Trends in Vitamin B12 Level Testing in Patients on Metformin From 2000 to 2020.

Background and Objectives: Metformin is one of the primary pharmacologic agents for managing type 2 diabetes mellitus (T2DM). However, it has been associated with interference in vitamin B12 absorption and deficiency. Vitamin B12 deficiency and T2DM can present diagnostic challenges for polyneuropathy. Diagnosis is essential for guiding treatment, yet the use of vitamin B12 level testing in this population may have dwindled over time amid changing practice guidelines. This study examines trends over time in the use of vitamin B12 level testing among patients on metformin. Methods: This retrospective trend analysis used data from TriNetX, a real-world, longitudinal clinical database. Patients treated with metformin from 2000 to 2020 were identified using Rx Concept Unique Identifier codes. The number of patients who underwent vitamin B12 level testing at any time after 1 month from metformin initiation was tabulated. Patients were grouped by the year of B12 level testing. Trends in B12 level testing were assessed using the Jonckheere-Terpstra statistical test (P<.05). Results: Out of 4,203,020 patients prescribed metformin, 1,055,995 (25.1%) underwent B12 level testing. The highest proportion of patients tested was in 2000 to 2002 (39.6%), while the lowest proportion was in 2018 to 2020 (20.1%). B12 testing utilization declined significantly by 19.5% from 2000-2002 to 2018-2020 (P=.001). Conclusions: In this study, we found that the use of vitamin B12 level testing in patients on metformin has significantly declined over the years, potentially impacting early detection of B12 deficiency. Future studies with more granular data from real-life practice are recommended to understand the precise reasons and impact of this trend.

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.

Early Celecoxib Use in Spontaneous Intracerebral Hemorrhage is Associated with Reduced Mortality.

BACKGROUND: Hemorrhagic strokes constitute 10-15% of all strokes and have the worst mortality and morbidity of all subtypes. Mortality and morbidity of spontaneous intracerebral hemorrhage (sICH) are often secondary to the effects of inflammation, brain edema, and swelling. Studies have shown that celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, reduces perihematomal edema formation and inflammation. This study aimed to examine the impact of celecoxib on sICH outcomes. METHODS: TriNetX, a multi-institutional research database, was retrospectively queried to identify patients with sICH. Outcomes in patients who received celecoxib within 5 days (cohort 1) were analyzed and compared to those in patients who did not receive celecoxib (cohort 2). The primary end point was mortality within 1 year of sICH. Secondary end points included ventilator dependence, tracheostomy, percutaneous endoscopic gastrostomy tube placement, craniotomy, deep venous thrombosis, pulmonary embolism, ischemic stroke, transient ischemia attack, myocardial infarction, and seizures. Further analysis was performed to assess these outcomes for patients treated with ibuprofen, a nonselective COX inhibitor. RESULTS: After propensity score matching, 833 patients were identified in each cohort based on celecoxib use. Mortality at 1 year was significantly reduced in patients with sICH receiving celecoxib compared to those who did not (13.33% vs. 17.77%; p = 0.0124). Risks of ventilator dependence, tracheostomy, percutaneous endoscopic gastrostomy tube placement, craniotomy, deep venous thrombosis, pulmonary embolism, ischemic stroke, transient ischemia attack, myocardial infarction, and seizures were not significantly increased in patients who received celecoxib within 5 days of sICH compared to those who did not receive celecoxib. There was no significant difference in mortality between patients based on ibuprofen administration. CONCLUSIONS: There exists a growing interest in using COX-2 as a potential target strategy for neuroprotection in patients with sICH, with some evidence of a mortality benefit in small cohort studies. This study shows that early celecoxib use is associated with decreased mortality in patients with sICH.

Systematic Review of Cerebrospinal Fluid Biomarker Discovery in Neuro-Oncology: A Roadmap to Standardization and Clinical Application.

Effective diagnosis, prognostication, and management of CNS malignancies traditionally involves invasive brain biopsies that pose significant risk to the patient. Sampling and molecular profiling of cerebrospinal fluid (CSF) is a safer, rapid, and noninvasive alternative that offers a snapshot of the intracranial milieu while overcoming the challenge of sampling error that plagues conventional brain biopsy. Although numerous biomarkers have been identified, translational challenges remain, and standardization of protocols is necessary. Here, we systematically reviewed 141 studies (Medline, SCOPUS, and Biosis databases; between January 2000 and September 29, 2022) that molecularly profiled CSF from adults with brain malignancies including glioma, brain metastasis, and primary and secondary CNS lymphomas. We provide an overview of promising CSF biomarkers, propose CSF reporting guidelines, and discuss the various considerations that go into biomarker discovery, including the influence of blood-brain barrier disruption, cell of origin, and site of CSF acquisition (eg, lumbar and ventricular). We also performed a meta-analysis of proteomic data sets, identifying biomarkers in CNS malignancies and establishing a resource for the research community.

Incidence of tethered cord syndrome in neurofibromatosis types 1 and 2 pediatric patients: a population-level analysis.

PURPOSE: Tethered spinal cord syndrome (TCS) is characterized by cutaneous attachments on the filum terminale that stretch the spinal cord, leading to musculoskeletal and urogenital sequelae. While the neurocutaneous associations with TCS remain undefined, a recent study reports a high incidence of TCS among a pediatric neurofibromatosis (NF) cohort. This present study utilizes a population-level database to estimate TCS incidence among pediatric patients with neurofibromatosis types 1 and 2 (NF1, NF2). METHODS: The TriNetX Research Network was queried to identify patients diagnosed with NF and/or TCS before the age of 21. Symptomatic TCS requiring surgical intervention was identified using corresponding procedural codes within 12 months following TCS diagnosis. Odds ratios (OR) were calculated to measure the associations of NF1/NF2 with TCS. RESULTS: 19,426 pediatric NF patients were evaluated (NF1: 18,383, NF2: 1042). The average ages of TCS diagnosis among NF1, NF2, and non-NF patients were 12, 16, and 9 years, respectively. The incidence of TCS was 1.2% in NF1 patients and 7.3% in NF2 patients, compared to 0.074% in the general population. The associations of NF incidence with TCS were significantly increased in both NF1 (OR 16.42; 14.38-18.76) and NF2 (OR 105.58; 83.56-133.40) patients compared to the general population. Symptomatic TCS requiring surgical intervention was not significantly associated with NF1/NF2 patients compared to the general TCS population. CONCLUSION: This analysis demonstrates a high incidence of TCS but delayed intervention in pediatric NF patients. Considering TCS counseling, spinal MRI, and earlier intervention may be warranted for NF patients experiencing musculoskeletal symptomatology.

Training Program Factors Most Important to Women When Selecting an Otolaryngology Residency.

OBJECTIVES: The aim of the study was to determine factors that female resident physicians find most influential when choosing an otolaryngology residency program. METHODS: A three-part survey was sent to current female otolaryngology residents via email evaluating the importance of 19 characteristics impacting program choice. The 19 factors were scored from 1 (least important) to 5 (most important). The participants also ranked their personal top five most influential factors. Data were analyzed using descriptive statistics. RESULTS: One-hundred and fifty of 339 contacted residents participated. Most were aged 30-39 (63%), white (70%), and married (43%). Eighty-five percent had no children, and 52% did not plan to have children during residency. The highest scoring factors derived from Likert scale ratings included resident camaraderie (4.5 ± 0.8), resident happiness (4.4 ± 0.8), and case variety/number (4.4 ± 0.8). The lowest scoring factors were number of fellows (2.9 ± 1.1), attitudes toward maternity leave (2.7 ± 1.3), and maternity leave policies (2.4 ± 1.2). The top five most influential factors and the percentage selecting this were resident camaraderie (57%), resident happiness (57%), academic reputation (51%), case variety/number (47%), and early surgical/clinical experience (44%). Gender-specific factors were infrequently selected. However, 51 (34%) ranked at least one gender-specific factor within their top five list. CONCLUSION: Non-gender-related factors, like resident camaraderie and surgical experiences, were most valued by women. Conversely, gender-specific factors were less critical and infrequently ranked. Ninety-nine residents (64%) rated exclusively gender-neutral characteristics in their top five list of most influential factors. Our data offer insight into program characteristics most important to female otolaryngology residents, which may assist residency programs hoping to match female applicants. LEVEL OF EVIDENCE: NA Laryngoscope, 134:600-606, 2024.

Urology Match: Important Factors Women Consider When Choosing a Residency Training Program.

OBJECTIVE: To determine factors that women urology resident physicians rate as most influential when selecting residency programs. METHODS: Surveys were emailed to female urology residents during the 2021-2022 academic year. Residents scored 19 factors influencing residency program choice from 1 "least" to 5 "most" important and ranked their top 5 most influential factors. Data were analyzed via descriptive statistics and quantile regression. RESULTS: One hundred thirty-six (37%) of 367 female urology residents who received the survey participated. Eighty-two percent had no children and 57% did not plan to have children during residency. The three highest scoring factors derived from Likert scale ratings were resident camaraderie (4.6 ±â€¯0.5 [mean ±â€¯SD]), resident happiness (4.6 ±â€¯0.6), and case variety/number (4.4 ±â€¯0.8). As a whole, the lowest scoring characteristics were attitudes toward maternity leave (2.6 ±â€¯1.2) and maternity leave policies (2.5 ±â€¯1.2). Married residents were more likely than those who were single and engaged/in a committed relationship to rank attitudes and policies toward maternity leave as more important (3 vs 2 vs 2, P <.0001). Residents with children were more likely than those without children to rank maternity leave policies as more important (3 vs 2, P <.0001). CONCLUSION: As a whole, women urology residents prioritized non-gender-related factors. However, gender-specific factors were rated highly by married residents and those with children or planning to have children. Urology training programs may use these results to highlight desirable characteristics to aid recruitment of female residents.

Simultaneous versus staged bilateral carpal tunnel release via open and endoscopic surgeries: a retrospective propensity score-matched patient comorbidity analysis.

OBJECTIVE: Carpal tunnel syndrome (CTS) presents bilaterally in nearly 60%-70% of affected patients. Bilateral carpal tunnel release (CTR) can be performed in a staged or simultaneous fashion. There remains a limited understanding of the optimal preoperative factors to use for patient selection when determining simultaneous versus staged bilateral CTR. Moreover, it is unclear how these factors influence postoperative outcomes. In this study, the authors aimed to identify and compare preoperative comorbidities and postoperative outcomes in patients who had undergone simultaneous versus staged open and endoscopic bilateral CTR. METHODS: The authors performed a retrospective analysis of data collected from the TriNetX database. Patients with bilateral CTS who had been treated from February 1, 2002, to February 1, 2022, were dichotomized by their bilateral release approach: simultaneous or staged within 3 months. The resulting groups were analyzed separately by open versus endoscopic techniques. Next, cohorts were analyzed for preoperative comorbidities to identify possible factors for surgical determination. Then, they were propensity score matched on demographics and comorbidities. Postoperative outcomes within 6 months of surgery were measured with and without matching. RESULTS: After matching, 9286 and 3709 patients remained in the open and endoscopic groups, respectively. Those who had undergone staged surgeries via an open or endoscopic approach had more preoperative comorbidities. After matching, staged open release was associated with significantly higher rates of postprocedural care, hand/joint pain, limb pain, trigger finger, and upper respiratory tract infections. Simultaneous open release was associated with higher rates of emergency room visits. Staged endoscopic release was associated with significantly higher rates of postprocedural care, limb pain, and trigger finger. No significant outcomes were favored in the simultaneous endoscopic group. CONCLUSIONS: Before matching, patients who had undergone staged CTR had significantly higher rates of preoperative medical comorbidities compared with patients in the simultaneous CTR group. Moreover, staged CTR was significantly associated with higher rates of postoperative complications. After matching on demographics and comorbidities, staged CTR was still associated with higher rates of postoperative complications, suggesting that preoperative comorbidities do not influence postoperative outcome. Further prospective studies could be used to validate these results and provide new findings for the management and treatment of these groups.

Early Celecoxib use in Patients with Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) can cause rapid brain inflammation. There is debate over the safety and efficacy of anti-inflammatory agents in its treatment. With a particular focus on cyclooxygenase 2 (COX2) selective inhibition, we sought to determine the impact of celecoxib versus no celecoxib treatment on outcomes in patients with TBI and compare these with outcomes associated with nonselective COX inhibition (ibuprofen) and corticosteroid (dexamethasone) treatment. METHODS: This retrospective cohort study used TriNetX, a large publicly available global health research network, to gather clinical data extracted from the electronic medical records. Using International Classification of Diseases, Tenth Revision and pharmacy codes, we identified patients with TBI who were and were not treated with celecoxib, ibuprofen, and dexamethasone. Analysis was performed on propensity-matched and unmatched cohorts, which were matched on demographics, comorbidities, and neurological injuries. Our primary end point was 1-year survival. Secondary end points were ventilator and tracheostomy dependence, gastrostomy tube placement, seizures, and craniotomy. RESULTS: After propensity score matching, a total of 1443 patients were identified in both the celecoxib and no celecoxib cohorts. Ninety-two (6.4%) patients in the celecoxib cohort died within 1 year following TBI versus 145 (10.0%) in the no celecoxib cohort (odds ratio 0.61; 95% confidence interval 0.46-0.80; p = 0.0003). The 1-year survival rate was 96.1% in the celecoxib cohort versus 93.1% in the no celecoxib cohort (p < 0.0001). At the end of the 1-year period, celecoxib was associated with significantly lower gastrostomy tube dependence (p = 0.017), seizure activity (p = 0.027), and myocardial infarction (p = 0.021) compared with the control cohort. Ibuprofen was also associated with higher 1-year survival probability and lower rates of post-TBI complications. Dexamethasone was broadly associated with higher morbidity but was associated with higher 1-year survival probability compared with the no dexamethasone cohort. CONCLUSIONS: Early celecoxib and ibuprofen use within 5 days post TBI was associated with higher 1-year survival probabilities and fewer complications. With emerging yet controversial preclinical evidence to suggest that COX inhibition improves TBI outcomes, this population-level study offers suggestive support for these drugs' clinical benefit, which should be pursued in prospective clinical studies.

Career satisfaction in women surgeons: A systematic review and meta-analysis.

BACKGROUND: Career satisfaction among women surgeons have been well-reported in literature. This study provides a comprehensive review to understand career satisfaction and its contributory factors among female surgeons. METHODS: PRISMA guidelines were utilized to extract studies for systematic review and meta-analysis. Outcomes assessed included surgical career satisfaction, career reconsideration, work-life balance, and gender bias and discrimination (GBD). Odds ratios were calculated comparing women to men for each outcome. RESULTS: This study demonstrated that female surgeons were less likely to endorse overall career satisfaction (OR, 0.68; 95% CI, 0.55-0.85) and work-life balance satisfaction (OR, 0.61; 95% CI, 0.40-0.92) compared to male surgeons. It also revealed that women surgeons were more likely to report workplace GBD (OR, 13.82; 95% CI, 4.37-43.65). CONCLUSIONS: Future interventions may be necessary to increase career and work-life balance satisfaction among women surgeons while reconciling the need to ensure they are adequately informed of the obligations of a surgical career.

Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid.

It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.

Photodynamic Therapy for Glioblastoma: Illuminating the Path toward Clinical Applicability.

Glioblastoma (GBM) is the most common adult brain cancer. Despite extensive treatment protocols comprised of maximal surgical resection and adjuvant chemo-radiation, all glioblastomas recur and are eventually fatal. Emerging as a novel investigation for GBM treatment, photodynamic therapy (PDT) is a light-based modality that offers spatially and temporally specific delivery of anti-cancer therapy with limited systemic toxicity, making it an attractive option to target GBM cells remaining beyond the margins of surgical resection. Prior PDT approaches in GBM have been predominantly based on 5-aminolevulinic acid (5-ALA), a systemically administered drug that is metabolized only in cancer cells, prompting the release of reactive oxygen species (ROS), inducing tumor cell death via apoptosis. Hence, this review sets out to provide an overview of current PDT strategies, specifically addressing both the potential and shortcomings of 5-ALA as the most implemented photosensitizer. Subsequently, the challenges that impede the clinical translation of PDT are thoroughly analyzed, considering relevant gaps in the current PDT literature, such as variable uptake of 5-ALA by tumor cells, insufficient tissue penetrance of visible light, and poor oxygen recovery in 5-ALA-based PDT. Finally, novel investigations with the potential to improve the clinical applicability of PDT are highlighted, including longitudinal PDT delivery, photoimmunotherapy, nanoparticle-linked photosensitizers, and near-infrared radiation. The review concludes with commentary on clinical trials currently furthering the field of PDT for GBM. Ultimately, through addressing barriers to clinical translation of PDT and proposing solutions, this review provides a path for optimizing PDT as a paradigm-shifting treatment for GBM.

Awake craniotomies in the pediatric population: a systematic review.

OBJECTIVE: Awake craniotomy (AC) is employed to maximize tumor resection while preserving neurological function in eloquent brain tissue. This technique is used frequently in adults but remains poorly established in children. Its use has been limited due to concern for children's neuropsychological differences compared with adults and how these differences may interfere with the safety and feasibility of the procedure. Among studies that have reported pediatric ACs, complication rates and anesthetic management vary. This systematic review was performed to comprehensively analyze outcomes and synthesize anesthetic protocols of pediatric ACs. METHODS: The authors followed PRISMA guidelines to extract studies that reported AC in children with intracranial pathologies. The Medline/PubMed, Ovid, and Embase databases were searched from database inception to 2021, using the terms ("awake") AND ("Pediatric*" OR "child*") AND (("brain" AND "surgery") OR "craniotomy"). Data extracted included patient age, pathology, and anesthetic protocol. Primary outcomes assessed were premature conversion to general anesthesia, intraoperative seizures, completion of monitoring tasks, and postoperative complications. RESULTS: Thirty eligible studies published from 1997 to 2020 were included that described a total of 130 children ranging in age from 7 to 17 years who had undergone AC. Of all patients reported, 59% were male and 70% had left-sided lesions. Procedure indications included the following etiologies: tumors (77.6%), epilepsy (20%), and vascular disorders (2.4%). Four (4.1%) of 98 patients required conversion to general anesthesia due to complications or discomfort during AC. In addition, 8 (7.8%) of 103 patients experienced intraoperative seizures. Furthermore, 19 (20.6%) of 92 patients had difficulty completing monitoring tasks. Postoperative complications occurred in 19 (19.4%) of 98 patients and included aphasia (n = 4), hemiparesis (n = 2), sensory deficit (n = 3), motor deficit (n = 4), or others (n = 6). The most commonly reported anesthetic techniques were asleep-awake-asleep protocols using propofol, remifentanil or fentanyl, a local scalp nerve block, and with or without dexmedetomidine. CONCLUSIONS: The findings of this systematic review suggest the tolerability and safety of ACs in the pediatric population. Although pediatric intracranial pathologies pose etiologies that certainly may benefit from AC, there is a need for surgeons and anesthesiologists to perform individualized risk-benefit analyses due to the risks associated with awake procedures in children. Age-specific, standardized guidelines for preoperative planning, intraoperative mapping, monitoring tasks, and anesthesia protocols will help to continue minimizing complications, while improving tolerability, and streamlining workflow in the treatment of this patient population.

Early costs and complications of first-line low-grade glioma treatment using a large national database: Limitations and future perspectives.

Introduction: Diffuse Low-grade gliomas (DLGG, WHO Grade II) are a heterogenous group of tumors comprising 13-16% of glial tumors. While maximal safe resection is endorsed as the best approach to DLGG, compared to more conservative interventions like stereotactic biopsy, the added costs and risks have not been systematically evaluated. The purpose of this study was to better understand the complication rates and costs associated with each intervention. Methods: A retrospective cohort study using data from the IBM Watson Health MarketScan® Commercial Claims and Encounters database was conducted, using the International Classification of Diseases, Ninth Revision (ICD-9) codes corresponding to DLGG (2005-2014). Current Procedure Terminology, 4th Edition (CPT-4) codes were used to differentiate resection and biopsy cohorts. Inverse weighting by the propensity score was used to balance baseline potential confounders (age, sex, pre-op seizure, geographic region, year, Charleston Comorbidity Index). Complication rates, hospital mortality, readmission, and costs were compared between groups. Results: We identified 5,784 and 3,635 patients undergoing resection and biopsy, respectively, for initial DLGG management. Resection was associated with greater 30-day complications (29.17% vs. 26.34%; p < 0.05). However, this association became non-significant after inverse propensity weighting (adjusted odds ratio = 1.09; 0.98-1.20). There was no statistically significant difference in unadjusted, 30-day hospital mortality (p = 0.06) or re-admission (p = 0.52). Resection was associated with higher 90-day total costs (p < 0.0001) and drug costs (p < 0.0001). Biopsy was associated with greater index procedure costs (p < 0.0001). Long-term outcomes and evaluation of DLGG subtypes was not possible given limitations in the metrics recorded in MarketScan and lack of specificity in the ICD coding system. Conclusion: Resection was not associated with an increase in the adjusted complication rate after balancing for baseline prognostic factors. Total costs and drug costs were higher with resection of DLGG, but the index procedure costs were higher for biopsy. This data should help to facilitate prospective health economic analyses in the future to understand the cost-effectiveness, and impact on quality of life, for DLGG interventions. However, the use of large national databases for studying long-term outcomes in DLGG management should be discouraged until there is greater specificity in the ICD coding system for DLGG subtypes.

Female Neurosurgery Residency Program Directors in the United States: A Cross-sectional Descriptive Analysis.

BACKGROUND: The residency program director (PD) position is a valued leadership appointment in academic medicine. PDs are responsible for the success of their program and its residents. The objective of this study is to provide a cross-sectional analysis of baseline demographics and academic backgrounds of current neurosurgery program directors. METHODS: Data was compiled on neurosurgery PDs and their residency programs, as of the end of May 2021, using publicly available resources including Doximity, FREIDA, and Healthgrades. The Mann-Whitney and Fisher exact tests were used for statistical analysis. RESULTS: Of 113 PDs identified, 91.15% are male (P < 0.01). The majority of PDs (88.5%) received their medical degrees from U.S. medical schools. The average age of current PDs is 54 years, and the average age at appointment was 48 years. Compared to their male counterparts, female PDs are more likely to be younger at appointment (41 vs. 48 years; P = 0.001) and while holding the same position (45 vs. 55 years; P = 0.001). As a result, female PDs experience less time to appointment after residency (8.6 years vs. 14.7 years, P = 0.013). There are no significant differences regarding the gender of the PD and university affiliation, current appointment, completion of a fellowship, and resident gender ratios. CONCLUSIONS: The position of neurosurgery residency PD is dominated by fellowship-trained men in their late 40s to 50s. The gender ratio of neurosurgery residents is consistent with the underrepresentation of women in this position. With increasing female representation in neurosurgery, more women may assume this leadership position and begin to hasten the gender balance.

Pregnancy in spina bifida patients: a comparative analysis of peripartum procedures and complications.

PURPOSE: Spina bifida (SB) is caused by a failure in neural tube closure that can present with lower extremity sensory deficits, paralysis, and hydrocephalus. Medical advances have allowed increased pregnancies among SB patients, but management and pregnancy-associated complications have not been thoroughly investigated. The objective is to delineate peripartum procedures and complications in patients with SB. METHODS: A national de-identified database, TriNetX, was retrospectively queried to evaluate pregnant SB patients and the general population. Procedures and complications were investigated using corresponding ICD-10 and CPT codes within 1 year of pregnancy diagnosis. RESULTS: 11,405 SB patients were identified and compared to 9,269,084 non-SB patients. SB patients were significantly more likely to undergo cesarean delivery (1.200; 95% CI [1.133-1.271]) and less likely to receive neuraxial analgesia (0.406; 95% CI [0.383-0.431]). Additionally, patients with SB had an increased risk of seizures (3.922; 95% CI [3.529-4.360]) and venous thromboembolism (VTE) (3.490; 95% CI [3.070-3.969]). Risks of preeclampsia and hemorrhage were comparable. SB patients with hydrocephalus and Chiari malformation type 1 (CM-1) or type 2 (CM-2) were compared to patients without these comorbid conditions. This sub-group analysis showed a significantly increased risk of having cesarean deliveries (SB with hydrocephalus: 12.55%, S.B. with CM-1 or CM-2: 12.81% vs. SB without hydrocephalus or CM, 6.16%) and VTE (3.74%, 2.43% vs. 0.81%). There were also increased risks of hemorrhage and seizures and decreased use of neuraxial analgesia, but the sample size was insufficient. CONCLUSION: SB patients were more likely to undergo cesarean section and exhibit peripartum complications compared to those without SB.

Pregnancy and Childbirth in Women With Meningioma.

Background Ten percent of women of childbearing age have histologically confirmed meningioma. To date, little is known regarding pregnancy-related outcomes for women with meningioma. Methods We used a de-identified database network (TriNetX's Research Network, https://trinetx.com/) to gather information on pregnant patients with meningioma (cohort 1) versus pregnant patients without meningioma (cohort 2). The primary outcome of interest included the impact of meningioma on mortality at one year. Secondary endpoints included ectopic or molar pregnancy, cesarean section, abortion, preterm labor, depression, pre-eclampsia/eclampsia, and craniotomy. Odds ratios (OR) with 95% confidence intervals (CI) were used to measure levels of association between each cohort and the outcomes of interest. Results A total of 1,739 patients were identified in each cohort following propensity-score matching. Mortality was seen in 23 patients (1.32%) in cohort 1 versus 26 patients (1.41%) in cohort 2 (OR 0.88, 95% CI {0.50, 1.55}, p=0.66). Ectopic/ molar pregnancy was seen in 31 (1.78%) versus 42 (2.42%) patients in cohorts 1 and 2, respectively (OR 0.73, 95% CI {0.046,1.17}, p=0.19). Cesarean section was seen in 126 (7.25%) versus 164 (9.43%) patients, respectively (OR 0.75, 95% CI {0.59,0.97}, p=0.020). Abortion was seen in 128 (7.36%) versus 183 (10.52%) patients, respectively (OR 0.68, 95% CI {0.53,0.86}, p=0.0011). Preterm labor was seen in 75 (4.31%) versus 119 (6.84%) patients, respectively (OR 0.61, 95% CI {0.46,0.83}, p=0.0012). Depression was seen in 258 (14.84%) versus 270 (15.53%) patients, respectively (OR 0.95, 95% CI {0.79,1.14}, p=0.57). Pre-eclampsia/eclampsia was seen in 3.11% versus 5.52% patients, respectively (OR 0.55, 95% CI {0.39,0.77}, p=0.0005). Craniotomy was seen in 74 (4.26%) versus 0 (0%) patients in cohort 1 and cohort 2, respectively. Conclusion Patients with meningioma were not at higher risk for pregnancy complications, including ectopic/molar pregnancy, cesarean section, abortion, preterm labor, pre-eclampsia/eclampsia, and mortality, compared to their non-meningioma counterparts. Still, coordinated care by neurosurgical and obstetrical providers may benefit women with meningiomas who are planning for pregnancy or are currently pregnant.

Neuropharmacological Study of Posaconazole for Glioblastoma: A Phase 0 Clinical Trial Protocol.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain tumor with a universally poor prognosis. GBMs express elevated levels of hexokinase 2 (HK2), catalyzing the critical step in glycolysis and influencing several oncogenic pathways. Previous preclinical work has suggested a role for repurposed posaconazole (PCZ) in downregulating HK2 activity, reducing lactate and pyruvate production, interfering with tumor cell metabolism, and increasing mouse survival. OBJECTIVE: To establish brain tumor penetrance, neuropharmacokinetic profile, and mechanistic effect on tumor cell metabolism of PCZ in adults with GBM. METHODS: This is an open label, nonrandomized, parallel arm trial involving patients with GBM. Cohorts will receive PCZ (intervention, n = 5) or will not receive PCZ (control, n = 5), followed by tumor resection and microdialysis catheter placement. Dialysate, plasma, and tumor samples will be analyzed for lactate and pyruvate concentrations. Tumor samples will also be assessed for PCZ concentration, HK2 expression, angiogenesis, and apoptosis. PCZ's neuropharmacokinetics will be determined based on the concentration vs time profile and area under the curve 0 to 24 hours of PCZ concentration in the brain interstitium. EXPECTED OUTCOMES: (1) Increased PCZ concentration in contrast-enhancing brain regions compared with nonenhancing regions; (2) inverse correlation between lactate/pyruvate and PCZ concentrations in dialysate samples from treated patients, over time; and (3) decreased HK2 activity in PCZ-treated tumor samples. DISCUSSION: A successful trial will support the decision to proceed to advanced phase trials. Any tumor penetration by PCZ, with concomitant effect on glycolysis, warrants further in-depth analysis, as therapeutic options for these deadly tumors are currently limited.

Association of Low-Grade Glioma Diagnosis and Management Approach with Mental Health Disorders: A MarketScan Analysis 2005-2014.

Low-grade gliomas (LGGs) comprise 13-16% of glial tumors. As survival for LGG patients has been gradually improving, it is essential that the effects of diagnosis and disease progression on mental health be considered. This retrospective cohort study queried the IBM Watson Health MarketScan® Database to describe the incidence and prevalence of mental health disorders (MHDs) among LGG patients and identify associated risk factors. Among the 20,432 LGG patients identified, 12,436 (60.9%) had at least one MHD. Of those who never had a prior MHD, as documented in the claims record, 1915 (16.7%) had their first, newly diagnosed MHD within 12 months after LGG diagnosis. Patients who were female (odds ratio (OR), 1.14, 95% confidence intervals (CI), 1.03-1.26), aged 35-44 (OR, 1.20, 95% CI, 1.03-1.39), and experienced glioma-related seizures (OR, 2.19, 95% CI, 1.95-2.47) were significantly associated with MHD incidence. Patients who underwent resection (OR, 2.58, 95% CI, 2.19-3.04) or biopsy (OR, 2.17, 95% CI, 1.68-2.79) were also more likely to develop a MHD compared to patients who did not undergo a first-line surgical treatment. These data support the need for active surveillance, proactive counseling, and management of MHDs in patients with LGG. Impact of surgery on brain networks affecting mood should also be considered.

Repurposing Quinacrine for Treatment of Malignant Mesothelioma: In-Vitro Therapeutic and Mechanistic Evaluation.

Malignant mesothelioma (MM) is a rare type of cancer primarily affecting mesothelial cells lining the pleural cavity. In this study, we propose to repurpose quinacrine (QA), a widely approved anti-malarial drug, for Malignant Pleural Mesothelioma (MPM) treatment. QA demonstrates high degree of cytotoxicity against both immortalized and primary patient-derived cell lines with sub-micromolar 50% inhibitory concentration (IC50) values ranging from 1.2 µM (H2452) to 5.03 µM (H28). Further, QA also inhibited cellular migration and colony formation in MPM cells, demonstrated using scratch and clonogenic assays, respectively. A 3D-spheroid cell culture experiment was performed to mimic in-vivo tumor conditions, and QA was reported to be highly effective in this simulated cellular model. Anti-angiogenic properties were also discovered for QA. Autophagy inhibition assay was performed, and results revealed that QA successfully inhibited autophagy process in MPM cells, which has been cited to be one of the survival pathways for MPM. Annexin V real-time apoptosis study revealed significant apoptotic induction in MPM cells following QA treatment. Western blots confirmed inhibition of autophagy and induction of apoptosis. These studies highlight anti-mesothelioma efficacy of QA at low doses, which can be instrumental in developing it as a stand-alone treatment strategy for MPM.