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The study objective was to evaluate a single institution experience with adult stereotactic intracranial biopsies and review any projected cost savings as a result of bypassing intensive care unit (ICU) admission and limited routine head computed tomography (CT). The authors retrospectively reviewed all stereotactic intracranial biopsies performed at a single institution between February 2012 and March 2019. Primary data collection included ICU length of stay (LOS), hospital LOS, ICU interventions, need for reoperation, and CT use. Secondarily, location of lesion, postoperative hematoma, neurological deficit, pathology, and preoperative coagulopathy data were collected. There were 97 biopsy cases (63% male). Average age, ICU LOS, and total hospital stay were 58.9 years (range; 21–92 years), 2.3 days (range; 0–40 days), and 8.8 days (range 1–115 days), respectively. Seventy-five (75 of 97) patients received a postoperative head CT. No patients required medical or surgical intervention for complications related to biopsy. Eight patients required transfer from the ward to the ICU (none directly related to biopsy). Nine patients transferred directly to the ward postoperatively (none required transfer to ICU). Of the patients who did not receive CT or went directly to the ward, none had extended LOS or required transfer to ICU for neurosurgical concerns. Eliminating routine head CT and ICU admission translates to approximately $584,971 in direct cost savings in 89 cases without a postoperative ICU requirement. These practice changes would save patients’ significant hospitalization costs, decrease healthcare expenditures, and allow for more appropriate hospital resource use.

Glioblastoma (GBM) is a rare malignancy in children. The United States Surveillance, Epidemiology, and End Results (SEER) database allows large-scale analyses of clinical characteristics and prognostic features. We used it to study patients aged20 years with histologically confirmed GBM (2000-2010) and examined the relationship between patient demographics, tumor characteristics, patterns of treatment, and outcomes. The primary outcome was disease-specific survival. 302 subjects were identified, with median age 11 years. Median follow-up was 32 months (95% CI 27-39). 34.4% had gross total resection (GTR). 61% underwent radiation after surgery (17% of subjects3 years, 67% of those aged 4-19 years). Median survival and 2-year survival rates were 20 months and 46.9%, respectively. In multivariate analyses, age, tumor location, extent of resection, and year of diagnosis were significantly associated with the primary outcome. Compared to those aged 0-4 years, subjects aged 5-9 years and 10-14 years had higher risk of mortality. Infratentorial tumor location (HR 2.0, 95% CI 1.2-3.3, p = 0.007) and subtotal resection (HR 2.04, 95% CI 1.4-3.0, p 0.001) were associated with increased mortality. Later year of diagnosis was significantly associated with decreased risk of death (HR 0.93, 95% CI 0.9-0.99, p = 0.031). There was no association between sex, race, region, or tumor size and the primary outcome. Repeat analyses examining all-cause mortality identified the same risk factors as for CNS cancer-specific mortality. Younger age, supratentorial location, GTR, and later year of diagnosis were associated with improved survival.

The belief that July, when resident physicians’ training year begins, may be associated with increased risk of patient morbidity and mortality is known as the “July effect.” This study aimed to compare complication rates after pediatric neurosurgical procedures in the first versus last academic quarters in two national datasets. Data were extracted from the National Surgical Quality Improvement Program-Pediatrics (NSQIP-P) database for year 2012 for 30-day complication events and the Kids’ Inpatient Database (KID) for year 2012 for in-hospital complication events after pediatric neurosurgical procedures. Descriptive and analytic statistical methods were used to characterize the impact of seasonal variation between the first and last quarters on complications. Three thousand six hundred twenty-four procedures in the NSQIP-P dataset and 14,855 hospitalizations in KID were included in the study cohort. No significant difference was observed between the first and fourth quarters for these complication events: wound disruption/dehiscence, wound infection, nerve injury, bleeding requiring transfusion, central line-associated BSI, deep venous thrombosis/pulmonary embolism, urinary tract infection, renal failure, re-intubation/pulmonary failure, cardiac arrest, stroke, coma, and death. There was no difference in the average length of stay or average length of surgical time. In the NSQIP-P, the first quarter was associated with a significantly increased incidence of pneumonia and unplanned re-operation; there was a trend towards increased incidence of unplanned re-admission and sepsis. In KID, there was no difference in the rate of pneumonia or sepsis. For the majority of morbidity and mortality events, no significant difference was found in occurrence rates between the first and last quarters.

Introduction: This study compared transsphenoidal (TS) and transfrontal (TF) approaches to craniopharyngioma utilizing a national database. Methods: The Kids' Inpatient Database (2003, 2006, and 2009) was surveyed for patients with a diagnosis of craniopharyngioma who underwent a subset of surgical interventions to compare TS and TF surgery. Demographics, hospital variables, and complications/comorbidities were analyzed with multivariate regression. Results: 314 admissions (TS = 104, TF = 210) were identified. The mean age was 14.8 (TS) versus 9.8 (TF) years (p < 0.001). The mean number of diagnoses was 4.6 (TS) versus 6.2 (TF) (p < 0.001). Diabetes insipidus was associated with 38% (TS) and 69% (TF). Cerebrospinal fluid (CSF) leak affected 19% TS and 4% TF resections. Other complications and comorbidities included postoperative stroke (2% TS vs. 5% TF), panhypopituitarism (5 vs. 8%), death (0 vs. 1%), cranial nerve deficits (1 vs. 6%), thrombotic events (7 vs. 17%), and seizures (0 vs. 12%). 98% of patients were discharged home after a mean 6-day length of stay (LOS) after TS, whereas 90% of TF patients had a LOS of 12 days. TS cases were more likely to be privately insured (68%) and from higher income brackets (61%) than TF ones (56 and 2%, respectively) (p < 0.05). In multivariate regression models adjusting for age, sex, race, number of diagnoses, surgical approach, hospital volume, and insurance type, the TS approach was associated with an increased incidence of CSF leak (OR 10, p < 0.001). More documented diagnoses (OR 16-60, p < 0.01) and TF approach (OR 2.6, p < 0.01) were associated with an increased incidence of other complications and comorbidities. Age younger than 10 (β-coefficient 2.3, p = 0.01), more diagnoses (β-coefficient 1.2, p < 0.001), and TF approach (β- coefficient 3.0, p < 0.01) were associated with increased LOS. A higher number of diagnoses were associated with nonhome discharge destinations (β-coefficient 1.29, p < 0.001). Conclusion: TS surgery was associated with an increased incidence of CSF leak but shorter LOS; TF surgery was associated with an increased incidence of other complications. Patients undergoing TS surgery were more likely to have private insurance and a higher family income bracket.

Endoscopic third ventriculostomy (ETV) is an alternative to ventriculoperitoneal shunting for treatment of hydrocephalus. Studies have reported favorable outcomes for up to three-quarters of adult patients. We performed the first ETV outcomes study using an administrative claims database, examining current practice for adult patients in the United States. We interrogated the Truven Health MarketScan® database for Current Procedural Terminology codes corresponding to ETV and ventriculoperitoneal shunt from 2003- to 2011, including patients over 18years and data from initial and subsequent hospitalizations. ETV failure was defined as any subsequent ETV or shunt procedure. Five hundred twenty-five patients underwent ETV with 6months minimum follow-up. Mean age was 45.9years (range: 18-86years). Mean follow-up was 2.2years (SD: 1.6years, range: 0.5-8.4years). Etiology of hydrocephalus was 21.3% tumor, 9.0% congenital/aqueductal stenosis, 15.8% hemorrhage, and 53.9% others. ETV was successful in 74.7% of patients. Of 133 who failed, 25 had repeat ETV; 108 had shunt placement. Longer length of stay for index surgery was associated with higher risk of failure (hazard ratio (HR): 1.03, p

The vagus nerve stimulator (VNS) has been shown to provide a safe, albeit costly, treatment for intractable epilepsy. We aimed to analyze the incidence, timing, and clinical/demographic associations of revision surgery post-VNS implantation in epilepsy patients. The Thomson Reuters MarketScan database, containing data from 23-50million individuals, was used. Epilepsy patients receiving VNS implantations from 2003 to 2009 were identified by Current Procedural Terminology and International Classification Of Diseases Ninth Revision codes. Incidence and timing of subsequent implant-related surgeries were recorded. Events were described using time-to-event methodology, with Kaplan-Meier failure estimation/Cox proportional hazard models adjusted for clinical/demographic factors. In 1234 patients, average incidence of revision surgeries over 6years of follow-up were

To examine the impact of demographic factors, including insurance type, family income, and race/ethnicity, on patient age at the time of surgical intervention for craniosynostosis surgery in the US.The Kids' Inpatient Database was queried for admissions of children younger than 3 years of age undergoing craniosynostosis surgery in 2009. Descriptive data regarding age at surgery for various substrata are reported. Multivariate regression was used to evaluate the effect of patient and hospital characteristics on the age at surgery.Children with private insurance were, on average, 6.8 months of age (95% CI 6.2-7.5) at the time of surgery; children with Medicaid were 9.1 months old (95% CI 8.4-9.8). White children received surgery at mean age of 7.2 months (95% CI 6.5-8.0) and black and Hispanic children at a mean age of 9.1 months (95% CI 8.2-10.1). Multivariate regression analysis found Medicaid insurance (beta coefficient [B]=1.93, P.001), black or Hispanic race/ethnicity (B=1.34, P=.022), and having 2 or more chronic conditions (B=2.86, P.001) to be significant independent predictors of older age at surgery.Public insurance and nonwhite race/Hispanic ethnicity were statistically significant predictors for older age at surgery, adjusted for sex, zip code median family income, year, and hospital factors such as size, type, region, and teaching status. Further research into these disparities is warranted.

We aimed to examine the impact of demographic and treatment factors on overall survival among spinal ependymoma patients.Using data from Surveillance, Epidemiology, and End Results (SEER) from 1990-2008, we evaluated subjects with histologically confirmed spinal cord ependymoma.We identified 1,353 patients with spinal ependymoma (mean age 43.5 years). Among these, 26 had anaplastic ependymoma (AE), 374 had myxopapillary ependymoma (MPE), and 953 had other low-grade ependymoma (non-MPE). Median follow-up was 61 months. Overall survival at 5 years was 97% for MPE, 92% for low-grade non-MPE, and 73% for AE. Gross total resection (GTR) was achieved in 58% of subjects with MPE, 51% with low-grade non-MPE, and 50% with AE. Radiation occurred more often after subtotal resection (STR) than after GTR, and more often among those with anaplastic histology. Histology and extent of surgical resection were significant prognostic factors in multivariate analyses. Compared to MPE, subjects with low-grade non-MPE had a higher risk of mortality at 5 years (HR 2.35, P = 0.03), as did subjects with AE (HR 8.63, P 0.01). Compared to GTR, STR was associated with an increased risk of mortality at 5 years (HR 2.2, P = 0.01), as was biopsy only (HR 2.05, P = 0.03) and no surgery (HR 4.97, P 0.01). Among patients with either STR or GTR, adjuvant radiotherapy did not confer a survival benefit at 5 years (STR: HR 2.29, P = 0.07, and GTR: HR 2.2, P = 0.12).We found that lower grade histology and higher extent of surgical resection were significant prognostic factors for more favourable survival outcomes for spinal ependymoma patients.

Object Tethered cord (TC) is a neurological disorder caused by tissue attachments that limit the normal movement of the spinal cord. A TC can be unmasked by a cutaneous abnormality or manifest clinically in myriad neurological, urological, and orthopedic symptoms. The relationship between TC and height is previously unknown. This study investigates the association between TC release and changes in height profiles in the pediatric population. Methods Fifty-two children undergoing first-time TC release at a single institution were examined retrospectively. Clinical symptoms, radiographic findings, pre- and postoperative height, and height-for-age percentiles were recorded and analyzed. Results Children with TC experienced a statistically significant increase in age-adjusted height percentiles after TC release (p = 0.0028), with a mean increase of 7 percentile points (from 48.1st to 54.9th percentile). When stratified by age, children 5 years or older (5–18 years) demonstrated a mean percentile increase of 10 percentile points (from 46.7th to 56.4th percentile) (p = 0.0001). Among the same age group, this effect scaled significantly with age (p = 0.02, beta coefficient −1.3). There was no significant difference in height-for-age after detethering surgery in children younger than 5 years. There was no significant association between the presence of clinical symptoms or specific radiographic findings and height outcomes after surgery. Overall, 56% of TC-related clinical symptoms improved after detethering (mean follow-up 4.6 months). Among children younger than 5 years, 82% of TC-related clinical symptoms improved after detethering (average follow-up 4.5 months); in children 5–18 years, 47% of symptoms improved after detethering (average follow-up 4.8 months). Conclusions The authors observed a statistically significant gain in height-for-age percentiles in children undergoing surgical release of TC. The authors' data suggest that such gains may be more significant in older children (≥ 5 years) and the increase appears to scale positively with youth in the older cohort. In this study, postoperative height gains did not appear to correlate with the presence of TC-related clinical symptoms or radiographic findings. Further investigation is necessary to elucidate any potential correlation between release of TC and height changes in children postoperatively.

The adaptor protein 1A complex (AP-1A) transports cargo between the trans-Golgi network (TGN) and endosomes. In professional secretory cells, AP-1A also retrieves material from immature secretory granules (SGs). The role of AP-1A in SG biogenesis was explored using AtT-20 corticotrope tumor cells expressing reduced levels of the AP-1A μ1A subunit. A two-fold reduction in μ1A resulted in a decrease in TGN cisternae and immature SGs and the appearance of regulated secretory pathway components in non-condensing SGs. Although basal secretion of endogenous SG proteins was unaffected, secretagogue-stimulated release was halved. The reduced μ1A levels interfered with the normal trafficking of carboxypeptidase D (CPD) and peptidylglycine α-amidating monooxygenase-1 (PAM-1), integral membrane enzymes that enter immature SGs. The non-condensing SGs contained POMC products and PAM-1, but not CPD. Based on metabolic labeling and secretion experiments, the cleavage of newly synthesized PAM-1 into PHM was unaltered, but PHM basal secretion was increased in sh-μ1A PAM-1 cells. Despite lacking a canonical AP-1A binding motif, yeast two-hybrid studies demonstrated an interaction between the PAM-1 cytosolic domain and AP-1A. Co-immunoprecipitation experiments with PAM-1 mutants revealed an influence of the luminal domains of PAM-1 on this interaction. Thus, AP-1A is crucial for normal SG biogenesis, function and composition.

Primary intramedullary spinal cord tumors are a rare entity, comprising 4–10 % of all spinal cord tumors. The current report presents data on intramedullary spinal cord anaplastic astrocytomas and glioblastomas in adults using the national surveillance, epidemiology, and end results database (1973–2008), and evaluates the impact of demographic and treatment factors on survival. Eighty nine adults were evaluated (mean age of 43 years); 49 % of patients had anaplastic astrocytoma and 51 % of patients had glioblastoma. 88 % of patients had surgical intervention and 85 % of patients had radiotherapy. In univariate analysis, male gender (HR = 0.50, CI: 0.29–0.86, P = 0.01), surgical treatment (HR = 0.37, CI: 0.15–0.93, P = 0.03), and tumor histology (HR = 1.83, CI: 1.06–3.18, P = 0.03) were significant predictors of survival. Results remained significant or marginally significant after multivariate adjustment analyses. Adjuvant radiotherapy and age at diagnosis did not have a significant influence on survival. Future prospective studies from collaborative institutions combining richer detail in perioperative treatment, radiotherapy dosing, chemotherapy treatment, neurologic examinations, functional outcomes, and quality of life measures would contribute to more concrete, evidence-based treatment protocols for adult patients with primary malignant spinal cord astrocytomas.

Object Attention deficit hyperactivity disorder (ADHD) and traumatic brain injury (TBI) are significant independent public health concerns in the pediatric population. This study explores the impact of a premorbid diagnosis of ADHD on outcome following mild TBI. Methods The charts of all patients with a diagnosis of mild closed head injury (CHI) and ADHD who were admitted to Children's Hospital of Pittsburgh between January 2003 and December 2010 were retrospectively reviewed after institutional review board approval was granted. Patient demographics, initial Glasgow Coma Scale (GCS) score, hospital course, and King's Outcome Scale for Childhood Head Injury (KOSCHI) score were recorded. The results were compared with a sample of age-matched controls admitted with a diagnosis of CHI without ADHD. Results Forty-eight patients with mild CHI and ADHD, and 45 patients with mild CHI without ADHD were included in the statistical analysis. Mild TBI due to CHI was defined as an initial GCS score of 13–15. The ADHD group had a mean age of 12.2 years (range 6–17 years), and the control group had a mean age of 11.14 years (range 5–16 years). For patients with mild TBI who had ADHD, 25% were moderately disabled (KOSCHI Score 4b), and 56% had completely recovered (KOSCHI Score 5b) at follow-up. For patients with mild TBI without ADHD, 2% were moderately disabled and 84% had completely recovered at follow-up (p < 0.01). Patients with ADHD were statistically significantly more disabled after mild TBI than were control patients without ADHD, even when controlling for age, sex, initial GCS score, hospital length of stay, length of follow-up, mechanism of injury, and presence of other (extracranial) injury. Conclusions Patients who sustain mild TBIs in the setting of a premorbid diagnosis of ADHD are more likely to be moderately disabled by the injury than are patients without ADHD.

Tyrosine-based signals fitting the YXXO motif mediate sorting of transmembrane proteins to endosomes, lysosomes, the basolateral plasma membrane of polarized epithelial cells, and the somatodendritic domain of neurons through interactions with the homologous μ1, μ2, μ3, and μ4 subunits of the corresponding AP-1, AP-2, AP-3, and AP-4 complexes. Previous x-ray crystallographic analyses identified distinct binding sites for YXXO signals on μ2 and μ4, which were located on opposite faces of the proteins. To elucidate the mode of recognition of YXXO signals by other members of the μ family, we solved the crystal structure at 1.85 A resolution of the C-terminal domain of the μ3 subunit of AP-3 (isoform A) in complex with a peptide encoding a YXXO signal (SDYQRL) from the trans-Golgi network protein TGN38. The μ3A C-terminal domain consists of an immunoglobulin-like β-sandwich organized into two subdomains, A and B. The YXXO signal binds in an extended conformation to a site on μ3A subdomain A, at a location similar to the YXXO-binding site on μ2 but not μ4. The binding sites on μ3A and μ2 exhibit similarities and differences that account for the ability of both proteins to bind distinct sets of YXXO signals. Biochemical analyses confirm the identification of the μ3A site and show that this protein binds YXXO signals with 14–19 μm affinity. The surface electrostatic potential of μ3A is less basic than that of μ2, in part explaining the association of AP-3 with intracellular membranes having less acidic phosphoinositides.

Background: The purpose of this study was to use the National Cancer Institutes’ Surveillance, Epidemiology, and End Results (SEER) database to perform a large-scale analysis of brainstem anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Use of the SEER database gave us a larger sample size of this rare tumor type, allowing for the analysis of the relationship between prognostic factors and survival. Materials and Methods: We selected pediatric patients (