levels of procoagulant MPs were compared between isolated sTBI patients and age- and gender-matched healthy controls (HC). Patients were stratified according to their PMP, EMP, and TFMP levels, respectively (high ≥HC median and low < HC median). RESULTS: Isolated sTBI resulted in an increased generation of PMPs (456.6 [228-919] vs. 249.1 [198.9-404.5]; P = 0.01) and EMPs (301.5 [118.8-586.7] vs. 140.9 [124.9-286]; P = 0.09) compared to HCs. Also, 5.3% of MPs expressed TF (380 [301-710]) in HCs, compared to 6.6% MPs (484 [159-484]; P = 0.87) in isolated sTBI patients. Early TBI-associated coagulopathy (TBI-AC) was seen in 50 (41.6%) patients. PMP (380 [139-779] vs. 523.9 [334-927]; P = 0.19) and EMP (242 [86-483] vs. 344 [168-605]; P = 0.81) counts were low in patients with TBI-AC, compared to patients without TBI-AC. CONCLUSION: Our results suggest that enhanced cellular activation and procoagulant MP generation are predominant after isolated sTBI. TBI-AC was associated with low plasma PMPs count compared to the count in patients without TBI-AC. Low PMPs may be involved with the development of TBI-AC.