Malignant Brain Tumors Research Articles

Nanomedicine in Management of Cerebral Infarction and Brain Cancer: Role of Inflammation.

Cerebral infarction, the blockage of blood vessels in the brain, is generally an age-related illness. Factors such as unhealthy diets, stressful behaviours and decreased environmental consistency with physiological barriers also contribute to increased casualties. Long-term brain function reconstruction and successful drug therapy are needed. The most frequent malignant brain tumour, glioblastoma, has been linked to variations in mitochondrial ROS, chaperone-mediated autophagy, and the interaction between lncRNA (BC200) and miRNA. Glioblastoma stem cells express high levels of ATP/P2X7 receptors, promoting survival by activating M2 muscarinic receptors. This expert opinion provides an overview of the latest experimental drug therapies aimed at protecting against and restoring cerebral stroke. Nanomedicine overcomes the challenges associated with traditional therapy and physiological obstacles in the treatment of cerebral infarction by improving stroke management, including diagnosis, imaging, and treatment, addressing a diverse range of associated factors.

Procedural volume is linearly associated with mortality, major complications, and readmissions in patients undergoing malignant brain tumor resection.

Improved outcomes have been noted in patients undergoing malignant brain tumor resection at high-volume centers. Studies have arbitrarily chosen high-volume dichotomous cutoffs and have not evaluated volume-outcome associations at specific institutional procedural volumes. We sought to establish the continuous association of volume with patient outcomes and identify cutoffs significantly associated with mortality, major complications, and readmissions. We hypothesized that a linear volume-outcome relationship can estimate likelihood of adverse outcomes when comparing any two volumes. The patient cohort was identified with ICD-10 coding in the Nationwide Readmissions Database(NRD). The association of volume and mortality, major complications, and 30-/90-day readmissions were evaluated in multivariate analyses. Volume was used as a continuous variable with two/three-piece splines, with various knot positions to reflect the best model performance, based on the Quasi Information Criterion(QIC). From 2016 to 2018, 34,486 patients with malignant brain tumors underwent resection. When volume was analyzed as a continuous variable, mortality risk decreased at a steady rate of OR 0.988 per each additional procedure increase for hospitals with 1-65 cases/year(95% CI 0.982-0.993, p < 0.0001). Risk of major complications decreased from 1 to 41 cases/year(OR 0.983, 95% CI 0.979-0.988, p < 0.0001), 30-day readmissions from 1 to 24 cases/year(OR 0.987, 95% CI 0.979-0.995, p = 0.001) and 90-day readmissions from 1 to 23 cases/year(OR 0.989, 95% CI 0.983-0.995, p = 0.0003) and 24-349 cases/year(OR 0.9994, 95% CI 0.999-1, p = 0.01). In multivariate analyses, institutional procedural volume remains linearly associated with mortality, major complications, and 30-/90-day readmission up to specific cutoffs. The resulting linear association can be used to calculate relative likelihood of adverse outcomes between any two volumes.

Tenovin-6 exhibits inhibitory effects on the growth of Sonic Hedgehog (SHH) medulloblastoma, as evidenced by both in vitro and in vivo studies

Medulloblastoma (MB) is the most common malignant brain tumor in children. Within MB, tumors driven by the Sonic Hedgehog (SHH) pathway represent the most heterogeneous subtype, known as SHH subtype medulloblastoma (SHH-MB).Tenovin-6, a recognized p53 activator, has been demonstrated to inhibit autophagy and modulate sirtuin activity, underscoring its potential as a novel therapeutic agent across various malignancies. However, its efficacy in treating SHH-MB remains unexplored. This study aims to investigate the inhibitory effects of tenovin-6 on SHH-MB and elucidate its underlying signaling pathways.We assessed the impact of tenovin-6 on cell proliferation through the CCK-8 and colony formation assays. The scratch and transwell invasion assays were utilized to evaluate the drug’s effects on metastasis. Apoptosis and reactive oxygen species (ROS) levels were measured using flow cytometry. Potential signaling pathways were identified via transcriptomics and quantitative PCR (qPCR).Our in vivo studies involved a mouse xenograft model to explore tenovin-6′s anticancer efficacy against SHH-MB. The findings indicate that tenovin-6 not only inhibits cell proliferation and metastasis in SHH-MB cell lines but also promotes apoptosis, which is closely linked to its proliferation-inhibiting properties. Additionally, animal experiments confirmed that tenovin-6 suppresses MB growth in vivo. We discovered that tenovin-6 reduces intracellular ROS levels and inhibits autophagy in SHH-MB by disrupting the fusion of autophagosomes with lysosomes, likely through inducing autophagosome formation.

Disrupted glutamate homeostasis as a target for glioma therapy.

Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). Gliomas, malignant brain tumors with a dismal prognosis, alter glutamate homeostasis in the brain, which is advantageous for their growth, survival, and invasion. Alterations in glutamate homeostasis result from its excessive production and release to the extracellular space. High glutamate concentration in the tumor microenvironment destroys healthy tissue surrounding the tumor, thus providing space for glioma cells to expand. Moreover, it confers neuron hyperexcitability, leading to epilepsy, a common symptom in glioma patients. This mini-review briefly describes the biochemistry of glutamate production and transport in gliomas as well as the activation of glutamate receptors. It also summarizes the current pre-clinical and clinical studies identifying pharmacotherapeutics targeting glutamate transporters and receptors emerging as potential therapeutic strategies for glioma.

Patient reported outcomes and short-term adjustment trajectories following gamma knife radiosurgery for benign brain tumor

Purpose Patient reported outcomes (PROs) in the context of Gamma Knife Stereotactic Radiosurgery (GKSRS) for benign brain tumor have been under-researched. This study examined changes in PROs and adjustment trajectories post-GKSRS. Method 50 adults (54% female) aged on average 53.18 (SD = 14.76) years with benign brain tumor were assessed 1 week before GKSRS, 1–2 weeks post-GKSRS, and at 3-month follow-up. Telephone-based questionnaires of anxiety and depressive symptoms, cognitive function, symptom burden, and health-related quality of life (HRQoL) were completed. Results Significant improvements in HRQoL, perceived cognitive ability, anxiety, and total brain tumor symptoms were evident between pre-GKSRS and 3-month follow-up. Conversely, there was a significant short-term increase in depressive symptoms at post-GKSRS; however, levels did not differ from pre-GKSRS at follow-up. No significant changes were evident on PROs of headaches or fatigue. About half of the participants (46–51%) experienced reliable improvement in global HRQoL, and one-third (31–34%) reported improved anxiety symptoms. Increased depressive symptoms was seen in 34% of participants post-GKSRS and 18% at follow-up. Conclusions At 3 months post-GKSRS, improvements in HRQoL, anxiety, perceived cognitive ability, and total brain tumor symptoms were evident. Routine monitoring and support for pre-GKSRS anxiety and depressive symptoms post-GKSRS is recommended.

Stimuli-Responsive Polymeric Nanocarriers Accelerate On-Demand Drug Release to Combat Glioblastoma.

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a poor prognosis and limited treatment options. Drug delivery by stimuli-responsive nanocarriers holds great promise for improving the treatment modalities of GBM. At the beginning of the review, we highlighted the stimuli-active polymeric nanocarriers carrying therapies that potentially boost anti-GBM responses by employing endogenous (pH, redox, hypoxia, enzyme) or exogenous stimuli (light, ultrasonic, magnetic, temperature, radiation) as triggers for controlled drug release mainly via hydrophobic/hydrophilic transition, degradability, ionizability, etc. Modifying these nanocarriers with target ligands further enhanced their capacity to traverse the blood-brain barrier (BBB) and preferentially accumulate in glioma cells. These unique features potentially lead to more effective brain cancer treatment with minimal adverse reactions and superior therapeutic outcomes. Finally, the review summarizes the existing difficulties and future prospects in stimuli-responsive nanocarriers for treating GBM. Overall, this review offers theoretical guidelines for developing intelligent and versatile stimuli-responsive nanocarriers to facilitate precise drug delivery and treatment of GBM in clinical settings.

Analysis of High-Dose Ascorbate-Induced Cytotoxicity in Human Glioblastoma Cells and the Role of Dehydroascorbic Acid and Iron.

Several studies have demonstrated, both in vitro and in animal models, the anti-tumor efficacy of high-dose ascorbate treatment against a variety of tumor entities, including glioblastoma, the most common and aggressive primary malignant brain tumor. The aim of this study was to investigate the effects of high-dose ascorbate as well as dehydroascorbic acid on human glioblastoma cell lines and to evaluate different treatment conditions for the combined administration of ascorbate with magnesium (Mg2+) and iron (Fe3+). Intracellular levels of reactive oxygen species and the induction of cell death following ascorbate treatment were also investigated. We demonstrated high cytotoxicity and antiproliferative efficacy of high-dose ascorbate in human glioblastoma cells, whereas much weaker effects were observed for dehydroascorbic acid. Ascorbate-induced cell death was independent of apoptosis. Both the reduction in cell viability and the ascorbate-induced generation of intracellular reactive oxygen species could be significantly increased by incubating the cells with Fe3+ before ascorbate treatment. This work demonstrates, for the first time, an increase in ascorbate-induced intracellular ROS formation and cytotoxicity in human glioblastoma cells by pre-treatment of the tumor cells with ferric iron, as well as caspase-3 independence of cell death induced by high-dose ascorbate. Instead, the cell death mechanism caused by high-dose ascorbate in glioblastoma cells shows evidence of ferroptosis. The results of the present work provide insights into the efficacy and mode of action of pharmacological ascorbate for the therapy of glioblastoma, as well as indications for possible approaches to increase the effectiveness of ascorbate treatment.

Current methods of postsurgical rehabilitation in benign brain tumor patients

Current methods of postsurgical rehabilitation in benign brain tumor patients

The causal relationship between CSF metabolites and GBM: a two-sample mendelian randomization analysis

BackgroundGlioblastoma multiforme (GBM) is a highly aggressive primary malignant brain tumor characterized by rapid progression, poor prognosis, and high mortality rates. Understanding the relationship between cerebrospinal fluid (CSF) metabolites and GBM is crucial for identifying potential biomarkers and pathways involved in the pathogenesis of this devastating disease.MethodsIn this study, Mendelian randomization (MR) analysis was employed to investigate the causal relationship between 338 CSF metabolites and GBM. The data for metabolites were obtained from a genome-wide association study summary dataset based on 291 individuals, and the GBM data was derived from FinnGen included 91 cases and 174,006 controls of European descent. The Inverse Variance Weighted method was utilized to estimate the causal effects. Supplementary comprehensive assessments of causal effects between CSF metabolites and GBM were conducted using MR-Egger regression, Weighted Median, Simple Mode, and Weighted Mode methods. Additionally, tests for heterogeneity and pleiotropy were performed.ResultsThrough MR analysis, a total of 12 identified metabolites and 2 with unknown chemical properties were found to have a causal relationship with GBM. 1-palmitoyl-2-stearoyl-gpc (16:0/18:0), 7-alpha-hydroxy-3-oxo-4-cholestenoate, Alpha-tocopherol, Behenoyl sphingomyelin (d18:1/22:0), Cysteinylglycine, Maleate, Uracil, Valine, X-12,101, X-12,104 and Butyrate (4:0) are associated with an increased risk of GBM. N1-methylinosine, Stachydrine and Succinylcarnitine (c4-dc) are associated with decreased GBM risk.ConclusionIn conclusion, this study sheds light on the intricate interplay between CSF metabolites and GBM, offering novel perspectives on disease mechanisms and potential treatment avenues. By elucidating the role of CSF metabolites in GBM pathogenesis, this research contributes to the advancement of diagnostic capabilities and targeted therapeutic interventions for this aggressive brain tumor. Further exploration of these findings may lead to improved management strategies and better outcomes for patients with GBM.

Diffusion-weighted MR image analysis based on gamma distribution model for differentiating benign and malignant brain tumors.

Considering the invasiveness of the biopsy method, we attempted to evaluate the ability of the gamma distribution model using magnetic resonance imaging images to stage and grade benign and malignant brain tumors. A total of 42 patients with malignant brain tumors (including glioma, lymphoma, and choroid plexus papilloma) and 24 patients with benign brain tumors (meningioma) underwent diffusion-weighted imaging using five b-values ranging from 0 to 2000 s/mm2 with a 1.5 T scanner. The gamma distribution model is expected to demonstrate the probability of water molecule distribution based on the apparent diffusion coefficient. For all tumors, the apparent diffusion coefficient, shape parameter (κ), and scale parameter (θ) were calculated for each b-value. In the staging step, the fractions (ƒ1, ƒ2, ƒ3) expected to reflect the intracellular, and extracellular diffusion and perfusion were investigated. Diffusion <1 × 10-4 mm2/s (ƒ1), 1 × 10-4 mm2/s < Diffusion > 3 × 10-4 mm2/s (ƒ2), and Diffusion >3 × 10-4 mm2/s (ƒ3); in the grading step, fractions were determined to check heavily restricted diffusion. Diffusion lower than 0.3 × 10-4 mm2/s (ƒ11). Diffusion lower than 0.5 × 10-4 mm2/s (ƒ12). Diffusion lower than 0.8 × 10-4 mm2/s (ƒ13). The findings were analyzed using nonparametric statistics and receiver operating characteristic curve diagnostic performance. Gamma model parameters (κ, ƒ1, ƒ2, ƒ3) showed a satisfactory difference in differentiating meningioma from glioma. For b value = 2000 s/mm2, ƒ1 had a better diagnostic performance than κ and apparent diffusion coefficient (sensitivity, 88%; specificity, 68%; P < .001). The best diagnostic performance was related to ƒ3 in b = 2000 s/mm2 (area under the curve = 0.891, sensitivity = 83%, specificity = 80%, P < .001). In the grading step, ƒ12 (area under the curve = 0.870, sensitivity = 92%, specificity = 72%, P < .001) had the best diagnostic performance in differentiating high-grade from low-grade gliomas with b = 2000 s/mm2. The findings of our study highlight the potential of using a gamma distribution model with diffusion-weighted imaging based on multiple b-values for grading and staging brain tumors. Its potential integration into routine clinical practice could advance neurooncology and improve patient outcomes through more accurate diagnosis and treatment planning.

Functional MRI Assessment of Brain Activity Patterns Associated with Reading in Medulloblastoma Survivors.

Medulloblastoma, a malignant brain tumor primarily affecting children, poses significant challenges to patients and clinicians due to its complex treatment and potential long-term cognitive consequences. While recent advancements in treatment have significantly improved survival rates, survivors often face cognitive impairments, particularly in reading, impacting their quality of life. According to the double deficit theory, reading impairments are caused by deficits in one or both of two independent reading-related functions: phonological awareness and rapid visual naming. This longitudinal study investigates neurofunctional changes related to reading in medulloblastoma survivors in comparison to controls using functional MRI acquired during rapid automatized naming tasks over three annual visits. Support vector machine classification of functional MRI data reveals a progressive divergence in brain activity patterns between medulloblastoma survivors and healthy controls over time, suggesting delayed effects of cancer treatment on brain function. Alterations in brain regions involved in visual processing and orthographic recognition during rapid naming tasks imply disruptions in the ventral visual pathway associated with normal orthographic processing. These alterations are correlated with performance in tasks involving sound awareness, reading fluency, and word attack. These findings underscore the dynamic nature of post-treatment neurofunctional alterations and the importance of early identification and intervention to address cognitive deficits in survivors.

Eslicarbazepine induces apoptosis and cell cycle arrest in C6 glioma cells in vitro and suppresses tumor growth in an intracranial rat model

BackgroundGlioblastoma multiforme (GBM) is the most malignant brain tumor, with a poor prognosis and life expectancy of 14–16 months after diagnosis. The standard treatment for GBM consists of surgery, radiotherapy, and chemotherapy with temozolomide. Most patients become resistant to treatment after some time, and the tumor recurs. Therefore, there is a need for new drugs to manage GBM. Eslicarbazepine (ESL) is a well-known antiepileptic drug belonging to the dibenzazepine group with anticancer potentials. In this study, for the first time, we evaluated the potential effects of ESL on C6 cell growth, both in vitro and in vivo, and examined its molecular effects.MethodsTo determine the effect of ESL on the c6 cell line, cell viability, proliferation, and migration were evaluated by MTT assay, colony formation, and wound healing assay. Also, apoptosis and cell cycle were examined by flow cytometry, qRT-PCR, and western blotting. In addition, an intracranial model in Wistar rats was used to investigate the effect of ESL in vivo, and the tumor size was measured using both Caliper and MRI.ResultsThe obtained results are extremely consistent and highly encouraging. C6 cell viability, proliferation, and migration were significantly suppressed in ESL-treated C6 cells (p < 0.001), as determined by cell-based assays. ESL treatment led to significant enhancement of apoptosis (p < 0.01), as determined by flow cytometry, and upregulation of genes involved in cell apoptosis, such as the Bax/Bcl2 ratio at RNA (p < 0.05) and protein levels (5.37-fold). Flow cytometric analysis of ESL-treated cells revealed G2/M phase cell cycle arrest. ESL-treated cells demonstrated 2.49-fold upregulation of p21 alongside, 0.22-fold downregulation of cyclin B1, and 0.34-fold downregulation of cyclin-dependent kinase-1 at the protein level. Administration of ESL (30 mg/kg) to male rats bearing C6 intracranial tumors also suppressed the tumor volume and weight (p < 0.01).ConclusionsBased on these novel findings, ESL has the potential for further experimental and clinical studies in glioblastoma.Graphical abstract

Pre-Clinical Models for CAR T-Cell Therapy for Glioma.

Immunotherapy represents a transformative shift in cancer treatment. Among myriad immune-based approaches, chimeric antigen receptor (CAR) T-cell therapy has shown promising results in treating hematological malignancies. Despite aggressive treatment options, the prognosis for patients with malignant brain tumors remains poor. Research leveraging CAR T-cell therapy for brain tumors has surged in recent years. Pre-clinical models are crucial in evaluating the safety and efficacy of these therapies before they advance to clinical trials. However, current models recapitulate the human tumor environment to varying degrees. Novel in vitro and in vivo techniques offer the opportunity to validate CAR T-cell therapies but also have limitations. By evaluating the strengths and weaknesses of various pre-clinical glioma models, this review aims to provide a roadmap for the development and pre-clinical testing of CAR T-cell therapies for brain tumors.

Cost of medical care for malignant brain tumors at hospitals in the Japan Clinical Oncology Group brain-tumor study group.

This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. The most used regimen (46.8%) for GBM in patients aged ≤74years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.

Systematic transcriptomic analysis of childhood medulloblastoma identifies N6- methyladenosine-dependent lncRNA signatures associated with molecular subtype, immune cell infiltration, and prognosis.

Medulloblastoma, the most common malignant pediatric brain tumor, is classified into four main molecular subgroups, but group 3 and group 4 tumors are difficult to subclassify and have a poor prognosis. Rapid point-of-care diagnostic and prognostic assays are needed to improve medulloblastoma risk stratification and management. N6-methyladenosine (m6A) is a common RNA modification and long non-coding RNAs (lncRNAs) play a central role in tumor progression, but their impact on gene expression and associated clinical outcomes in medulloblastoma are unknown. Here we analyzed 469 medulloblastoma tumor transcriptomes to identify lncRNAs co-expressed with m6A regulators. Using LASSO-Cox analysis, we identified a five-gene m6A-associated lncRNA signature (M6LSig) significantly associated with overall survival, which was combined in a prognostic clinical nomogram. Using expression of the 67 m6A-associated lncRNAs, a subgroup classification model was generated using the XGBoost machine learning algorithm, which had a classification accuracy > 90%, including for group 3 and 4 samples. All M6LSig genes were significantly correlated with at least one immune cell type abundance in the tumor microenvironment, and the risk score was positively correlated with CD4 + naïve T cell abundance and negatively correlated with follicular helper T cells and eosinophils. Knockdown of key m6A writer genes METTL3 and METTL14 in a group 3 medulloblastoma cell line (D425-Med) decreased cell proliferation and upregulated many M6LSig genes identified in our in silico analysis, suggesting that the signature genes are functional in medulloblastoma. This study highlights a crucial role for m6A-dependent lncRNAs in medulloblastoma prognosis and immune responses and provides the foundation for practical clinical tools that can be rapidly deployed in clinical settings.

CSF1R Ligands Expressed by Murine Gliomas Promote M-MDSCs to Suppress CD8+ T Cells in a NOS-Dependent Manner.

Glioblastoma (GBM) is the most common malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a subset of myeloid cells, expressing monocytic (M)-MDSC markers and dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate the TME. This study evaluated the mechanism of CCR2+/CX3CR1+ M-MDSC differentiation and T cell suppressive function in murine glioma models. We determined that bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Glioma-secreted CSF1R ligands M-CSF and IL-34 were identified as key drivers of M-MDSC differentiation while adenosine and iNOS pathways were implicated in the M-MDSC suppression of T cells. Mining a human GBM spatial RNAseq database revealed a variety of different pathways that M-MDSCs utilize to exert their suppressive function that is driven by complex niches within the microenvironment. These data provide a more comprehensive understanding of the mechanism of M-MDSCs in glioblastoma.

CEP-1347 Boosts Chk2-Mediated p53 Activation by Ionizing Radiation to Inhibit the Growth of Malignant Brain Tumor Cells.

Radiation therapy continues to be the cornerstone treatment for malignant brain tumors, the majority of which express wild-type p53. Therefore, the identification of drugs that promote the ionizing radiation (IR)-induced activation of p53 is expected to increase the efficacy of radiation therapy for these tumors. The growth inhibitory effects of CEP-1347, a known inhibitor of MDM4 expression, on malignant brain tumor cell lines expressing wild-type p53 were examined, alone or in combination with IR, by dye exclusion and/or colony formation assays. The effects of CEP-1347 on the p53 pathway, alone or in combination with IR, were examined by RT-PCR and Western blot analyses. The combination of CEP-1347 and IR activated p53 in malignant brain tumor cells and inhibited their growth more effectively than either alone. Mechanistically, CEP-1347 and IR each reduced MDM4 expression, while their combination did not result in further decreases. CEP-1347 promoted IR-induced Chk2 phosphorylation and increased p53 expression in concert with IR in a Chk2-dependent manner. The present results show, for the first time, that CEP-1347 is capable of promoting Chk2-mediated p53 activation by IR in addition to inhibiting the expression of MDM4 and, thus, CEP-1347 has potential as a radiosensitizer for malignant brain tumors expressing wild-type p53.

Characteristics of Patients Hospitalized to Community Hospitals With Malignant Brain Tumors and Factors Associated With Discharge Destination.

Our main objective was to compare the characteristics and hospital outcomes of patients with primary and metastatic brain malignancies and to investigate the associated factors related to hospital outcomes. We conducted a retrospective, cross-sectional study of 1628 patients with brain malignancies from 8 community hospitals between 2017 and 2022 who were identified using International Classification of Disease codes. A stepwise logistic regression was used to identify demographics and clinical characteristics associated with in-hospital mortality and home discharge. The median age was 65 years old, with 72.5% of patients having metastatic brain malignancies. After 7.2 days of hospital stay, 49.2% were discharged home, and 102 patients expired during hospitalization. Increased age, medical coverage by Medicare, hemiplegia or paraplegia, lower initial hemoglobin level, increased length of stay, and the use of electrolyte replacement, antibiotics, laxatives, heparin, and anticonvulsants were associated with a decreased likelihood of discharge to home. No medical insurance, Medicaid insurance coverage, comorbidities of cerebrovascular disorder, the need to stay in the intensive care unit, patient safety indicator events, and the use of antibiotics, oral analgesics, and ipratropium-albuterol were associated with increased odds of in-hospital mortality. We identified several predictor variables that delineate differences between both mortality risk and home discharge in patients with primary and metastatic brain tumors. Understanding these predictor variables can be helpful in improving the acute and post-acute care of this population.

Utility of combining frailty and comorbid disease indices in predicting outcomes following craniotomy for adult primary brain tumors: A mixed-effects model analysis using the nationwide readmissions database

ObjectiveThe escalating healthcare expenditures in the United States, particularly in neurosurgery, necessitate effective tools for predicting patient outcomes and optimizing resource allocation. This study explores the utility of combining frailty and comorbidity indices, specifically the Johns Hopkins Adjusted Clinical Groups (JHACG) frailty index and the Elixhauser Comorbidity Index (ECI), in predicting hospital length of stay (LOS), non-routine discharge, and one-year readmission in patients undergoing craniotomy for benign and malignant primary brain tumors. MethodsLeveraging the Nationwide Readmissions Database (NRD) for 2016–2019, we analyzed data from 645 patients with benign and 30,991 with malignant tumors. Frailty, ECI, and frailty + ECI were assessed as predictors using generalized linear mixed-effects models. Receiver operating characteristic (ROC) curves evaluated predictive performance. ResultsPatients in the benign tumor cohort had a mean LOS of 8.1 ± 15.1 days, and frailty + ECI outperformed frailty alone in predicting non-routine discharge (AUC 0.829 vs. 0.820, p = 0.035). The malignant tumor cohort patients had a mean LOS of 7.9 ± 9.1 days. In this cohort, frailty + ECI (AUC 0.821) outperformed both frailty (AUC 0.744, p < 0.0001) and ECI alone (AUC 0.809, p < 0.0001) in predicting hospital LOS. Frailty + ECI (AUC 0.831) also proved superior to frailty (AUC 0.809, p < 0.0001) and ECI alone (AUC 0.827, p < 0.0001) in predicting non-routine discharge location for patients with malignant tumors. All indices performed comparably to one another as a predictor of readmission in both cohorts. ConclusionThis study highlights the synergistic predictive capacity of frailty + ECI, especially in malignant tumor cases, and further suggests that comorbid diseases may greatly influence perioperative outcomes more than frailty. Enhanced risk assessment could aid clinical decision-making, patient counseling, and resource allocation, ultimately optimizing patient outcomes.

Mechanistic Insights on Metformin and Arginine Implementation as Repurposed Drugs in Glioblastoma Treatment.

As the most common and aggressive primary malignant brain tumor, glioblastoma is still lacking a satisfactory curative approach. The standard management consisting of gross total resection followed by radiotherapy and chemotherapy with temozolomide only prolongs patients' life moderately. In recent years, many therapeutics have failed to give a breakthrough in GBM treatment. In the search for new treatment solutions, we became interested in the repurposing of existing medicines, which have established safety profiles. We focused on the possible implementation of well-known drugs, metformin, and arginine. Metformin is widely used in diabetes treatment, but arginine is mainly a cardiovascular protective drug. We evaluated the effects of metformin and arginine on total DNA methylation, as well as the oxidative stress evoked by treatment with those agents. In glioblastoma cell lines, a decrease in 5-methylcytosine contents was observed with increasing drug concentration. When combined with temozolomide, both guanidines parallelly increased DNA methylation and decreased 8-oxo-deoxyguanosine contents. These effects can be explained by specific interactions of the guanidine group with m5CpG dinucleotide. We showed that metformin and arginine act on the epigenetic level, influencing the foreground and potent DNA regulatory mechanisms. Therefore, they can be used separately or in combination with temozolomide, in various stages of disease, depending on desired treatment effects.