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66 result(s) for "Cofano, Fabio"
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Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy
Spinal cord injury (SCI) constitutes an inestimable public health issue. The most crucial phase in the pathophysiological process of SCI concerns the well-known secondary injury, which is the uncontrolled and destructive cascade occurring later with aberrant molecular signaling, inflammation, vascular changes, and secondary cellular dysfunctions. The use of mesenchymal stem cells (MSCs) represents one of the most important and promising tested strategies. Their appeal, among the other sources and types of stem cells, increased because of their ease of isolation/preservation and their properties. Nevertheless, encouraging promise from preclinical studies was followed by weak and conflicting results in clinical trials. In this review, the therapeutic role of MSCs is discussed, together with their properties, application, limitations, and future perspectives.
Systematic Review on Tumor Microenvironment in Glial Neoplasm: From Understanding Pathogenesis to Future Therapeutic Perspectives
Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved.
Laser Interstitial Thermotherapy (LITT) in Recurrent Glioblastoma: What Window of Opportunity for This Treatment?
Laser Interstitial Thermotherapy is a minimally invasive treatment option in neurosurgery for intracranial tumors, including recurrent gliomas. The technique employs the thermal ablation of target tissue to achieve tumor control with real-time monitoring of the extent by magnetic resonance thermometry, allowing targeted thermal injury to the lesion. Laser Interstitial Thermotherapy has gained interest as a treatment option for recurrent gliomas due to its minimally invasive nature, shorter recovery times, ability to be used even in patients with numerous comorbidities, and potential to provide local tumor control. It can be used as a standalone treatment or combined with other therapies, such as chemotherapy or radiation therapy. We describe the most recent updates regarding several studies and case reports that have evaluated the efficacy and safety of Laser Interstitial Thermotherapy for recurrent gliomas. These studies have reported different outcomes, with some demonstrating promising results in terms of tumor control and patient survival, while others have shown mixed outcomes. The success of Laser Interstitial Thermotherapy depends on various factors, including tumor characteristics, patient selection, and the experience of the surgical team, but the future direction of treatment of recurrent gliomas will include a combined approach, comprising Laser Interstitial Thermotherapy, particularly in deep-seated brain regions. Well-designed prospective studies will be needed to establish with certainty the role of Laser Interstitial Thermotherapy in the treatment of recurrent glioma.
Accuracy and Safety Between Robot-Assisted and Conventional Freehand Fluoroscope-Assisted Placement of Pedicle Screws in Thoracolumbar Spine: Meta-Analysis
Background and Objectives: Robotic-assisted surgery (RS) has progressively emerged as a promising technology in modern thoracolumbar spinal surgery, offering the potential to enhance accuracy and improve clinical outcomes. To date, the benefits of robot-assisted techniques in thoracolumbar spinal surgery remain controversial. The objective of this study was to assess the efficacy and safety of RS compared to fluoroscopy-assisted surgery (FS) in spinal fusion procedures. Materials and Methods: In accordance with the PRISMA guidelines, a systematic review and meta-analysis was conducted, using REVMAN V5.3 software. The review protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO) website with the following registration number: CRD42024567193. Results: Eighteen studies were included in the meta-analysis with a total of 1566 patients examined. The results demonstrated a worse accuracy in FS in cases with major violations of the peduncular cortex (D–E grades, according to Gertzbein’s classification) [(odds ratio (OR) 0.47, 95%-CI 0.28 to 0.80, I2 0%]. In addition, a lower complication rate was shown in the RS group compared to the FS group, specifically regarding the need for surgical revision due to screw mispositioning (OR 0.28-CI 0.17 to 0.48, I2 98%). Conclusions: Advantages of robot-assisted techniques were demonstrated in terms of postoperative complications, revision surgery rates, and the accuracy of screw placement. While RS represents a valuable and promising technological advancement in thoracolumbar spinal surgery, future studies are needed to further explore its advantages in thoracolumbar spinal surgery and to identify which spinal surgical approach has greater advantages when using the robot.
Fluorescence-Guided Surgery for High-Grade Gliomas: State of the Art and New Perspectives
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.
Skull base reconstruction: A question of flow? A critical analysis of 521 endoscopic endonasal surgeries
Post-operative CSF leak still represents the main drawback of Endoscopic Endonasal Approach (EEA), and different reconstructive strategies have been proposed in order to decrease its rate. To critically analyze the effectiveness of different adopted reconstruction strategies in patients that underwent EEA. Adult patients with skull base tumor surgically treated with EEA were retrospectively analyzed. Data recorded for each case concerned patient demographics, type of surgical approach, histotype, anatomical site of surgical approach, intra-operative CSF leak grade (no leak (INL), low flow (ILFL), high flow (IHFL)), reconstructive adopted strategy, Lumbar Drain positioning, post-operative CSF leak rate and intra/post-operative complications. A total number of 521 patients (January 2012-December 2019) was included. Intra-operative CSF leak grade showed to be associated with post-operative CSF leak rate. In particular, the risk to observe a post-operative CSF leak was higher when IHFL was encountered (25,5%; Exp(B) 16.25). In particular, vascularized multilayered reconstruction and fat use showed to be effective in lowering post-operative CSF leaks in IHFL (p 0.02). No differences were found considering INL and ILFL groups. Yearly post-operative CSF leak rate analysis showed a significative decreasing trend. Intra-operative CSF leak grade strongly affected post-operative CSF leak rate. Multilayer reconstruction with fat and naso-septal flap could reduce the rate of CSF leak in high risk patients. Reconstructive strategies should be tailored according also to the type and the anatomical site of the approach.
Ventriculoatrial shunt remains a safe surgical alternative for hydrocephalus: a systematic review and meta-analysis
Hydrocephalus is a commonly encountered pathology in the neurosurgical practice. Since the first permanent ventriculo-subarachnoid-subgaleal shunt described by Mikulicz in 1893, there were multiple attempts to find solutions for draining the excess production/less reabsorption of the cerebrospinal fluid (CSF) from the brain. Nowadays, the most common technique is the ventriculoperitoneal shunt (VPS), whereas the ventriculoatrial shunt (VAS) is applied only in some rare conditions. To date there are still no specific guidelines or strong evidence in literature that guide the surgeon in the choice between the two methods, and the decision usually relies on the confidence and expertise of the surgeon. Considering the lack of established recommendations, this systematic review and meta-analysis aims to evaluate the effectiveness and safety of these two shunting techniques. This systematic review was conducted following the PRISMA protocol (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). No chronological limits of study publications were included. Prospective and retrospective clinical studies, and reports of case series with at least five patients per group and reporting data on comparison between VAS and VPS techniques were eligible for inclusion. Nine studies reporting 3197 patients meeting the inclusion and exclusion criteria were identified and included in the quantitative synthesis. The risk of shunt dysfunction/obstruction was significantly lower in the VAS group [odds ratio (OR) 0.49, 95%-CI 0.34–0.70, I 2 0%]. The risk of infection was not significantly different between the two groups (OR 1.02, 95%-CI 0.59–1.74, I 2 0%). The risk of revision was not significantly different between the two groups; however, the heterogeneity between the studies was significant (OR 0.73, 95%-CI 0.36–1.49, I 2 91%). Additionally, the risk of death was not significantly different between the two groups; however, the heterogeneity between the studies was high (OR 1.93, 95%-CI 0.81–4.62, I 2 64%). VAS remains a safe surgical alternative for hydrocephalus. The results of this study highlight a lower risk of shunt dysfunction/obstruction variable in the VAS group, with no significant statistical differences regarding the occurrence of at least one infection-related complication. In consequence, the choice between these two techniques must be tailored to the specific characteristics of the patient. Protocol Registration : The review protocol was registered and published in Prospective Register of Systematic Reviews (PROSPERO) ( www.crd.york.ac.uk/PROSPERO ) website with registration number: CRD42023479365.
Osteogenic potential of human adipose derived stem cells (hASCs) seeded on titanium trabecular spinal cages
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.
Deep Learning for MRI Segmentation and Molecular Subtyping in Glioblastoma: Critical Aspects from an Emerging Field
Deep learning (DL) has been applied to glioblastoma (GBM) magnetic resonance imaging (MRI) assessment for tumor segmentation and inference of molecular, diagnostic, and prognostic information. We comprehensively overviewed the currently available DL applications, critically examining the limitations that hinder their broader adoption in clinical practice and molecular research. Technical limitations to the routine application of DL include the qualitative heterogeneity of MRI, related to different machinery and protocols, and the absence of informative sequences, possibly compensated by artificial image synthesis. Moreover, taking advantage from the available benchmarks of MRI, algorithms should be trained on large amounts of data. Additionally, the segmentation of postoperative imaging should be further addressed to limit the inaccuracies previously observed for this task. Indeed, molecular information has been promisingly integrated in the most recent DL tools, providing useful prognostic and therapeutic information. Finally, ethical concerns should be carefully addressed and standardized to allow for data protection. DL has provided reliable results for GBM assessment concerning MRI analysis and segmentation, but the routine clinical application is still limited. The current limitations could be prospectively addressed, giving particular attention to data collection, introducing new technical advancements, and carefully regulating ethical issues.