sTBI Patients Research Articles

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR-219a-5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1.

Circulating microRNAs (miRNAs) have emerged as diagnostic and prognostic biomarkers for traumatic brain injury (TBI). However, a comprehensive characterization of the serum miRNA profile in patients with TBI and the roles of these potential markers in neuronal regulation have rarely been reported. In this study, the levels of 754 serum miRNAs were initially determined in two pooled samples of 15 severe traumatic brain injury (sTBI) patients and 15 healthy controls using a TaqMan Low Density Array. The markedly upregulated miRNAs in sTBI patients were subsequently validated individually by quantitative reverse-transcription PCR (RT-qPCR) in another larger cohort consisting of 81 sTBI patients, 81 mild traumatic brain injury (mTBI) patients and 82 age/sex-matched healthy controls. Seven miRNAs, including miR-103a-3p, miR-219a-5p, miR-302d-3p, miR-422a, miR-518f-3p, miR-520d-3p and miR-627, were significantly upregulated in both sTBI and mTBI patients compared with their expression in controls. Among these miRNAs, miR-219a-5p not only discriminated sTBI and mTBI patients from controls but also discriminated between sTBI and mTBI patients. We further show here that in the neuronal cell injury model, upregulated miR-219a-5p inhibits the expression of CCNA2 and CACUL1 and further regulates akt/Foxo3a and p53/Bcl-2 signaling pathways, causing a notable change in the expression of cleaved caspase-3, thereby inducing neuronal apoptosis. These results indicate that these seven selected miRNAs could serve as novel biomarkers for TBI. In particular, miR-219a-5p is a potentially valuable indicator of the diagnosis, prognosis of TBI and appears to regulate neuronal apoptosis and death.

Modeling the return to consciousness after severe traumatic brain injury at a large academic level 1 trauma center.

Severe traumatic brain injury (sTBI) carries significant morbidity and mortality. It remains difficult to counsel families on functional prognosis and plan research initiatives aimed at treating traumatic coma. In order to better address these problems, the authors set out to develop statistical models using retrospective data to identify admission characteristics that correlate with time until the return of consciousness, defined as the time to follow commands (TFC). These results were then used to create a TFC score, allowing for rapid identification of patients with predicted prolonged TFC. Data were reviewed and collected from medical records of sTBI patients with Glasgow Coma Scale (GCS) motor subscores ≤ 5 who were admitted to Stony Brook University Hospital from January 2011 to July 2018. Data were used to calculate descriptive statistics and build binary logistic regression models to identify admission characteristics that correlated with in-hospital mortality and in-hospital command-following. A Cox proportional hazards model was used to identify admission characteristics that correlated with the length of TFC. A TFC score was developed using the significant variables identified in the Cox regression model. There were 402 adult patients who met the inclusion criteria for this study. The average age was 50.5 years, and 122 (30.3%) patients were women. In-hospital mortality was associated with older age, higher Injury Severity Score (ISS), higher Rotterdam score (head CT grading system), and the presence of bilateral fixed and dilated pupils (p < 0.01). In-hospital command-following was anticorrelated with age, ISS, Rotterdam score, and the presence of a single fixed and dilated pupil (p < 0.05). TFC was anticorrelated with age, ISS, Rotterdam score, and the presence of a single fixed and dilated pupil. Additionally, patients who sustained injuries from falls from standing height had a shorter average TFC. The 3 significant variables from the Cox regression model that explained the most variance were used to create a 4-point TFC score. The most significant of these characteristics were Rotterdam head CT scores, high impact traumas, and the presence of a single fixed and dilated pupil. Importantly, the presence of a single fixed and dilated pupil was correlated with longer TFC but no increase in likelihood of in-hospital mortality. The creation of the 4-point TFC score will allow clinicians to quickly identify patients with predicted prolonged TFC and estimate the likelihood of command-following at different times after injury. Discussions with family members should take into account the likelihood that patients will return to consciousness and survive after TBI.

Effect of step decompression combined with decompressive craniectomy on prognosis of patients with severe traumatic brain injury

Objective To investigate the efficacy of step decompression combined with decompressive craniectomy in treating severe traumatic brain injury (sTBI). Methods A retrospective case series study was conducted to analyze the clinical data of 192 patients with sTBI admitted to Changsha Traditional Chinese Medicine Hospital from January 2016 to April 2018. There were 149 males and 43 females, aged 11-79 years, with an average of 50.1 years. The Glasgow coma score (GCS) was 7-8 points in 57 patients, 5-6 points in 45 patients, and 3-4 points in 90 patients. There were 55 patients with unilateral pupil dilation and 88 patients with bilateral pupil dilation. All patients were treated with step decompression and decompressive craniectomy. GCS and pupil sizes before and after operation, intraoperative diffuse brain swelling and acute encephalocele, intraoperative and postoperative delayed bleeding, secondary surgery, mortality during hospitalization, and Glasgow outcome score (GOS) 6 months after injury were recorded. Results At 24 hours after operation, the GCS was 7-8 points in 87 patients, 5-6 points in 51 patients, and 3-4 points in 54 patients. The consciousness was significantly improved ( P<0.01), and the pupil was reduced in 56 patients (P<0.01). There were four patients with diffuse brain swelling during operation (2.1%), 11 patients with acute encephalocele(5.7%), seven patients with delayed bleeding (3.6%), 27 patients with postoperative delayed bleeding (14.1%), 17 patients receiving secondary surgery (9.7%). Thirty-eight patients died during hospitalization (19.8%). The results of GOS follow-up of 6 months were as follows: there were 50 patients with good recovery (30.0%), 36 patients with moderate disability (24.5%), 15 patients with severe disability (10.2%), 46 patients with persist vegetative states (31.3%), and seven patients died (4.8%). Conclusion For sTBI patients, step decompression combined with decompressive craniectomy can significantly reduce intraoperative diffuse brain swelling and encephalocele, intraoperative, and postoperative delayed bleeding, thus improving the prognosis. Key words: Brain injuries; Brain edema; Decompressive craniectomy

Dynamic changes in peripheral blood-targeted miRNA expression profiles in patients with severe traumatic brain injury at high altitude

BackgroundThe aim of this work is to detect and compare the peripheral blood miRNA expression profiles in patients with severe traumatic brain injury (sTBI) 2, 12, 24, 48, and 72 h after injury at high altitude and to predict the target genes of differential expressed miRNAs.MethodsTwenty sTBI patients from high-altitude areas were randomly selected according to the inclusion and exclusion criteria and were divided into five groups: the 2-h group, 12-h group, 24-h group, 48-h group, and 72-h group. Peripheral blood miRNA expression profiles were detected using real-time quantitative PCR (qRT-PCR).ResultsThe expression levels of miR-18a, miR-203, miR-146a, miR-149, miR-23b, and miR-let-7b in peripheral blood showed significant differences between the 2-h group and the 12-h group. The expression levels of miR-203, miR-146a, miR-149, miR-23b, and miR-let-7f in peripheral blood were up-regulated in the 24-h group. In the 48-h group, the expression levels of miR-181d, miR-29a, and miR-18b were upregulated. In the 72-h group, the expression levels of miR-203, miR-146a, miR-149, miR-23b, and miR-let-7f changed. The main target genes of the differentiation expressed miRNAs were genes that regulate inflammatory responses, apoptosis, and DNA damage/repair.ConclusionsmiRNAs may be involved in the pathogenesis of sTBI by dynamically regulating the target genes that regulate inflammatory responses, apoptosis, and DNA damage/repair pathways.

Serum soluble TWEAK levels in severe traumatic brain injury and its prognostic significance

BackgroundSevere traumatic brain injury (sTBI) is characterized by a high mortality. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in inflammation. We determined serum soluble TWEAK (sTWEAK) levels with respect to its prognostic ability. MethodsThis was a single-center prospective, observational study that was performed from December 2014 to December 2017. A total of 114 sTBI patients who met the inclusion criteria and 114 randomly selected healthy controls were included in the study. Serum sTWEAK levels were gauged. Patients were followed-up until death or completion of 6 months. Poor outcome was referred to as Glasgow outcome scale score of 1–3. ResultsIn comparison with controls, patients displayed predominantly higher serum sTWEAK levels. Serum sTWEAK levels were strongly correlated with Glasgow coma scale scores and serum C-reactive protein levels. 32 patients (28.1%) died and 60 patients (52.6%) suffered from a poor outcome. Receiver operating characteristic curve analysis clearly showed that serum sTWEAK levels had substantially high predictive performance for 6-month mortality and poor outcome. Serum sTWEAK emerged as an independent predictor for 6-month mortality, overall survival and poor outcome. ConclusionsRaised serum sTWEAK levels are closely related to increasing inflammatory response, elevated trauma severity and worse clinical outcome after sTBI.

Efficacy of decompressive craniectomy combined with ipsilateral external ventricular drainage for severe traumatic brain injury

Objective To investigate the efficacy of decompressive craniectomy (DC) combined with ipsilateral external ventricular drainage (iEVD) for severe traumatic brain injury (sTBI). Methods A retrospective case control study was performed on the clinical data of 54 sTBI patients admitted to the First People's Hospital of Taizhou from January 2015 to March 2018. There were 38 males and 18 females, aged 18-72 years [ (51.8±15.4)years]. The Glasgow Coma Scale (GCS) of patients ranged from 3 to 8 points. Among 54 patients, 27 received DC treatment, including 18 males and nine females aged (50.1±2.9)years (DC group); 27 patients received DC combined with iEVD, including 18 males and nine females aged (53.4±3.1)years (DC-iEVD group). Intracranial pressure after surgery and complications (hydrocephalus and subdural hygroma) 2 weeks after surgery, andModified Rankin Scale (mRS) 3 months after surgery were compared between the two groups. Results All patients were followed up for 2.5-4 months [(3.0±0.8)months]. No significant difference was found in intracranial pressure at postoperative 12 hours and 24 hours between the two groups (P>0.05). However, the intracranial pressure of DC-iEVD group were significantly lower than those of DC group at 36, 48, 60 and 72 hours after operation (P 0.05). The subdural effusion incidence 2 weeks after surgery of DC-iEVD group was 19% (5/27), while that of DC group was 44% (12/27)(P 0.05). Conclusion For sTBI, combined use of DC and iEVD can better control intracranial pressure and reduce the occurrence of subdural effusion. Key words: Brain injuries; Decompressive craniectomy; Drainage; Subdural effusion; Hydrocephalus

Intracranial Pressure Monitoring in Experimental Traumatic Brain Injury: Implications for Clinical Management.

Traumatic brain injury (TBI) is often associated with long-term disability and chronic neurological sequelae. One common contributor to unfavorable outcomes is secondary brain injury, which is potentially treatable and preventable through appropriate management of patients in the neurosurgical intensive care unit. Intracranial pressure (ICP) is currently the predominant neurological-specific physiological parameter used to direct the care of severe TBI (sTBI) patients. However, recent clinical evidence has called into question the association of ICP monitoring with improved clinical outcome. The detailed cellular and molecular derangements associated with intracranial hypertension (IC-HTN) and their relationship to injury phenotype and neurological outcomes are not completely understood. Various animal models of TBI have been developed, but the clinical applicability of ICP monitoring in the pre-clinical setting has not been well-characterized. Linking basic mechanistic studies in translational TBI models with investigation of ICP monitoring that more faithfully replicates the clinical setting will provide clinical investigators with a more informed understanding of the pathophysiology of IC-HTN, thus facilitating development of improved therapies for sTBI patients.

Risk factors of post traumatic cerebral infarction after craniotomy for severe traumatic brain injury

Objective To investigate the risk factors associated with post traumatic cerebral infarction (PTCI) after craniotomy hematoma evacuation for severe traumatic brain injury (sTBI) so as to provide clinical reference for the early prevention of postoperative PTCI. Methods A retrospective case control study was conducted to analyze the clinical data of 558 sTBI patients who received craniotomy hematoma evacuation admitted to Changsha Hospital of Traditional Chinese Medicine from October 2006 to June 2016. There were 340 males and 218 females, aged 15-71 years, with an average of 47.8 years. Among them, 75 patients were at the age of less than 30 years, 315 were at 30-50 years, and 168 were above 50 years. According to the Glasgow coma score (GCS), there were 127 patients with 3-4 points, 124 with 5-6 points, and 307 with 7-8 points. The patients were divided into PTCI group (51 patients) and non-PTCI group (507 patients). The related indicators of the two groups of patients after admission were collected, including gender, age, injury cause, GCS, skull base fracture, traumatic subarachnoid hemorrhage (tSAH), cerebral hernia, hypotension, the time from injury to craniotomy, and whether decompressive craniectomy was performed. Univariate analysis was first performed for these factors, followed by multivariate logistic regression analysis. Results There were no significant differences in gender, age, injury cause, skull base fracture, and decompressive craniectomy between PTCI group and control group (P>0.05). In the PTCI group, there were 29 patients with GCS of 3-4 points, 17 with 5-6 points, and five with 7-8 points; there were 48 patients with tSAH, 37 patients with cerebral hernia, and 18 patients with hypotension. In terms of the time from injury to craniotomy, it took 12 hours in four. In the non-PTCI group, there were 98 patients with GCS of 3-4 points, 107 with 5-6 points, and 302 with 7-8 points. There were 34 patients with tSAH, 117 with cerebral hernia, and 35 with hypotension. In terms of the time from injury to craniotomy, it took 12 hours in 15. The differences between the two groups were statistically significant (P<0.05). Multivariate logistic regression analysis indicated that GCS of 3-6 points, tSAH, cerebral hernia, time from injury to craniotomy, and hypotension were significantly associated with PTCI after operation for sTBI (P<0.01). Conclusions GCS of 3-6 points, tSAH, cerebral hernia, duration from injury to craniotomy, and hypotension time >3 hours are the high risk factors of PTCI in sTBI patients after craniotomy. For patients with these high risk factors, craniotomy should be performed in time, and the perioperative blood pressure and intracranial pressure stability should be maintained so as to relieve vasospasm. Key words: Brain injuries; Decompressive craniectomy; Cerebral infarction; Hypotension

A prospective study on serum secreted protein acidic and rich in cysteine-like 1 as a prognostic marker for severe traumatic brain injury

BackgroundSecreted protein acidic and rich in cysteine-like 1 (SPARCL1) regulates synaptic stability with upregulation throughout axonal regeneration. Our study aims to determine the correlation of serum SPARCL1 concentrations with the severity and in-hospital mortality of severe traumatic brain injury (sTBI). MethodsA total of 102 consecutively recruited patients admitted for sTBI and 102 randomly selected healthy controls were included in this observational prospective study. Serum SPARCL1 concentrations were measured and correlated with Glasgow coma scale (GCS) scores and in-hospital mortality using multivariate analysis. ResultsCompared with controls (median, 0.22 ng/ml; interquartile range, 0.19–0.41 ng/ml), patients had significantly higher SPARCL1 concentrations (median, 3.29 ng/ml; interquartile range, 1.88–4.37; P < 0.001). There was an independently correlation between SPARCL1 concentrations and GCS scores (t = −7.011, P < 0.001). We found a high area under receiver operating curve (AUC) of serum SPARCL1 concentrations to predict in-hospital mortality (AUC, 0.822; 95% confidence interval, 0.734–0.891). In the multiple logistic regression analysis, serum SPARCL1 concentrations >3.29 ng/ml was independently associated with in-hospital mortality (odds ratio = 10.052, 95% confidence interval = 1.918–52.686, P = 0.006). ConclusionsThe novel findings of our study are that sTBI patients had an increase of serum SPARCL1 concentrations, and that there is an association between high serum SPARCL1 concentrations and sTBI mortality or trauma severity.

Glutamine enriched enteral nutrition for severe traumatic brain injury: a meta-analysis

Objective To evaluate the efficacy of Glutamine enriched enteral nutrition in the treatment of severe traumatic brain injury (sTBI). Methods PubMed, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, and Wanfang databases were searched to identify randomized controlled trials (RCT) on the application of Glutamine enriched enteral nutrition for severe TBI patients from database establishment time to May 2017. Two investigators screened the literature strictly according to the inclusion and exclusion criteria, extracted the data, evaluated the literature quality, and performed meta-analysis using RevMan 5.3 software. The effects of glutamine enhanced enteral nutrition on albumin content, immunoglobulin G (IgG) level, the incidence of diarrhea, incidence of pulmonary infection, blood glucose, Glasgow Coma Scale (GCS), length of hospital stay, and mortality were evaluated. Results A total of 17 articles involving 939 sTBI patients were included, with 512 patients in Glutamine group and 427 controls in control group. There were no significant differences in the length of hospital stay and mortality between the two groups (P>0.05). Significant differences were found in albumin content (95%CI 0.19- 2.54, Z=2.27, P<0.05), level of IgG (95%CI 0.67-1.80, Z=4.25, P<0.01), incidence of diarrhea (95%CI 0.23-0.57, Z=4.41, P<0.01), incidence of lung infections (95%CI 0.14-0.56, Z=3.62, P<0.01), blood sugar (95%CI -2.53--0.52, Z=2.98, P<0.01), and the GCS score (95%CI 0.50-2.68, Z=1.49, P<0.01) between the two groups. Conclusion Compared with routine enteral nutrition, Glutamine enriched enteral nutrition can increase albumin content and IgG level, reduce the incidence of diarrhea and lung infections, reduce blood sugar, and improve the GCS score, but it cannot shorten hospital stay or reduce mortality. Key words: Glutamine; Enteral nutrition; Brain injuries; Meta-analysis

Safety and Reliability of Bedside, Single Burr Hole Technique for Intracranial Multimodality Monitoring in Severe Traumatic Brain Injury.

We aimed to provide a systematic description of our 2-year experience using a standardized bedside, single burr hole approach to intracranial multimodality monitoring (MMM) in patients with severe traumatic brain injury (sTBI), focusing on safety and probe reliability. We performed this observational cohort study at a university-affiliated, Level I trauma center with dedicated 20-bed neuroscience intensive care unit. We included 43 consecutive sTBI patients who required MMM to guide clinical care based on institutional protocol and had a four-lumen bolt placed to measure intracranial pressure, brain tissue oxygen, regional cerebral blood flow, brain temperature, and intracranial electroencephalography. sTBI patients were aged 41.6 ± 17.5years (mean ± SD) and 84% were men. MMM devices were placed at a median of 12.5h (interquartile range [IQR] 9.0-21.4h) after injury and in non-dominant frontal lobe in 72.1% of cases. Monitoring was conducted for a median of 97.1h (IQR 46.9-124.6h) per patient. While minor hemorrhage, pneumocephalus, or small bone chips were common, only one (2.4%) patient experienced significant hemorrhage related to device placement. Radiographically, device malpositioning was noted in 13.9% of patients. Inadvertent device discontinuation occurred for at least one device in 58% of patients and was significantly associated with the frequency of travel for procedures or imaging. Devices remained in place for > 80% of the total monitoring period and generated usable data > 50% of that time. A standardized, bedside single burr hole approach to MMM was safe. Despite some probe-specific recording limitations, MMM provided real-time measurements of intracranial pressure, oxygenation, regional cerebral blood flow, brain temperature, and function.

Association between uncooperativeness and the glucose metabolism of patients with chronic behavioral disorders after severe traumatic brain injury: a cross-sectional retrospective study

BakgroundPatients with behavioral disorders following severe traumatic brain injury (sTBI) often have disorders of consciousness that make expressing their emotional distress difficult. However, no standard method for assessing the unsettled and unforeseen responses that are associated with behavioral disorders has yet to be established. Because the thalamus is known to play a role in maintaining consciousness and cognition, we used 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) to examine the association between brain glucose metabolism in the thalamus and behavioral disorders.MethodsWe retrospectively analyzed 70 consecutive patients with sTBI who had been involved in motor vehicle accidents. To assess behavioral disorders, we evaluated 18 symptoms using the Brief Psychiatric Rating Scale (BPRS): Emotional Withdrawal, Conceptual Disorganization, Tension, Mannerisms and Posturing, Motor Retardation, Uncooperativeness, Blunted Affect, Excitement, Somatic Concern, Anxiety, Feeling of Guilt, Grandiosity, Depressive Mood, Hostility, Suspiciousness, Hallucinatory Behavior, Unusual Thought Content, and Disorientation. First, we identified clinical characteristics of sTBI patients with behavioral disorders. Next, we retrospectively analyzed 18F-FDG-PET/CT data to assess how thalamic activity was related with abnormal behaviors.ResultsTwenty-six patients possessed the minimum communicatory ability required for psychiatric interview. Among them, 15 patients (57.7%) were diagnosed with behavioral disorder, 14 of whom had reached a stable psychiatric state after about 426.6 days of treatment. Excitement (13 patients) and uncooperativeness (10 patients) were the most frequently observed symptoms. Available 18F-FDG-PET/CT data indicated that thalamic glucose metabolism was imbalanced and lateralized (p = 0.04) in 6 patients who exhibited uncooperativeness.ConclusionsBehavioral symptoms of excitement and uncooperativeness were common in patients with sTBI, although most symptoms improved as the chronic stage continued. Our data support the idea that imbalanced laterality of glucose metabolism in the thalamus might be related to behavioral disorders characterized by uncooperativeness.Trial registrationUMIN 000029531. Registered 27 March 2017, retrospectively registered.

Serum S100A12 as a prognostic biomarker of severe traumatic brain injury

BackgroundS100A12 is related to acute brain injury and inflammation. We investigated the clinical prognostic value of serum S100A12 in patients with severe traumatic brain injury (sTBI). MethodsSerum S100A12, S100B, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) concentrations were measured in 102 healthy controls and 102 sTBI patients. We recorded 30-day mortality and in-hospital major adverse events (IMAEs) including acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction. Trauma severity was assessed by admission Glasgow Coma Scale scores. ResultsWhen compared to the controls, serum S100A12, S100B, CRP, IL-6 and TNF-α concentrations were significantly increased in the patients. Serum concentrations of S100A12 significantly correlated with admission Glasgow Coma Scale scores and serum concentrations of S100B, CRP, IL-6 and TNF-α. Patients with any IMAEs or non-survivors within 30 days had obviously higher serum concentrations of S100A12, S100B, CRP, IL-6 and TNF-α than other remaining ones. Serum S100A2 was independently associated with IMAEs and 30-day mortality and overall survival. Receiver operating characteristic curve analysis showed that S100A12 concentrations had significant discriminatory ability for patients at risk of any IMAEs and death within 30 days. ConclusionS100A12 might be associated with brain inflammation and evaluation of serum concentrations of S100A12 could be helpful in the early prognostic prediction in sTBI patients.

Acute Traumatic Endotheliopathy in Isolated Severe Brain Injury and Its Impact on Clinical Outcome.

Study design: Prospective observational cohort. Objective: To investigate the difference in plasma levels of syndecan-1 (due to glycocalyx degradation) and soluble thrombomodulin (due to endothelial damage) in isolated severe traumatic brain injury (TBI) patients with/without early coagulopathy. A secondary objective was to compare the effects of the degree of TBI endotheliopathy on hospital mortality among patients with TBI-associated coagulopathy (TBI-AC). Methods: Data was prospectively collected on isolated severe TBI (sTBI) patients with Glasgow Coma Scale (GCS) ≤8 less than 12 h after injury admitted to a level I trauma centre. Isolated sTBI patients with samples withdrawn prior to blood transfusion were stratified by conventional coagulation tests as coagulopathic (prothrombin time (PT) ≥ 16.7 s, international normalized ratio (INR) ≥ 1.27, and activated partial thromboplastin time (aPTT) ≥ 28.8 s) and non-coagulopathic. Twenty healthy controls were also included. Plasma levels of thrombomodulin and syndecan-1 were estimated by ELISA. With receiver operating characteristic curve (ROC) analysis, we defined endotheliopathy as a syndecan-1 cut-off level that maximized the sum of sensitivity and specificity for predicting TBI-AC. Results: Inclusion criteria were met in 120 cases, with subjects aged 35.5 ± 12.6 years (88.3% males). TBI-AC was identified in 50 (41.6%) patients, independent of age, gender, and GCS, but there was an association with acidosis (60%; p = 0.01). Following isolated sTBI, we found insignificant changes in soluble thrombomodulin (sTM) levels between patients with isolated TBI and controls, and sTM levels were lower in coagulopathic compared to non-coagulopathic patients. Elevations in plasma syndecan-1 (ng/mL) levels were seen compared to control (31.1(21.5–30.6) vs. 24.8(18.5–30.6); p = 0.08). Syndecan-1(ng/mL) levels were significantly elevated in coagulopathic compared to non-coagulopathic patients (33.7(21.6–109.5) vs. 29.9(19.239.5); p = 0.03). Using ROC analysis (area under the curve = 0.61; 95% Confidence Interval (CI) 0.50 to 0.72), we established a plasma syndecan-1 level cutoff of ≥30.5 ng/mL (sensitivity % = 55.3, specificity % = 52.3), with a significant association with TBI-associated coagulopathy. Conclusion: Subsequent to brain injury, elevated syndecan-1 shedding and endotheliopathy may be associated with early coagulation abnormalities. A syndecan-1 level ≥30.5 ng/mL identified patients with TBI-AC, and may be of importance in guiding management and clinical decision-making.

The cost of a pediatric neurocritical care program for traumatic brain injury: a retrospective cohort study

BackgroundInpatient care for children with severe traumatic brain injury (sTBI) is expensive, with inpatient charges averaging over $70,000 per case (Hospital Inpatient, Children Only, National Statistics. Diagnoses– clinical classification software (CCS) principal diagnosis category 85 coma, stupor, and brain damage, and 233 intracranial injury. Diagnoses by Aggregate charges [https://hcupnet.ahrq.gov/#setup]). This ranks sTBI in the top quartile of pediatric conditions with the greatest inpatient costs (Hospital Inpatient, Children Only, National Statistics. Diagnoses– clinical classification software (CCS) principal diagnosis category 85 coma, stupor, and brain damage, and 233 intracranial injury. Diagnoses by Aggregate charges [https://hcupnet.ahrq.gov/#setup]). The Brain Trauma Foundation developed sTBI intensive care guidelines in 2003, with revisions in 2012 (Kochanek, Carney, et. al. PCCM 3:S1-S2, 2012). These guidelines have been widely disseminated, and are associated with improved health outcomes (Pineda, Leonard. et. al. LN 12:45-52, 2013), yet research on the cost of associated hospital care is limited. The objective of this study was to assess the costs of providing hospital care to sTBI patients through a guideline-based Pediatric Neurocritical Care Program (PNCP) implemented at St. Louis Children’s Hospital, a pediatric academic medical center in the Midwest United States.MethodsThis is a retrospective cohort study. We used multi-level regression to estimate pre−/post−implementation effects of the PNCP program on inflation adjusted total cost of in-hospital sTBI care. The study population included 58 pediatric patient discharges in the pre-PNCP implementation group (July 15, 1999 - September 17, 2005), and 59 post-implementation patient discharges (September 18, 2005 - January 15, 2012).ResultsImplementation of the PNCP was associated with a non-significant difference in the cost of care between the pre- and post-implementation periods (eβ = 1.028, p = 0.687).ConclusionsImplementation of the PNCP to support delivery of guideline-based care for children with sTBI did not change the total per-patient cost of in-hospital care. A key strength of this study was its use of hospital cost data rather than charges. Future research should consider the longitudinal post-hospitalization costs of this approach to sTBI care.

Decision making in very severe traumatic brain injury (Glasgow Coma Scale 3-5): a literature review of acute neurosurgical management.

Patients presenting with an early Glasgow Coma Scale (GCS) Score of 3-5 after blunt or penetrating skull-brain assaults are categorized as having sustained a very severe traumatic brain injury (vs-TBI). This category is often overlooked in literature. Impact on patients and families lives however is huge and the question "whether to surgically treat or not" frequently poses a dilemma to treating physicians. Little is known about mortality and outcome, compared to what is known for the group of severe TBI patients (s-TBI) (GCS 3-8). The main goal of this review was creating more awareness for the neurosurgical treatment of this patient group. A literature search (2000-2017) was conducted discussing "severe TBI (GCS 3-8)", "(neuro)surgical management" and "outcome". Ultimately 45 out of 2568 articles were included for further analysis. Mortality rates and unfavorable outcome are high for s-TBI patients and as expected higher for vs-TBI patients. Mortality rates reach up to 100% for specific subgroups with GCS=3 and bilaterally fixed dilated pupils. Functional outcome was generally poor, but sometimes, although seldom, favorable in specific groups of vs-TBI patients after neurosurgical intervention. Factors like initial GCS, pupillary abnormalities and age seem to be associated with worse outcome. Overall this literature review showed high rates of unfavorable outcome and mortality for vs-TBI patients. However, some studies, reporting relatively low mortality rates, reported "good" outcome for specific groups of vs-TBI patients. It is concluded that clinical decision making, in particular those on treatment limitations, should never be taken based on the GCS alone.

ICP management in patients suffering from traumatic brain injury: a systematic review of randomized controlled trials.

Severe traumatic brain injury (sTBI) is a major cause of morbidity and mortality. Intracranial pressure (ICP) monitoring and management form the cornerstone of treatment paradigms for sTBI in developed countries. We examine the available randomized controlled trial (RCT) data on the impact of ICP management on clinical outcomes after sTBI. A systematic review of the literature on ICP management following sTBI was performed to identify pertinent RCT articles. We identified six RCT articles that examined whether ICP monitoring, decompressive craniectomy, or barbiturate coma improved clinical outcomes after sTBI. These studies support (1) the utility of ICP monitoring in the management of sTBI patients and (2) craniectomy and barbiturate coma as effective methods for the management of intracranial hypertension secondary to sTBI. However, despite adequate ICP control in sTBI patients, a significant proportion of surviving patients remain severely disabled. If one sets the bar at the level of functional independence, then the RCT data raises questions pertaining to the utility of decompressive craniectomy and barbiturate coma in the setting of sTBI.

Incidence of critical illness-related corticosteroid insufficiency after severe traumatic brain injury and its correlations with prognosis

Objective To observe the incidence of critical illness-related corticosteroid insufficiency (CIRCI) after severe traumatic brain injury (sTBI) and investigate the relationship between CIRCI and prognosis. Methods This prospective cohort study enrolled 89 sTBI patients (68 males and 21 females; at age range of 15-80 years) hospitalized within 24 hours after sTBI from June 2014 to December 2015. The Glasgow coma scale (GCS) was ≤8 points. The causes of injury included extensive contusion of brain (44 cases), subdural hematoma (21 cases), epidural hematoma (11 cases), primary brain stem injury (8 cases) and diffuse axonal injury (5 cases). Adrenocorticotropic hormone (ACTH) stimulation tests were done within 36 hours after sTBI to identify CIRCI patients. The patients were divided into CIRCI group (50 cases) and non-CIRCI group (39 cases). Moreover, the patients were categorized into survival group (62 cases) and death group (27 cases) based on survival status. The GCS score, mechanical ventilation time, cerebral hernia, survival time and mortality within 28 days were observed in two groups. Results The incidence of CIRCI in sTBI patients was as high as 56% (50/89). Compared with the non-CIRCI group, the CIRCI group had lower GCS [(5.3±1.7)points vs. (6.1±1.4)points, P<0.05], and sTBI patients with CIRCI were mechanically ventilated for a longer period of time [(9.9±2.8)days vs. (7.5±1.6)days, P<0.05]. In comparison with non-CIRCI patients, the incidence of brain herniation in sTBI patients with CIRCI was higher (58% vs. 21%, P<0.01). The total fatality rate within 28 days was 30% (27/89). The survival time of CIRCI group was significantly shorter than that of non-CIRCI group (P<0.05). The fatality rate in the CIRCI group was significantly higher than that of the non-CIRCI group [40% (20/50) vs. 18% (7/39), P<0.05]. The incidence of CIRCI in death group was significantly higher than that of the survival group [74% (20/27) vs. 48% (30/62), P<0.05]. Conclusions The incidence of CIRCI in STBI patients is high. The sTBI patients with CIRCI has significantly higher incidence of brain hernia, longer mechanical ventilation time, higher 28-day mortality and shorter survival time compared with non-CIRCI patients. Key words: Brain injuries; Adrenocorticotropic hormone; Prognosis

Clinical efficacy of acute intraoperative encephalocele prevention strategy for severe traumatic brain injury

Objective: To explore the clinical efficacy of prevention strategy for acute intraoperative encephalocele of patients with severe traumatic brain injury (sTBI). Methods: A total of 173 patients with sTBI, who treated in Emergency Neurosurgery Department of Shandong University Qilu Hospital from January, 2011 to September, 2015 were collected and divided into research group and control group, according to their therapeutic strategy.The clinical data during hospitalization and prognosis 1 year after injury was analyzed retrospectively to clarify the effect of acute encephalocele prevention strategy. Results: There were no statistically significant differences in sex, age, preoperative Glasgow coma scale score and imaging type of lesion between patients from the two groups.The highest intraoperative intracranial pressure in the research group and control group were (35.71±4.13) mmHg and(34.85±3.81) mmHg, respectively.The acute encephalocele incidence of the research group (7 cases, 6.5%) was significantly lower than that of the control group (13 cases, 19.7%) (P<0.01). Subgroup analysis showed that the incidence of acute encephalocele in patients with only unilateral lesions was low (1.3%), while higher (19.4%) in patients with both unilateral lesions and other secondary lesions or diffuse brain swelling.The prognosis of the patients was evaluated by Glasgow Outcome Scale according to the follow-up 1 year after injury, and it was suggested that the percentage of patients with good outcome in the research group (62 cases, 57.9%) was remarkably higher than that in the control group (26 cases, 39.4%) (P=0.018). Conclusions: For sTBI patients with high risk of acute encephalocele, prevention strategy was found to be able to retard the progression of delayed hematoma and diffuse brain swelling, prevent the acute encephalocele during operation, and then significantly improve the prognosis.

The clinical application of transcranial doppler ultrasonography in severe traumatic brain injury post decompressive craniectomy

Objective To explore the clinical application of transcranial doppler ultrasonography (TCD) in severe traumatic brain injury (sTBI)post decompressive craniectomy. Methods A retrospective study was conducted on 58 patients with sTBI who were admitted to Neurosurgical Intensive Care Unit of Tangdu Hospital, the Fourth Military Medical University From January 2015 to October 2016. All patients underwent hematoma evacuation, decompressive craniectomy and placement of intracerebral pressure (ICP) probe. The parameters of cerebral blood flow including mean velocity (Vmean), end of diastolic (Vedv) and pulsatility index (PI) in sTBI patients were measured by TCD post operation to assess the cerebral blood supply. Results The trend of Vmean and Vedv manifested U-shaped mode during the next 7 days, reaching the lowest levels [(72.5±22.6) cm/s and (43.6±19.8) cm/s, respectively] on day 3. There was significant difference in the value of Vmean between day 3 and day 1, 2, 5, 6, 7 (all P<0.05). There was significant difference in the value of Vedv between day 3 and day 1, 2, 6, 7 (all P<0.05). The trend of pulsatility index (PI) and intracranial pressure (ICP) showed parabolic shape during the next 7 days, reaching the highest level [(1.5±0.7) and (17.2±4.5)mmHg, respectively] on day 4. Significant difference was observed in ICP between day 4 and day 1, 2, 3, 6, 7 (P<0.05). The incidence of cerebral hyperemia showed the trend of declining during the next 7 days. There was significant difference in cerebral hyperemia between day 1 and day 5, 6, 7 (all P<0.05). The incidence of cerebral ischemia was up to 36.2% (12/58) on day 4, and it was significantly higher than that on day 1 (P<0.05). The incidence of cerebral vasospasm showed the rising trend and reached the highest level (15.5%) on day 6, which had significant difference compared with the incidences on day 1, 2 and 3 (all P<0.05). Conclusion TCD, as a noninvasive, portable, easy-to-use monitoring tool, could help effectively evaluate postoperative changes of cerebral hemodynamics in patients with sTBI. Key words: Craniocerebral trauma; Ultrasonography, doppler, transcranial; Decompressive craniectomy