Using metabolomics to predict severe traumatic brain injury outcome (GOSE) at 3 and 12 months.

BACKGROUND: Prognostication is very important to clinicians and families during the early management of severe traumatic brain injury (sTBI), however, there are no gold standard biomarkers to determine prognosis in sTBI. As has been demonstrated in several diseases, early measurement of serum metabolomic profiles can be used as sensitive and specific biomarkers to predict outcomes. METHODS: We prospectively enrolled 59 adults with sTBI (Glasgow coma scale, GCS ≤ 8) in a multicenter Canadian TBI (CanTBI) study. Serum samples were drawn for metabolomic profiling on the 1st and 4th days following injury. The Glasgow outcome scale extended (GOSE) was collected at 3- and 12-months post-injury. Targeted direct infusion liquid chromatography-tandem mass spectrometry (DI/LC-MS/MS) and untargeted proton nuclear magnetic resonance spectroscopy (1H-NMR) were used to profile serum metabolites. Multivariate analysis was used to determine the association between serum metabolomics and GOSE, dichotomized into favorable (GOSE 5-8) and unfavorable (GOSE 1-4), outcomes. RESULTS: Serum metabolic profiles on days 1 and 4 post-injury were highly predictive (Q2 > 0.4-0.5) and highly accurate (AUC > 0.99) to predict GOSE outcome at 3- and 12-months post-injury and mortality at 3 months. The metabolic profiles on day 4 were more predictive (Q2 > 0.55) than those measured on day 1 post-injury. Unfavorable outcomes were associated with considerable metabolite changes from day 1 to day 4 compared to favorable outcomes. Increased lysophosphatidylcholines, acylcarnitines, energy-related metabolites (glucose, lactate), aromatic amino acids, and glutamate were associated with poor outcomes and mortality. DISCUSSION: Metabolomic profiles were strongly associated with the prognosis of GOSE outcome at 3 and 12 months and mortality following sTBI in adults. The metabolic phenotypes on day 4 post-injury were more predictive and significant for predicting the sTBI outcome compared to the day 1 sample. This may reflect the larger contribution of secondary brain injury (day 4) to sTBI outcome. Patients with unfavorable outcomes demonstrated more metabolite changes from day 1 to day 4 post-injury. These findings highlighted increased concentration of neurobiomarkers such as N-acetylaspartate (NAA) and tyrosine, decreased concentrations of ketone bodies, and decreased urea cycle metabolites on day 4 presenting potential metabolites to predict the outcome. The current findings strongly support the use of serum metabolomics, that are shown to be better than clinical data, in determining prognosis in adults with sTBI in the early days post-injury. Our findings, however, require validation in a larger cohort of adults with sTBI to be used for clinical practice.

Hinge craniotomy versus standard decompressive hemicraniectomy: an experimental preclinical comparative study.

INTRODUCTION: Decompressive craniectomy (DC) is the most common surgical procedure to manage increased intracranial pressure (ICP). Hinge craniotomy (HC), which consists of fixing the bone operculum with a pivot, is an alternative method conceived to avoid some DC-related complications; nonetheless, it is debated whether it can provide enough volume expansion. In this study, we aimed to analyze the volume and ICP obtained with HC using an experimental cadaver-based preclinical model and compare the results to baseline and DC. METHODS: Baseline conditions, HC, and DC were compared on both sides of five anatomical specimens. Volume and ICP values were measured with a custom-made system. Local polynomial regression was used to investigate volume differences. RESULTS: The area of the bone opercula resulting from measurements was 115.55 cm2; the mean supratentorial volume was 955 mL. HC led to intermediate results compared to baseline and DC. At an ICP of 50 mmHg, HC offers 130 mL extra space but 172 mL less than a DC. Based on local polynomial regression, the mean volume difference between HC and the standard craniotomy was 10%; 14% between DC and HC; both are higher than the volume of brain herniation reported in the literature in the clinical setting. The volume leading to an ICP of 50 mmHg at baseline was less than the volume needed to reach an ICP of 20 mmHg after HC (10.05% and 14.95% from baseline, respectively). CONCLUSIONS: These data confirm the efficacy of HC in providing sufficient volume expansion. HC is a valid intermediate alternative in case of potentially evolutionary lesions and non-massive edema, especially in developing countries.

New diagnosis of cancer in mild and moderate/severe traumatic brain injury patients in a 12-year population-based study.

BACKGROUND: Traumatic brain injury (TBI) has been reported as a risk factor for brain cancer development. However, the magnitude of the impact of TBI on systemic cancer development has not been clarified. METHODS: A retrospective longitudinal cohort study was conducted using the Taiwan Longitudinal Health Insurance Database between January 2000 and December 2011. A total of 35,306 patients were initially enrolled, and 14,795 patients with mild TBI and 14,795 patients with moderate/severe TBI were matched using the National Health Insurance Research Database in Taiwan. The Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of TBI adjusted for potential confounding factors. RESULTS: After matching, the results showed that patients with moderate/severe TBI had a high mortality rate (17.7% vs. 10.4%) and shorter time interval from TBI to death (mean 3.6 years vs. 5.8 years). No differences were observed in cancer incidence (4.1% vs. 4.1%) or risk factors for mortality between mild and moderate/severe TBI patients. However, patients aged between 46 and 55 years, female patients, and patients with pre-existing renal disease had a significant higher cancer incidence risk in moderate/severe TBI compared with mild TBI patients. The top 15 most common cancers showed that mild TBI patients had a higher percentage of head and neck cancer. The overall mortality rate in all TBI patients diagnosed with cancer was about 50%, and the cancer-specific mortality is approximately 85% in death of TBI patients with cancer. CONCLUSIONS: We concluded that the incidence risk of a new cancer diagnosis and mortality risk of TBI patients with cancer between the mild TBI and moderate/severe TBI patients were not significantly different.

Severe Traumatic Brain Injury in children-paradigm of decompressive craniectomy compared to a historic cohort.

PURPOSE: Traumatic brain injury (TBI) is one of the leading causes of death and disability in children. Medical therapy remains limited, and decompressive craniectomy (DC) is an established rescue therapy in case of elevated intracranial pressure (ICP). Much discussion deals with clinical outcome after severe TBI treated with DC, while data on the pediatric population is rare. We report our experience of treating severe TBI in two different treatment setups at the same academic institution. METHODS: Forty-eight patients (≤ 16 years) were hospitalized with severe TBI (GCS ≤ 8 points) between 2008 and 2018 in a pediatric intensive care unit (ICU) at a specialized tertiary pediatric care center. Data on treatment, clinical status, and outcome was retrospectively analyzed. Outcome data included Glasgow Outcome Scale (GOS) at 3-, 12-, and 36-month follow-up. Data was compared to a historic cohort with 53 pediatric severe TBI patients treated at the same institution in a neurointensive care unit between 1996 and 2007. Ethical approval was granted (EA2/076/21). RESULTS: Between 2008 and 2018, 11 patients were treated with DC. Compared to the historic cohort, patients were younger and GCS was worse, while in-hospital mortality and clinical outcome remained similar. A trend towards more aggressive EVD placement and the internal paradigm change for treatment in a specialized pediatric ICU was observed. CONCLUSIONS: In children with severe TBI treated over two decades, clinical outcome was comparable and mostly favorable in two different treatment setups. Consequent therapy is warranted to maintain the positive potential for favorable outcome in children with severe TBI.

Comparative effectiveness of intracranial hypertension management guided by ventricular versus intraparenchymal pressure monitoring: a CENTER-TBI study.

OBJECTIVE: To compare outcomes between patients with primary external ventricular device (EVD)-driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)-driven treatment. METHODS: The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with "center" as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome. RESULTS: A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36-1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34-2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs. CONCLUSION: We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor-guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group. PROTOCOL: The core study is registered with ClinicalTrials.gov , number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582).

Poor outcome in frail elderly patient after severe TBI.

OBJECTIVE: To investigate the influence of frailty in elderly with severe TBI on mortality and functional outcome. METHOD: 126 patients with TBI aged 60 years or older and with a presenting Glasgow Coma Scale score of 8 or lower were retrospectively included. To investigate frailty, we used the CSHA Clinical Frailty Scale. The primary outcome measures were mortality, and the secondary outcome measures were Glasgow Outcome Scale Extended (GOSE) at discharge and GOSE at 6 months after trauma. RESULTS: High frailty was a significant predictor for mortality (OR 2.38, p 0.047), if adjusted for the injury severity scale. High frailty was also a significant predictor for poor functional outcome after 6 months (OR 4.35, p 0.03). After 6 months, the GOSE of the low frailty group was significantly higher than in the high frailty group (p 0.019). Also, the improvement of the GOSE was significant in the low frailty group (p 0.007), while in the high frailty group there was no significant improvement of the GOSE (p 0.546) after 6 months. CONCLUSION: Frailty has a significant impact on outcome in elderly with severe TBI. There is a higher mortality in the frail elderly and there is less recovery after TBI.

Cerebral Energy Status and Altered Metabolism in Early Severe TBI: First Results of a Prospective 31P-MRS Feasibility Study.

OBJECTIVE: Severe traumatic brain injury (sTBI) represents a serious public health issue with high morbidity and mortality. Neuroimaging plays a crucial role in the evaluation of sTBI patients. Phosphorous magnetic resonance spectroscopy (31P-MRS) is an imaging technique for evaluation of energy metabolites. The aim of this study is to evaluate the feasibility and the diagnostic potential of ultra-early 31P-MRS to detect changes in cerebral energy metabolism in sTBI. METHODS: Adult patients with sTBI presenting with GCS ≤ 8 being eligible for MRI were prospectively included in the study and MRI was performed within 72 h after trauma. Imaging was performed using a 3 Tesla MRI. 31P-MRS data from the structurally affected side were compared to data from normal appearing contralateral areas symmetrically to the location of the traumatic lesions, and to data of matched healthy controls. RESULTS: Ten sTBI patients (3 female, 7 male), aged between 20 and 75 years, with a mean initial GCS of 6 were analyzed. MRI was performed 61 h (mean, range 37-71 h) after trauma. Statistical analysis revealed no significant differences between the lesioned side and contralaterally. An increased PCr/ATP ratio and a decreased PME/PDE ratio were present in structurally normal appearing, but traumatized tissue when compared to the healthy population, thus indicating significant differences in ATP resynthesis and membrane turnover (F (2,33), P = 0.005 and, P = 0.027, respectively). CONCLUSION: 31P-MRS could provide a better understanding of pertinent global changes in cerebral energy metabolism in sTBI patients under general anesthesia.

Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury.

Noninvasive, affordable circulating biomarkers for difficult-to-diagnose mild traumatic brain injury (mTBI) are an unmet medical need. Although blood microRNA (miRNA) levels are reportedly altered after traumatic brain injury (TBI), their diagnostic potential for mTBI remains inconclusive. We hypothesized that acutely altered plasma miRNAs could serve as diagnostic biomarkers both in the lateral fluid percussion injury (FPI) model and clinical mTBI. We performed plasma small RNA-sequencing from adult male Sprague-Dawley rats (n = 31) at 2 days post-TBI, followed by polymerase chain reaction (PCR)-based validation of selected candidates. miR-9a-3p, miR-136-3p, and miR-434-3p were identified as the most promising candidates at 2 days after lateral FPI. Digital droplet PCR (ddPCR) revealed 4.2-, 2.8-, and 4.6-fold elevations in miR-9a-3p, miR-136-3p, and miR-434-3p levels (p < 0.01 for all), respectively, distinguishing rats with mTBI from naïve rats with 100% sensitivity and specificity. DdPCR further identified a subpopulation of mTBI patients with plasma miR-9-3p (n = 7/15) and miR-136-3p (n = 5/15) levels higher than one standard deviation above the control mean at <2 days postinjury. In sTBI patients, plasma miR-9-3p levels were 6.5- and 9.2-fold in comparison to the mTBI and control groups, respectively. Thus, plasma miR-9-3p and miR-136-3p were identified as promising biomarker candidates for mTBI requiring further evaluation in a larger patient population.

Multidisciplinary attentive treatment for patients with chronic disorders of consciousness following severe traumatic brain injury in the NASVA of Japan.

Primary Objective: The aim of this study was to demonstrate the clinical outcomes of long-term multidisciplinary attentive treatment (MAT) in patients with chronic disorders of consciousness (DOC) due to severe traumatic brain injury (TBI) following automotive accidents.Research Design: Five hundred and ten patients (mean age: 40.4 years) were enrolled in this retrospective study.Methods and Procedures: Patients were provided MAT for one to several years in the eight medical facilities of the National Agency for Automotive Safety and Victims' Aid (NASVA) in Japan. Clinical status for consciousness, communication, and activities of daily living were evaluated using the NASVA grading system.Outcomes and results: Following MAT, NASVA scores at discharge were significantly improved compared to those at admission in every patient subgroup including sex, age, NASVA score, and association with/without hypoxic encephalopathy at admission. Younger age, shorter interval between injury and admission, and better neurocognitive function at admission were found to be significant and independent factors for a good prognosis.Conclusions: MAT can partially improve the cognitive and physical abilities of patients with chronic DOC. From the perspective of not only restoring a patient's daily life, but also reducing the caregiver's burden, this type of treatment program warrants more public attention.

Elevated cerebrospinal fluid concentrations of N-acetylaspartate correlate with poor outcome in a pilot study of severe brain trauma.

Primary objective: Examine the correlation between acute cerebrospinal fluid (CSF) levels of N-acetylaspartate (NAA) and injury severity upon admission in addition to long-term functional outcomes of severe traumatic brain injury (TBI). Design and rationale: This exploratory study assessed CSF NAA levels in the first four days after severe TBI, and correlated these findings with Glasgow Coma Scale (GCS) score and long-term outcomes at 3, 6, 12, and 24 months post-injury. Methods: CSF was collected after passive drainage via an indwelling ventriculostomy placed as standard of care in a total of 28 people with severe TBI. NAA levels were assayed using triple quadrupole mass spectrometry. Functional outcomes were assessed using the Glasgow Outcomes Scale (GOS) and Disability Rating Scale (DRS). Results: In this pilot study, better functional outcomes, assessed using the GOS and DRS, were found in individuals with lower acute CSF NAA levels after TBI. Key findings were that average NAA level was associated with GCS (p = .02), and GOS at 3 (p = .01), 6 (p = .04), 12 (p = .007), and 24 months (p = .002). Implications: The results of this study add to a growing body of neuroimaging evidence that raw NAA values are reduced and variable after TBI, potentially impacting patient outcomes, warranting additional exploration into this finding. This line of inquiry could lead to improved diagnosis and prognosis in patients with TBI.

Plasma matrix metalloproteinase-9 levels predict intensive care unit mortality early after severe traumatic brain injury.

OBJECTIVES: Matrix metalloproteinase-9 (MMP-9) is an inducible metalloproteinase that can degrade the cerebrovascular matrix leading to disruption of the blood-brain barrier and exacerbation of oedema in neurotrauma. Therefore, our aim was to determine whether MMP-9 plasma levels were associated with intensive care unit (ICU) mortality after severe traumatic brain injury (TBI) despite the presence of extracerebral injuries. METHODS: This cohort enrolled 80 patients who suffered severe TBI (Glasgow Coma Scale: 3-8 at hospital admission). The plasma MMP-9 level was determined by enzyme-linked immunosorbent assay assay at ICU admission. RESULTS: Severe TBI was associated with a 32.5% ICU mortality rate. There was no association between the presence of extracerebral injuries (72.5% of the patients) and ICU mortality (P = 0.419). Higher plasma MMP-9 concentrations were associated with fatal outcome: 181.1 ± 16.0 ng/mL for survivors and 257.0 ± 23.2 ng/mL for nonsurvivors (mean ± S.E.M., P = 0.009). In contrast, there was no significant difference between MMP-9 levels and associated lesions: 220.8 ± 26.3 ng/mL for isolated TBI and 196.8 ± 15.8 ng/mL for patients with extracerebral injuries (P = 0.397). CONCLUSION: Increased plasma MMP-9 levels predicted short-term fatal outcome following severe TBI, regardless the presence of extracerebral injuries.

A prospective pilot study on serum cleaved tau protein as a neurological marker in severe traumatic brain injury.

OBJECTIVE: Neurotrauma has been labelled as a "silent epidemic" affecting both the developed and the developing nations. To date, no single brain-specific biomarker has been unanimously accepted for routine clinical use in TBI. Our study aims to determine the correlation of "cleaved-tau protein" in severe traumatic brain injury (TBI) with Glasgow Coma Scale (GCS) at the time of admission, mode of injury, CT findings and outcome at discharge. METHODS: The study has been approved by the institutional ethical committee. 40 cases with severe TBI and 40 randomly selected healthy controls were included in this prospective study. Venous blood samples were collected and serum cleaved tau protein levels were measured and correlated with gender, mode of injury, CT findings GCS score and GOS score at discharge. RESULTS: In the severe TBI group, the mean serum cleaved tau protein levels in males were 91.65 ± 41.34 pg/ml (mean ± S.D.), and females were 104.43 ± 53.08 pg/ml (mean ± S.D.), (p = 0.27). Mean serum C-tau level in study group was 95.48 ± 44.87 pg/ml (range 36.44-192.34), 95% C.I. (81.13-109.83) and in controls was 33.82 ± 13.65 pg/ml (range 2.48-66.54), 95% C.I. (29.46-38.19) (p < 0.001). The distribution of serum C-tau was in severe TBI group varied in all categories of GCS at 0th day (p < 0.001). Serum cleaved tau protein levels in the good outcome group were 74.26 ± 25.43 pg/ml (mean ± S.D.), range 36.44-144.54, 95% C.I. (63.52-85.00) and the poor-outcome group were 127.32 ± 49.40 pg/ml, range 66.65-192.34, 95% C.I. (100.99-153.64) (p = 0.001). CONCLUSION: In severe TBI, serum cleaved tau protein levels were significantly higher as compared to the controls in this prospective study. However, results of this study are preliminary in nature and there is a need to undertake larger prospective studies to reach a definitive conclusion.

Plasma brain-derived neurotrophic factor levels after severe traumatic brain injury.

OBJECTIVE: Severe traumatic brain injury (TBI) is associated with a 30-70% mortality rate. Nevertheless, in clinical practice there are no effective biomarkers for the prediction of fatal outcome following severe TBI. Therefore, the aim was to determine whether brain-derived neurotrophic factor (BDNF) plasma levels are associated with intensive care unit (ICU) mortality in patients with severe TBI. METHODS: This prospective study enrolled 120 male patients who suffered severe TBI (Glasgow Coma Scale 3-8 at emergency room admission). The plasma BDNF level was determined at ICU admission (mean 6.4 hours after emergency room admission). RESULTS: Severe TBI was associated with a 35% mortality rate and 64% of the patients presented severe TBI with multi-trauma. The mean plasma BDNF concentration among the severe TBI victims was 704.2 ± 63.4 pg ml(-1) (±SEM). Nevertheless, there were no significant differences between BDNF levels in the survivor (700.2 ± 82.8 pg ml(-1)) or non-survivor (711.6 ± 97.4 pg ml(-1)) groups (p = 0.238) or in the isolated TBI (800.4 ± 117.4 pg ml(-1)) or TBI with multi-trauma groups (650.5 ± 73.9 pg ml(-1)) (p = 0.109). CONCLUSIONS: Plasma BDNF concentrations did not correlate with either short-term fatal outcome or type of injury following severe TBI.

Association Between Relative Anemia and Early Functional Recovery After Severe Traumatic Brain Injury (TBI).

BACKGROUND: Severe traumatic brain injury is associated with a multi-systemic response and changes in metabolic demand. Patients requiring intracranial pressure monitoring or cerebrospinal fluid diversion, often signifies a greater severity of injury. For this group, the association between RBC transfusion, transfusion thresholds, and clinical recovery is unknown. In this study, we studied the association between transfusion and clinical recovery for severe traumatic brain injury patients requiring external ventricular drain or intracranial pressure monitor placement. METHODS: Eighty-nine patients with a primary diagnosis of traumatic brain injury requiring implantation of either an intracranial pressure monitor or external ventricular drainage device were identified. All patients were managed in a Level 1 Trauma facility by board-certified neuro-intensive care practitioners for the course of their intensive care unit duration. The correlation between transfusion and clinical recovery, defined by change in Glasgow Coma Scale was assessed. RESULTS: Thirty-four patients required surgical decompression, and 56.18 % of the cumulative cohort were transfused during admission. Overall, transfusion was not associated with significant clinical recovery (change in GCS > 3) for Hgb threshold of 7 mg/dL (<3, 29.03 vs. ≥3, 37.93 %; p = 0.49), nor for higher stratifications (8 mg/dL, p = 0.63; 9 mg/dL, p = 0.79, 10 mg/dL, p = 1). For patients who required transfusions at thresholds ≥8 mg/dL, there was a positive association with decreased length of hospitalization, [p = 0.01; <8 mg/dL: 22 (12-33), ≥8 mg/dL: 14 (7.75-20)] [median (IQR)]. Similarly, length of ICU stay was shorter for patients transfused at thresholds ≥9 mg/dL, (p = 0.02). CONCLUSIONS: From our studies, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a decrease in length of hospitalization for patients with transfusion thresholds of Hgb ≥ 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population. In patients admitted for primary severe traumatic brain injury, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a noticeable decrease in length of hospitalization for patients with transfusion thresholds of Hgb ≥ 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population.

Long-term functional outcome after moderate-to-severe paediatric traumatic brain injury.

BACKGROUND: Long-term follow-up studies after severe and moderate pediatric traumatic brain injury (TBI) are not common and inconclusive. Most studies focused on neurobehavioural sequelae, less data is reported about age appropriate function. Different prognostic factors were noted over past decades. METHODS: A prospective historical study describing the functional long-term outcome after childhood moderate and severe TBI was conducted. Seventy-seven children who suffered either severe or moderate TBI were followed for an average of ten years and clinical functional outcome was recorded. Factors influencing prognosis were investigated. RESULTS: All children but six were integrated into educational systems after discharge from rehabilitation settings (department and day-care); 61% of children who suffered severe-moderate TBI were able to function within their normative age peers. Positive outcome predictors were Glasgow Coma Scale (GCS) >5, length of unconsciousness (LOC) <11 days, Functional Independence Measure (FIM) and Intelligence Quotient (IQ) at discharge from rehabilitation, length of acute hospitalization and rehabilitation. Negative outcome predictors were vegetative state at admission to rehabilitation and associated anoxic brain injury. CONCLUSIONS: Guarded optimistic functional outcome can be expected after severe or moderate childhood TBI.

Propensity weighted analysis of chemical venous thromboembolism prophylaxis agents in isolated severe traumatic brain injury: An EAST sponsored multicenter study.

BACKGROUND: In patients with severe traumatic brain injury (TBI), clinicians must balance preventing venous thromboembolism (VTE) with the risk of intracranial hemorrhagic expansion (ICHE). We hypothesized that low molecular weight heparin (LMWH) would not increase risk of ICHE or VTE as compared to unfractionated heparin (UH) in patients with severe TBI. METHODS: Patients ≥ 18 years of age with isolated severe TBI (AIS ≥ 3), admitted to 24 level I and II trauma centers between January 1, 2014 to December 31, 2020 and who received subcutaneous UH and LMWH injections for chemical venous thromboembolism prophylaxis (VTEP) were included. Primary outcomes were VTE and ICHE after VTEP initiation. Secondary outcomes were mortality and neurosurgical interventions. Entropy balancing (EBAL) weighted competing risk or logistic regression models were estimated for all outcomes with chemical VTEP agent as the predictor of interest. RESULTS: 984 patients received chemical VTEP, 482 UH and 502 LMWH. Patients on LMWH more often had pre-existing conditions such as liver disease (UH vs LMWH 1.7 % vs. 4.4 %, p = 0.01), and coagulopathy (UH vs LMWH 0.4 % vs. 4.2 %, p < 0.001). There were no differences in VTE or ICHE after VTEP initiation. There were no differences in neurosurgical interventions performed. There were a total of 29 VTE events (3 %) in the cohort who received VTEP. A Cox proportional hazards model with a random effect for facility demonstrated no statistically significant differences in time to VTE across the two agents (p = 0.44). The LMWH group had a 43 % lower risk of overall ICHE compared to the UH group (HR = 0.57: 95 % CI = 0.32-1.03, p = 0.062), however was not statistically significant. CONCLUSION: In this multi-center analysis, patients who received LMWH had a decreased risk of ICHE, with no differences in VTE, ICHE after VTEP initiation and neurosurgical interventions compared to those who received UH. There were no safety concerns when using LMWH compared to UH. LEVEL OF EVIDENCE: Level III, Therapeutic Care Management.

Outcomes following surgical intervention for acute hemorrhage in severe traumatic brain injury: a review of the National Trauma Data Bank.

OBJECTIVE: Severe traumatic brain injury (TBI) is a public health issue posing significant morbidity and mortality to afflicted patients. While the effect of time to surgery as the primary factor for survival has been extensively studied, long-term dispositional outcomes following intracranial hemorrhage evacuation have not been well described in the literature. Therefore, the aim of this study was to elicit potential prognostic factors in patients presenting with severe TBI that may have a significant impact on discharge disposition. METHODS: The authors searched the National Trauma Data Bank (NTDB) for patients included between 2010 and 2019, solely focusing on those with a Glasgow Coma Scale score ≤ 8, signifying severe TBI, and with associated intracranial hemorrhage treated via surgical intervention. Numerous characteristics were analyzed, including demographics (age, sex, race, ethnicity, payment status), discharge disposition, time to surgery, pupillary response, midline shift (> 5 mm), and postoperative inpatient complications and comorbidities. Disposition included routine discharge to home, discharge to home with home health services (HHSs), discharge to acute inpatient rehabilitation (AIR), discharge to a skilled nursing facility (SNF)/long-term acute care hospital (LTACH), and death. RESULTS: The authors analyzed data on 7308 patients, 69.6% of whom were White and 11.2% of whom were Black. More young Black and Hispanic patients had severe TBI events than their matched elders, whereas more elderly White patients had severe TBI events than their matched younger counterparts. The most common disposition across all ages was SNF/LTACH. Septuagenarians and octogenarians were 12.1 and 21 times more likely, respectively, to die following a severe TBI than their younger counterparts (p < 0.001). Patients aged 18-29 were 1.7 times more likely to be discharged with HHSs (p < 0.001). Minority race/ethnicity groups were less likely to be discharged to AIR. As age increased, a patient's intensive care unit stay increased by 15 days (p < 0.001) and total hospital length of stay increased by 25 days (p < 0.001). CONCLUSIONS: Neurosurgical evacuation of intracranial hemorrhage in severe TBI has variable long-term morbidity. Utilizing the largest collection of trauma data within the United States, the authors present quantitative evidence on discharge disposition. Understanding these tangible points can help neurosurgeons present potential outcomes to patients, promote preventative care, and generate tangible conversations with patients and their family members.

A meta-analysis of cognitive and functional outcomes in severe brain trauma cases.

Background: Severe traumatic brain injuries (TBIs) are an important health issue worldwide, which are associated with harmful side effects. This meta-analysis investigates the cognitive and functional outcomes in severe brain trauma cases. It assesses the impact on memory, verbal and visual abilities, attention, learning, and the presence of depression. The study provides a comprehensive overview of the consequences of severe brain trauma injury on cognitive and functional domains. Objective: The main objective of the current comprehensive meta-analysis study is to assess and analyze the impact of severe TBI on functional and cognitive outcomes, including verbal, visual, attention, learning, memory, and emotional stability. Methods: We collected data from three online databases, including PubMed, Cochrane Library, and Embase. Case-control trials related to severe TBI association with cognitive and functional outcomes were included. Verbal strength, visual functions, learning abilities, attention, memory, and depression were considered primary outcomes. Results: We have included 13 case-control studies with 1,442 subjects in this meta-analysis, which provide adequate data to determine the pooled effect size for targeted outcomes. The effect of severe TBI on the inducement of depression and impairment of memory, verbal, visual, attention, and learning abilities compared to the control group showed statistically significant outcomes (p < 0.05). Conclusion: Severe TBI is strongly associated with impaired cognitive and functional abilities, including visual and verbal disabilities, impaired memory, depression inducement, attention deficits, and learning disabilities.

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

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

Use of magnetic source imaging to assess recovery after severe traumatic brain injury-an MEG pilot study.

Rationale: Severe TBI (sTBI) is a devastating neurological injury that comprises a significant global trauma burden. Early comprehensive neurocritical care and rehabilitation improve outcomes for such patients, although better diagnostic and prognostic tools are necessary to guide personalized treatment plans. Methods: In this study, we explored the feasibility of conducting resting state magnetoencephalography (MEG) in a case series of sTBI patients acutely after injury (~7 days), and then about 1.5 and 8 months after injury. Synthetic aperture magnetometry (SAM) was utilized to localize source power in the canonical frequency bands of delta, theta, alpha, beta, and gamma, as well as DC-80 Hz. Results: At the first scan, SAM source maps revealed zones of hypofunction, islands of preserved activity, and hemispheric asymmetry across bandwidths, with markedly reduced power on the side of injury for each patient. GCS scores improved at scan 2 and by scan 3 the patients were ambulatory. The SAM maps for scans 2 and 3 varied, with most patients showing increasing power over time, especially in gamma, but a continued reduction in power in damaged areas and hemispheric asymmetry and/or relative diminishment in power at the site of injury. At the group level for scan 1, there was a large excess of neural generators operating within the delta band relative to control participants, while the number of neural generators for beta and gamma were significantly reduced. At scan 2 there was increased beta power relative to controls. At scan 3 there was increased group-wise delta power in comparison to controls. Conclusion: In summary, this pilot study shows that MEG can be safely used to monitor and track the recovery of brain function in patients with severe TBI as well as to identify patient-specific regions of decreased or altered brain function. Such MEG maps of brain function may be used in the future to tailor patient-specific rehabilitation plans to target regions of altered spectral power with neurostimulation and other treatments.