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High-grade gliomas are aggressive tumors that require multimodal management and gross total resection is considered to be the first crucial step of treatment. Because of their infiltrative nature, intraoperative differentiation of neoplastic tissue from normal parenchyma can be challenging. For these reasons, in the recent years, neurosurgeons have increasingly performed this surgery under the guidance of tissue fluorescence. Sodium fluoresceine and 5-aminolevulinic acid represent the 2 main compounds that allow real-time identification of residual malignant tissue and have been associated with improved gross total resection and radiological outcomes. Though presenting different profiles of sensitivity and specificity and further investigations concerning cost-effectiveness are need, Sodium fluoresceine, 5-aminolevulinic acid and new phluorophores, such as Indocyanine green, represent some of the most important tools in the neurosurgeon’s hands to achieve gross total resection.

PurposeRelated to the development and diffusion of ALIF and XLIF, it is possible to correct sagittal malalignment in selected cases of lumbar degenerative discopathy with a relatively low invasiveness. Still, the malposition or the inappropriate size of the implanted cages may lead to the subsidence of the vertebral endplates with loss of correction as well as a decrease in the potential to restore spinal biomechanics in the long run. The aim of this study is to evaluate safety, feasibility, and preliminary clinical and radiological results when using custom-made, trabecular titanium cages in ALIF and XLIF procedures. MethodsWe prospectively evaluated 18 consecutive patients who underwent either an ALIF or an XLIF procedure with the implant of a custom-made, trabecular titanium cage for lumbar degenerative disease with sagittal imbalance, with a minimum of 1-year clinical and radiological follow-up. ResultsAfter a mean follow-up of 14 months, the Oswestry score dropped to a mean of 13 from a preoperative value of 48 (p < 0.0001). Lumbar lordosis was significantly improved, especially in the lower lumbar segment L4-S1 (+ 11 ± 7°; p < 0.0001). No cases of subsidence were noted.ConclusionsCustom-made, trabecular titanium cages allowed a segmental, steady, durable sagittal correction via ALIF and XLIF approaches. The absence of cage subsidence at 1 year encourages further studies on a larger cohort with longer follow-up.Graphic abstractThese slides can be retrieved under Electronic Supplementary Material.

Background: Progressive multifocal leukoencephalopathy (PML) is a rare but fatal disease caused by John Cunningham virus (JCV) in immunocompromised individuals, with no effective antiviral treatment currently available. This study aimed to evaluate the feasibility of adoptive JCV-specific T lymphocyte therapy in patients with PML. Methods: Nineteen patients meeting the 2013 consensus criteria for “definite PML” were included, and JCV-specific T lymphocytes expanded from autologous or allogeneic peripheral blood mononuclear cells (PBMCs) using JCV antigen-derived peptides were administered. Clinical outcomes were monitored through neuroimaging and biological markers. Results: The mean age at diagnosis was 56.5 years, with a mean time to treatment of three months. Patients received a median of two infusions. At 12 months, six patients (31.6%) survived, while 13 (68.4%) had died, primarily due to PML progression. Survivors had a higher median baseline Karnofsky performance scale (KPS) score (50% vs. 30%, p = 0.41) and a significantly shorter diagnosis delay. MRI assessment showed a reduced disease burden in survivors, and JCV-DNA copy numbers decreased overall. One case of immune reconstitution inflammatory syndrome (IRIS) was observed. Conclusions: Adoptive JCV-specific T lymphocytes may represent a safe therapeutic option for PML patients, and the MRI burden and JCV-DNA copy may serve as biomarkers for disease monitoring.

Spine degenerative conditions are becoming increasingly prevalent, affecting about 5.7% of the population in Europe, resulting in a significant reduction of life’s quality. Up to now, many materials have been used in manufacturing cage implants, used as graft substitutes, to achieve immediate and long-term spinal fixation. Particularly, titanium and its alloys are emerging as valuable candidates to develop new types of cages. The aim of this in vitro study was to evaluate the adhesion, proliferation and osteogenic differentiation of adipose derived mesenchymal stem cells (ASCs) seeded on trabecular titanium cages. ASCs adhered, proliferated and produced an abundant extracellular matrix during the 3 weeks of culture. In the presence of osteogenic medium, ASCs differentiated into osteoblast-like cells: the expression of typical bone genes, as well as the alkaline phosphatase activity, was statistically higher than in controls. Furthermore, the dispersive spectrometry microanalysis showed a marked increase of calcium level in cells grown in osteogenic medium. Plus, our preliminary data about osteoinduction suggest that this titanium implant has the potential to induce the ASCs to produce a secretome able to trigger a shift in the ASCs phenotype, possibly towards the osteogenic differentiation, as illustrated by the qRT-PCR and ALP biochemical assay results. The trabecular porous organization of these cages is rather similar to the cancellous bone structure, thus allowing the bone matrix to colonize it efficiently; for these reasons we can conclude that the architecture of this cage may play a role in modulating the osteoinductive capabilities of the implant, thus encouraging its engagement in in vivo studies for the treatment of spinal deformities and diseases.

Study Design: Literature review. Objectives: An increasing number of obese patients requires operative care for degenerative spinal disorders. The aim of this review is to analyze the available evidence regarding the role of obesity on outcomes after spine surgery. Peri-operative complications and clinical results are evaluated for both cervical and lumbar surgery. Furthermore, the contribution of MIS techniques for lumbar surgery to play a role in reducing risks has been analyzed. Methods: Only articles published in English in the last 10 years were reviewed. Inclusion criteria of the references were based on the scope of this review, according to PRISMA guidelines. Moreover, only paper analyzing obesity-related complications in spine surgery have been selected and thoroughly reviewed. Each article was classified according to its rating of evidence using the Sacket Grading System. Results: A total number of 1636 articles were found, but only 130 of them were considered to be relevant after thorough evaluation and according to PRISMA checklist. The majority of the included papers were classified according to the Sacket Grading System as Level 2 (Retrospective Studies). Conclusion: Evidence suggest that obese patients could benefit from spine surgery and outcomes be satisfactory. A higher rate of peri-operative complications is reported among obese patients, especially in posterior approaches. The use of MIS techniques plays a key role in order to reduce surgical risks. Further studies should evaluate the role of multidisciplinary counseling between spine surgeons, nutritionists and bariatric surgeons, in order to plan proper weight loss before elective spine surgery.

Abstract PurposeDegenerative spondylolisthesis (DS) is a debilitating condition that carries a high economic burden. As the global population ages, the number of patients over 80 years old demanding spinal fusion is constantly rising. Therefore, neurosurgeons often face the important decision as to whether to perform surgery or not in this age group, commonly perceived at high risk for complications.MethodsSix hundred seventy-eight elder patients, who underwent posterolateral lumbar fusion for DS (performed in three different centers) from 2012 to 2020, were screened for medical, early and late surgical complications and for the presence of potential preoperative risk factors. Patients were divided in three categories based on their age: (1) 60–69 years, (2) 70–79 years, (3) 80 and over. Multiple logistic regression was used to determine the predictive power of age and of other risk factors (i.e., ASA score; BMI; sex; presence or absence of insulin-dependent and -independent diabetes, use of anticoagulants, use of antiaggregants and osteoporosis) for the development of postoperative complications.ResultsIn univariate analysis, age was significantly and positively correlated with medical complications. However, when controls for other risk factors were added in the regressions, age never reached significance, with the only noticeable exception of cerebrovascular accidents. ASA score and BMI were the two risk factors that significantly correlated with the higher numbers of complication rates (especially medical).ConclusionPatients of different age but with comparable preoperative risk factors share similar postoperative morbidity rates. When considering octogenarians for lumbar arthrodesis, the importance of biological age overrides that of chronological.

Glioblastoma (GBM) is the most common and aggressive central nervous system tumor, requiring multimodal management. Due to its malignant behavior and infiltrative growth pattern, GBM is one of the most difficult tumors to treat and gross total resection is still considered to be the first crucial step. The deep understanding of GBM microenvironment and the possibility of manipulating the patient’s innate and adaptive immune system to fight the neoplasm represent the base of immunotherapeutic strategies that currently express the future for the fight against GBM. Despite the immunotherapeutic approach having been successfully adopted in several solid and haematologic neoplasms, immune resistance and the immunosuppressive environment make the use of these strategies challenging in GBM treatment. We describe the most recent updates regarding new therapeutic strategies that target the immune system, immune checkpoint inhibitors, chimeric antigen receptor T cell therapy, peptide and oncolytic vaccines, and the relevant mechanism of immune resistance. However, no significant results have yet been obtained in studies targeting single molecules/pathways. The future direction of GBM therapy will include a combined approach that, in contrast to the inescapable current treatment modality of maximal resection followed by chemo- and radiotherapy, may combine a multifaceted immunotherapy treatment with the dual goals of directly killing tumor cells and activating the innate and adaptive immune response.

PurposeThe eXtreme Lateral Interbody Fusion (XLIF) approach has gained increasing importance in the last decade. This multicentric retrospective cohort study aims to assess the incidence of major complications in XLIF procedures performed by experienced surgeons and any relationship between the years of experience in XLIF procedures and the surgeon’s rate of severe complications.MethodsNine Italian members of the Society of Lateral Access Surgery (SOLAS) have taken part in this study. Each surgeon has declared how many major complications have been observed during his surgical experience and how they were managed. A major complication was defined as an injury that required reoperation, or as a complication, whose sequelae caused functional limitations to the patient after one year postoperatively. Each surgeon was finally asked about his years of experience in spine surgery and XLIF approach. Pearson correlation test was used to evaluate the association between the surgeon’s years of experience in XLIF and the rate of major complications; a p-value of last than 0.05 was considered significant.ResultsWe observed 14 major complications in 1813 XLIF procedures, performed in 1526 patients. The major complications rate was 0.7722%. Ten complications out of fourteen needed a second surgery. Neither cardiac nor respiratory nor renal complications were observed. No significant correlation was found between the surgeon's years of experience in the XLIF procedure and the number of major complications observed.ConclusionXLIF revealed a safe and reliable surgical procedure, with a very low rate of major complications, when performed by an expert spine surgeon.