External assessment of preoperative scores for predicting outcome after microvascular decompression for trigeminal neuralgia.

OBJECTIVE: Recently, two scoring systems have been developed for predicting pain-free outcomes after microvascular decompression (MVD). Evaluation of these scores on large external datasets has been limited. In this study, the authors aimed to evaluate the performance of published MVD scoring systems in predicting pain-free outcome. METHODS: A total of 458 patients who underwent MVD for trigeminal neuralgia (TN) between 2007 and 2020 and had at least 6 months of follow-up were included in this study. Hardaway and Panczykowski scores were retrospectively computed for each patient and compared with postoperative pain recurrence and pain-free duration. RESULTS: The mean ± SD area under the receiver operating characteristic curve for predicting any pain recurrence after MVD was 0.567 ± 0.081 using the Hardaway score and 0.546 ± 0.085 using the Panczykowski score. On log-rank tests and Kaplan-Meier analysis, the patients with Hardaway scores of 0-2 had significantly shorter pain-free survival times after MVD than did those with a score of 3. Patients with a Panczykowski score of 1 had a significantly shorter pain-free duration after surgery compared with both patients with scores of 2-3 and patients with scores of 4-5. Patients with Panczykowski scores of 2-3 also had significantly shorter pain-free duration compared with patients with scores of 4-5. CONCLUSIONS: Both the Hardaway and Panczykowski scores may be useful for predicting postoperative pain-free duration in TN patients, and their utility may be greatest when scores are clustered. Continued refinement of both scoring systems will help to improve our ability to predict patient outcomes after MVD.

Hemoglobin Drop is Associated with Early Post-operative Stroke Following Revascularization Surgery for Moyamoya Disease.

BACKGROUND: Postoperative stroke is a potentially devastating neurological complication following surgical revascularization for Moyamoya disease. We sought to evaluate whether peri-operative hemoglobin levels were associated with the risk of early post-operative stroke following revascularization surgery in adult Moyamoya patients. METHODS: Adult patients having revascularization surgeries for Moyamoya disease between 1999-2022 were identified through single institutional retrospective review. Logistic regression analysis was used to test for the association between hemoglobin drop and early postoperative stroke. RESULTS: In all, 106 revascularization surgeries were included in the study. A stroke occurred within 7 days after surgery in 9.4% of cases. There were no significant associations between the occurrence of an early postoperative stroke and patient age, gender, or race. Mean postoperative hemoglobin drop was greater in patients who suffered an early postoperative stroke compared with patients who did not (2.3±1.1 g/dL vs. 1.3±1.1 g/dL, respectively; P=0.034). Patients who experienced a hemoglobin drop post-operatively had 2.03 times greater odds (95% confidence interval, 1.06-4.23; P=0.040) of having a stroke than those whose hemoglobin levels were stable. Early postoperative stroke was also associated with an increase in length of hospital stay (P<0.001), discharge to a rehabilitation facility (P=0.014), and worse modified Rankin scale at 1 month (P=0.001). CONCLUSION: This study found a significant association between hemoglobin drop and early postoperative stroke following revascularization surgery in adult patients with Moyamoya disease. Based on our findings, it may be prudent to avoid hemoglobin drops in Moyamoya patients undergoing surgical revascularization.

Preoperative Opioid Use and Postoperative Outcomes in Patients Undergoing Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND AND OBJECTIVES: The prescription of opioid analgesics for trigeminal neuralgia (TN) is controversial, and their effect on postoperative outcomes for patients with TN undergoing microvascular decompression (MVD) has not been reported. We aimed to describe the relationship between preoperative opioid use and postoperative outcomes in patients with TN undergoing MVD. METHODS: We reviewed the records of 920 patients with TN at our institution who underwent an MVD between 2007 and 2020. Patients were sorted into 2 groups based on preoperative opioid usage. Demographic information, comorbidities, characteristics of TN, preoperative medications, pain and numbness outcomes, and recurrence data were recorded and compared between groups. Multivariate ordinal regression, Kaplan-Meier survival analysis, and Cox proportional hazards were used to assess differences in pain outcomes between groups. RESULTS: One hundred and forty-five (15.8%) patients in this study used opioids preoperatively. Patients who used opioids preoperatively were younger (P = .04), were more likely to have a smoking history (P < .001), experienced greater pain in modified Barrow Neurological Institute pain score at final follow-up (P = .001), and were more likely to experience pain recurrence (P = .01). In addition, patients who used opioids preoperatively were more likely to also have been prescribed TN medications including muscle relaxants and antidepressants preoperatively (P < .001 and P < .001, respectively). On multivariate regression, opioid use was an independent risk factor for greater postoperative pain at final follow-up (P = .006) after controlling for variables including female sex and age. Opioid use was associated with shorter time to pain recurrence on Kaplan-Meier analysis (P = .005) and was associated with increased risk for recurrence on Cox proportional hazards regression (P = .008). CONCLUSION: Preoperative opioid use in the setting of TN is associated with worse pain outcomes and increased risk for pain recurrence after MVD. These results indicate that opioids should be prescribed cautiously for TN and that worse post-MVD outcomes may occur in patients using opioids preoperatively.

Awake Versus Asleep Craniotomy for Patients With Eloquent Glioma: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions. METHODS: MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day). RESULTS: Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD] = MD = 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30). CONCLUSION: Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.

The Role of γδ T-Lymphocytes in Glioblastoma: Current Trends and Future Directions.

Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research avenues for future studies. Using the PubMed, ScienceDirect, and JSTOR databases, we performed a review of the literature studying the biology of γδ T cells and their role in GBM treatment. We identified 15 studies focused on γδ T cells in human GBM. Infiltrative γδ T cells can incite antitumor immune responses in certain TMEs, though rapid tumor progression and TME hypoxia may impact the extent of tumor suppression. In the studies, available findings have shown both the potential for robust antitumor activity and the risk of protumor activity. While γδ T cells have potential as a therapeutic agent against GBM, the technical challenges of extracting, isolating, and expanding γδ T cells, and the activation of antitumoral versus protumoral cascades, remain barriers to their application. Overcoming these limitations may transform γδ T cells into a promising immunotherapy in GBM.

Frailty Predicts Worse Pain Outcomes for Older TN Patients Treated with Microvascular Decompression.

BACKGROUND: Trigeminal neuralgia (TN) is a debilitating orofacial pain disorder. Recent data from a national database suggest that microvascular decompression (MVD) in frail patients is associated with more postoperative complications. However, the long-term pain outcomes for frail TN patients are not known. We aimed to elucidate the relationship between frailty and long-term pain outcomes after MVD for TN. METHODS: From 2007 to 2020, 368 TN patients aged ≥60 years underwent MVD at our institution. Patient demographics, clinical characteristics, postoperative complications, and long-term pain outcomes were recorded. Frailty was assessed using the modified 5-item frailty index (mFI-5) score, and the patients were dichotomized into nonfrail (mFI-5 <2) and frail (mFI-5 >1). Differences were assessed via the t test, χ2 test, multivariate ordinal regression, and Cox proportional hazards analysis. RESULTS: Of the 368 patients analyzed, 9.8% were frail. The frail patients were significantly older (P = 0.02) with a higher body mass index (P = 0.01) and a greater incidence of comorbidities (P < 0.001). Frail patients presented with significantly higher pain levels at the final follow-up (P = 0.04). On multivariate analysis, frailty was independently associated with more pain at follow-up (P = 0.01), as was younger age, female sex, and black race. The relationship between frailty and postoperative pain recurrence showed a trend toward significance (P = 0.06), and younger age and black race were significantly associated with recurrence. CONCLUSIONS: Frail patients undergoing MVD are at risk of worse long-term pain outcomes. Our results provide clinicians with useful information pertaining to the influence of frailty on the long-term efficacy of MVD in treating TN.

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.

Venous thromboembolism in aneurysmal subarachnoid hemorrhage: Risk factors and timing of chemoprophylaxis.

INTRODUCTION: Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality among patients recovering from aneurysmal subarachnoid hemorrhage (aSAH). Prophylactic heparin reduces the risk of VTE, but the optimal timing for its initiation among aSAH patients remains unclear. OBJECTIVE: To conduct a retrospective study assessing risk factors for VTE and optimal timing of chemoprophylaxis in patients treated for aSAH. METHODS: From 2016-2020, 194 adult patients were treated for aSAH at our institution. Patient demographics, clinical diagnoses, complications, pharmacologic interventions, and outcomes were recorded. Risk factors for symptomatic VTE (sVTE) were analyzed via Chi-squared, univariate, and multivariate regression. RESULTS: In total 33 patients presented with sVTE (25 DVT, 14 PE). Patients with sVTE had longer hospital stays (p < 0.01) and worse outcomes at one-month (p < 0.01) and three-month follow-up (p = 0.02). Univariate predictors of sVTE included male sex (p = 0.03), Hunt Hess score (p = 0.01), Glasgow Coma scale (p = 0.02), intracranial hemorrhage (p = 0.03), hydrocephalus requiring external ventricular drain (EVD) placement (p < 0.01), and mechanical ventilation (p < 0.01). Only hydrocephalus requiring EVD (p = 0.01) and ventilator use (p = 0.02) remained significant upon multivariate analysis. Patients with delayed heparin introduction were significantly more likely to sustain sVTE on univariate analysis (p = 0.02) with a trend-level significance on multivariate analysis (p = 0.07). CONCLUSIONS: Patients with aSAH are more likely to develop sVTE following use of perioperative EVD or mechanical ventilation. sVTE leads to longer hospital stays and worse outcomes among patients treated for aSAH. Delayed heparin initiation increases the risk of sVTE. Our results may help guide surgical decision-making during recovery from aSAH and improve VTE-related postoperative outcomes.

Use of tubular retractors to access deep brain lesions: A case series.

BACKGROUND: Deep-seated intracranial lesions can be accessed using blade retractors that may disrupt white matter tracts, exert pressure on adjacent tissue, and lead to post-operative venous injury. Tubular retractors may minimize disruption to white matter tracts by radially dispersing pressure onto surrounding tissue. This study characterizes perioperative outcomes in patients undergoing biopsy or resection of intracranial pathologies using tubular retractors. METHODS: Adult patients (≥18 years) undergoing neurosurgical intervention using tubular retractors at a single health system (January 2016-February 2022) were identified through chart review. Demographics, disease characteristics, management data, and clinical outcomes were collected. RESULTS: A total of 49 patients were included; 23 (47%) had primary brain tumors, 8 (16%) metastases, 6 (12%) intracranial hemorrhage (ICH), 5 (10%) cavernomas, and 7 (14%) other pathologies. Lesions were located subcortically (n = 19, 39%), intraventricularly (n = 15, 31%), and in deep gray matter (n = 11, 22%). Gross total resection (GTR) or near GTR was achieved in 21 of 26 (80.8%) patients with intracranial lesions where GTR was the goal of surgery; 10 of 11 (90.9%) biopsies in patients with masses were diagnostic. Five of six (83.3%) ICHs were totally or near totally evacuated. Seventeen patients (35%) had major complications post-operatively. The most common complications were DVT/PE (n = 7, 14%) and seizures (n = 6, 12%). For patients who experienced post-operative seizures, 3 had seizures preoperatively and 1 had seizures in the context of electrolyte derangements. No patients died of post-operative complications. CONCLUSION: This operative approach may facilitate safe and efficacious biopsy or resection of deep-seated intracranial pathologies.

Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators.

Due to their immunosuppressive role, tumor-infiltrating regulatory T cells (TI-Tregs) represent attractive immuno-oncology targets. Analysis of TI vs. peripheral Tregs (P-Tregs) from 36 patients, across four malignancies, identified 17 candidate master regulators (MRs) as mechanistic determinants of TI-Treg transcriptional state. Pooled CRISPR-Cas9 screening in vivo, using a chimeric hematopoietic stem cell transplant model, confirmed the essentiality of eight MRs in TI-Treg recruitment and/or retention without affecting other T cell subtypes, and targeting one of the most significant MRs (Trps1) by CRISPR KO significantly reduced ectopic tumor growth. Analysis of drugs capable of inverting TI-Treg MR activity identified low-dose gemcitabine as the top prediction. Indeed, gemcitabine treatment inhibited tumor growth in immunocompetent but not immunocompromised allografts, increased anti-PD-1 efficacy, and depleted MR-expressing TI-Tregs in vivo. This study provides key insight into Treg signaling, specifically in the context of cancer, and a generalizable strategy to systematically elucidate and target MR proteins in immunosuppressive subpopulations.

CAR T Cell Therapy in Glioblastoma: Overcoming Challenges Related to Antigen Expression.

Glioblastoma (GBM) is the most common primary brain tumor, yet prognosis remains dismal with current treatment. Immunotherapeutic strategies have had limited effectiveness to date in GBM, but recent advances hold promise. One such immunotherapeutic advance is chimeric antigen receptor (CAR) T cell therapy, where autologous T cells are extracted and engineered to express a specific receptor against a GBM antigen and are then infused back into the patient. There have been numerous preclinical studies showing promising results, and several of these CAR T cell therapies are being tested in clinical trials for GBM and other brain cancers. While results in tumors such as lymphomas and diffuse intrinsic pontine gliomas have been encouraging, early results in GBM have not shown clinical benefit. Potential reasons for this are the limited number of specific antigens in GBM, their heterogenous expression, and their loss after initiating antigen-specific therapy due to immunoediting. Here, we review the current preclinical and clinical experiences with CAR T cell therapy in GBM and potential strategies to develop more effective CAR T cells for this indication.

Resection of Condylar Skull Base Tumor via Combined Far Lateral and Infrajugular Approaches with Single-Stage Occipitocervical Fusion.

Epithelioid hemangioma is a rare vascular mesenchymal tumor with a paucity of reports of cranial involvement. In particular, guidance on treatment for lateral skull base lesions is lacking, despite this being a highly technically challenging location. Nuances in the management decisions for this tumor type are discussed. Two major challenges with this location are proximity to critical neurovascular structures and managing secondary craniocervical instability. We present a patient with a lateral skull base epithelioid hemangioma treated with transcondylar resection, single-stage occipitocervical fusion, and adjuvant radiation and chemotherapy. The patient consented to both the procedure and the published report of her case including imaging. Obtaining tissue was necessary for diagnosis. Maximal safe resection, resection of a tumor such that the greatest clinical benefit is achieved with the minimum risk, was favored given the location and vascularity of the lesion. Occipitocervical fusion was recommended given ongoing bony destruction by the tumor and further expected iatrogenic instability upon resection. This was performed as a single stage given expected need for postoperative adjuvant radiation therapy and dynamic neck pain (Video 1). Surgical planning and decision making are detailed, including rationale and potential risks and benefits. We discuss positioning, equipment needs, and the importance of a multidisciplinary surgical team. Park bench positioning was used for part 1, left-sided extended far lateral and infratemporal fossa presigmoid approaches. For part 2, occipitocervical fusion, the patient was transitioned to prone position. The anatomy is highlighted in labeled pictures of the approach and dissection, and surgical video is presented for key surgical steps. Preoperative and postoperative imaging is analyzed. A desirable clinical outcome was obtained.

Predictors of surgical site infection in glioblastoma patients undergoing craniotomy for tumor resection.

OBJECTIVE: Surgical site infections (SSIs) burden patients and healthcare systems, often requiring additional intervention. The objective of this study was to identify the relationship between preoperative predictors inclusive of scalp incision type and postoperative SSI following glioblastoma resection. METHODS: The authors retrospectively reviewed cases of glioblastoma resection performed at their institution from December 2006 to December 2019 and noted preoperative demographic and clinical presentations, excluding patients missing these data. Preoperative nutritional indices were available for a subset of cases. Scalp incisions were categorized as linear/curvilinear, reverse question mark, trapdoor, or frontotemporal. Patients were dichotomized by SSI incidence. Multivariable logistic regression was used to determine predictors of SSI. RESULTS: A total of 911 cases of glioblastoma resection were identified, 30 (3.3%) of which demonstrated postoperative SSI. There were no significant differences in preoperative malnutrition or number of surgeries between SSI and non-SSI cases. The SSI cases had a significantly lower preoperative Karnofsky Performance Status (KPS) than the non-SSI cases (63.0 vs 75.1, p < 0.0001), were more likely to have prior radiation history (43.3% vs 26.4%, p = 0.042), and were more likely to have received steroids both preoperatively and postoperatively (83.3% vs 54.5%, p = 0.002). Linear/curvilinear incisions were more common in non-SSI than in SSI cases (56.9% vs 30.0%, p = 0.004). Trapdoor scalp incisions were more frequent in SSI than non-SSI cases (43.3% vs 24.2%, p = 0.012). On multivariable analysis, a lower preoperative KPS (OR 1.04, 95% CI 1.02-1.06), a trapdoor scalp incision (OR 3.34, 95% CI 1.37-8.49), and combined preoperative and postoperative steroid administration (OR 3.52, 95% CI 1.41-10.7) were independently associated with an elevated risk of postoperative SSI. CONCLUSIONS: The study findings indicated that SSI risk following craniotomy for glioblastoma resection may be elevated in patients with a low preoperative KPS, a trapdoor scalp incision during surgery, and steroid treatment both preoperatively and postoperatively. These data may help guide future operative decision-making for these patients.

Machine Learning Models for Predicting Postoperative Outcomes following Skull Base Meningioma Surgery.

Objective While predictive analytic techniques have been used to analyze meningioma postoperative outcomes, to our knowledge, there have been no studies that have investigated the utility of machine learning (ML) models in prognosticating outcomes among skull base meningioma patients. The present study aimed to develop models for predicting postoperative outcomes among skull base meningioma patients, specifically prolonged hospital length of stay (LOS), nonroutine discharge disposition, and high hospital charges. We also validated the predictive performance of our models on out-of-sample testing data. Methods Patients who underwent skull base meningioma surgery between 2016 and 2019 at an academic institution were included in our study. Prolonged hospital LOS and high hospital charges were defined as >4 days and >$47,887, respectively. Elastic net logistic regression algorithms were trained to predict postoperative outcomes using 70% of available data, and their predictive performance was evaluated on the remaining 30%. Results A total of 265 patients were included in our final analysis. Our cohort was majority female (77.7%) and Caucasian (63.4%). Elastic net logistic regression algorithms predicting prolonged LOS, nonroutine discharge, and high hospital charges achieved areas under the receiver operating characteristic curve of 0.798, 0.752, and 0.592, respectively. Further, all models were adequately calibrated as determined by the Spiegelhalter Z -test ( p >0.05). Conclusion Our study developed models predicting prolonged hospital LOS, nonroutine discharge disposition, and high hospital charges among skull base meningioma patients. Our models highlight the utility of ML as a tool to aid skull base surgeons in providing high-value health care and optimizing clinical workflows.

Supercharged chimeric antigen receptor T cells in solid tumors.

Chimeric antigen receptor (CAR) T cells have demonstrated success in treating select hematological malignancies, but their activity in solid tumors has been comparably modest. Challenges specific to treating solid tumors include trafficking and distribution throughout the tumor site, overcoming the immunosuppressive tumor microenvironment (TME), and identifying antigenic targets that are widely expressed and indispensable to tumor biology. In this issue of the JCI, Tian et al. describe the use of bicistronic CAR T cells that target multiple antigens expressed in neuroblastoma to overcome antigenic heterogeneity. Combining this approach with interventions that enhance T cell trafficking and prevent acquired dysfunction in the TME may lead to a long-awaited breakthrough in the clinical implementation of CAR T cells for the treatment of solid tumors.

The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke.

The immune response to ischemic stroke is an area of study that is at the forefront of stroke research and presents promising new avenues for treatment development. Upon cerebral vessel occlusion, the innate immune system is activated by danger-associated molecular signals from stressed and dying neurons. Microglia, an immune cell population within the central nervous system which phagocytose cell debris and modulate the immune response via cytokine signaling, are the first cell population to become activated. Soon after, monocytes arrive from the peripheral immune system, differentiate into macrophages, and further aid in the immune response. Upon activation, both microglia and monocyte-derived macrophages are capable of polarizing into phenotypes which can either promote or attenuate the inflammatory response. Phenotypes which promote the inflammatory response are hypothesized to increase neuronal damage and impair recovery of neuronal function during the later phases of ischemic stroke. Therefore, modulating neuroimmune cells to adopt an anti-inflammatory response post ischemic stroke is an area of current research interest and potential treatment development. In this review, we outline the biology of microglia and monocyte-derived macrophages, further explain their roles in the acute, subacute, and chronic stages of ischemic stroke, and highlight current treatment development efforts which target these cells in the context of ischemic stroke.

Substance Use Disorders Are Independently Associated with Hospital Readmission Among Patients with Brain Tumors.

BACKGROUND: Research on the effects of substance use disorders (SUDs) on postoperative outcomes within neurosurgical oncology has been limited. Therefore, the present study sought to quantify the effect of having a SUD on hospital length of stay, postoperative complication incidence, discharge disposition, hospital charges, 90-day readmission rates, and 90-day mortality rates following brain tumor surgery. METHODS: The present study used data from patients who received surgical resection for brain tumor at a single institution between January 1, 2017, and December 31, 2019. The Mann-Whitney U test was used for bivariate analysis of continuous variables and Fisher exact test was used for bivariate analysis of categorical variables. Multivariate analysis was conducted using logistic regression models. RESULTS: Our study cohort included a total of 2519 patients, 124 (4.9%) of whom had at least 1 SUD. More specifically, 90 (3.6%) patients had an alcohol use disorder, 27 (1.1%) had a cannabis use disorder, and 12 (0.5%) had an opioid use disorder. On bivariate analysis, 90-day hospital readmission was the only postoperative outcome significantly associated with a SUD (odds ratio 2.21, P = 0.0011). When controlling for patient age, sex, race, marital status, insurance, brain tumor diagnosis, 5-factor modified frailty index score, American Society of Anesthesiologists score, and surgery number, SUDs remained significantly and independently associated with 90-day readmission (odds ratio 1.82, P = 0.013). CONCLUSIONS: In patients with brain tumor, SUDs significantly and independently predict 90-day hospital readmission after surgery. Targeted management of patients with SUDs before and after surgery can optimize patient outcomes and improve the provision of high-value neurosurgical care.

Synthesizing Molecular and Immune Characteristics to Move Beyond WHO Grade in Meningiomas: A Focused Review.

No portion of this manuscript has previously been presented. Meningiomas, the most common primary intracranial tumors, are histologically categorized by the World Health Organization (WHO) grading system. While higher WHO grade is generally associated with poor clinical outcomes, a significant subset of grade I tumors recur or progress, indicating a need for more reliable models of meningioma behavior. Several groups have developed risk scores based on molecular or immunologic characteristics. These classification schemes show promise, with several models preliminarily demonstrating similar or superior accuracy to WHO grading. Improved understanding of immune system recognition and targeting of meningioma subtypes is necessary to advance the predictive power, as well as develop new therapies. Here, we characterize meningioma molecular drivers, predictive of recurrence and progression, and describe specific aspects of the immune response to meningiomas while highlighting critical questions and ongoing research. Relevant manuscripts of interest were identified using a systematic approach and synthesized into this focused review. Finally, we summarize the ongoing and completed clinical trials for immunotherapy in meningiomas and offer perspective on future directions.

Social determinants of health and the prediction of 90-day mortality among brain tumor patients.

OBJECTIVE: Within the neurosurgical oncology literature, the effect of structural and socioeconomic factors on postoperative outcomes remains unclear. In this study, the authors quantified the effects of social determinant of health (SDOH) disparities on hospital complications, length of stay (LOS), nonroutine discharge, 90-day readmission, and 90-day mortality following brain tumor surgery. METHODS: The authors retrospectively reviewed the records of brain tumor patients who had undergone resection at a single institution in 2017-2019. The prevalence of SDOH disparities among patients was tracked using International Classification of Diseases Ninth and Tenth Revisions (ICD-9 and ICD-10) codes. Bivariate (Mann-Whitney U-test and Fisher's exact test) and multivariate (logistic and linear) regressions revealed whether there was an independent relationship between SDOH status and postoperative outcomes. RESULTS: The patient cohort included 2519 patients (mean age 55.27 ± 15.14 years), 187 (7.4%) of whom experienced at least one SDOH disparity. Patients who experienced an SDOH disparity were significantly more likely to be female (OR 1.36, p = 0.048), Black (OR 1.91, p < 0.001), and unmarried (OR 1.55, p = 0.0049). Patients who experienced SDOH disparities also had significantly higher 5-item modified frailty index (mFI-5) scores (p < 0.001) and American Society of Anesthesiologists (ASA) classes (p = 0.0012). Experiencing an SDOH disparity was associated with a significantly longer hospital LOS (p = 0.0036), greater odds of a nonroutine discharge (OR 1.64, p = 0.0092), and greater odds of 90-day mortality (OR 2.82, p = 0.0016) in the bivariate analysis. When controlling for patient demographics, tumor diagnosis, mFI-5 score, ASA class, surgery number, and SDOH status, SDOHs independently predicted hospital LOS (coefficient = 1.22, p = 0.016) and increased odds of 90-day mortality (OR 2.12, p = 0.028). CONCLUSIONS: SDOH disparities independently predicted a prolonged hospital LOS and 90-day mortality in brain tumor patients. Working to address these disparities offers a new avenue through which to reduce patient morbidity and mortality following brain tumor surgery.

Pediatric glioblastoma: mechanisms of immune evasion and potential therapeutic opportunities.

Pediatric glioblastoma is relatively rare compared with its adult counterpart but is associated with a similarly grim prognosis. Available data indicate that pediatric glioblastomas are molecularly distinct from adult tumors, and relatively little is known about the pediatric glioblastoma tumor microenvironment (TME). Cancer immunotherapy has emerged as a new pillar of cancer treatment and is revolutionizing the care of patients with many advanced solid tumors, including melanoma, non-small cell lung cancer, head and neck cancer, and renal cell carcinoma. Unfortunately, attempts to treat adult glioblastoma with current immunotherapies have had limited success to date. Nevertheless, the immune milieu in pediatric glioblastoma is distinct from that found in adult tumors, and evidence suggests that pediatric tumors are less immunosuppressive. As a result, immunotherapies should be specifically evaluated in the pediatric context. The purpose of this review is to explore known and emerging mechanisms of immune evasion in pediatric glioblastoma and highlight potential opportunities for implementing immunotherapy in the treatment of these devastating pediatric brain tumors.