Fluorescein-mediated sonodynamic therapy (FL-SDT) is an extremely promising approach for glioma treatment, resulting from the combination of low-intensity focused ultrasound (FUS) with a sonosensitizer. In the present study, we evaluated the efficacy and immunomodulation of SDT with fluorescein as the sonosensitizer in immunocompetent GL261 glioma mice for the first time. In vitro studies demonstrated that the exposure of GL261 cells to FL-SDT induced immunogenic cell death and relevant upregulation of MHC class I, CD80 and CD86 expression. In vivo studies were then performed to treat GL261 glioma-bearing mice with FL-SDT, fluorescein alone, or FUS alone. Perturbation of the glioma-associated macrophage subset within the immune microenvironment was induced by all the treatments. Notably, a relevant depletion of myeloid-derived suppressor cells (MDSCs) and concomitant robust infiltration of CD8+ T cells were observed in the SDT-FL-treated mice, resulting in a significant radiological delay in glioma progression and a consequent improvement in survival. Tumor control and improved survival were also observed in mice treated with FL alone (median survival 41.5 days, p > 0.0001 compared to untreated mice), reflecting considerable modulation of the immune microenvironment. Interestingly, a high circulating lymphocyte-to-monocyte ratio and a very low proportion of MDSCs were predictive of better survival in FL- and FL-SDT-treated mice than in untreated and FUS-treated mice, in which elevated monocyte and MDSC frequencies correlated with worse survival. The immunostimulatory potential of FL-SDT treatment and the profound modulation of most immunosuppressive components within the microenvironment encouraged the exploration of the combination of FL-SDT with immunotherapeutic strategies.

Background and Objectives: Binocular optical microscopy (OM) paved the way for a new era in brain and spine neurosurgery fields with the introduction of microsurgery. Despite its enormous contribution to modern neurosurgery, OM presents some intrinsic limitations that surgeons need to face during procedures such as prolonged non-ergonomic positions and decreased vision quality to the assistant eyepiece. To overcome these limitations, in recent years, new operative tools have been introduced, such as exoscopes. Here, we present our experience with exoscopes in spine surgery. Materials and Methods: In the period between January 2022 and December 2023, we gradually implemented the use of a high-definition 4K-3D exoscope (ORBEYE^TM, Olympus, Japan) in patients undergoing spinal surgery. Results: A total of 243 patients underwent spine surgery with exoscope magnification (47 intradural tumors, 99 lumbar degenerative cases, 79 cervical degenerative cases, 5 dorsal calcified disk herniations, 4 dural arteriovenous fistulas (dAVFs), and 9 others). We compared this cohort with a similar cohort of patients operated in the same period using OM based on different endpoints: operating time, complication rate, and infection rate. We did not find any statistically significant difference in any of the endpoints between these two groups. Conclusions: In our experience, the exoscope provides a better resolution of spinal anatomy and higher quality real-time images of the surgery for the entire OR team and improves the ergonomic posture of both surgeons, without lengthening the operating time and without increasing the rate of adverse events. Prospective studies with a larger cohort of patients are needed to further validate these findings.