Beta-blockers and glioma: a systematic review of preclinical studies and clinical results

Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro.Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Passive data use for ethical digital public health surveillance in a postpandemic world

There is a fundamental need to establish the most ethical and effective way of tracking disease in the postpandemic era. The ubiquity of mobile phones is generating large amounts of passive data (collected without active user participation) that can be used as a tool for tracking disease. Although discussions of pragmatism or economic issues tend to guide public health decisions, ethical issues are the foremost public concern. Thus, officials must look to history and current moral frameworks to avoid past mistakes and ethical pitfalls. Past pandemics demonstrate that the aftermath is the most effective time to make health policy decisions. However, an ethical discussion of passive data use for digital public health surveillance has yet to be attempted, and little has been done to determine the best method to do so. Therefore, we aim to highlight four potential areas of ethical opportunity and challenge: (1) informed consent, (2) privacy, (3) equity, and (4) ownership

Outcomes of retreatment for intracranial aneurysms - a meta-analysis

Long term results from the International Subarachnoid Hemorrhage Trial (ISAT) and Barrow Ruptured Aneurysm Trial (BRAT) indicate considerably higher retreatment rates for aneurysms treated with coiling compared to clipping, but do not report the outcome of retreatment. The aim of this meta-analysis was to evaluate retreatment related outcomes.A meta-analysis in accordance with PRISMA guidelines was conducted using Medline search engines PubMed and EMBASE to identify articles describing outcomes after retreatment for intracranial aneurysms. Pooled prevalence rates for complete occlusion rate and mortality were calculated. Outcomes of different treatment and retreatment combinations were not compared because of indication bias. Twenty-five articles that met the inclusion criteria were included in the meta-analysis. Surgery after coiling had a pooled complete occlusion rate of 91.2% (95%-CI: 87.0-94.1) and a pooled mortality rate of 5.6% (95%-CI: 3.7-8.3). Coiling after coiling had a pooled complete occlusion rate of 51.3% (95%-CI: 22.1-78.0) and a pooled mortality rate of 0.8% (95%-CI: 0.15-3.7). Surgery after surgery did not provide a pooled estimate for complete occlusion as only one study was identified but had a pooled mortality rate of 5.9% (95%-CI: 3.1-11.2). Coiling after surgery had a pooled complete occlusion rate of 56.1% (95%-CI: 11.4- 92.7) and a pooled mortality rate of 9.3% (95%-CI: 4.1-19.9). All pooled incidence rates were produced using random-effect models.Conclusion:Surgical retreatment was associated with a high complete occlusion rate but considerable mortality. Conversely, endovascular retreatment was associated with low mortality but also a low complete occlusion rate. Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Extracellular vesicle-mediated bilateral communication between glioblastoma and astrocytes

Glioblastoma the most aggressive form of brain cancer, comprises a complex mixture of tumor cells and nonmalignant stromal cells, including neurons, astrocytes, microglia, infiltrating monocytes/macrophages, lymphocytes, and other cell types. All nonmalignant cells within and surrounding the tumor are affected by the presence of glioblastoma. Astrocytes use multiple modes of communication to interact with neighboring cells. Extracellular vesicle-directed intercellular communication has been found to be an important component of signaling between astrocytes and glioblastoma in tumor progression. In this review, we focus on recent findings on extracellular vesicle-mediated bilateral crosstalk, between glioblastoma cells and astrocytes, highlighting the protumor and antitumor roles of astrocytes in glioblastoma development.Chemical Immunolog

When Time Is Critical, Is Informed Consent Less So? A Discussion of Patient Autonomy in Emergency Neurosurgery

Neurosurgical interventions frequently occur in an emergency setting. In this setting, patients often have impaired consciousness and are unable to directly express their values and wishes regarding their treatment. The limited time available for clinical decision making has great ethical implications, as the informed consent procedure may become compromised. The ethical situation may be further challenged by different views between the patient, family members, and the neurosurgeon; the presence of advance directives; the use of an innovative procedure; or if the procedure is part of a research project. This moral opinion piece presents the implications of time constraints and a lack of patient capacity for autonomous decision making in emergency neurosurgical situations. Potential solutions to these challenges are presented that may help to improve ethical patient management in emergency settings. Emergency neurosurgery challenges the respect of autonomy of the patient. The outcome in most scenarios will rely on the neurosurgeon acting in a professional way to manage each unique situation in an ethically sound manner.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Beta-blockers and glioma: a systematic review of preclinical studies and clinical results

Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care

Comparative analysis identifies similarities between the human and murine microglial sensomes

One of the essential functions of microglia is to continuously sense changes in their environment and adapt to those changes. For this purpose, they use a set of genes termed the sensome. This sensome is comprised of the most abundantly expressed receptors on the surface of microglia. In this study, we updated previously identified mouse microglial sensome by incorporating an additional published RNAseq dataset into the data-analysis pipeline. We also identified members of the human microglial sensome using two independent human microglia RNAseq data sources. Using both the mouse and human microglia sensomes, we identified a key set of genes conserved between the mouse and human microglial sensomes as well as some differences between the species. We found a key set of 57 genes to be conserved in both mouse and human microglial sensomes. We define these genes as the "microglia core sensome". We then analyzed expression of genes in this core sensome in five different datasets from two neurodegenerative disease models at various stages of the diseases and found that, overall, changes in the level of expression of microglial sensome genes are specific to the disease or condition studied. Our results highlight the relevance of data generated in mice for understanding the biology of human microglia, but also stress the importance of species-specific gene sets for the investigation of diseases involving microglia. Defining this microglial specific core sensome may help identify pathological changes in microglia in humans and mouse models of human disease.Chemical Immunolog

Safe surgery for glioblastoma: recent advances and modern challenges

One of the major challenges during glioblastoma surgery is balancing between maximizing extent of resection and preventing neurological deficits. Several surgical techniques and adjuncts have been developed to help identify eloquent areas both preoperatively (fMRI, nTMS, MEG, DTI) and intraoperatively (imaging (ultrasound, iMRI), electrostimulation (mapping), cerebral perfusion measurements (fUS)), and visualization (5-ALA, fluoresceine)). In this review, we give an update of the state-of-the-art management of both primary and recurrent glioblastomas. We will review the latest surgical advances, challenges, and approaches that define the onco-neurosurgical practice in a contemporary setting and give an overview of the current prospective scientific efforts

Fibrinolytics and intraventricular hemorrhage: a systematic review and meta-analysis

Intraventricular hemorrhage (IVH) is an independent poor prognostic factor in subarachnoid and intra-parenchymal hemorrhage. The use of intraventricular fibrinolytics (IVF) has long been debated, and its exact effects on outcomes are unknown. A systematic review and meta-analysis were performed in accordance with the PRISMA guidelines to assess the impact of IVF after non-traumatic IVH on mortality, functional outcome, intracranial bleeding, ventriculitis, time until clearance of third and fourth ventricles, obstruction of external ventricular drains (EVD), and shunt dependency. Nineteen studies were included in the meta-analysis, totaling 1020 patients. IVF was associated with lower mortality (relative risk [RR] 0.58; 95% confidence interval [CI] 0.47-0.72), fewer EVD obstructions (RR 0.41; 95% CI 0.22-0.74), and a shorter time until clearance of the ventricles (median difference [MD] - 4.05 days; 95% CI - 5.52 to - 2.57). There was no difference in good functional outcome, RR 1.41 (95% CI 0.98-2.03), or shunt dependency, RR 0.93 (95% CI 0.70-1.22). Correction for publication bias predicted an increased risk of intracranial bleeding, RR 1.67 (95% CI 1.01-2.74) and a lower risk of ventriculitis, RR 0.68 (95% CI 0.45-1.03) in IVH patients treated with IVF. IVF was associated with improved survival, faster clearance of blood from the ventricles and fewer drain obstructions, but further research is warranted to elucidate the effects on ventriculitis, long-term functional outcomes, and re-hemorrhage.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

GlioM&M: Web-based Tool for Studying Circulating and Infiltrating Monocytes and Macrophages in Glioma

Monocytes, macrophages and microglia make up a large part of the glioma environment and have an important role in maintaining and propagating glioma progression. Targeting these cells to inhibit their tumor-promoting effect and reprogramming them into an anti-tumor phenotype is a potential therapeutic approach for glioma. In this study we analyzed the transcriptomes of eight different monocyte subgroups derived from the brain and the blood of glioma-bearing mice. We compared the expression profile of blood-derived monocytes versus tumor-infiltrating monocytes and found increased expression of both pro- and anti-inflammatory pathways in tumor infiltrating monocytes. To help disseminate these datasets, we created a user-friendly web-based tool accessible at www.glioma-monocytes.com. This tool can be used for validation purposes and to elucidate gene expression profiles of tumor-interacting monocytes and macrophages as well as blood-derived circulating monocytes. This tool can also be used to identify new markers and targets for therapy in these different cell populations.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie