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.
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.
The possible benefits of using semantic language models in the early diagnosis of major ischemic stroke (MIS) based on artificial intelligence (AI) are still underestimated. The present study strives ...to assay the feasibility of the word2vec word embedding-based model in decreasing the risk of false negatives during the triage of patients with suspected MIS in the emergency department (ED).
The main ICD-9 codes related to MIS were used for the 7-year retrospective data collection of patients managed at the ED with a suspected diagnosis of stroke. The data underwent "tokenization" and "lemmatization". The word2vec word-embedding algorithm was used for text data vectorization.
Out of 648 MIS, the word2vec algorithm successfully identified 83.9% of them, with an area under the curve of 93.1%.
Natural language processing (NLP)-based models in triage have the potential to improve the early detection of MIS and to actively support the clinical staff.
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.
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.
Optic foraminotomy (OF) has been recently proposed as an alternative to anterior clinoidectomy (AC) for selected types of paraclinoid aneurysms. In this study, OF and AC were compared for small ...superior-projecting paraclinoid aneurysms assuming visual and angiographic results as outcome measures. Indications for OF are also discussed.
Data of patients who underwent surgery for a paraclinoid aneurysm in the last 10 years were collected across 3 tertiary hospitals. Small to regular-size and superior projecting aneurysms were sorted. Multiple and complex aneurysms were excluded. Records of patients who went through OF were compared with those of patients who underwent AC. Neurologic outcome was reported as a modified Rankin Scale. Aneurysm complete occlusion rate and rate of approach-related worsened vision were selected as outcome measures of efficacy and safety, respectively, of the OF versus AC. Unpaired t test and χ2 test were used for numerical and categorical variables, respectively. A P value less than 0.05 was considered statistically significant.
OF and AC groups involved 18 and 25 patients, respectively. Complication rate, overall neurologic outcome, rate of approach-related worsened vision, and complete occlusion rate did not differ between the groups. The average follow-up was 51 ± 34 and 60 ± 41 months in the OF and AC groups, respectively.
Compared to AC, OF did not show either a higher rate of approach-related worsened vision or a lower aneurysm complete occlusion rate. OF can be considered a valid alternative to the AC for small superior-projecting dorsal ICA wall paraclinoid aneurysms.
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.
Intraaxial tumors of the central lobe are challenging lesions to deal with because of the high eloquence of this anatomic area.1,2 Diffusion tensor imaging magnetic resonance imaging and fluorescein ...(F) have proven to be useful in the planning and execution, respectively of glioma surgery.3-9 Nevertheless, the advantages of intraoperative use of augmented reality (AR) with diffusion tensor imaging−based high-definition fiber tractography (HDFT) are still underestimated.
In the AR HDFT-F technique reported by our group, the integration of AR into the microscope comes through the BrainLAB Curve navigation platform (BrainLAB AG, Munich Germany), Smartbrush software (BrainLAB AG), KINEVO 900 surgical microscope (Carl Zeiss, Oberkochen, Germany), and YELLOW 560 filter (Carl Zeiss).9 The microscope establishes a wired autodetection of the navigation platform, and the eyepiece functions as a “see-through display” of the AR images, which are overlapped onto the surgical field.
Video 1 shows the technical key aspects of the intraoperative use of the AR HDFT-F technique in the maximal safe anatomic resection of a postcentral gyrus high-grade glioma.