Enhancing the quality of evidence, comparability, and reproducibility in brain arteriovenous malformations treated with open surgery research: a systematic review and proposal of a reporting guideline for surgical and clinical outcomes.

Brain Arteriovenous Malformations (bAVMs) are rare but high-risk developmental anomalies of the vascular system. Microsurgery through craniotomy is believed to be the mainstay standard treatment for many grades of bAVMs. However, a significant challenge emerges in the existing body of clinical studies on open surgery for bAVMs: the lack of reproducibility and comparability. This study aims to assess the quality of studies reporting clinical and surgical outcomes for bAVMs treated by open surgery and develop a reporting guideline checklist focusing on essential elements to ensure comparability and reproducibility. This is a systematic literature review that followed the PRISMA guidelines with the search in Medline, Embase, and Web of Science databases, for studies published between January 1, 2018, and December 1, 2023. Included studies were scrutinized focusing on seven domains: (1) Assessment of How Studies Reported on the Baseline Characteristics of the Patient Sample; (2) Assessment and reporting on bAVMs grading, anatomical characteristics, and radiological aspects; (3) Angioarchitecture Assessment and Reporting; (4) Reporting on Pivotal Concepts Definitions; (5) Reporting on Neurosurgeon(s) and Staff Characteristics; (6) Reporting on Surgical Details; (7) Assessing and Reporting Clinical and Surgical Outcomes and AEs. A total of 47 studies comprising 5,884 patients were included. The scrutiny of the studies identified that the current literature in bAVM open surgery is deficient in many aspects, ranging from fundamental pieces of information of methodology to baseline characteristics of included patients and data reporting. Included studies demonstrated a lack of reproducibility that hinders building cumulative evidence. A bAVM Open Surgery Reporting Guideline with 65 items distributed across eight domains was developed and is proposed in this study aiming to address these shortcomings. This systematic review identified that the available literature regarding microsurgery for bAVM treatment, particularly in studies reporting clinical and surgical outcomes, lacks rigorous scientific methodology and quality in reporting. The proposed bAVM Open Surgery Reporting Guideline covers all essential aspects and is a potential solution to address these shortcomings and increase transparency, comparability, and reproducibility in this scenario. This proposal aims to advance the level of evidence and enhance knowledge regarding the Open Surgery treatment for bAVMs.

The association between motor and non-motor symptoms in essential tremor patients being evaluated for deep brain stimulation surgery.

BACKGROUND: Non-motor symptoms, including depression and cognitive impairment, are common in essential tremor (ET), but associations between these symptoms and tremor are poorly understood. METHODS: A retrospective, single-institution, cohort study evaluated 140 patients with ET undergoing evaluation for deep brain stimulation (DBS) surgery. The Fahn-Tolosa-Marin (FTM) or Washington Heights-Inwood Genetic Study of ET (WHIGET) scale was used to grade tremor. Tremor scores were divided into quartiles. Patients underwent clinical neuropsychological evaluations that included a comprehensive cognitive test battery and Beck Depression Inventory-II (BDI-II). Subgroup analysis was performed with groups who met criteria for depression (BDI-II > 14) or overall cognitive impairment (<9th percentile on at least two dissimilar cognitive tests). Independent samples t-tests were used for continuous variables and chi square tests for categorical variables. Univariable and multivariable regressions were used to determine relationships between tremor and non-motor scores. RESULTS: Tremor quartile was correlated with language domain performance (p = 0.044) but not depression scores. FTM score was associated with BDI-II (ß = 0.940, p = 0.010), language (ß = -0.936, p = 0.012), and visuospatial domain (ß = -0.836, p = 0.025) scores, such that worse tremor was associated with more depression and worse language and visuospatial function. WHIGET score was not associated with any neuropsychological scores on multivariable regression. CONCLUSION: FTM score was associated with language, visuospatial, and mood symptoms, suggesting a relationship between the severity of these symptom types. Different tremor scores capture different motor symptoms and relationships with nonmotor symptoms.

Global Economic Evaluation of the Reported Costs of Deep Brain Stimulation.

INTRODUCTION: Despite the known benefits of deep brain stimulation (DBS), the cost of the procedure can limit access and can vary widely. Our aim was to conduct a systematic review of the reported costs associated with DBS, as well as the variability in reporting cost-associated factors to ultimately increase patient access to this therapy. METHODS: A systematic review of the literature for cost of DBS treatment was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Embase databases were queried. Olsen & Associates (OANDA) was used to convert all reported rates to USD. Cost was corrected for inflation using the US Bureau of Labor Statistics Inflation Calculator, correcting to April 2022. RESULTS: Twenty-six articles on the cost of DBS surgery from 2001 to 2021 were included. The median number of patients across studies was 193, the mean reported age was 60.5 ± 5.6 years, and median female prevalence was 38.9%. The inflation- and currency-adjusted mean cost of the DBS device was USD 21,496.07 ± USD 8,944.16, the cost of surgery alone was USD 14,685.22 ± USD 8,479.66, the total cost of surgery was USD 40,942.85 ± USD 17,987.43, and the total cost of treatment until 1 year of follow-up was USD 47,632.27 ± USD 23,067.08. There were no differences in costs observed across surgical indication or country. CONCLUSION: Our report describes the large variation in DBS costs and the manner of reporting costs. The current lack of standardization impedes productive discourse as comparisons are hindered by both geographic and chronological variations. Emphasis should be put on standardized reporting and analysis of reimbursement costs to better assess the variability of DBS-associated costs in order to make this procedure more cost-effective and address areas for improvement to increase patient access to DBS.

Complications associated with combined direct and indirect bypass in Moyamoya Disease: A meta-analysis.

Bypass revascularization helps prevent complications in Moyamoya Disease (MMD). To systematically review complications associated with combined direct and indirect (CB) bypass in MMD and analyze differences between the adult and pediatric populations. A systematic literature review was conducted per PRISMA guidelines. PUBMED, Cochrane Library, Web of Science, and CINAHL, were queried from January 1980 to March 2022. Complications were defined as any event in the immediate post-surgical period of a minimum 3 months follow-up. Exclusion criteria included lack of surgical complication reports, non-English articles, and CB unspecified or reported separately. 18 final studies were included of 1580 procured. 1151 patients (per study range = 10-150, mean = 63.9) were analyzed. 9 (50.0%) studies included pediatric patients. There were 32 total hemorrhagic, 74 total ischemic and 16 total seizure complications, resulting in a rate of 0.04 (95% CI 0.03, 0.06), 0.7 (95% CI 0.04, 0.10) and 0.03 (95% CI 0.02, 0.05), respectively. The rate of hemorrhagic complications in the pediatric showed no significant difference from the adult subgroup (0.03 (95% CI 0.01-0.08) vs. 0.06 (95% CI 0.04-0.10, p = 0.19), such as the rate of ischemic complications (0.12 (95% CI 0.07-0.23) vs. 0.09 (95% CI 0.05-0.14, p = 0.40). Ischemia is the most common complication in CB for MMD. Pediatric patients had similar hemorrhagic and ischemic complication rates compared to adults.

Cost considerations for vestibular schwannoma screening and imaging: a systematic review.

Vestibular schwannomas (VS) account for approximately 8% of all intracranial neoplasms. Importantly, the cost of the diagnostic workup for VS, including the screening modalities most commonly used, has not been thoroughly investigated. Our aim is to conduct a systematic review of the published literature on costs associated with VS screening. A systematic review of the literature for cost of VS treatment was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The terms "vestibular schwannoma," "acoustic neuroma," and "cost" were queried using the PubMed and Embase databases. Studies from all countries were considered. Cost was then corrected for inflation using the US Bureau of Labor Statistics Inflation Calculator, correcting to April 2022. The search resulted in an initial review of 483 articles, of which 12 articles were included in the final analysis. Screening criteria were used for non-neurofibromatosis type I and II patients who complained of asymmetric hearing loss, tinnitus, or vertigo. Patients included in the studies ranged from 72 to 1249. The currency and inflation-adjusted mean cost was $418.40 (range, $21.81 to $487.03, n = 5) for auditory brainstem reflex and $1433.87 (range, $511.64 to $1762.15, n = 3) for non-contrasted computed tomography. A contrasted magnetic resonance imaging (MRI) scan was found to have a median cost of $913.27 (range, $172.25-$2733.99; n = 8) whereas a non-contrasted MRI was found to have a median cost of $478.62 (range, $116.61-$3256.38, n = 4). In terms of cost reporting, of the 12 articles, 1 (8.3%) of them separated out the cost elements, and 10 (83%) of them used local prices, which include institutional costs and/or average costs of multiple institutions. Our findings describe the limited data on published costs for screening and imaging of VS. The paucity of data and significant variability of costs between studies indicates that this endpoint is relatively unexplored, and the cost of screening is poorly understood.

Post-mastectomy Breast Reconstruction Using Gas vs Saline Tissue Expanders: Does the Fill Type Matter?

The most common reconstruction technique following mastectomy is a two-stage technique that involves tissue expansion followed by definitive implant-based reconstruction (IBR). Tissue expanders (TEs) have classically used saline for initial fill; however, TEs with an initial gas fill (GTE) - including the CO2-based AeroForm TE and TEs initially filled with atmospheric air - have been increasingly used in the past decade. We aim to compare the outcomes in breast reconstruction for tissue expanders initially filled with saline vs. gas. PubMed was queried for studies comparing gas and saline-filled tissue expanders (STEs) used in IBR. A meta-analysis was performed on major postoperative outcomes and the required expansion and definitive reconstruction time. Eleven studies were selected and included in the analysis. No significant differences existed between tissue expansion with GTEs versus STEs for eleven of the thirteen postoperative outcomes investigated. Out of the complications investigated, only the risk of infection/cellulitis/abscess formation was significantly lower in the GTE cohort (OR = 0.62; 95% CI = 0.47 to 0.82; P = 0.0009). The time to definitive reconstruction was also significantly lower in the GTE cohort (MD = -45.85 days; 95% CI = -57.80 to -33.90; P < 0.00001). The total time to full expansion approached significance in the GTE cohort (MD = -20.33 days; 95% CI = -41.71 to 1.04; P = 0.06). A cost analysis considering TE cost and infection risk determined that GTE use saved a predicted $2,055.34 in overall healthcare costs. Surgical outcomes for both fill types are predominantly similar; however, GTEs were associated with a significantly decreased risk of postoperative infection compared to saline filled TEs. GTEs can also reduce healthcare expenditures and require less time until definitive reconstruction after placement.

Does recovery after sport-related concussion vary by time point in a season? A multi-sport investigation.

OBJECTIVE: Seasonality, or the specific point in time within a season in which the injury occurs, may have an impact on the recovery following sport-related concussions (SRCs). In a cohort of high school athletes across multiple sports, the authors sought to investigate the impact of seasonality on 1) concussion frequency, 2) acute symptom presentation (initial Post-Concussion Symptom Scale [PCSS] score), and 3) recovery outcomes, including the time to return to learn (RTL), symptom resolution (SR), and return to play (RTP). METHODS: A retrospective, single-institution, cohort study was conducted with adolescent athletes aged 14-19 years who sustained an SRC between November 2017 and April 2022 and presented to a multidisciplinary specialty concussion clinic. The time from first practice to the end of the regular season was evenly trichotomized into early, middle, and late season. Teams that participated in the playoffs were included in a subanalysis. One-way ANOVA and independent t-tests were used to compare PCSS scores, RTL, SR, and RTP across seasonality. Univariable and multivariable regressions were used to determine predictors for recovery, defined as total days from initial visit to each outcome. RESULTS: Of the 1504 eligible athletes, 620 high school athletes met inclusion criteria; 491 (79.2%) sustained a concussion during the regular season with 73 (14.9%), 136 (27.7%), and 282 (57.4%) concussions occurring in the early, middle, and late seasons, respectively. No differences were seen for initial PCSS score, RTL, SR, or RTP across early-, middle-, and late-season concussions. The initial PCSS score was significantly higher for playoff compared with regular-season concussions (playoffs: 33.4 ± 27.5; regular season: 23.3 ± 22.8; t = -1.979, p = 0.048). A subanalysis of playoff concussions (n = 24) compared with regular-season concussions showed that concussion in the playoffs was associated with a higher initial PCSS score in univariable (ß = 0.093, p = 0.048) and multivariable (ß = 0.112, p = 0.014) analyses. CONCLUSIONS: The majority of concussions occurred during the late-season period. No difference in acute symptoms or recovery outcomes was seen when comparing the three regular season time points. Playoff concussions were associated with significantly increased symptom scores compared with nonplayoff concussions.

Recent Trends in Successful Neurosurgery Resident Matriculation: A Retrospective and Bibliometric Analysis.

BACKGROUND: Prior literature has demonstrated barriers to successful residency matching, including sex, medical school background, and international medical graduate status. Our aim is to characterize the recent trends in successfully-matched residents, with particular attention to geography and academic productivity. METHODS: Resident information, including demographics and educational background, was gathered from program websites. Bibliometric analysis focused on PubMed publications from the top neurosurgery journals. A top 20 medical school was defined using the US News Rankings for research in 2022. Regression analyses were performed to explore the associations between total and first-author publications and other relevant factors, correcting for graduate studies. RESULTS: A total of 114 institutions and 946 residents were included in the final analysis. Of the 845 with medical school information, 62 (7.3%) completed medical school internationally and 181 of 783 (23.1%) came from a top 20 medical school. Male residents had a higher proportion of residents with international undergraduate and international medical school degrees when compared to female residents [32 (7.5%) vs. 4 (2.4%), P = 0.021; 52 (8.6%) vs. 10 (4.2%), P = 0.026; respectively]. The multivariate regression analysis demonstrated a significant increase in publications for international medical school graduates (B = 8.3, P < 0.001), top tier medical school graduate (B = 1.3, P = 0.022), and male sex (B = 1.20, P = 0.019) for total number of publications. CONCLUSIONS: Geographical factors, reported sex, and graduation status have influenced how resident candidates are perceived. Understanding these trends is vital for future resident matching. Addressing gender and educational diversity is essential to foster inclusivity and research-driven environments in neurosurgery residency programs.

Gene deletion of the PACAP/VIP receptor, VPAC2R, alters glycemic responses during metabolic and psychogenic stress in adult female mice.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and the homologous peptide, vasoactive intestinal peptide (VIP), participate in glucose homeostasis using insulinotropic and counterregulatory processes. The role of VIP receptor 2 (VPAC2R) in these opposing actions needs further characterization. In this study, we examined the participation of VPAC2R on basal glycemia, fasted levels of glucoregulatory hormones and on glycemia responses during metabolic and psychogenic stress using gene-deleted (Vipr2-/- ) female mice. The mean basal glycemia was significantly greater in Vipr2-/- in the fed state and after an 8-h overnight fast as compared to wild-type (WT) mice. Insulin tolerance testing following a 5-h fast (morning fast, 0.38 U/kg insulin) indicated no effect of genotype. However, during a more intense metabolic challenge (8 h, ON fast, 0.25 U/kg insulin), Vipr2-/- females displayed significantly impaired insulin hypoglycemia. During immobilization stress, the hyperglycemic response and plasma epinephrine levels were significantly elevated above basal in Vipr2-/- , but not WT mice, in spite of similar stress levels of plasma corticosterone. Together, these results implicate participation of VPAC2R in upregulated counterregulatory processes influenced by enhanced sympathoexcitation. Moreover, the suppression of plasma GLP-1 levels in Vipr2-/- mice may have removed the inhibition on hepatic glucose production and the promotion of glucose disposal by GLP-1. qPCR analysis indicated deregulation of central gene markers of PACAP/VIP signaling in Vipr2-/- , upregulated medulla tyrosine hydroxylase (Th) and downregulated hypothalamic Vip transcripts. These results demonstrate a physiological role for VPAC2R in glucose metabolism, especially during insulin challenge and psychogenic stress, likely involving the participation of sympathoadrenal activity and/or metabolic hormones.

Social Determinants of Health in Imaging-based Cancer Screening: A Case-based Primer with Strategies for Care Improvement.

Health disparities, preventable differences in the burden of disease and disease outcomes often experienced by socially disadvantaged populations, can be found in nearly all areas of radiology, including emergency radiology, neuroradiology, nuclear medicine, image-guided interventions, and imaging-based cancer screening. Disparities in imaging-based cancer screening are especially noteworthy given the far-reaching population health impact. The social determinants of health (SDoH) play an important role in disparities in cancer screening and outcomes. Through improved understanding of how SDoH can drive differences in health outcomes in radiology, radiologists can effectively provide patient-centered, high-quality, and equitable care. Radiologists and radiology practices can become active partners in efforts to assist patients along their imaging journey and overcome existing barriers to equitable cancer screening care for traditionally marginalized populations. As radiology exists at the intersection of diagnostic imaging, image-guided diagnostic intervention, and image-guided treatment, radiologists are uniquely positioned to design these strategies. Cost-effective and socially conscious strategies that address barriers to equitable care can improve both public health and equitable health outcomes. Potential strategies include championing supportive health policy, reducing out-of-pocket costs, increasing price transparency, improving education and outreach efforts, ensuring that appropriate language translation services are available, providing individualized assistance with appointment scheduling, and offering transportation assistance and childcare. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

A Novel Orthoplastic Reconstruction of Relapsed Clubfoot With Total Ankle Arthroplasty.

Congenital clubfoot is addressed in infancy and rarely persists into adulthood. Ankle arthroplasty is an increasingly popular surgical intervention for patients with ankle arthritis since it allows a natural ankle range of motion and completely replaces a degenerative hindfoot. Here, we describe the first successful total ankle arthroplasty (TAA) for a patient with previously treated congenital clubfoot that reverted later in life. To address the patient's poor soft-tissue integument and reduce the likelihood of post-surgical complications, a perioperative latissimus muscle-free flap was performed. This two-staged, novel orthoplastic intervention addressed our patient's ankle issues and appears to be a viable option for clubfoot patients.

Current Trends in Autologous Breast Reconstruction and the Implications of Impending Changes to Insurance Reimbursement.

Introduction In 2019, the Centers for Medicare & Medicaid Services (CMS) combined all autologous breast flap procedures under one billing code, effective from December 31, 2024. This change will result in equal insurance reimbursement rates for popular flap options, such as transverse rectus abdominis muscle (TRAM) and deep inferior epigastric perforator (DIEP) flaps, which were previously billed separately using S-codes based on complexity. Methods This study aimed to analyze insurance code changes for autologous breast reconstruction flap procedures. Data were collected from the American Society of Plastic Surgeons' annual plastic surgery statistics reports, including specific insurance codes and case volumes from 2007 to 2020. A comprehensive analysis was conducted to assess recent trends in flap utilization rates, documenting any modifications or additions to the existing codes and their implementation years. Results The study analyzed billing codes and case volumes for autologous breast reconstruction procedures, with a focus on the DIEP flap and other alternatives. Non-autologous breast reconstruction procedures showed consistently higher case volumes compared to autologous procedures from 2007 to 2020. Notably, the popularity of the DIEP flap surpassed that of other flap options after 2011. Conclusion The removal of S-codes for autologous breast reconstruction by CMS and the subsequent potential decrease in insurance coverage for the DIEP flap may lead to a decrease in its utilization and a shift toward more invasive options, like the TRAM flap. This change could result in financial burdens for patients and widen socioeconomic disparities in breast reconstruction, limiting access to preferred reconstructive methods and impacting patient autonomy and overall well-being.

Current State of Brazilian Neurosurgery: Evaluation of Burden of Care and Case Volume.

BACKGROUND: Low- and middle-income countries (LMICs) bear a heavier burden of neurosurgical diseases than high-income countries. Brazil, a growing middle-income country, holds promise as a health care market. However, there exists a lack of information to characterize the state of neurosurgical practice and access to care in Brazil. This study aimed to characterize neurosurgical practice in Brazil and identify barriers to care. METHODS: A collaborative survey was developed with Brazilian neurosurgeons and distributed by the Brazilian Society of Neurosurgery. The survey gathered demographic information, practice characteristics, case volume, referral patterns, income sources, and assessed barriers using a Likert scale. Descriptive statistics were employed for data analysis. RESULTS: One-hundred and forty-nine neurosurgeons participated (response rate: 17.5%), representing various states in Brazil. Neurosurgeons practiced in more than 4 different hospital systems on average, with most consultations and procedures occurring in public hospitals. Common procedures included tumor surgeries, general neurosurgery, spine surgeries, trauma surgeries, and hydrocephalus management. Equipment shortage and systemic issues were identified as major barriers to care. CONCLUSIONS: Neurosurgical practice in Brazil exhibits diverse age distribution, widespread distribution across states, and involvement in both public and private hospitals. Survey insights shed light on neurosurgical workload and neurosurgical practice characterization. Lack of equipment and inadequate postoperative resources pose significant barriers to care. The findings highlight the need for investments in equipment, critical care facilities, and improved health care system coordination to enhance access to neurosurgical care in Brazil.

Does earlier vestibular therapy after sport-related concussion lead to faster recovery?

OBJECTIVE: Many patients experience vestibular dysfunction following a sport-related concussion (SRC). Vestibular rehabilitation therapy has recently become more well established. In a cohort of athletes with SRC, the authors sought to 1) assess the relationship between symptoms at the initial clinic visit and time to referral for vestibular therapy, and 2) evaluate whether earlier referral to vestibular therapy was associated with faster recovery, as defined as days to return to learn (RTL), symptom resolution (SR), and return to play (RTP). METHODS: A retrospective cohort study was conducted using a regional multidisciplinary concussion center's database. Patients aged 12-23 years diagnosed with SRC who received vestibular rehabilitation therapy between October 2017 and October 2021 were included. Demographics and Post-Concussion Symptom Scale (PCSS) scores were extracted. The independent variable of interest was time to vestibular therapy referral. The three outcome variables were RTL, SR, and RTP. Spearman's rho correlation (rho) was used to evaluate the relationship between total PCSS score and individual symptoms (balance problems, blurred vision, and dizziness) and time to referral for vestibular therapy. Multivariable linear regression was performed to determine the impact of time to vestibular therapy on the three outcomes of RTL, SR, and RTP. Covariates included initial symptom burden, age, and prior concussions. RESULTS: Forty-two concussed athletes were referred for vestibular therapy (mean age 16.8 ± 2.7 years; 54.8% female). The mean time from concussion to the initial clinic visit was 22.4 ± 20.2 days, and the mean time from the initial clinic visit to vestibular therapy referral was 4.9 ± 11.3 days. Initial total PCSS scores (rho[37] = 0.05, p = 0.78) and individual symptoms, including balance problems (rho[33] = -0.004, p = 0.98), blurred vision (rho[34] = -0.17, p = 0.33), and dizziness (rho[33] = 0.07, p = 0.67), were not correlated with time to referral for vestibular therapy. Multivariable linear regression analysis found that earlier vestibular therapy referral was predictive of shorter days to SR (p = 0.002) and RTP (p = 0.02) but not RTL (p = 0.59). CONCLUSIONS: In athletes with SRC referred for vestibular therapy, earlier vestibular therapy referral was significantly associated with faster time to RTP and SR. Future investigations should focus on identifying common postconcussive signs and symptoms that serve as indications for referral to vestibular therapy.

The Neurosurgery Match: COVID-19 Comparison and Bibliometric Analysis.

BACKGROUND: Because of the effect of COVID-19 on academic opportunities, as well as limitations on travel, away rotations and in-person interviews, COVID-19-related changes could impact the neurosurgical resident demographics. Our aim was to retrospectively review the demographics of the previous 4 years of neurosurgery residents, provide bibliometric analysis of successful applicants, and analyze for the effects of COVID-19 on the match cycle. METHODS: All American Association of Neurological Surgeons' residency program websites were examined for a list of demographic characteristics for current postgraduate years 1 to 4. Gathered information included gender, undergraduate and medical institution and state, medical degree status, and prior graduate programs. RESULTS: A total of 114 institutions and 946 residents were included in the final review. Most (676, or 71.5%) of the residents included in the analysis were male. Of the 783 who studied within the United States, 221 (28.2%) residents stayed within the same state of his or her medical school. Fewer residents (104 of 555, or 18.7%) stayed within the same state of his or her undergraduate school. Demographic information and geographic switching relative to medical school, undergraduate school, and hometown showed no significant changes between pre-COVID-19 and COVID-19-matched cohorts overall. The median number of publications per resident significantly increased for the COVID-19-matched cohort (median, 1; interquartile range [IQR], 0-4.75) when compared with the non-COVID-19-matched cohort (median, 1; IQR, 0-3, P = 0.004), as did first author publications (median, 1; IQR, 0-1 vs. median, 1; IQR, 0-1; P = 0.015), respectively. The number of residents matching into the same region in the Northeast relative to undergraduate degree was significantly greater after COVID-19 (56 [58%] versus 36 [42%], P = 0.026). The West demonstrated a significant increase in the mean number of total publications (4.0 ± 8.5 vs. 2.3 ± 4.2, P = 0.02) and first author publications (1.24 ± 2.33 vs. 0.68 ± 1.47, P = 0.02) after COVID-19, with the increase in first author publications being significant in a test of medians. CONCLUSIONS: Herein we characterized the most recently matched neurosurgery applicants, paying particular attention to changes over time in relation to the onset of the pandemic. Apart from publication volume, characteristics of residents and geographical preferences did not change with the influence of COVID-19-induced changes in the application process.

The current state of global contribution to open access publishing in neurosurgery: A bibliometric analysis.

•The top three countries made up 56.7% of the total open-access (OA) contributions.•Low and lower-middle-income countries are less than 8% of the total OA publications.•There is a disparity in academic voice in the neurosurgical literature.•Disparities potentially affect neurosurgery practice and knowledge dissemination.

Glucoregulatory disruption in male mice offspring induced by maternal transfer of endocrine disrupting brominated flame retardants in DE-71.

Introduction: Polybrominated diphenyl ethers (PBDEs) are commercially used flame retardants that bioaccumulate in human tissues, including breast milk. PBDEs produce endocrine and metabolic disruption in experimental animals and have been associated with diabetes and metabolic syndrome (MetS) in humans, however, their sex-specific diabetogenic effects are not completely understood. Our past works show glucolipid dysregulation resulting from perinatal exposure to the commercial penta-mixture of PBDEs, DE-71, in C57BL/6 female mice. Methods: As a comparison, in the current study, the effects of DE-71 on glucose homeostasis in male offspring was examined. C57BL/6N dams were exposed to DE-71 at 0.1 mg/kg/d (L-DE-71), 0.4 mg/kg/d (H-DE-71), or received corn oil vehicle (VEH/CON) for a total of 10 wks, including gestation and lactation and their male offspring were examined in adulthood. Results: Compared to VEH/CON, DE-71 exposure produced hypoglycemia after a 11 h fast (H-DE-71). An increased fast duration from 9 to 11 h resulted in lower blood glucose in both DE-71 exposure groups. In vivo glucose challenge showed marked glucose intolerance (H-DE-71) and incomplete clearance (L- and H-DE-71). Moreover, L-DE-71-exposed mice showed altered glucose responses to exogenous insulin, including incomplete glucose clearance and/or utilization. In addition, L-DE-71 produced elevated levels of plasma glucagon and the incretin, active glucagon-like peptide-1 (7-36) amide (GLP-1) but no changes were detected in insulin. These alterations, which represent criteria used clinically to diagnose diabetes in humans, were accompanied with reduced hepatic glutamate dehydrogenase enzymatic activity, elevated adrenal epinephrine and decreased thermogenic brown adipose tissue (BAT) mass, indicating involvement of several organ system targets of PBDEs. Liver levels of several endocannabinoid species were not altered. Discussion: Our findings demonstrate that chronic, low-level exposure to PBDEs in dams can dysregulate glucose homeostasis and glucoregulatory hormones in their male offspring. Previous findings using female siblings show altered glucose homeostasis that aligned with a contrasting diabetogenic phenotype, while their mothers displayed more subtle glucoregulatory alterations, suggesting that developing organisms are more susceptible to DE-71. We summarize the results of the current work, generated in males, considering previous findings in females. Collectively, these findings offer a comprehensive account of differential effects of environmentally relevant PBDEs on glucose homeostasis and glucoregulatory endocrine dysregulation of developmentally exposed male and female mice.

Developmental exposure to indoor flame retardants and hypothalamic molecular signatures: Sex-dependent reprogramming of lipid homeostasis.

Polybrominated diphenyl ethers (PBDEs) are a class of flame-retardant organohalogen pollutants that act as endocrine/neuroendocrine disrupting chemicals (EDCs). In humans, exposure to brominated flame retardants (BFR) or other environmentally persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and novel organophosphate flame retardants has been associated with increasing trends of diabetes and metabolic disease. However, the effects of PBDEs on metabolic processes and their associated sex-dependent features are poorly understood. The metabolic-disrupting effects of perinatal exposure to industrial penta-PBDE mixture, DE-71, on male and female progeny of C57BL/6N mouse dams were examined in adulthood. Dams were exposed to environmentally relevant doses of PBDEs daily for 10 weeks (p.o.): 0.1 (L-DE-71) and 0.4 mg/kg/d (H-DE-71) and offspring parameters were compared to corn oil vehicle controls (VEH/CON). The following lipid metabolism indices were measured: plasma cholesterol, triglycerides, adiponectin, leptin, and liver lipids. L-DE-71 female offspring were particularly affected, showing hypercholesterolemia, elevated liver lipids and fasting plasma leptin as compared to same-sex VEH/CON, while L- and H-DE-71 male F1 only showed reduced plasma adiponectin. Using the quantitative Folch method, we found that mean liver lipid content was significantly elevated in L-DE-71 female offspring compared to controls. Oil Red O staining revealed fatty liver in female offspring and dams. General measures of adiposity, body weight, white and brown adipose tissue (BAT), and lean and fat mass were weighed or measured using EchoMRI. DE-71 did not produce abnormal adiposity, but decreased BAT depots in L-DE-71 females and males relative to same-sex VEH/CON. To begin to address potential central mechanisms of deregulated lipid metabolism, we used RT-qPCR to quantitate expression of hypothalamic genes in energy-regulating circuits that control lipid homeostasis. Both doses of DE-71 sex-dependently downregulated hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, Gshr in female offspring while H-DE-71 downregulated Npy in exposed females relative to VEH/CON. In contrast, exposed male offspring displayed upregulated Stat3 and Mc4r. Intestinal barrier integrity was measured using FITC-dextran since it can lead to systemic inflammation that leads to liver damage and metabolic disease, but was not affected by DE-71 exposure. These findings indicate that maternal transfer of PBDEs disproportionately endangers female offspring to lipid metabolic reprogramming that may exaggerate risk for adult metabolic disease.