Variations in the genomic profiles and clinical behavior of meningioma by racial and ethnic group.

OBJECTIVE: The influence of socioeconomic factors on racial disparities among patients with sporadic meningiomas is well established, yet other potential causative factors warrant further exploration. The authors of this study aimed to determine whether there is significant variation in the genomic profile of meningiomas among patients of different races and ethnicities and its correlation with clinical outcomes. METHODS: The demographic, genomic, and clinical data of patients aged 18 years and older who had undergone surgery for sporadic meningioma between September 2008 and November 2021 were analyzed. Statistical analyses were performed to detect differences across all racial/ethnic groups, as were direct comparisons between Black and non-Black groups plus Hispanic and non-Hispanic groups. RESULTS: This study included 460 patients with intracranial meningioma. Hispanic patients were significantly younger at surgery (53.9 vs 60.2 years, p = 0.0006) and more likely to show symptoms. Black patients had a higher incidence of anterior skull base tumors (OR 3.2, 95% CI 1.7-6.3, p = 0.0008) and somatic hedgehog mutations (OR 5.3, 95% CI 1.6-16.6, p = 0.003). Hispanics were less likely to exhibit the aggressive genomic characteristic of chromosome 1p deletion (OR 0.28, 95% CI 0.07-1.2, p = 0.06) and displayed higher rates of TRAF7 somatic driver mutations (OR 2.96 95% CI 1.1-7.8, p = 0.036). Black patients had higher rates of recurrence (OR 2.6, 95% CI 1.3-5.2, p = 0.009) and shorter progression-free survival (PFS; HR 2.9, 95% CI 1.6-5.4, p = 0.002) despite extents of resection (EORs) similar to those of non-Black patients (p = 0.745). No significant differences in overall survival were observed among groups. CONCLUSIONS: Despite similar EORs, Black patients had worse clinical outcomes following meningioma resection, characterized by a higher prevalence of somatic hedgehog mutations, increased recurrence rates, and shorter PFS. Meanwhile, Hispanic patients had less aggressive meningiomas, a predisposition for TRAF7 mutations, and no difference in PFS. These findings could inform the care and treatment strategies for meningiomas, and they establish the foundation for future studies focusing on the genomic origins of these observed differences.

Frailty and postoperative outcomes in brain tumor patients: a systematic review subdivided by tumor etiology.

PURPOSE: Frailty has gained prominence in neurosurgical oncology, with more studies exploring its relationship to postoperative outcomes in brain tumor patients. As this body of literature continues to grow, concisely reviewing recent developments in the field is necessary. Here we provide a systematic review of frailty in brain tumor patients subdivided by tumor type, incorporating both modern frailty indices and traditional Karnofsky Performance Status (KPS) metrics. METHODS: Systematic literature review was performed using PRISMA guidelines. PubMed and Google Scholar were queried for articles related to frailty, KPS, and brain tumor outcomes. Only articles describing novel associations between frailty or KPS and primary intracranial tumors were included. RESULTS: After exclusion criteria, systematic review yielded 52 publications. Amongst malignant lesions, 16 studies focused on glioblastoma. Amongst benign tumors, 13 focused on meningiomas, and 6 focused on vestibular schwannomas. Seventeen studies grouped all brain tumor patients together. Seven studies incorporated both frailty indices and KPS into their analyses. Studies correlated frailty with various postoperative outcomes, including complications and mortality. CONCLUSION: Our review identified several patterns of overall postsurgical outcomes reporting for patients with brain tumors and frailty. To date, reviews of frailty in patients with brain tumors have been largely limited to certain frailty indices, analyzing all patients together regardless of lesion etiology. Although this technique is beneficial in providing a general overview of frailty's use for brain tumor patients, given each tumor pathology has its own unique etiology, this combined approach potentially neglects key nuances governing frailty's use and prognostic value.

Associations of race and socioeconomic status with outcomes after intracranial meningioma resection: a systematic review and meta-analysis.

PURPOSE: Social determinants of health broadly affect healthcare access and outcomes. Studies report that minorities and low socioeconomic status (SES) patients undergoing intracranial meningioma resection demonstrate worse outcomes and higher mortality rates. This systematic review and meta-analysis summarizes the available research reporting racial and SES disparities in intracranial meningioma resection outcomes. METHODS: A systematic review was conducted using PRISMA guidelines and included peer-reviewed, English-language articles from the United States between 2000 and 2022 that reported racial and SES disparities in meningioma outcomes. Outcomes included overall survival (OS), extent of resection (EOR), hospitalization costs, length of stay (LOS), 30-day readmission, recurrence, and receipt of surgery and adjuvant radiotherapy. A quantitative meta-analysis was performed only on survival outcomes by race. All other variables were summarized as a systematic review. RESULTS: 633 articles were identified; 19 studies met inclusion criteria. Black or low SES patients were more likely to have increased hospitalization costs, rates of 30-day readmission, LOS, recurrence and less likely to undergo surgery, gross total resection, and adjuvant radiotherapy for their tumors. Six studies were used for the quantitative meta-analysis of race and OS. Compared to White patients, Black patients had significantly worse survival outcomes, and Asian patients had significantly better survival outcomes. CONCLUSION: Disparities in outcomes exist for patients who undergo surgery for meningioma, such that Black and low SES patients have worse outcomes. The literature is quite sparse and contains confounding relationships not often accounted for appropriately. Further studies are needed to help understand these disparities to improve outcomes.

Clinical and genomic differences in supratentorial versus infratentorial NF2 mutant meningiomas.

OBJECTIVE: Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities-however, they can also be found in the posterior fossa. The authors investigated whether NF2 mutant meningiomas differ in clinical and genomic features based on their location relative to the tentorium. METHODS: Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic NF2 mutant meningiomas were reviewed and analyzed. RESULTS: A total of 191 NF2 mutant meningiomas were included (165 supratentorial, 26 infratentorial). Supratentorial NF2 mutant meningiomas were significantly associated with edema (64.0% vs 28.0%, p < 0.001); higher grade-i.e., WHO grade II or III (41.8% vs 3.9%, p < 0.001); elevated Ki-67 (55.0% vs 13.6%, p < 0.001); and larger volume (mean 45.5 cm3 vs 14.9 cm3, p < 0.001). Furthermore, supratentorial tumors were more likely to harbor the higher-risk feature of chromosome 1p deletion (p = 0.038) and had a larger fraction of the genome altered with loss of heterozygosity (p < 0.001). Infratentorial meningiomas were more likely to undergo subtotal resection than supratentorial tumors (37.5% vs 15.8%, p = 0.021); however, there was no significant difference in overall (p = 0.2) or progression-free (p = 0.4) survival. CONCLUSIONS: Supratentorial NF2 mutant meningiomas are associated with more aggressive clinical and genomic features as compared with their infratentorial counterparts. Although infratentorial tumors have higher rates of subtotal resection, there is no associated difference in survival or recurrence. These findings help to better inform surgical decision-making in the management of NF2 mutant meningiomas based on location, and may guide postoperative management of these tumors.

Epstein-Barr virus-associated primary intracranial leiomyosarcoma in an immunocompetent patient: illustrative case.

BACKGROUND: Primary intracranial leiomyosarcomas (PILMSs) are extremely rare tumors arising from smooth muscle connective tissue. PILMSs have been shown to be associated with Epstein-Barr virus (EBV). Thus far, EBV-associated PILMS has been exclusively described in immunocompromised patients. OBSERVATIONS: A 40-year-old male presented with a 2-year history of left-sided headaches, nausea, and vomiting. Magnetic resonance imaging demonstrated a large, heterogeneously enhancing, lobulated, dura-based mass arising from the left middle cranial fossa with associated edema and mass effect. The patient underwent an uncomplicated resection of suspected meningioma; neuropathology revealed the exceedingly rare diagnosis of EBV-associated PILMS. Follow-up testing for human immunodeficiency virus (HIV) and other immunodeficiencies confirmed the patient's immunocompetent status. LESSONS: Primary intracranial smooth muscle tumors are often misdiagnosed as meningiomas due to their similar appearance on imaging. PILMSs have a poor prognosis and gross total resection is the mainstay of treatment in the absence of clear recommendations for management. Prompt diagnosis and resection are important; therefore, these tumors should be included in the differential of dura-based tumors, especially among immunocompromised patients. Although EBV-associated PILMSs usually occur in immunocompromised individuals, their presence cannot be ruled out in immunocompetent patients.

Implementation of Canada's youth justice minimum age of 12: implications for children in Canada and globally.

Youth justice minimum age thresholds vary widely and are garnering increased global attention. In 1984, legislation in Canada excluded all children under age 12 from its youth justice system, yet few studies have examined implementation of the statute. We interviewed 22 experts across Canada to understand how the law functions and to guide responses in Canada and other nations. We used an inductive, thematic analysis process. Experts reported that excluding children under 12 from Canada's youth justice system has been effective in eliminating juvenile legal processing for children under 12, and promoting responses that identify and address the root causes of children's disruptive behavior outside of the legal system. Experts noted that addressing key gaps in funding and community service provision can reduce service variation by geography, race or ethnicity, socio-economic status, and ability or disability status and can enhance youths' success. Canada's experience suggests that for optimal implementation, minimum age laws should be coupled with robust funding and sufficient service provision to achieve racial justice and health equity.

Applying a Health Development Lens to Canada's Youth Justice Minimum Age Law.

OBJECTIVES: We applied a Life Course Health Development (LCHD) framework to examine experts' views on Canada's youth justice minimum age law of 12, which excludes children aged 11 and under from the youth justice system. METHODS: We interviewed 21 experts across Canada to understand their views on Canada's youth justice minimum age of 12. The 7 principles of the LCHD model (health development, unfolding, complexity, timing, plasticity, thriving, harmony) were used as a guiding framework for qualitative data analysis to understand the extent to which Canada's approach aligns with developmental science. RESULTS: Although the LCHD framework was not directly discussed in the interviews, the 7 LCHD framework concepts emerged in the analyses and correlated with 7 justice principles, which we refer to as "LCHD Child Justice Principles." Child involvement in the youth justice system was considered to be developmentally inappropriate, with alternative systems and approaches regarded as better suited to support children and address root causes of disruptive behaviors, so that all children could reach their potential and thrive. CONCLUSIONS: Canada's approach to its minimum age law aligns with the LCHD framework, indicating that Canada's approach adheres to concepts of developmental science. Intentionally applying LCHD-based interventions may be useful in reducing law enforcement contact of adolescents in Canada, and of children and adolescents in the United States, which currently lacks a minimum age law.

Resilience to aging is a heterogeneous characteristic defined by physical stressors.

Physical resilience, the capacity to respond to and recover from a stressful event, declines with advancing age. Individuals respond differently to physical stressors across their lifespans. While the biological underpinnings of resilience remain unclear, a plausible determinant is the capacity of an individual's cellular and molecular levels to return to homeostasis after a physical challenge. Impaired resilience may not only be a consequence of aging but could also be a contributing factor to the aging process. Therefore, resilience at relatively younger ages could be predictive of future health and lifespan. By utilizing standardized physical challenges and measuring stress response patterns, the relative resilience of individuals can be quantified and classified. Current preclinical research suggests that several physical stressors could be used to measure resilience in clinical aging studies. A mechanistic understanding of why some individuals are more resilient to physical stressors than others could help identify protective factors and therapeutic ways to promote healthy aging.

Generation and characterization of a tractable C. elegans model of tauopathy.

Alzheimer's disease(AD) is an age-associated neurodegenerative disease that results in deterioration of memory and cognitive function. As a currently untreatable disorder, AD has emerged as one of the defining biomedical challenges of our time. Thus, new approaches that can examine the cellular and molecular mechanisms underlying age-related AD pathology are sorely needed. One of the hallmarks of Alzheimer's disease is the hyperphosphorylation of the tau protein. Caenorhabditis elegans have been previously used to study the genetic pathways impacted by tau proteotoxic stress; however, currently, available C. elegans tau models express the human protein solely in neurons, which are unresponsive to global RNA interference (RNAi). This limits powerful RNAi screening methods from being utilized effectively in these disease models. Our goal was to develop a C. elegans tau model that has pronounced tau-induced disease phenotypes in cells that can be modified by feeding RNAi methods. Towards this end, we generated a novel C. elegans transgenic line with codon-optimized human 0N4R V337M tau expressed in the body wall muscle under the myo-3 promoter. Immunoblotting experiments revealed that the expressed tau is phosphorylated on epitopes canonically associated with human AD pathology. The tau line has significantly reduced health metrics, including egg laying, growth rate, paralysis, thrashing frequency, crawling speed, and lifespan. These defects are suppressed by RNAi directed against the tau mRNA. Taken together, our results suggest that this alternative tau genetic model could be a useful tool for uncovering the mechanisms that influence the hyperphosphorylation and toxicity of human tau via RNAi screening and other approaches.

Short-term oral rapamycin prevents age-related learning impairment in mice.

Effective treatments to prevent or delay age-related learning impairment are not generally available. In a preliminary preclinical study, mice 20 months of age were fed a diet containing 14 ppm rapamycin, an inhibitor of mTOR, for three months and then tested in a spatial navigation task. Mice fed the nonmedicated control diet showed learning impairment while mice fed the rapamycin diet were not learning impaired. This observation provides support for additional preclinical studies and suggests that short-term rapamycin treatment could be a possible strategy for preventing or delaying age-related cognitive impairment in people.

Resilience to acute sleep deprivation is associated with attenuation of hippocampal mediated learning impairment.

BACKGROUND: Sleep deprivation is a universal issue that affects individuals in different ways. While some individuals experience a deficit in performance, others experience resiliency as they maintain high levels of physical and mental activity. Sleep loss is known to cause cognitive dysfunction in areas such as learning and memory, but little is known about neural mechanisms that contribute to resilience to this adverse effect. METHODS: An existing database of a learning paradigm in sleep deprived and non-sleep deprived 16 to 18-month old C57BL/6 mice was used to identify fast learners and slow learners based on an R2 value representing the learning curve of each individual mouse. RESULTS: Results showed that sleep deprived mice had more slow learners compared to fast learners whereas non-sleep-deprived mice showed the opposite. Hippocampal immunohistochemistry and digital imaging analysis showed sleep deprived, fast learners expressed lower levels of monocyte chemoattractant protein-1 and histone deacetylase 2 and higher levels of synaptophysin and brain-derived neurotrophic factor compared to sleep-deprived slow learners. CONCLUSIONS: These observations provide evidence to suggest that sleep-deprived mice that performed well in a cognitive assay show less hippocampal mediated learning impairment and provide the rationale for further investigations into neurobiological resilience to sleep deprivation with increasing age.