Granulocyte- Macrophage Colony-Stimulating Factor Reverses Immunosuppression Acutely Following a Traumatic Brain Injury and Hemorrhage Polytrauma in a Juvenile Male Rat Model.

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extracranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of granulocyte macrophage colony-stimulating factor (GM-CSF) could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit. Prepubescent male rats were injured using a controlled cortical impact model and then subjected to removal of 25% blood volume (TBI/H). Sham animals underwent surgery without injury induction, and the treatment groups were sham and injured animals treated with either saline vehicle or 50 µg/kg GM-CSF. GM-CSF was administered following injury and then daily until sacrifice at post-injury day (PID) 7. Immune function was measured by assessing tumor necrosis factor-α (TNF-α) levels in whole blood and spleen following ex vivo stimulation with pokeweed mitogen (PWM). Brain samples were assessed by multiplex enzyme-linked immunosorbent assay (ELISA) for cytokine levels and by immunohistochemistry for microglia and astrocyte proliferation. Neuronal cell count was examined using cresyl violet staining. Motor coordination was evaluated using the Rotarod performance test. Treatment with GM-CSF was associated with a significantly increased response to PWM in both whole blood and spleen. GM-CSF in injured animals did not lead to increases in levels of pro-inflammatory cytokines in brain samples but was associated with significant increases in counted astrocytes. Finally, while injured animals treated with saline showed a significant impairment on behavioral testing, injured animals treated with GM-CSF performed similarly to uninjured animals. GM-CSF treatment in animals with combined injury led to increased systemic immune cell response in whole blood and spleen in the acute phase following injury. Improved immune response was not associated with elevated pro-inflammatory cytokine levels in the brain or functional impairment.

Recommendations for reproducibility of cerebrospinal fluid extracellular vesicle studies.

Cerebrospinal fluid (CSF) is a clear, transparent fluid derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste and transports extracellular components to remote sites in the brain. Given its contact with the brain and the spinal cord, CSF is the most informative biofluid for studies of the central nervous system (CNS). In addition to other components, CSF contains extracellular vesicles (EVs) that carry bioactive cargoes (e.g., lipids, nucleic acids, proteins), and that can have biological functions within and beyond the CNS. Thus, CSF EVs likely serve as both mediators of and contributors to communication in the CNS. Accordingly, their potential as biomarkers for CNS diseases has stimulated much excitement for and attention to CSF EV research. However, studies on CSF EVs present unique challenges relative to EV studies in other biofluids, including the invasive nature of CSF collection, limited CSF volumes and the low numbers of EVs in CSF as compared to plasma. Here, the objectives of the International Society for Extracellular Vesicles CSF Task Force are to promote the reproducibility of CSF EV studies by providing current reporting and best practices, and recommendations and reporting guidelines, for CSF EV studies. To accomplish this, we created and distributed a world-wide survey to ISEV members to assess methods considered 'best practices' for CSF EVs, then performed a detailed literature review for CSF EV publications that was used to curate methods and resources. Based on responses to the survey and curated information from publications, the CSF Task Force herein provides recommendations and reporting guidelines to promote the reproducibility of CSF EV studies in seven domains: (i) CSF Collection, Processing, and Storage; (ii) CSF EV Separation/Concentration; (iii) CSF EV Size and Number Measurements; (iv) CSF EV Protein Studies; (v) CSF EV RNA Studies; (vi) CSF EV Omics Studies and (vii) CSF EV Functional Studies.

Defining Pediatric Trauma Center Resource Utilization: Multidisciplinary Consensus-Based Criteria from the Pediatric Trauma Society.

BACKGROUND: Pediatric trauma triage and transfer decisions should incorporate the likelihood that an injured child will require pediatric trauma center (PTC) resources. Resource utilization may be a better basis than mortality risk when evaluating pediatric injury severity. However, there is currently no consensus definition of PTC resource utilization that encompasses the full scope of PTC services. METHODS: Consensus criteria were developed in collaboration with the Pediatric Trauma Society (PTS) Research Committee using a modified Delphi approach. An expert panel was recruited representing the following pediatric disciplines: prehospital care, emergency medicine, nursing, general surgery, neurosurgery, orthopedics, anesthesia, radiology, critical care, child abuse, and rehabilitation medicine. Resource utilization criteria were drafted from a comprehensive literature review, seeking to complete the following sentence: "Pediatric patients with traumatic injuries have used PTC resources if they..." Criteria were then refined and underwent three rounds of voting to achieve consensus. Consensus was defined as agreement of 75% or more panelists. Between the second and third voting rounds, broad feedback from attendees of the PTS annual meeting was obtained. RESULTS: The Delphi panel consisted of 18 members from 15 institutions. Twenty initial draft criteria were developed based on literature review. These criteria dealt with airway interventions, vascular access, initial stabilization procedures, fluid resuscitation, blood product transfusion, abdominal trauma/solid organ injury management, intensive care monitoring, anesthesia/sedation, advanced imaging, radiologic interpretation, child abuse evaluation, and rehabilitative services. After refinement and panel voting, 14 criteria achieved the >75% consensus threshold. The final consensus criteria were reviewed and endorsed by the PTS Guidelines Committee. CONCLUSIONS: This study defines multidisciplinary consensus-based criteria for PTC resource utilization. These criteria are an important step toward developing a gold standard, resource-based, pediatric injury severity metric. Such metrics can help optimize system-level pediatric trauma triage based on likelihood of requiring PTC resources. LEVEL OF EVIDENCE/STUDY TYPE: Level II, diagnostic test/criteria.

Long-Term Functional Outcome Following Neurosurgical Intervention for Suspected Abusive Head Trauma.

BACKGROUND: The purpose of this study was to evaluate the long-term functional and neurodevelopmental outcomes in pediatric patients who underwent neurosurgical intervention following suspected abusive head trauma (AHT). METHODS: We performed a single-center retrospective review (January 1, 2007, to December 31, 2019) of patients aged less than three years who had intracranial injury suspicious for AHT and received a neurosurgical procedure. Long-term functional outcome was measured using the Pediatric Cerebral Performance Category (PCPC), Pediatric Overall Performance Category (POPC), and the Mullen Scales of Early Learning (MSEL). RESULTS: Seventy-seven patients were identified; 53 survived to discharge and had at least one-year follow-up. To examine long-term functional outcome, PCPC at the last available visit was examined and found to be 1 or 2 (normal to mild disability) for 64% of patients and 3 or 4 (moderate to severe disability) for 36%. The last available MSEL composite score for neurodevelopmental assessment also demonstrated that 13% of patients scored in the "average" range, 17% in the "below average" range, and 70% in the "very low" range. There was no statistical difference in the last available PCPC or POPC score or the last available MSEL score for patients who received a craniotomy when compared with those who received an intracranial shunt. CONCLUSIONS: For patients with AHT who survived to discharge, functional improvements over time were noted in both patients who received craniotomy or who simply required shunt placement. These results suggest that, for patients who survive to discharge, operative management of AHT can lead to reasonable long-term functional outcomes.

Prothrombin Complex Concentrate Utilization in Children's Hospitals.

Prothrombin complex concentrates (PCCs) are used to manage bleeding in critically ill children. We performed a repeat cross-sectional study using the Pediatric Health Information System registry to describe PCC utilization in the U.S. children's hospitals over time and determine the relationship between PCC use and specific risk factors for bleeding. We included children < 18 years who received three-factor or four-factor PCC during hospital admission between January 2015 and December 2020 to describe the association between PCC therapy, anticoagulation therapies, and inherited or acquired bleeding diatheses. PCC use steadily increased over the 6-year study period (from 1.3 to 4.6 per 10,000 encounters). Patients exhibited a high degree of critical illness, with 85.0% requiring intensive care unit admission and a mortality rate of 25.8%. PCCs were used in a primarily emergent or urgent fashion (32.6 and 39.3%, respectively) and more frequently in surgical cases (79.0% surgical vs. 21.0% medical). Coding analysis suggested a low rate of chronic anticoagulant use which was supported by review of concomitant anticoagulant medications. PCC use is increasing in critically ill children and does not correlate with specific anticoagulant therapy use or other bleeding risk factors. These findings suggest PCC use is not limited to vitamin K antagonist reversal. Indications, efficacy, and safety of PCC therapy in children require further study.

Occult pediatric skull fracture and implications for delay in diagnosis: illustrative case.

BACKGROUND: After being struck in the left side of the head by a thin metal rod, a 10-year-old, previously healthy male presented to an urgent care clinic with a subcentimeter scalp laceration in the midline parietal area and a normal neurological exam. Evaluation included skull radiographs, which did not demonstrate a definitive fracture. Following laceration repair, the patient was discharged to home. OBSERVATIONS: Subsequently, progressive neurological symptoms prompted his family to bring him back for evaluation 2 days later, and computed tomography (CT) and magnetic resonance imaging (MRI) revealed an open, depressed skull fracture. Surgical intervention was performed with debridement and closure. The patient was placed on a course of intravenous antibiotics and had no subsequent evidence of infection. LESSONS: In cases involving potential cranial perforation by a thin projectile, use of CT imaging or MRI, rather than plain radiographs, may prevent a delay in diagnosis and subsequent complications.

Catheter-associated deep vein thrombosis in children with severe traumatic brain injury: A single-center experience.

BACKGROUND: This study was performed to describe the single-center experience of deep vein thrombosis (DVT) in children with severe traumatic brain injury (sTBI) who were mechanically ventilated with a central line, and to identify potentially modifiable risk factors. It was hypothesized that children with DVT would have a longer duration of central venous line (CVL) and a higher use of hypertonic saline (HTS) compared to those without DVT. PROCEDURE/METHODS: This was a retrospective study of children (0-18 years) with sTBI, who were intubated, had a CVL, and a minimum intensive care unit (ICU) stay of 3 days. Children were analyzed by the presence or absence of DVT. HTS use was evaluated using milliliter per kilogram (ml/kg) of 3% equivalents. Univariable and multivariable logistic regression models were used to determine which factors were associated with DVT. RESULTS: Seventy-seven children met inclusion criteria, 23 (29.9%) had a DVT detected in an extremity. On univariable analysis, children with DVT identified in an extremity had prolonged CVL use (14 vs. 8.5 days, p = .021) and longer duration of mechanical ventilation (15 vs. 10 days, p = .013). HTS 3% equivalent ml/kg was not different between groups. On multivariable analysis, mechanical ventilation duration was associated with DVT detection in an extremity, whereas neither CVL duration nor HTS use had an association. CONCLUSIONS: There was a high incidence of extremity DVT detected in children with sTBI who received invasive mechanical ventilation and had a CVL. HTS administration was not associated with DVT detection in an extremity.

Biomechanical effects of a halo orthotic on a pediatric anthropomorphic test device in a simulated frontal motor vehicle collision.

Objective: Cervical spine injuries in children under 10 frequently involve the craniocervical junction. In patients too small for conventional spinal instrumentation, treatment may involve placement of a halo orthotic, and these patients will frequently be discharged home in a halo orthotic. To date, little research has been done on the biomechanics of motor vehicle collisions involving young children in halo orthotics. To better understand possible safety concerns, we applied a halo orthotic to an appropriately sized anthropomorphic test device (ATD, or crash test dummy) on an acceleration sled to simulate a frontal motor vehicle collision.Methods: For the tests, a Hybrid III 3-year-old ATD was instrumented with head and chest accelerometers, head angular rate sensors, a six-axis upper neck load cell, and a chest linear potentiometer. Four tests were conducted on an acceleration sled, and kinematics were recorded with high speed video. Testing variables included 1) with or without a halo orthotic and 2) with a standard booster seat or a commercially available harness vest.Results: The halo orthotic reduced flexion and extension but was associated with increased rotation, especially in the condition of a halo orthotic with a standard booster seat. Increased cervical distraction was noted with the halo orthotic, and this was especially increased in the condition of a halo orthotic with the harness vest.Conclusions: The biomechanics of a child involved in a motor vehicular collision may be dramatically altered with a halo orthotic, as modeled by an acceleration sled test. While cervical spine flexion and extension are reduced with the halo orthotic, rotation appears to increase. Immobilization from a halo orthotic also appears to increase cervical distraction, especially when used in conjunction with a harness vest. Further testing is needed to determine the safest restraints for this small, but at-risk, population.

Association between synthetic sealants and increased complication rates in posterior fossa decompression with duraplasty for Chiari malformations regardless of graft type.

OBJECTIVE: Dural sealants are commonly used in posterior fossa decompression with duraplasty (PFDD) for Chiari malformation type I (CMI). Prior evidence suggests that combining certain sealants with some graft material is associated with an increased rate of complications. In 2018, the authors noted an increased rate of symptomatic pseudomeningocele and aseptic meningitis after PFDD in CMI patients. The authors utilized retrospective and prospective analyses to test the hypothesis that complication rates increase with the use or combination of certain sealants and grafts. METHODS: The analysis was split into 2 periods. The authors retrospectively reviewed patients who underwent PFDD for CMI at their center between August 12, 2011, and December 31, 2018. The authors then eliminated use of DuraSeal on the basis of the retrospective analysis and prospectively examined complication rates from January 1, 2019, to August 4, 2021. The authors defined a complication as symptomatic pseudomeningocele, bacterial or aseptic meningitis, cerebrospinal fluid leak, subdural hygroma, hydrocephalus, surgical site infection, or wound dehiscence. RESULTS: From 2011 to 2018, complications occurred in 24.5% of 110 patients. Sealant choice was correlated with complication rates: no sealant (0%), Tisseel (6%), and DuraSeal (15.3%) (p < 0.001). No difference in complication rate was noted on the basis of choice of graft material (p = 0.844). After eliminating DuraSeal, the authors followed 40 patients who underwent PFDD after 2018. The complication rate decreased to 12.5%. All complications after 2018 were associated with Tisseel. CONCLUSIONS: At the authors' single center, use of sealants in PFDD surgery for CMI, especially DuraSeal, was correlated with a higher complication rate. Eliminating DuraSeal led to a significant decrease in the rate of symptomatic pseudomeningocele and aseptic meningitis.

Developing a National Trauma Research Action Plan: Results from the Pediatric Research Gap Delphi Survey.

BACKGROUND: In 2016, the National Academies of Sciences, Engineering, and Medicine trauma report recommended a National Trauma Research Action Plan to "strengthen trauma research and ensure that the resources available for this research are commensurate with the importance of injury and the potential for improvement in patient outcomes." With a contract from the Department of Defense, the Coalition for National Trauma Research created 11 expert panels to address this recommendation, with the goal of developing a comprehensive research agenda, spanning the continuum of trauma and burn care. This report outlines the work of the group focused on pediatric trauma. METHODS: Experts in pediatric trauma clinical care and research were recruited to identify gaps in current clinical pediatric trauma research, generate research questions, and establish the priority of these questions using a consensus-driven Delphi survey approach. Using successive surveys, participants were asked to rank the priority of each research question on a 9-point Likert scale categorized to represent priority. Consensus was defined as >60% agreement within the priority category. Priority questions were coded based on a dictionary of 118 National Trauma Research Action Plan taxonomy concepts in 9 categories to support comparative analysis across all panels. RESULTS: Thirty-seven subject matter experts generated 625 questions. A total of 493 questions (79%) reached consensus on priority level. Of those reaching consensus, 159 (32%) were high, 325 (66%) were medium, and 9 (2%) were low priority. The highest priority research questions related to surgical interventions for traumatic brain injury (intracranial pressure monitoring and craniotomy); the second highest priority was hemorrhagic shock. The prehospital setting was the highest priority phase of care. CONCLUSION: This diverse panel of experts determined that most significant pediatric trauma research gaps were in traumatic brain injury, hemorrhagic shock, and the prehospital phase of care. These research domains should be top priorities for funding agencies. LEVEL OF EVIDENCE: Therapeutic / Care Management; Level IV.

Implementation of a Level 1 Neuro Trauma Activation at a Tertiary Pediatric Trauma Center.

INTRODUCTION: Timely management improves outcomes in patients with traumatic brain injury (TBI), especially those requiring operative intervention. We implemented a "Level 1 Neuro" (L1N) trauma activation for severe TBI, aiming to decrease times to intervention. METHODS: We evaluated whether an L1N activation was associated with shorter times to operating room (OR) incision and pediatric intensive care unit (PICU) admission using multivariable regression models. Trauma patients with severe TBI undergoing operative intervention or PICU admission from January 2008-October 2020 met inclusion. The L1N cohort included patients meeting our institution's L1N criteria. The L1 and L2 cohorts included head injury patients with hAIS ≥3 and an L1 or L2 activation, respectively. RESULTS: Median hAIS, GCS, Rotterdam CT score, and ISS were 4.5 (4-5), 8 (3-15), 2 (1-3), and 17 (11-26), respectively. We demonstrate clinically shorter times to OR incision among L1N traumas (93.3 min) compared to L1 (106.7 min; P = 0.73) and L2 cohorts (133.5 min; P = 0.03). We also demonstrate clinically shorter times to anesthesia among L1N traumas (51.9 min) compared to L1 (70.1 min; P = 0.13) and L2 cohorts (101.3 min; P < 0.01). Median GCS, ISS and hAIS in the PICU patients were 10 (IQR:3-15), 17 (11-26), and 4 (3-4), respectively. We demonstrate clinically shorter times to PICU among L1N traumas (82.1 min) and the L2 cohort (154.7 min; P < 0.01). CONCLUSIONS: An L1N activation is associated with shorter times to anesthesia and OR management. Enhancing communication with standardized neurotrauma activation has the potential to improve timeliness of care in severe pediatric TBI.

Central nervous system injury-induced immune suppression.

Central nervous system trauma is a common cause of morbidity and mortality. Additionally, these injuries frequently occur in younger individuals, leading to lifetime expenses for patients and caregivers and the loss of opportunity for society. Despite this prevalence and multiple attempts to design a neuroprotectant, clinical trials for a pharmacological agent for the treatment of traumatic brain injury (TBI) or spinal cord injury (SCI) have provided disappointing results. Improvements in outcome from these disease processes in the past decades have been largely due to improvements in supportive care. Among the many challenges facing patients and caregivers following neurotrauma, posttraumatic nosocomial infection is a significant and potentially reversible risk factor. Multiple animal and clinical studies have provided evidence of posttraumatic systemic immune suppression, and injuries involving the CNS may be even more prone, leading to a higher risk for in-hospital infections following neurotrauma. Patients who have experienced neurotrauma with nosocomial infection have poorer recovery and higher risks of long-term morbidity and in-hospital mortality than patients without infection. As such, the etiology and reversal of postneurotrauma immune suppression is an important topic. There are multiple possible etiologies for these posttraumatic changes including the release of damage-associated molecular patterns, the activation of immunosuppressive myeloid-derived suppressor cells, and sympathetic nervous system activation. Postinjury systemic immunosuppression, particularly following neurotrauma, provides a challenge for clinicians but also an opportunity for improvement in outcome. In this review, the authors sought to outline the evidence of postinjury systemic immune suppression in both animal models and clinical research of TBI, TBI polytrauma, and SCI.

Clinically aggressive pediatric spinal ependymoma with novel MYC amplification demonstrates molecular and histopathologic similarity to newly described MYCN-amplified spinal ependymomas.

Primary spinal cord tumors contribute to ≤ 10% of central nervous system tumors in individuals of pediatric or adolescent age. Among intramedullary tumors, spinal ependymomas make up ~ 30% of this rare tumor population. A twelve-year-old male presented with an intradural, extramedullary mass occupying the dorsal spinal canal from C6 through T2. Gross total resection and histopathology revealed a World Health Organization (WHO) grade 2 ependymoma. He recurred eleven months later with extension from C2 through T1-T2. Subtotal resection was achieved followed by focal proton beam irradiation and chemotherapy. Histopathology was consistent with WHO grade 3 ependymoma. Molecular profiling of the primary and recurrent tumors revealed a novel amplification of the MYC (8q24) gene, which was confirmed by fluorescence in situ hybridization studies. Although MYC amplification in spinal ependymoma is exceedingly rare, a newly described classification of spinal ependymoma harboring MYCN (2p24) amplification (SP-MYCN) has been defined by DNA methylation-array based profiling. These individuals typically present with a malignant progression and dismal outcomes, contrary to the universally excellent survival outcomes seen in other spinal ependymomas. DNA methylation array-based classification confidently classified this tumor as SP-MYCN ependymoma. Notably, among the cohort of 52 tumors comprising the SP-MYCN methylation class, none harbor MYC amplification, highlighting the rarity of this genomic amplification in spinal ependymoma. A literature review comparing our individual to reported SP-MYCN tumors (n = 26) revealed similarities in clinical, histopathologic, and molecular features. Thus, we provide evidence from a single case to support the inclusion of MYC amplified spinal ependymoma within the molecular subgroup of SP-MYCN.

Traumatic brain injury and hemorrhage in a juvenile rat model of polytrauma leads to immunosuppression and splenic alterations.

BACKGROUND: Traumatic brain injury (TBI) is a common cause of morbidity and mortality. We have previously shown that TBI with a concurrent extra-cranial injury reliably leads to post-injury suppression of the innate immune system, but the impact of this injury on the adaptive immune system is unknown. We present data showing that combined injury reduced immune response as assayed in both blood and spleen samples and that these changes parallel apoptosis in the spleen. To assess the clinical relevance of these changes, we examined lungs for spontaneous bacterial colonization. METHODS: For these studies, prepubescent (28 day old) rats were injured using a controlled cortical impact model and then 25% blood volume removal by arteriotomy, and injured animals were compared with sham injured animals. Blood and spleen samples at post-injury day 1 were incubated with or without immunostimulant and examined for IFN-γ production using an Eli-Spot assay. Spleen samples were also examined for apoptosis using Annexin V staining, and lungs were harvested and plated on blood agar to examine for spontaneous bacterial colonization. RESULTS: Stimulations of whole blood and spleen samples with phorbol 12-myristate 13-acetate/ionomycin (PMA/I) at post-injury day 1 were associated with significant decreases in IFN-γ-positive cells/million in injured animals. Stimulation of whole blood with either PMA/I or pokeweed mitogen led to reduced tumor necrosis factor alpha production. Spleen from injured animals showed a marked increase in apoptosis. Lung samples showed a 300% increase in colonies per plate in injured animals. CONCLUSIONS: These data suggest that the combined injury can lead to adaptive immunosuppression, and our findings further suggest a potential role for the spleen in altering leukocyte function following injury.

Customised hybrid CT-MRI 3D-printed model for grade V spondylolisthesis in an adolescent.

3D-printed patient-specific models provide added value for initial clinical diagnosis, preoperative surgical and implant planning and patient and trainee education. 3D spine models are usually designed using CT data, due to the ability to rapidly image osseous structures with high spatial resolution. Combining CT and MRI to derive a composite model of bony and neurological anatomy can potentially provide even more useful information for complex cases. We describe such a case involving an adolescent with a grade V spondylolisthesis in which a composite model was manufactured for preoperative and intraoperative evaluation and guidance. We provide a detailed workflow for creating such models and outline their potential benefit in guiding a multidisciplinary team approach.

YAP1-FAM118B Fusion Defines a Rare Subset of Childhood and Young Adulthood Meningiomas.

Meningiomas are a central nervous system tumor primarily afflicting adults, with <1% of cases diagnosed during childhood or adolescence. Somatic variation in NF2 may be found in ∼50% of meningiomas, with other genetic drivers (eg, SMO, AKT1, TRAF7) contributing to NF2 wild-type tumors. NF2 is an upstream negative regulator of YAP signaling and loss of the NF2 protein product, Merlin, results in YAP overexpression and target gene transcription. This mechanism of dysregulation is described in NF2-driven meningiomas, but further work is necessary to understand the NF2-independent mechanism of tumorigenesis. Amid our institutional patient-centric comprehensive molecular profiling study, we identified an individual with meningioma harboring a YAP1-FAM118B fusion, previously reported only in supratentorial ependymoma. The tumor histopathology was remarkable, characterized by prominent islands of calcifying fibrous nodules within an overall collagen-rich matrix. To gain insight into this finding, we subsequently evaluated the genetic landscape of 11 additional pediatric and adolescent/young adulthood meningioma patients within the Children's Brain Tumor Tissue Consortium. A second individual harboring a YAP1-FAM118B gene fusion was identified within this database. Transcriptomic profiling suggested that YAP1-fusion meningiomas are biologically distinct from NF2-driven meningiomas. Similar to other meningiomas, however, YAP1-fusion meningiomas demonstrated overexpression of EGFR and MET. DNA methylation profiling further distinguished YAP1-fusion meningiomas from those observed in ependymomas. In summary, we expand the genetic spectrum of somatic alteration associated with NF2 wild-type meningioma to include the YAP1-FAM118B fusion and provide support for aberrant signaling pathways potentially targetable by therapeutic intervention.

Use of viscoelastic monitoring and prothrombin complex concentrate in a paediatric patient with polytrauma and severe traumatic brain injury.

Viscoelastic monitoring (VEM) tools, such as rotational thrombelastometry, have been used extensively to measure coagulopathy in adults but have received less attention in paediatric care. The presented case involves a 5-year-old boy who was brought to the emergency department after a motor vehicle collision with a Glasgow Coma Scale score of 6T and extensive injuries, including a subdural hematoma. VEM was used to monitor the patient's coagulopathy and to inform treatment measures by allowing real-time visualisation of the patient's coagulation status. VEM was additionally used to direct blood product replacement in preparation for neurosurgical intervention, and 4-factor prothrombin complex concentrate (PCC) was used to help reverse the coagulopathy. The patient underwent successful hemicraniectomy after improvement of his coagulopathy. In paediatrics, VEM and PCC are increasingly being used for post-trauma coagulopathy, and this case highlights their potential promise and the need for further research.

Validation of the Surgical Intervention for Traumatic Injury scale in the pediatric population.

OBJECTIVE: While the Glasgow Coma Scale (GCS) has been effective in describing severity in traumatic brain injury (TBI), there is no current method for communicating the possible need for surgical intervention. This study utilizes a recently developed scoring system, the Surgical Intervention for Traumatic Injury (SITI) scale, which was developed to efficiently communicate the potential need for surgical decompression in adult patients with TBI. The objective of this study was to apply the SITI scale to a pediatric population to provide a tool to increase communication of possible surgical urgency. METHODS: The SITI scale uses both radiographic and clinical findings, including the GCS score on presentation, pupillary examination, and CT findings. To examine the scale in pediatric TBI, a neurotrauma database at a level 1 pediatric trauma center was retrospectively evaluated, and the SITI score for all patients with an admission diagnosis of TBI between 2010 and 2015 was calculated. The primary endpoint was operative intervention, defined as a craniotomy or craniectomy for decompression, performed within the first 24 hours of admission. RESULTS: A total of 1524 patients met inclusion criteria for the study during the 5-year span: 1469 (96.4%) were managed nonoperatively and 55 (3.6%) patients underwent emergent operative intervention. The mean SITI score was 4.98 ± 0.31 for patients undergoing surgical intervention and 0.41 ± 0.02 for patients treated nonoperatively (p < 0.0001). The area under the receiver operating characteristic (AUROC) curve was used to examine the diagnostic accuracy of the SITI scale in this pediatric population and was found to be 0.98. Further evaluation of patients presenting with moderate to severe TBI revealed a mean SITI score of 5.51 ± 0.31 in 40 (15.3%) operative patients and 1.55 ± 0.02 in 221 (84.7%) nonoperative patients, with an AUROC curve of 0.95. CONCLUSIONS: The SITI scale was designed to be a simple, objective communication tool regarding the potential need for surgical decompression after TBI. Application of this scale to a pediatric population reveals that the score correlated with the perceived need for emergent surgical intervention, further suggesting its potential utility in clinical practice.