Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available ...therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells that comprise ~50% of all brain cells and are therefore likely to establish direct contact with GBM cells. As other tumor cell types can hijack fibroblasts or immune cells to facilitate tumor growth, GBM cells can actually activate astrocytes, namely, the tumor associated astrocytes (TAAs), to promote GBM invasion in the healthy tissue. TAAs have thus been shown to be involved in GBM cells growth and limited response to radiation or chemotherapy (i.e., Temozolomide). Nevertheless, even though the interest in the cancer research community is increasing, the role of TAAs during GBM development is still overlooked. Yet, obtaining an in‐depth understanding of the mechanisms by which TAAs influence GBM progression might lead to the development of new therapeutic strategies. This article therefore reports the different levels of GBM progression at which TAAs have been recently described to be involved in, including tumor cells' proliferation/invasion and resistance to therapies, especially through the activity of extracellular vesicles.
Main Points
Astrocytes get activated into tumor‐associated astrocytes (TAAs) during glioblastoma (GBM) growth.
The TAAS fraction is a source of potential new targets and biomarkers for future therapeutic strategies against GBM.
The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear.
From 2004 through 2014, we randomly assigned 408 ...patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to "upper good recovery" no injury-related problems) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively.
The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03).
At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups. (Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 .).
Background Extracellular vesicles (EVs) hold promise for improving our understanding of radiotherapy response in glioblastoma due to their role in intercellular communication within the tumour ...microenvironment (TME). However, methodologies to study EVs are evolving with significant variation within the EV research community. Methods We conducted a systematic review to critically appraise EV isolation and characterisation methodologies and how this influences our understanding of the findings from studies investigating radiotherapy and EV interactions in glioblastoma. 246 articles published up to 24/07/2023 from PubMed and Web of Science were identified using search parameters related to radiotherapy, EVs, and glioblastoma. Two reviewers evaluated study eligibility and abstracted data. Results In 26 articles eligible for inclusion (16 investigating the effects of radiotherapy on EVs, five investigating the effect of EVs on radiation response, and five clinical studies), significant heterogeneity and frequent omission of key characterisation steps was identified, reducing confidence that the results are related to EVs and their cargo as opposed to co-isolated bioactive molecules. However, the results are able to clearly identify interactions between EVs and radiotherapy bi-directionally within different cell types within the glioblastoma TME. These interactions facilitate transferable radioresistance and oncogenic signalling, highlighting that EVs are an important component in the variability of glioblastoma radiotherapy response. Conclusions Future multi-directional investigations interrogating the whole TME are required to improve subsequent clinical translation, and all studies should incorporate up to date controls and reporting requirements to increase the validity of their findings. This would be facilitated by increased collaboration between less experienced and more experienced EV research groups. Keywords: Glioblastoma, Radiotherapy, Extracellular vesicles
Glioblastoma (GBM) is one of the most aggressive solid tumors for which treatment options and biomarkers are limited. Small extracellular vesicles (sEVs) produced by both GBM and stromal cells are ...central in the inter-cellular communication that is taking place in the tumor bulk. As tumor sEVs are accessible in biofluids, recent reports have suggested that sEVs contain valuable biomarkers for GBM patient diagnosis and follow-up. The aim of the current study was to describe the protein content of sEVs produced by different GBM cell lines and patient-derived stem cells. Our results reveal that the content of the sEVs mirrors the phenotypic signature of the respective GBM cells, leading to the description of potential informative sEV-associated biomarkers for GBM subtyping, such as CD44. Overall, these data could assist future GBM in vitro studies and provide insights for the development of new diagnostic and therapeutic methods as well as personalized treatment strategies.
Telehealth clinics have been used in many specialities, including neurosurgery, to improve access for patients in rural communities. The introduction of nurse navigators involved with the patient ...before, during and after the clinic was evaluated. Clinics were held in a rural hospital with a nurse navigator present in the clinic with the patient, and the physician consulting remotely. A patient satisfaction survey and audit were conducted following ten telehealth clinics. Twenty-one new patients were able to be contacted out of 31 (68%) with an 11 question structured survey. Eighteen out of 21 (86%) stated they were satisfied with the quality of the clinic compared with an in-person clinic. Overall satisfaction scores of 7-10 were scored by 18/21 patients (86%) on a scale of 1-10. An estimated 10785 km of travel was saved for patients going to a rural hospital clinic rather than the neurosurgical centre. This study shows that the supportive role of nurse navigators throughout the patient telehealth clinic pathway merits further continuing evaluation.
Pressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of ...patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making.
A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020.
Regional neurosurgical units outside London (as the pandemic was more advanced at time of study).
Representatives from all units were invited to collect data on new patients discussed at their MDT meetings during the study period. Each unit decided if management decision for each patient had changed due to COVID-19.
Primary outcome measures included number of patients where the decision to undergo surgery changed compared with standard management usually offered by that MDT. Secondary outcome measures included changes in surgical extent, numbers referred to MDT, number of patients denied surgery not receiving any treatment and reasons for any variation across the UK.
18 units (75%) provided information from 80 MDT meetings that discussed 1221 patients. 10.7% of patients had their management changed-the majority (68%) did not undergo surgery and more than half of this group not undergoing surgery had no active treatment. There was marked variation across the UK (0%-28% change in management). Units that did not change management could maintain capacity with dedicated oncology lists. Low volume units were less affected.
COVID-19 has had an impact on patients requiring surgery for malignant brain tumours, with patients receiving different treatments-most commonly not receiving surgery or any treatment at all. The variations show dedicated cancer operating lists may mitigate these pressures.
This study was registered with the Royal College of Surgeons of England's COVID-19 Research Group (https://www.rcseng.ac.uk/coronavirus/rcs-covid-research-group/).
Glioblastoma (GB) is an aggressive type of tumour for which therapeutic options and biomarkers are limited. GB diagnosis mostly relies on symptomatic presentation of the tumour and, in turn, brain ...imaging and invasive biopsy that can delay its diagnosis. Description of easily accessible and effective biomarkers present in biofluids would thus prove invaluable in GB diagnosis. Extracellular vesicles (EVs) derived from both GB and stromal cells are essential to intercellular crosstalk in the tumour bulk, and circulating EVs have been described as a potential reservoir of GB biomarkers. Therefore, EV-based liquid biopsies have been suggested as a promising tool for GB diagnosis and follow up. To identify GB specific proteins, sEVs were isolated from plasma samples of GB patients as well as healthy volunteers using differential ultracentrifugation, and their content was characterised through mass spectrometry. Our data indicate the presence of an inflammatory biomarker signature comprising members of the complement and regulators of inflammation and coagulation including VWF, FCGBP, C3, PROS1, and SERPINA1. Overall, this study is a step forward in the development of a non-invasive liquid biopsy approach for the identification of valuable biomarkers that could significantly improve GB diagnosis and, consequently, patients' prognosis and quality of life.
Study Design
Systematic review and meta-analysis.
Objective
To evaluate systematically the complications of prolonged cervical immobilisation in a hard collar.
Methods
Following registration with ...PROSPERO, a systematic search of electronic databases (MEDLINE, EMBASE) was conducted. Two reviewers independently screened the search results according to pre-determined search criteria. Data was extracted and tabulated. Joanna Briggs Institute checklists were used for assessing the quality of included studies.
Results
The search identified 773 articles. A total of 25 studies were selected for final inclusion. The results largely comprised a mixture of case reports/series, cohort studies and reviews. The most commonly reported complications were pressure ulcers, dysphagia and increased intracranial pressure. A pressure ulcer pooled prevalence of 7% was calculated. There was insufficient data for quantitative analysis of any other complication.
Conclusions
There is significant morbidity from prolonged hard collar immobilisation, even amongst younger patients. Whilst based upon limited and low-quality evidence, these findings, combined with the low-quality evidence for the efficacy of hard collars, highlights a knowledge gap for future research.
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