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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.
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Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Humanos , Camundongos , Animais , Receptor 4 Toll-Like/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Interleucina-6/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Citocinas/metabolismo , Macrófagos/metabolismo , Inflamação/etiologia , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar Aguda/metabolismo , Hemoglobinas/metabolismo , Síndrome do Desconforto Respiratório/complicações , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
BACKGROUND: Machine learning models can help anesthesiology clinicians assess patients and make clinical and operational decisions, but well-designed human-computer interfaces are necessary for machine learning model predictions to result in clinician actions that help patients. Therefore, the goal of this study was to apply a user-centered design framework to create a user interface for displaying machine learning model predictions of postoperative complications to anesthesiology clinicians. METHODS: Twenty-five anesthesiology clinicians (attending anesthesiologists, resident physicians, and certified registered nurse anesthetists) participated in a 3-phase study that included (phase 1) semistructured focus group interviews and a card sorting activity to characterize user workflows and needs; (phase 2) simulated patient evaluation incorporating a low-fidelity static prototype display interface followed by a semistructured interview; and (phase 3) simulated patient evaluation with concurrent think-aloud incorporating a high-fidelity prototype display interface in the electronic health record. In each phase, data analysis included open coding of session transcripts and thematic analysis. RESULTS: During the needs assessment phase (phase 1), participants voiced that (a) identifying preventable risk related to modifiable risk factors is more important than nonpreventable risk, (b) comprehensive patient evaluation follows a systematic approach that relies heavily on the electronic health record, and (c) an easy-to-use display interface should have a simple layout that uses color and graphs to minimize time and energy spent reading it. When performing simulations using the low-fidelity prototype (phase 2), participants reported that (a) the machine learning predictions helped them to evaluate patient risk, (b) additional information about how to act on the risk estimate would be useful, and (c) correctable problems related to textual content existed. When performing simulations using the high-fidelity prototype (phase 3), usability problems predominantly related to the presentation of information and functionality. Despite the usability problems, participants rated the system highly on the System Usability Scale (mean score, 82.5; standard deviation, 10.5). CONCLUSIONS: Incorporating user needs and preferences into the design of a machine learning dashboard results in a display interface that clinicians rate as highly usable. Because the system demonstrates usability, evaluation of the effects of implementation on both process and clinical outcomes is warranted.
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Design Centrado no Usuário , Interface Usuário-Computador , Humanos , Grupos Focais , Registros Eletrônicos de Saúde , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
PURPOSE: Patients and caregivers impacted by myelomeningocele (MMC) use online discussion board forums to create community and share information and concerns about this complex medical condition. We aim to identify the primary concerns expressed on these forums with the goal of understanding gaps in care that may merit investment of resources to improve care received by this population. METHODS: Anonymous posts from online MMC discussion boards were compiled using internet search engines. Posts were then analyzed using an adaptation of the Grounded Theory Method, a three-step system involving open, axial, and selective coding of the data by two independent researchers to identify common themes. RESULTS: Analysis of 400 posts written primarily by parents (n = 342, 85.5%) and patients (n = 45, 11.25%) yielded three overarching themes: questions surrounding quality of life, a lack of support for mothers of children with MMC, and confusion with a complex healthcare system. Many posts revealed concerns about management and well-being with MMC, including posts discussing symptoms and related conditions (n = 299, 75.75%), treatments (n = 259, 65.75%), and emotional aspects of MMC (n = 146, 36.5%). Additionally, families, especially mothers, felt a lack of support in their roles as caregivers. Finally, in 118 posts (29.5%), patients and families expressed frustration with navigating a complex healthcare system and finding specialists whose opinions they trusted. CONCLUSIONS: MMC is a complex medical condition that impacts patients and families in unique ways. Analysis of online discussion board posts identified key themes to be addressed in order to improve the healthcare experiences of those impacted by MMC.
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Cuidadores , Meningomielocele , Humanos , Meningomielocele/psicologia , Cuidadores/psicologia , Feminino , Masculino , Qualidade de Vida/psicologia , Pesquisa Qualitativa , Pais/psicologia , Criança , Adulto , InternetRESUMO
Non-invasive imaging biomarkers are useful for prognostication in patients with traumatic brain injury (TBI) at high risk for morbidity with invasive procedures. The authors present findings from a scoping review discussing the pertinent biomarkers. Embase, Ovid-MEDLINE, and Scopus were queried for original research on imaging biomarkers for prognostication of TBI in adult patients. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. Data was synthesized and confidence evaluated with the linked evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Our search yielded 3104 unique citations, 44 of which were included in this review. Study populations varied in TBI severity, as defined by Glasgow Coma Scale (GCS), including: mild (n=9), mild and moderate (n=3), moderate and severe (n=7), severe (n=6), and all GCS scores (n=17). Diverse imaging modalities were used for prognostication, predominantly computed tomography (CT) only (n=11), magnetic resonance imaging (MRI) only (n=9), and diffusion tensor imaging (DTI) (N=9). The biomarkers included diffusion coefficient mapping, metabolic characteristics, optic nerve sheath diameter, T1-weighted signal changes, cortical cerebral blood flow, axial versus extra-axial lesions, T2-weighted gradient versus spin echo, translocator protein levels, and trauma imaging of brainstem areas. The majority (93%) of studies identified that the imaging biomarker of interest had a statistically significant prognostic value; however, these are based on a very low to low level of quality of evidence. No study directly compared the effects on specific TBI treatments on the temporal course of imaging biomarkers. The current literature is insufficient to make a strong recommendation about a preferred imaging biomarker for TBI, especially considering GRADE criteria revealing low quality of evidence. Rigorous prospective research of imaging biomarkers of TBI is warranted to improve the understanding of TBI severity.
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Lesões Encefálicas Traumáticas , Imagem de Tensor de Difusão , Adulto , Humanos , Estudos Prospectivos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Biomarcadores , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The neurosurgical match involves selecting future neurosurgeons who will comprise the future national workforce, based on a competitive ranking process of applicants. We aimed to identify which sociodemographic and academic factors influence competitiveness and rank position in the match. METHODS: A Council of State Neurosurgical Societies (CSNS) survey was distributed to current U.S. neurosurgical residents. The primary outcome measure was self-reported rank position of matched program. Variables included sociodemographic and academic metrics. Fisher exact, logistic regression, and t tests were performed. RESULTS: Among the 72 respondents, median United States Medical Licensing Examination Step 1 score was 248, 34.7% were Alpha Omega Alpha inductees, 77.8% completed 1-3 sub-internship rotations, median number of publications was 5, and 13.9% had a Ph.D. Sociodemographic analysis demonstrated that 69.4% were male and 30.6% were female. Applicants with a home neurosurgery program or of female gender had statistically significantly higher odds of matching into a top 3 program on their rank list (odds ratio = 9 and odds ratio = 6, respectively). Female applicants exhibited similar mean, but less variance, compared with male respondents for United States Medical Licensing Examination Step 1 scores and number of publications. Respondents with a top 3 program match were more likely to agree that the home program supported their pursuance of neurosurgery. CONCLUSIONS: Two sociodemographic factors were independently associated with high match rank: presence of home neurosurgery program and female gender. Female respondents reported consistently strong academic metrics (similar mean, but less variance, compared with male respondents).
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Internato e Residência , Neurocirurgia , Humanos , Masculino , Feminino , Estados Unidos , Neurocirurgia/educação , Neurocirurgiões , Inquéritos e Questionários , Procedimentos NeurocirúrgicosRESUMO
OBJECTIVE: Patients and their caregivers utilize online discussion board forums as a means to seek and exchange information about their or a loved one's condition. It is important for providers to be aware of such concerns and experiences. The goal of this study was to identify the primary concerns expressed on these discussion boards regarding Chiari malformation type I (CM) and to help guide clinicians in understanding patient challenges in the treatment of CM. METHODS: The authors performed thematic analysis of anonymous online discussion board posts as identified through internet search engines. They then adopted a previously developed grounded theory method that utilizes a three-tiered coding and grouping process of posts based on commonly discovered content themes. RESULTS: Analysis of 400 discussion board posts identified four distinct themes raised by CM patients and their caregivers: the path to diagnosis, symptoms experienced, surgical intervention, and high emotional burden. Although each individual experience was unique, the path toward a CM diagnosis was expressed as a journey involving multiple physicians, alternative diagnoses, and feelings of dismissal from providers. The most common reported symptoms included dizziness, headaches, neck and back pain, sensory issues, weakness and paresthesias of the extremities, speech issues, and general fatigue. Additionally, there was an overall sense of uncertainty from patients seeking advice regarding surgical intervention, with users expressing diverse sentiments that included both positive and negative outcomes regarding surgical treatment. Lastly, a wide range of emotions was expressed related to a CM diagnosis, including concern, worry, anxiety, depression, stress, fear, and frustration. CONCLUSIONS: CM is a frequent imaging diagnosis identified in patients presenting with a wide range of symptoms, and as a result this leads to a diverse set of patient experiences. Analysis of CM patient and caregiver discussion boards revealed key themes that clinicians may address when counseling for CM.
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Malformação de Arnold-Chiari , Cuidadores , Humanos , Malformação de Arnold-Chiari/cirurgia , CefaleiaRESUMO
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.
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Disparidades em Assistência à Saúde , Neurocirurgia , Humanos , Criança , Estados Unidos , Grupos Raciais , Procedimentos Neurocirúrgicos , BibliometriaRESUMO
Aneurysmal subarachnoid hemorrhage (SAH) carries significant mortality and morbidity, with nearly half of SAH survivors having major cognitive dysfunction that impairs their functional status, emotional health, and quality of life. Apart from the initial hemorrhage severity, secondary brain injury due to early brain injury and delayed cerebral ischemia plays a leading role in patient outcome after SAH. While many strategies to combat secondary brain injury have been developed in preclinical studies and tested in late phase clinical trials, only one (nimodipine) has proven efficacious for improving long-term functional outcome. The causes of these failures are likely multitude, but include use of therapies targeting only one element of what has proven to be multifactorial brain injury process. Conditioning is a therapeutic strategy that leverages endogenous protective mechanisms to exert powerful and remarkably pleiotropic protective effects against injury to all major cell types of the CNS. The aim of this article is to review the current body of evidence for the use of conditioning agents in SAH, summarize the underlying neuroprotective mechanisms, and identify gaps in the current literature to guide future investigation with the long-term goal of identifying a conditioning-based therapeutic that significantly improves functional and cognitive outcomes for SAH patients.
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Lesões Encefálicas , Isquemia Encefálica , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Hemorragia Subaracnóidea/terapia , Hemorragia Subaracnóidea/tratamento farmacológico , Qualidade de Vida , Nimodipina , Isquemia Encefálica/tratamento farmacológico , Lesões Encefálicas/complicações , Vasoespasmo Intracraniano/etiologiaRESUMO
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)â =â 1.12, 95%CI: 1.10-1.14; Pâ <â .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)â =â 9.02, 95%CI: 8.87-9.17 vs. Q1: AAIRâ =â 9.33, 95%CI: 9.08-9.59; IRRâ =â 0.97, 95%CI: 0.94-1.00; Pâ =â .0409). Increased likelihood of surgical treatment was associated with Asian or Pacific Islander non-Hispanic individuals (compared to White non-Hispanic (WNH)) (ORâ =â 1.28, 95%CI: 1.23-1.33, Pâ <â .001) and males (ORâ =â 1.31, 95%CI: 1.29-1.33, Pâ <â .001). Black non-Hispanic individuals (ORâ =â 0.90, 95%CI: 0.88-0.92, Pâ <â .001) and those residing in metropolitan areas (ORâ =â 0.96, 95%CI: 0.96-0.96, Pâ <â .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 survivalâ =â 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.
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Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Masculino , Humanos , Estados Unidos/epidemiologia , Incidência , Meningioma/epidemiologia , Classe Social , Neoplasias Meníngeas/epidemiologiaRESUMO
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.
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OBJECTIVE: The number of cerebrovascular (CV) surgeons has grown with the rise of endovascular neurosurgery. However, it is unclear whether the number of CV surgeon-scientists has concomitantly increased. With increasing numbers of CV neurosurgeons in the US workforce, the authors analyzed associated changes in National Institutes of Health (NIH) and Neurosurgery Research and Education Foundation (NREF) funding trends for CV surgeons over time. METHODS: Publicly available data were collected on currently practicing academic CV surgeons in the US. Inflation-adjusted NIH funding between 2009 and 2021 was surveyed using NIH RePORTER and Blue Ridge Institute for Medical Research data. The K12 Neurosurgeon Research Career Development Program and NREF grant data were queried for CV-focused grants. Pearson R correlation, chi-square analysis, and the Mann-Whitney U-test were used for statistical analysis. RESULTS: From 2009 to 2021, NIH funding increased: in total (p = 0.0318), to neurosurgeons (p < 0.0001), to CV research projects (p < 0.0001), and to CV surgeons (p = 0.0018). During this time period, there has been an increase in the total number of CV surgeons (p < 0.0001), the number of NIH-funded CV surgeons (p = 0.0034), and the percentage of CV surgeons with NIH funding (p = 0.370). Additionally, active NIH grant dollars per CV surgeon (p = 0.0398) and the number of NIH grants per CV surgeon (p = 0.4257) have increased. Nevertheless, CV surgeons have been awarded a decreasing proportion of the overall pool of neurosurgeon-awarded NIH grants during this time period (p = 0.3095). In addition, there has been a significant decrease in the number of K08, K12, and K23 career development awards granted to CV surgeons during this time period (p = 0.0024). There was also a significant decline in the proportion of K12 (p = 0.0044) and downtrend in early-career NREF (p = 0.8978) grant applications and grants awarded during this time period. Finally, NIH-funded CV surgeons were more likely to have completed residency less recently (p = 0.001) and less likely to have completed an endovascular fellowship (p = 0.044) as compared with non-NIH-funded CV surgeons. CONCLUSIONS: The number of CV surgeons is increasing over time. While there has been a concomitant increase in the number of NIH-funded CV surgeons and the number of NIH grants awarded per CV surgeon in the past 12 years, there has also been a significant decrease in CV surgeons with K08, K12, and K23 career development awards and a downtrend in CV-focused K12 and early-career NREF applications and awarded grants. The latter findings suggest that the pipeline for future NIH-funded CV surgeons may be in decline.
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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.
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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.
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Neuroma Acústico , Humanos , Neuroma Acústico/genética , Neuroma Acústico/metabolismo , Neuroma Acústico/patologia , Ecossistema , Multiômica , Células de Schwann/metabolismo , Transdução de Sinais/fisiologia , Análise de Célula Única , Microambiente TumoralRESUMO
OBJECTIVE: Although individuals underrepresented in medicine (URM) make up 33% of the United States population, only 12.6% of medical school graduates identify as URM; the same percentage of URM students comprises neurosurgery residency applicants. More information is needed to understand how URM students are making specialty decisions and their perceptions of neurosurgery. The authors aimed to evaluate the differences between URM and non-URM medical students and residents in terms of the factors that contribute to specialty decision-making and perceptions of neurosurgery. METHODS: A survey was administered to all medical students and resident physicians at a single Midwestern institution to assess factors influencing medical student specialty decision-making and perceptions of neurosurgery. Likert scale responses converted to numerical values on a 5-point scale (strongly agree was the high score of 5) were analyzed with the Mann-Whitney U-test. The chi-square test was performed on the binary responses to examine associations between categorical variables. Semistructured interviews were conducted and analyzed using the grounded theory method. RESULTS: Of 272 respondents, 49.2% were medical students, 51.8% were residents, and 11.0% identified as URM. URM medical students considered research opportunities more than non-URM medical students in specialty decision-making (p = 0.023). When specialty decision-making factors were assessed, URM residents less strongly considered the technical skill required (p = 0.023), their perceived fit in the field (p < 0.001), and seeing people like them in the field (p = 0.010) than their non-URM counterparts when making specialty decisions. Within both medical student and resident respondent cohorts, the authors found no significant differences between URM and non-URM respondents in terms of their specialty decision-making being affected by medical school experiences such as shadowing, elective rotations, family exposure, or having a mentor in the field. URM residents were more concerned about the opportunity to work on health equity issues in neurosurgery than non-URM residents (p = 0.005). The predominant theme that emerged from interviews was the need for more intentional efforts to recruit and retain URM individuals in medicine and specifically neurosurgery. CONCLUSIONS: URM students may make specialty decisions differently than non-URM students. URM students were more hesitant toward neurosurgery due to their perceived lack of opportunity for health equity work in neurosurgery. These findings further inform optimization of both new and existing initiatives to improve URM student recruitment and retention in neurosurgery.
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Internato e Residência , Neurocirurgia , Estudantes de Medicina , Humanos , Estados Unidos , Etnicidade , Grupos Minoritários/educação , Neurocirurgia/educação , Inquéritos e QuestionáriosRESUMO
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.
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Internato e Residência , Neurocirurgia , Estudantes de Medicina , Gravidez , Humanos , Masculino , Feminino , Neurocirurgia/educação , Escolha da Profissão , Neurocirurgiões , Inquéritos e QuestionáriosRESUMO
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.
Assuntos
Distinções e Prêmios , Pesquisa Biomédica , Neurocirurgia , Estados Unidos , Humanos , Criança , Neurocirurgiões , Organização do Financiamento , National Institutes of Health (U.S.)RESUMO
OBJECTIVE: The objective of this study was to evaluate opportunities for early clinical exposure to neurosurgery at US allopathic medical schools and to assess associations between early exposure and recruitment into neurosurgery. METHODS: The authors conducted a standardized review of online curriculum documentation for all US allopathic medical schools, including descriptive review of opportunities for clinical neurosurgical training among medical students. Chi-square analysis was used to compare baseline characteristics of institutions. Logistic regression was performed to assess factors predictive of early exposure to clinical neurosurgery, defined as completion of a formal rotation at least 6 months prior to Electronic Residency Application Service submission. RESULTS: Among 155 allopathic US medical schools, 143 are fully accredited by the Liaison Committee on Medical Education. Eleven schools have no affiliated hospitals with a neurosurgery practice, and 26 do not have an American Association of Neurological Surgeons (AANS) medical student chapter. Overall, 94 (60.6%) have a traditional preclinical curriculum lasting 21-25 months, 50 (32.3%) offer an intermediate preclinical period of 15-20 months, and 11 (7.1%) report a short preclinical curriculum of 12-14 months. Early formal exposure to clinical neurosurgery was offered by 113 schools (72.9%). Early clinical exposure to neurosurgery was associated with a short (100%) or intermediate (76%) preclinical curriculum, as compared with a traditional curriculum (68.1%; p = 0.066). Early exposure was significantly associated with a shorter preclinical curriculum (OR 0.784, p = 0.005). AANS medical student chapters were present at a high majority of schools with early exposure (OR 4.114, p = 0.006). Medical schools with a higher percentage of graduating medical students matching into neurosurgery were associated with a shorter preclinical curriculum length (ß = -0.287, p < 0.001), were more commonly private medical schools (ß = 0.338, p < 0.001), and had early clinical exposure to neurosurgery (ß = 0.191, p = 0.032). CONCLUSIONS: Early exposure to clinical neurosurgery is available at most US allopathic medical schools and is associated with shorter preclinical curricula and institutions with AANS medical student chapters. Medical schools with a higher proportion of medical students entering neurosurgery had a shorter preclinical curriculum length and early clinical exposure to neurosurgery. Further study is recommended to characterize the impact of early exposure on long-term pedagogical outcomes.
Assuntos
Educação Médica , Internato e Residência , Neurocirurgia , Estudantes de Medicina , Humanos , Estados Unidos , Neurocirurgia/educação , Currículo , Neurocirurgiões , Faculdades de MedicinaRESUMO
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.
RESUMO
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.
Assuntos
Neurocirurgia , Cirurgiões Ortopédicos , Cirurgiões , Humanos , Masculino , Estados Unidos , Feminino , Estudos Transversais , Neurocirurgiões , Cirurgiões/educação , Neurocirurgia/educaçãoRESUMO
OBJECTIVE: Characterizing changes in the geographic distribution of neurosurgeons in the United States (US) may inform efforts to provide a more equitable distribution of neurosurgical care. Herein, the authors performed a comprehensive analysis of the geographic movement and distribution of the neurosurgical workforce. METHODS: A list containing all board-certified neurosurgeons practicing in the US in 2019 was obtained from the American Association of Neurological Surgeons membership database. Chi-square analysis and a post hoc comparison with Bonferroni correction were performed to assess differences in demographics and geographic movement throughout neurosurgeon careers. Three multinomial logistic regression models were performed to further evaluate relationships among training location, current practice location, neurosurgeon characteristics, and academic productivity. RESULTS: The study cohort included 4075 (3830 male, 245 female) neurosurgeons practicing in the US. Seven hundred eighty-one neurosurgeons practice in the Northeast, 810 in the Midwest, 1562 in the South, 906 in the West, and 16 in a US territory. States with the lowest density of neurosurgeons included Vermont and Rhode Island in the Northeast; Arkansas, Hawaii, and Wyoming in the West; North Dakota in the Midwest; and Delaware in the South. Overall, the effect size, as measured by Cramér's V statistic, between training stage and training region is relatively modest at 0.27 (1.0 is complete dependence); this finding was reflected in the similarly modest pseudo R2 values of the multinomial logit models, which ranged from 0.197 to 0.246. Multinomial logistic regression with L1 regularization revealed significant associations between current practice region and residency region, medical school region, age, academic status, sex, or race (p < 0.05). On subanalysis of the academic neurosurgeons, the region of residency training correlated with an advanced degree type in the overall neurosurgeon cohort, with more neurosurgeons than expected holding Doctor of Medicine and Doctor of Philosophy degrees in the West (p = 0.021). CONCLUSIONS: Female neurosurgeons were less likely to practice in the South, and neurosurgeons in the South and West had reduced odds of holding academic rather than private positions. The Northeast was the most likely region to contain neurosurgeons who had completed their training in the same locality, particularly among academic neurosurgeons who did their residency in the Northeast.