A review on diffuse glioma and gene transfer technologies and the impact of COVID-19 on neurosurgical oncology service provision

1) Diffuse glioma is one of the most devastating cancers know in terms of morbidity and mortality. During the last decade, the mortality rate has seen a very modest change. Due to the rapid improvement in understanding the glioma-genesis, evolution, and genetic landscape, a new classification has emerged, improving the diagnostic accuracy. However, the new knowledge acquired has not been translated into novel therapeutic therapies. The treatment regime has mostly relied on maximal surgical resection and chemo/radiotherapy. Nevertheless, gross macroscopic surgical resection is allowing for a significant number of tumour cells to be left behind. Glioma Stem Cells (GSCs) left behind can acquire chemo-resistant properties and exhibit a plethora of characteristics that enable cell survival and growth, leading to an aggressive tumour recurrence. It is now increasingly recognised that IDH mutations are linked to the development of glioma and tumour reoccurrence. IDH mutations can lead to genetic and epigenetic changes promoting cell proliferation, tumour invasion and immune evasion as well as preventing differentiation. Understanding these pathways will allow for new rational therapeutic interventions in an attempt to improve patient outcomes. 2) Gene delivery is the process whereby foreign genomic material is inserted into a host cell or organism. A number of viral and non-viral gene transfer system have been developed in the last few decades. However, no system to date has been used without certain limitations. Here we critically appraise and outline, the advantages, disadvantages, and common uses of viral and non-viral methods. 3) The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic brings new challenges to the management of neuro-oncology patients. In the West Midlands (WM) a population of 5.7 million is served by three neuro-oncology centres. NHS service delivery was reconfigured to cope with SARS-CoV-2 infections. Here we report the impact at three centres with low (CLOW), medium (CMED) and high (CHIGH) levels of SARS-COV-2 mortality on referrals and diagnosis, surgical safety and quality and clinical management during the pandemic. Data were collected either prospectively or retrospectively using electronic clinical records from each centre during period 1 (before lockdown) and period 2 of SARS-CoV-2 (complete lockdown). Referral into specialist care pathways fell by 40% leading to reductions in diagnostic surgery of over 30% as a result of SARS-COV-2 related changes in healthcare provision and help-seeking behaviour. For SARS-COV-2 negative patients, surgical morbidity, 30-day readmission and 30-day mortality were unaffected by changes in management, but operations took longer, and there was an increase in patients with post-operative residual disease. There were no readmissions with SARS-COV-2 infection within 30 days of surgery. Access to radiotherapy and chemotherapy was reduced with patients suffering from the most aggressive cancers being more severely impacted. Future planning should consider accelerating access to advanced molecular diagnostic technologies to refine clinical decision making and the use of chemotherapy. Regional networking solutions could optimise the use of resources and maintain a higher standard of care, allowing patients to continue to receive the best possible care

Maize as Energy Crop

Maize is the predominant raw material (together with sugar cane) for the production of bioethanol, the most common and widespread biofuel, and at the same time the predominant raw material for biogas production, with the highest yields in Europe. The advantage of maize biomass over other energy plants is the fact that biomass occurs after harvesting the seed and does not require the use of a different area for its development. The main drawback of the use of maize biomass is the negative effects of removing crop residues on fertility and the physical properties of the soil. Bioethanol’s share of global biofuel production is over 94%, as many countries are replacing a portion of their fossil fuels with biofuels, according to international regulations. The choice of crops used as feedstock for the production of bioethanol is strongly associated with local climatic factors. About 60% of world bioethanol production is made with cane raw material in the Central and South American countries, with Brazil leading, while the remaining 40% from other crops with North America producing bioethanol almost exclusively from maize, and the EU uses as raw material raw starch (cereals and maize) as well as crops such as sugar beet and sweet sorghum

The evolution of an SBNS-accredited NANSIG simulated skills workshop for aspiring neurosurgical trainees: an analysis of qualitative and quantitative data.

Funder: Newcastle UniversityBACKGROUND: The Neurology and Neurosurgery Interest Group (NANSIG) neurosurgical skills workshop is novel in teaching neurosurgical skills solely to medical students and foundation trainees in the UK. The aim is to offer an affordable option for a high-fidelity simulation course enabling students to learn and practise specific neurosurgical skills in a safe, supervised environment. METHODS: A 10-delegate cohort was quantitatively assessed at the NANSIG neurosurgical skills workshop. Two assessors used a novel modified Objective Structured Assessment of Technical Skills (mOSATS) assessment tool, comprising 5 domains ranked according to a 5-point scale to rate delegates' ability to create a burr hole. Qualitative data from previous workshops were collected, consisting of open-ended, closed-ended and 5-point Likert scale responses to pre- and post-workshop questionnaires. Data were analysed using SPSS® software. RESULTS: Delegates scored a mean total of 62.1% (21.75/35) and 85.1% (29.8/35) in pre- and post-workshop assessments respectively revealing a statistically significant improvement. Regarding percentage of improvement, no significant difference was shown amongst candidates when comparing the number of neurosurgical cases observed and/or assisted in the past. There was no significant difference in the overall rating between the last two workshops (4.89 and 4.8 out of 5, respectively). One hundred percent of the attendees reported feeling more confident in assisting in theatre after the last two workshops. CONCLUSION: We show that a simulation workshop cannot only objectively quantify the improvement of surgical skill acquisition but can also be beneficial regardless of the extent of prior experience

Impact of COVID-19 pandemic on surgical neuro-oncology multi-disciplinary team decision making: a national survey (COVID-CNSMDT Study).

OBJECTIVES: 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. DESIGN: A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020. SETTING: Regional neurosurgical units outside London (as the pandemic was more advanced at time of study). PARTICIPANTS: 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 AND SECONDARY OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: 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. STUDY REGISTRATION: 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/)

Achaiki Iatriki : official publication of the medical society of western Greece and Peloponnesus

In the current issue, the editorial by Cauchi et al. argues for eco-friendly measures in endoscopy and emphasies the role of healthcare providers in reducing waste. The editorial adeptly employs the three Rs (Reduce, Reuse, Recycle) framework to tackle waste management, offering practical solutions. The editorial by Milionis et al. focuses on the reverse cascade screening for paediatric familial hypercholesterolaemia (FH), which is an upcoming tool for public health. Advantages, practices, and challenges regarding FH are thoroughly discussed. Lastly, the editorial by Fousekis et al. presents the main aspects of a chronic immune-mediated cutaneous disease, dermatitis herpetiformis (DH), which constitutes an extraintestinal manifestation of celiac disease, including its diagnosis, pathogenesis, and management. Moreover, this issue includes three review articles. The review article by Krontira et al. discusses the evolving data on the epidemiology, diagnostic approach and appropriate management of foreign body and caustic substance ingestion, based on updated guidelines published by gastroenterological and endoscopic societies. The review by Halliasos et al. provides data on the clinical presentation, diagnosis, and management of metastatic acute spinal cord compression, focusing on the importance of a multidisciplinary team approach, including spine surgeons, radiation oncologists, medical oncologists, palliative care clinicians, physiotherapists, and psychologists. Lastly, the review by Schinas et al. outlines the potential of immune modulation in the treatment of infections and the need for individualised approaches in the modern world of personalised medicine by examining some of the key strategies and immune-based therapies being developed to combat infectious diseases.peer-reviewe

Review of Classification Systems for Adult Acquired Flatfoot Deformity/Progressive Collapsing Foot Deformity and the Novel Development of the Triple Classification Delinking Instability/Deformity/Reactivity and Foot Type

Abstract: Background Classifications of AAFD/PCFD have evolved with an increased understanding of the pathology involved. A review of classification systems helps identify deficiencies and respective contributions to the evolution in understanding the classification of AAFD/PCFD. Methods Using multiple electronic database searches (Medline, PubMed) and Google search, original papers classifying AAFD/PCFD were identified. Nine original papers that met the inclusion criteria were identified. Results Johnson’s original classification and multiple variants provided a significant leap in understanding and communicating the pathology but remained tibialis posterior tendon-focused. Drawbacks of these classifications include the implication of causality, line-arity of progression through stages, an oversimplification of stage 2 deformity, and a failure to understand that multiple tendons react, not just tibialis posterior. Later classifications, such as the PCFD classification, are deformity-centric. Early ligament laxity/instability in normal attitude feet and all stages of cavus feet can present with pain and instability with minor/no deformity. These may not be captured in deformity-based classifications. The authors developed the ‘Triple Classification’ (TC) understanding that primary pathology is a progressive ligament failure/laxity that presents as tendon reactivity, deformity, and painful impingement, variably manifested depending on starting foot morphology. In this classification, starting foot morphology is typed, ligament laxities are staged, and deformity is zoned. Conclusions This review has identified deficiencies within classification systems for AAFD/PCFD to delink ligament laxity, deformity, and foot type and develop the ‘Triple classification’. Advantages of the TC may include representing foot types with no deformity, defining complex secondary instabilities, delinking foot types, tendon re-activity/ligament instability, and deformity to represent these independently in a new classification system.N

Mutant IDH in Gliomas: Role in Cancer and Treatment Options.

Altered metabolism is a common feature of many cancers and, in some cases, is a consequence of mutation in metabolic genes, such as the ones involved in the TCA cycle. Isocitrate dehydrogenase (IDH) is mutated in many gliomas and other cancers. Physiologically, IDH converts isocitrate to α-ketoglutarate (α-KG), but when mutated, IDH reduces α-KG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at elevated levels in IDH mutant tumours, and in the last decade, a massive effort has been made to develop small inhibitors targeting mutant IDH. In this review, we summarise the current knowledge about the cellular and molecular consequences of IDH mutations and the therapeutic approaches developed to target IDH mutant tumours, focusing on gliomas

Mutant IDH in Gliomas: Role in Cancer and Treatment Options.

Peer reviewed: TrueAltered metabolism is a common feature of many cancers and, in some cases, is a consequence of mutation in metabolic genes, such as the ones involved in the TCA cycle. Isocitrate dehydrogenase (IDH) is mutated in many gliomas and other cancers. Physiologically, IDH converts isocitrate to α-ketoglutarate (α-KG), but when mutated, IDH reduces α-KG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at elevated levels in IDH mutant tumours, and in the last decade, a massive effort has been made to develop small inhibitors targeting mutant IDH. In this review, we summarise the current knowledge about the cellular and molecular consequences of IDH mutations and the therapeutic approaches developed to target IDH mutant tumours, focusing on gliomas

Microglia and macrophages in glioblastoma: landscapes and treatment directions.

Publication status: PublishedGlioblastoma is the most common primary malignant tumour of the central nervous system and remains uniformly and rapidly fatal. The tumour-associated macrophage (TAM) compartment comprises brain-resident microglia and bone marrow-derived macrophages (BMDMs) recruited from the periphery. Immune-suppressive and tumour-supportive TAM cell states predominate in glioblastoma, and immunotherapies, which have achieved striking success in other solid tumours have consistently failed to improve survival in this 'immune-cold' niche context. Hypoxic and necrotic regions in the tumour core are found to enrich, especially in anti-inflammatory and immune-suppressive TAM cell states. Microglia predominate at the invasive tumour margin and express pro-inflammatory and interferon TAM cell signatures. Depletion of TAMs, or repolarisation towards a pro-inflammatory state, are appealing therapeutic strategies and will depend on effective understanding and classification of TAM cell ontogeny and state based on new single-cell and spatial multi-omic in situ profiling. Here, we explore the application of these datasets to expand and refine TAM characterisation, to inform improved modelling approaches, and ultimately underpin the effective manipulation of function

Extramedullary malignant melanotic schwannoma of the spine: Case report and an up to date systematic review of the literature.

Background Melanotic schwannoma is a rare variant of schwannoma. Extramedullary melanotic schwannoma originates in the vicinity of nerve roots mimicking other intervertebral disc disorders. Therefore, T1 and T2-weighted MRI sequences become an essential tool for diagnosis. Aside from case reports, no large studies exist to provide consensus on the signal intensities in T1 and T2-weighted MR imaging. Moreover, no clear evidence is available to delineate prognosis. Here, a case report is presented together with a subsequent systematic review of the literature regarding this rare entity. Case description A 45-year old female presented with a one-year history of insidious onset of neck pain and paraesthesia. Magnetic resonance imaging confirmed an extramedullary lesion along the C6 nerve root with T1-weighted hyperintensity and T2-weighted hypointensity. Despite two surgical decompressions and adjuvant immunotherapy, the patient unfortunately passed away due to metastatic progression. Discussion According to the systematic review conducted, in over half of the cases of extramedullary melanotic schwannoma, there is local reoccurrence and/or distal metastasis. Moreover, in 64.7% and 70.6% of the cases, the T1-weighted image of the lesion appears hyperintense and hypointense on a T2-weighted image, respectively. It is an aggressive variant of schwannoma, one of the most commonly observed extramedullary tumours presenting to neurosurgical practice. Conclusion Our results highlight that specific T1 and T2-weighted imaging findings can provide valuable information, enabling early suspicion, influencing the surgical aims and strategy and the timely commencement of relevant immunotherapy. Considering the poor prognosis, early adjuvant therapy with other modalities should be considered