Bruno Zilli Peroni

Background: Glioblastoma (GBM) represents the most aggressive and lethal primary malignancy of the central nervous system in adults. Although clinical trials evaluating immunotherapy strategies have increased substantially in recent years, the available evidence remains highly fragmented. This scoping review aimed to synthesize the available evidence from clinical trials investigating immunotherapy for newly diagnosed GBM. Methods: PubMed, Scopus, Embase, and Web of Science were searched from inception to July 2026 for clinical trials of first-line immunotherapy in adults with newly diagnosed GBM; recurrent, mixed-setting, preclinical, and abstract-only reports were excluded. Outcomes were overall survival (OS) and progression-free survival (PFS), adverse events, and treatment-related deaths. Results: Six therapeutic classes were represented: immune checkpoint inhibitors (13 reports), peptide and neoantigen vaccines (12), dendritic cell vaccines (10), adoptive cell therapies (5), oncolytic viral and gene therapies (3), and autologous formalin-fixed tumor vaccines (2). The evidence base was predominantly early-phase: 36 of 45 studies enrolled fewer than 100 patients, only 14 included a randomized comparison, and 5 were phase III. Median OS ranged from 11.5 to 38.4 months and median PFS from 1.3 to 60.1 months, the highest estimates arising from small, highly selected single-arm cohorts. No randomized trial improved OS. Important adverse events were rare and almost exclusively confined to checkpoint inhibitor trials. Conclusions: Immunotherapy in newly diagnosed GBM is feasible and tolerable but has not improved survival, with outcomes still determined more by MGMT promoter status and extent of resection than by treatment assignment. Biomarker-enriched selection, lymphocyte-sparing design and rational combinations are required in future trials.

Background: Neurosurgery depends heavily on implanted biomaterials, and the endovascular treatment of intracranial aneurysms (IAs) is the paradigmatic case, since coils, flow diverters and intrasaccular devices achieve durable occlusion only through intrasaccular thrombus organization and endothelial coverage of the neck, both governed by the local flow environment. Computational fluid dynamics (CFD) resolves that environment but is too slow and too solver-dependent for clinical or device design use. Graph and geometric deep learning operates natively on the unstructured meshes in which vascular anatomy and implanted scaffolds are represented and has been proposed as the technology that would close this gap. Methods: Four databases were searched up to 29 July 2026 for original studies developing or validating graph-based or geometric deep learning applied to IA geometry, with a hemodynamic or clinical outcome. Screening and extraction were performed in duplicate; risk of bias with PROBAST and artificial intelligence signaling items, reporting with TRIPOD+AI, and synthesis followed SWiM. Results: Twelve studies (2021 to 2026) were included: seven clinical (1965 aneurysms, plus 81 externally) and five computational (up to 984 geometries). Learned geometric representations discriminated rupture, growth and post-embolization recanalization better than morphological indices and then PHASES, reaching an area under the curve of 0.795 to 0.97 internally. Graph and point cloud surrogates reproduced hemodynamic fields with normalized errors of 2% to 5% in seconds rather than hours, and one transformer-based graph network predicted the extent and timing of intra-aneurysmal thrombus formation over a reactive surface. External validation was reached by two studies, and clinical utility was achieved in one; discrimination fell from 0.85 to 0.71 in one external test, and surrogate error rose from 4.1% to 19.1% on patient-derived anatomy. No model was trained on a device-laden geometry. Additionally, 5/7 clinical studies classified cross-sectional rupture status rather than prospectively predicting future rupture. Conclusions: Graph and geometric deep learning has substantially reduced the computational burden of hemodynamic analysis, but reliable generalization to unseen patient-specific anatomy remains a relevant challenge. Shared patient-specific benchmarks, prespecified external validation, reporting of calibration, and extension of training corpora to implanted anatomy are necessary next steps towards virtual evaluation of neurovascular biomaterials.

BACKGROUND AND OBJECTIVES: Bypass surgery is an important option for treating complex intracranial aneurysms (IAs) and Moyamoya disease (MMD), particularly when conventional approaches are insufficient. However, the literature remains heterogeneous, with important limitations in reporting quality that hinder reproducibility and comparability. We aimed to evaluate the current evidence and propose a reporting guideline to improve transparency and methodological rigor. METHODS: We searched PubMed, Embase, and Web of Science databases. Eligible studies were observational or randomized studies reporting clinical and/or surgical outcomes of bypass for IAs or MMD, including a sample size of ≥3 patients, and published in English between January 1, 2000, and January 1, 2025. Assessment focused on key domains: (1) Assessment of reported baseline characteristics; (2) assessment and reporting on imaging methods and pathology characteristics; (3) reporting on pivotal concept definitions; (4) reporting on neurosurgeon(s) and staff characteristics; (5) reporting on the anesthetic protocol; (6) reporting on vascular procedure details; (7) reporting on antiaggregant and anticoagulation protocol; (8) assessing and reporting on clinical and surgical outcomes, besides adverse events; (9) reporting on retreatment details; and (10) funding and conflicts of interest declarations. RESULTS: Thirty studies were included. Our assessment revealed substantial reporting gaps across all domains pertinent to bypass. A bypass reporting guideline was developed and organized into 10 domains, featuring a pragmatic checklist composed of one common domain and disease-specific sections for IA and MMD. The guideline emphasizes detailed technical reporting, graft patency assessment and verification, perioperative antithrombotic management, and standardized clinical and radiological outcome measures. CONCLUSION: This systematic review on bypass surgery for IA and MMD identified substantial methodological and reporting limitations that compromise evidence quality and comparability. The proposed reporting guideline provides a structured framework to address these gaps, enhancing transparency, reproducibility, and standardization, with the potential to strengthen the evidence base and improve patient care.

BACKGROUND AND OBJECTIVES: Clival chordoma is a rare, locally invasive tumor originating from notochord remnants. The endoscopic endonasal approach (EEA) offers direct midline access, but the ideal balance between radicality and safety remains debated because of perioperative complications and mortality. The aim of this study was to synthesize oncologic and safety outcomes of EEA for clival chordomas, focusing on extent of resection, recurrence, and complications. METHODS: PubMed, Embase, Scopus, and Web of Science were searched through September 2025. We included observational studies of clival chordoma treated through EEA reporting extent of resection and outcomes. Exclusion criteria included alternative approaches, nonchordoma histologies, non-English/Spanish/Portuguese reports, series with 2 . RESULTS: We included 18 observational studies comprising 1197 patients. The mean follow-up was 55.1 months. Pooled gross total resection was 48.3% (95% CI: 39.6-57.6; I ² = 94%). Near-total, subtotal, and partial resection rates were 29.2%, 27.2%, and 9%, respectively. Mortality during follow-up was 10.8% (95% CI: 5.7-19.4; I ² = 83%). Pooled cerebrospinal fluid leak rate was 12.4% (95% CI: 6.8%-16.6%; I ² = 64%). Complications included cranial nerve palsy 7.5% (95% CI: 4.4%-12.4%; I ² = 68%), paresis 4.1% (95% CI: 2.3%-7.1%; I ² = 40%), diplopia 3.7% (95% CI: 0.0%-13.4%; I ² = 51%), brain infarction 1.2% (95% CI: 0.02.8%; I ² = 14%), major hemorrhage 0.3% (95% CI: 0.0%-1.3%; I ² = 6%), and hematoma 0.2% (95% CI: 0.0%-1.2%; I ² = 0%). CONCLUSION: In contemporary EEA for clival chordomas, about half of the patients achieve gross total resection. Recurrence approaches ∼32% at reported follow-up. Morbidity is driven chiefly by cranial nerve deficits (∼8%), whereas major vascular and bleeding events are uncommon. PROSPERO REGISTRATION NUMBER: CRD420251155783.

Endoscopic techniques have enabled minimally invasive approaches in neurosurgery, providing shorter recovery times and favorable outcomes. Among these, the endoscopic transorbital approach (ETOA) has emerged as a versatile surgical modality. Despite the growing body of evidence, complication rates associated with ETOA have not yet been systematically evaluated. We systematically searched PubMed, Embase, Scopus, and Web of Science up to March 2026. We included studies enrolling ≥ 5 patients who underwent ETOA as the sole surgical modality to treat both skull base and orbital lesions, providing data on early or long-term complications. A single-group meta-analysis was performed using a random-effects model with 95% confidence intervals. Heterogeneity was assessed with the I² statistic and further explored through Baujat plots and sensitivity analyses. A total of 11 observational studies, comprising 269 patients, were included. Overall, 21 different pathologies were reported. Meningioma represented the most frequent lesion (60.6% of cases), followed by schwannoma (12.0%), cavernous hemangioma (4.6%), and glioma (2.7%). Mean follow-up was 27.6 ± 15.1 months. CSF leak was observed in 1% (95% CI: 0.00 to 0.04, I² = 46.5%), and wound infection was observed in 3% (95% CI: 0.01 to 0.07, I²=0%). Ptosis occurred in 4% (95% CI: 0.00 to 0.14, I²=79.4%) and diplopia occurred in 6% (95% CI: 0.01 to 0.14, I²=68.9%). Medial gaze palsy occurred in 9% (95% CI: 0.04 to 0.18, I²=8.8%). Improvement in visual function was seen in 47% (95% CI: 0.22 to 0.73, I²=88.7%). Visual dysfunction occurred in 1% (95% CI: 0.00 to 0.04, I²=48.6%). Transient facial numbness occurred in 16% (95% CI: 0.09 to 0.25, I²=35.0%). Mortality was 0% (95% CI: 0.00 to 0.02, I²=28.7%). ETOA is a safe and promising technique for managing a wide range of skull base and orbital lesions. Future prospective and comparative studies are needed to refine indications and validate its long-term efficacy.

Background: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the sinonasal cavity, often presenting with nonspecific symptoms and requiring complex multidisciplinary management. Case Description: A 55-year-old male developed progressive anosmia and recurrent epistaxis. Imaging revealed an invasive lesion involving the nasal cavity, paranasal sinuses, and intracranial space, along with cervical lymph node metastases. Diagnosis was confirmed histologically. Patient underwent craniofacial approach, cervical lymphadenectomy, and adjuvant radiotherapy. Despite aggressive treatment, early recurrence occurred in both nasal and intracranial compartments. With curative options exhausted, the patient was transitioned to palliative care. Conclusion: ONB has a high risk of recurrence, typically occurring years after initial treatment. However, early recurrence, as seen in this case, is rare and associated with aggressive tumor features such as high-grade histology and incomplete resection. These cases present significant therapeutic challenges and underscore the importance of close surveillance and further research into optimal management strategies for early recurrent ONB.