Journal of neurosurgery
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Journal of neurosurgery · May 2023
Randomized Controlled TrialSurgery for glioblastomas in the elderly: an Association des Neuro-oncologues d'Expression Française (ANOCEF) trial.
The role of surgery in the treatment of malignant gliomas in the elderly is not settled. The authors conducted a randomized trial that compared tumor resection with biopsy only-both followed by standard therapy-in such patients. ⋯ This study suggests that debulking surgery is safe, and-compared to biopsy-is associated with a less severe deterioration of quality of life and autonomy, as well as a significant although modest improvement of PFS in elderly patients suffering from newly diagnosed malignant glioma. Although resection does not provide a significant survival benefit in the elderly, the authors believe that the risk/benefit analysis favors an attempt at optimal tumor resection in this population, provided there is careful preoperative geriatric evaluation. Clinical trial registration no.: NCT02892708 (ClinicalTrials.gov).
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Journal of neurosurgery · May 2023
Gene expression analysis during progression of malignant meningioma compared to benign meningioma.
Meningioma is the most common primary intracranial neoplasm. Only 1%-3% of meningiomas are malignant according to the 2016 WHO criteria (WHO grade III). High-grade meningiomas present specific gene expression signatures indicating aggressive growth or recurrence. However, changes in gene expression and in neuroinflammatory gene expression signatures in WHO grade III meningiomas and during progression from WHO grade I or II to grade III are unknown. ⋯ The authors found gene expression changes in low-grade meningiomas that predated histological transformation to grade III meningiomas. Neuroinflammation genes distinguished grade III from grade I meningiomas.
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Journal of neurosurgery · May 2023
Use of heparin to rescue immunosuppressive monocyte reprogramming by glioblastoma-derived extracellular vesicles.
The profound immunosuppression found in glioblastoma (GBM) patients is a critical barrier to effective immunotherapy. Multiple mechanisms of tumor-mediated immune suppression exist, and the induction of immunosuppressive monocytes such as myeloid-derived suppressor cells (MDSCs) is increasingly appreciated as a key part of this pathology. GBM-derived extracellular vesicles (EVs) can induce the formation of MDSCs. The authors sought to identify the molecular consequences of these interactions in myeloid cells in order to identify potential targets that could pharmacologically disrupt GBM EV-monocyte interaction as a means to ameliorate tumor-mediated immune suppression. Heparin-sulfate proteoglycans (HSPGs) are a general mechanism by which EVs come into association with their target cells, and soluble heparin has been shown to interfere with EV-HSPG interactions. The authors sought to assess the efficacy of heparin treatment for mitigating the effects of GBM EVs on the formation of MDSCs. ⋯ The authors demonstrated that GBM EVs induce broad but reproducible reprogramming in monocytes, with enrichment of pathways that may portend an immunosuppressive phenotype. The authors further demonstrated that GBM EV-monocyte interactions are potentially druggable targets for overcoming tumor-mediated immune suppression, with heparin inhibition of EV-monocyte interactions demonstrating proof of principle.
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Journal of neurosurgery · May 2023
Nerve transfers for brachial plexus injuries: grading of volitional control.
After brachial plexus injuries (BPIs), nerve transfers are used to restore lost muscle function. Brain plasticity underlies the process of regaining volitional control, which encompasses disconnection of the original donor nerve-related programs and reconnection to acceptor nerve programs. To the authors' knowledge, the levels of disconnection and reconnection have never been studied systematically. In this study, the authors developed a novel 4-point plasticity grading scale (PGS) and assessed the degree of volitional control achieved, identifying clinical correlations with this score. ⋯ Just around 20% of the authors' patients developed a complete disconnection of the donor program along with complete independent control over the reinnervated muscle. Incomplete disconnection was present in the vast majority of the patients, and the level of disconnection and control was poor in approximately 15% of patients. Brain plasticity underlies patient ability to regain volitional control after a nerve transfer, but this capacity is limited.