Resident Salary Compared to Living Wages at United States Training Institutions.

OBJECTIVE: To compare living wages and salaries at US residency programs. SUMMARY BACKGROUND DATA: It is unknown how resident salary compares to living wages across the United States (US). METHODS: Cross-sectional analysis of publicly available resident salary affordability from training centers with post-graduate-year (PGY)-1 through PGY-7 resident compensation for 2022-2023 was compared with the Massachusetts Institute of Technology (MIT) Living-Wage Calculator. Resident salary to living wage ratios were calculated using PGY-4 salary for each family composition. Univariate and multivariable analysis of PGY-4 salary affordability was performed, accounting for proportion of expected living wages to taxes, transportation, housing, healthcare, childcare, and food, as well as unionization and state income-tax. RESULTS: 118 residency programs, representing over 60% of US trainees, were included, 20 (17%) of which were unionized. Single-parent families were unable to earn a living wage until PGY-7. Residents with 1 child in 2-adult (single-income) and 2-adult (dual-income) families earn below living wages until PGY-5 and PGY-3, respectively. Residents with more than 1 child never earn a living wage. Multivariable regression analysis using PGY-4 salary: living wage ratios in single-child, 2-parent homes showed food expense and unionization status were consistent predictors of affordability. Unionization was associated with lower affordability pre-stipend, almost equivalent affordability post-stipend, and lower affordability post-stipend and union dues. CONCLUSIONS: Resident salaries often preclude residents with children from earning a living wage. Unionization is not associated with increased resident affordability in this cross-sectional analysis. All annual reimbursement data should be centrally compiled, and additional stipends should be considered for residents with children.

J-Difference editing (MEGA) of lactate in the human brain at 3T.

PURPOSE: The need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J-difference editing of lactate, threonine can be co-edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow-band editing 180° pulses (E180) in MEGA-PRESS acquisitions to resolve separately the 1.3-ppm resonances of lactate and threonine. METHODS: Two 45.3-ms rectangular E180 pulses, which had negligible effects 0.15-ppm away from the carrier frequency, were implemented in a MEGA-PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow-band E180 MEGA and another MEGA-PRESS sequence with broad-band E180 pulses were evaluated in six healthy subjects. RESULTS: The 45.3-ms E180 MEGA offered a difference-edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad-band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet-resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N-acetylaspartate at 12 mM. CONCLUSION: Narrow-band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels.

Clinical and descriptive characteristics associated with high-grade meningioma in a large clinical series.

PURPOSE: We studied 571 patients with intracranial meningioma for clinical characteristics and tumor location associated with high grade meningioma (WHO II/III). MATERIALS AND METHODS: Patients were participants in a multicentre epidemiologic study of risk factors for primary brain tumors including meningioma recruited from September 2005 to November 2019. We included patients 18 or older with a recent diagnosis of a primary intracranial meningioma of any subtype (ICD9/10: 9530-0, 9531-0, 9532-0, 9537-0, 9533-0, 9534-0, 9530-0, 9538-1, 9538-3) who were enrolled at neuro-oncology and neuro-surgery clinics in the southeastern U.S. RESULTS: The median patient age was 58 years (IQR: 48-68) and the majority of patients were female (n = 415; 72.7%) and Caucasian (n = 516; 90.4%). Most patients were symptomatic (n = 460; 80.6%) and their tumours more commonly occurred in a non-skull base location (n = 298; 52.2%). A total of 86 patients (15.0%) had a WHO grade II/III meningioma. Compared to patients with WHO grade I tumours, patients with WHO II/III meningiomas were over 3-times more likely to be male (odds ratio (OR): 3.25; 95% confidence interval (CI): 1.98, 5.35) adjusting for age, race, symptomatic presentation, and skull-based location. Moreover, a WHO grade II/III meningioma was substantially less likely to be observed in asymptomatic patients (OR: 0.15, 95% CI: 0.04, 0.42), and in patients with a skull-based tumour (OR: 0.40, 95% CI: 0.24, 0.66), adjusting for other factors. Male gender, symptomatic tumour, and a non-skull base location were independently associated with WHO grade II/III meningioma. CONCLUSION: These findings may shed additional light on the underlying pathogenesis of meningioma.

Outcomes following surgical resection of cystic intracranial meningiomas.

INTRODUCTION: Cystic meningiomas are rare, accounting for 2-7% of all intracranial meningiomas. Little is known regarding whether these meningiomas behave differently compared to solid meningiomas. We sought to study this relatively uncommon imaging appearance of meningioma and to evaluate its clinical significance. METHODS: A single-institution retrospective cohort study of surgically-treated meningioma patients between 2000 and 2019 was conducted. Cystic meningioma was defined as a tumor with an intratumoral or peritumoral cyst present on preoperative imaging. Demographics, preoperative imaging, histopathology characteristics, operative data, and surgical outcomes were reviewed. Imaging variables, histopathology and outcomes were reported for cystic meningiomas and compared with non-cystic meningiomas. Univariate/multivariable analyses were conducted. RESULTS: Of 737 total meningiomas treated surgically, 38 (5.2%) were cystic. Gross total resection (GTR) was achieved in 84.2% of cystic meningioma patients. Eighty-two percent of cystic meningiomas were WHO grade I (n = 31), 15.7% were grade II and 2.6% were grade III. Most cystic meningiomas had low Ki-67/MIB-1 proliferation index (n = 24, 63.2%). A total of 18.4% (n = 7) patients with cystic meningioma had recurrence compared to 12.2% (n = 80) of patients with non-cystic meningioma (p = 0.228). No significant difference in median time to recurrence was observed between cystic and non-cystic meningiomas (25.4, Q1:13.9, Q3:46.9 months vs. 13.4, Q1:8.6, Q3:35.5 months, p = 0.080). CONCLUSIONS: A small portion of intracranial meningiomas have cystic characteristics on imaging. Cystic meningiomas are frequently WHO grade I, have low proliferation index, and had similar outcomes compared to non-cystic meningioma. Cysts in meningioma may not be a surrogate to determine aggressive meningioma behavior.

Matched case-control analysis of outcomes following surgical resection of incidental meningioma.

PURPOSE: The management of incidentally discovered meningioma remains controversial. We sought to compare outcomes following surgical resection of incidental meningioma to a matched cohort of symptomatic meningiomas. METHODS: A retrospective single-center case-control study was conducted for patients undergoing resection of incidental meningioma from 2000 to 2019. A 1:1 case-control matching for incidental and symptomatic meningioma was performed using the following variables: age at initial visit, gender, tumor location/size, and presence of peritumoral edema. Primary outcomes included (1) WHO grading/histopathological subtype/MIB-1 index, (2) extent of resection (gross total resection or subtotal resection), and (3) recurrence. Outcomes were compared between groups using descriptive/bivariate analyses. RESULTS: A total of 91 incidental meningiomas were analyzed. Trauma was the most common reason (n = 19, 21%) to obtain imaging, and tumor size the leading reason to operate (n = 37, 41%). Median time-to-surgery from initial clinical encounter was 5-months (Q1:3, Q3:16.5). More incidental meningioma patients (n = 47, 52%) were privately insured compared to their matched symptomatic cohort (n = 30, 33%) (P = 0.006). Patients with incidental meningioma had significantly higher mean Karnofsky Performance Scale at time-of-surgery (93.2, SD:11.1 vs. 81.4, SD:12.7) (P < 0.001). There were no significant differences in primary/secondary outcomes between the groups. Incidental meningioma was not associated with recurrence on Cox proportional hazards analysis (HR: 0.795, 95%CI: 0.3-2.1, P = 0.637). CONCLUSION: Matched case-control analysis demonstrated no significant differences in clinical, histopathological, and functional outcomes following resection of incidental and symptomatic meningioma. While non-operative management with close follow-up and serial imaging is preferred for incidental meningiomas, those undergoing resection when indicated can anticipate similar safety and efficacy as symptomatic meningiomas.

Hyperoxemia and Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Cerebral vasospasm is a major contributor to disability and mortality after aneurysmal subarachnoid hemorrhage. Oxidation of cell-free hemoglobin plays an integral role in neuroinflammation and is a suggested source of tissue injury after aneurysm rupture. This study sought to determine whether patients with subarachnoid hemorrhage and cerebral vasospasm were more likely to have been exposed to early hyperoxemia than those without vasospasm. METHODS: This single-center retrospective cohort study included adult patients presenting with aneurysmal subarachnoid hemorrhage to Vanderbilt University Medical Center between January 2007 and December 2017. Patients with an ICD-9/10 diagnosis of aneurysmal subarachnoid hemorrhage were initially identified (N = 441) and subsequently excluded if they did not have intracranial imaging, arterial PaO2 values or died within 96 h post-rupture (N = 96). The final cohort was 345 subjects. The degree of hyperoxemia was defined by the highest PaO2 measured within 72 h after aneurysmal rupture. The primary outcome was development of cerebral vasospasm, which included asymptomatic vasospasm and delayed cerebral ischemia (DCI). Secondary outcomes were mortality and modified Rankin Scale. RESULTS: Three hundred and forty five patients met inclusion criteria; 218 patients (63%) developed vasospasm. Of those that developed vasospasm, 85 were diagnosed with delayed cerebral ischemia (DCI, 39%). The average patient age of the cohort was 55 ± 13 years, and 68% were female. Ninety percent presented with Fisher grade 3 or 4 hemorrhage (N = 310), while 42% presented as Hunt-Hess grade 4 or 5 (N = 146). In univariable analysis, patients exposed to higher levels of PaO2 by quintile of exposure had a higher mortality rate and were more likely to develop vasospasm in a dose-dependent fashion (P = 0.015 and P = 0.019, respectively). There were no statistically significant predictors that differentiated asymptomatic vasospasm from DCI and no significant difference in maximum PaO2 between these two groups. In multivariable analysis, early hyperoxemia was independently associated with vasospasm (OR = 1.15 per 50 mmHg increase in PaO2 [1.03, 1.28]; P = 0.013), but not mortality (OR = 1.10 [0.97, 1.25]; P = 0.147) following subarachnoid hemorrhage. CONCLUSIONS: Hyperoxemia within 72 h post-aneurysmal rupture is an independent predictor of cerebral vasospasm, but not mortality in subarachnoid hemorrhage. Hyperoxemia is a variable that can be readily controlled by adjusting the delivered FiO2 and may represent a modifiable risk factor for vasospasm.

Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics.

Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with ≥40% AA (AFR≥0.4 ), and ≥15% NAA (AMR≥0.15 ), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 × 10-4 ; 11p11.12, p = 7.0 × 10-4 ) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR≥0.4 . In addition, we identified a peak at rs1620291 (p = 4.36 × 10-6 ) in 7q21.3. Among AMR≥0.15 , we found an association between increased EA in one region (12q24.21, p = 8.38 × 10-4 ), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 × 10-4 ). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies.

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

BACKGROUND: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. METHODS: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. CONCLUSIONS: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; initially registered 19 September 2002.

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.

Handedness and the risk of glioma.

Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case-control study (1849 glioma cases and 1354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas). In the case-control study, we found a significant inverse association between left handedness and glioma risk, with left-handed persons exhibiting a 35% reduction in the risk of developing glioma [odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51-0.83] after adjustment for age, gender, race, education, and state of residence; similar inverse associations were observed for GBM (OR = 0.69, 95% CI 0.52-0.91), and non-GBM (OR = 0.59, 95% CI 0.42-0.82) subgroups. The association was consistent in both males and females, and across age strata, and was observed in both glioblastoma and in lower grade tumors. In the prospective cohort study, we found no association between handedness and glioma risk (hazards ratio = 0.92, 95% CI 0.67-1.28) adjusting for age, gender, and race. Further studies on this association may help to elucidate mechanisms of pathogenesis in glioma.

Older age at the completion of linear growth is associated with an increased risk of adult glioma.

PURPOSE: To examine the association of age when adult height was attained with glioma risk. METHODS: We analyzed data from a US-based case-control study of glioma risk factors. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated between age at attainment of adult height and glioma risk. Multivariate models were adjusted for age, race, sex, education, and state of residence. We examined associations overall, and according to glioma grade, sex, and final adult height. RESULTS: The study set included n = 951 controls and n = 776 cases, with a median age of 56 (18-92); the majority was male (53.8%) and identified as Caucasian. Older age at height completion was associated with an increased risk of glioma. A significant positive trend was observed both for glioblastoma (OR 1.10; 95% CI 1.04-1.17 per 1-year increase in age) and lower grade non-glioblastoma subtypes combined (OR 1.18; 95% CI 1.10-1.28 per year increase in age). The association was observed in men and women, and in all categories of final adult height. CONCLUSIONS: We observed for the first time a positive association between glioma risk and a prolonged adolescent growth phase. Our results suggest a role for factors governing the timing and intensity of growth in adolescence as risk-determining exposures in adult glioma.

Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis.

The ventricular-subventricular zone (V-SVZ), which lies in the walls of the lateral ventricles (LV), is the largest neurogenic niche within the adult brain. Whether radiographic contact with the LV influences survival in glioblastoma (GBM) patients remains unclear. We assimilated and analyzed published data comparing survival in GBM patients with (LV+GBM) and without (LV-GBM) radiographic LV contact. PubMed, EMBASE, and Cochrane electronic databases were searched. Fifteen studies with survival data on LV+GBM and LV-GBM patients were identified. Their Kaplan-Meier survival curves were digitized and pooled for generation of median overall (OS) and progression free (PFS) survivals and log-rank hazard ratios (HRs). The log-rank and reported multivariate HRs after accounting for the common predictors of GBM survival were analyzed separately by meta-analyses. The calculated median survivals (months) from pooled data were 12.95 and 16.58 (OS), and 4.54 and 6.25 (PFS) for LV+GBMs and LV-GBMs, respectively, with an overall log-rank HRs of 1.335 [1.204-1.513] (OS) and 1.387 [1.225-1.602] (PFS). Meta-analysis of log-rank HRs resulted in summary HRs of 1.58 [1.35-1.85] (OS, 10 studies) and 1.41 [1.22-1.64] (PFS, 5 studies). Meta-analysis of multivariate HRs resulted in summary HRs of 1.35 [1.14-1.58] (OS, 6 studies) and 1.64 [0.88-3.05] (PFS, 3 studies). Patients with GBM contacting the LV have lower survival. This effect may be independent of the common predictors of GBM survival, suggesting a clinical influence of V-SVZ contact on GBM biology.

Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum.

The clinical effect of radiographic contact of glioblastoma (GBM) with neurogenic zones (NZ)-the ventricular-subventricular (VSVZ) and subgranular (SGZ) zones-and the corpus callosum (CC) remains unclear and, in the case of the SGZ, unexplored. We investigated (1) if GBM contact with a NZ correlates with decreased survival; (2) if so, whether this effect is associated with a specific NZ; and (3) if radiographic contact with or invasion of the CC by GBM is associated with decreased survival. We retrospectively identified 207 adult patients who underwent cytoreductive surgery for GBM followed by chemotherapy and/or radiation. Age, preoperative Karnofsky performance status score (KPS), and extent of resection were recorded. Preoperative MRIs were blindly analyzed to calculate tumor volume and assess its contact with VSVZ, SGZ, CC, and cortex. Overall (OS) and progression free (PFS) survivals were calculated and analyzed with multivariate Cox analyses. Among the 207 patients, 111 had GBM contacting VSVZ (VSVZ+GBMs), 23 had SGZ+GBMs, 52 had CC+GBMs, and 164 had cortex+GBMs. VSVZ+, SGZ+, and CC+ GBMs were significantly larger in size relative to their respective non-contacting controls. Multivariate Cox survival analyses revealed GBM contact with the VSVZ, but not SGZ, CC, or cortex, as an independent predictor of lower OS, PFS, and early recurrence. We hypothesize that the VSVZ niche has unique properties that contribute to GBM pathobiology in adults.

Analgesic use and the risk of primary adult brain tumor.

Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma.

The relative value of postoperative versus preoperative Karnofsky Performance Scale scores as a predictor of survival after surgical resection of glioblastoma multiforme.

The Karnofsky Performance Scale (KPS) score is a widespread metric to stratify patient prognosis and determine appropriate management in glioblastoma multiforme(GBM). Low preoperative KPS values have been associated with shorter overall survival (OS). However, surgical resection can have a dramatic effect on a patient's functional status which subsequently alters their KPS score. To determine the predictive value of preoperative verses postoperative KPS scores in terms of OS in patients with GBM. We conducted a retrospective review of 163 patients who underwent initial surgical intervention for pathologically proven GBM at our institution between 2003 and 2013. Pre and postoperative performance status, demographic, operative, and treatment variables were recorded for each patient. Multivariate regression analysis identified predictors of prolonged OS. The adequacy index was calculated to compare the predictive value of preoperative and postoperative KPS score. Median preoperative and postoperative KPS scores were 70 and 80, respectively. Overall, 92 (57 %) patients experienced an improvement in their KPS score, 40 (25 %) remained stable, and 29 (18 %) declined. Higher postoperative KPS (P = 0.0001), radiation therapy (P < 0.0001), younger age (P = 0.0443) and the absence of diabetes (P = 0.0006) were each independently associated with increased OS in a multivariate regression model. Postoperative KPS score has superior predictive value compared to pre-operative KPS score (A = 0.758 vs. 1.002). Postoperative KPS scores have superior predictive capabilities in terms of OS in GBM and should replace preoperative KPS scores when estimating prognosis in this population.

Circadian pathway genes in relation to glioma risk and outcome.

PURPOSE: There is growing evidence that circadian disruption may alter risk and aggressiveness of cancer. We evaluated common genetic variants in the circadian gene pathway for associations with glioma risk and patient outcome in a US clinic-based case-control study. METHODS: Subjects were genotyped for 17 candidate single nucleotide polymorphisms in ARNTL, CRY1, CRY2, CSNK1E, KLHL30, NPAS2, PER1, PER3, CLOCK, and MYRIP. Unconditional logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk under three inheritance models (additive, dominant, and recessive). Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 441 patients with high-grade tumors. Survival associations were validated using The Cancer Genome Atlas (TCGA) dataset. RESULTS: A variant in PER1 (rs2289591) was significantly associated with overall glioma risk (per variant allele OR 0.80; 95 % CI 0.66-0.97; p trend = 0.027). The variant allele for CLOCK rs11133391 under a recessive model increased risk of oligodendroglioma (OR 2.41; 95 % CI 1.31-4.42; p = 0.005), though not other glioma subtypes (p for heterogeneity = 0.0033). The association remained significant after false discovery rate adjustment (p = 0.008). Differential associations by gender were observed for MYRIP rs6599077 and CSNK1E rs1534891 though differences were not significant after adjustment for multiple testing. No consistent mortality associations were identified. Several of the examined genes exhibited differential expression in glioblastoma multiforme versus normal brain in TCGA data (MYRIP, ARNTL, CRY1, KLHL30, PER1, CLOCK, and PER3), and expression of NPAS2 was significantly associated with a poor patient outcome in TCGA patients. CONCLUSION: This exploratory analysis provides some evidence supporting a role for circadian genes in the onset of glioma and possibly the outcome of glioma.

Reproductive factors and risk of primary brain tumors in women.

Gender-specific incidence patterns and the presence of hormonal receptors on tumor cells suggest that sex hormones may play a role in the onset of primary brain tumors. However, epidemiological studies on the relation of hormonal risk factors to the risk of brain tumors have been inconsistent. We examined the role of reproductive factors in the onset of glioma and meningioma in a case-control study conducted in the Southeastern US that included 507 glioma cases, 247 meningioma cases, and 695 community-based and friend controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) adjusting for age, race, US state of residence, and education. An older age at menarche was associated with an increased risk of glioma (≥ 15 vs. ≤ 12 years: OR 1.65; 95% CI 1.11-2.45), with a stronger association observed in pre-menopausal (OR 2.22; 95% CI 1.12-4.39) than post-menopausal (OR 1.55; 95% CI 0.93-2.58) women. When compared to controls, meningioma cases were more likely to have undergone natural menopause (OR 1.52; 95% CI 1.04-2.21) whereas glioma cases were less likely to be long term users of oral contraceptives (OR 0.47; 95% CI 0.33-0.68). Increasing parity was not related to the risk of either tumor. Current findings are consistent with a limited role for hormones in the onset of brain tumors in women. Results contribute to a growing body of evidence that a later age at menarche increases the risk of glioma in women.

Techniques to Reduce the Rate of Infection in Surgeries for Cerebrospinal Fluid Shunting in Adults.

OBJECTIVE: Cerebrospinal fluid shunt placement is associated with high rates of infection. Multiple standardized protocols, particularly in pediatric populations, have been proposed to mitigate this infection rate. We sought to determine the effectiveness of a standardized shunt infection protocol in a large adult population. METHODS: A retrospective cohort study of adults presenting for primary cerebrospinal fluid shunt placement from 2012 to 2022. The primary outcome of interest was shunt infection. The primary exposure of interest was implementation of the shunt protocol (began October 2015). Secondary exposures of interest included use and type of perioperative antibiotics and total operating room time. RESULTS: In total, 820 patients were included, 140 before protocol implementation and 680 after protocol implementation. The overall number of infections over the study period was 15 (1.8% infection rate), with 8 infections preprotocol (5.7%) and 7 infections during the protocol period (1.0%). The infection protocol was associated with a decreased infection rate (odds rato [OR] 0.18, 95% confidence interval [CI] 0.05-0.58, P = 0.002). Total operating room time (OR 1.38 per 30-minute increase, 95% CI 1.05-1.81, P = 0.021) was associated with increased infection rate. Patients who received antibiotics with primarily gram-positive coverage (cefazolin or equivalent) did not have significantly different odds of shunt infection as patients who received broad-spectrum coverage (OR 2.10, 95% CI 0.56-7.88, P = 0.274). CONCLUSIONS: The implementation of an evidence-based perioperative shunt infection protocol is an effective method to decrease shunt infections. Broad-spectrum perioperative antibiotics may not have greater efficacy than gram-positive only coverage, but more research is required.

Lumbar Drain Use during Middle Fossa Approaches for Nonneoplastic Pathology of the Skull Base.

Introduction The middle fossa craniotomy (MFCs) is commonly utilized for spontaneous cerebrospinal fluid (CSF) leaks, encephaloceles, and superior semicircular canal dehiscence (SSCD). This study compares postoperative outcomes of MFCs with and without LD use. Methods A retrospective cohort study of adults over the age of 18 years presenting for the repair of nonneoplastic CSF leak, encephalocele, or SSCD via MFC from 2009 to 2021 was conducted. The main exposure of interest was the placement of an LD. The primary outcome was the presence of postoperative complications (acute/delayed neurologic deficit, meningitis, intracranial hemorrhage, and stroke). Secondary outcomes included operating room (OR) time, length of stay, recurrence, and need for reoperation. Results In total, 172 patients were included, 96 of whom received an LD and 76 who did not. Patients not receiving an LD were more likely to receive intraoperative mannitol ( n = 24, 31.6% vs. n = 16, 16.7%, p = 0.02). On univariate logistic regression, LD placement did not influence overall postoperative complications (OR: 0.38, 95% confidence interval [CI]: 0.05-2.02, p = 0.28), CSF leak recurrence (OR: 0.75, 95% CI: 0.25-2.29, p = 0.61), or need for reoperation (OR: 1.47, 95% CI: 0.48-4.96, p = 0.51). While OR time was shorter for patients not receiving LD (349 ± 71 vs. 372 ± 85 minutes), this difference was not statistically significant ( p = 0.07). Conclusion No difference in postoperative outcomes was observed in patients who had an intraoperative LD placed compared to those without LD. Operative times were increased in the LD cohort, but this difference was not statistically significant. Given the similar outcomes, we conclude that LD is not necessary to facilitate safe MCF for nonneoplastic skull base pathologies.

Velociraptor: Cross-Platform Quantitative Search Using Hallmark Cell Features.

A key challenge for single cell discovery analysis is to identify new cell types, describe them quantitatively, and seek these novel cells in new studies often using a different platform. Over the last decade, tools were developed to address identification and quantitative description of cells in human tissues and tumors. However, automated validation of populations at the single cell level has struggled due to the cytometry field's reliance on hierarchical, ordered use of features and on platform-specific rules for data processing and analysis. Here we present Velociraptor, a workflow that implements Marker Enrichment Modeling in three cross-platform modules: 1) identification of cells specific to disease states, 2) description of hallmark features for each cell and population, and 3) searching for cells matching one or more hallmark feature sets in a new dataset. A key advance is that Velociraptor registers cells between datasets, including between flow cytometry and quantitative imaging using different, overlapping feature sets. Four datasets were used to challenge Velociraptor and reveal new biological insights. Working at the individual sample level, Velociraptor tracked the abundance of clinically significant glioblastoma brain tumor cell subsets and characterized the cells that predominate in recurrent tumors as a close match for rare, negative prognostic cells originally observed in matched pre-treatment tumors. In patients with inborn errors of immunity, Velociraptor identified genotype-specific cells associated with GATA2 haploinsufficiency. Finally, in cross-platform analysis of immune cells in multiplex imaging of breast cancer, Velociraptor sought and correctly identified memory T cell subsets in tumors. Different phenotypic descriptions generated by algorithms or humans were shown to be effective as search inputs, indicating that cell identity need not be described in terms of per-feature cutoffs or strict hierarchical analyses. Velociraptor thus identifies cells based on hallmark feature sets, such as protein expression signatures, and works effectively with data from multiple sources, including suspension flow cytometry, imaging, and search text based on known or theoretical cell features.