Safety assessment of intraparenchymal central nervous system biopsies: Single institution healthcare value review.

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.

Publisher Correction: α-SNAP is expressed in mouse ovarian granulosa cells and plays a key role in folliculogenesis and female fertility.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Patient and treatment factors associated with survival among pediatric glioblastoma patients: A Surveillance, Epidemiology, and End Results study.

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 aged <20 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 subjects <3 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.

α-SNAP is expressed in mouse ovarian granulosa cells and plays a key role in folliculogenesis and female fertility.

The balance between ovarian folliculogenesis and follicular atresia is critical for female fertility and is strictly regulated by a complex network of neuroendocrine and intra-ovarian signals. Despite the numerous functions executed by granulosa cells (GCs) in ovarian physiology, the role of multifunctional proteins able to simultaneously coordinate/modulate several cellular pathways is unclear. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (α-SNAP) is a multifunctional protein that participates in SNARE-mediated membrane fusion events. In addition, it regulates cell-to-cell adhesion, AMPK signaling, autophagy and apoptosis in different cell types. In this study we examined the expression pattern of α-SNAP in ovarian tissue and the consequences of α-SNAP (M105I) mutation (hyh mutation) in folliculogenesis and female fertility. Our results showed that α-SNAP protein is highly expressed in GCs and its expression is modulated by gonadotropin stimuli. On the other hand, α-SNAP-mutant mice show a reduction in α-SNAP protein levels. Moreover, increased apoptosis of GCs and follicular atresia, reduced ovulation rate, and a dramatic decline in fertility is observed in α-SNAP-mutant females. In conclusion, α-SNAP plays a critical role in the balance between follicular development and atresia. Consequently, a reduction in its expression/function (M105I mutation) causes early depletion of ovarian follicles and female subfertility.

Is there a "July effect" in pediatric neurosurgery?

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: For the majority of morbidity and mortality events, no significant difference was found in occurrence rates between the first and last quarters.

Transfrontal and Transsphenoidal Approaches to Pediatric Craniopharyngioma: A National Perspective.

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 (ß-coefficient 2.3, p = 0.01), more diagnoses (ß-coefficient 1.2, p < 0.001), and TF approach (ß- coefficient 3.0, p < 0.01) were associated with increased LOS. A higher number of diagnoses were associated with nonhome discharge destinations (ß-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.

Outcomes of endoscopic third ventriculostomy in adults.

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<0.001), as was history of previous shunt (HR: 2.45, p<0.001). Among patients with repeat surgeries, median time to failure was 25days. This study represents a longitudinal analysis of nationwide ETV practice over 9years. Success rate in this large cohort is similar to that published by other single-center retrospective studies. Age and geographic variation may be associated with surgeon choice of ETV or shunt placement after failure of the initial ETV.

Revision surgeries following vagus nerve stimulator implantation.

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 <1%, <3%, 4-10%, and <1% for VNS electrode revision, battery revision/removal, battery replacement/implantation, and infection washout, respectively. For electrode revision and battery revision/replacement, the incidence was higher in the first year and for battery replacement in later years. Age, sex, insurance type, or geographic region did not significantly impact event occurrence. Implant-related revision surgeries are rare. Some events occur more often in certain follow-up years than others; none are significantly impacted by age, sex, insurance type, or geographic region. The most common reason for revision was battery replacement several years after VNS placement.

Complications after craniosynostosis surgery: comparison of the 2012 Kids' Inpatient Database and Pediatric NSQIP Database.

OBJECT Research conducted using large administrative data sets has increased in recent decades, but reports on the fidelity and reliability of such data have been mixed. The goal of this project was to compare data from a large, administrative claims data set with a quality improvement registry in order to ascertain similarities and differences in content. METHODS Data on children younger than 12 months with nonsyndromic craniosynostosis who underwent surgery in 2012 were queried in both the Kids' Inpatient Database (KID) and the American College of Surgeons Pediatric National Surgical Quality Improvement Program (Peds NSQIP). Data from published clinical craniosynostosis surgery series are reported for comparison. RESULTS Among patients younger than 12 months of age, a total of 1765 admissions were identified in KID and 391 in Peds NSQIP in 2012. Only nonsyndromic patients were included. The mean length of stay was 3.2 days in KID and 4 days in Peds NSQIP. The rates of cardiac events (0.5% in KID, 0.3% in Peds NSQIP, and 0.4%-2.2% in the literature), stroke/intracranial bleeds (0.4% in KID, 0.5% in Peds NSQIP, and 0.3%-1.2% in the literature), infection (0.2% in KID, 0.8% in Peds NSQIP, and 0%-8% in the literature), wound disruption (0.2% in KID, 0.5% in Peds NSQIP, 0%-4% in the literature), and seizures (0.7% in KID, 0.8% in Peds NSQIP, 0%-0.8% in the literature) were low and similar between the 2 data sets. The reported rates of blood transfusion (36% in KID, 64% in Peds NSQIP, and 1.7%-100% in the literature) varied between the 2 data sets. CONCLUSIONS Both the KID and Peds NSQIP databases provide large samples of surgical patients, with more cases reported in KID. The rates of complications studied were similar between the 2 data sets, with the exception of blood transfusion events where the retrospective chart review process of Peds NSQIP captured almost double the rate reported in KID.

Analysis of survival in pediatric high-grade brainstem gliomas: A population-based study.

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 (<18 years old) from the SEER database with histologically confirmed diagnoses of primary high-grade gliomas (World Health Organization Grade III/IV) of the brainstem. In univariate and multivariate analysis, we analyzed the relationship between demographic (age, gender, race, diagnosis date), histologic (AA, GBM), and treatment (surgery, radiation) factors on survival. RESULTS: In our cohort of 124 patients, those with AA had a median survival of 13 months and those with GBM 9 months. Higher-grade tumors were associated with statistically significantly increased mortality (hazard ratio [HR]: 1.74, confidence intervals [CIs]: 1.17-2.60). Surgical intervention was associated with a significantly lower mortality, either alone (HR: 0.14, CI: 0.04-0.5) or in combination with radiation (HR: 0.35, CI: 0.15-0.82). Radiation therapy alone was significantly associated with decreased mortality within the first 9 months after diagnosis but not with overall mortality. No demographic characteristics were significantly associated with mortality. CONCLUSIONS: Outcome remains poor in the pediatric high-grade brainstem glioma population. Survival is correlated with lower-grade tumor histology, radiation therapy only in the first 9 months after diagnosis, and surgical resection.

Predictors of survival in patients with spinal ependymoma.

OBJECTIVES: We aimed to examine the impact of demographic and treatment factors on overall survival among spinal ependymoma patients. METHODS: Using data from Surveillance, Epidemiology, and End Results (SEER) from 1990-2008, we evaluated subjects with histologically confirmed spinal cord ependymoma. RESULTS: 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). DISCUSSION: 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.

The Impact of Insurance, Race, and Ethnicity on Age at Surgical Intervention among Children with Nonsyndromic Craniosynostosis.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Trends in outcomes, complications, and hospitalization costs for hemispherectomy in the United States for the years 2000-2009.

OBJECTIVE: Hemispherectomy is an established surgical treatment for carefully selected pediatric patients with intractable epilepsy. Published perioperative data report low mortality rates and seizure reduction rates of 50-89%. This study investigates trends in the demographics, hospital utilization, and in-hospital complication rates of patients undergoing hemispherectomy over the past decade in the United States, using the nationally representative Kids' Inpatient Database (KID). METHODS: The KID was queried for all discharges with the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code for hemispherectomy in the years 2000, 2003, 2006, and 2009. The patient cohorts from these four time points were compared, analyzing differences in demographic data, insurance and payer status, total cost, length of stay, in-hospital mortality, and complications. National estimates and 95% confidence intervals are reported given the weighted sample design of KID. RESULTS: This study identified an estimated total of 552 hospital admissions for hemispherectomy surgery during the years studied in this cohort. The incidence of this procedure increased from 1.2/100,000 admissions in 2000 to 2.2/100,000 in 2009 (p=0.05). Mean age was 6.7 years (range 0-20). There were no significant changes in demographics (age, gender, or race), hospital descriptors (size or type), insurance type, or zip code income quartile. There was a significant increase in total cost, from $42,807 in 2003 to $57,443 in 2009 (p=0.015) (adjusted to 2009 dollars). There were no trends in postoperative complications. In-hospital mortality occurred in five subjects (0.9%). Ventricular shunt placement during hemispherectomy hospitalizations increased over time from 6.7% to 16.5% (p=0.056). Hospitals that performed two or more hemispherectomies yearly had a significantly decreased incidence of in-hospital mortality (odds ratio [OR] 0.08, p=0.04) and an increased incidence of blood transfusion (OR 3.7, p=0.01) compared to hospitals that performed 0-1 procedures a year. SIGNIFICANCE: Hemispherectomy procedures increased slightly in frequency over the past decade, with no change in demographic characteristics of the patients over time. Rates of mortality and perioperative complications remained low. Total costs have increased significantly over time. In-hospital mortality was lower in higher volume hospitals.

Treatment of pediatric Grade II spinal ependymomas: a population-based study.

OBJECT: Grade II spinal cord ependymomas occurring in pediatric patients are exceptionally rare neoplasms. In this paper the authors use a national cancer database to determine patient demographics, treatment patterns, and associated outcomes of this cohort. METHODS: The Surveillance Epidemiology and End Results (SEER) database was used to analyze subjects younger than 18 years with histologically confirmed diagnoses of Grade II spinal cord ependymoma from the years 1973 to 2008. Descriptive data on the demographic characteristics of this cohort and the associated treatment patterns are shown. The Kaplan-Meier method was used to estimate overall survival at 1, 2, 5, and 10 years. RESULTS: This cohort comprised 64 pediatric subjects with Grade II spinal ependymoma. The median age was 13 years, nearly half of the patients were male, and most were white (84%). The median follow-up was 9.2 years. Overall survival at 5 and 10 years was 86% and 83%, respectively. Gross-total resection was achieved in 57% of subjects, and radiation therapy was administered to 36%. Radiation therapy was administered to 78% of subjects after subtotal resection but only to 19% of patients after gross-total resection; this difference was significant (p < 0.001). In a multivariate regression model analyzing sex, age at diagnosis, year of diagnosis, radiotherapy, and extent of resection, female sex was found to be an independent predictor of decreased mortality (HR 0.15 [95% CI 0.02-0.94], p = 0.04). CONCLUSIONS: These data show long-term outcomes for pediatric patients with Grade II spinal ependymoma. Radiotherapy was more likely to be administered in cases of subtotal resection than in cases of gross-total resection. Female sex is associated with decreased mortality, while other demographic or treatment modalities are not.

Putative height acceleration following tethered cord release in children.

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.

AP-1A controls secretory granule biogenesis and trafficking of membrane secretory granule proteins.

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 twofold 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. Coimmunoprecipitation 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.

Prognostic factors and survival in primary adult high grade brainstem astrocytoma: a population based study from 1973-2008.

Adult brainstem astrocytomas are a rare and heterogeneous group of malignancies. Most reports represent low-grade gliomas. This study used the Surveillance, Epidemiology and End Results (SEER) database to analyze the association between survival and demographic factors, tumor histology, and treatment characteristics among adult patients with high-grade brainstem astrocytoma (HGBSA). Adult patients with histologically confirmed diagnoses of primary HGBSA were studied. In univariate and multivariate analysis, we investigated the effect of demographics, tumor histology and treatment modality on survival. Overall median survival in the cohort of 240 adult patients was 7months, with 1, 2, 5 and 10year survival rates of 33.2%, 19.7%, 10.1%, and 8.3%, respectively. Age >50years (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.45-2.70, p<0.001) and grade IV versus grade III tumor (HR 1.61, 95% CI 1.15-2.26, p=0.006) were associated with statistically significant increased mortality in multivariate analyses. Surgical intervention trended toward association with lower mortality (HR 0.68, 95% CI 0.47-1.01, p=0.055). Our findings suggest that in patients with HGBSA, younger age and lower-grade histology are associated with better prognosis. Surgical intervention trended towards a significant association with better outcome, while radiation treatment was not associated with a statistically significant benefit in survival.