Assessing Mobility in Patients With Glioblastoma Using Digital Phenotyping-Piloting the Digital Assessment in Neuro-Oncology.

BACKGROUND AND OBJECTIVES: Digital phenotyping (DP) enables objective measurements of patient behavior and may be a useful tool in assessments of quality-of-life and functional status in neuro-oncology patients. We aimed to identify trends in mobility among patients with glioblastoma (GBM) using DP. METHODS: A total of 15 patients with GBM enrolled in a DP study were included. The Beiwe application was used to passively collect patient smartphone global positioning system data during the study period. We estimated step count, time spent at home, total distance traveled, and number of places visited in the preoperative, immediate postoperative, and late postoperative periods. Mobility trends for patients with GBM after surgery were calculated by using local regression and were compared with preoperative values and with values derived from a nonoperative spine disease group. RESULTS: One month postoperatively, median values for time spent at home and number of locations visited by patients with GBM decreased by 1.48 h and 2.79 locations, respectively. Two months postoperatively, these values further decreased by 0.38 h and 1.17 locations, respectively. Compared with the nonoperative spine group, values for time spent at home and the number of locations visited by patients with GBM 1 month postoperatively were less than control values by 0.71 h and 2.79 locations, respectively. Two months postoperatively, time spent at home for patients with GBM was higher by 1.21 h and locations visited were less than nonoperative spine group values by 1.17. Immediate postoperative values for distance traveled, maximum distance from home, and radius of gyration for patients with GBM increased by 0.346 km, 2.24 km, and 1.814 km, respectively, compared with preoperative values. CONCLUSIONS: :Trends in patients with GBM mobility throughout treatment were quantified through the use of DP in this study. DP has the potential to quantify patient behavior and recovery objectively and with minimal patient burden.

Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas.

The lack of reliable predictive biomarkers to guide effective therapy is a major obstacle to the advancement of therapy for high-grade gliomas, particularly glioblastoma (GBM), one of the few cancers whose prognosis has not improved over the past several decades. With this pilot clinical trial (number NCT04135807), we provide first-in-human evidence that drug-releasing intratumoral microdevices (IMDs) can be safely and effectively used to obtain patient-specific, high-throughput molecular and histopathological drug response profiling. These data can complement other strategies to inform the selection of drugs based on their observed antitumor effect in situ. IMDs are integrated into surgical practice during tumor resection and remain in situ only for the duration of the otherwise standard operation (2 to 3 hours). None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens. Analysis of the specimens provided preliminary evidence of the robustness of the readout, compatibility with a wide array of techniques for molecular tissue interrogation, and promising similarities with the available observed clinical-radiological responses to temozolomide. From an investigational aspect, the amount of information obtained with IMDs allows characterization of tissue effects of any drugs of interest, within the physiological context of the intact tumor, and without affecting the standard surgical workflow.

External Ventricular Drains versus Intraparenchymal Pressure Monitors in the Management of Moderate to Severe Traumatic Brain Injury: Experience at Two Academic Centers over a Decade.

OBJECTIVE: The choice between external ventricular drain (EVD) and intraparenchymal monitor (IPM) for managing intracranial pressure in moderate-to-severe traumatic brain injury (msTBI) patients remains controversial. This study aimed to investigate factors associated with receiving EVD versus IPM and to compare outcomes and clinical management between EVD and IPM patients. METHODS: Adult msTBI patients at 2 similar academic institutions were identified. Logistic regression was performed to identify factors associated with receiving EVD versus IPM (model 1) and to compare EVD versus IPM in relation to patient outcomes after controlling for potential confounders (model 2), through odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 521 patients, 167 (32.1%) had EVD and 354 (67.9%) had IPM. Mean age, sex, and Injury Severity Score were comparable between groups. Epidural hemorrhage (EDH) (OR 0.43, 95% CI 0.21-0.85), greater midline shift (OR 0.90, 95% CI 0.82-0.98), and the hospital with higher volume (OR 0.14, 95% CI 0.09-0.22) were independently associated with lower odds of receiving an EVD whereas patients needing a craniectomy were more likely to receive an EVD (OR 2.04, 95% CI 1.12-3.73). EVD patients received more intense medical treatment requiring hyperosmolar therapy compared to IPM patients (64.1% vs. 40.1%). No statistically significant differences were found in patient outcomes. CONCLUSIONS: While EDH, greater midline shift, and hospital with larger patient volume were associated with receiving an IPM, the need for a craniectomy was associated with receiving an EVD. EVD patients received different clinical management than IPM patients with no significant differences in patient outcomes.

Under pressure-mechanisms and risk factors for orthodontically induced inflammatory root resorption: a systematic review.

BACKGROUND: The application of orthodontic forces causes root resorption of variable severity with potentially severe clinical ramifications. OBJECTIVE: To systematically review reports on the pathophysiological mechanisms of orthodontically induced inflammatory root resorption (OIIRR) and the associated risk factors based on in vitro, experimental, and in vivo studies. SEARCH METHODS: We undertook an electronic search of four databases and a separate hand-search. SELECTION CRITERIA: Studies reporting on the effect of orthodontic forces with/without the addition of potential risk factors on OIIRR, including (1) gene expression in in-vitro studies, the incidence root resorption in (2) animal studies, and (3) human studies. DATA COLLECTION AND ANALYSIS: Potential hits underwent a two-step selection, data extraction, quality assessment, and systematic appraisal performed by duplicate examiners. RESULTS: One hundred and eighteen articles met the eligibility criteria. Studies varied considerably in methodology, reporting of results, and variable risk of bias judgements.In summary, the variable evidence identified supports the notion that the application of orthodontic forces leads to (1) characteristic alterations of molecular expression profiles in vitro, (2) an increased rate of OIIRR in animal models, as well as (3) in human studies. Importantly, the additional presence of risk factors such as malocclusion, previous trauma, and medications like corticosteroids increased the severity of OIIRR, whilst other factors decreased its severity, including oral contraceptives, baicalin, and high caffeine. CONCLUSIONS: Based on the systematically reviewed evidence, OIIRR seems to be an inevitable consequence of the application of orthodontic forces-with different risk factors modifying its severity. Our review has identified several molecular mechanisms that can help explain this link between orthodontic forces and OIIRR. Nevertheless, it must be noted that the available eligible literature was in part significantly confounded by bias and was characterized by substantial methodological heterogeneity, suggesting that the results of this systematic review should be interpreted with caution. REGISTRATION: PROSPERO (CRD42021243431).

Deep neural networks allow expert-level brain meningioma segmentation and present potential for improvement of clinical practice.

Accurate brain meningioma segmentation and volumetric assessment are critical for serial patient follow-up, surgical planning and monitoring response to treatment. Current gold standard of manual labeling is a time-consuming process, subject to inter-user variability. Fully-automated algorithms for meningioma segmentation have the potential to bring volumetric analysis into clinical and research workflows by increasing accuracy and efficiency, reducing inter-user variability and saving time. Previous research has focused solely on segmentation tasks without assessment of impact and usability of deep learning solutions in clinical practice. Herein, we demonstrate a three-dimensional convolutional neural network (3D-CNN) that performs expert-level, automated meningioma segmentation and volume estimation on MRI scans. A 3D-CNN was initially trained by segmenting entire brain volumes using a dataset of 10,099 healthy brain MRIs. Using transfer learning, the network was then specifically trained on meningioma segmentation using 806 expert-labeled MRIs. The final model achieved a median performance of 88.2% reaching the spectrum of current inter-expert variability (82.6-91.6%). We demonstrate in a simulated clinical scenario that a deep learning approach to meningioma segmentation is feasible, highly accurate and has the potential to improve current clinical practice.

Oral Contraceptive and Menopausal Hormone Therapy Use and Risk of Pituitary Adenoma: Cohort and Case-Control Analyses.

CONTEXT: No prospective epidemiologic studies have examined associations between use of oral contraceptives (OCs) or menopausal hormone therapy (MHT) and risk of pituitary adenoma in women. OBJECTIVE: Our aim was to determine the association between use of OC and MHT and risk of pituitary adenoma in two separate datasets. METHODS: We evaluated the association of OC/MHT with risk of pituitary adenoma in the Nurses' Health Study and Nurses' Health Study II by computing multivariable-adjusted hazard ratios (MVHR) of pituitary adenoma by OC/MHT use using Cox proportional hazards models. Simultaneously, we carried out a matched case-control study using an institutional data repository to compute multivariable-adjusted odds ratios (MVOR) of pituitary adenoma by OC/MHT use. RESULTS: In the cohort analysis, during 6 668 019 person-years, 331 participants reported a diagnosis of pituitary adenoma. Compared to never-users, neither past (MVHR = 1.05; 95% CI, 0.80-1.36) nor current OC use (MVHR = 0.72; 95% CI, 0.40-1.32) was associated with risk. For MHT, compared to never-users, both past (MVHR = 2.00; 95% CI, 1.50-2.68) and current use (MVHR = 1.80; 95% CI, 1.27-2.55) were associated with pituitary adenoma risk, as was longer duration (MVHR = 2.06; 95% CI, 1.42-2.99 comparing more than 5 years of use to never, P trend = .002). Results were similar in lagged analyses, when stratified by body mass index, and among those with recent health care use. In the case-control analysis, we included 5469 cases. Risk of pituitary adenoma was increased with ever use of MHT (MVOR = 1.57; 95% CI, 1.35-1.83) and OC (MVOR = 1.27; 95% CI, 1.14-1.42) compared to never. CONCLUSION: Compared to never use, current and past MHT use and longer duration of MHT use were positively associated with higher risk of pituitary adenoma in 2 independent data sets. OC use was not associated with risk in the prospective cohort analysis and was associated with only mildly increased risk in the case-control analysis.

A non-uniform quantization scheme for visualization of CT images.

Medical science heavily depends on image acquisition and post-processing for accurate diagnosis and treatment planning. The introduction of noise degrades the visual quality of the medical images during the capturing process, which may result in false perception. Therefore, medical image enhancement is an essential topic of research for the improvement of image quality. In this paper, a clustering-based contrast enhancement technique is presented for computed tomography (CT) images. Our approach uses the recursive splitting of data into clusters targeting the maximum error reduction in each cluster. This leads to grouping similar pixels in every cluster, maximizing inter-cluster and minimizing intra-cluster similarities. A suitable number of clusters can be chosen to represent high precision data with the desired bit-depth. We use 256 clusters to convert 16-bit CT scans to 8-bit images suitable for visualization on standard low dynamic range displays. We compare our method with several existing contrast enhancement algorithms and show that the proposed technique provides better results in terms of execution efficiency and quality of enhanced images.

Surgical and Peri-Operative Considerations for Brain Metastases.

INTRODUCTION: Brain metastases are the most common brain tumors in adults, whose management remains nuanced. Improved understanding of risk factors for surgical complications and mortality may guide treatment decisions. METHODS: A nationwide, multicenter analysis was conducted with a retrospective cohort. Adult patients in the 2012-2015 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) databases who received a craniotomy for resection of brain metastasis were included. RESULTS: 3500 cases were analyzed, of which 17% were considered frail and 24% were infratentorial. The most common 30-day medical complications were venous thromboembolism (3%, median time-to-event [TTE] 4.5 days), pneumonia (4%, median TTE 6 days), and urinary tract infections (2%, median TTE 5 days). Reoperation and unplanned readmission occurred in 5% and 12% of patients, respectively. Infratentorial approach and frailty were associated with reoperation before discharge (OR 2.0 for both; p=0.01 and p=0.03 respectively), but not after discharge. Infratentorial approaches conferred heightened risk for readmission for hydrocephalus (OR 5.1, p=0.02) and reoperation for cerebrospinal fluid diversion (OR 7.1, p<0.001).Overall 30-day mortality was 4%, with nearly three-quarters occurring after discharge. Pre-frailty and frailty were associated with increased odds for post-discharge mortality (OR 1.7 and 2.7, p<0.05), but not pre-discharge mortality. We developed a model to identify pre-/peri-operative variables associated with death, including frailty, thrombocytopenia, and high American Society of Anesthesiologists score (AUROC 0.75). CONCLUSIONS: Optimization of metrics contributing to patient frailty and heightened surveillance in patients with infratentorial metastases may be considered in the peri-operative period.

Pearls for Interpreting Neurosurgical Systematic Reviews and Meta-Analyses: Lessons From a Collaborative Effort.

Systematic reviews and meta-analyses in the neurosurgical literature have surged in popularity over the last decade. It is our concern that, without a renewed effort to critically interpret and appraise these studies as high or low quality, we run the risk of the quality and value of evidence-based medicine in neurosurgery being misinterpreted. Correspondingly, we have outlined 4 major domains to target in interpreting neurosurgical systematic reviews and meta-analyses based on the lessons learned by a collaboration of clinicians and academics summarized as 4 pearls. The domains of (1) heterogeneity, (2) modeling, (3) certainty, and (4) bias in neurosurgical systematic reviews and meta-analyses were identified as aspects in which the authors' approaches have changed over time to improve robustness and transparency. Examples of how and why these pearls were adapted were provided in areas of cranial neuralgia, spine, pediatric, and neuro-oncology to demonstrate how neurosurgical readers and writers may improve their interpretation of these domains. The incorporation of these pearls into practice will empower neurosurgical academics to effectively interpret systematic reviews and meta-analyses, enhancing the quality of our evidence-based medicine literature while maintaining a critical focus on the needs of the individual patients in neurosurgery.

Recurrence of Rathke's cleft cysts based on gross total resection of cyst wall: a meta-analysis.

Rathke's cleft cysts (RCCs) are benign growths of the embryological Rathke's pouch. Surgical decompression provides effective symptomatic relief in most cases; however, the effect of gross total resection (GTR) of the cyst wall on recurrence, as well as pituitary function, is unclear. The aim of this meta-analysis was to pool the current literature and ascertain the recurrence control afforded by GTR of the cyst wall compared with subtotal resection (STR). Searches of seven electronic databases from inception to January 2019 were conducted following PRISMA guidelines, resulting in 476 articles to be screened. Outcomes were analyzed using meta-analysis of proportions. A total of 10 retrospective cohort studies satisfied selection criteria, describing 655 surgically managed RCC cases, with 254 (39%) and 401 (61%) achieving GTR and STR of the cyst wall, respectively. GTR was associated with significantly reduced overall RCC recurrence by fixed-effects (FE) modeling (RR, 0.66; 95% CI, 0.45-0.96), but not by random effects (RE) modeling (RR, 0.75; 95% CI, 0.51-1.12). Based on both models, GTR was associated with significantly reduced symptomatic recurrence (RE model, RR, 0.37, 95% CI, 0.14-0.95) and significantly increased postoperative diabetes insipidus (RE model, RR, 2.60; 95% CI, 1.34-5.03). There was insufficient data to evaluate other pituitary axes in this context. The current evidence indicates that GTR of the RCC cyst wall has the potential to affect the incidence of overall and symptomatic RCC recurrences, as well as drive postoperative DI incidence. However, expectations of clinical and pragmatic benefit following cyst wall resection should be titrated carefully against the potential for postoperative and pituitary morbidities which currently remain poorly defined. Greater granularity is required to understand all factors that can influence recurrence and quality of life when evaluating resection of RCC.

Surgical resection of granular cell tumor of the sellar region: three indications.

PURPOSE: This case series evaluates the surgical management of granular cell tumor (GCT) of the sellar region. This rare entity presents a unique diagnostic and surgical challenge. METHODS: Institutional neuropathology databases at Brigham and Women's Hospital and Massachusetts General Hospital were searched for cases with a tissue diagnosis of GCT, and with a location in the sellar region. Patient, treatment, tumor, and follow-up data were extracted. RESULTS: Three patients had a diagnosis of GCT of the sellar region occurring over an 18-year period. All three patients were followed postoperatively at our multidisciplinary pituitary center (median follow-up = 30 months; range 12-30 months). Hormonal disturbances, an incidental lesion requiring diagnosis, and neurological symptoms were indications for surgery in these patients. Two patients underwent a craniotomy and one underwent endoscopic transsphenoidal surgery. All three patients were free of tumor recurrence at last follow-up. In one case tested, positive thyroid transcription factor-1 (TTF-1) immunohistochemistry was observed. CONCLUSION: GCT is generally a benign tumor of the sellar region. Surgical resection is the standard treatment, more recently with transsphenoidal surgery when indicated. Surgical resection results in optimal outcome for patients.

A hierarchical integration deep flexible neural forest framework for cancer subtype classification by integrating multi-omics data.

BACKGROUND: Cancer subtype classification attains the great importance for accurate diagnosis and personalized treatment of cancer. Latest developments in high-throughput sequencing technologies have rapidly produced multi-omics data of the same cancer sample. Many computational methods have been proposed to classify cancer subtypes, however most of them generate the model by only employing gene expression data. It has been shown that integration of multi-omics data contributes to cancer subtype classification. RESULTS: A new hierarchical integration deep flexible neural forest framework is proposed to integrate multi-omics data for cancer subtype classification named as HI-DFNForest. Stacked autoencoder (SAE) is used to learn high-level representations in each omics data, then the complex representations are learned by integrating all learned representations into a layer of autoencoder. Final learned data representations (from the stacked autoencoder) are used to classify patients into different cancer subtypes using deep flexible neural forest (DFNForest) model.Cancer subtype classification is verified on BRCA, GBM and OV data sets from TCGA by integrating gene expression, miRNA expression and DNA methylation data. These results demonstrated that integrating multiple omics data improves the accuracy of cancer subtype classification than only using gene expression data and the proposed framework has achieved better performance compared with other conventional methods. CONCLUSION: The new hierarchical integration deep flexible neural forest framework(HI-DFNForest) is an effective method to integrate multi-omics data to classify cancer subtypes.

Predicting Readmission and Reoperation for Benign Cranial Nerve Neoplasms: A Nationwide Analysis.

OBJECTIVE: Readmission and reoperation are risks in the resection of benign cranial nerve tumors (BCNTs). This report analyzes the impact of patient-level and surgical factors on these adverse outcomes. METHODS: This retrospective cohort review comprised patients with a diagnosis of BCNT enrolled in the American College of Surgeons National Surgical Quality Improvement Program registry from 2011 to 2015. Multivariate logistic regression was used to determine the impact of select medical and operative factors on the primary outcomes of readmission and reoperation within 30 days, adjusted for relevant covariates. RESULTS: We identified 996 patients who underwent resection of a BCNT. The most frequent major complications were readmission (11%), reoperation (8%), surgical site infections (2.6%), and venous thromboembolism (1.5%). The most frequent indications for readmission were management of infection (2.5%), cerebrospinal fluid leak (2.3%), and hydrocephalus (0.5%). Repair of cranial and meningeal defects (3.0%), correction of lagophthalmos (1.2%), and repair of middle ear defects (1.0%) were the most common indications for reoperation. Logistic regression revealed that extremes of age were associated with readmission, whereas preoperative steroid usage, long operative time, and postoperative length of stay >3 days were associated with reoperation (P < 0.05). Obesity trended toward an association with readmission and reoperation. CONCLUSIONS: Extremes of age were associated with readmission; preoperative steroid use, long operative time, and postoperative length of stay >3 days were associated with reoperation. Surgeons should consider these factors when assessing risk of postoperative complications for BCNTs.

Endocrine function and gland volume after endoscopic transsphenoidal surgery for nonfunctional pituitary macroadenomas.

OBJECTIVELoss of pituitary function due to nonfunctional pituitary adenoma (NFPA) may be due to compression of the pituitary gland. It has been proposed that the size of the gland and relative perioperative gland expansion may relate to recovery of pituitary function, but the extent of this is unclear. This study aims to assess temporal changes in hormonal function after transsphenoidal resection of NFPA and the relationship between gland reexpansion and endocrine recovery.METHODSPatients who underwent endoscopic transsphenoidal surgery by a single surgeon for resection of a nonfunctional macroadenoma were selected for inclusion. Patients with prior pituitary surgery or radiosurgery were excluded. Patient characteristics and endocrine function were extracted by chart review. Volumetric segmentation of the pre- and postoperative (≥ 6 months) pituitary gland was performed using preoperative and long-term postoperative MR images. The relationship between endocrine function over time and clinical attributes, including gland volume, were examined.RESULTSOne hundred sixty eligible patients were identified, of whom 47.5% were female; 56.9% of patients had anterior pituitary hormone deficits preoperatively. The median tumor diameter and gland volume preoperatively were 22.5 mm (interquartile range [IQR] 18.0-28.8 mm) and 0.18 cm3 (IQR 0.13-0.28 cm3), respectively. In 55% of patients, endocrine function normalized or improved in their affected axes by median last clinical follow-up of 24.4 months (IQR 3.2-51.2 months). Older age, male sex, and larger tumor size were associated with likelihood of endocrine recovery. Median time to recovery of any axis was 12.2 months (IQR 2.5-23.9 months); hypothyroidism was the slowest axis to recover. Although the gland significantly reexpanded from preoperatively (0.18 cm3, IQR 0.13-0.28 cm3) to postoperatively (0.33 cm3, IQR 0.23-0.48 cm3; p < 0.001), there was no consistent association with improved endocrine function.CONCLUSIONSRecovery of endocrine function can occur several months and even years after surgery, with more than 50% of patients showing improved or normalized function. Tumor size, and not gland volume, was associated with preserved or recovered endocrine function.

Thirty-Day Outcomes After Craniotomy for Primary Malignant Brain Tumors: A National Surgical Quality Improvement Program Analysis.

BACKGROUND: Despite improved perioperative management, the rate of postoperative morbidity and mortality after brain tumor resection remains considerably high. OBJECTIVE: To assess the rates, causes, timing, and predictors of major complication, extended length of stay (>10 d), reoperation, readmission, and death within 30 d after craniotomy for primary malignant brain tumors. METHODS: Patients were extracted from the National Surgical Quality Improvement Program registry (2005-2015) and analyzed using multivariable logistic regression. RESULTS: A total of 7376 patients were identified, of which 948 (12.9%) experienced a major complication. The most common major complications were reoperation (5.1%), venous thromboembolism (3.5%), and death (2.6%). Furthermore, 15.6% stayed longer than 10 d, and 11.5% were readmitted within 30 d after surgery. The most common reasons for reoperation and readmission were intracranial hemorrhage (18.5%) and wound-related complications (11.9%), respectively. Multivariable analysis identified older age, higher body mass index, higher American Society of Anesthesiologists (ASA) classification, dependent functional status, elevated preoperative white blood cell count (white blood cell count [WBC], >12 000 cells/mm3), and longer operative time as predictors of major complication (all P < .001). Higher ASA classification, dependent functional status, elevated WBC, and ventilator dependence were predictors of extended length of stay (all P < .001). Higher ASA classification and elevated WBC were predictors of reoperation (both P < .001). Higher ASA classification and dependent functional status were predictors of readmission (both P < .001). Older age, higher ASA classification, and dependent functional status were predictors of death (all P < .001). CONCLUSION: This study provides a descriptive analysis and identifies predictors for short-term complications, including death, after craniotomy for primary malignant brain tumors.

Presentation, Treatment, and Long-Term Outcome of Intrasellar Chordoma: A Pooled Analysis of Institutional, SEER (Surveillance Epidemiology and End Results), and Published Data.

BACKGROUND: Chordoma that occurs primarily in the sella turcica is rare and presents unique treatment challenges. OBJECTIVE: The purpose of this study was to determine common features, treatment approaches, and survival characteristics of intrasellar chordoma. METHODS: Institutional databases, the SEER (Surveillance Epidemiology and End Results) database, and PubMed/EMBASE were queried for chordoma with a primarily intrasellar component. The SEER database was also queried for adult skull base chordoma. Patient-level data were extracted where available. Kaplan-Meier survival analyses were conducted. RESULTS: Among 80 cases, the mean age at presentation was 55.6 (standard deviation, 15.9), with a female predominance (1.16:1.00). Patients experienced symptoms for a mean duration of 19.0 months, including cranial nerve deficits, hypopituitarism, and hyperprolactinemia. Among patients receiving treatment, 77.5% underwent surgery. In addition, less than half of the patients (n = 34, 47.3%) received adjuvant radiation therapy. The 5-year overall survival (OS) of intrasellar chordoma was 60.0% (standard error [SE], 6.9). Patients aged 40 years and younger had a 5-year OS of 80.8% (SE, 12.2), compared with patients older than 40 years, who had an OS of 55.4% (SE, 7.7) (Mantel-Cox, P = 0.044). Males experienced a lower 5-year OS (44.0; SE, 9.7) than did females (76.8; SE, 8.5), (Mantel-Cox, P = 0.003). Median OS was greater in patients with skull base chordoma than in patients with intrasellar chordoma (Mantel-Cox, P = 0.046). CONCLUSIONS: Intrasellar chordoma presents frequently with visual disturbances and hyperprolactinemia and has a slightly higher incidence in females. Young age predicts a better prognosis. Intrasellar chordoma has a lower overall survival than has skull base chordoma.

Venous thromboembolism and intracranial hemorrhage after craniotomy for primary malignant brain tumors: a National Surgical Quality Improvement Program analysis.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), frequently complicates the postoperative course of primary malignant brain tumor patients. Thromboprophylactic anticoagulation is commonly used to prevent VTE at the risk of intracranial hemorrhage (ICH). We extracted all patients who underwent craniotomy for a primary malignant brain tumor from the National Surgical Quality Improvement Program (NSQIP) registry (2005-2015) to perform a time-to-event analysis and identify relevant predictors of DVT, PE, and ICH within 30 days after surgery. Among the 7376 identified patients, the complication rates were 2.6, 1.5, and 1.3% for DVT, PE, and ICH, respectively. VTE was the second-most common major complication and third-most common reason for readmission. ICH was the most common reason for reoperation. The increased risk of VTE extends beyond the period of hospitalization, especially for PE, whereas ICH occurred predominantly within the first days after surgery. Older age and higher BMI were overall predictors of VTE. Dependent functional status and longer operative times were predictive for VTE during hospitalization, but not for post-discharge events. Admission two or more days before surgery was predictive for DVT, but not for PE. Preoperative steroid usage and male gender were predictive for post-discharge DVT and PE, respectively. ICH was associated with various comorbidities and longer operative times. This multicenter study demonstrates distinct critical time periods for the development of thrombotic and hemorrhagic events after craniotomy. Furthermore, the VTE risk profile depends on the type of VTE (DVT vs. PE) and clinical setting (hospitalized vs. post-discharge patients).

Extent of surgical resection and tumor size predicts prognosis in granular cell tumor of the sellar region.

BACKGROUND: Rarely, granular cell tumor (GCT) occurs in the sellar region. The natural history of this clinical entity is not well known. This study sought to determine the clinical features and long-term outcome of GCT of the sellar region. METHODS: Institutional databases, the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, and PubMed/EMBASE were searched for GCT of the sellar region. Patient-level data were extracted where available, including age, sex, symptoms, tumor size and location, presumed diagnosis, surgical approach and result, subtotal resection (STR) and gross-total resection (GTR), use of radiation, and outcome. The primary endpoints of recurrence and survival were determined. RESULTS: A total of 141 cases were analyzed. The mean age at diagnosis was 48.9 (SD 15.3) with a female predominance (sex ratio 1.49:1). Almost all patients experienced either or both neurological and endocrine symptoms. The most common pre-operative diagnosis was pituitary adenoma. Approximately 60% of patients were treated with surgery, 57.7% with a craniotomy, and 39.7% with a transsphenoidal approach. The 5-year overall survival (OS) was 84.7% (standard error, SE 4.2). Patients with tumors less than 2.5 cm experienced a greater 5-year OS (100.0%) than patients with tumors 2.5 cm or larger (74.0%, SE: 11.7), (Mantel-Cox, p = 0.024). GTR resulted in a greater 5-year OS (95.7%, SE 4.3) than STR (88.8%, SE 5.5) and no surgery or biopsy alone (75.0%, SE 15.3) (Mantel-Cox, p = 0.016). The use of radiation therapy did not improve OS. The 5-year progression-free survival rate was 80.8% (SE 9.2). CONCLUSIONS: Granular cell tumor of the sellar region is a relatively benign neoplasm with neurological and endocrine clinical manifestations. Surgical resection is appropriate for management. Tumor size and extent of resection influence overall survival.

Surgical Resection and Cellular Proliferation Index Predict Prognosis for Patients with Papillary Glioneuronal Tumor: Systematic Review and Pooled Analysis.

BACKGROUND: Although the World Health Organization classifies papillary glioneuronal tumor (PGNT) as a grade I tumor, several malignant cases have been reported. In this study, we examined the clinical and prognostic characteristics of PGNT. METHODS: PubMed, Embase, and institutional databases were queried for patient-level reports of PGNT, resulting in identification of 138 cases. Descriptive and Kaplan-Meier survival analyses were conducted. The threshold of significance was 0.05. RESULTS: The mean age at presentation was 26.9 ± 16.3 years, and the incidence was higher in males (1.42:1). Tumors with a high Ki-67 index (≥5) were more likely to exhibit perilesional edema and ring enhancement on magnetic resonance imaging, trending toward significance (P = 0.114 and 0.113, respectively). Compared with tumors with a low Ki-67 index (<5), those with a high Ki-67 index were more likely to be treated with subtotal resection (STR) than with gross total resection (GTR) (Kruskal-Wallis test, P = 0.006) and with radiation therapy (χ2 test, P = 0.010). At 5 years post-treatment, PGNT had a mean progression-free survival (PFS) of 85.9 ± 3.9%. Males had a better 5-year PFS than females (94.0 ± 3.4% vs. 74.8 ± 7.8%; Mantel-Cox test, P = 0.002). Two-year PFS was higher after GTR than after STR (91.9 ± 3.6% vs. 46.7 ± 21.4%; Mantel-Cox test, P < 0.001). A low Ki-67 index was associated with a higher 5-year PFS compared with a high Ki-67 index (94.8 ± 3.6% vs. 55.6 ± 12.9%; Mantel-Cox test, P < 0.001). CONCLUSIONS: PGNT is a benign tumor of young adults, but can present atypically as high grade. Male sex, low cellular proliferation, and maximal surgical resection are positive prognostic indicators for PGNT.

Antibacterial prophylaxis for gram-positive and gram-negative infections in cranial surgery: A meta-analysis.

BACKGROUND: Perioperative antibiotic prophylaxis against gram positive and gram negative infections is considered standard of care in the perioperative management of patients undergoing cranial surgery. The antibiotic regimen which best reduces the risk of surgical site infections (SSIs) remains controversial. OBJECTIVES: A systematic literature review and meta-analysis were conducted to examine the effect of various prophylactic antibiotics on infection incidence among patients undergoing cranial surgeries. METHODS: A comprehensive search was conducted on Pubmed, EMBASE and Cochrane databases through October 2014 for studies that evaluated the efficacy of antibiotic prophylaxis among patients undergoing cranial surgeries. Pooled effect estimates using both fixed- and random-effect models were calculated. RESULTS: Eight articles were included in the meta-analysis, with a combined total of 1655 cranial procedures. Among these, 74 cases of SSIs were reported after patients received a single antibiotic or a combination of 2 or more antibiotics (pooled incidence of SSIs=6.00%; 95% CI=4.80%, 7.50%; fixed-effects model; I2=73.7%; P-heterogeneity<0.01). Incidence of SSI was 1.00% (95% CI=0.40%, 2.60%) for non-MRSA gram-positive bacterial infections; 2.70% (95% CI=0.90%, 8.00%) for gram-negative bacterial infections; 6.00% (95% CI=4.50%, 7.80%) for gram negative, and non-MRSA gram-positive bacterial infections; and 11.3% (95% CI=7.20%, 17.4%) for gram negative and MRSA gram-positive bacterial infections. Subgroup analysis revealed an effect modification by drug class (P=0.05) and infection type (P-interaction=0.01). More specifically, lincosamides (2.70%; n=1 group), glycopeptides (2.80%; n=1), third generation cephalosporins (5.30%; n=2), antibiotics combination (4.90%; n=4), and penicillin-family antibiotics (5.90%, n=1) offered better coverage against infections than first generation cephalosporins (22.0%; n=2). A meta-regression analysis on study length was not significant (P=0.13). Random-effect models were not materially different form fixed-effects. No evidence of publication bias was found. CONCLUSION: Lincosamides, glycopeptides, third generation cephalosporins, other combinations of prophylactic antibiotics, or penicillin-family antibiotics alone offer better coverage against SSIs than first generation cephalosporin among cranial surgery patients.