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Simple Summary: Glioblastoma is one of the most aggressive brain tumors, with poor survival and early recurrence rates. The development of effective immunotherapy treatments has been limited by the infiltration-resistant and immunosuppressive tumor microenvironments of these tumors. γδ T cells are unconventional T cells that have the potential to overcome these challenges through their unique recognition of molecular targets on glioblastoma cells. Nonetheless, challenges exist in the utilization of these cells, including their isolation, expansion, and potential for protumor activity. In this review, we discuss the biology of γδ T cells and their role in immunotherapy for glioblastoma and propose several research avenues for future studies. Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research avenues for future studies. Using the PubMed, ScienceDirect, and JSTOR databases, we performed a review of the literature studying the biology of γδ T cells and their role in GBM treatment. We identified 15 studies focused on γδ T cells in human GBM. Infiltrative γδ T cells can incite antitumor immune responses in certain TMEs, though rapid tumor progression and TME hypoxia may impact the extent of tumor suppression. In the studies, available findings have shown both the potential for robust antitumor activity and the risk of protumor activity. While γδ T cells have potential as a therapeutic agent against GBM, the technical challenges of extracting, isolating, and expanding γδ T cells, and the activation of antitumoral versus protumoral cascades, remain barriers to their application. Overcoming these limitations may transform γδ T cells into a promising immunotherapy in GBM. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) is a common primary brain tumor with a short median overall survival despite aggressive treatment with resection, chemotherapy, and radiation therapy. Focused ultrasound (FUS) represents a promising new therapeutic approach for treatment of GBM. Unlike imaging forms of ultrasound, FUS can successfully penetrate the skull surrounding the brain, allowing for non-invasive ablation of tumor tissue. FUS can also temporarily disrupt the blood–brain barrier, a microvascular network that prohibits diffusion of most therapeutic agents, allowing chemotherapeutic drugs to penetrate the tumor. Other modalities are under investigation and include means of stimulating the immune system and sensitizing tumors to radiation therapy. The feasibility and safety of transcranial FUS has been illustrated in animal models and clinical trials. Precise results can be obtained under guidance from magnetic resonance imaging, limiting side effects. Successful outcomes from clinical trials will likely continue to motivate investigation and innovation of FUS technology for GBM. Glioblastoma (GBM) is an aggressive primary astrocytoma associated with short overall survival. Treatment for GBM primarily consists of maximal safe surgical resection, radiation therapy, and chemotherapy using temozolomide. Nonetheless, recurrence and tumor progression is the norm, driven by tumor stem cell activity and a high mutational burden. Focused ultrasound (FUS) has shown promising results in preclinical and clinical trials for treatment of GBM and has received regulatory approval for the treatment of other neoplasms. Here, we review the range of applications for FUS in the treatment of GBM, which depend on parameters, including frequency, power, pulse duration, and duty cycle. Low-intensity FUS can be used to transiently open the blood–brain barrier (BBB), which restricts diffusion of most macromolecules and therapeutic agents into the brain. Under guidance from magnetic resonance imaging, the BBB can be targeted in a precise location to permit diffusion of molecules only at the vicinity of the tumor, preventing side effects to healthy tissue. BBB opening can also be used to improve detection of cell-free tumor DNA with liquid biopsies, allowing non-invasive diagnosis and identification of molecular mutations. High-intensity FUS can cause tumor ablation via a hyperthermic effect. Additionally, FUS can stimulate immunological attack of tumor cells, can activate sonosensitizers to exert cytotoxic effects on tumor tissue, and can sensitize tumors to radiation therapy. Finally, another mechanism under investigation, known as histotripsy, produces tumor ablation via acoustic cavitation rather than thermal effects. [ABSTRACT FROM AUTHOR]

Augmented reality (AR) navigation refers to novel technologies that superimpose images, such as radiographs and navigation pathways, onto a view of the operative field. The development of AR navigation has focused on improving the safety and efficacy of neurosurgical and orthopedic procedures. In this review, the authors focus on 3 types of AR technology used in spine surgery: AR surgical navigation, microscope-mediated heads-up display, and AR head-mounted displays. Microscope AR and head-mounted displays offer the advantage of reducing attention shift and line-of-sight interruptions inherent in traditional navigation systems. With the U.S. Food and Drug Administration's recent clearance of the XVision AR system (Augmedics, Arlington Heights, IL), the adoption and refinement of AR technology by spine surgeons will only accelerate. [ABSTRACT FROM AUTHOR]

Background and Objectives: Oligodendrogliomas are defined by IDH1/2 mutation and codeletion of chromosome arms 1p/19q. Although previous studies identified CIC, FUBP1, and TERTp as frequently altered in oligodendrogliomas, the clinical relevance of these molecular signatures is unclear. Moreover, previous studies predominantly used research panels that are not readily available to providers and patients. Accordingly, we explore genomic alterations in molecularly defined oligodendrogliomas using clinically standardized next-generation sequencing (NGS) panels., Methods: A retrospective single-center study evaluated adults with pathologically confirmed IDH-mutant, 1p/19q-codeleted oligodendrogliomas diagnosed between 2005 and 2021. Genetic data from formalin-fixed, paraffin-embedded specimens were analyzed with the NGS Solid Tumor Panel at the Johns Hopkins Medical Laboratories, which tests more than 400 cancer-related genes. Kaplan-Meier plots and log-rank tests compared progression-free survival (PFS) and overall survival by variant status. χ2 tests, t-tests, and Wilcoxon rank-sum tests were used to compare clinical characteristics between genomic variant status in the 10 most frequently altered genes., Results: Two hundred and seventy-seven patients with molecularly defined oligodendrogliomas were identified, of which 95 patients had available NGS reports. Ten genes had 9 or more patients with a genomic alteration, with CIC, FUBP1, and TERTp being the most frequently altered genes (n = 60, 23, and 22, respectively). Kaplan-Meier curves showed that most genes were not associated with differences in PFS or overall survival. At earlier time points (PFS <100 months), CIC alterations conferred a reduction in PFS in patients (P = .038)., Conclusion: Our study confirms the elevated frequency of CIC, FUBP1, and TERTp alterations in molecularly defined oligodendrogliomas and suggests a potential relationship of CIC alteration to PFS at earlier time points. Understanding these genomic variants may inform prognosis or therapeutic recommendations as NGS becomes routine., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: Pedicle screw placement guidance is critical in spinal fusions, and spinal surgery robots aim to improve accuracy and reduce complications. Current literature has yet to compare the relative merits of available robotic systems. In this review, the authors aimed to 1) assess the current state of spinal robotics literature; 2) conduct a meta-analysis of robotic performance based on accuracy, speed, and safety; and 3) offer recommendations for robotic system selection., Methods: Following PRISMA guidelines, the authors conducted a systematic literature review across PubMed, Embase, Cochrane Library, Web of Science, and Scopus as of April 28, 2022, for studies on approved robots for placing lumbar pedicle screws. Three reviewers screened and extracted data relating to the study characteristics, accuracy rate, intraoperative revisions, and reoperations. Secondary performance metrics included operative time, blood loss, and radiation exposure. The authors statistically compared the performance of the robots using a random-effects model to account for variation within and between the studies. Each robot was also compared with performance benchmarks of traditional techniques including freehand, fluoroscopic, and CT-navigated insertion. Finally, we performed a Duval and Tweedie trim-and-fill test to assess for the presence of publication bias., Results: The authors identified 46 studies, describing 4670 patients and 25,054 screws, that evaluated 4 different robotic systems: Mazor X, ROSA, ExcelsiusGPS, and Cirq. The weighted accuracy rates of Gertzbein-Robbins classification grade A or B screws were as follows: ExcelsiusGPS, 98.0%; ROSA, 98.0%; Mazor, 98.2%; and Cirq, 94.2%. No robot was significantly more accurate than the others. However, the accuracy of the ExcelsiusGPS was significantly higher than that of traditional methods, and the accuracies of the Mazor and ROSA were significantly higher than that of fluoroscopy. The intraoperative revision rates were Cirq, 0.55%; ROSA, 0.91%; Mazor, 0.98%; and ExcelsiusGPS, 1.08%. The reoperation rates were Cirq, 0.28%; ExcelsiusGPS, 0.32%; and Mazor, 0.76% (no reoperations were reported for ROSA). Operative times were similar for all robots. Both the ExcelsiusGPS and Mazor were associated with significantly less blood loss than the ROSA. The Cirq had the lowest radiation exposure. Robots tended to be more accurate and generally their use was associated with fewer reoperations and less blood loss than freehand, fluoroscopic, or CT-navigated techniques., Conclusions: Robotic platforms perform comparably based on key metrics, with high accuracy rates and low intraoperative revision and reoperation rates. The spinal robotics publication rate will continue to accelerate, and choosing a robot will depend on the context of the practice.

Competing Interests: Competing interests: None declared.

Background: Synthetic computed tomography (sCT) can be created from magnetic resonance imaging (MRI) utilizing newer software. sCT is yet to be explored as a possible alternative to routine CT (rCT). In this study, rCT scans and MRI-derived sCT scans were obtained on a cadaver. Morphometric analysis was performed comparing the 2 scans. The ExcelsiusGPS robot was used to place lumbosacral screws with both rCT and sCT images., Observations: In total, 14 screws were placed. All screws were grade A on the Gertzbein-Robbins scale. The mean surface distance difference between rCT and sCT on a reconstructed software model was -0.02 ± 0.05 mm, the mean absolute surface distance was 0.24 ± 0.05 mm, and the mean absolute error of radiodensity was 92.88 ± 10.53 HU. The overall mean tip distance for the sCT versus rCT was 1.74 ± 1.1 versus 2.36 ± 1.6 mm (p = 0.24); mean tail distance for the sCT versus rCT was 1.93 ± 0.88 versus 2.81 ± 1.03 mm (p = 0.07); and mean angular deviation for the sCT versus rCT was 3.2° ± 2.05° versus 4.04°± 2.71° (p = 0.53)., Lessons: MRI-based sCT yielded results comparable to those of rCT in both morphometric analysis and robot-assisted lumbosacral screw placement in a cadaver study.

Objective: Here we investigate the ability of low-intensity ultrasound (LIUS) applied to the spinal cord to modulate the transmission of motor signals., Methods: Male adult Sprague-Dawley rats (n = 10, 250-300 g, 15 weeks old) were used in this study. Anesthesia was initially induced with 2% isoflurane carried by oxygen at 4 L/min via a nose cone. Cranial, upper extremity, and lower extremity electrodes were placed. A thoracic laminectomy was performed to expose the spinal cord at the T11 and T12 vertebral levels. A LIUS transducer was coupled to the exposed spinal cord, and motor evoked potentials (MEPs) were acquired each minute for either 5- or 10-minutes of sonication. Following the sonication period, the ultrasound was turned off and post-sonication MEPs were acquired for an additional 5 minutes., Results: Hindlimb MEP amplitude significantly decreased during sonication in both the 5- (p < 0.001) and 10-min (p = 0.004) cohorts with a corresponding gradual recovery to baseline. Forelimb MEP amplitude did not demonstrate any statistically significant changes during sonication in either the 5- (p = 0.46) or 10-min (p = 0.80) trials., Conclusion: LIUS applied to the spinal cord suppresses MEP signals caudal to the site of sonication, with recovery of MEPs to baseline after sonication., Significance: LIUS can suppress motor signals in the spinal cord and may be useful in treating movement disorders driven by excessive excitation of spinal neurons.

Background: Hemangiomas are common benign vascular lesions that rarely present with pain and neurological deficits. Symptomatic lesions are often treated with endovascular embolization. However, transarterial embolization can be technically challenging depending on the size and caliber of the vessels. Moreover, embolization can result in osteonecrosis and vertebral collapse., Observations: Here the authors report the first case of a T10 vertebral hemangioma treated with transpedicular Onyx embolization aided by a robotic platform that guided pedicle cannulation and Craig needle placement. An intravenous catheter was attached to the needle and dimethylsulfoxide was infused, followed by Onyx under real-time fluoroscopy. Repeat angiography demonstrated significantly reduced contrast opacification of the vertebral body without compromise of the segmental artery. A T9-11 pedicle screw fixation was performed to optimize long-term stability. The patient's symptoms improved and was stable at the 6-month follow-up., Lessons: Transpedicular embolization of vertebral hemangiomas can be performed successfully under robotic navigation guidance, avoiding complications seen with the intra-arterial approach and allowing for simultaneous pedicle screw fixation to prevent collapse and delayed kyphotic deformity. During the same procedure, a biopsy specimen can be collected for pathology. This technique can help to alleviate patient symptoms while avoiding complications associated with transarterial embolization or open resection.

Low-intensity focused ultrasound (LIFU) uses ultrasonic pulsations at lower intensities than ultrasound and is being tested as a reversible and precise neuromodulatory technology. Although LIFU-mediated blood-brain barrier (BBB) opening has been explored in detail, no standardized technique for blood-spinal cord barrier (BSCB) opening has been established to date. Therefore, this protocol presents a method for successful BSCB disruption using LIFU sonication in a rat model, including descriptions of animal preparation, microbubble administration, target selection and localization, as well as BSCB disruption visualization and confirmation. The approach reported here is particularly useful for researchers who need a fast and cost-effective method to test and confirm target localization and precise BSCB disruption in a small animal model with a focused ultrasound transducer, evaluate the BSCB efficacy of sonication parameters, or explore applications for LIFU at the spinal cord, such as drug delivery, immunomodulation, and neuromodulation. Optimizing this protocol for individual use is recommended, especially for advancing future preclinical, clinical, and translational work.

Spinal cord injury (SCI) is a devastating disease with limited effective treatment options. Animal paradigms are vital for understanding the pathogenesis of SCI and testing potential therapeutics. The porcine model of SCI is increasingly favored because of its greater similarity to humans. However, its adoption is limited by the complexities of care and range of testing parameters. Researchers need to consider swine selection, injury method, post-operative care, rehabilitation, behavioral outcomes, and histology metrics. Therefore, we systematically reviewed full-text English-language articles to evaluate study characteristics used in developing a porcine model and summarize the interventions that have been tested using this paradigm. A total of 63 studies were included, with 33 examining SCI pathogenesis and 30 testing interventions. Studies had an average sample size of 15 pigs with an average weight of 26 kg, and most used female swine with injury to the thoracic cord. Injury was most commonly induced by weight drop with compression. The porcine model is amenable to testing various interventions, including mean arterial pressure augmentation ( n  = 7), electrical stimulation ( n  = 6), stem cell therapy ( n  = 5), hypothermia ( n  = 2), biomaterials ( n  = 2), gene therapy ( n  = 2), steroids ( n  = 1), and nanoparticles ( n  = 1). It is also notable for its clinical translatability and is emerging as a valuable pre-clinical study tool. This systematic review can serve as a guideline for researchers implementing and testing the porcine SCI model., Competing Interests: Nicholas Theodore has received royalties from, holds stock ownership in, has consulted for, and has served on the scientific advisory board/other office for Globus Medical., (© Carly Weber-Levine et al., 2022; Published by Mary Ann Liebert, Inc.)