Predictive Models of Long-Term Outcome in Patients with Moderate to Severe Traumatic Brain Injury are Biased Toward Mortality Prediction.

BACKGROUND: The prognostication of long-term functional outcomes remains challenging in patients with traumatic brain injury (TBI). Our aim was to demonstrate that intensive care unit (ICU) variables are not efficient to predict 6-month functional outcome in survivors with moderate to severe TBI (msTBI) but are mostly associated with mortality, which leads to a mortality bias for models predicting a composite outcome of mortality and severe disability. METHODS: We analyzed the data from the multicenter randomized controlled Continuous Hyperosmolar Therapy in Traumatic Brain-Injured Patients trial and developed predictive models using machine learning methods and baseline characteristics and predictors collected during ICU stay. We compared our models' predictions of 6-month binary Glasgow Outcome Scale extended (GOS-E) score in all patients with msTBI (unfavorable GOS-E 1-4 vs. favorable GOS-E 5-8) with mortality (GOS-E 1 vs. GOS-E 2-8) and binary functional outcome in survivors with msTBI (severe disability GOS-E 2-4 vs. moderate to no disability GOS-E 5-8). We investigated the link between ICU variables and long-term functional outcomes in survivors with msTBI using predictive modeling and factor analysis of mixed data and validated our hypotheses on the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. RESULTS: Based on data from 370 patients with msTBI and classically used ICU variables, the prediction of the 6-month outcome in survivors was inefficient (mean area under the receiver operating characteristic 0.52). Using factor analysis of mixed data graph, we demonstrated that high-variance ICU variables were not associated with outcome in survivors with msTBI (p = 0.15 for dimension 1, p = 0.53 for dimension 2) but mostly with mortality (p < 0.001 for dimension 1), leading to a mortality bias for models predicting a composite outcome of mortality and severe disability. We finally identified this mortality bias in the IMPACT model. CONCLUSIONS: We demonstrated using machine learning-based predictive models that classically used ICU variables are strongly associated with mortality but not with 6-month outcome in survivors with msTBI, leading to a mortality bias when predicting a composite outcome of mortality and severe disability.

Caregiver reported long-term outcomes in children with major trauma and traumatic brain injuries: A single-centre retrospective study.

Introduction: We aim to investigate the functional outcomes and long-term health-related quality of life (HRQOL) in children with major trauma associated with traumatic brain injury (TBI). Method: We performed a retrospective review of records among patients >2 and ≤16 years old in a tertiary paediatric hospital between January 2014 and October 2019 with major trauma (Injury Severity Score of ≥16) and TBI of all severities. We recorded each child's Glasgow Outcome Scale-Extended Pediatric Version (GOS-E Peds) at 12 months post-injury and Pediatric Quality of Life Inventory (PedsQL) scores at 6 and 12 months post-injury based on the parent proxy-report scales. Results: We included 53 patients with a median age of 9.0 years old (interquartile range 2.3-15.5). Most injuries were due to falls (30, 56.6%) or road traffic collisions (15, 28.3%); 41 patients (77.3%) required intensive care while 30 patients (56.6%) underwent neurosurgical intervention. Most patients (43, 81.1%) had GOS-E Peds scores of ≤2 at 12 months post-injury. We reported a significant mean difference between the 6- and 12-month parent-reported scores for physical functioning (6.6, 95% confidence interval [CI] 0.3-12.8, P=0.041), psychosocial functioning (4.1, 95% CI 1.0-7.2, P=0.012) and overall scores (5.0, 95% CI 1.4-8.7, P=0.008). Compared with the validated PedsQL scores, our mean scores were higher across all domains at 12 months. Conclusion: With current standard of care, parents of children with major trauma and TBI reported gains in quality of life, physical, psychosocial and overall function between 6 and 12 months post-injury.

Post-traumatic hyperoxia after pediatric TBI.

OBJECTIVE: Hyperoxia has been suggested as a mechanism for secondary injury following adult traumatic brain injury (TBI), but its effects have not been well described in pediatric patients. METHODS: Pediatric (≤18yo) TBI patients were identified in a prospective institutional registry from October 2008 to April 2022. The first, highest, and the Area Under the Curve (AUC) PaO2 in the first 24 hours were collected and calculated for each patient from arterial blood gas reports after admission to the ICU. Neurological outcome after 6 months was measured using dichotomized modified Rankin Scale (mRS) and Glasgow Outcome Scale - Extended (GOS-E). Multivariable logistic regression models were used to determine if the three measurements for hyperoxia predicted an unfavorable outcome after controlling for well-established clinical and imaging predictors of outcome. RESULTS: We identified 98 pediatric patients with severe accidental TBI during the study period. Hyperoxia (PaO2 > 300 mmHg) occurred in 33% of the patients. The presence of elevated PaO2 values, determined by all three evaluations of hyperoxia, was not associated with unfavorable outcome after 6 months. CONCLUSION: Utilizing multiple methods to assess exposure, hyperoxia was present in a substantial number of patients with severe TBI but was not associated with an unfavorable outcome.

A Model Predicting the 6-Month Disability of Patients With Traumatic Brain Injury to Assess the Quality of Care in Intensive Care Units: Results from the CREACTIVE Study.

Assessing quality of care is essential for improving the management of patients experiencing traumatic brain injury (TBI). This study aimed at devising a rigorous framework to evaluate the quality of TBI care provided by intensive care units (ICUs) and applying it to the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) consortium, which involved 83 ICUs from seven countries. The performance of the centers was assessed in terms of patients' outcomes, as measured by the 6-month Glasgow Outcome Scale-Extended (GOS-E). To account for the between-center differences in the characteristics of the admitted patients, we developed a multinomial logistic regression model estimating the probability of a four-level categorization of the GOS-E: good recovery (GR), moderate disability (MD), severe disability (SD), and death or vegetative state (D/VS). A total of 5928 patients admitted to the participating ICUs between March 2014 and March 2019 were analyzed. The model included 11 predictors and demonstrated good discrimination (area under the receiver operating characteristic [ROC] curve in the validation set for GR: 0.836, MD: 0.802, SD: 0.706, D/VS: 0.890) and calibration, both overall (Hosmer-Lemeshow test p value: 0.87) and in several subgroups, defined by prognostically relevant variables. The model was used as a benchmark for assessing quality of care by comparing the observed number of patients experiencing GR, MD, SD, and D/VS to the corresponding numbers expected in each category by the model, computing observed/expected (O/E) ratios. The four center-specific ratios were assembled with polar representations and used to provide a multidimensional assessment of the ICUs, overcoming the loss of information consequent to the traditional dichotomizations of the outcome in TBI research. The proposed framework can help in identifying strengths and weaknesses of current TBI care, triggering the changes that are necessary to improve patient outcomes.

Isotonic balanced fluid versus 0.9% saline in patients with moderate to severe traumatic brain injury: A double-blinded randomised controlled trial.

BACKGROUND AND IMPORTANCE: Traumatic brain injury (TBI) is a global health concern with significant economic impact. Optimal fluid therapy aims to restore intravascular volume, maintain cerebral perfusion pressure and blood flow, thus preventing secondary brain injury. While 0.9% saline (NS) is commonly used, concerns about acid-base and electrolyte imbalance and development of acute kidney injury (AKI) lead to consideration of balanced fluids as an alternative. OBJECTIVES: This study aimed to compare the outcomes of patients with moderate to severe TBI treated with Sterofundin (SF) versus NS. DESIGN, SETTINGS AND PARTICIPANTS: A double-blinded randomised controlled trial of patients aged 18 to 65 years with TBI was conducted at the University Malaya Medical Centre from February 2017 to November 2019. INTERVENTION OR EXPOSURE: Patients were randomly assigned to receive either NS or SF. The study fluids were administered for 72 h as continuous infusions or boluses. Participants, investigators, and staff were blinded to the fluid type. OUTCOMES MEASURE AND ANALYSIS: The primary outcome was in-hospital mortality. Relative risk (RR) with 95% confidence interval (CI) was calculated. MAIN RESULTS: A total of 70 patients were included in the analysis, with 38 in the NS group and 32 in the SF group. The in-hospital mortality rate were 3 (7.9%) in the NS group vs. 4 (12.5%) in the SF group, RR = 1.29 (95% CI, 0.64 to 2.59; p = 0.695). No patients developed AKI and required renal replacement therapy. ICP on day 3 was significantly higher in the SF group (18.60 ± 9.26) compared to 12.77 ± 3.63 in the NS group, (95% CI, -11.46 to 0.20; p = 0.037). There were no significant differences in 3-day biochemical parameters and cerebral perfusion pressure, ventilator-free days, length of ICU stay, or Glasgow Outcome Scale-Extended (GOS-E) score at 6 months. CONCLUSIONS: In patients with moderate to severe TBI, the use of SF was not associated with reduced in-hospital mortality, development of AKI, or improved 6-month GOS-E when compared to NS.

Implementation of Multimodal Stimulation and Physical Therapy in Improving the Level of Consciousness and Recovery in Acute Disseminated Encephalomyelitis.

This case report aims to explore the use of multimodal sensory stimulation and physical therapy in rehabilitating a 30-year-old female patient with severe acute disseminated encephalomyelitis (ADEM). ADEM, characterized by autoimmune demyelination in the central nervous system, presents challenges in clinical management, particularly in cases with severe motor deficits and coordination issues. The patient's progress was measured using the Glasgow Coma Scale (GCS), Extended Glasgow Outcome Scale (GOS-E), and Coma Recovery Scale-Revised (CRS-R). The patient showed significant improvement in consciousness levels, functional status, and cognitive and neurological function. The study concludes that a collaborative approach involving both therapeutic modalities and active family participation contributed positively to the patient's recovery.

Effects of inpatient rehabilitation after acute care on functional and quality-of-life outcomes in children with severe traumatic brain injury.

OBJECTIVE: Few studies have assessed the effectiveness of the rehabilitation process in children surviving severe traumatic brain injury (TBI). We evaluated whether receiving inpatient rehabilitation after acute hospitalization was associated with better functional outcomes compared to receiving only non-inpatient rehabilitation in children with severe TBI and explored an effect modification for Glasgow Coma Scale (GCS) score at hospital discharge. METHODS: We included 254 children who received rehabilitation following severe TBI from a multinational observational study. The Pediatric Glasgow Outcome Scale - Extended (GOS-E Peds), parent/guardian-reported and child-reported Pediatric Quality of Life Inventory (PedsQL) at 12 months post-injury were assessed and described using summary statistics. Unadjusted and propensity score-weighted linear/ordinal logistic regression modeling were also performed. RESULTS: 180 children received inpatient rehabilitation and 74 children received only non-inpatient rehabilitation after acute hospitalization. Among children with a GCS<13 at discharge, those receiving inpatient rehabilitation had a more favorable GOS-E Peds score (OR = 0.12, p = 0.045). However, no such association was observed in children with a higher GCS. We found no differences in PedsQL scores between rehabilitation groups. CONCLUSIONS: Future studies are warranted to confirm the benefits of inpatient rehabilitation for children with more severely impaired consciousness when medically stable.

Hospitals with and without neurosurgery: a comparative study evaluating the outcome of patients with traumatic brain injury.

BACKGROUND: We leveraged the data of the international CREACTIVE consortium to investigate whether the outcome of traumatic brain injury (TBI) patients admitted to intensive care units (ICU) in hospitals without on-site neurosurgical capabilities (no-NSH) would differ had the same patients been admitted to ICUs in hospitals with neurosurgical capabilities (NSH). METHODS: The CREACTIVE observational study enrolled more than 8000 patients from 83 ICUs. Adult TBI patients admitted to no-NSH ICUs within 48 h of trauma were propensity-score matched 1:3 with patients admitted to NSH ICUs. The primary outcome was the 6-month extended Glasgow Outcome Scale (GOS-E), while secondary outcomes were ICU and hospital mortality. RESULTS: A total of 232 patients, less than 5% of the eligible cohort, were admitted to no-NSH ICUs. Each of them was matched to 3 NSH patients, leading to a study sample of 928 TBI patients where the no-NSH and NSH groups were well-balanced with respect to all of the variables included into the propensity score. Patients admitted to no-NSH ICUs experienced significantly higher ICU and in-hospital mortality. Compared to the matched NSH ICU admissions, their 6-month GOS-E scores showed a significantly higher prevalence of upper good recovery for cases with mild TBI and low expected mortality risk at admission, along with a progressively higher incidence of poor outcomes with increased TBI severity and mortality risk. CONCLUSIONS: In our study, centralization of TBI patients significantly impacted short- and long-term outcomes. For TBI patients admitted to no-NSH centers, our results suggest that the least critically ill can effectively be managed in centers without neurosurgical capabilities. Conversely, the most complex patients would benefit from being treated in high-volume, neuro-oriented ICUs.

Outcomes of severe lower limb injury with Mangled Extremity Severity Score ≥ 7.

AIMS: Complex fractures of the femur and tibia with associated severe soft tissue injury are often devastating for the individual. The aim of this study was to describe the two-year patient-reported outcomes of patients in a civilian population who sustained a complex fracture of the femur or tibia with a Mangled Extremity Severity Score (MESS) of ≥ 7, whereby the score ranges from 2 (lowest severity) to 11 (highest severity). METHODS: Patients aged ≥ 16 years with a fractured femur or tibia and a MESS of ≥ 7 were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (January 2007 to December 2018). Cases were grouped into surgical amputation or limb salvage. Descriptive analysis were used to examine return to work rates, three-level EuroQol five-dimension questionnaire (EQ-5D-3L), and Glasgow Outcome Scale-Extended (GOS-E) outcomes at 12 and 24 months post-injury. RESULTS: In all, 111 patients were included: 90 (81%) patients who underwent salvage and 21 (19%) patients with surgical amputation. The mean age of patients was 45.8 years (SD 15.8), 93 (84%) were male, 37 (33%) were involved in motor vehicle collisions, and the mean MESS score was 8.2 (SD 1.4). Two-year outcomes in the cohort were poor: six (7%) patients achieved a GOS-E good recovery, the mean EQ-5D-3L summary score was 0.52 (SD 0.27), and 17 (20%) patients had returned to work. CONCLUSION: A small proportion of patients with severe lower limb injury (MESS ≥ 7) achieved a good level of function 24 months post-injury. Further follow-up is needed to better understand the long-term trajectory of these patients, including delayed amputation, hospital readmissions, and healthcare utilization. Cite this article: Bone Joint J 2021;103-B(4):769-774.

Global mean diffusivity: A radiomarker discriminating good outcome long term after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a chronic pathology responsible for cognitive disorders impacting outcome. Global clinical outcome several years after TBI may be associated with anatomical sequelae. Anatomical lesions are not well described because characterizing diffuse axonal injury and brain atrophy require using specific MRI sequences with quantitative measures. The best radiologic parameter to describe the lesions long term after TBI is not known. OBJECTIVE: We aimed to first, assess the global volumetric and diffusion parameters related to long-term outcome after TBI and second, define the most discriminating parameter. METHODS: In this observational study, we included 96 patients with severe TBI and 22 healthy volunteers. The mean delay after TBI was 63.2 months [range 31-119]. The Glasgow Outcome Scale Extended (GOS-E) was used to assess the global long-term clinical outcome. All patients underwent multimodal MRI with measures of brain volume, ventricle volume, global fractional anisotropy (FA) and global mean diffusivity (MD). RESULTS: All 96 participants had significant impairment in global FA, global MD, brain volume and ventricle volume as compared with the 22 controls (P<0.01). Only global MD significantly differed between the "good recovery" group (GOS-E score 7-8) and the other two groups: GOS-E scores 3-4 and 5-6. Brain volume significantly differed between the GOS-E 7-8 and 3-4 groups. Global MD was the most discriminating radiological parameter for the "good recovery" group versus other patients, long term after TBI. FA appeared less relevant at this time. Global atrophy was higher in patients than controls but lacked reliability to discriminate groups of patients. CONCLUSION: Global mean diffusivity seems a more promising radiomarker than global FA for discriminating good outcome long term after TBI. Further work is needed to understand the evolution of these long-term radiological parameters after TBI.

Impact of frailty on surgery for glioblastoma: a critical evaluation of patient outcomes and caregivers' perceptions in a developing country.

OBJECTIVE: The authors aimed to evaluate the impact of age and frailty on the surgical outcomes of patients with glioblastoma (GBM) and to assess caregivers' perceptions regarding postdischarge care and challenges faced in the developing country of India. METHODS: This was a retrospective study of patients with histopathologically proven GBM from 2009 to 2018. Data regarding the clinical and radiological characteristics as well as surgical outcomes were collected from the institute's electronic database. Taking Indian demographics into account, the authors used the cutoff age of 60 years to define patients as elderly. Frailty was estimated using the 11-point modified frailty index (mFI-11). Patients were divided into three groups: robust, with an mFI score of 0; moderately frail, with an mFI score of 1 or 2; and severely frail, with an mFI score ≥ 3. A questionnaire-based survey was done to assess caregivers' perceptions about postdischarge care. RESULTS: Of the 276 patients, there were 93 (33.7%) elderly patients and 183 (66.3%) young or middle-aged patients. The proportion of severely frail patients was significantly more in the elderly group (38.7%) than in the young or middle-aged group (28.4%) (p < 0.001). The authors performed univariate and multivariate analysis of associations of different short-term outcomes with age, sex, frailty, and Charlson Comorbidity Index. On the multivariate analysis, only frailty was found to be a significant predictor for in-hospital mortality, postoperative complications, and length of hospital and ICU stay (p < 0.001). On Cox regression analysis, the severely frail group was found to have a significantly lower overall survival rate compared with the moderately frail (p = 0.001) and robust groups (p < 0.001). With the increase in frailty, there was a concomitant increase in the requirement for readmissions (p = 0.003), postdischarge specialist care (p = 0.001), and help from extrafamilial sources (p < 0.001). Greater dissatisfaction with psychosocial and financial support among the caregivers of severely frail patients was seen as they found themselves ill-equipped to provide postdischarge care at home (p < 0.001). CONCLUSIONS: Frailty is a better predictor of poorer surgical outcomes than chronological age in terms of duration of hospital and ICU stay, postoperative complications, and in-hospital mortality. It also adds to the psychosocial and financial burdens of the caregivers, making postdischarge care challenging.

Early coagulopathy in children with isolated blunt head injury is associated with mortality and poor neurological outcomes.

OBJECTIVE: Traumatic brain injury (TBI) is the leading cause of long-term disability and death in children and adolescents globally. Long-term adverse outcomes, including physical, cognitive, and behavioral sequelae, have been reported after TBI in a significant number of pediatric patients. In this study the authors sought to investigate the epidemiology of TBI-associated coagulopathy and its association with mortality and poor neurological outcome in a pediatric population with isolated moderate to severe blunt head injury treated at the authors' institution. METHODS: This retrospective study was conducted in the children's emergency department between January 2010 and December 2016. Children < 18 years old who presented with isolated moderate to severe blunt head injury were included in the study. The authors collected data on patient demographics, clinical presentation, and TBI management. Outcomes studied were death and poor neurological outcome defined by a score of < 7 (death, moderate to severe neurological disability) at 6 months postinjury on the pediatric version of the Glasgow Outcome Scale-Extended (GOS-E Peds). RESULTS: In 155 pediatric patients who presented with isolated moderate to severe blunt head injury, early coagulopathy was observed in 33 (21.3%) patients during the initial blood investigations done in the emergency department. The mean (SD) age of the study group was 7.03 (5.08) years and the predominant mechanism of injury was fall from height (65.2%). The median Abbreviated Injury Scale of the head (AIS head) score was 4 and the median GCS score was 13 (IQR 12-15). TBI-associated coagulopathy was independently associated with GOS-E Peds score < 7 (p = 0.02, adjusted OR 6.07, 95% CI 1.32-27.83). The overall mortality rate was 5.8%. After adjusting for confounders, only AIS head score and hypotension at triage remained significantly associated with TBI-associated coagulopathy. CONCLUSIONS: TBI-associated coagulopathy was independently associated with GOS-E Peds score < 7 at 6 months postinjury. Larger prospective studies are needed to investigate the use of TBI-associated coagulopathy to prognosticate these critical clinical outcomes.

Effects of Minocycline on Neurological Outcomes In Patients With Acute Traumatic Brain Injury: A Pilot Study.

Traumatic brain injury (TBI) is a public health problem worldwide. Secondary damage of brain injury begins within a few minutes after the trauma and can last a long time. It can be reversible, unlike primary injury. Therefore, therapeutic intervention can be used. The aims of this study were to assess the effects of minocycline on neurological function and serum S100B protein and neuron-specific enolase (NSE) levels in patients with moderate to severe TBI. Patients with acute onset of TBI and surgical evacuation of hematoma were randomized to receive either minocycline 100 mg orally twice daily or placebo for 7 days. The primary outcomes included changes in level of S100B and NSE at different time points during the trial. Additionally, changes in Glasgow coma scale (GCS) score were evaluated. The Glasgow Outcome Scale-Extended (GOS-E) score at 6 months after injury was assessed in discharge patients. Thirty four patients were randomized into the placebo (n = 20) and treatment (n = 14) groups. There was a marginal statistically significant differences in the normalized value of S100B between groups (p < 0.1). The reduction in serum NSE level from baseline to day 5 was statistically significant (p = 0.01) in minocycline group while it was not significantly decrease in placebo group (p = 0.2). Also, GCS improvement over time within the minocycline group was significant (p = 0.04) while was not significant in placebo group (p = 0.11). The GOS-E scores were not significantly different between minocycline and placebo group. Based on this study, it seems that the use of minocycline may be effective in acute TBI.

Outcome following postneurosurgical Acinetobacter meningitis: an institutional experience of 72 cases.

OBJECTIVE: The authors aimed to evaluate the antimicrobial susceptibility pattern of Acinetobacter isolates responsible for nosocomial meningitis/ventriculitis in the neurosurgical ICU. The authors also sought to identify the risk factors for mortality following Acinetobacter meningitis/ventriculitis. METHODS: This was a retrospective study of 72 patients admitted to the neurosurgical ICU between January 2014 and December 2018 with clinical and microbiological diagnosis of nosocomial postneurosurgical Acinetobacter baumanii meningitis/ventriculitis. Electronic medical data on clinical characteristics, underlying pathology, CSF cytology, antibiotic susceptibilities, and mortality were recorded. To evaluate the outcome following nosocomial postneurosurgical Acinetobacter meningitis/ventriculitis, patients were followed up until discharge or death in the hospital. Kaplan-Meier survival analysis and multivariable Cox proportional hazards models were used to compute factors affecting survival. RESULTS: The study population was divided into two groups depending on the final outcome of whether the patient died or survived. Forty-three patients (59.7%) were included in the survivor group and 29 patients (40.3%) were included in the nonsurvivor group. Total in-hospital mortality due to Acinetobacter meningitis/ventriculitis was 40.3% (29 cases), with a 14-day mortality of 15.3% and a 30-day mortality of 25%. The 43 (59.7%) patients who survived had a mean length of hospital stay of 44 ± 4 days with a median Glasgow Outcome Scale-Extended score at discharge of 6. On univariate analysis, age > 40 years (p = 0.078), admission Glasgow Coma Scale (GCS) score ≤ 8 (p = 0.003), presence of septic shock (p = 0.011), presence of external ventricular drain (EVD) (p = 0.03), CSF white blood cell (WBC) count > 200 cells/mm3 (p = 0.084), and comorbidities (diabetes, p = 0.036; hypertension, p = 0.01) were associated with poor outcome. Carbapenem resistance was not a risk factor for mortality. According to a multivariable Cox proportional hazards model, age cutoff of 40 years (p = 0.016, HR 3.21), GCS score cutoff of 8 (p = 0.006, HR 0.29), CSF WBC count > 200 cells/mm3 (p = 0.01, HR 2.76), presence of EVD (p = 0.001, HR 5.42), and comorbidities (p = 0.017, HR 2.8) were found to be significant risk factors for mortality. CONCLUSIONS: This study is the largest case series reported to date of postneurosurgical Acinetobacter meningitis/ventriculitis. In-hospital mortality due to Acinetobacter meningitis/ventriculitis was high. Age older than 40 years, GCS score less than 8, presence of EVD, raised CSF WBC count, and presence of comorbidities were risk factors for mortality.

Use of magnetic resonance imaging in severe pediatric traumatic brain injury: assessment of current practice.

OBJECTIVE: There is no consensus on the optimal timing and specific brain MRI sequences in the evaluation and management of severe pediatric traumatic brain injury (TBI), and information on current practices is lacking. The authors performed a survey of MRI practices among sites participating in a multicenter study of severe pediatric TBI to provide information for designing future clinical trials using MRI to assess brain injury after severe pediatric TBI. METHODS: Information on current imaging practices and resources was collected from 27 institutions participating in the Approaches and Decisions after Pediatric TBI Trial. Multiple-choice questions addressed the percentage of patients with TBI who have MRI studies, timing of MRI, MRI sequences used to investigate TBI, as well as the magnetic field strength of MR scanners used at the participating institutions and use of standardized MRI protocols for imaging after severe pediatric TBI. RESULTS: Overall, the reported use of MRI in pediatric patients with severe TBI at participating sites was high, with 40% of sites indicating that they obtain MRI studies in > 95% of this patient population. Differences were observed in the frequency of MRI use between US and international sites, with the US sites obtaining MRI in a higher proportion of their pediatric patients with severe TBI (94% of US vs 44% of international sites reported MRI in at least 70% of patients with severe TBI). The reported timing and composition of MRI studies was highly variable across sites. Sixty percent of sites reported typically obtaining an MRI study within the first 7 days postinjury, with the remainder of responses distributed throughout the first 30-day postinjury period. Responses indicated that MRI sequences sensitive for diffuse axonal injury and ischemia are frequently obtained in patients with TBI, whereas perfusion imaging and spectroscopy techniques are less common. CONCLUSIONS: Results from this survey suggest that despite the lack of consensus or guidelines, MRI is commonly obtained during the acute clinical setting after severe pediatric TBI. The variation in MRI practices highlights the need for additional studies to determine the utility, optimal timing, and composition of clinical MRI studies after TBI. The information in this survey describes current clinical MRI practices in children with severe TBI and identifies important challenges and objectives that should be considered when designing future studies.

Long-term follow-up of pediatric head trauma patients treated at Mulago National Referral Hospital in Uganda.

In Brief: This study used telephone surveys as a novel method of measuring health outcomes and tracking healthcare utilization in pediatric head trauma patients at the national referral hospital in Uganda. As the first-ever long-term follow-up of this patient population in Uganda, this work establishes a baseline of pediatric head trauma outcomes and lays the groundwork for tracking and improving outcomes for similar patients in low-resource settings.

Neural tube defects in Uganda: follow-up outcomes from a national referral hospital.

OBJECTIVE: Children with neural tube defects (NTDs) require timely surgical intervention coupled with long-term management by multiple highly trained specialty healthcare teams. In resource-limited settings, outcomes are greatly affected by the lack of coordinated care. The purpose of this study was to characterize outcomes of spina bifida patients treated at Mulago National Referral Hospital (MNRH) through follow-up phone surveys. METHODS: All children presenting to MNRH with NTDs between January 1, 2014, and August 31, 2015, were eligible for this study. For those with a documented telephone number, follow-up phone surveys were conducted with the children's caregivers to assess mortality, morbidity, follow-up healthcare, and access to medical resources. RESULTS: Of the 201 patients, the vast majority (n = 185, 92%) were diagnosed with myelomeningocele. The median age at presentation was 6 days, the median length of stay was 20 days, and the median time to surgery was 10 days. Half of the patients had documented surgeries, with 5% receiving multiple procedures (n = 102, 51%): 80 defect closures (40%), 32 ventriculoperitoneal shunts (15%), and 1 endoscopic third ventriculostomy (0.5%). Phone surveys were completed for 53 patients with a median time to follow-up of 1.5 years. There were no statistically significant differences in demographics between the surveyed and nonrespondent groups. The 1-year mortality rate was 34% (n = 18). At the time of survey, 91% of the survivors (n = 30) have received healthcare since their initial discharge from MNRH, with 67% (n = 22) returning to MNRH. Hydrocephalus was diagnosed in 29 patients (88%). Caregivers reported physical deficits in 39% of patients (n = 13), clubfoot in 18% (n = 6), and bowel or bladder incontinence in 12% (n = 4). The surgical complication rate was 2.5%. Glasgow Outcome Scale-Extended pediatric revision scores were correlated with upper good recovery in 58% (n = 19) of patients, lower good recovery in 30% (n = 10), and moderate disability in 12% of patients (n = 4). Only 5 patients (15%) reported access to home health resources postdischarge. CONCLUSIONS: This study is the first to characterize the outcomes of children with NTDs that were treated at Uganda's national referral hospital. There is a great need for improved access to and coordination of care in antenatal, perioperative, and long-term settings to improve morbidity and mortality.

Long-term outcome in traumatic brain injury patients with midline shift: a secondary analysis of the Phase 3 COBRIT clinical trial.

OBJECTIVE: Following traumatic brain injury (TBI), midline shift of the brain at the level of the septum pellucidum is often caused by unilateral space-occupying lesions and is associated with increased intracranial pressure and worsened morbidity and mortality. While outcome has been studied in this population, the recovery trajectory has not been reported in a large cohort of patients with TBI. The authors sought to utilize the Citicoline Brain Injury Treatment (COBRIT) trial to analyze patient recovery over time depending on degree of midline shift at presentation. METHODS: Patient data from the COBRIT trial were stratified into 4 groups of midline shift, and outcome measures were analyzed at 30, 90, and 180 days postinjury. A recovery trajectory analysis was performed identifying patients with outcome measures at all 3 time points to analyze the degree of recovery based on midline shift at presentation. RESULTS: There were 892, 1169, and 895 patients with adequate outcome data at 30, 90, and 180 days, respectively. Rates of favorable outcome (Glasgow Outcome Scale-Extended [GOS-E] scores 4-8) at 6 months postinjury were 87% for patients with no midline shift, 79% for patients with 1-5 mm of shift, 64% for patients with 6-10 mm of shift, and 47% for patients with > 10 mm of shift. The mean improvement from unfavorable outcome (GOS-E scores 2 and 3) to favorable outcome (GOS-E scores 4-8) from 1 month to 6 months in all groups was 20% (range 4%-29%). The mean GOS-E score for patients in the 6- to 10-mm group crossed from unfavorable outcome (GOS-E scores 2 and 3) into favorable outcome (GOS-E scores 4-8) at 90 days, and the mean GOS-E of patients in the > 10-mm group nearly reached the threshold of favorable outcome by 180 days postinjury. CONCLUSIONS: In this secondary analysis of the Phase 3 COBRIT trial, TBI patients with less than 10 mm of midline shift on admission head CT had significantly improved functional outcomes through 180 days after injury compared with those with greater than 10 mm of midline shift. Of note, nearly 50% of patients with > 10 mm of midline shift achieved a favorable outcome (GOS-E score 4-8) by 6 months postinjury.

Neurosurgical management in children with bleeding diathesis: auditing neurological outcome.

OBJECTIVE The aim of this study was to assess the outcome of neurosurgical treatment in children with bleeding diathesis and also to evaluate the current management plan applied in the authors' service. METHODS The authors retrospectively analyzed all cases in which neurosurgical procedures were performed in pediatric patients presenting with intracranial hematoma due to an underlying bleeding tendency over a 5-year period at their institution. They evaluated the patients' neurological symptoms from the initial referral, hematological abnormalities, surgical treatment, neurological outcome, and scores on the Pediatric Glasgow Outcome Scale-Extended (GOS-E Peds) obtained 1 year after the last operation. RESULTS Five patients with a bleeding diathesis who underwent surgery for intracranial hematoma were identified; the diagnosis was hemophilia A in 3 cases, idiopathic thrombocytopenic purpura in 1 case, and severe aplastic anemia in 1 case. Intracerebral hematoma (ICH) (n = 4) and acute subdural hematoma (n = 1) were confirmed on radiological investigations. In 2 of the 4 patients with ICH, the diagnosis of bleeding diathesis was made for the first time on presentation. Four patients (all male) were younger than 2 years; the patient with severe aplastic anemia and spontaneous ICH was 15 years old and female. The duration of symptoms varied from 24 hours to 5 days. Neurological examination at 1 year's follow-up showed complete recovery (GOS-E Peds score of 1) in 3 cases and mild weakness (GOS-E Peds score of 2) in 2 cases. CONCLUSIONS Neurosurgical management of patients with bleeding diathesis should be carried out in a tertiary-care setting with multidisciplinary team management, including members with expertise in neuroimaging and hematology, in addition to neurosurgery. Early diagnosis and prompt treatment of a bleeding diathesis is crucial for full neurological recovery.

Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study.

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating cerebrovascular event with long-term morbidity and mortality. Patients who survive the initial bleeding are likely to suffer further early brain injury arising from a plethora of pathological processes. These may result in a worsening of outcome or death in approximately 25% of patients and may contribute to longer-term cognitive dysfunction in survivors. Inflammation, mediated by the cytokine interleukin-1 (IL-1), is an important contributor to cerebral ischemia after diverse forms of brain injury, including aSAH. Its effects are attenuated by its naturally occurring antagonist, IL-1 receptor antagonist (IL-1Ra [anakinra]). The authors hypothesized that administration of additional subcutaneous IL-1Ra would reduce inflammation and associated plasma markers associated with poor outcome following aSAH. METHODS This was a randomized, open-label, single-blinded study of 100 mg subcutaneous IL-1Ra, administered twice daily in patients with aSAH, starting within 3 days of ictus and continuing until 21 days postictus or discharge from the neurosurgical center, whichever was earlier. Blood samples were taken at admission (baseline) and at Days 3-8, 14, and 21 postictus for measurement of inflammatory markers. The primary outcome was difference in plasma IL-6 measured as area under the curve between Days 3 and 8, corrected for baseline value. Secondary outcome measures included similar area under the curve analyses for other inflammatory markers, plasma pharmacokinetics for IL-1Ra, and clinical outcome at 6 months. RESULTS Interleukin-1Ra significantly reduced levels of IL-6 and C-reactive protein (p < 0.001). Fibrinogen levels were also reduced in the active arm of the study (p < 0.002). Subcutaneous IL-1Ra was safe, well tolerated, and had a predictable plasma pharmacokinetic profile. Although the study was not powered to investigate clinical effect, scores of the Glasgow Outcome Scale-extended at 6 months were better in the active group; however, this outcome did not reach statistical significance. CONCLUSIONS Subcutaneous IL-1Ra is safe and well tolerated in aSAH. It is effective in reducing peripheral inflammation. These data support a Phase III study investigating the effect of IL-1Ra on outcome following aSAH. Clinical trial registration no.: EudraCT: 2011-001855-35 ( www.clinicaltrialsregister.eu ).