Vacuolar Proton-Translocating ATPase May Take Part in the Drug Resistance Phenotype of Glioma Stem Cells.

The vacuolar proton-translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism underlying carcinogenesis is mainly based on anaerobic glycolytic reactions. Moreover, neoplastic cells use the V-ATPase to extrude chemotherapy drugs into the extra-cellular compartment as a drug resistance mechanism. In glioblastoma (GBM), the most malignant and incurable primary brain tumor, the expression of this pump is upregulated, making it a new possible therapeutic target. In this work, the bafilomycin A1-induced inhibition of V-ATPase in patient-derived glioma stem cell (GSC) lines was evaluated together with temozolomide, the first-line therapy against GBM. In contrast with previous published data, the proposed treatment did not overcome resistance to the standard therapy. In addition, our data showed that nanomolar dosages of bafilomycin A1 led to the blockage of the autophagy process and cellular necrosis, making the drug unusable in models which are more complex. Nevertheless, the increased expression of V-ATPase following bafilomycin A1 suggests a critical role of the proton pump in GBM stem components, encouraging the search for novel strategies to limit its activity in order to circumvent resistance to conventional therapy.

Exoscopic microneurosurgery in pediatric brain tumors: an ideal tool for complex and peculiar anatomo-topographic scenarios?

PURPOSE: Since its introduction in the 1950s, the microsurgical paradigm has revolutionized neurosurgery. New technologies have been introduced over the years trying to overcome limits of the classical operating microscope. The recently developed 3D exoscopes represent a potential new paradigm for micro-neurosurgery. We analyzed our own experience with a 4 K-3D exoscope in a series of pediatric brain tumors to verify its advantages and limitations in comparison to the operating microscope and in light of the literature. METHODS: Twenty-five pediatric patients with brain tumors underwent surgery at our Institute; the population has been analyzed and described. A score to evaluate the exoscopes and compare it to the operating microscope was considered and postoperatively applied to each single case. RESULTS: The exoscope appears to be at least comparable to the operating microscope (OM) in all analyzed aspects. In the case of deep-seated or fourth ventricle tumors, the exoscope seems to be superior to the microscope. A surgeon-dependent learning curve is necessary for neurosurgeons to be confident with the exoscope. CONCLUSION: Exoscopes appear to be as safe and effective as operating microscopes in pediatric neuro-oncological surgery. They have some advantages that make them superior to microscopes, particularly regarding surgeon ergonomics and fatigue, visual field qualities, and higher choice of intraoperative viewing angles.

Reducing the Gap in Neurosurgical Education in LMICs: A Report of a Non-Profit Educational Program.

INTRODUCTION: Central to neurosurgical care, neurosurgical education is particularly needed in low- and middle-income countries (LMICs), where opportunities for neurosurgical training are limited due to social and economic constraints and an inadequate workforce. The present paper aims (1) to evaluate the validity and usability of a cadaver-free hybrid system in the context of LMICs and (2) to report their learning needs and whether the courses meet those needs via a comprehensive survey. METHODS: From April to November 2021, a non-profit initiative consisting of a series of innovative cadaver-free courses based on virtual and practical training was organized. This project emerged from a collaboration between the Young Neurosurgeons Forum of the World Federation of Neurological Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and UpSurgeOn, an Italian hi-tech company specialized in simulation technologies, creator of the UpSurgeOn Box, a hyper-realistic simulator of cranial approaches fused with augmented reality. Over that period, 11 cadaver-free courses were held in LMICs using remote hands-on Box simulators. RESULTS: One hundred sixty-eight participants completed an online survey after course completion of the course. The anatomical accuracy of simulators was overall rated high by the participant. The simulator provided a challenging but manageable learning curve, and 86% of participants found the Box to be very intuitive to use. When asked if the sequence of mental training (app), hybrid training (Augmented Reality), and manual training (the Box) was an effective method of training to fill the gap between theoretical knowledge and practice on a real patient/cadaver, 83% of participants agreed. Overall, the hands-on activities on the simulators have been satisfactory, as well as the integration between physical and digital simulation. CONCLUSIONS: This project demonstrated that a cadaver-free hybrid (virtual/hands-on) training system could potentially participate in accelerating the learning curve of neurosurgical residents, especially in the setting of limited training possibilities such as LMICs, which were only worsened during the COVID-19 pandemic.

Is Advanced Age a Factor That Influences the Clinical Outcome of Single- or Double-Level MIS-TLIF? A Single-Center Study with a Minimum Two-Year Follow-Up on 103 Consecutive Cases.

As life expectancy rises, more elderly people undergo spinal fusion surgery to treat lumbar degenerative diseases. The MIS-TLIF technique, which minimizes soft tissue manipulation, is a promising fusion technique for frailer patients. The aim of this study was to investigate if older age is a significant factor in the clinical outcome of single- or double-level MIS-TLIF. A cross-sectional study was conducted on 103 consecutive patients. Data were compared between younger (<65 y.o.) and older (≥65 y.o.) patients. We observed no significant differences between baseline characteristics of the two groups apart from the frequency of disk space treated, with a relative predominance of L3-L4 space treated in the elderly (10% vs. 28%, p = 0.01) and L5-S1 space in younger patients (36% vs. 5%, p = 0.006). There was no significant difference in complication rate, surgical satisfaction, EQ 5D-5L, or Oswestry Disability Index (ODI) global or specific scores, with the exception of the EQ 5D-5L "mobility" score, where older patients fared worse (1.8 ± 1.1 vs. 2.3 ± 1.4; p = 0.05). The minimal invasiveness of the surgical technique, age-related specific outcome expectations, and biomechanical issues are all potential factors influencing the lack of age group differences in outcome scores.

Exoscope as a Teaching Tool: A Narrative Review of the Literature.

Recently, the emergence of the three-dimensional (3D) exoscope has proven to be a viable alternative to the operative microscope (OM) as a novel workhorse of microneurosurgical procedures. Through its current iteration, the 3D exoscope has been demonstrated to be at least equivalent to the operative microscope in terms of surgical outcomes in many settings. With its superior ergonomics and simplicity of use, the 3D exoscope has been shown in multiple studies to be a powerful visualizing tool during surgical procedures. Moreover, the exoscopic systems, through their current iterations and by means of a high-resolution 3D monitor and 3D glasses, have allowed all participants present in the operative room to attain an unprecedented level of intraoperative visualization of anatomical structures and surgical maneuvers which are traditionally available only to the first operator. Although long-term data are still lacking regarding its future as a replacement of the OM, the 3D exoscope has revealed itself as an intense subject of discussion in neurosurgery regarding its implication for surgical education, especially for residents and junior neurosurgeons. This article is a review of the current state of the literature on the role of the exoscope in surgical education, underlining its strength as a learning tool and its potential future implications in terms of surgical education.

Middle meningeal artery embolization for chronic subdural hematomas. A systematic review of the literature focused on indications, technical aspects, and future possible perspectives.

Background: Chronic subdural hematoma (CSDH) is one of the most common neurosurgical diseases that affect elderly and fragile patients and as a consequence, management can be challenging. Surgery represents the standard treatment; however, alternative options are under investigation. Middle meningeal artery (MMA) embolization is considered a minimally invasive treatment although with poor evidence. In this review, we tried to summarize the findings about MMA embolization as a treatment for a CSDH to provide a useful guidance for clinical practice and for future speculative aspects. Methods: Literature review on PubMed until March 2021 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. We conducted a research on PubMed with a various combinations of the keywords "CSDH" and "middle meningeal artery" and "embolization," "refractory subdural hematoma," and then we reviewed the references of the relevant studies as additional source of eligible articles. Results: Among the 35 studies eligible for this review, 22 were case series, 11 were case reports, one was a technical note, and 1 was a randomized trial. A total of 746 patients were found in the literature. Failure rate of MMA embolization was between 3.9 and 8.9% of the cases according the indication to treat CSDH (upfront vs. after surgery). Conclusion: The global impression deriving from the data available and the literature is that MMA embolization is a safe procedure with very low complications and with a low failure rate, both when associated with surgery or in case of a standalone treatment.