Barriers to neurosurgery for medical students: a national study focused on the intersectionality of gender and race.

OBJECTIVE: Despite 51.2% of medical school graduates being female, only 29.8% of neurosurgery residency applicants are female. Furthermore, only 12.6% of neurosurgery applicants identify as underrepresented in medicine (URM). Evaluating the entry barriers for female and URM students is crucial in promoting the equity and diversity of the neurosurgical workforce. The objective of this study was to evaluate barriers to neurosurgery for medical students while considering the interaction between gender and race. METHODS: A Qualtrics survey was distributed widely to US medical students, assessing 14 factors of hesitancy toward neurosurgery. Likert scale responses, representing statement agreeability, converted to numeric values on a 7-point scale were analyzed by Mann-Whitney U-test and ANOVA comparisons with Bonferroni correction. RESULTS: Of 540 respondents, 68.7% were female and 22.6% were URM. There were 22.6% male non-URM, 7.4% male URM, 53.5% female non-URM, and 15.2% female URM respondents. The predominant reasons for hesitancy toward neurosurgery included work/life integration, length of training, competitiveness of residency position, and perceived malignancy of the field. Females were more hesitant toward neurosurgery due to maternity/paternity needs (p = 0.005), the absence of seeing people like them in the field (p < 0.001), and opportunities to pursue health equity work (p < 0.001). Females were more likely to have difficulties finding a mentor in neurosurgery who represented their identities (p = 0.017). URM students were more hesitant toward neurosurgery due to not seeing people like them in the field (p < 0.001). Subanalysis revealed that when students were stratified by both gender and URM status, there were more reasons for hesitancy toward neurosurgery that had significant differences between groups (male URM, male non-URM, female URM, and female non-URM students), suggesting the importance of intersectionality in this analysis. CONCLUSIONS: The authors highlight the implications of gender and racial diversity in the neurosurgical workforce on medical student interest and recruitment. Their findings suggest the importance of actively working to address these barriers, including 1) maternity/paternity policy reevaluation, standardization, and dissemination; and 2) actively providing resources for the creation of mentorship relationships for both women and URM students in an effort to create a workforce that aligns with the changing demographics of medical graduates to continue to improve diversity in neurosurgery.

Laser interstitial thermal therapy for new and recurrent meningioma: a prospective and retrospective case series.

OBJECTIVE: Meningiomas are the most common primary brain tumors in adults and a subset are aggressive lesions resistant to standard therapies. Laser interstitial thermal therapy (LITT) has been successfully applied to other brain tumors, and recent work aims to explore the safety and long-term outcome experiences of LITT for both new and recurrent meningiomas. The authors' objective was to report safety and outcomes data of the largest cohort of LITT-treated meningioma patients to date. METHODS: Eight United States-based hospitals enrolled patients with meningioma in the Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN) prospective multicenter registry and/or contributed additional retrospective enrollments for this cohort study. Demographic, procedural, safety, and outcomes data were collected and analyzed using standard statistical methods. RESULTS: Twenty adult patients (12 prospective and 8 retrospective) with LITT-targeted meningiomas were accrued. Patients underwent LITT for new (6 patients) and recurrent (14 patients) tumors (ranging from the 1st to 12th recurrence). The 30-day complication rate was 10%. Twenty percent of patients (4/20) had exhausted all other treatment options. Median length of follow-up was 1.3 years. One-third of new (2/6) and one-half of recurrent (7/14) meningiomas had disease progression during follow-up. One-year estimated local control (LC), progression-free survival, and overall survival rates were 55.3%, 48.4%, and 86.3%, respectively. In the 12 patients who had ≥ 91% ablative coverage, 1-year estimated LC was 61.4%. The complication rate was 10% (2/20), with 1 complication being transient and resolving postoperatively. CONCLUSIONS: This cohort study supports the safety of the procedure for this tumor type. LITT can offer a much-needed treatment option, especially for patients with multiply recurrent meningiomas who have limited remaining alternatives.

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.

Association of county-level socioeconomic status with meningioma incidence and outcomes.

BACKGROUND: Prior literature suggests that individual socioeconomic status (SES) may influence incidence, treatments, and survival of brain tumor cases. We aim to conduct the first national study to evaluate the association between US county-level SES and incidence, treatment, and survival in meningioma. METHODS: The Central Brain Tumor Registry of the United States analytic dataset, which combines data from CDC's National Program of Cancer Registries (NPCR) and National Cancer Institute's Surveillance, Epidemiology, and End Results Program, was used to identify meningioma cases from 2006 to 2019. SES quintiles were created using American Community Survey data. Logistic regression models were used to evaluate associations between SES and meningioma. Cox proportional hazard models were constructed to assess the effect of SES on survival using the NPCR analytic dataset. RESULTS: A total of 409 681 meningioma cases were identified. Meningioma incidence increased with higher county-level SES with Q5 (highest quintile) having a 12% higher incidence than Q1 (incidence rate ratios (IRR) = 1.12, 95%CI: 1.10-1.14; P < .0001). The Hispanic group was the only racial-ethnic group that had lower SES associated with increased meningioma incidence (Q5: age-adjusted incidence ratio (AAIR) = 9.02, 95%CI: 8.87-9.17 vs. Q1: AAIR = 9.33, 95%CI: 9.08-9.59; IRR = 0.97, 95%CI: 0.94-1.00; P = .0409). Increased likelihood of surgical treatment was associated with Asian or Pacific Islander non-Hispanic individuals (compared to White non-Hispanic (WNH)) (OR = 1.28, 95%CI: 1.23-1.33, P < .001) and males (OR = 1.31, 95%CI: 1.29-1.33, P < .001). Black non-Hispanic individuals (OR = 0.90, 95%CI: 0.88-0.92, P < .001) and those residing in metropolitan areas (OR = 0.96, 95%CI: 0.96-0.96, P < .001) were less likely to receive surgical treatment compared to WNH individuals. Overall median survival was 137 months, and survival was higher in higher SES counties (Q5 median survival = 142 months). CONCLUSIONS: Higher county-level SES was associated with increased meningioma incidence, surgical treatment, and overall survival. Racial-ethnic stratification identified potential disparities within the meningioma population. Further work is needed to understand the underpinnings of socioeconomic and racial disparities for meningioma patients.

Cell-free hemoglobin triggers macrophage cytokine production via TLR4 and MyD88.

Cell-free hemoglobin (CFH) is elevated in the airspace of patients with acute respiratory distress syndrome (ARDS) and is sufficient to cause acute lung injury in a murine model. However, the pathways through which CFH causes lung injury are not well understood. Toll-like receptor 4 (TLR4) is a mediator of inflammation after detection of damage- and pathogen-associated molecular patterns. We hypothesized that TLR4 signaling mediates the proinflammatory effects of CFH in the airspace. After intratracheal CFH, BALBc mice deficient in TLR4 had reduced inflammatory cell influx into the airspace [bronchoalveolar lavage (BAL) cell counts, median TLR4 knockout (KO): 0.8 × 104/mL [IQR 0.4-1.2 × 104/mL], wild-type (WT): 3.0 × 104/mL [2.2-4.0 × 104/mL], P < 0.001] and attenuated lung permeability (BAL protein, TLR4KO: 289 µg/mL [236-320], WT: 488 µg/mL [422-536], P < 0.001). These mice also had attenuated production of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the airspace. C57Bl/6 mice lacking TLR4 on myeloid cells only (LysM.Cre+/-TLR4fl/fl) had reduced cytokine production in the airspace after CFH, without attenuation of lung permeability. In vitro studies confirm that WT primary murine alveolar macrophages exposed to CFH (0.01-1 mg/mL) had dose-dependent increases in IL-6, IL-1 ß, CXC motif chemokine ligand 1 (CXCL-1), TNF-α, and IL-10 (P < 0.001). Murine MH-S alveolar-like macrophages show TLR4-dependent expression of IL-1ß, IL-6, and CXCL-1 in response to CFH. Primary alveolar macrophages from mice lacking TLR4 adaptor proteins myeloid differentiation primary response 88 (MyD88) or TIR-domain-containing adapter-inducing interferon-ß (TRIF) revealed that MyD88KO macrophages had 71-96% reduction in CFH-dependent proinflammatory cytokine production (P < 0.001), whereas macrophages from TRIFKO mice had variable changes in cytokine responses. These data demonstrate that myeloid TLR4 signaling through MyD88 is a key regulator of airspace inflammation in response to CFH.NEW & NOTEWORTHY Cell-free hemoglobin (CFH) is elevated in the airspace of most patients with acute respiratory distress syndrome and causes severe inflammation. Here, we identify that CFH contributes to macrophage-induced cytokine production via Toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) signaling. These data increase our knowledge of the mechanisms through which CFH contributes to lung injury and may inform development of targeted therapeutics to attenuate inflammation.

A Systematic Review of the State of Neurosurgical Disparities Research: Past, Present, and Future.

BACKGROUND: The social determinants of health, which influence healthcare access, patient outcomes, and population-level burden of disease, contribute to health disparities experienced by marginalized patient populations. In the present study, we sought to evaluate the landscape of health disparities research within neurosurgery. METHODS: Embase, Ovid-MEDLINE, Scopus, Web of Science, Cochrane Library, and ProQuest Dissertations databases were queried for original research on health disparities regarding access to, outcomes of, and/or postoperative management after neurosurgical procedures in the United States. RESULTS: Of 883 studies screened, 196 were included, of which 144 had a neurosurgery-affiliated author. We found a significant increase in the number of neurosurgical disparities reports beginning in 2010, with only 10 studies reported before 2010. Of the included studies, 3.1% used prospective methods and 63.8% used data from national registries. The disparities analyzed were racial/ethnic (79.6%), economic/socioeconomic (53.6%), gender (18.9%), and disabled populations (0.5%), with 40.1% analyzing multiple or intersecting disparities. Of the included reports, 96.9% were in phase 1 (detecting phase of disparities research), with a few studies in phase 2 (understanding phase), and none in phase 3 (reducing phase). The spine was the most prevalent subspecialty evaluated (34.2%), followed by neuro-oncology (19.9%), cerebrovascular (16.3%), pediatrics (10.7%), functional (9.2%), general neurosurgery (5.1%), and trauma (4.1%). Senior authors with a neurosurgical affiliation accounted for 79.2% of the reports, 93% of whom were academically affiliated. CONCLUSIONS: Although a recent increase has occurred in neurosurgical disparities research within the past decade, most studies were limited to the detection of disparities without understanding or evaluating any interventions for a reduction in disparities. Future research in neurosurgical disparities should incorporate the latter 2 factors to reduce disparities and improve outcomes for all patients.

Spatial Computing for preoperative planning and postoperative evaluation of single-position lateral approaches in spinal revision surgery.

Spatial computing (SC) in a surgical context offers reconstructed interactive four-dimensional models of radiological imaging. Preoperative and postoperative assessment with SC can offer more insight into personalized surgical approaches. Spine surgery has benefitted from the use of perioperative SC assessment. Herein, we describe the use of SC to perform a perioperative assessment of a revision spinal deformity surgery. A 79-year-old wheelchair-bound male presented to the neurosurgery clinic with a history of chronic lumbar pain associated with bilateral lower extremity weakness. His surgical history is significant for an L2-L5 lumbar decompression with posterior fixation 1 year prior. On examination, there were signs of thoracic myelopathy. Imaging revealed his previous instrumentation, pseudoarthrosis, and cord compression. We perform a two-staged operation to address the thoracic spinal cord compression and myelopathy, pseudoarthrosis, and malalignment with a lack of global spinal harmony. His imaging is driven by a spatial computing and SC environment and offers support for the diagnosis of his L2-3 and L4-5 pseudoarthrosis on the reconstructed SC-based computed tomography scan. SC enabled the assessment of the configuration of the psoas muscle and course of critical neurovascular structures in addition to graft sizing, trajectory and approach, evaluation of the configuration and durability of the anterior longitudinal ligament, and the overlying abdominal viscera. SC increases the familiarity of the patient's specific anatomy and enhances perioperative assessment. As such, SC can be used to preoperatively plan for spinal revision surgery.

Medical student specialty decision-making and perceptions of neurosurgery. Part 1: Role of gender.

OBJECTIVE: Although women account for 50% of medical school graduates, less than 30% of neurosurgery residency applicants and less than 10% of neurosurgeons are female. In order to diversify the field of neurosurgery and recruit more women, it is necessary to understand why there is a disproportionately low entry rate into neurosurgery by female medical students. Factors contributing to specialty decision-making and perceptions of neurosurgery among medical students and residents, specifically differences by gender, have not been studied. The authors aimed to investigate these differences using quantitative and qualitative methods. METHODS: A Qualtrics survey was administered at the authors' institution to all medical students and resident physicians to assess factors influencing medical specialty decision-making and perceptions of neurosurgery. Likert scale responses converted to numerical values on a 5-point scale were analyzed with the Mann-Whitney U-test. The chi-square test was performed on binary responses. Semistructured interviews were conducted in a subset of survey respondents and were analyzed by using the grounded theory method. RESULTS: Of the 272 survey respondents, 48.2% were medical students and 61.0% were female. When making specialty decisions, female medical students considered maternity/paternity leave more (p = 0.028) than their male counterparts. Female medical students were more hesitant toward neurosurgery due to maternity/paternity needs (p = 0.031) and the technical skill required (p = 0.020) than male medical students. Across both genders, the majority of medical students were hesitant toward neurosurgery due to opportunities for work/life integration (93%), length of training (88%), malignancy of the field (76%), and perceived happiness of the people in the field (76%). Female residents indicated they were more likely than male residents to consider the perceived happiness of the people in the field (p = 0.003), shadowing experiences (p = 0.019), and elective rotations (p = 0.004) when making specialty decisions. Two major themes emerged from the semistructured interviews: 1) maternity needs were more of a concern for women and 2) length of training was a concern for many individuals. CONCLUSIONS: Compared with their male counterparts, female students and residents consider different factors and experiences when choosing a medical specialty and have different perceptions of neurosurgery. Exposure to and education within neurosurgery, specifically maternity needs, may help address hesitancy in pursuing a neurosurgical career among female medical students. However, cultural and structural factors may need to be addressed within neurosurgery in order to ultimately increase representation of women.

Geographic Distribution in Training and Practice of Academic Neurological and Orthopedic Spine Surgeons in the United States.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: This study aimed to stratify the geographic distribution of academic spine surgeons in the United States, analyzing how this distribution highlights differences in academic, demographic, professional metrics, and gaps in access to spine care. METHODS: Spine surgeons were identified using American Association of Neurological Surgeons and American Academy of Orthopedic Surgeons databases, categorizing into geographic regions of training and practice. Departmental websites, National Institutes of Health (NIH) RePort Expenditures and Results, Google Patent, and NIH icite databases were queried for demographic and professional metrics. RESULTS: Academic spine surgeons (347 neurological; 314 orthopedic) are predominantly male (95%) and few have patents (23%) or NIH funding (4%). Regionally, the Northeast has the highest proportion per capita (3.28 surgeons per million), but California is the state with the highest proportion (13%). The Northeast has the greatest regional retention post-residency at 74%, followed by the Midwest (59%). The West and South are more associated with additional degrees. Neurosurgery-trained surgeons hold more additional degrees (17%) than orthopedic surgeons (8%), whereas more orthopedic surgeons hold leadership positions (34%) than neurosurgeons (20%). CONCLUSIONS: Academic spine surgeons are found at the highest proportion in the Northeast and California; the Northeast has the greatest regional retention. Spine neurosurgeons have more additional degrees, whereas spine orthopedic surgeons have more leadership positions. These results are relevant to training programs looking to correct geographic disparities, surgeons in search of training programs, or students in pursuit of spine surgery.

Impact of Neurosurgery Research and Education Foundation awards on subsequent grant funding and career outcomes of neurosurgeon-scientists.

OBJECTIVE: The Neurosurgery Research and Education Foundation (NREF) provides diverse funding opportunities for in-training and early-career neurosurgeon-scientists. The authors analyzed the impact of NREF funding on the subsequent career success of neurosurgeons in obtaining research funding and academic achievements. METHODS: The NREF database was queried to identify NREF winners from 2000 to 2015. The award recipients were surveyed to obtain information about their demographic characteristics, academic career, and research funding. Only subsequent research support with an annual funding amount of $50,000 or greater was included. The primary outcome was the NREF impact ratio, defined as the ratio between NREF award research dollars and subsequent grant funding dollars. The secondary outcomes were time to subsequent grant funding as principal investigator (PI), clinical practice settings, and final academic position achieved. RESULTS: From 2000 to 2015, 158 neurosurgeons received 164 NREF awards totaling $8.3 million (M), with $1.7 M awarded to 46 Young Clinician Investigators (YCIs), $1.5 M to 18 Van Wagenen Fellows (VWFs), and $5.1 M to 100 resident Research Fellowship Grant (RFG) awardees. Of all awardees, 73% have current academic appointments, and the mean ± SD number of publications and H-index were 71 ± 82 and 20 ± 15, respectively. The overall response rate to our survey was 70%, and these respondents became the cohort for our analysis. In total, respondents cumulatively obtained $776 M in post-NREF award grant funding, with the most common sources of funding including the National Institutes of Health ($327 M) and foundational awards ($306 M). The NREF impact ratios for awardees were $1:$381 for YCI, $1:$113 for VWF, and $1:$41 for resident RFG. Awardees with NREF projects in functional neurosurgery, pediatric neurosurgery, and neuro-oncology had the highest NREF impact ratios of $1:$194, $1:$185, and $1:$162, respectively. Of respondents, 9% became department chairs, 26% became full professors, 82% received at least 1 subsequent research grant, and 66% served as PI on a subsequent research grant after receiving their NREF awards. CONCLUSIONS: In-training and early-career neurosurgeons who were awarded NREF funding had significant success in acquiring subsequent grant support, research productivity, and achievements of academic rank. NREF grants provide a tremendous return on investment across various career stages and subspecialities. They also appeared to have a broader impact on trajectory of research and innovation within the field of neurosurgery.

Corrigendum: Identification and management of aggressive meningiomas.

[This corrects the article DOI: 10.3389/fonc.2022.851758.].

Etiology- and region-specific characteristics of transependymal cerebrospinal fluid flow.

OBJECTIVE: Transependymal flow (TEF) of CSF, often delineated as T2-weighted hyperintensity adjacent to the lateral ventricles on MRI, is a known imaging finding, usually in the setting of CSF flow disturbances. Specific radiological features of TEF and their relationships with clinical markers of hydrocephalus and underlying disease pathology are not known. Here, the authors describe the radiological features and clinical associations of TEF with implications for CSF circulation in the setting of intracranial pathology. METHODS: After obtaining IRB review and approval, the authors reviewed the radiological records of all patients who underwent intracranial imaging with CT or MRI at St. Louis Children's Hospital, St. Louis, Missouri, between 2008 and 2019 to identify individuals with TEF. Then, under direct review of imaging, TEF pattern, degree, and location and underlying pathology and other radiological and clinical features pertaining to CSF circulation and CSF disturbances were noted. RESULTS: TEF of CSF was identified in 219 patients and was most prevalent in the setting of neoplasms (72%). In 69% of the overall cohort, TEF was seen adjacent to the anterior aspect of the frontal horns and the posterior aspect of the occipital horns of the lateral ventricles, and nearly half of these patients also had TEF dorsal to the third ventricle near the splenium of the corpus callosum. This pattern was independently associated with posterior fossa medulloblastoma when compared with pilocytic astrocytoma (OR 4.75, 95% CI 1.43-18.53, p = 0.0157). Patients with congenital or neonatal-onset hydrocephalus accounted for 13% of patients and were more likely to have TEF circumferentially around the ventricles without the fronto-occipital distribution. Patients who ultimately required permanent CSF diversion surgery were more likely to have the circumferential TEF pattern, a smaller degree of TEF, and a lack of papilledema at the time of CSF diversion surgery. CONCLUSIONS: CSF transmigration across the ependyma is usually restricted to specific periventricular regions and is etiology specific. Certain radiological TEF characteristics are associated with tumor pathology and may reflect impaired or preserved ependymal fluid handling and global CSF circulation. These findings have implications for TEF as a disease-specific marker and in understanding CSF handling within the brain.

Identification and Management of Aggressive Meningiomas.

Meningiomas are common primary central nervous system tumors derived from the meninges, with management most frequently entailing serial monitoring or a combination of surgery and/or radiation therapy. Although often considered benign lesions, meningiomas can not only be surgically inaccessible but also exhibit aggressive growth and recurrence. In such cases, adjuvant radiation and systemic therapy may be required for tumor control. In this review, we briefly describe the current WHO grading scale for meningioma and provide demonstrative cases of treatment-resistant meningiomas. We also summarize frequently observed molecular abnormalities and their correlation with intracranial location and recurrence rate. We then describe how genetic and epigenetic features might supplement or even replace histopathologic features for improved identification of aggressive lesions. Finally, we describe the role of surgery, radiotherapy, and ongoing systemic therapy as well as precision medicine clinical trials for the treatment of recurrent meningioma.