Circulating platelets (PLTs) are able to affect glioblastoma (GBM) microenvironment by supplying oncopromoter and pro-angiogenic factors. Among these mediators, sphingosine-1-phophate (S1P) has emerged as a potent bioactive lipid enhancing cell proliferation and survival. Here, we investigated the effect of “tumor education”, characterizing PLTs from GBM patients in terms of activation state, protein content, and pro-angiogenic potential. PLTs from healthy donors (HD-PLTs) and GBM patients (GBM-PLTs) were collected, activated, and analyzed by flow cytometry, immunofluorescence, and Western blotting. To assess the pro-angiogenic contribution of GBM-PLTs, a functional cord formation assay was performed on GBM endothelial cells (GECs) with PLT-releasate. GBM-PLTs expressed higher positivity for P-selectin compared to HD-PLTs, both in basal conditions and after stimulation with adenosine triphosphate (ADP) and thrombin receptor activating peptide (TRAP). PLTs showed higher expression of VEGFR-1, VEGFR-2, VWF, S1P, S1PR1, SphK1, and SPNS. Interestingly, increased concentrations of VEGF and its receptors VEGFR1 and VEGFR2, VWF, and S1P were found in GBM-PLT-releasate with respect to HD-PLTs. Finally, GBM-PLT-releasate showed a pro-angiogenic effect on GECs, increasing the vascular network’s complexity. Overall, our results demonstrated the contribution of PLTs to GBM angiogenesis and aggressiveness, advancing the potential of an anti-PLT therapy and the usefulness of PLT cargo as predictive and monitoring biomarkers.

Deep brain stimulation (DBS) is a well-established treatment that significantly improves the motor symptoms of patients with Parkinson’s disease (PD); however, patients may experience post-operative psychological distress and social maladjustments. This phenomenon has been shown to be related to patients’ pre-operative cognitive representations, such as expectations. In this systematic review, we discuss the findings on the role of the expectations of patients with PD regarding the clinical outcomes of DBS to identify areas of intervention to improve pre-operative patient education and promote successful post-operative psychosocial adjustment. PubMed was searched for relevant articles published up to 16 January 2023. Of the 84 identified records, 10 articles focusing on the treatment expectations of patients with PD undergoing DBS were included in this review. The selected studies were conducted among cohorts of patients with different DBS targets, among which the most common was the bilateral subthalamic nucleus. Overall, the data showed that patients’ expectations contribute to treatment efficacy. Experiments investigating the placebo effect itself have shown clinical improvement after the induction of positive therapeutic expectations; conversely, unrealistic treatment expectations can affect patient satisfaction after surgery, clinical outcomes, and subjective well-being. This review highlights the need for routine clinical practice to better investigate and manage patients' pre-operative expectations, as well as multidisciplinary education to improve patient satisfaction and psychosocial adjustment after DBS.

Cavernous hemangioma are the most common benign lesions of the orbit. Their surgical resection is still challenging and several surgical approaches have been proposed. We present the case of a 59-year-old woman with a cavernous hemangioma of the orbital apex, which was diagnosed incidentally. The hemangioma was extraconal and involved mainly the medial orbital apex; it also extended to the pterygoid fossa, to the middle fossa, to the maxillary and sphenoid sinuses. The surgical resection was performed by a pure endoscopic transphenoidal, transmaxillary, transethmoidal approach, achieving a total removal. The patient had a transient and incomplete paresis of the VI cranial nerve on the left side and did not experience other postoperative complications. The endoscopic endonasal approach proved successful in the management of this case and it should be considered in the surgical management of extraconal orbital apex lesions with medial or inferior extension.

Glioblastoma is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. Glioblastoma shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), has demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including glioblastoma. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss metformin’s potential antitumoral effects on glioblastoma, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of glioblastoma patients.