Optimizing Surgical Outcomes for Intracranial Epidermoid Tumors: A Retrospective Analysis of Clinical Predictors, Surgical Decisions, and Patient Clustering.

BACKGROUND/OBJECTIVE: Intracranial epidermoid tumors (ETs) are rare, benign lesions that present significant challenges in neurosurgical management due to their propensity to encase vital neurovascular structures. We aimed to evaluate the impact of clinical, demographic, and tumor-specific factors on surgical decisions (gross total resection [GTR] vs. subtotal resection [STR]) and outcomes and identify patient clusters with distinct profiles and outcomes post-resection. METHODS: We retrospectively analyzed 72 patients with ET treated from 1998 to 2022, employing multivariable logistic regression for GTR versus STR predictors and Kaplan-Meier curves for progression-free survival (PFS). K-prototype clustering classified patients based on clinical data. RESULTS: The mean age of our cohort was 39.8 ± 20.1 years. About 13.9% of patients had a recurrence, with a median PFS of 108 months (interquartile range: 57 -206). Seizures significantly predicted GTR (P < 0.05), whereas adherence to critical structures reduced GTR likelihood (P < 0.05). Initial surgeries more often achieved GTR, correlating with longer PFS (P < 0.0001) and reduced recurrence (P < 0.01) versus re-operations. Cluster analysis identified three distinct groups, with the initial GTR cluster showing superior PFS and the lowest recurrence (P < 0.0001 and P < 0.01, respectively). Statistically significant predictors of PFS included age and preoperative seizure presence, with older age favoring longer PFS (P < 0.01) and seizures associated with reduced PFS (P < 0.01). In addition, patients with previous surgeries showed a trend toward shorter PFS (P < 0.05). CONCLUSIONS: This study emphasizes the importance of tailored surgical strategies in managing intracranial ETs, advocating for GTR to optimize long-term outcomes where possible. Future prospective studies are essential to further refine treatment approaches, enhancing survival for ET patients.

Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

INTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid  (CSF) biomarkers for AD-related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact. METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. RESULTS: AD pathology on biopsy correlates with CSF ß-amyloid-42/40, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/ß-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data. DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking. HIGHLIGHTS: AD CSF biomarkers correlate with CNS pathology and transcriptomic changes. Seven proteins correlate with CNS pathology and gene expression changes. Inflammatory and neuronal gene expression changes correlate with YKL-40 and NPTXR, respectively. CSF metabolomic analysis identifies pathways that correlate with biopsy data. Fatty acid metabolic pathways correlate with ß-amyloid pathology.

Impact of Microsurgical Reconstruction Timing on the Risk of Free Flap Loss in Acute Burns: Systematic Review and Meta-Analysis.

Background: Free tissue transfer is usually considered as a last resort in severe burn cases, when skin substitutes and local flaps are not viable options. Prior studies have demonstrated a free flap loss rate ranging from 0% to 44%. The aim of this study is to identify the ideal timing to perform free flap reconstruction in acute burn-related injuries to minimize free flap loss. Methods: A systematic review and meta-analysis was performed and reported according to PRISMA guidelines. PubMed, Embase, Web of Science, and Cochrane Library databases were queried. The review protocol was registered on PROSPERO database (CRD42023404478). Three time intervals from day of injury were identified: (1) 0-4 days, (2) 5-21 days, and (3) 22 days-6 weeks. The primary outcome was total free flap loss. Results: A total of 17 articles met inclusion criteria. The analysis included 275 free flaps performed in 260 patients (88% men, 12% women) affected by acute burn injuries. The pooled prevalence of free flap failure in the three time intervals (0-4 days, 5-21 days, and 22 days-6 weeks) were 7.32% [95% confidence interval (CI): 2.38%-20.37%], 16.55% (95% CI: 11.35%-23.51%), and 6.74% (95% CI: 3.06%-14.20%), respectively. Conclusions: Free flap reconstruction carries a high risk of failure in patients with acute burn. However, timing of the reconstruction appears to influence surgical outcomes. Free flap reconstruction performed between 5 and 21 days from burn injury had a trend toward higher flap loss rates and should be discouraged.

Free Flap Failure and Contracture Recurrence in Delayed Burn Reconstruction: A Systematic Review and Meta-analysis.

Background: Free tissue transfer is often considered a last resort in burn reconstruction due to its complexity and associated risks. A comprehensive review on free flap outcomes in delayed burn reconstruction is currently lacking. The study aimed to evaluate the available evidence on the failure and contracture recurrence rates in free flap delayed burn reconstruction. Methods: A systematic review and meta-analysis was conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The protocol was registered on PROSPERO (CRD42023404478). The following databases were accessed: Embase, PubMed, Web of Science, and Cochrane Library. The measured outcomes were free flap loss and contracture recurrence rate. Results: Of the 1262 retrieved articles, 40 qualified for inclusion, reporting on 1026 free flaps performed in 928 patients. The mean age was 29.25 years [95% confidence interval (CI), 24.63-33.88]. Delayed burn reconstruction was performed at an average of 94.68 months [95% CI, - 9.34 to 198.70] after initial injury, with a follow-up period of 23.02 months [95% CI, 4.46-41.58]. Total flap loss rate was 3.80% [95% CI, 2.79-5.16] and partial flap loss rate was 5.95% [95% CI, 4.65-7.57]. Interestingly, burn contracture recurrence rate was 0.62% [95% CI, 0.20-1.90]. Conclusions: This systematic review provides a comprehensive evaluation of the free flap outcomes in delayed burn reconstruction. The flap loss rate was relatively low, given the complexity of the procedure and potential risks. Furthermore, burn contracture rate was found to be extremely low. This study demonstrates that free flaps are a safe and effective option for delayed burn reconstruction.

Tunable Viscoelasticity of Alginate Hydrogels via Serial Autoclaving.

Alginate hydrogels are widely used as biomaterials for cell culture and tissue engineering due to their biocompatibility and tunable mechanical properties. Reducing alginate molecular weight is an effective strategy for modulating hydrogel viscoelasticity and stress relaxation behavior, which can significantly impact cell spreading and fate. However, current methods like gamma irradiation to produce low molecular weight alginates suffer from high cost and limited accessibility. Here, a facile and cost-effective approach to reduce alginate molecular weight in a highly controlled manner using serial autoclaving is presented. Increasing the number of autoclave cycles results in proportional reductions in intrinsic viscosity, hydrodynamic radius, and molecular weight of the polymer while maintaining its chemical composition. Hydrogels fabricated from mixtures of the autoclaved alginates exhibit tunable mechanical properties, with inclusion of lower molecular weight alginate leading to softer gels with faster stress relaxation behaviors. The method is demonstrated by establishing how viscoelastic relaxation affects the spreading of encapsulated fibroblasts and glioblastoma cells. Results establish repetitive autoclaving as an easily accessible technique to generate alginates with a range of molecular weights and to control the viscoelastic properties of alginate hydrogels, and demonstrate utility across applications in mechanobiology, tissue engineering, and regenerative medicine.

Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

INTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early AD pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify CSF biomarkers for AD-related CNS pathophysiologic changes using tissue and fluids with early pathology, free of post-mortem artifact. METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. RESULTS: AD pathology on biopsy correlates with CSF ß-amyloid-40/42, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/ß-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights 7 core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data.. DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.

The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging.

C. elegans undergo age-dependent declines in muscle organization and function, similar to human sarcopenia. The chaperone UNC-45 is required to fold myosin heads after translation and is likely used for refolding after thermally- or chemically-induced unfolding. UNC-45's TPR region binds HSP-90 and its UCS domain binds myosin heads. We observe early onset sarcopenia when UNC-45 is reduced at the beginning of adulthood. There is sequential decline of HSP-90, UNC-45, and MHC B myosin. A mutation in age-1 delays sarcopenia and loss of HSP-90, UNC-45, and myosin. UNC-45 undergoes age-dependent phosphorylation, and mass spectrometry reveals phosphorylation of six serines and two threonines, seven of which occur in the UCS domain. Additional expression of UNC-45 results in maintenance of MHC B myosin and suppression of A-band disorganization in old animals. Our results suggest that increased expression or activity of UNC-45 might be a strategy for prevention or treatment of sarcopenia.

CHD2 Regulates Neuron-Glioma Interactions in Pediatric Glioma.

High-grade gliomas (HGG) are deadly diseases for both adult and pediatric patients. Recently, it has been shown that neuronal activity promotes the progression of multiple subgroups of HGG. However, epigenetic mechanisms that govern this process remain elusive. Here we report that the chromatin remodeler chromodomain helicase DNA-binding protein 2 (CHD2) regulates neuron-glioma interactions in diffuse midline glioma (DMG) characterized by onco-histone H3.1K27M. Depletion of CHD2 in H3.1K27M DMG cells compromises cell viability and neuron-to-glioma synaptic connections in vitro, neuron-induced proliferation of H3.1K27M DMG cells in vitro and in vivo, activity-dependent calcium transients in vivo, and extends the survival of H3.1K27M DMG-bearing mice. Mechanistically, CHD2 coordinates with the transcription factor FOSL1 to control the expression of axon-guidance and synaptic genes in H3.1K27M DMG cells. Together, our study reveals a mechanism whereby CHD2 controls the intrinsic gene program of the H3.1K27M DMG subtype, which in turn regulates the tumor growth-promoting interactions of glioma cells with neurons. Significance: Neurons drive the proliferation and invasion of glioma cells. Here we show that chromatin remodeler chromodomain helicase DNA-binding protein 2 controls the epigenome and expression of axon-guidance and synaptic genes, thereby promoting neuron-induced proliferation of H3.1K27M diffuse midline glioma and the pathogenesis of this deadly disease.

Use of Recommended Neurodiagnostic Evaluation Among Patients With Drug-Resistant Epilepsy.

Importance: Interdisciplinary practice parameters recommend that patients with drug-resistant epilepsy (DRE) undergo comprehensive neurodiagnostic evaluation, including presurgical assessment. Reporting from specialized centers suggests long delays to referral and underuse of surgery; however, longitudinal data are limited to characterize neurodiagnostic evaluation among patients with DRE in more diverse US settings and populations. Objective: To examine the rate and factors associated with neurodiagnostic studies and comprehensive evaluation among patients with DRE within 3 US cohorts. Design, Setting, and Participants: A retrospective cross-sectional study was conducted using the Observational Medical Outcomes Partnership Common Data Model including US multistate Medicaid data, commercial claims data, and Columbia University Medical Center (CUMC) electronic health record data. Patients meeting a validated computable phenotype algorithm for DRE between January 1, 2015, and April 1, 2020, were included. No eligible participants were excluded. Exposure: Demographic and clinical variables were queried. Main Outcomes and Measures: The proportion of patients receiving a composite proxy for comprehensive neurodiagnostic evaluation, including (1) magnetic resonance or other advanced brain imaging, (2) video electroencephalography, and (3) neuropsychological evaluation within 2 years of meeting the inclusion criteria. Results: A total of 33 542 patients with DRE were included in the Medicaid cohort, 22 496 in the commercial insurance cohort, and 2741 in the CUMC database. A total of 31 516 patients (53.6%) were women. The proportion of patients meeting the comprehensive evaluation main outcome in the Medicaid cohort was 4.5% (n = 1520); in the commercial insurance cohort, 8.0% (n = 1796); and in the CUMC cohort, 14.3% (n = 393). Video electroencephalography (24.9% Medicaid, 28.4% commercial, 63.2% CUMC) and magnetic resonance imaging of the brain (35.6% Medicaid, 43.4% commercial, 52.6% CUMC) were performed more regularly than neuropsychological evaluation (13.0% Medicaid, 16.6% commercial, 19.2% CUMC) or advanced imaging (3.2% Medicaid, 5.4% commercial, 13.1% CUMC). Factors independently associated with greater odds of evaluation across all 3 data sets included the number of inpatient and outpatient nonemergency epilepsy visits and focal rather than generalized epilepsy. Conclusions and Relevance: The findings of this study suggest there is a gap in the use of diagnostic studies to evaluate patients with DRE. Care setting, insurance type, frequency of nonemergency visits, and epilepsy type are all associated with evaluation. A common data model can be used to measure adherence with best practices across a variety of observational data sources.

The Development and Management of Neck Burn Scar Contracture Recurrence: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Burn neck contractures pose a great challenge for reconstructive surgeons. A paucity of literature exist regarding long-term outcomes based on different surgical management strategies. The aim of this study was to evaluate the long-term outcomes of the treatment of neck burn scar contractures and evaluate surgical strategies according to their long-term effectiveness and associated complications. METHODS: A retrospective cohort study was conducted to review outcomes of neck contractures release after burn injury. All patients operated on between January 2009 and February 2023 at a single institution were included. RESULTS: A total of 20 patients developed neck burn scar contracture and were included in this study. The mean age was 32.9 ± 20.3 years. The burn injuries were most commonly thermal (n = 19, 95%). All burn injuries were full-thickness burns, with an average neck defect size of 130.5 ± 106.0 cm2. Overall, 45 surgical scar release procedures were performed on the 20 patients who developed a neck contracture. Patients underwent 1.65 ± 1.04 surgeries on average to address neck contracture. Although 25% of patients only received 1 surgery to treat neck contracture, some patients underwent as many as 8 surgeries. Contracture recurrence (CR) was the most common complication and occurred in 28.9% of the cases. The mean percentage total body surface area did not significantly differ in CR patients (26.7% ± 14.9%) and no-CR patients (44.5% ± 30.2%). However, there was a significant difference (P = 0.01) in the average neck defect size between CR patients (198.5 ± 108.3 cm2) and no-CR patients (81.1 ± 75.1 cm2). CONCLUSIONS: This study showed that risk factors for initial burn scar contractures may differ from those associated with CR, highlighting the importance of neck defect size as a predictor. The study also examines various surgical approaches, with Z-plasty showing promise for managing CR. However, the absence of data on neck range of motion is a limitation. This research underscores the complexity of managing CR and emphasizes the need for ongoing postoperative monitoring.

Fourteen-Year Experience in Burn Eyelid Reconstruction and Complications Recurrence: A Retrospective Cohort Study.

BACKGROUND: Loss of vision and other ocular defects are a concern with eyelid burn sequelae. This most commonly progresses from eyelid contracture to cicatricial ectropion and lagophthalmos. When left untreated, these may lead to exposure keratitis, ulceration, infection, perforation, and loss of vision. In the case of full-thickness eyelid burns, release and grafting are required. However, there is a paucity of studies on outcomes in eyelid burn surgery treatment, despite concern for permanent ocular damage or loss of vision. The aim of the study is to describe the complication rates in burn eyelid reconstruction at a single center for 14 years. METHODS: A retrospective cohort study was performed of all patients who had sustained eyelid burns and required reconstruction between April 2009 and February 2023. Medical records were obtained from patients' charts. Collected data include demographics, medical history, type of injury, indication for surgery, procedure performed, and complications. RESULTS: A total of 14 patients and 25 eyelids underwent eyelid reconstruction of the 901 total patients with burn-related injuries requiring plastic surgery reconstruction. These patients underwent 54 eyelid surgeries with a mean follow-up time of 13.1 ± 17.1 months. Patients were 71% men and 29% women, with a mean age of 45.1 ± 15.6 years. In 53.7% (n = 29) of the cases, the simultaneous reconstruction of both the upper and lower eyelids was necessary. The reconstruction of the upper and lower eyelid alone represented a smaller percentage (25.9% and 20.4%, respectively). On average, the patients received 3.9 ± 3.5 eyelid surgeries. The overall complication rate was 53.7% (n = 29). The most common complication was ectropion (42.6%, n = 23). Other complications included eye injury (25.9%, n = 14), lagophthalmos (24.1%, n = 13), local infection (7.4%, n = 4), and graft loss (5.6%, n = 3). CONCLUSION: Periorbital burns represent a major challenge that may require complex surgical intervention. Full-thickness skin graft remains the standard of care for patients with eyelid burns. However, there is a high incidence of ectropion that may require reoperation. Further studies examining the conditions of successful eyelid burn procedures may provide guidance on when patients may benefit from eyelid reconstruction during their burn treatment.

Surgical Excision of Burn Wounds.

Burn injuries affect patients of all ages, and timely surgical debridement and excision commence to protect dermal vascularity and integrity, improve healing, and minimize scarring. Several tools may be used for burn wound excision, which is performed either tangentially or down to muscular fascia. Once wounds are optimized from a tissue viability and healing standpoint, coverage may be obtained through grafts or secondary intention healing for more superficial injuries. A collaborative team of plastic and general surgeons, anesthesiologists, nutritionists, and therapists can provide improved patient care throughout the perioperative period, leading to improvements in overall patient morbidity and mortality.

Awake intraoperative mapping for the prevention of amusia.

The authors describe the awake surgical mapping of music skills for patients who require resection in brain areas that may support musical abilities. A 65-year-old man was diagnosed with an anterolateral right temporal nonenhancing lesion, likely a diffusely infiltrating glioma, after presenting with several episodes of altered taste and smell and one episode of loss of consciousness. The patient specializes in music and music technology and has composed scores for films. An awake surgery was planned in a semiseated position. Prerecorded melodies were designed preoperatively as a surrogate for a composition skill task. These consisted of 10- to 15-second musical clips played during bipolar electrical stimulation of the overlying cortex and were divided into three segments: listen, play, and accuracy check. During the "listen" phase, the patient listened to a musical prompt. During the "play" phase, he played a musical response on a keyboard. Stimulation at multiple temporal neocortical sites was negative for any alteration in task performance. The patient did well postoperatively with excellent clinical and radiographic results and returned to composing music without functional compromise. Musical composition tasks can be performed safely intraoperatively for patients with musical expertise. Whether stimulating more posterior nondominant temporal neocortex or other cortical or white matter locations can disrupt this task remains undetermined.

Glioma-Induced Alterations in Excitatory Neurons are Reversed by mTOR Inhibition.

Gliomas are highly aggressive brain tumors characterized by poor prognosis and composed of diffusely infiltrating tumor cells that intermingle with non-neoplastic cells in the tumor microenvironment, including neurons. Neurons are increasingly appreciated as important reactive components of the glioma microenvironment, due to their role in causing hallmark glioma symptoms, such as cognitive deficits and seizures, as well as their potential ability to drive glioma progression. Separately, mTOR signaling has been shown to have pleiotropic effects in the brain tumor microenvironment, including regulation of neuronal hyperexcitability. However, the local cellular-level effects of mTOR inhibition on glioma-induced neuronal alterations are not well understood. Here we employed neuron-specific profiling of ribosome-bound mRNA via 'RiboTag,' morphometric analysis of dendritic spines, and in vivo calcium imaging, along with pharmacological mTOR inhibition to investigate the impact of glioma burden and mTOR inhibition on these neuronal alterations. The RiboTag analysis of tumor-associated excitatory neurons showed a downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development, and an upregulation of transcripts encoding cytoskeletal proteins involved in dendritic spine turnover. Light and electron microscopy of tumor-associated excitatory neurons demonstrated marked decreases in dendritic spine density. In vivo two-photon calcium imaging in tumor-associated excitatory neurons revealed progressive alterations in neuronal activity, both at the population and single-neuron level, throughout tumor growth. This in vivo calcium imaging also revealed altered stimulus-evoked somatic calcium events, with changes in event rate, size, and temporal alignment to stimulus, which was most pronounced in neurons with high-tumor burden. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed the glioma-induced alterations on the excitatory neurons, including the alterations in ribosome-bound transcripts, dendritic spine density, and stimulus evoked responses seen by calcium imaging. These results point to mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma - manifested by alterations in ribosome-bound mRNA, dendritic spine density, and stimulus-evoked neuronal activity. Collectively, our work identifies the pathological changes that tumor-associated excitatory neurons experience as both hyperlocal and reversible under the influence of mTOR inhibition, providing a foundation for developing therapies targeting neuronal signaling in glioma.

Brain tumor-related epilepsy management: A Society for Neuro-oncology (SNO) consensus review on current management.

Tumor-related epilepsy (TRE) is a frequent and major consequence of brain tumors. Management of TRE is required throughout the course of disease and a deep understanding of diagnosis and treatment is key to improving quality of life. Gross total resection is favored from both an oncologic and epilepsy perspective. Shared mechanisms of tumor growth and epilepsy exist, and emerging data will provide better targeted therapy options. Initial treatment with antiseizure medications (ASM) in conjunction with surgery and/or chemoradiotherapy is typical. The first choice of ASM is critical to optimize seizure control and tolerability considering the effects of the tumor itself. These agents carry a potential for drug-drug interactions and therefore knowledge of mechanisms of action and interactions is needed. A review of adverse effects is necessary to guide ASM adjustments and decision-making. This review highlights the essential aspects of diagnosis and treatment of TRE with ASMs, surgery, chemotherapy, and radiotherapy while indicating areas of uncertainty. Future studies should consider the use of a standardized method of seizure tracking and incorporating seizure outcomes as a primary endpoint of tumor treatment trials.

Free Flap Failure and Complications in Acute Burns: A Systematic Review and Meta-analysis.

Background: Severe acute burn injuries represent a challenge to the reconstructive surgeon. Free flap reconstruction might be required in cases of significant critical structure exposure and soft tissue deficits, when local options are unavailable. This study aimed to determine the free flap complication rate in acute burn patients. Methods: A systematic review and meta-analysis were conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and registered on the International Prospective Register of Systematic Reviews database (CRD42023404478). The following databases were accessed: Embase, PubMed, Web of Science, and Cochrane Library. The primary outcome was the free flap failure rate. Results: The study identified 31 articles for inclusion. A total of 427 patients (83.3% men, 16.7% women) accounting for 454 free flaps were included. The mean patient age was 36.21 [95% confidence interval (CI), 31.25-41.16]. Total free flap loss rate was 9.91% [95% CI, 7.48%-13.02%], and partial flap loss was 4.76% [95% CI, 2.66%-8.39%]. The rate of venous thrombosis was 6.41% [95% CI, 3.90%-10.36%] and arterial thrombosis was 5.08% [95% CI, 3.09%-8.26%]. Acute return to the operating room occurred in 20.63% [16.33%-25.71%] of cases. Stratified by body region, free flaps in the lower extremity had a failure rate of 8.33% [95% CI, 4.39%-15.24%], whereas in the upper extremity, the failure rate was 6.74% [95% CI, 3.95%-11.25%]. Conclusion: This study highlights the high risk of free flap complications and failure in acute burn patients.

MGMT Promoter Methylation Predicts Overall Survival after Chemotherapy for 1p/19q-Codeleted Gliomas.

PURPOSE: While MGMT promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy and guides treatment decisions in glioblastoma, its role in grade 2 and 3 glioma remains unclear. Recent data suggest that mMGMT is prognostic of progression-free survival in 1p/19q-codeleted oligodendrogliomas, but an effect on overall survival (OS) has not been demonstrated. EXPERIMENTAL DESIGN: We identified patients with newly diagnosed 1p/19q-codeleted gliomas and known MGMT promoter status in the National Cancer Database from 2010 to 2019. Multivariable Cox proportional hazards regression modeling was used to assess the effect of mMGMT on OS after adjusting for age, sex, race, comorbidity, grade, extent of resection, chemotherapy, and radiotherapy. RESULTS: We identified 1,297 eligible patients, 938 (72.3%) of whom received chemotherapy in their initial course of treatment. The MGMT promoter was methylated in 1,009 (77.8%) patients. Unmethylated MGMT (uMGMT) was associated with worse survival compared with mMGMT [70% {95% confidence interval (CI), 64%-77%} vs. 81% (95% CI, 78%-85%); P < 0.001; adjusted HR (aHR), 2.35 (95% CI, 1.77-3.14)]. uMGMT was associated with worse survival in patients who received chemotherapy [63% (95% CI, 55-73%) vs. 80% (95% CI, 76%-84%); P < 0.001; aHR, 2.61 (95% CI, 1.89-3.60)] but not in patients who did not receive chemotherapy [P = 0.38; HR, 1.31 (95% CI, 0.71-2.42)]. Similar results were observed regardless of World Health Organization grade and after single- or multiagent chemotherapy. CONCLUSIONS: Our study demonstrates an association between mMGMT and OS in 1p/19q-codeleted gliomas. MGMT promoter status should be considered as a stratification factor in future clinical trials of 1p/19q-codeleted gliomas that use OS as an endpoint.