Purpose
To assess the rate, timing of diagnosis, and repairing strategies of vascular injuries in thoracic and lumbar spine surgery as their relationship to the approach.
Methods
PubMed, Medline, and ...Embase databases were utilized for a comprehensive literature search based on keywords and mesh terms to find articles reporting iatrogenic vascular injury during thoracic and lumbar spine surgery. English articles published in the last ten years were selected. The search was refined based on best match and relevance.
Results
Fifty-six articles were eligible, for a cumulative volume of 261 lesions. Vascular injuries occurred in 82% of instrumented procedures and in 59% during anterior approaches. The common iliac vein (CIV) was the most involved vessel, injured in 49% of anterior lumbar approaches. Common iliac artery, CIV, and aorta were affected in 40%, 28%, and 28% of posterior approaches, respectively. Segmental arteries were injured in 68% of lateral approaches. Direct vessel laceration occurred in 81% of cases and recognized intraoperatively in 39% of cases.
Conclusions
Incidence of iatrogenic vascular injuries during thoracic and lumbar spine surgery is low but associated with an overall mortality rate up to 65%, of which less than 1% for anterior approaches and more than 50% for posterior ones.
Anterior approaches for instrumented procedures are at risk of direct avulsion of CIV. Posterior instrumented fusions are at risk for injuries of iliac vessels and aorta. Lateral routes are frequently associated with lesions of segmental vessels. Suture repair and endovascular techniques are useful in the management of these severe complications.
Aberrant nitric oxide synthase 2 (NOS2) expression has been suggested as an interesting therapeutic target that is being implicated as a component of the molecular profile of several human malignant ...tumors, including glioblastoma, which is the most aggressive brain tumor with limited therapeutic options and poor prognosis. The aim of the present work was to evaluate the effect of 1400W, a specific NOS2 inhibitor, on human glioma cells in terms of clonogenic potential, proliferation, migration rate, and neurosphere generation ability. NOS2 expression was determined by Western blotting. Nitric oxide (NO) production was measured through nitrite level determination. The trypan blue exclusion test and the plate colony formation assay were performed to evaluate cell proliferation and clonogenic potential. Cell proliferation and migration ability was assessed by the
wound-healing assay. Neurosphere generation in a specific stemcell medium was investigated. NOS2 was confirmed to be expressed in both the glioma cell line and a human glioma primary culture, and overexpressed in relative derived neurospheres. Experiments that aimed to evaluate the influence of 1400W on U-87 MG, T98G (glioblastoma cell lines) and primary glioma cells sustained the crucial role played by NOS2 in proliferation, colony formation, migration, and neurosphere generation, thus supporting the emerging relevance of a NOS2/NO system as a prognostic factor for glioma malignancy and recurrence.
The relevance of nitric oxide synthase 2 (NOS2) as a prognostic factor in Glioblastoma Multiforme (GBM) malignancy is emerging. We analyzed the effect of NOS2 inhibitor 1400W on the autophagic flux ...and extracellular vesicle (EV) secretion in U87MG glioma cells. The effects of glioma stem cells (GSC)-derived EVs on adherent U87MG were evaluated. Cell proliferation and migration were examined while using Cell Counting Kit-8 assay (CCK-8) and scratch wound healing assay. Cell cycle profile and apoptosis were analyzed by flow cytometry. Autophagy-associated acidic vesicular organelles were detected and quantified by acridine orange staining. The number and size of EVs were assessed by nanoparticle tracking analysis. EV ultrastructure was verified by transmission electron microscopy (TEM). WB was used to analyze protein expression and acid sphingomyelinase was determined through ceramide levels. 1400W induced autophagy and EV secretion in both adherent U87MG and GSCs. EVs secreted by 1400W-treated GSC, but not those from untreated cells, were able to inhibit adherent U87MG cell growth and migration while also inducing a relevant level of autophagy. The hypothesis of NOS2 expression as GBM profile marker or interesting therapeutic target is supported by our findings. Autophagy and EV release following treatment with the NOS2 inhibitor could represent useful elements to better understand the complex biomolecular frame of GBM.
To review and discuss surgical treatment options for giant intracranial aneurysms (GIAs), focusing on indications, technical aspects, and results, along with some illustrative cases.
We reviewed the ...data of 82 consecutive patients surgically managed between January 2000 and December 2019 for treatment of a GIA.
Male sex and hemorrhage at presentation were prevalent. The average follow-up was 81.2 ± 45 months. The anterior circulation was involved in 76.8% of GIAs. If the GIA showed a clear neck, minimal atherosclerosis, or intrasaccular thrombosis, and ≤2 branches arising from the neck, it was reconstructed. This procedure was possible in 78% of cases. The technique also involved temporary clipping, remodeling, and thrombectomy, as well as fragmentation techniques. Angioarchitectural features other than these techniques underwent bypass and aneurysm trapping. Most bypasses were extracranial to intracranial and high flow. Flow capacity, collateral circulation, and availability of the donor vessel mainly affected the choice of the type of bypass. Overall, successful exclusion of the GIA was 91.4%. The need for retreatment and complication rate were 3.6% and 19.5%, respectively. A good overall outcome (modified Rankin Scale score 0–3) was achieved in 84.2% of patients, and mortality was 10%.
Microneurosurgical techniques still maintain a significant role for most GIAs, with a high durability and acceptable rate of morbidity and mortality. Clip reconstruction is the first-line surgical treatment option, whereas bypass is indicated in cases of planned or unplanned sacrifice of the parent artery to prevent long-term ischemic complications.
Introduction
During surgery for lesions in eloquent areas the goal is to achieve the widest resection possible, without loss of neurological function. Intraoperative seizures may lead to abandonment ...of the procedure or damages to the patient. Awareness regarding the predictors of IOS would help the surgeon. The aim of this retrospective study was to identify the factors associated with the occurrence of IOS in patients who underwent awake surgery for removal of gliomas in eloquent areas.
Methods
This was a retrospective analysis of prospectively collected data of 109 patients who underwent awake craniotomy between January 2010 and December 2017 for removal of gliomas. IOS were defined as tonic–clonic seizures or loss of consciousness resulting in communication difficulties with the patient occurring during cortical and subcortical mapping.
Results
A total of 109 patients were included in this study and IOS occurred in 9 (8.2%) patients. Demographic and clinical factors were comparable between patients with and without IOS. In the IOS group, 7 (77.8%) patients had seizures preoperatively and 4 (57.1%) were on more than one perioperative antiepileptic drugs (AED).
Conclusions
The current series add some hints to the poorly studied IOS risk during awake surgery. The risk of IOS appears to be relatively higher in patients with anteriorly located tumors and in patients operated without intraoperative brain activity monitoring and different patterns of stimulation for language and sensory-motor mapping. Further studies are needed to clarify the role of intraoperative techniques.
The resilience of high-grade gliomas (HGGs) against conventional chemotherapies is due to their heterogeneous genetic landscape, adaptive phenotypic changes, and immune escape mechanisms. Innovative ...immunotherapies have been developed to counteract the immunosuppressive capability of gliomas. Nevertheless, further research is needed to assess the efficacy of the immuno-based approach. The aim of this study is to review the newest immunotherapeutic approaches for glioma, focusing on the drug types, mechanisms of action, clinical pieces of evidence, and future challenges. A PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)-based literature search was performed on PubMed/Medline and ClinicalTrials.gov databases using the keywords "active/adoptive immunotherapy," "monoclonal antibodies," "vaccine," and "engineered T cell.", combined with "malignant brain tumor", "high-grade glioma." Only articles written in English published in the last 10 years were selected, filtered based on best relevance. Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. In several preclinical and clinical trials, adoptive immunotherapies, including T, natural killer, and natural killer T engineered cells, have been shown to be potential treatment options for relapsing gliomas. Systemic temozolomide is considered the backbone for newly diagnosed HGGs. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed.
Introduction: PTEN gene mutations are frequently found in the genetic landscape of high-grade gliomas since they influence cell proliferation, proangiogenetic pathways, and antitumoral immune ...response. The present bioinformatics analysis explores the PTEN gene expression profile in HGGs as a prognostic factor for survival, especially focusing on the related immune microenvironment. The effects of PTEN mutation on the susceptibility to conventional chemotherapy were also investigated. Methods: Clinical and genetic data of GBMs and normal tissue samples were acquired from The Cancer Genome Atlas (TCGA)-GBM and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan−Meier survival curves were applied to estimate the overall survival (OS) and disease-free survival (DFS). The Genomics of Drug Sensitivity in Cancer platform was chosen to assess the response of PTEN-mutated GBMs to temozolomide (TMZ). p < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and PTEN status was assessed through Spearman’s correlation analysis. Results: PTEN was found mutated in 22.2% of the 617 TCGA-GBMs patients, with a higher log2-transcriptome per million reads compared to the GTEx group (255 samples). Survival curves revealed a worse OS and DFS, albeit not significant, for the high-PTEN profile GBMs. Spearman’s analysis of immune cells demonstrated a strong positive correlation between the PTEN status and infiltration of Treg (ρ = 0.179) and M2 macrophages (ρ = 0.303). The half-maximal inhibitor concentration of TMZ was proven to be lower for PTEN-mutated GBMs compared with PTEN wild-types. Conclusions: PTEN gene mutations prevail in GBMs and are strongly related to poor prognosis and least survival. The infiltrating immune lymphocytes Treg and M2 macrophages populate the glioma microenvironment and control the mechanisms of tumor progression, immune escape, and sensitivity to standard chemotherapy. Broader studies are required to confirm these findings and turn them into new therapeutic perspectives.
microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and ...progression of brain arteriovenous malformations (bAVMs). Accordingly, here we examine miRNA signatures related to bAVMs and associated gene expression. In so doing we expound on the potential prognostic, diagnostic, and therapeutic significance of miRNAs in the clinical management of bAVMs.
A PRISMA-based literature review was performed using PubMed/Medline database with the following search terms: "brain arteriovenous malformations", "cerebral arteriovenous malformations", "microRNA", and "miRNA". All preclinical and clinical studies written in English, regardless of date, were selected. For our bioinformatic analyses, miRWalk and miRTarBase machine learning algorithms were employed; the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was quired for associated pathways/functions.
four studies were ultimately included in the final analyses. Sequencing data consistently revealed the decreased expression of miR-18a in bAVM-endothelial cells, resulting in increased levels of vascular endodermal growth factor (VEGF), Id-1, matrix metalloproteinase, and growth signals. Our analyses also suggest that the downregulation of miR-137 and miR-195* within vascular smooth muscle cells (VSMCs) may foster the activation of inflammation, aberrant angiogenesis, and phenotypic switching. In the peripheral blood, the overexpression of miR-7-5p, miR-629-5p, miR-199a-5p, miR-200b-3p, and let-7b-5p may contribute to endothelial proliferation and nidus development. The machine learning algorithms employed confirmed associations between miRNA-related target networks, vascular rearrangement, and bAVM progression.
miRNAs expression appears to be critical in managing bAVMs' post-transcriptional signals. Targets of microRNAs regulate canonical vascular proliferation and reshaping. Although additional scientific evidence is needed, the identification of bAVM miRNA signatures may facilitate the development of novel prognostic/diagnostic tools and molecular therapies for bAVMs.
Introduction: High-grade gliomas (HGGs) still have a high rate of recurrence and lethality. Gene therapies were projected to overcome the therapeutic resilience of HGGs, due to the intrinsic genetic ...heterogenicity and immune evasion pathways. The present literature review strives to provide an updated overview of the novel gene therapies for HGGs treatment, highlighting evidence from clinical trials, molecular mechanisms, and future perspectives. Methods: An extensive literature review was conducted through PubMed/Medline and ClinicalTrials.gov databases, using the keywords “high-grade glioma,” “glioblastoma,” and “malignant brain tumor”, combined with “gene therapy,” “oncolytic viruses,” “suicide gene therapies,” “tumor suppressor genes,” “immunomodulatory genes,” and “gene target therapies”. Only articles in English and published in the last 15 years were chosen, further screened based on best relevance. Data were analyzed and described according to the PRISMA guidelines. Results: Viruses were the most vehicles employed for their feasibility and transduction efficiency. Apart from liposomes, other viral vehicles remain largely still experimental. Oncolytic viruses and suicide gene therapies proved great results in phase I, II preclinical, and clinical trials. Tumor suppressor, immunomodulatory, and target genes were widely tested, showing encouraging results especially for recurrent HGGs. Conclusions: Oncolytic virotherapy and suicide genes strategies are valuable second-line treatment options for relapsing HGGs. Immunomodulatory approaches, tumor suppressor, and target genes therapies may implement and upgrade standard chemoradiotherapy. Future research aims to improve safety profile and prolonging therapeutic effectiveness. Further clinical trials are needed to assess the efficacy of gene-based therapies.
The management of thoracolumbar junction (TLJ) fractures, involving the restoring anatomical stability and biomechanics properties, still remains a challenge for neurosurgeons.Despite the high ...frequency of these injuries, specific treatment guidelines, set on biomechanical properties, have not yet been assumed. The present study is meant to propose an evidence-based treatment algorithm. The primary aim for the protocol validation was the assessment of postoperative neurological recovery. The secondary objectives concerned the evaluation of residual deformity and rate of hardware failure. Technical nuances of surgical approaches and drawbacks were further discussed.
Clinical and biomechanical data of patients harboring a single TLJ fracture, surgically managed between 2015 and 2020, were collected. Patients' cohorts were ranked into 4 groups according to Magerl's Type, McCormack Score, Vaccaro PLC point, Canal encroachment, and Farcy Sagittal Index. The outcome measures were the early/late Benzel-Larson Grade and postoperative kyphosis degree to estimate neurological status and residual deformity, respectively.
32 patients were retrieved, 7, 9, 8, and 8 included within group 1, 2, 3, and 4, respectively. Overall neurological outcomes significantly improved for all patients at every follow-up stage (p < 0.0001). Surgeries gained a complete restoration of post-traumatic kyphosis in the entire cohort (p < 0.0001), except for group 4 which experienced a later worsening of residual deformity.
The choice of the most appropriate surgical approach for TLJ fractures is dictated by morphological and biomechanical characteristics of fracture and the grade of neurological involvement. The proposed surgical management protocol was reliable and effective, although further validations are needed.
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