BACKGROUND Resection of thalamic and other subcortical tumors has historically been associated with high morbidity and mortality. Laser interstitial thermal therapy (LITT) followed by craniotomy for resection of ablated tumor is a promising new combined technique. Here the authors describe the first application of this technique in a pediatric patient. OBSERVATIONS A 6-year-old boy presented with 6 weeks of progressive right hemibody weakness and aphasia. Imaging demonstrated a 4.5-cm left basal ganglia/thalamic mass with moderate hydrocephalus. He underwent endoscopic third ventriculostomy with biopsy, which was positive for diffuse midline glioma. He subsequently received LITT with craniotomy for resection of ablated tumor, after which he remained at his neurological baseline and proceeded with adjuvant radiation therapy. LESSONS This case study demonstrated the feasibility and safety of combined LITT with tumor resection, even in a pediatric patient, for debulking deep lesions that would be difficult to treat with either LITT or resection alone. However, intraoperatively the authors found that the post-LITT tissue had a firmer consistency than anticipated with poor borders, resulting in similar surgical complexity as resection of similar lesions without pre-resection LITT. https://thejns.org/doi/10.3171/CASE251030

Immunotherapies involving toll-like receptor 9 (TLR9) agonists can promote anti-tumor immune responses in various preclinical models. However, the adoption of systemically-administered TLR9 agonists for glioblastoma (GBM) is limited by poor trafficking to the tumor and an immunosuppressive tumor microenvironment (TME). Conjugating tumor-targeting peptides represents a potential solution to these issues and may unleash the efficacy of TLR9 agonists in GBM. Syngeneic GL261-luc glioma cells were orthotopically implanted in 6–8-week-old female C57BL/6J mice. Mice were intraperitoneally injected with either vehicle (phosphate-buffered saline), 200 ug anti-programmed cell death protein 1 (PD1) antibody, 250 ug PIP-CpG V3, or both anti-PD1 and PIP-CpG V3, on days 10, 12, and 14 post-tumor implantation. Mice were either monitored for survival or euthanized on day 17 for immunological assays. Systemic administration of PIP-CpG V3 monotherapy and combination therapy with anti-PD1 + PIP-CpG V3 increased the median survival of GL261 tumor-bearing mice (PIP-CpG V3: p = 0.049, combination: p = 0.012). Flow cytometry analysis of tumor-bearing brains revealed significantly increased infiltration of CD8+ T cells (PIP-CpG V3: p < 0.0001, combination: p < 0.0001) and CD11b+ MHCII+ CD11c+ dendritic cells (DCs) (PIP-CpG V3: p < 0.0001, combination: p < 0.0001) in groups that received PIP-CpG V3, relative to vehicle mice. Additionally, PIP-CpG V3 therapy induced upregulation of various immune activation markers (CD69, CD86, PD-L1) across different immune cell subsets, including DCs, NK cells, B cells, and other myeloid cells in tumor-bearing brains. PIP-CpG V3 improved survival of GL261 tumor-bearing mice, both by itself and in combination with anti-PD1. Flow cytometry immunophenotyping indicates that PIP-CpG V3 can remodel the glioma microenvironment, resulting in a higher proportion of CD8+ T cells and DCs as well as upregulation of activation markers on diverse immune subsets.

Glioblastoma (GBM) resists conventional treatment in large part because the blood–brain barrier (BBB) and its tumor-modified counterpart, the blood–tumor barrier (BTB), form a spatially heterogeneous, actively regulated interface that governs transport. In this setting, permeability, perfusion, and efflux are decoupled so radiographic contrast enhancement is an imperfect surrogate for true therapeutic exposure. Based on breakthroughs in vascular biology, imaging, and transport modeling, single-cell and spatial profiling, and translational delivery studies, we demonstrate how vascular co-option, hypoxia-induced remodeling, and barrier dysregulation generate gradients from relatively intact margins to leaky but sparsely perfused cores. In addition to their function in regulating molecular traffic, perivascular cells and astrocyte programs affect local immune niches that enable myeloid suppression and exclusion of T-cells and suppress systemic immunotherapies. New tools, from novel MRI/PET methods to intravital microscopy and microphysiologic “BBB-on-chip” platforms, facilitate quantitative measurement of regional transport and drug levels. These observations indicate three interrelated paths to enhanced therapy: temporarily normalizing or reversibly opening the barrier, avoiding it by targeted regional delivery, and rationally designing drugs that account for transport and efflux limitations. The integration of barrier modulation with immunotherapies in preclinical models enhances intratumoral exposure and efficacy. Lessons from other neurologic illnesses highlight both the dangers of uncontrolled opening and the potential of localized, reversible modulation. We support a “BBB-first” paradigm that treats the barrier as a quantifiable, targetable organ and demands trials stratified by barrier phenotype and correlating clinical outcome with regional exposure and immune access.

Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and high recurrence rates. The complex immune microenvironment of GBM is highly infiltrated by tumor-associated microglia and macrophages (TAM). TAMs are known to be heterogeneous in their functional and metabolic states and can transmit either protumoral or antitumoral signals to glioma cells. Here, we performed bulk RNA sequencing and single-cell RNA sequencing on samples from patients with GBM, which revealed increased ATP synthase expression and oxidative phosphorylation activity in TAMs located in the tumor core relative to the tumor periphery. Both in vitro and in vivo models displayed similar trends of augmented TAM mitochondrial activity, along with elevated mitochondrial fission, glucose uptake, mitochondrial membrane potential, and extracellular ATP (eATP) production by TAMs in the presence of GBM cells. Tumor-secreted factors, including GM-CSF, induced the increase in TAM eATP production. Elevated eATP in the GBM microenvironment promoted glioma growth and invasion by activating the P2X purinoceptor 7 (P2X7R) on glioma cells. Inhibition of the eATP-P2X7R axis attenuated tumor cell viability in vitro and reduced tumor size and prolonged survival in glioma-bearing mouse models. Overall, this study revealed elevated TAM-derived eATP in GBM and provided the basis for targeting the eATP-P2X7R signaling axis as a therapeutic strategy in GBM. Significance: Glioblastoma-mediated metabolic reprogramming in tumor-associated microglia increases ATP secretion that supports cancer cell proliferation and invasion by activating P2X7R, which can be inhibited to attenuate tumor growth.

PURPOSE Data on lines of therapy (LOTs) for cancer treatment are important for clinical oncology research, but LOTs are not explicitly recorded in electronic health records (EHRs). We present an efficient approach for clinical data abstraction and a flexible algorithm to derive LOTs from EHR-based medication data on patients with glioblastoma multiforme (GBM). METHODS Nonclinicians were trained to abstract the diagnosis of GBM from EHRs, and their accuracy was compared with abstraction performed by clinicians. The resulting data were used to build a cohort of patients with confirmed GBM diagnosis. An algorithm was developed to derive LOTs using structured medication data, accounting for the addition and discontinuation of therapies and drug class. Descriptive statistics were calculated and time-to-next-treatment (TTNT) analysis was performed using the Kaplan-Meier method. RESULTS Treating clinicians as the gold standard, nonclinicians abstracted GBM diagnosis with a sensitivity of 0.98, specificity 1.00, positive predictive value 1.00, and negative predictive value 0.90, suggesting that nonclinician abstraction of GBM diagnosis was comparable with clinician abstraction. Of 693 patients with a confirmed diagnosis of GBM, 246 patients contained structured information about the types of medications received. Of them, 165 (67.1%) received a first-line therapy (1L) of temozolomide, and the median TTNT from the start of 1L was 179 days. CONCLUSION We described a workflow for extracting diagnosis of GBM and LOT from EHR data that combines nonclinician abstraction with algorithmic processing, demonstrating comparable accuracy with clinician abstraction and highlighting the potential for scalable and efficient EHR-based oncology research.

INTRODUCTION: Geniculate neuralgia (GN) is a rare pain condition involving the nervus intermedius (NI), a branch of the facial nerve. The current standard for surgical intervention consists of a retrosigmoid craniotomy with sectioning of the NI. However, few case reports/series exist detailing the outcomes of GN surgical treatment. METHODS: We reviewed patient charts involving craniotomies for GN performed by a single surgeon between November 2020 and December 2022. RESULTS: Three patients underwent two craniotomies for GN. GN patients were largely female (91.30%) and White, non-Hispanic/Latino (78.26%). Nearly all GN patients had a concurrent diagnosis of trigeminal neuralgia (n = 22, 95.65%) and some also had a concurrent diagnosis of glossopharyngeal neuralgia (n = 9, 39.13%). Vascular contact with cranial nerves VII and VIII was reported in four procedures. 22 procedures (84.62%) resulted in profound pain relief, with BNI pain score decreasing from 5 to 1 between pre-op and latest follow-up. No patients experienced unexpected hearing loss compared to baseline at latest follow-up. One patient experienced facial paralysis on the side of surgery and two patients experienced some form of vestibular dysfunction at latest follow-up. Of 26 total procedures, 20 included NI sectioning. Initial craniotomies in which the NI was sectioned (n = 18) resolved GN pain 88.89% of the time whereas craniotomies without NI sectioning (n = 5) resolved GN pain 60% of the time. CONCLUSIONS: NI sectioning is an effective means of achieving GN pain relief. Post-operative complications including unexpected hearing loss, facial paralysis, and vestibular dysfunction were infrequently observed in our series.

Background The COVID-19 pandemic disrupted healthcare access and utilization throughout the US, with variable impact on patients of different socioeconomic status (SES) and race. We characterize pre-pandemic and pandemic demographic and SES trends of lumbar fusion patients in the US. Methods Adults undergoing first-time lumbar fusion 1/1/2004-3/31/2021 were assessed in Clinformatics® Data Mart for patient age, geographical location, gender, race, education level, net worth, and Charlson Comorbidity Index (CCI). Multivariable regression models were used to evaluate the significance of trends over time, with a focus on pandemic trends 2020-2021 versus previous trends 2004-2019. Results 217,204 patients underwent lumbar fusions, 1/1/2004-3/31/2021. The numbers and per capita rates of lumbar fusions increased 2004-2019 and decreased in 2020 (first year of COVID-19 pandemic), with large variation in geographic distribution. There was overall a significant decrease in proportion of White patients undergoing lumbar fusion over time (OR=0.997, p<0.001), though they were more likely to undergo surgery during the pandemic (OR=1.016, p<0.001). From 2004-2021, patients were more likely to be educated beyond high school. Additionally, patients in the highest (>$500K) and lowest (<$25K) net worth categories had significantly more fusions over time (p<0.001). During the pandemic (2020-2021), patients in higher net worth groups were more likely to undergo lumbar fusions ($150K-249K & $250K-499K: p<0.001) whereas patients in the lowest net worth group had decreased rate of surgeries (p<0.001). Lastly, patients’ CCI increased significantly from 2004 to 2021 (coefficient=0.124, p<0.001), and this trend held true during the pandemic (coefficient=0.179, p<0.001). Conclusions To the best of our knowledge, our work represents the most comprehensive and recent characterization of SES variables in lumbar fusion rates. Unsurprisingly, lumbar fusions decreased overall with the onset of the COVID-19 pandemic. Importantly, disparities in fusion patients across patient race and wealth widened during the pandemic, reversing years of progress, a lesson we can learn for future public health emergencies.

BACKGROUND:Cervical fusion rates increased in the U.S. exponentially 1990-2014, but trends leading up to/during the COVID-19 pandemic have not been fully evaluated by patient socioeconomic status (SES). Here, we provide the most recent, comprehensive characterization of demographic and SES trends in cervical fusions, including during the pandemic. METHODS:We collected the following variables on adults undergoing cervical fusions, 1/1/2004-3/31/2021, in Optum's Clinformatics Data Mart: age, Charlson Comorbidity Index, provider's practicing state, gender, race, education, and net worth. We performed multivariate linear and logistic regression to evaluate associations of cervical fusion rates with SES variables. RESULTS:Cervical fusion rates increased 2004-2016, then decreased 2016-2020. Proportions of Asian, Black, and Hispanic patients undergoing cervical fusions increased (OR = 1.001,1.001,1.004, P < 0.01), with a corresponding decrease in White patients (OR = 0.996, P < 0.001) over time. There were increases in cervical fusions in higher education groups (OR = 1.006, 1.002, P < 0.001) and lowest net worth group (OR = 1.012, P < 0.001). During the pandemic, proportions of White (OR = 1.015, P < 0.01) and wealthier patients (OR ≥ 1.015, P < 0.01) undergoing cervical fusions increased. CONCLUSIONS:We present the first documented decrease in annual cervical surgery rates in the U.S. Our data reveal a bimodal distribution for cervical fusion patients, with racial-minority, lower-net-worth, and highly-educated patients receiving increasing proportions of surgical interventions. White and wealthier patients were more likely to undergo cervical fusions during the COVID-19 pandemic, which has been reported in other areas of medicine but not yet in spine surgery. There is still considerable work needed to improve equitable access to spine care for the entire U.S. POPULATION:

BACKGROUND CONTEXT: Bone morphogenic protein (BMP) promotes bony fusion but increases costs. Recent trends in BMP use among Medicare patients have not been well -characterized. PURPOSE: To assess utilization trends, complication, payments, and costs associated with BMP use in spinal fusion in a Medicare-insured population.STUDY DESIGN/SETTING: Retrospective cohort study.PATIENT SAMPLE: Total of 316,070 patients who underwent spinal fusion in a 20% sample of Medicare-insured patients, 2006 to 2015. OUTCOME MEASURES: Utilization trends across time and geography, complications, pay-ments, and costs.METHODS: Patients were stratified by fusion type and diagnosis. Multivariable logistic and linear regression were used to adjust for the effect of baseline characteristics on complications and total payments or cost, respectively.RESULTS: BMP was used in 60,249 cases (19.1%). BMP utilization rates decreased from 23.1% in 2006 to 12.0% in 2015, most significantly in anterior cervical (7.5%-3.1%), posterior cervical (17.0%-8.3%), and posterior lumbar fusions (31.5%-15.8%). There are significant state-and region-level geographic differences in BMP utilization. Across all years, states with the highest BMP use were Indiana (28.5%), Colorado (26.6%), and Nevada (25.7%). States with the lowest BMP use were Maine (2.3%), Vermont (8.2%), and Mississippi (10.4%). After multivariate risk adjustment, BMP use was associated with decreased overall complications in thoracic (odds ratios [OR] [95% confidence intervals [CI]): 0.89 [0.81-0.99]) and anterior lumbar fusions (OR [95% CI]: 0.89 [0.84-0.95]), as well as increased reoperation rates in anterior cervical (OR [95% CI]: 1.11 [1.04-1.19]), posterior cervical (OR (95% CI): 1.14 (1.04-1.25)), thoracic (OR (95% CI): 1.32 (1.23-1.41)), and posterior lumbar fusions (OR (95% CI): 1.11 (1.06-1.16)). BMP use was also associated with greater total costs, independent of fusion type, after multivariate risk adjust-ment (p<.0001). Payments, however, were comparable between groups in anterior and posterior cervical fusion with or without BMP. BMP use was associated with greater total payments in thoracic, anterior lumbar, and posterior lumbar fusions. Notably, the difference in payments was smaller than the associated cost increase in all fusion types.CONCLUSIONS: BMP use has declined across all fusion types over the last decade, after a peak in 2007. While BMP is associated with greater costs, reimbursement does not increase proportion-ally with BMP cost.(c) 2023 Elsevier Inc. All rights reserved.

ABSTRACT New anabolic medications (abaloparatide and romosozumab) were recently approved for osteoporosis, and data suggest that prescribing antiresorptive medications after a course of anabolic medications offers better outcomes. This study aimed to characterize prescription trends, demographics, geographical distributions, out‐of‐pocket costs, and treatment sequences for anabolic and antiresorptive osteoporosis medications. Using a commercial claims database (Clinformatics Data Mart), adult patients with osteoporosis from 2003 to 2021 were retrospectively reviewed and stratified based on osteoporosis medication class. Patient demographics and socioeconomic variables, provider types, and out‐of‐pocket costs were collected. Multivariable regression analyses were used to identify independent predictors of receiving osteoporosis treatment. A total of 2,988,826 patients with osteoporosis were identified; 616,635 (20.6%) received treatment. Patients who were female, Hispanic or Asian, in the Western US, had higher net worth, or had greater comorbidity burden were more likely to receive osteoporosis medications. Among patients who received medication, 31,112 (5.0%) received anabolic medication; these were more likely to be younger, White patients with higher education level, net worth, and greater comorbidity burden. Providers who prescribed the most anabolic medications were rheumatologists (18.5%), endocrinologists (16.8%), and general internists (15.3%). Osteoporosis medication prescriptions increased fourfold from 2003 to 2020, whereas anabolic medication prescriptions did not increase at this rate. Median out‐of‐pocket costs were $17 higher for anabolic than antiresorptive medications, though costs for anabolic medications decreased significantly from 2003 to 2020 (compound annual growth rate: −0.6%). A total of 8388 (1.4%) patients tried two or more osteoporosis medications, and 0.6% followed the optimal treatment sequence. Prescription of anabolic osteoporosis medications has not kept pace with overall osteoporosis treatment, and there are socioeconomic disparities in anabolic medication prescription, potentially driven by higher median out‐of‐pocket costs. Although prescribing antiresorptive medications after a course of anabolic medications offers better outcomes, this treatment sequence occurred in only 0.6% of the study cohort. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Background: Electronic health records represent a large data source for outcomes research, but the majority of EHR data is unstructured (e.g. free text of clinical notes) and not conducive to computational methods. While there are currently approaches to handle unstructured data, such as manual abstraction, structured proxy variables, and model-assisted abstraction, these methods are time-consuming, not scalable, and require clinical domain expertise. This paper aims to determine whether selective prediction, which gives a model the option to abstain from generating a prediction, can improve the accuracy and efficiency of unstructured clinical data abstraction.Methods: We trained selective prediction models to identify the presence of four distinct clinical variables in free-text pathology reports: primary cancer diagnosis of glioblastoma (GBM, n = 659), resection of rectal adenocarcinoma (RRA, n = 601), and two procedures for resection of rectal adenocarcinoma: abdominoperineal resection (APR, n = 601) and low anterior resection (LAR, n = 601). Data were manually abstracted from pathology reports and used to train L1-regularized logistic regression models using term-frequency-inverse-document-frequency features. Data points that the model was unable to predict with high certainty were manually abstracted. Findings: All four selective prediction models achieved a test-set sensitivity, specificity, positive predictive value, and negative predictive value above 0.91. The use of selective prediction led to sizable gains in automation (anywhere from 57% to 95% reduction in manual abstraction of charts across the four outcomes). For our GBM classifier, the selective prediction model saw improvements to sensitivity (0.94 to 0.96), specificity (0.79 to 0.96), PPV (0.89 to 0.98), and NPV (0.88 to 0.91) when compared to a non-selective classifier.Interpretation: Selective prediction using utility-based probability thresholds can facilitate unstructured data extraction by giving 'easy' charts to a model and 'hard' charts to human abstractors, thus increasing efficiency while maintaining or improving accuracy.Funding Information: No funding was received to support this work. Declaration of Interests: AS reports stock ownership in Roche (RHHVF). JHC reports royalties from Reaction Explorer LLC; consulting fees from National Institute of Drug Abuse Clinical Trials Network, Tuolc Inc, Roche Inc; and payment for expert testimony from Younker Hyde MacFarlane PLLC and Sutton Pierce.Ethics Approval Statement: Ethics approval was granted through Stanford University IRB (#50031).

Patients with high-grade glioma have a poor prognosis and an average survival of less than 15 months, which is associated with an increase in tumor-associated microglia and macrophages (TAMs). TAMs in the glioma microenvironment are traditionally thought to suppress antitumor immune responses and are metabolically reprogrammed by glioma. However, it is unknown whether metabolic processes, like ATP synthesis, in TAMs can directly affect glioma growth. Through RNAseq, we identified a novel subpopulation that had elevated metabolic expression patterns. These TAMs (TMEM119+) had increased protein expression of ATP synthases and VDAC1, and surprisingly only TAMs located within the tumor center had increased mitochondrial energy potential. In vitro and ex vivo co-culture assays determined that activated TAMs increased the expression of metabolic, growth, and survival genes in high-grade glioma cells. These activated TAMs produced higher levels of extracellular ATP, which in turn increased glioma cell viability. Inhibition studies identified P2X purinoceptor 7 (P2X7R) as a key player in the TAMs ATP-induced glioma survival. Our findings demonstrate for the first time that a subpopulation of TAMs induced a more tumorigenic microenvironment through the secretion of ATP.

Immunotherapy is a promising therapeutic domain for the treatment of gliomas. However, clinical trials of various immunotherapeutic modalities have not yielded significant improvements in patient survival. Preclinical models for glioma research should faithfully represent clinically observed features regarding glioma behavior, mutational load, tumor interactions with stromal cells, and immunosuppressive mechanisms. In this review, we dive into the common preclinical models used in glioma immunology, discuss their advantages and disadvantages, and highlight examples of their utilization in translational research.

Improvements in bioengineering methodology and tools have allowed for significant progress in the development of therapeutics and diagnostics in medicine, as well as progress in many other diverse industries, such as materials manufacturing, food and agriculture, and consumer goods. Glioblastomas present significant challenges to adequate treatment, in part due to their immune-evasive and manipulative nature. Rational-design bioengineering using novel scaffolds, biomaterials, and inspiration across disciplines can push the boundaries in treatment development to create effective therapeutics for glioblastomas. In this review, we will discuss bioengineering strategies currently applied across diseases and disciplines to inspire creative development for GBM immunotherapies.

Gliomas are intrinsic brain tumors that originate from glial cells. Glioblastoma (GBM) is the most aggressive glioma type and resistant to immunotherapy, mainly due to its unique immune environment. Dimensional data analysis reveals that the intra-tumoral heterogeneity of immune cell populations in the glioma microenvironment is largely made up of cells of myeloid lineage. Conventional therapies of combined surgery, chemotherapy and radiotherapy have achieved limited improvements in the prognosis of glioma patients, as myeloid cells are prominent mediators of immune and therapeutic responses—like immunotherapy resistance—in glioma. Myeloid cells are frequently seen in the tumor microenvironment (TME), and they are polarized to promote tumorigenesis and immunosuppression. Reprogramming myeloid cells has emerged as revolutionary, new types of immunotherapies for glioma treatment. Here we detail the current advances in classifying epigenetic, metabolic, and phenotypic characteristics and functions of different populations of myeloid cells in glioma TME, including myeloid-derived suppressor cells (MDSCs), glioma-associated microglia/macrophages (GAMs), glioma-associated neutrophils (GANs), and glioma-associated dendritic cells (GADCs), as well as the mechanisms underlying promotion of tumorigenesis. The final goal of this review will be to provide new insights into novel therapeutic approaches for specific targeting of myeloid cells to improve the efficacy of current treatments in glioma patients.

To ensure excellent postoperative clinical outcomes while preserving critical neurologic function, neurosurgeons who manage patients with intra-axial brain tumors can use intraoperative technologies and tools to achieve maximal safe resection. Neurosurgical oncology revolves around safe and optimal extent of resection, which further dictates subsequent treatment regimens and patient outcomes. Various methods can be adapted for treating both primary and secondary intra-axial brain lesions. We present a review of recent advances and published research centered on different innovative tools and techniques, including fluorescence-guided surgery, new methods of drug delivery, and minimally invasive procedural options.

BACKGROUND CONTEXT Previous studies have characterized utilization rates and cost of BMP use in spinal fusion, but factors that affect these relationships need further investigation. PURPOSE To characterize the utilization, cost and payments for BMP use in spinal fusion among Medicare beneficiaries. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE We identified all adult patients who underwent spinal fusion from 2006-2015 in the 20% Medicare inpatient file (n=316,070). OUTCOME MEASURES BMP utilization rates, total cost, and total payments. METHODS Patient age, sex, race, geographical region, Charlson Comorbidity Index (CCI) and length of stay were gathered. Primary outcomes included surgical utilization rates, total cost (calculated via Medicare charges and hospital-specific charge-to-cost ratios), and total Medicare payments for spinal fusion. RESULTS BMP was used in 60,249 cases (19.1%). Rates of BMP use in spinal fusion decreased from 23.1% in 2006 to 12.0% in 2015. BMP use decreased from 9.6%, 24.2%, and 31.3% in 2006 to 4.6%, 17.8%, and 16.0% in 2015 in cervical, thoracic, and lumbosacral cases, respectively. Largest rates of decline were in anterior cervical (-59.3%), posterior cervical (-51.4%) and posterior lumbar (-50.0%) fusions. States with the highest BMP use were Indiana (28.5%), Colorado (26.6%) and Nevada (25.7%); lowest were Maine (2.3%), Vermont (8.2%) and Mississippi (10.4%). Patients who received intraoperative BMP were more likely to be older, female, White and with greater comorbidity burden. The cases were more often deformity cases, performed in the Midwest/West, revisions and longer fusion length. BMP use was associated with increased length of stay, independent of fusion type. BMP use was associated with increased total cost in all fusions, and increased total payments in thoracic, anterior lumbar and posterior lumbar fusions. CONCLUSIONS Rate of BMP use in spinal fusion has decreased among Medicare beneficiaries from 2006-2015. Although BMP use increases procedure cost, Medicare payments are comparable. Certain patient and surgical factors may affect rate of BMP use in spine fusion. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs. Previous studies have characterized utilization rates and cost of BMP use in spinal fusion, but factors that affect these relationships need further investigation. To characterize the utilization, cost and payments for BMP use in spinal fusion among Medicare beneficiaries. Retrospective cohort study. We identified all adult patients who underwent spinal fusion from 2006-2015 in the 20% Medicare inpatient file (n=316,070). BMP utilization rates, total cost, and total payments. Patient age, sex, race, geographical region, Charlson Comorbidity Index (CCI) and length of stay were gathered. Primary outcomes included surgical utilization rates, total cost (calculated via Medicare charges and hospital-specific charge-to-cost ratios), and total Medicare payments for spinal fusion. BMP was used in 60,249 cases (19.1%). Rates of BMP use in spinal fusion decreased from 23.1% in 2006 to 12.0% in 2015. BMP use decreased from 9.6%, 24.2%, and 31.3% in 2006 to 4.6%, 17.8%, and 16.0% in 2015 in cervical, thoracic, and lumbosacral cases, respectively. Largest rates of decline were in anterior cervical (-59.3%), posterior cervical (-51.4%) and posterior lumbar (-50.0%) fusions. States with the highest BMP use were Indiana (28.5%), Colorado (26.6%) and Nevada (25.7%); lowest were Maine (2.3%), Vermont (8.2%) and Mississippi (10.4%). Patients who received intraoperative BMP were more likely to be older, female, White and with greater comorbidity burden. The cases were more often deformity cases, performed in the Midwest/West, revisions and longer fusion length. BMP use was associated with increased length of stay, independent of fusion type. BMP use was associated with increased total cost in all fusions, and increased total payments in thoracic, anterior lumbar and posterior lumbar fusions. Rate of BMP use in spinal fusion has decreased among Medicare beneficiaries from 2006-2015. Although BMP use increases procedure cost, Medicare payments are comparable. Certain patient and surgical factors may affect rate of BMP use in spine fusion.

Background and Objective: Immunotherapy has yielded significant improvements in survival for many cancer types, but its impact on glioblastoma (GBM) has been relatively muted. There is a growing interest in understanding the role of cancer metabolism and its role in tumor growth and therapeutic response. Thus, it is equally important to consider the clinical implications of immune cell metabolism on cancer progression and implications for therapeutic development. Our objective is to present new developments in immunometabolic research that are relevant to immunotherapy development for high-grade gliomas. Methods: A literature search and review was conducted, regarding original research articles studying metabolic pathways of immune cells in high-grade gliomas. Searches were conducted in PubMed and Embase databases on May 15 and June 13, 2022. English-language original research articles were selected and prioritized based on their inclusion of findings related to metabolic changes in myeloid and lymphoid cells in the glioma tumor microenvironment. Key Content and Findings: There are many metabolic mechanisms by which immune cells in high-grade gliomas, like GBM, contribute to tumor growth and persistence via immunosuppression and high therapeutic resistance. There are also several ways that metabolic optimization has already been shown to improve immunotherapies already in clinical trials or in use, including dendritic cell vaccines and chimeric antigen receptor T cells. Conclusions: The implications of immunometabolic research presented here should be taken into consideration in future research and immunotherapy development of high-grade gliomas for our best chances at improving patient survival.