Association of initial assessment variables and mortality in severe pediatric traumatic brain injury.

Background: Predictive scales have been used to prognosticate long-term outcomes of traumatic brain injury (TBI), but gaps remain in predicting mortality using initial trauma resuscitation data. We sought to evaluate the association of clinical variables collected during the initial resuscitation of intubated pediatric severe patients with TBI with in-hospital mortality. Methods: Intubated pediatric trauma patients <18 years with severe TBI (Glasgow coma scale (GCS) score ≤8) from January 2011 to December 2020 were included. Associations between initial trauma resuscitation variables (temperature, pulse, mean arterial blood pressure, GCS score, hemoglobin, international normalized ratio (INR), platelet count, oxygen saturation, end tidal carbon dioxide, blood glucose and pupillary response) and mortality were evaluated with multivariable logistic regression. Results: Among 314 patients, median age was 5.5 years (interquartile range (IQR): 2.2-12.8), GCS score was 3 (IQR: 3-6), Head Abbreviated Injury Score (hAIS) was 4 (IQR: 3-5), and most had a severe (25-49) Injury Severity Score (ISS) (48.7%, 153/314). Overall mortality was 26.8%. GCS score, hAIS, ISS, INR, platelet count, and blood glucose were associated with in-hospital mortality (all p<0.05). As age and GCS score increased, the odds of mortality decreased. Each 1-point increase in GCS score was associated with a 35% decrease in odds of mortality. As hAIS, INR, and blood glucose increased, the odds of mortality increased. With each 1.0 unit increase in INR, the odds of mortality increased by 1427%. Conclusions: Pediatric patients with severe TBI are at substantial risk for in-hospital mortality. Studies are needed to examine whether earlier interventions targeting specific parameters of INR and blood glucose impact mortality.

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.

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.

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.

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.

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.

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.

Innate immune suppression after traumatic brain injury and hemorrhage in a juvenile rat model of polytrauma.

Traumatic injury in children is known to cause immune suppression. Polytrauma involving a traumatic brain injury (TBI) may increase this degree of immune suppression, which increases the risk of developing nosocomial infections, potentially causing secondary brain injury and worsening patient outcomes. Despite the high prevalence of polytrauma with TBI in children, mechanisms of immune suppression following such injuries remain poorly understood. Here, we used a combined animal injury model of TBI and hemorrhage to assess immune function after polytrauma. Pre-pubescent rats were injured using a prefrontal controlled cortical impact method and a controlled hemorrhage by femoral arteriotomy. Immune function was measured by whole blood ex-vivo tumor necrosis factor alpha production capacity following incubation with lipopolysaccharide, measuring the percentage of monocytes by flow cytometry, and by examining concentrations of plasma cytokines. The degree of brain injury was sufficient to produce deficits in spatial memory testing (Barnes maze). Both hemorrhage and TBI with hemorrhage (combined injury) reduced several of the measured plasma cytokines, as compared with TBI alone. The combined injury correlated with reduced concentration of monocytes and reduced tumor necrosis factor alpha production capacity at post-injury day 1. These results demonstrate that this animal model can be used to study post-injury immune suppression.

The Surgical Intervention for Traumatic Injury Scale: A Clinical Tool for Traumatic Brain Injury.

INTRODUCTION: There is no widely used method for communicating the possible need for surgical intervention in patients with traumatic brain injury (TBI). This study describes a scoring system designed to communicate the potential need for surgical decompression in TBI patients. The scoring system, named the Surgical Intervention for Traumatic Injury (SITI), was designed to be objective and easy to use. METHODS: The SITI scale uses radiographic and clinical findings, including the Glasgow Coma Scale Score, pupil examination, and findings noted on computed tomography. To examine the scale, we used the patient database for the Progesterone for the Treatment of Traumatic Brain Injury III (ProTECT III) trial, and retrospectively applied the SITI scale to these patients. RESULTS: Of the 871 patients reviewed, 164 (18.8%) underwent craniotomy or craniectomy, and 707 (81.2%) were treated nonoperatively. The mean SITI score was 5.1 for patients who underwent surgery and 2.5 for patients treated nonoperatively (P<0.001). The area under the receiver operating characteristic curve was 0.887. CONCLUSION: The SITI scale was designed to be a simple, objective, clinical decision tool regarding the potential need for surgical decompression after TBI. Application of the SITI scale to the ProTECT III database demonstrated that a score of 3 or more was well associated with a perceived need for surgical decompression. These results further demonstrate the potential utility of the SITI scale in clinical practice.

Correction of Progressive Severe Cervical Kyphosis in a 21-Month-Old Patient With NF1: Surgical Technique and Review of Literature.

BACKGROUND: Severe cervical kyphosis in the setting of neurofibromatosis type 1 (NF1) is a rare manifestation of the disease in the pediatric population. Dystrophic and immature bone complicate the placement of hardware necessary for surgical correction of alignment and a review of the literature yields 4 cases of pediatric patients with NF1 requiring surgical intervention in which the youngest patient was 10 yr old. OBJECTIVE: To report the case of an 11-mo-old female with NF1 who presented with a plexiform cervical neurofibroma and focal cervical kyphosis. A comprehensive review of the literature and a detailed description of nonsurgical and surgical management for this patient population is described. METHODS: A literature review was completed for article reviewing management of pediatric patients with cervical spine injuries and NF1. The patient's chart was reviewed and the patient was followed for a year to provide adequate follow-up. Institutional Review Board (IRB)/ethics committee approval and patient consent were neither required nor sought for this study. RESULTS: The literature was reviewed, summarized, and utilized for operative planning and postoperative management. Postoperative imaging and 1-yr follow-up imaging showed anterior construct and lateral mass fusion, restoration of cervical alignment, and no neurological deficits. CONCLUSION: This is the youngest reported patient to have surgical cervical kyphosis correction in the setting of NF1. A review of the literature helped develop a long-term plan and shape a novel same-day front-back-front approach to restore alignment that will be of use to teams managing these complex patients in the future.

A Novel Technique for Distal Shunt Revision: Retrospective Analysis of Guidewire-Assisted Distal Catheter Replacement.

BACKGROUND: Ventriculoperitoneal shunt revision is a common procedure. Disconnection and fracture of the distal catheter remain a common cause of ventriculoperitoneal shunt malfunction. OBJECTIVE: To describe a novel procedure for peritoneal replacement of the distal catheter by using a guidewire and a modified Seldinger technique (guidewire-assisted distal catheter replacement) and retrospectively evaluate the results of the surgical procedure. METHODS: Between September 2005 and December 2013, 68 patients were treated by a single surgeon (DMW) with distal catheter replacement using our technique. In brief, the previously placed distal catheter was exposed at its entry site into the abdomen. A soft guidewire with hydrophilic coating was inserted down the distal catheter into the peritoneum. The distal catheter was then removed over the guidewire, leaving the guidewire in place. A peel-away sheath and dilator were then inserted over the guidewire, and the dilator and guidewire were removed. The new distal catheter was then passed from the valve to the abdomen and was then fed through the peel-away sheath into the peritoneum. Charts were retrospectively reviewed for preoperative presentation, operative technique, and postoperative outcome. Records were specifically examined for any early or late complications. RESULTS: The mean patient age at surgery was 13 years. No immediate acute complications were noted. Of the 68 total patients, 45 patients had more than 6 months of follow-up. Of the 68 patients, 7 patients required another distal revision after guidewire-assisted distal catheter replacement. CONCLUSION: Distal shunt malfunction due to a mechanical failure is a common reason for shunt revision. We describe a technique for guidewire-assisted distal catheter replacement.

Progesterone treatment shows benefit in a pediatric model of moderate to severe bilateral brain injury.

PURPOSE: Controlled cortical impact (CCI) models in adult and aged Sprague-Dawley (SD) rats have been used extensively to study medial prefrontal cortex (mPFC) injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI) in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury. METHODS: Twenty-eight-day old (PND 28) male Sprague Dawley rats received sham (n = 24) or CCI (n = 47) injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight) or vehicle injections on post-injury days (PID) 1-7, subjected to behavioral testing from PID 9-27, and analyzed for lesion size at PID 28. RESULTS: The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats. CONCLUSION: Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits.

Neuroendoscopic Resection of Intraventricular Tumors and Cysts through a Working Channel with a Variable Aspiration Tissue Resector: A Feasibility and Safety Study.

Pure neuroendoscopic resection of intraventricular lesions through a burr hole is limited by the instrumentation that can be used with a working channel endoscope. We describe a safety and feasibility study of a variable aspiration tissue resector, for the resection of a variety of intraventricular lesions. Our initial experience using the variable aspiration tissue resector involved 16 patients with a variety of intraventricular tumors or cysts. Nine patients (56%) presented with obstructive hydrocephalus. Patient ages ranged from 20 to 88 years (mean 44.2). All patients were operated on through a frontal burr hole, using a working channel endoscope. A total of 4 tumors were resected in a gross total fashion and the remaining intraventricular lesions were subtotally resected. Fifteen of 16 patients had relief of their preoperative symptoms. The 9 patients who presented with obstructive hydrocephalus had restoration of cerebrospinal fluid flow though one required a ventriculoperitoneal shunt. Three patients required repeat endoscopic resections. Use of a variable aspiration tissue resector provides the ability to resect a variety of intraventricular lesions in a safe, controlled manner through a working channel endoscope. Larger intraventricular tumors continue to pose a challenge for complete removal of intraventricular lesions.

Shunt infection in the first year of life.

OBJECT: Children younger than 1 year of age are unique in their physiology and comorbidities. Reports in the literature suggest that the risk factors for shunt infection may be different in this population compared with older children. Importantly, these infants often have other congenital malformations requiring various surgical interventions, which impose an additional risk of infection. METHODS: In the 3-year period between 2008 and 2010, 270 patients underwent initial CSF shunt placement during the 1st year of life. Clinical characteristics, hospital course, and shunt infections were prospectively recorded in the practice and hospital electronic medical record. Special attention was given to types and timing of other invasive procedures and their relationship with shunt infection. RESULTS: The average gestational age was 33.6 weeks, and the average birth weight was 2333 g. The average weight at the time of shunt insertion was 4281 g. Prior to shunt insertion, 120 patients underwent 148 surgical procedures, including ventricular access device insertion (n = 63), myelomeningocele closure (n = 37), and cardiac procedures (n = 11), among others. In the 12-month period after shunt insertion, 121 of the 270 patients underwent 135 surgical procedures, which included 79 CSF shunt revisions. Shunt infection occurred in 22 patients, and organisms were identified in 20 cases. Univariate analysis showed that of the very prematurely born infants (gestational age < 30 weeks), those who underwent preshunt cardiac surgery and any surgical procedures within 30 days after the shunt insertion were at a greater risk of shunt infection. In multivariate analysis, preshunt cardiac surgery and surgical procedures within 30 days postshunt placement were significant risk factors independent of gestational age, birth weight, and history of shunt revisions. CONCLUSIONS: The results of this study suggest that surgical procedures within 30 days after shunt insertion and preshunt cardiac surgery are associated with a greater risk of shunt infection in children in whom these devices were inserted during the 1st year of life.

Surgical technique for spinal cord delivery of therapies: demonstration of procedure in gottingen minipigs.

This is a compact visual description of a combination of surgical technique and device for the delivery of (gene and cell) therapies into the spinal cord. While the technique is demonstrated in the animal, the procedure is FDA-approved and currently being used for stem cell transplantation into the spinal cords of patients with ALS. While the FDA has recognized proof-of-principle data on therapeutic efficacy in highly characterized rodent models, the use of large animals is considered critical for validating the combination of a surgical procedure, a device, and the safety of a final therapy for human use. The size, anatomy, and general vulnerability of the spine and spinal cord of the swine are recognized to better model the human. Moreover, the surgical process of exposing and manipulating the spinal cord as well as closing the wound in the pig is virtually indistinguishable from the human. We believe that the healthy pig model represents a critical first step in the study of procedural safety.

Neuroprotective efficacy of estrogen in experimental spinal cord injury in rats.

Spinal cord injury (SCI) leads to neurological deficits and motor dysfunction. Methylprednisolone, the only drug used for treating SCI, renders limited neuroprotection and remains controversial. Estrogen is one of the most potent multiactive neuroprotective agents and it is currently under investigation in our laboratory for its efficacy in SCI. The present review briefly summarizes our earlier findings on the therapeutic potential of pharmacological/supraphysiological levels of estrogen in SCI and outlines our ongoing research, highlighting the efficacy of physiological levels of estrogen against neuronal injury, axonal degeneration, and gliosis and also the molecular mechanisms of such neuroprotection in experimental SCI. Furthermore, our ongoing studies designed to explore the different translational potential of estrogen therapy suggest that this multiactive steroid may act as an adjunct therapy to promote angiogenesis, thus enhancing the functional recovery following chronic SCI. Taken together, these studies confirm that estrogen is a potential therapeutic agent for treating SCI.