Moderate Traumatic Brain Injury Group Research Articles

Subdural haematoma in the elderly: management and outcomes of a UK Major Trauma Centre

Background An estimated 40% of all traumatic brain injury (TBI) occurs in ≥70-year-olds with a high prevalence of traumatic subdural haematoma (tSDH). It is anticipated that an expanding elderly population will lead to a proportional increase in the incidence of patients with tSDH presenting to UK trauma centres, but the long-term clinical outcomes and factors influencing functional outcomes in this patient group remain poorly understood. Aim To examine the management and clinical outcomes for elderly (≥70 years) patients diagnosed with tSDH. Methods Patient data for this single-centre, retrospective cohort study were analysed from a Major Trauma Centre (MTC) electronic patient records between January 2013 and December 2019. Results Two hundred and eighty patients were included, 43% aged 70–79, 42% aged 80–89 and 15% >90. In total, 37% underwent a surgical intervention. The 6-month survival in the severe, moderate, and mild TBI groups was 14%, 43%, and 67%, respectively. The 6-month survival in the surgical group was 58%, vs. 60% in the conservatively managed group. Surgical intervention did not significantly impact Extended Glasgow Coma Score (GOS-E) at 6 months, regardless of injury severity. Advanced age (p = 0.04), mixed intracranial injuries (p < 0.0001), craniotomies (p = 0.03), and poor premorbid performance status (p = 0.02) were associated with worse survival and functional outcomes. Conclusions Our study demonstrated that increasing age, increasing severity of TBI and poorer premorbid performance status were associated with significantly poorer 6-month survival and functional outcomes in elderly patients with tSDH. Burr hole evacuation was associated with better functional outcomes compared to craniotomy, but overall, there was no significant difference in the outcomes of the surgical and non-surgical groups. We identified strong risk factors for death and poor functional outcomes at 6-months which are important to consider when counselling patients and families about the long-term prognosis of elderly patients with tSDH and can help guide clinical decision-making.

More to the story than executive function: Effortful control soon after injury predicts long-term functional and social outcomes following pediatric traumatic brain injury in young children.

To examine the impact of early traumatic brain injury (TBI) on effortful control (EC) over time and the relationship of EC and executive functioning (EF) to long-term functional and social outcomes. Parents of children (N = 206, ages 3-7) with moderate-to-severe TBI or orthopedic injuries (OIs) rated EC using the Child Behavior Questionnaire at 1 (pre-injury), 6, 12, and 18 months post-injury. Child functioning and social competence were assessed at 7 years post-injury. Mixed models examined the effects of injury, time since injury, and their interaction on EC. General linear models examined the associations of pre-injury EC and EC at 18 months with long-term functional and social outcomes. Models controlled for EF to assess the unique contribution of EC to outcomes. Children with severe TBI had significantly lower EC than both the OI and moderate TBI groups at each post-injury time point. Both pre-injury and 18-month EC were associated with long-term outcomes. Among those with low EC at baseline, children with moderate and severe TBI had more functional impairment than those with OI; however, no group differences were noted at high levels of EC. EC had main effects on parent-reported social competence that did not vary by injury type. Findings suggest that EC is sensitive to TBI effects and is a unique predictor of functional outcomes, independent of EF. High EC could serve as a protective factor, and as such measures of EC could be used to identify children for more intensive intervention.

The requirement of propofol for induction of anesthesia in patients with traumatic brain injury determined using bilateral bispectral index and target controlled infusion - An observational cohort study.

Patients with traumatic brain injury (TBI) frequently require emergency surgery. There is a paucity of literature with regard to anesthetic requirements in these patients. The aim of the study was to compare the dose of propofol required for induction of anesthesia in patients with different grades of TBI. This prospective, observational study included patients with mild, moderate, and severe grades of TBI undergoing emergency surgery within 48 h of injury. Bispectral Index (BIS) values were recorded using a bilateral BIS sensor. Anesthesia was induced with a target controlled infusion (TCI) pump. Once BIS reached 40, plasma (Cp) and effect-site (Ce) concentration and total dose of propofol required were noted from the TCI pump. Of the 96 patients recruited, 27, 36, and 33 patients belonged to mild, moderate, and severe TBI (sTBI) groups, respectively. The Ce of propofol in mild, moderate, and sTBI groups was 6 ± 0.9, 5.82 ± 0.98, and 4.48 ± 1.5 μg/mL (P < 0.001), and the dose of propofol required was 1.9 ± 0.2, 1.8 ± 0.4, 1.41 ± 0.5 mg/kg, respectively (P < 0.001). Baseline BIS on the injured side was 80 ± 7.8, 71 ± 9.4, 55 ± 11.6, and on the uninjured side was 89 ± 5.5, 81 ± 8.4, and 65 ± 12 in mild, moderate, and sTBI groups, respectively. The requirement of propofol was reduced in patients with sTBI. The dose of propofol required for induction of anesthesia as determined using Ce was significantly lower only between sTBI and mild TBI and not between patients with sTBI and moderate TBI or between mild and moderate head injury. BIS values were significantly different between the groups (highest in mild TBI and lowest in sTBI) and between normal and injured sides within each group.

Glial fibrillary acidic protein level on admission can predict severe traumatic brain injury in patients with severe multiple trauma: A single-center retrospective observational study.

This study aimed to clarify whether the glial fibrillary acidic protein (GFAP) and soluble protein-100β (S100β) can predict severe traumatic brain injury (TBI) in patients with severe multiple trauma. This is a single-center retrospective observational study of 179 patients with severe multiple trauma. The GFAP and S100β were measured upon patient arrival at the hospital. We divided the patients into the severe TBI group (with a Traumatic Coma Data Bank classification of ≥III), the non-severe TBI group (non-TBI group [absence of abnormality on the computed tomography scan and extracranial injury], and the mild to moderate TBI group [TCDB classification I and II]). We compared biomarker levels between the two groups and then evaluated the accuracy of predicting severe TBI using a receiver operating characteristic curve. A total of 41 patients had severe TBI, and 138 had non-severe TBI. Mean GFAP levels were significantly higher in the severe TBI group (median, 6000pg/mL; interquartile range [IQR], 651-15,548pg/mL) than in the non-severe TBI group (median, 149pg/mL; IQR, 0-695pg/mL) (p<0.0001). In contrast, there was no significant difference in S100β levels between the severe TBI group (median, 64pg/mL; IQR, 0-536pg/mL) and non-severe TBI group (median, 117pg/mL; IQR, 0-403pg/mL) (p=0.637). The area under the receiver operating characteristic curve was 0.810 (p<0.0001) for GFAP and 0.476 (p=0.908) for S100β. For the GFAP, the optimal cutoff value for detecting severe TBI was 947pg/mL (sensitivity, 75.6%; specificity, 78.3%). In patients with severe multiple trauma, the GFAP level at hospital arrival could predict severe TBI, whereas the S100β level was not a useful predictor.

Healing After Moderate to Severe TBI Takes Time

Healing After Moderate to Severe TBI Takes Time

A Novel Histological Technique to Assess Severity of Traumatic Brain Injury in Rodents: Comparisons to Neuroimaging and Neurological Outcomes.

Here we evaluate an alternative protocol to histologically examine blood-brain barrier (BBB) breakdown, brain edema, and lesion volume following traumatic brain injury (TBI) in the same set of rodent brain samples. We further compare this novel histological technique to measurements determined by magnetic resonance imaging (MRI) and a neurological severity score (NSS). Sixty-six rats were randomly assigned to a sham-operated, mild TBI, moderate TBI, or severe TBI group. 48 h after TBI, NSS, MRI and histological techniques were performed to measure TBI severity outcome. Both the histological and MRI techniques were able to detect measurements of severity outcome, but histologically determined outcomes were more sensitive. The two most sensitive techniques for determining the degree of injury following TBI were NSS and histologically determined BBB breakdown. Our results demonstrate that BBB breakdown, brain edema, and lesion volume following TBI can be accurately measured by histological evaluation of the same set of brain samples.

Apolipoprotein e (APOE) ε4 genotype influences memory performance following remote traumatic brain injury in U.S. military service members and veterans

The purpose of this study was to examine the association between the apolipoprotein E (APOE) ε4 allele and neurocognitive functioning following traumatic brain injury (TBI) in military service members and veterans (SMVs). Participants included 176 SMVs with a history of remote TBI (≥1 year post-injury), categorized into mild (n = 100), moderate (n = 40), and severe (n = 36) TBI groups. Participants completed a neuropsychological assessment and APOE genotyping (n = 46 ε4+, n = 130 ε4-). Neurocognitive composite scores representing memory, executive functioning, and visual processing speed were computed. ANCOVAs adjusting for race, education, combat exposure, and PTSD symptom severity showed a significant main effect of ε4 on the memory composite, such that ε4+ SMVs exhibited poorer memory performance than ε4- SMVs. When ε2 allele carriers were removed from the analyses, associations with memory were strengthened, demonstrating a possible protective effect of the ε2 allele. No main effect of TBI group was identified on any cognitive composite, nor were there any significant TBI group × ε4 status interactions for any cognitive composite. Future studies with larger samples are needed to verify these findings, but our results suggest an important relationship between ε4 status and memory functioning following remote TBI of all severities.

Gender differences in adult traumatic brain injury according to the Glasgow coma scale: A multicenter descriptive study

PurposePatients’ gender, which can be one of the most important determinants of traumatic brain injury (TBI) outcomes, is also likely to interact with many other outcome variables of TBI. This multicenter descriptive study investigated gender differences in epidemiological, clinical, treatment, mortality, and variable characteristics in adult TBI patients. MethodsThe selection criteria were defined as patients who had been diagnosed with TBI and were admitted to the hospital between January 1, 2016 and December 31, 2018. A total of 4468 adult TBI patients were enrolled at eight University Hospitals. Based on the list of enrolled patients, the medical records of the patients were reviewed and they were registered online at each hospital. The registered patients were classified into three groups according to the Glasgow coma scale (GCS) score: mild (13–15), moderate (9−12), and severe (3–8), and the differences between men and women in each group were investigated. The risk factors of moderated and severe TBI compared to mild TBI were also investigated. ResultsThe study included 3075 men and 1393 women and the proportion of total males was 68.8%. Among all the TBI patients, there were significant differences between men and women in age, past history, and GCS score. While the mild and severe TBI groups showed significant differences in age, past history, and clinical symptoms, the moderate TBI group showed significant differences in age, past history, cause of justice, and diagnosis. ConclusionTo the best of our knowledge, this multicenter study is the first to focus on gender differences of adult patients with TBI in Korea. This study shows significant differences between men and women in many aspects of adult TBI. Therefore, gender differences should be strongly considered in TBI studies.

Loss of Nociceptin/Orphanin FQ peptide receptor protects against traumatic brain injury (TBI)‐induced deficits in male and female rats

Introduction : Traumatic brain injury (TBI) is a leading cause of death and disability in the United States and often chronically affects mental and physical health and overall quality of life. We previously reported that acute treatment of blast TBI with a Nociceptin/OrphaninFQ (N/OFQ) peptide receptor (NOP) antagonist improved vestibulomotor deficits in male rats, corresponding to TBI-induced increases in NOP and its endogenous neuropeptide N/OFQ. The goal of this study is to determine whether the absence of NOP protects against neurological and behavioral sequelae of TBI in male and female KO rats compared to WT. Methods Male and female Wistar NOP receptor knockout (NOP KO) and wildtype (WT) rats received either a sham craniotomy, mild TBI (mTBI) or moderate TBI (ModTBI) controlled cortical impact (CCI) to the left cerebral hemisphere. Injury severity and recovery were assessed using modified neurological severity score (mNSS) on days 1 and 8 post-TBI. Vestibulomotor function was determined using the rotarod. Nociceptive sensitivity to mechanical and thermal stimuli were determined by measuring hind paw withdrawal threshold (PWT) to plastic filaments and by measuring tail flick latency (TFL) from radiant heat, respectively, prior to injury (baseline) and on days 2, 4, and 7 post-TBI. The presence of anxiety-like symptoms was assessed using the elevated plus maze (EPM) on day 7 post-TBI. Data were analyzed by two-way ANOVA with or without repeated measures (as appropriate). Results Rats of both genotypes and sexes showed complete neurological recovery (mNSS<1) following mTBI, and partial recovery following ModTBI by day 8. Mild and ModTBI produced significant vestibular deficits in rat rotarod performance on days 1-8 post-TBI in WT male (n=7-8). In WT females (n=8), ModTBI produced vestibular deficits on days 1-7, whereas mTBI only produced vestibular deficits on days 1-4. Interestingly, neither male (n=5-6) nor female (n=3) mTBI NOP KO rats exhibited vestibulomotor deficits. ModTBI caused significant vestibular deficits only on day 1 post-TBI in male and female NOP KO rats. Rotarod performance in WT females was significantly worse than KO females on days 2-4 post TBI following moderate injury (*p<0.05), and on days 4-7 following mild injury (*p<0.05). WT males (n=7-8) and females (n=8) exhibited thermal hyperalgesia and mechanical allodynia throughout the study, with little difference between mild and moderate TBI groups. KO males (n=3) developed no thermal hyperalgesia after either mild or ModTBI. Only ModTBI rats developed mechanical allodynia, and it lasted throughout the study. KO females (n=3) showed both thermal and mechanical hypersensitivity on day 2 and only mechanical hypersensitivity on day 4. No differences in anxiety-like behaviors were found between any of the groups. Conclusion The N/OFQ-NOP system contributes to vestibular deficits and hyperalgesia associated with TBI; the absence of NOP protects against TBI-induced vestibulomotor deficits and nociceptive hypersensitivity.

Role of Diffusion Tensor Imaging Combined with Neuron-Specific Enolase and S100 calcium-binding protein B Detection in Predicting the Prognosis of Moderate and Severe Traumatic Brain Injury

Background Traumatic brain injury (TBI) seriously affects the quality of life of patients. The present study evaluated the role of diffusion tensor imaging (DTI) combined with Neuron-Specific Enolase (NSE) and S100 calcium-binding protein B (S100B) protein in predicting the prognosis of moderate and severe TBI. Methods The TBI patients were divided into moderate TBI (TBIm) and severe TBI (TBIs) groups according to the Glasgow Coma Scale (GCS) after admission. The patients were then divided into good and poor prognosis groups according to the Glasgow Outcome Scale (GOS); moreover, their follow-ups were recorded at 3 and 6 months after injury. This study also included 65 healthy individuals with matched age and gender as the control group. The fractional anisotropy (FA) values of DTI, serum neuron-specific enolase (NSE), and S100B protein levels were detected in this study. The data were analyzed in SPSS software (version 22.0) to evaluate the role of DTI combined with NSE and S100B protein in predicting the prognosis in TBIm and TBIs. Results: After TBI, the FA values of DTI in the TBI group were lower than those in the control group (P&lt;0.05); moreover, the serum NSE and S100B values in the TBI group were higher than those in the control group (P&lt;0.05). In the TBIm patients, the FA values of the corpus callosum in the good prognosis group were higher than that in the poor prognosis group (P&lt;0.05); however, there was no significant difference between the two groups regarding the FA values of the internal capsule and the cerebral peduncle (P&gt;0.05). The serum levels of NSE and S100B in the good prognosis group were significantly lower than those in the poor prognosis group (P&lt;0.05). In the TBIs patients, the FA value of all areas in the good prognosis group was significantly higher than that in the poor prognosis group (P&lt;0.05). However, there was no significant difference between the two prognosis groups regarding the serum levels of NSE and S100B (P&gt;0.05). Conclusion Although DTI combined with NSE and S100B protein can effectively predict the prognosis of patients with moderate and severe TBI in the early stages, various other measures have been used in the studies to predict the prognosis of TBI patients. Accordingly, comparison with other measures is essential in further studies.

Neurocognitive and Affective Sequelae Following Complicated Mild and Moderate Traumatic Brain Injury: A Case Series.

Traumatic brain injury (TBI) leads to various sequelae that affect the day-to-day functioning of patients. However, there is a dearth of studies investigating these sequelae in complicated mild TBI and moderate TBI patients. The prime objective of the present study was to present the neurocognitive and affective profile of complicated mild and moderate TBI patients along with to compare the neurocognitive and affective sequelae in patients with complicated mild and moderate TBI. Twenty-two patients with complicated mild TBI and 17 patients with Moderate TBI, each with an intracranial lesion were recruited from level 1 trauma center in Varanasi. All patients were assessed with neurocognitive measures, Rivermead Post Concussive Symptoms Questionnaire, and Hospital Anxiety and Depression Scale. The patients' profiles were presented as clinical series using descriptive analysis. Further, comparison was done by using the Chi-square test and Fisher's exact test. Findings revealed that complicated mild TBI patients reported significantly higher psychological distress and post head injury symptoms in comparison to patients with moderate TBI. Further, the complicated mild TBI and moderate TBI groups showed differences with respect to verbal fluency, mental speed, and flexibility tasks. Complicated mild TBI and moderate TBI groups have not differed significantly on most of the cognitive tasks. Furthermore, affective symptoms were found more prominent in complicated mild TBI group as compared to the moderate TBI group.

Sleep Disturbances in Young Adults with Childhood Traumatic Brain Injury: Relationship with Fatigue, Depression, and Quality of Life

ABSTRACT Objective This study assessed the consequences of childhood traumatic brain injury (TBI) on sleep, fatigue, depression, and quality of life (QoL) outcomes and explored the relationships between these variables at 20 years following childhood TBI. Participants We followed up 54 young adults with mild, moderate, and severe TBI, and 13 typically developing control (TDC) participants, recruited at the time of TBI. Methods Sleep was assessed with the Pittsburgh Sleep Quality Index and actigraphy. Results At 20 years postinjury, results showed no significant difference between whole TBI group and TDC participants on subjective sleep quality; however, the moderate TBI group reported significantly poorer subjective sleep quality compared to those with severe TBI. Poorer subjective sleep was associated with increased symptoms of fatigue, depression, and poorer perceptions of General Health in the TBI group. Actigraphic sleep efficiency, fatigue, depression, and QoL outcomes were not significantly different between TBI and TDC or among TBI severity groups. Conclusions These preliminary findings underscore associations between subjective sleep disturbance, fatigue, depression, and QoL in this TBI sample, and mostly comparable outcomes in sleep, fatigue, depression, and QoL between the TBI and TDC groups. Further research is required to clarify these findings.

Spectroscopic detection of traumatic brain injury severity and biochemistry from the retina.

Traumatic brain injury (TBI) is a major burden on healthcare services worldwide, where scientific and clinical innovation is needed to provide better understanding of biochemical damage to improve both pre-hospital assessment and intensive care monitoring. Here, we present an unconventional concept of using Raman spectroscopy to measure the biochemical response to the retina in an ex-vivo murine model of TBI. Through comparison to spectra from the brain and retina following injury, we elicit subtle spectral changes through the use of multivariate analysis, linked to a decrease in cardiolipin and indicating metabolic disruption. The ability to classify injury severity via spectra of the retina is demonstrated for severe TBI (82.0 %), moderate TBI (75.1 %) and sham groups (69.4 %). By showing that optical spectroscopy can be used to explore the eye as the window to the brain, we lay the groundwork for further exploitation of Raman spectroscopy for indirect, non-invasive assessment of brain chemistry.

Impact of Traumatic Brain Injury on Clinical Institute Withdrawal Assessment Use in Trauma Patients: A Descriptive Study.

Alcohol withdrawal syndrome (AWS) and traumatic brain injury (TBI) present with similar signs and symptoms, yet their treatment strategies differ greatly. AWS treatment includes the Clinical Institute Withdrawal Assessment (CIWA) protocol, which grades withdrawal signs and symptoms. A major purpose of CIWA is to guide the addition and titration of central nervous system (CNS) depressants, most commonly benzodiazepines. Conversely, best practice is to avoid these same CNS depressants in the setting of TBI. Thus, patients with TBI presenting with AWS risk may receive undesirable interventions that could worsen outcome. To describe the relationship of TBI diagnosis with CIWA protocol scores and intervention implementation. Retrospective cohort observational study. Single university-based, level one trauma center. Three hundred seventy-five patients with head trauma or AWS classification, identified through the trauma center's trauma registry. CIWA protocol and related medication use. Frequency of elevated CIWA score, length of CIWA administration, and medication administration incidence were abstracted from patients' medical records. The percentage of elevated CIWA scores increased significantly with TBI severity, from 4.5%(0-60) in the No TBI group, up to 12.5% (0-36) in the Mild TBI group, 27.1% (0-57) in the Moderate TBI group, and 50.0% (14-77) in the Severe TBI group. Nominally, lorazepam use showed a similar pattern of escalation with TBI severity, but it did not reach statistical significance. Haloperidol use did significantly escalate with higher TBI severity. No group differences were observed for total lorazepam equivalents or length on the CIWA protocol. TBI diagnosis and higher TBI severity level correlate with higher CIWA scores, but neither increased nor decreased benzodiazepine usage was observed. Antipsychotic use did escalate with TBI diagnosis and severity. The risks versus benefits of minimizing benzodiazepines in patients with TBI who are at risk for AWS warrant future study.

Different changes in granulocyte-colony stimulating factor and its correlation with inflammatory biomarkers in patients after traumatic brain injury.

This study analyzed changes in granulocyte-colony stimulating factor (G-CSF) and its correlation with leukocyte and neutrophil counts in patients after traumatic brain injury (TBI). Sixty TBI patients were included retrospectively. The serum levels of G-CSF, tumor necrosis factor-α (TNF-α), and peripheral leukocyte and neutrophil counts at different time points were measured and analyzed, and the 6-month functional outcomes were monitored. The levels of G-CSF in mild and moderate TBI groups were higher than the control at the first three time points. G-CSF in the severe TBI group increased slowly and peaked at day 7, and was only significantly different from the control at day 7 and 14. The leukocyte and neutrophil counts of the mild group gradually decreased, but a second increase after day 4 was observed in the severe group. The cell counts were higher in the severe group compared to other groups. A positive correlation between G-CSF and leukocyte and neutrophil counts was observed in the severe group at day 1. G-CSF positively correlated with TNF-α in the severe group at day 4 and 7. In severe patients with a good outcome, G-CSF level at day 7 was significantly higher than those with a poor outcome. The G-CSF levels in the severe TBI group exhibited a different pattern from those in the mild and moderate TBI groups, and these levels positively correlated with inflammatory biomarkers. Higher G-CSF levels in severe TBI at day 7 indicated a good outcome at 6 months.

The effective connectivity of the default mode network following moderate traumatic brain injury

The effective connectivity can reveal the causal relationships between nodes of the Default Mode Network (DMN), which may reveal any impairment to the network following moderate traumatic brain injury (MTBI). Eight sub-acute MTBI patients and eight controls were recruited for this study. The results indicated that effective connectivity (EC) within MTBI group was higher in number and strength compared to the controls. Moreover, the network hubs within DMN are associated with increased connection strength in MTBI group. The ECs in MTBI are also largely influenced by top-down backward connections. In conclusion, the network reorganization within the DMN reflects the effect of MTBI and may subsequently impair other brain functions. This knowledge can be used to correctly identify the patient for appropriate trauma management.

Traumatic brain injury enhances the formation of heterotopic ossification around the hip: an animal model study.

The incidence of heterotopic ossification (HO) is at its highest when trauma of the hip or pelvis concurs with traumatic brain injury (TBI). The pathogenic mechanisms underlying the neurogenic enhancement of the formation of HO remain, however, poorly understood. Hence, the goal of the present study was to develop a novel small animal model that combines hip and brain trauma that can prove the enhancement of HO around the hip after TBI. Forty male Wistar rats were divided into four groups, to undergo hip surgery alone (group 1), hip surgery + moderate TBI (group 2), hip surgery + severe TBI (group 3) and only severe TBI (group 4). The femoral canal was reamed up to 2mm and a muscle lesion was made to simulate hip surgery. An established controlled cortical impact model was used to create a TBI. Twelve weeks after surgery, the hip with the proximal half of the femur and the pelvic bone was removed and subjected to micro-computed tomography (µCT) analysis. A quantitative analysis using a modified Brooker score as well as a quantitative analysis using a bone-to-tissue ratio was used. No HO could be found in all the ten animals that did not undergo hip surgery (group 4). In the animals that did undergo surgery to the hip, no HO was found in only one animal (group 1). All the other animals developed HO. In this study, significantly more HO was found in animals that underwent an additional severe TBI. The newly developed rat model, with a combined hip and brain trauma, showed an enhancement of the HO formation around the hip after severe TBI.

Recovery Trajectories and Long-Term Outcomes in Traumatic Brain Injury: A Secondary Analysis of the Phase 3 Citicoline Brain Injury Treatment Clinical Trial

Prospects for recovery after traumatic brain injury (TBI) are often underestimated, potentially leading to withdrawal of care in the comatose TBI patient who may ultimately have a favorable outcome with aggressive care. Outcomes and trajectories of recovery in a large series of patients with TBI were evaluated at 30, 90, and 180 days postinjury. A secondary analysis of the phase 3 Citicoline Brain Injury Treatment (COBRIT) trial was performed analyzing recovery trajectories and long-term outcomes at 30, 90, and 180 days postinjury. A Glasgow Outcome Scale-Extended (GOS-E) score of 5 or higher was considered favorable. Pearson χ2 analysis was used, and a P value of 0.05 was considered significant. A locally weighted, polynomial regression model was used to model recovery trajectories in a nonlinear fashion. Subjects with TBI in the COBRIT trial had high rates of favorable outcome (57% of severe TBI, 86% of moderate TBI, and 93% of complicated mild TBI) at 6-month follow-up. These favorable outcomes often converted from high rates of unfavorable outcome at initial 1-month follow-up (85% of severe TBI, 57% of moderate TBI, and 21% of complicated mild TBI). Recovery trajectories had not plateaued at 6 months, suggesting that further improvement occurs beyond 6 months postinjury. In this secondary analysis of the COBRIT trial, most patients had favorable outcomes by the GOS-E at 6 months postinjury in all complicated mild and moderate TBI groups, with over half of patients with severe TBI achieving a favorable outcome as well. Of subjects in a vegetative state (GOS-E score 2) at 1 month postinjury, 18% improved to a favorable outcome by 6 months postinjury. There was substantial improvement in all groups from 1 to 6 months, and this improvement may continue beyond 6 months. Clinical trials in TBI should consider recovery curves with repeated measures to assess outcomes because arbitrary single-moment outcome determination likely underestimates treatment effect in TBI care.

Expression profile of plasma microRNAs and their roles in diagnosis of mild to severe traumatic brain injury.

Traumatic brain injury (TBI) is associated with trauma-related death. In this study, we evaluated differences in the expression of plasma microRNAs (miRNAs) in patients with different degrees of TBI, and explored the potential of miRNAs for use as diagnostic TBI biomarkers. The miRNA microarray results showed upregulation of 65, 33, and 16 miRNAs and downregulation of 29, 27, and 6 miRNAs in patients with mild, moderate, and severe TBI, respectively, compared with healthy controls. Thirteen miRNAs (seven upregulated and six downregulated) were found to be present in all TBI groups. Seven upregulated miRNAs were selected for validation in an enlarged cohort of samples and showed good diagnostic accuracy. The expression levels of miR-3195 and miR-328-5p were higher in the severe TBI group than in the mild and moderate TBI groups. In summary, our study demonstrates different expression profiles in plasma miRNAs among patients with mild to severe TBI. A subset of seven miRNAs can be used for diagnosis of TBI. Moreover, miR-3195 and miR-328-5p may be utilized during diagnosis to distinguish mild and moderate TBI from severe TBI.

A Prospective Analysis of Derangement of Coagulation Profile in Adult and Pediatric Age Group in Moderate-to-Severe Traumatic Brain Injury

Abstract Background and Aim of Study Coagulopathy is a common occurrence following traumatic brain injury (TBI). Various studies have reported the incidence and risk factors of coagulopathy and their correlation with poor outcome in adult as well as pediatric age group. In our study, we aim to analyze trauma-induced coagulopathy in adult and pediatric patients. Methods Adult (&gt; 18 years) and pediatric (&lt; 18 years) patients of TBI admitted in the intensive care unit of a trauma center of a tertiary care center had been studied from August 2015 to March 2018. Patients were further subdivided into moderate and severe TBI based on Glasgow Coma Scale (GCS) of 9 to 12 and &lt; 9, respectively. Coagulation profile (prothrombin time [PT], activated partial thromboplastin time [APTT], thrombin time, fibrinogen, and D-dimer) and arterial blood gas (ABG) analysis were done on day of admission and on days 3 and 7. Coagulation profiles were analyzed in both the age groups, and risk factors were studied and correlated with the mortality and morbidity based on the Glasgow outcome score. Results Two hundred patients including 143 adults and 57 pediatric patients were included. Mean age among the adult and pediatric population was 31.51 ± 16.83 and 11.5 ± 5.90 years, respectively. In adults, 96 (83.62%) out of 116 in severe TBI group and 20 (74.07%) out of 27 in moderate TBI group developed coagulopathy, and in pediatric age group, 14 (70%) out of 20 in moderate TBI and 30 (81.08%) out of 37 in severe TBI developed coagulopathy. Midline shift was significantly associated with coagulopathy in both the age groups (p value &lt; 0.039). Mortality was not significantly different in patients with coagulopathy between the age groups, but improved status as per the Glasgow outcome score was more in pediatric age group. Conclusion The development of coagulopathy is a frequent complication in patients with moderate to severe TBI in both age groups. Even though it is not closely associated with death in this study, it may be regarded as a marker of injury severity.