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Purpose: A systematic review was conducted to investigate differences in incidence and primary origin of synchronous brain metastasis (sBM) in varying racial groups with different primary cancers., Methods: Adhering to PRISMA 2020 guidelines a search was conducted using PubMed and Ovid databases for publications from January 2000 to January 2023, with search terms including combinations of "brain metastasis," "race," "ethnicity," and "incidence." Three independent reviewers screened for inclusion criteria encompassing studies clearly reporting primary cancer sites, patient demographics including race, and synchronous BM (sBM) incidence., Results: Of 806 articles, 10 studies comprised of mainly adult patients from the United States met final inclusion for data analysis. Higher sBM incidence proportions were observed in American Indian/Alaska native patients for primary breast (p < 0.001), colorectal (p = 0.015), and esophageal cancers (p = 0.024) as well as in Asian or Pacific islanders for primary stomach (p < 0.001), thyroid (p = 0.006), and lung/bronchus cancers (p < 0.001) yet higher proportions in White patients for malignant melanoma (p < 0.001). Compared to White patients, Black patients had higher sBM incidence likelihood in breast cancer (OR = 1.27, p = 0.01) but lower likelihood in renal (OR = 0.46, p < 0.001) and esophageal cancers (OR = 0.31, p = 0.005). American Indian/Alaska native patients had a higher sBM likelihood (OR = 3.78, p = 0.004) relative to White patients in esophageal cancer., Conclusions: These findings reveal several comparative racial differences in sBM incidence arising from different primary cancer origins, underscoring a need for further research to explain these variations. Identifying the factors contributing to these disparities holds the potential to promote greater equity in oncological care according to cancer type., (© 2024. The Author(s).)

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., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: According to the 2017 World Health Organization classification of neuro-endocrine tumors, pituitary adenomas (PAs) are classified according to immunoexpression of the pituitary-specific transcription factors (TFs). A small subset of PAs exhibit multiple TF staining on immunohistochemistry and we present a series of 27 pathologically-confirmed cases of dual TF staining PAs (dsTF-PAs), and report clinically relevant implications., Methods: A retrospective chart review of a multi-institutional database of patients with PAs surgically resected between 2008-2021 was performed. PAs expressing immunopositivity 2+ TFs. Patient demographics, neuro-imaging characteristics, histopathologic findings, and clinical data were collected., Results: Twenty-seven patients had pathologically verified dsTF-PAs, of whom 17 were female (63%), with ages ranging from 20-84 years. Twenty-three (85.2%) patients harbored functional PAs, with acromegaly being the most common functional subtype (86.4%). The most common combination of TFs within a single tumor was PIT-1/SF-1 (85.2%). Six PAs exhibited Knosp cavernous sinus invasion grades of 3 or 4 and the Ki-67 labeling index was ≥3% in 6 patients (24.0%) and all stained for PIT-1/SF-1. Hormonal remission was achieved in 78% of functional dsTF-PAs. No PAs showed evidence of recurrence or progression over the mean follow-up period of 28.5 months., Conclusions: PAs exhibiting dsTF-PAs represent a small but clinically relevant diagnostic subset of PAs according to the 2021 World Health Organization criteria, as a majority are GH-producing. Precise classification using TF staining plays a key role in understanding the biology of these tumors. Favorable outcomes can be achieved in this subset of PAs with evolving TF classification., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the association between birth characteristics, including parental sociodemographic characteristics, and early-onset pituitary adenoma (PA) and craniopharyngioma., Methods: Leveraging the population-based California Linkage Study of Early-onset Cancers, we identified the birth characteristics of incident cases with PA (n = 1,749) or craniopharyngioma (n = 227) who were born from 1978 to 2015 and diagnosed 1988-2015, as well as controls in a 50:1 ratio matched on birth year. Adjusted odds ratios (OR) and 95% confidence interval (CI) estimates were computed using unconditional multivariable logistic regression., Results: Males had a lower risk of PA than females (OR = 0.37, 95%CI: 0.34-0.41), and Black (OR = 1.55, 95%CI: 1.30-1.84) or Hispanic (OR = 1.53, 95%CI: 1.34-1.74) individuals had a higher risk compared to non-Hispanic Whites. Older maternal age was positively associated with PA (OR = 1.09, 95%CI: 1.04-1.15 per 5 years, p < 0.01), as was higher maternal education (OR = 1.12, 95%CI: 1.04-1.20 per year, p < 0.01). There were no statistically significant associations between birthweight (OR = 1.04, 95%CI: 0.99-1.09 per 500 g, p = 0.12), birth plurality, or birth order and PA. When stratified by race and ethnicity, the significant association with maternal education was identified only for non-Hispanic White individuals. On multivariable logistic regression, no statistically significant associations were identified between birth characteristics and incidence of craniopharyngioma, except that risk was higher among Hispanic (OR = 1.45, 95%CI: 1.01-2.08) compared to non-Hispanic White individuals., Conclusion: In this large, population-based study, female sex, older maternal age, higher maternal education, and Hispanic ethnicity and Black race compared to non-Hispanic White race, were associated with an increased risk of PA in children and young adults., (© 2023. The Author(s).)

Objective: The objective of this study was to evaluate the association between county-level socioeconomic status (SES) and the incidence of and surgical treatment for pituitary adenoma (PA)., Methods: Using the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results database, the authors identified the average annual age-adjusted incidence rates and calculated odds ratios (ORs) for surgical treatment of PA, stratified by a county-level index for SES, race/ethnicity, metropolitan status, and other confounders., Results: From 2006 to 2018, 167,121 PA cases were identified. There was no significant trend in the incidence of PA by county-level SES overall (incidence rate ratio [IRR] 0.98, 95% CI 0.96-1.00, p = 0.05, comparing highest to lowest quintile of SES). Among Asian or Pacific Islander (API; IRR 0.82, 95% CI 0.71-0.95, p = 0.007) and American Indian/Alaska Native (AIAN) participants (IRR 0.82, 95% CI 0.71-0.95, p = 0.009), the incidence of PA was statistically significantly lower with higher SES, while among Black individuals, the incidence of PA was higher with higher SES (IRR 1.10, 95% CI 1.05-1.15, p < 0.001, comparing 5th to 1st quintile of SES). Higher SES quintile was associated with surgical treatment of PA (OR 1.04, 95% CI 0.99-1.09, comparing highest to lowest quintile, p value for trend = 0.02). Males were more likely than females to undergo surgery (OR 1.50, 95% CI 1.47-1.53, p < 0.001), and Black (OR 0.89, 95% CI 0.86-0.91, p < 0.001) and AIAN individuals (OR 0.88, 95% CI 0.78-0.99, p = 0.04) were less likely to undergo surgery than White individuals, whereas API individuals were more likely to undergo surgery (OR 1.15, 95% CI 1.09-1.21, p < 0.001)., Conclusions: Higher county-level SES in the US was associated with a higher incidence of PA among Black individuals, but not among White individuals, while API and AIAN individuals had a lower PA incidence with higher SES. After multivariable adjustment, higher county-level SES was associated with surgical treatment of PA, and White and API individuals were significantly more likely to undergo surgery than Black or AIAN individuals.

Background: We evaluated the potential role of birth characteristics in the etiology of early-onset meningioma., Methods: Leveraging a population-based linkage of California birth records (from 1978 to 2015) and cancer registry data (from 1988 to 2015), we identified 362 nonmalignant meningioma cases aged 0-37 years and selected 18 100 controls matched on year of birth. Cases and controls were compared with regard to birth characteristics, with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) estimated from unconditional multivariable logistic regression models. We also conducted stratified analyses by race/ethnicity and age., Results: Female sex (compared to male: OR = 1.43, 95% CI: 1.16 to 1.79; P  < .01) and Black race (compared to White: OR = 1.46, 95% CI: 1.02 to 2.07; P  = .04) were associated with higher risk of meningioma. Higher birth order (OR = 0.90, 95% CI: 0.81 to 0.99 per additional birth position; P  = .04) was associated with a lower risk. No significant associations were observed between birthweight, gestational age, delivery mode, maternal age, or maternal education and meningioma risk. In the non-Latino White subgroup, higher birthweight was associated with a higher risk of meningioma (OR = 1.20, 95% CI: 1.02 to 1.41 per 500 grams; P  = .03), but this was not recapitulated in the Latino subgroup. In age-stratified analyses, female sex was a risk factor for those diagnosed at the age of 20-37 years but not among younger individuals., Conclusions: In this large population-based study less prone to selection and recall bias, higher birth order was associated with a reduced risk of early-onset meningioma, while female sex and Black race were linked to an increased risk. There were also indications of differential associations by race/ethnicity and age of diagnosis., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: The abscopal effect is a rare phenomenon whereby local radiation induces a proposed immune-mediated anti-tumor effect at distant sites. Given the growing use of immunotherapies and systemic immune checkpoint inhibitors in neuro-oncologic practice, we aimed to review prior studies pertaining to this phenomenon in the context of tumor shrinkage both within the central nervous system as well as distant disease sites., Methods: A systematic review in accordance with the PRISMA guidelines was conducted to identify all studies which assessed the abscopal effect in patients with treated metastatic cancer to the brain and/or spine. Articles were included if they reported the abscopal effect in patients (case studies) or if the abscopal effect was explicitly analyzed in case series with cohorts of patients with metastatic brain or spine tumors. Laboratory investigations and clinical trials investigating new therapies were excluded., Results: Twenty reports met inclusion criteria [16 case reports, 4 case series ( n = 160), total n = 174]. Case reports of the abscopal effect were in relation to the following cancers: melanoma (6 patients), breast cancer (3), lung adenocarcinoma (2), non-small-cell lung cancer (2), hepatocellular carcinoma (1), and renal cell carcinoma (1). Eleven patients had irradiation to the brain and 2 to the spine. Patients undergoing whole brain radiotherapy (6) had an average dose of 33.6 Gy over 8-15 fractions, and those undergoing stereotactic radiosurgery (5) had an average dose of 21.5 Gy over 1-5 fractions. One patient had radiation to the body and an intracranial abscopal effect was observed. Most common sites of extracranial tumor reduction were lung and lymph nodes. Ten case studies (57%) showed complete resolution of extra-CNS tumor burden. Median progression-free survival was 13 months following radiation. Four papers investigated incidence of abscopal effects in patients with metastatic melanoma to the brain who received immune checkpoint inhibitor therapy ( n = 160); two papers found an abscopal effect in 35% and 52% of patients ( n = 16, 21 respectively), and two papers found no evidence of abscopal effects ( n = 61, 62)., Conclusions: Abscopal effects can occur following radiotherapy in patients with brain or spine metastases and is thought to be a result of increased anti-tumor immunity. The potential for immune checkpoint inhibitor therapy to be used in combination with radiotherapy to induce an abscopal effect is an area of active investigation., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Major vascular injury resulting in uncontrolled bleeding is a catastrophic and often fatal complication of minimally invasive surgery. At the outset of these events, surgeons do not know how much blood will be lost or whether they will successfully control the hemorrhage (achieve hemostasis). We evaluate the ability of a deep learning neural network (DNN) to predict hemostasis control ability using the first minute of surgical video and compare model performance with human experts viewing the same video. The publicly available SOCAL dataset contains 147 videos of attending and resident surgeons managing hemorrhage in a validated, high-fidelity cadaveric simulator. Videos are labeled with outcome and blood loss (mL). The first minute of 20 videos was shown to four, blinded, fellowship trained skull-base neurosurgery instructors, and to SOCALNet (a DNN trained on SOCAL videos). SOCALNet architecture included a convolutional network (ResNet) identifying spatial features and a recurrent network identifying temporal features (LSTM). Experts independently assessed surgeon skill, predicted outcome and blood loss (mL). Outcome and blood loss predictions were compared with SOCALNet. Expert inter-rater reliability was 0.95. Experts correctly predicted 14/20 trials (Sensitivity: 82%, Specificity: 55%, Positive Predictive Value (PPV): 69%, Negative Predictive Value (NPV): 71%). SOCALNet correctly predicted 17/20 trials (Sensitivity 100%, Specificity 66%, PPV 79%, NPV 100%) and correctly identified all successful attempts. Expert predictions of the highest and lowest skill surgeons and expert predictions reported with maximum confidence were more accurate. Experts systematically underestimated blood loss (mean error - 131 mL, RMSE 350 mL, R 2 0.70) and fewer than half of expert predictions identified blood loss > 500 mL (47.5%, 19/40). SOCALNet had superior performance (mean error - 57 mL, RMSE 295 mL, R 2 0.74) and detected most episodes of blood loss > 500 mL (80%, 8/10). In validation experiments, SOCALNet evaluation of a critical on-screen surgical maneuver and high/low-skill composite videos were concordant with expert evaluation. Using only the first minute of video, experts and SOCALNet can predict outcome and blood loss during surgical hemorrhage. Experts systematically underestimated blood loss, and SOCALNet had no false negatives. DNNs can provide accurate, meaningful assessments of surgical video. We call for the creation of datasets of surgical adverse events for quality improvement research., (© 2022. The Author(s).)

Objective: The aim of this study was to evaluate the association between zip code-level socioeconomic status (SES) and presenting characteristics and short-term clinical outcomes in patients with nonfunctioning pituitary adenoma (NFPA)., Methods: A retrospective review of prospectively collected data from the University of Southern California Pituitary Center was conducted to identify all patients undergoing surgery for pituitary adenoma (PA) from 2000 to 2021 and included all patients with NFPA with recorded zip codes at the time of surgery. A normalized socioeconomic metric by zip code was then constructed using data from the American Community Survey estimates, which was categorized into tertiles. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were constructed to estimate mean differences and multivariable-adjusted odds ratios for the association between zip code-level SES and presenting characteristics and outcomes., Results: A total of 637 patients were included in the overall analysis. Compared with patients in the lowest SES tertile, those in the highest tertile were more likely to be treated at a private (rather than safety net) hospital, and were less likely to present with headache, vision loss, and apoplexy. After multivariable adjustment for age, sex, and prior surgery, SES in the highest compared with lowest tertile was inversely associated with tumor size at diagnosis (-4.9 mm, 95% CI -7.2 to -2.6 mm, p < 0.001) and was positively associated with incidental diagnosis (multivariable-adjusted OR 1.72, 95% CI 1.02-2.91). Adjustment for hospital (private vs safety net) attenuated the observed associations, but disparities by SES remained statistically significant for tumor size. Despite substantial differences at presentation, there were no significant differences in length of stay or odds of an uncomplicated procedure by zip code-level SES. Patients from lower-SES zip codes were more likely to require postoperative steroid replacement and less likely to achieve gross-total resection., Conclusions: In this series, lower zip code-level SES was associated with more severe disease at the time of diagnosis for NFPA patients, including larger tumor size and lower rates of incidental diagnosis. Despite these differences at presentation, no significant differences were observed in short-term postoperative complications, although patients with higher zip code-level SES had higher rates of gross-total resection.

Importance: Increased risk of neurological and psychiatric conditions after traumatic brain injury (TBI) is well-defined. However, cardiovascular and endocrine comorbidity risk after TBI in individuals without these comorbidities and associations with post-TBI mortality have received little attention., Objective: To assess the incidence of cardiovascular, endocrine, neurological, and psychiatric comorbidities in patients with mild TBI (mTBI) or moderate to severe TBI (msTBI) and analyze associations between post-TBI comorbidities and mortality., Design, Setting, and Participants: This prospective longitudinal cohort study used hospital-based patient registry data from a tertiary academic medical center to select patients without any prior clinical comorbidities who experienced TBI from 2000 to 2015. Using the same data registry, individuals without head injuries, the unexposed group, and without target comorbidities were selected and age-, sex-, and race-frequency-matched to TBI subgroups. Patients were followed-up for up to 10 years. Data were analyzed in 2021., Exposures: Mild or moderate to severe head trauma., Main Outcomes and Measures: Cardiovascular, endocrine, neurologic, and psychiatric conditions were defined based on International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Associations between TBI and comorbidities, as well as associations between the comorbidities and mortality, were analyzed., Results: A total of 4351 patients with mTBI (median [IQR] age, 45 [29-57] years), 4351 patients with msTBI (median [IQR] age, 47 [30-58] years), and 4351 unexposed individuals (median [IQR] age, 46 [30-58] years) were included in analyses. In each group, 45% of participants were women. mTBI and msTBI were significantly associated with higher risks of cardiovascular, endocrine, neurologic, and psychiatric disorders compared with unexposed individuals. In particular, hypertension risk was increased in both mTBI (HR, 2.5; 95% CI, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9) groups. Diabetes risk was increased in both mTBI (HR, 1.9; 95% CI, 1.4-2.7) and msTBI (HR, 1.9; 95% CI, 1.4-2.6) groups, and risk of ischemic stroke or transient ischemic attack was also increased in mTBI (HR, 2.2; 95% CI, 1.4-3.3) and msTBI (HR, 3.6; 95% CI, 2.4-5.3) groups. All comorbidities in the TBI subgroups emerged within a median (IQR) of 3.49 (1.76-5.96) years after injury. Risks for post-TBI comorbidities were also higher in patients aged 18 to 40 years compared with age-matched unexposed individuals: hypertension risk was increased in the mTBI (HR, 5.9; 95% CI, 3.9-9.1) and msTBI (HR, 3.9; 95% CI, 2.5-6.1) groups, while hyperlipidemia (HR, 2.3; 95% CI, 1.5-3.4) and diabetes (HR, 4.6; 95% CI, 2.1-9.9) were increased in the mTBI group. Individuals with msTBI, compared with unexposed patients, had higher risk of mortality (432 deaths [9.9%] vs 250 deaths [5.7%]; P < .001); postinjury hypertension (HR, 1.3; 95% CI, 1.1-1.7), coronary artery disease (HR, 2.2; 95% CI, 1.6-3.0), and adrenal insufficiency (HR, 6.2; 95% CI, 2.8-13.0) were also associated with higher mortality., Conclusions and Relevance: These findings suggest that TBI of any severity was associated with a higher risk of chronic cardiovascular, endocrine, and neurological comorbidities in patients without baseline diagnoses. Medical comorbidities were observed in relatively young patients with TBI. Comorbidities occurring after TBI were associated with higher mortality. These findings suggest the need for a targeted screening program for multisystem diseases after TBI, particularly chronic cardiometabolic diseases.

We aimed to determine whether intake of pesticide residues from fruits and vegetables was associated with glioma. Within 3 prospective cohorts from 1998-2016-the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and Health Professionals Follow-up Study-we computed multivariable-adjusted hazard ratios (MVHRs) and 95% confidence intervals (CI) for glioma by quintiles of intake of low- and high-pesticide-residue fruits and vegetables using Cox proportional hazards regression. Fruits and vegetables were categorized as high or low residue using a validated method based on pesticide surveillance data. We confirmed 275 glioma cases across 2,745,862 person-years. A significant association was observed between intake of high-residue fruits and vegetables and glioma in NHS (MVHR = 2.99, 95% CI: 1.38, 6.44 comparing highest with lowest quintile, P for trend = 0.02). This was not identified in NHSII (MVHR = 0.52, 95% CI: 0.19, 1.45, P for trend = 0.20) or Health Professionals Follow-up Study (MVHR = 1.01, 95% CI: 0.42, 2.45, P for trend = 0.39). No significant associations were observed by intake of low-residue fruits and vegetables; overall intake was not significantly associated with glioma in any cohort. We found no evidence for an inverse relationship of fruit and vegetable intake with glioma. Although limited in power, this study suggests a possible association between fruit-and-vegetable pesticide residue intake and risk of glioma that merits further study., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Cervical spine injury screening is common practice for traumatic brain injury (TBI) patients. However, risk factors for concomitant thoracolumbar trauma remain unknown. We characterized epidemiology and clinical risk for concomitant thoracolumbar trauma in TBI., Methods: We conducted a multi-center, retrospective cohort analysis of TBI patients in the National Trauma Data Bank from 2011-2014 using multivariable logistic regression., Results: Out of 768,718 TBIs, 46,654 (6.1%) and 42,810 (5.6%) patients were diagnosed with thoracic and lumbar spine fractures, respectively. Only 11% of thoracic and 7% of lumbar spine fracture patients had an accompanying spinal cord injury at any level. The most common mechanism of injury was motor vehicle accident (67% of thoracic and 71% and lumbar fractures). Predictors for both thoracic and lumbar fractures included moderate (thoracic: OR 1.26, 95%CI 1.21-1.31; lumbar: OR 1.13, 95%CI 1.08-1.18) and severe Glasgow Coma Scale (GCS) score (OR 1.71, 95%CI 1.67-1.75; OR 1.17, 95%CI 1.13-1.20) compared to mild; epidural hematoma (OR 1.36, 95%CI 1.28-1.44; OR 1.1, 95%CI 1.04-1.19); lower extremity injury (OR 1.38, 95%CI 1.35-1.41; OR 2.50, 95%CI 2.45-2.55); upper extremity injury (OR 2.19, 95%CI 2.14-2.23; OR 1.15, 95%CI 1.13-1.18); smoking (OR 1.09, 95%CI 1.06-1.12; OR 1.12, 95%CI 1.09-1.15); and obesity (OR 1.39, 95%CI 1.34-1.45; OR 1.29, 95%CI 1.24-1.35). Thoracic injuries (OR 4.45; 95% CI 4.35-4.55) predicted lumbar fractures, while abdominal injuries (OR 2.02; 95% CI 1.97-2.07) predicted thoracic fractures., Conclusions: We identified GCS, smoking, upper and lower extremity injuries, and obesity as common risk factors for thoracic and lumbar spinal fractures in TBI., Competing Interests: Declaration of Competing Interest The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

This article reviews the current epidemiology of central nervous system tumors. Population-level basic epidemiology, nationally and internationally, and current understanding of germline genetic risk are discussed, with a focus on known and well-studied risk factors related to the etiology of central nervous system tumors., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Conversion of tryptophan to kynurenine may promote glioma growth and suppress antitumor immune response through activation of the aryl hydrocarbon receptor. Expression of the enzymes indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase-2 in the glioma microenvironment has been shown to mediate tryptophan catabolism, and the ratio between kynurenine and tryptophan is considered an indirect measure of this enzyme activity., Methods: We explored whether tryptophan, kynurenine, and the ratio of kynurenine to tryptophan (KTR) in pre-diagnostic blood samples was related to risk of glioma in a nested case-control study of 84 cases and 168 matched controls from two cohort studies - the Nurses' Health Study, and the Health Professionals Follow-Up Study. Tryptophan and kynurenine were measured by liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were used to estimate risk ratios (RRs) and 95% confidence intervals (95%CI) for the associations between tertiles of these analytes and glioma risk., Results: We observed no significant associations for either analyte or the ratio for risk of glioma overall. The RR for the highest KTR tertile compared to the lowest for all gliomas was 0.74 (95% CI: 0.34-1.59). All results were essentially unchanged in lagged analyses excluding the first two or four years of follow up, though data were sparse., Conclusion: Our findings do not provide support for an association between pre-diagnostic circulating KTR and risk of glioma., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The association between alcohol intake and incidence of pituitary adenoma has not been reported previously. We examined this association in three large, prospective cohort studies., Methods: Using data from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-Up Study, we computed multivariable-adjusted hazard ratios (MVHR) and 95% confidence intervals (CI) for pituitary adenoma by levels of alcohol intake using Cox proportional hazards regression., Results: We identified 292 incident cases of pituitary adenoma (225 among women, 67 among men) among 235,973 participants with 6,548,732 person-years of follow-up. Compared with intake of ≤ 0.5 g/day, cumulative average alcohol intake in all categories was associated with reduced risk of pituitary adenoma (MVHR = 0.60, 95% CI 0.43-0.83 for 0.5-≤ 2 g/day, MVHR = 0.57, 95% CI 0.41-0.79 for > 2.0-≤ 8.0, MVHR = 0.70, 95% CI 0.47-1.04 for > 8.0-≤ 15.0, and MVHR = 0.51, 95% CI 0.32-0.83 for > 15.0 g/day). Significant inverse findings were present in women and were similar but non-significant in men. For specific alcoholic beverages, inverse associations were statistically significant for total wine (MVHR = 0.58, 95% CI 0.43-0.79 comparing 0.5-≤ 2 to ≤ 0.5 g/day), red wine (MVHR = 0.65, 95% CI 0.46-0.92 comparing 0.5-≤ 2 to ≤ 0.5 g/day), and white wine (MVHR = 0.72, 95% CI 0.53-0.97 comparing 0.5-≤ 2 to ≤ 0.5 g/day). Results were consistent using baseline intake, recent intake, and with an 8-year lag., Conclusion: In three prospective cohorts, compared to almost no consumption, alcohol consumption was associated with reduced risk of pituitary adenoma. Sensitivity analyses suggest that these results are unlikely to be the result of reverse causation or diagnostic bias., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: The utility of robotic instrumentation is expanding in neurosurgery. Despite this, successful examples of robotic implementation for endoscopic endonasal or skull base neurosurgery remain limited. Therefore, the authors performed a systematic review of the literature to identify all articles that used robotic systems to access the sella or anterior, middle, or posterior cranial fossae., Methods: A systematic review of MEDLINE and PubMed in accordance with PRISMA guidelines performed for articles published between January 1, 1990, and August 1, 2021, was conducted to identify all robotic systems (autonomous, semiautonomous, or surgeon-controlled) used for skull base neurosurgical procedures. Cadaveric and human clinical studies were included. Studies with exclusively otorhinolaryngological applications or using robotic microscopes were excluded., Results: A total of 561 studies were identified from the initial search, of which 22 were included following full-text review. Transoral robotic surgery (TORS) using the da Vinci Surgical System was the most widely reported system (4 studies) utilized for skull base and pituitary fossa procedures; additionally, it has been reported for resection of sellar masses in 4 patients. Seven cadaveric studies used the da Vinci Surgical System to access the skull base using alternative, non-TORS approaches (e.g., transnasal, transmaxillary, and supraorbital). Five cadaveric studies investigated alternative systems to access the skull base. Six studies investigated the use of robotic endoscope holders. Advantages to robotic applications in skull base neurosurgery included improved lighting and 3D visualization, replication of more traditional gesture-based movements, and the ability for dexterous movements ordinarily constrained by small operative corridors. Limitations included the size and angulation capacity of the robot, lack of drilling components preventing fully robotic procedures, and cost. Robotic endoscope holders may have been particularly advantageous when the use of a surgical assistant or second surgeon was limited., Conclusions: Robotic skull base neurosurgery has been growing in popularity and feasibility, but significant limitations remain. While robotic systems seem to have allowed for greater maneuverability and 3D visualization, their size and lack of neurosurgery-specific tools have continued to prevent widespread adoption into current practice. The next generation of robotic technologies should prioritize overcoming these limitations.

Purpose: A classification system for cystic sellar lesions does not exist. We propose a novel classification scheme for these lesions based on the heterogeneity of the cyst wall/contents and the presence of a solid component on imaging., Methods: We retrospectively reviewed 205 patients' medical records (2008-2020) who underwent primary surgery for a cystic sellar lesion. Cysts were classified a priori into 1 of 4 cyst types based on the heterogeneity of the cyst wall/contents and the presence of a solid component imaging. There was high interrater reliability. Univariable and multivariable models were used to estimate the ability of cyst type to predict the two most common diagnoses: Rathke cleft cyst (RCC) and cystic pituitary adenoma., Results: The frequencies of RCC and cystic pituitary adenoma in our cohort were 45.4% and 36.4%, respectively. Non-neoplastic lesions (e.g., arachnoid cysts and RCC) were more likely to be Type 1 or 2, whereas cystic neoplasms (e.g., pituitary adenomas and craniopharyngiomas) were more likely to be Type 3 or 4 (p<0.0001). Higher cyst types, compared to Type 1, had higher odds of being cystic pituitary adenomas compared to RCCs (OR: 23.7, p=0.033, and 342.6, p <0.0001, for Types 2 and 4, respectively). Lesions with a fluid-fluid level on preoperative MRI also had higher odds of being pituitary adenomas (OR: 12.7; p=0.023). Cystic pituitary adenomas were more common in patients with obesity (OR: 5.0, p=0.003) or symptomatic hyperprolactinemia (OR: 11.5; p<0.001, respectively). The multivariable model had a positive predictive value of 82.2% and negative predictive value of 86.4%., Conclusion: When applied to the diagnosis of RCC versus cystic pituitary adenoma, higher cystic lesion types (Type 2 & 4), presence of fluid-fluid level, symptomatic hyperprolactinemia, and obesity were predictors of cystic pituitary adenoma. Further validation is needed, but this classification scheme may prove to be a useful tool for the management of patients with common sellar pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tavakol, Catalino, Cote, Boles, Laws and Bi.)

Purpose: The role of growth factors and inflammation in the onset of glioma is poorly understood, and conflicting reports of associations of circulating IGF-1 and inflammatory biomarkers with glioma risk exist in the literature. We examined associations between C-reactive protein (CRP), white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), and insulin-like growth factor-1 (IGF-1) and glioma risk in the UK Biobank cohort., Methods: Hazard ratios (HR) and 95% confidence intervals (CI) for glioma according to circulating biomarkers concentrations were calculated using Cox proportional hazards regression, adjusted for age, sex, race, and education. Analyses were conducted separately for glioma overall and by glioma subtype., Results: We identified 417 incident glioma cases among 428,537 participants with 3,255,815 person-years of follow up. Weak, non-significant associations were observed with increasing levels of these biomarkers for risk of glioma overall or by glioma subtype. Among women only, IGF-1 in the highest quartile was positively associated with glioma risk compared to the lowest quartile (HR=1.64, 95%CI: 1.03-2.60, p-trend=0.08), as was NLR (HR=1.54, 95%CI: 1.00-2.39, p-trend=0.05)., Conclusion: In this prospective cohort, we found no significant associations between the inflammatory biomarkers CRP and WBC and the development of glioma. NLR and IGF-1 were associated with risk in women, but not men. When considered with previous studies, further investigation of NLR and IGF-1 as markers of glioma risk appears warranted, particularly in women., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Flavonoids are a diverse group of plant constituents with demonstrated neuroprotective and anti-tumor effects. Flavonoid intake may decrease the risk of glioma, but the possibility of an association has not yet been investigated in humans., Objectives: We evaluated the association between dietary flavonoid consumption and the risk of glioma., Methods: We followed participants in the female Nurses' Health Study (1984-2014; n = 81,688) and Nurses' Health Study II (1991-2017; n = 95,228) and the male Health Professionals Follow-Up Study (1986-2014; n = 49,885). We used multivariable-adjusted Cox proportional hazards regression models to evaluate the associations between average long-term (up to 30 years) or recent (up to 12 years) dietary flavonoid intake (total flavonoids and each of 6 subclasses) and risks of incident glioma. Flavonoid intake was derived from validated quadrennial FFQs. Incident glioma was self-reported and confirmed by a medical record review or was determined by a medical record review after death., Results: We documented 536 incident cases of glioma across 5,936,386 person-years of follow-up. Long-term total flavonoid, flavan-3-ol, and polymeric flavonoid (polymer) intakes were associated with decreased glioma risks in pooled analyses comparing the highest to lowest quintiles of consumption [HR, 0.79 (95% CI, 0.59-1.05; P-trend = 0.04) for total flavonoids; 0.76 (95% CI, 0.57-1.01; P-trend = 0.04) for flavan-3-ols; and 0.82 (95% CI, 0.61-1.09; P-trend = 0.05) for polymers]. Associations with recent intake were weaker. There were no associations with other flavonoid subclasses. After additional adjustment for tea consumption, there were no associations between flavan-3-ol or polymer consumption and glioma., Conclusions: Increased dietary intakes of flavan-3-ol and polymeric flavonoids, especially those predominant in tea, were associated with decreased glioma risks in a prospective cohort of men and women., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Purpose: The association between alcohol intake and glioma remains unclear. We evaluated the association between alcohol intake and incidence of glioma in three large, prospective cohort studies with repeated alcohol assessments., Methods: We harnessed data from three studies with repeat alcohol assessment to compute hazard ratios (HR) and 95% confidence intervals (CI) for glioma by overall alcohol intake and intake from specific beverages using Cox proportional hazards regression, adjusted for age, cohort, body mass index, smoking status, and caloric intake. Analyses were conducted separately for glioma overall and for glioblastoma (GBM)., Results: We confirmed 554 incident glioma cases (362 GBM) among 237,505 participants with 6,216,378 person-years of follow up. Cumulative average alcohol intake was associated with reduced risk of glioma (HR = 0.75, 95%CI:0.56-0.99 comparing > 8-15 to ≤ 0.5 g/d; HR = 0.71, 95%CI:0.53-0.96 comparing > 15 g/d to ≤ 0.5 g/d). When stratified by sex, for the same comparisons, the HRs for men were 0.57 (95%CI:0.36-0.89) and 0.79 (0.53-1.16), and for women 0.90 (95%CI:0.62-1.30) and 0.62, 95%CI:0.39-0.97. Results were consistent when examining cumulative average, baseline, and recent intake, and with a 4 year lag., Conclusion: These results provide evidence against a positive association between alcohol intake and glioma risk. Alcohol intake was associated with reduced risk of glioma in both men and women., (© 2021. Springer Nature B.V.)

Purpose: Both long and short sleep duration have been linked with risk of some cancers, but evidence for glioma is lacking., Methods: Using prospective data from the UK Biobank (UKB), the Nurses' Health Study (NHS), and the Health Professionals Follow-Up Study (HPFS), we examined the association between self-reported hours of sleep and incident glioma in multivariable-adjusted Cox proportional hazards models., Results: In the UKB, compared to 7 h, sleep durations of < 7 h (HR = 0.90; 95% CI 0.70-1.16) or > 7 h (HR = 1.05; 95% CI 0.85-1.30) were not significantly associated with glioma risk. Likewise, no significant associations were found between sleep duration and glioma risk in the NHS/HPFS for either < 7 h (HR = 0.93; 95% CI 0.69-1.26) or > 7 h (HR = 1.22; 95% CI 0.94-1.57), compared to 7 h. Results were similar for low-grade and high-grade glioma, did not materially change after lagging 2 years, or after accounting for factors known to disrupt sleep., Conclusion: Sleep duration was not associated with incident glioma in either the UKB or the NHS/HPFS cohorts., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Sports injuries are known to present a high risk of spinal trauma. The authors hypothesized that different sports predispose participants to different injuries and injury severities., Methods: The authors conducted a retrospective cohort analysis of adult patients who experienced a sports-related traumatic spinal injury (TSI), including spinal fractures and spinal cord injuries (SCIs), encoded within the National Trauma Data Bank from 2011 through 2014. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were estimated., Results: The authors included 12,031 cases of TSI, which represented 15% of all sports-related trauma. The majority of patients with TSI were male (82%), and the median age was 48 years (interquartile range 32-57 years). The most frequent mechanisms of injury in this database were cycling injuries (81%), skiing and snowboarding accidents (12%), aquatic sports injuries (3%), and contact sports (3%). Spinal surgery was required during initial hospitalization for 9.1% of patients with TSI. Compared to non-TSI sports-related trauma, TSIs were associated with an average 2.3-day increase in length of stay (95% CI 2.1-2.4; p < 0.001) and discharge to or with rehabilitative services (adjusted OR 2.6, 95% CI 2.4-2.7; p < 0.001). Among sports injuries, TSIs were the cause of discharge to or with rehabilitative services in 32% of cases. SCI was present in 15% of cases with TSI. Within sports-related TSIs, the rate of SCI was 13% for cycling injuries compared to 41% and 49% for contact sports and aquatic sports injuries, respectively. Patients experiencing SCI had a longer length of stay (7.0 days longer; 95% CI 6.7-7.3) and a higher likelihood of adverse discharge disposition (adjusted OR 9.69, 95% CI 8.72-10.77) compared to patients with TSI but without SCI., Conclusions: Of patients with sports-related trauma discharged to rehabilitation, one-third had TSIs. Cycling injuries were the most common cause, suggesting that policies to make cycling safer may reduce TSI.

While chronic neurological effects from concussion have been studied widely, little is known about possible links between concussion and long-term medical and behavioral comorbidities. We performed a retrospective cohort study of 9205 adult patients with concussion, matched to non-concussion controls from a hospital-based electronic medical registry. Patients with comorbidities before the index visit were excluded. Behavioral and medical comorbidities were defined by International Classification of Diseases, Ninth and Tenth Revision codes. Groups were followed for up to 10 years to identify comorbidity incidence after a concussion. Cox proportional hazards models were used to calculate associations between concussion and comorbidities after multi-variable adjustment. Patients with concussion were 57% male (median age: 31; interquartile range [IQR] = 23-48 years) at enrollment with a median follow-up time of 6.1 years (IQR = 4.2-9.1) and well-matched to healthy controls. Most (83%) concussions were evaluated in outpatient settings (5% inpatient). During follow-up, we found significantly higher risks of cardiovascular risks developing including hypertension (hazard ratio [HR] = 1.7, 95% confidence interval [CI]: 1.5-1.9), obesity (HR = 1.7, 95% CI: 1.3-2.0), and diabetes mellitus (HR = 1.8, 95% CI: 1.4-2.3) in the concussion group compared with controls. Similarly, psychiatric and neurological disorders such as depression (HR = 3.0, 95% CI: 2.6-3.5), psychosis (HR = 6.0, 95% CI: 4.2-8.6), stroke (HR = 2.1 95% CI: 1.5-2.9), and epilepsy (HR = 4.4, 95% CI: 3.2-5.9) were higher in the concussion group. Most comorbidities developed less than five years post-concussion. The risks for post-concussion comorbidities were also higher in patients under 40 years old compared with controls. Patients with concussion demonstrated an increased risk of development of medical and behavioral health comorbidities. Prospective studies are warranted to better describe the burden of long-term comorbidities in patients with concussion.

Few prospective studies have evaluated the relation between fat-soluble vitamins and glioma risk. Using three cohorts-UK Biobank (UKB), Nurses' Health Study (NHS), and Health Professionals Follow-Up Study (HPFS), we investigated associations of pre-diagnostic concentrations of fat-soluble vitamins D, A, and E with incident glioma. In 346,785 participants (444 cases) in UKB, associations with vitamin D (25-hydroxyvitamin D [25(OH)D]) were evaluated by Cox proportional hazards regression. In NHS (52 cases, 104 controls) and HPFS (32 cases, 64 controls), associations with 25(OH)D, vitamin A (retinol), and vitamin E (α- and γ-tocopherol) were assessed using conditional logistic regression. Our results suggested plasma concentrations of 25(OH)D and retinol were not associated with glioma risk. Comparing the highest to lowest tertile, the multivariable hazard ratio (MVHR) for 25(OH)D was 0.87 (95% confidence interval [CI] 0.68-1.11) in UKB and the multivariable risk ratio (MVRR) was 0.97 (95% CI 0.51-1.85) in NHS and HPFS. In NHS and HPFS, the MVRR for the same comparison for retinol was 1.16 (95% CI 0.56-2.38). Nonsignificant associations were observed for α-tocopherol (MVRR tertile3vs1  = 0.61, 95% CI 0.29-1.32) and γ-tocopherol (MVRR tertile3vs1  = 1.30, 95% CI 0.63-2.69) that became stronger in 4-year lagged analyses. Further investigation is warranted on a potential association between α- and γ-tocopherol and glioma risk.

Objectives: The impact of demographics and comorbidities on the duration of COVID-19 nasopharyngeal swab PCR positivity remains unclear. The objective of our analysis is to determine the impact of age, intensive care unit (ICU) admission, comorbidities, and ethnicity on the duration of COVID-19 PCR positivity among hospitalized patients in a large group of hospital., Method: We studied 530 patients from a large hospital system and time to SARS-CoV-2 virus RNA PCR negativity at any-time during hospitalization or following discharge from the hospital was the primary endpoint. We included patients 18 years or older who tested positive for COVID-19 during an inpatient, outpatient, or emergency room visit between February 1, 2020, and April 14, 2020., Results: Overall, 315 (59.4%) of our patient population continued to have a positive SARS-CoV-2 virus RNA PCR 4 weeks after the initial positive test. We found that age>70 years, chronic kidney disease, hypertension, hyperlipidemia, obesity, or coronary artery disease are associated with persistent PCR positivity for more than 4 weeks after initial diagnosis., Conclusion: Age, and the presence of co-morbidities should be taken into consideration when interpreting a positive COVID PCR test., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aldhaeefi, Tahir, Cote, Izzy and Khoury.)

Purpose: Evidence is mixed on whether cholesterol plays a role in the pathogenesis of glioma. We explored the associations between circulating lipids and glioma risk in three prospective cohorts., Methods: Using prospective data from the UK Biobank, we examined the associations of total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides (TG) with glioma risk in multivariable (MV)-adjusted Cox proportional hazards models. Within the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS), we carried out a matched, nested case-control study to examine these same associations., Results: In the UK Biobank, 490 gliomas accrued over 2,358,964 person-years. TC was not significantly associated with glioma risk (MV HR = 1.20, 95% CI 0.89-1.61 for highest quartile vs. lowest, p-trend = 0.24). In 4-year lagged analyses (n = 229), higher TC was associated with significantly higher risk of glioma in men (MV HR = 2.26, 95% CI 1.32-3.89, p-trend = 0.002) but not women (MV HR = 1.28, 95% CI 0.61-2.68, p-trend = 0.72); similar findings emerged for HDL-C and, to a lesser extent, LDL-C. In the NHS/HPFS, no significant associations were found between cholesterol and glioma risk. No significant associations were identified for TG., Conclusion: In the UK Biobank, higher prediagnostic TC and HDL-C levels were associated with higher risk of glioma in 4-year lagged analyses, but not in non-lagged analyses, in men only. These findings merit further investigation, given that there are few risk factors and no reliable biomarkers of risk identified for glioma.

Context: No studies have examined the association between body habitus and incidence of pituitary adenoma., Objective: To determine if body mass index (BMI), waist circumference, body somatotype, or height are associated with risk of pituitary adenoma., Design: Pooled analysis of 3 prospective cohort studies., Setting: Population-based study., Participants: Participants of the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and the Health Professionals Follow-Up Study (HPFS), totaling 284 946 American health professionals., Exposures: BMI, waist circumference, body somatotype, and height., Outcome Measures: Self-reported incident pituitary adenoma. Multivariable (MV)-adjusted hazard ratios (HRs) of pituitary adenoma were estimated using Cox proportional hazards models., Results: During 7 350 156 person-years of follow-up, 387 incident pituitary adenomas were reported. Comparing BMI of ≥30 to <25 kg/m2, higher adult BMI was associated with higher risk of pituitary adenoma (MV HR = 1.74; 95% CI, 1.33-2.28), as was higher maximum adult BMI (MV HR = 1.76; 95% CI, 1.34-2.30), higher waist circumference (MV HR = 1.06; 95% CI, 1.04-1.09 per inch), and higher BMI during early adulthood (at age 18 to 21, MV HR = 2.65; 95% CI, 1.56-4.49). Taller adult height was associated with pituitary adenoma (MV HR = 1.05; 95% CI, 1.01-1.09 per inch). Overall findings were similar in women and men, although power was limited in men (n = 62 cases). Sensitivity analyses demonstrated that the association between adult BMI and pituitary adenoma extended to at least 14 years prior to diagnosis and that the results were not affected when analyses were restricted to participants with similar healthcare utilization., Conclusion: Higher BMI and waist circumference, from early adulthood to the time of diagnosis, were associated with higher risk of pituitary adenoma., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: VEGF is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase II study of pembrolizumab alone or with bevacizumab in recurrent glioblastoma., Patients and Methods: Eighty bevacizumab-naïve patients with recurrent glioblastoma were randomized to pembrolizumab with bevacizumab (cohort A, n = 50) or pembrolizumab monotherapy (cohort B, n = 30). The primary endpoint was 6-month progression-free survival (PFS-6). Assessed biomarkers included evaluation of tumor programmed death-ligand 1 expression, tumor-infiltrating lymphocyte density, immune activation gene expression signature, and plasma cytokines. The neurologic assessment in neuro-oncology (NANO) scale was used to prospectively assess neurologic function., Results: Pembrolizumab alone or with bevacizumab was well tolerated but of limited benefit. For cohort A, PFS-6 was 26.0% [95% confidence interval (CI), 16.3-41.5], median overall survival (OS) was 8.8 months (95% CI, 7.7-14.2), objective response rate (ORR) was 20%, and median duration of response was 48 weeks. For cohort B, PFS-6 was 6.7% (95% CI, 1.7-25.4), median OS was 10.3 months (95% CI, 8.5-12.5), and ORR was 0%. Tumor immune markers were not associated with OS, but worsened OS correlated with baseline dexamethasone use and increased posttherapy plasma VEGF (cohort A) and mutant IDH1 , unmethylated MGMT , and increased baseline PlGF and sVEGFR1 levels (cohort B). The NANO scale contributed to overall outcome assessment., Conclusions: Pembrolizumab was ineffective as monotherapy and with bevacizumab for recurrent glioblastoma. The infrequent radiographic responses to combinatorial therapy were durable. Tumor immune biomarkers did not predict outcome. Baseline dexamethasone use and tumor MGMT warrant further study as potential biomarkers in glioblastoma immunotherapy trials., (©2020 American Association for Cancer Research.)

Background: Diabetes insipidus (DI) is a recognized transient or permanent complication following transsphenoidal surgery (TSS) for pituitary tumors., Objective: To describe significant experience with the incidence of DI after TSS, identifying predictive characteristics and describing our diagnosis and management of postoperative DI., Methods: A retrospective analysis was performed of 700 patients who underwent endoscopic TSS for resection of pituitary adenoma (PA), Rathke cleft cyst (RCC), or craniopharyngioma. Inclusion criteria included at least 1 wk of follow-up for diagnosis of postoperative DI. Permanent DI was defined as DI symptoms and/or need for desmopressin more than 1 yr postoperatively. All patients with at least 1 yr of follow-up (n = 345) were included in analyses of permanent DI. Multivariable logistic regression models were constructed to identify predictors of transient or permanent postoperative DI., Results: The overall rate of any postoperative DI was 14.7% (103/700). Permanent DI developed in 4.6% (16/345). The median follow-up was 10.7 mo (range: 0.2-136.6). Compared to patients with PA, patients with RCC (odds ratio [OR] = 2.2, 95% CI: 1.2-3.9; P = .009) and craniopharyngioma (OR = 7.0, 95% CI: 2.9-16.9; P ≤ .001) were more likely to develop postoperative DI. Furthermore, patients with RCC (OR = 6.1, 95% CI: 1.8-20.6; P = .004) or craniopharyngioma (OR = 18.8, 95% CI: 4.9-72.6; P ≤ .001) were more likely to develop permanent DI compared to those with PA., Conclusion: Although transient DI is a relatively common complication of endoscopic and microscopic TSS, permanent DI is much less frequent. The underlying pathology is an important predictor of both occurrence and permanency of postoperative DI., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Background: There is a limited understanding of the impact of coronavirus disease 2019 (COVID-19) on the Latinx population. We hypothesized that Latinx patients would be more likely to be hospitalized and admitted to the intensive care unit (ICU) than White patients., Methods: We analyzed all patients with COVID-19 in 12 Massachusetts hospitals between February 1 and April 14, 2020. We examined the association between race, ethnicity, age, reported comorbidities, and hospitalization and ICU admission using multivariable regression., Results: Of 5190 COVID-19 patients, 29% were hospitalized; 33% required the ICU, and 4.3% died. Forty-six percent of patients were White, 25% Latinx, 14% African American, and 3% Asian American. Ethnicity and race were significantly associated with hospitalization. More Latinx and African American patients in the younger age groups were hospitalized than whites. Latinxs and African Americans disproportionally required the ICU, with 39% of hospitalized Latinx patients requiring the ICU compared with 33% of African Americans, 24% of Asian Americans, and 30% of Whites ( P  < .007). Within each ethnic and racial group, age and male gender were independently predictive of hospitalization. Previously reported preexisting comorbidities contributed to the need for hospitalization in all racial and ethnic groups ( P  < .05). However, the observed disparities were less likely related to reported comorbidities, with Latinx and African American patients being admitted at twice the rate of Whites, regardless of such comorbidities., Conclusions: Latinx and African American patients with COVID-19 have higher rates of hospitalization and ICU admission than White patients. The etiologies of such disparities are likely multifactorial and cannot be explained only by reported comorbidities., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Perioperative management of patients with sellar lesions is complex, requiring input from a multidisciplinary team of specialists for ongoing management of both endocrinological and neurosurgical issues. Here, the authors reviewed the experience of a single multidisciplinary center over 10 years to identify key postoperative practices that ensure positive outcomes for patients with sellar lesions who undergo transsphenoidal surgery., Methods: The authors performed a retrospective review of all transsphenoidal operations carried out by the senior author at a single center from April 2008 through November 2018. They included only adult patients and recorded perioperative management. They also reviewed the evolution of clinical practices for perioperative care at their institution to identify strategies for ensuring positive patient outcomes, and they reviewed the literature on select related topics., Results: In total, 1023 operations in 928 patients were reviewed. Of these, 712 operations were for pituitary adenomas (69.6%), and 122 were for Rathke cleft cysts (11.9%). The remainder included operations for craniopharyngiomas (3.6%), arachnoid cysts (1.7%), pituitary tumor apoplexy (1.0%), and other sellar pathologies (12.2%). Among the reviewed operations, the median hospital stay was 3 days (IQR 2-3). Patient management details during the pre-, intra-, and postoperative periods were identified, including both shared characteristics of all patients undergoing transsphenoidal surgery and unique characteristics that are specific to certain lesion types or patient populations., Conclusions: Patients with sellar lesions who undergo transsphenoidal surgery require complex, multidisciplinary perioperative care to monitor for common adverse events and to improve outcomes, but there is a dearth of high-quality evidence guiding most perioperative practices. Here, the authors reviewed practices at their institution across more than 1000 transsphenoidal operations that may help ensure successful patient outcomes.

Background: Glioblastoma (GB) is the most common and most lethal primary malignant brain tumor. Extent of surgical resection is one of the most important prognostic factors associated with improved survival. Historically, patients living in nonmetropolitan counties in the United States have limited access to optimal treatment and health care services. The aim of this study is to determine whether there is an association between urbanicity and surgical treatment patterns among US patients with primary GB., Methods: Cases with histologically confirmed, primary GB diagnosed between 2005 and 2015 were obtained from the Central Brain Tumor Registry of the United States (CBTRUS) in collaboration with the Centers for Disease Control and Prevention, and the National Cancer Institute. Multivariable logistic regression models were constructed to assess the association between urbanicity and receipt of surgical treatment (gross total resection [GTR]/subtotal resection [STR] vs biopsy only/none) and extent of resection (GTR vs STR), adjusted for age at diagnosis, sex, race, US regional division, and primary tumor site., Results: Patients residing in nonmetropolitan counties were 7% less likely to receive surgical treatment (odds ratio [OR] = 0.93, 95% CI: 0.89-0.96, P < .0001). Among those who received surgical treatment, metropolitan status was not significantly associated with receiving GTR vs STR (OR = 0.99, 95% CI: 0.94-1.04, P = .620)., Conclusions: Among US patients with GB, urbanicity is associated with receipt of surgical treatment, but among patients who receive surgery, urbanicity is not associated with extent of resection. These results point to potential differences in access to health care for those in nonmetropolitan areas that warrant further exploration., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tea and coffee have antioxidant and neuroprotective effects. Observational studies suggest that tea and coffee intake may reduce cancer risk, but data on glioma risk are inconclusive. We evaluated the association between tea, coffee and caffeine intake and glioma risk in the female Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) and the male Health Professionals Follow-Up Study (HPFS). Cumulative intake was derived from validated quadrennial food frequency questionnaires. Glioma cases were confirmed by medical record review. Multivariable-adjusted hazard ratios of glioma by beverage intake category were estimated using Cox proportional hazards models. We documented 554 incident cases of glioma (256 in NHS, 87 in NHSII and 211 in HPFS). Compared to <1 cup/week, higher tea consumption was borderline inversely associated with glioma risk in pooled cohorts (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.49-1.10 for >2 cups/day, p-trend = 0.05), but not in women (HR = 0.74, 95% CI: 0.47-1.18 for >2 cups/day, p-trend = 0.11) or men (HR = 0.70, 95% CI: 0.30-1.60 for >2 cups/day, p-trend = 0.30) separately. Overall, we observed no significant associations between caffeinated, decaffeinated or total coffee intake and glioma risk. There were no material differences in the results with baseline values, 8-year lagged responses, or when limited to glioblastoma (n = 362). In three large prospective cohort studies, tea intake was borderline inversely associated with glioma risk. No significant associations were observed for coffee intake and glioma risk. These results merit further exploration in prospective studies., (© 2019 UICC.)

Background: Although survival statistics in patients with glioblastoma multiforme (GBM) are well-defined at the group level, predicting individual patient survival remains challenging because of significant variation within strata., Objective: To compare statistical and machine learning algorithms in their ability to predict survival in GBM patients and deploy the best performing model as an online survival calculator., Methods: Patients undergoing an operation for a histopathologically confirmed GBM were extracted from the Surveillance Epidemiology and End Results (SEER) database (2005-2015) and split into a training and hold-out test set in an 80/20 ratio. Fifteen statistical and machine learning algorithms were trained based on 13 demographic, socioeconomic, clinical, and radiographic features to predict overall survival, 1-yr survival status, and compute personalized survival curves., Results: In total, 20 821 patients met our inclusion criteria. The accelerated failure time model demonstrated superior performance in terms of discrimination (concordance index = 0.70), calibration, interpretability, predictive applicability, and computational efficiency compared to Cox proportional hazards regression and other machine learning algorithms. This model was deployed through a free, publicly available software interface (https://cnoc-bwh.shinyapps.io/gbmsurvivalpredictor/)., Conclusion: The development and deployment of survival prediction tools require a multimodal assessment rather than a single metric comparison. This study provides a framework for the development of prediction tools in cancer patients, as well as an online survival calculator for patients with GBM. Future efforts should improve the interpretability, predictive applicability, and computational efficiency of existing machine learning algorithms, increase the granularity of population-based registries, and externally validate the proposed prediction tool., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: Sports injuries present a considerable risk of debilitating spinal injury. Here, the authors sought to profile the epidemiology and clinical risk of traumatic spinal injuries (TSIs) in pediatric sports injuries., Methods: The authors conducted a retrospective cohort analysis of pediatric patients who had experienced a sports-related TSI, including spinal fractures and spinal cord injuries, encoded in the National Trauma Data Bank in the period from 2011 to 2014., Results: Included in the analysis were 1723 cases of pediatric sports-related TSI, which represented 3.7% of all pediatric sports-related trauma. The majority of patients with TSI were male (81%), and the median age was 15 years (IQR 13-16 years). TSIs arose most often from cycling accidents (47%) and contact sports (28%). The most frequently fractured regions were the thoracic (30%) and cervical (27%) spine. Among patients with spinal cord involvement (SCI), the cervical spine was involved in 60% of cases.The average length of stay for TSIs was 2 days (IQR 1-5 days), and 32% of the patients required ICU-level care. Relative to other sports-related trauma, TSIs without SCI were associated with an increased adjusted mean length of stay by 1.8 days (95% CI 1.6-2.0 days), as well as the need for ICU-level care (adjusted odds ratio [aOR] 1.6, 95% CI 1.3-1.9). Also relative to other sports-related trauma, TSIs with SCI had an increased length of stay by 2.1 days (95% CI 1.8-2.6 days) and the need for ICU-level care (aOR 3.6, 95% CI 2.6-4.8).TSIs without SCI were associated with discharge to or with rehabilitative services (aOR 1.7, 95% CI 1.5-2.0), as were TSIs with SCI (aOR 4.0, 95% CI 3.2-4.9), both relative to other sports-related trauma. Among the patients with TSIs, predictors of the need for rehabilitation at discharge were having a laminectomy or fusion, concomitant lower-extremity injury, head injury, and thoracic injury. Although TSIs affected 4% of the study cohort, these injuries were present in 8% of patients discharged to or with rehabilitation services and in 17% of those who died in the hospital., Conclusions: Traumatic sports-related spinal injuries cause significant morbidity in the pediatric population, especially if the spinal cord is involved. The majority of TSI cases arose from cycling and contact sports accidents, underscoring the need for improving education and safety in these activities.

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.

Primary brain tumors account for ~1% of new cancer cases and ~2% of cancer deaths in the United States; however, they are the most commonly occurring solid tumors in children. These tumors are very heterogeneous and can be broadly classified into malignant and benign (or non-malignant), and specific histologies vary in frequency by age, sex, and race/ethnicity. Epidemiological studies have explored numerous potential risk factors, and thus far the only validated associations for brain tumors are ionizing radiation (which increases risk in both adults and children) and history of allergies (which decreases risk in adults). Studies of genetic risk factors have identified 32 germline variants associated with increased risk for these tumors in adults (25 in glioma, 2 in meningioma, 3 in pituitary adenoma, and 2 in primary CNS lymphoma), and further studies are currently under way for other histologic subtypes, as well as for various childhood brain tumors. While identifying risk factors for these tumors is difficult due to their rarity, many existing datasets can be leveraged for future discoveries in multi-institutional collaborations. Many institutions are continuing to develop large clinical databases including pre-diagnostic risk factor data, and developments in molecular characterization of tumor subtypes continue to allow for investigation of more refined phenotypes. Key Point 1. Brain tumors are a heterogeneous group of tumors that vary significantly in incidence by age, sex, and race/ethnicity.2. The only well-validated risk factors for brain tumors are ionizing radiation (which increases risk in adults and children) and history of allergies (which decreases risk).3. Genome-wide association studies have identified 32 histology-specific inherited genetic variants associated with increased risk of these tumors., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Statins have previously been shown to have protective effects for other cancers, but no prospective studies of statin use and glioma have been conducted. Methods We evaluated the association between statin use and risk of glioma in the female Nurses' Health Study (NHS, n = 114,419) and Nurses' Health Study II (NHSII, n = 115,813) and the male Health Professionals Follow-up Study (HPFS, n = 50,223). Glioma cases were confirmed by medical record review. Age and multivariable-adjusted hazard ratios of glioma by statin use were estimated using Cox proportional hazards models. Results In 4,430,700 person-years of follow-up, we confirmed 483 incident cases of glioma. Compared with never-users, ever statin use was associated with borderline increased risk of glioma in the combined cohorts (age-adjusted HR = 1.23, 95% CI 0.99-1.54), as was longer duration of statin use (HR = 1.48, 95% CI 1.08-2.03 comparing > 8 years of use to never use, p-trend = 0.01). We also observed a significant inverse association between hyperlipidemia and glioma in multivariable models (HR = 0.74, 95% CI 0.59-0.93 in combined cohorts), which was attenuated in lagged analyses. Compared to never use, in multivariable-adjusted models, ever statin use (HR = 1.43, 95% CI 1.10-1.86) and statin use duration (HR = 1.72, 95% CI 1.21-2.45, for > 8 years of use, p-trend = 0.003) were each significantly associated with increased glioma risk. Conclusion In contrast to case-control studies reporting inverse associations, we found borderline increased risk of glioma with statin use. Results were strengthened after adjustment for cardiovascular risk factors due to an unexpected inverse association between hyperlipidemia and glioma risk. Further studies of statin use, hyperlipidemia, and glioma risk are warranted.