bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allied Heath Professional Support in Adult Neuro-oncology; Before and During COVID
Authors: Melhuish Sara , Bulbeck Helen 
Published: October 2022

Abstract

AIMS
To understand the current levels of Allied Health Professional (AHP) provision within adult neuro-oncology in the UK, gain insight into perceived gaps and any impact of the COVID-19 pandemic on this provision, from the Health Care Professional’s (HCP) perspective.

METHOD
In collaboration with brainstrust (a brain tumour charity) and the author, a mixed-methods, on-line survey of HCPs working within adult neuro-oncology was designed, tested and distributed to HCPs registered on the charity’s HCP database. Quantitative data was analysed using simple descriptive statistics. Qualitative data was analysed using thematic analysis.

RESULTS
51 HCPs from multiple roles and teams across the UK responded. 66% (34) reported a service delivery gap, including a lack of specialist AHP support, with high geographical variability. During the COVID-19 pandemic, 60.8% (31) respondents identified a reduction in access to AHP support. 58.8% (30) respondents reported a change in appointment modality, with an increase in telephone and video appointments and a decrease in face-to-face appointments and home visits. This modality change was highlighted as a possible cause of reduced HCP awareness of symptom progression that was also reported.

CONCLUSION
There is paucity of data regarding AHP provision within adult neuro-oncology and the impact of the COVID-19 pandemic on this provision. This study highlights concerns regarding overall specialist AHP support which reduced further during the COVID-19 pandemic. The impact on patients is unknown and highlights a need for further research to inform development of national guidelines for specialist AHP provision and the use of telehealth for this complex patient group.
Outcome of Image-Guided Surgical Biopsy of Brain Lesions: A Single Centre Experience
Authors: Saleh ElGhamry Ahmed Mohammed Nabil , Simon Natalie , Eltayeb Mohamed , Surash Surash 
Published: October 2022

Abstract

AIMS
The aim of this study was to quantify the accuracy of surgical biopsy for brain lesions using different image-guidance techniques, in our tertiary neurosurgical centre.

METHOD
Retrospective data was collected from electronic and paper patient notes. Data collected included: age, sex, comorbidities, pre-operative functional images, surgeon grade, biopsy method, number of targets, number of samples, result from frozen section and fixed sample histopathology, complications, and length of stay. Methods of biopsy included: ultrasound-guided, frame-based biopsy and frameless Brainlab guided biopsy (free-hand, Varioguide and registration tool -guided).

RESULTS
A percentage of 11.5% of cases (total = 52) were US-guided biopsy. Navigated frameless biopsies comprised 76.9% of all cases. In these cases, 42.3% of cases were guided by the registration tool, 23% used a fixed “Varioguide” instrument alignment tool and 11.5% were completed using the free-hand method. Overall accuracy of biopsy for all cases was 82.69%. Accuracy rates of different frameless methods were: 81.8% for Brainlab registration- guided biopsy, 66.7% for Brainlab Varioguide biopsy and 100% for Brainlab free-hand frameless biopsies. The percentage of complications was 5.8%.

CONCLUSION
In our centre, the accuracy of image-guided surgical biopsy for brain lesions was as high as 82.69% with a low complication rate of 5.8%. The Brain lab free-hand technique had the highest diagnostic yield and safety amongst all frameless stereotactic techniques.
Diagnostic Evolution of Synchronous Arteriovenous Malformation & Glioblastoma: A Case Report
Authors: Davis Jillian , Goldspring Rob , Scott Ian , Smith Stuart , Chattopadhyay Arpita 
Published: October 2022

Abstract

AIMS
We present the clinical course, radiology and histopathology of a case with synchronous pathology and aim to highlight learning points and diagnostic pitfalls.

METHOD
Case Notes, Radiology and Pathology were reviewed.

RESULTS
A 25 year old female with learning difficulties presented acutely with collapse. Initial CT-imaging demonstrated a right peritrigonal parenchymal haematoma with intraventricular extension. CT-Angiography revealed small vessels around the haematoma but no definite underlying vascular abnormality. Whilst the standard MRI sequences appeared to confirm the CT findings, the patient was unable to tolerate the planned MR angiogram or post-contrast sequences. Three months later, Digital Subtraction Angiography (DSA) revealed an “unusual” arteriovenous malformation (AVM) at the site of the previous haematoma. Over the following two months, the patient represented twice with acute headaches. CT imaging each time demonstrated further re-bleeds, with increasing oedema. Consequently, another DSA was performed for attempted embolisation but striking differences in the appearance of the AVM were now evident. Stereotactic radiosurgery was scheduled, but a planning CT-scan six weeks later revealed, for the first time, appearances suggestive of an underlying high-grade neoplasm. A biopsy was performed which showed a Glioblastoma (CNS WHO, 2021; Grade 4) alongside an arteriovenous malformation with well-developed arterial and venous structures. Despite optimal ICU management post-operatively, the patient deteriorated and sustained irreversible brain damage from which she did not recover.

CONCLUSION
Synchronous Glioblastoma and AVM is rare and can cause diagnostic and surgical challenges. These difficulties and the proposed angiogenic effects of tumour factors, as underlying aetiological agents of these synchronous lesions, is discussed.
The Management and Outcomes of Butterfly Gliomas at a U.K. Neurosurgical Unit
Authors: Sinha Siddharth , Avnon Adam , Perera Andrea , Lavrador Jose Pedro , Ashkan Keyoumars 
Published: October 2022

Abstract

AIMS
Butterfly glioblastomas (bGBM) are a rare subset of WHO grade IV tumours, that carry a poor prognosis with a median survival ranging between 3 to 6 months. Our study aims to add to the literature on how these tumours should be best managed when presenting to a neurosurgical unit.

METHOD
We performed a retrospective analysis from January 2009 to June 2021 of the electronic patient records of single large neurosurgical centre in London. We assessed patient demographics, initial clinical presentation, tumour characteristics (location, mutation, volumetric size), clinical management and overall survival (Kaplan-Meier estimator).

RESULTS
42 cases of bGBM were identified. These patients were managed with radiotherapy alone (n=3), with biopsy +/- adjuvant therapy (n=36) or attempted surgical resection (n=3). A further 38 cases of suspected bGBM were identified based on presentation and radiological imaging, however these patients were managed conservatively and did not undergo tissue diagnosis. No significant difference in survival was seen between conservative management compared to biopsy alone, with radiotherapy only or chemotherapy only (P=0.499) However, survival was significantly increased when patients received adjuvant chemoradiotherapy following biopsy or resection (P=0.04).

CONCLUSION
Butterfly glioblastoma has a devastating prognosis. Our study would suggest that unless a patient completes full adjuvant therapy with both chemotherapy and radiotherapy following biopsy or resection, they should be managed conservatively. This avoids unnecessary procedural interventions and can be deemed cost saving to the NHS. A larger prospective cohort study is recommended.
5-Aminolevulinic Acid (5-ALA) Use at The Walton Centre NHS Foundation Trust (WCFT)
Authors: Bennett Ruth , Akinsanya Elizabeth 
Published: October 2022

Abstract

AIMS
To audit the use of 5-ALA at WCFT to determine adherence to NICE guidance [NG99] and the Trust guideline.

METHOD
Data was retrospectively evaluated from 77 patients prescribed 5-ALA at WCFT Jan 2020 – Jan 2022.

RESULTS
Of the 77 patients, 61 (79%) patients had 5-ALA induced fluorescence documented intraoperatively which aided resection and 7 patients (9%) had no confirmed fluorescence. In patients with no fluorescence noted, the administration time to operation time was variable. The remaining 9 patients (12%) had no documentation on the presence or absence of fluorescence. Prior to surgery, 67 patients had an MDT outcome of likely high grade glioma. 66 patients had this confirmed with histology post-surgical resection. The remaining patients had various MDT diagnosis documented including oligoastrocytoma, oligodendroglioma and lesion. 87% of patients had the correct dose of 20mg/kg prescribed. 14 patients (18%) did not have liver function tests (LFT) checked during admission as per Trust policy. Of those checked, 29 patients (37%) had new derangement of LFT.

CONCLUSION
The use of 5-ALA has aided surgical resection, enabling greater resection in the majority of patients prescribed for at WCFT. It has been used in accordance with NICE for HGG resections in 87% of cases. Some improvement could be made in ensuring the correct dose is prescribed and the appropriate monitoring (LFT) is carried out post procedure. Theatre documentation could be improved so future audit can more easily identify extent of resection and extent of fluorescence.
A Longitudinal Study to Evaluate Biomarkers in Brain Tumour Patients
Authors: Whiteside Ellen 
Published: October 2022

Abstract

AIMS
To monitor brain tumour patient blood for predictive and prognostic biomarkers, in a prospective longitudinal study. Continuing the research of Dr. Abel the results may be used to predict tumour recurrence and progression from low- to high-grade. The results may be useful in the clinical management of malignant glioma patients.

METHOD
A patented panel of biomarkers will be investigated using FFPE tissue and blood components from adult brain tumour patients in the North West region. Biomarker expression will be analysed in different molecular sub-types of glioma, grouped by IDH and methylation status. An evaluation will be conducted to determine if reference ranges can be created to distinguish between high-and low-grade tumours. Spectroscopic analysis of blood samples will be tested to determine if cancerous and non-cancerous can be differentiated from each other. There will be testing of selected miRNA’s for up and down regulation patterns. Sample Intervals: Initial diagnosis, 24 hours post-surgery, pre-therapy, post-radiotherapy, after adjuvant therapy, at 3 then 6 monthly post therapy, at recurrence or suspected recurrence and at intervals during further therapy and follow up.

RESULTS
There are no results to report at this point in the study time line. Testing to start in April 2022.

CONCLUSION
The potential impact of research would work towards lower patient risk and less invasive procedures. If used as a screening tool could allow high NHS savings. There could be an impact on patient experience and survival if recurrence could be detected [NICE guideline NG99] recommendation for research.
Palliative Carboplatin Chemotherapy in Previously Treated High-Grade Glioma: Real-World Efficacy and Safety
Authors: Gupta Meetakshi , Mulholland Paul , Wilson Elena , Fersht Naomi , Kosmin Michael 
Published: October 2022

Abstract

AIMS
Effective third-line chemotherapy options for patients after temozolomide (TMZ) and nitrosourea-based chemotherapy for high-grade glioma (HGG) are not well defined. The use of carboplatin is limited due to uncertainly around its effectiveness and tolerability.

METHOD
Patients with HGG treated with single-agent carboplatin chemotherapy between 2005-2021 were identified from our institutional database. Patient and treatment-related details were acquired from electronic hospital records. SPSS Statistics for Windows, (Version 23.0, IBM Corp.) was used for data analysis.

RESULTS
A total of 16 HGG patients were identified. This included 9 glioblastoma (GBM) and 3 anaplastic astrocytomas (AA). These 12 patients were used for further analysis. The median age was 48 (22-73) years. All patients initially received a flat dose of 450 mg intravenous carboplatin every 3-4 weeks. All had previously received high dose RT (54-60 Gy), and temozolomide and lomustine-based chemotherapy. Carboplatin was used as 3rd or 4th line treatment. The median number of cycles given was 3 (range: 1-12). Five had rapid decline in performance status after 1-3 cycles. Five patients required dose/ cycle length adjustment due to grade 1 or 2 haematological toxicity. Other than cumulative fatigue, no other &gt;/= grade 2 toxicities were reported. None required inpatient management for treatment toxicities. Median progression-free survival on carboplatin was 3 months (range 1-11 months) and overall survival was 8 months (range 1–26 months).

CONCLUSION
Carboplatin is a viable treatment option for HGG with acceptable toxicity rates. However, careful patient selection remains key to attaining maximum benefit.
The Evaluation of Novel Targets for CAR T Therapy in Glioblastoma
Authors: Alker Riza , Abel Peter , Griffiths David , Akhavan David 
Published: October 2022

Abstract

AIMS
The basis of this research revolves around the issue of limited expression of targetable tumour-specific antigens, heterogeneity, and mutation, which impede the development and success of CAR T therapy for glioblastoma. The research will identify an off-tumour cell target involved in tumour angiogenesis. The principal aim is to generate an off-tumour targeted CAR T and test their efficacy and safety in cell culture and animal models.

METHOD
Analyse the prevalence and distribution of the target molecules via immunohistochemistry (IHC). Confirm IHC results via mRNA extraction. Analyse the target molecule’s serum concentrations via the Luminex instrument. Generate the off-tumour targeted CAR T using lentivirus. Assess tumour burden and progression via a bioluminescent imaging system. Assess toxicity in vitro against human pericytes and in vivo by monitoring mouse weight and submitting histologic tissue for sectioning.

RESULTS
Utilise a scoring system to analyse the staining and correspond this to the serum concentrations to identify a blood-borne treatment response biomarker. If murine toxicity is observed, the CAR T construct will be affinity matured to selectively target molecules expressed at a cancerous level. A tandem bi-specific CAR T cells may also be created to mitigate immune escape and enhance anti-tumour efficacy.

CONCLUSION
The search for an off-tumour cell target for CAR T therapy in glioblastoma has not yet been completed. The discovery and validation of the novel molecule as a biomarker of treatment response would be a unique finding.
Discriminatory Ability of Gas Chromatography–Ion Mobility Spectrometry to Identify Patients Hospitalized With COVID-19 and Predict Prognosis
Authors: Nazareth Joshua , Pan Daniel , Kim Jee Whang , Leach Jack , Brosnan James G , Ahmed Adam , Brodrick Emma , Bird Paul , Wicaksono Alfian , Daulton Emma , Tang Julian W , Williams Caroline , Haldar Pranabashis , Covington James A , Pareek Manish , Sahota Amandip 
Published: October 2022

Abstract

Background
Rapid diagnostic and prognostic tests for coronavirus disease (COVID-19) are urgently required. We aimed to evaluate the diagnostic and prognostic ability of breath analysis using gas chromatography–ion mobility spectrometry (GC-IMS) in hospitalized patients with COVID-19.

Methods
Between February and May 2021, we took 1 breath sample for analysis using GC-IMS from participants who were admitted to the hospital for COVID-19, participants who were admitted to the hospital for other respiratory infections, and symptom-free controls, at the University Hospitals of Leicester NHS Trust, United Kingdom. Demographic, clinical, and radiological data, including requirement for continuous positive airway pressure (CPAP) ventilation as a marker for severe disease in the COVID-19 group, were collected.

Results
A total of 113 participants were recruited into the study. Seventy-two (64%) were diagnosed with COVID-19, 20 (18%) were diagnosed with another respiratory infection, and 21 (19%) were healthy controls. Differentiation between participants with COVID-19 and those with other respiratory tract infections with GC-IMS was highly accurate (sensitivity/specificity, 0.80/0.88; area under the receiver operating characteristics curve [AUROC], 0.85; 95% CI, 0.74–0.96). GC-IMS was also moderately accurate at identifying those who subsequently required CPAP (sensitivity/specificity, 0.62/0.80; AUROC, 0.70; 95% CI, 0.53–0.87).

Conclusions
GC-IMS shows promise as both a diagnostic tool and a predictor of prognosis in hospitalized patients with COVID-19 and should be assessed further in larger studies.
Brief Report: Prognostic relevance of 3q amplification in squamous cell carcinoma of the lung
Authors: Rous Fawzi Abu , Li Pin , Carskadon Shannon , Singh Sunny RK , Chacko Rebecca , Abushukair Hassan , Gadgeel Shirish , Palanisamy Nallasivam 
Published: October 2022

AbstractIntroductionAmplification of 3q is the most common genetic alteration identified in squamous cell carcinoma of the lung (LUSC) with the most frequent amplified region being 3q26-3q28.MethodsIn this analysis, we aim to describe the prognostic relevance of 3q by focusing on a minimal common region (MCR) of amplification within 3q constituted by 25 genes. We analyzed 511 cases of LUSC from The Cancer Genome Atlas (TCGA) and included 476 in the final analysis.ResultsWe identified a 25-gene MCR that was amplified in 221 (44.3%) cases and was associated with better disease specific-survival (DSS) (NR versus 9.25 years; 95% CI [5.24-NR]; log-rank p=0.011) and a progression-free interval (PFI) of 8 years (95% CI [5.1-NR]) versus 4.9 years (95% [3.5-NR]) (Log-rank p=0.020). Multivariable analysis revealed MCR amplification was associated with improved DSS and PFI.ConclusionAmplification of the 25-gene MCR within 3q was present in 44% of this cohort mainly composed of Caucasian patients with early-stage LUSC. This analysis is a strong indicator of the prognostic relevance of the 25-gene MCR within 3q. We are further evaluating its prognostic relevance in a racially diverse patient population with advanced LUSC.
Meta-analysis of GWAS for sea lice load in Atlantic salmon
Authors: Cáceres P. , Lopéz P. , Garcia B. , Cichero D. , Ødegård J. , Moen T. , Yáñez J.M. 
Published: October 2022

AbstractSea lice (Caligus rogercresseyi) is an ectoparasite that causes major production losses in the salmon aquaculture industry of the southern hemisphere. Atlantic salmon (Salmo salar) is an important salmonid for the aquaculture industry and a species which is highly susceptible to sea lice infestation. Genetic variation for resistance to sea lice, defined as parasite load, has been found in Atlantic salmon. In addition, sea lice load has been shown to be a polygenic trait, controlled by several quantitative trait loci (QTL) which have small to medium effect, making them difficult to map with sufficient statistical power when sample sizes are limited. The use of medium density single nucleotide polymorphisms (SNP) can also adversely affect the success of identifying genetic variants significantly associated to sea lice load. In order to improve the ability to detect QTL significantly associated to sea lice load, we combined genotype imputation from medium- to high SNP-density and performed genome-wide association studies (GWAS) across different populations of Atlantic salmon. The imputation of genotypes of 6,144 fish challenged against sea lice from four year-classes was performed to increase density from 70K SNPs to 600K SNPs. A meta-GWAS was then carried out for three different traits: lice count, lice density and log-lice density. Using this approach, we detected a genomic region highly associated to sea lice load on Atlantic salmon chromosomes (ssa) 3 and 12 pronounced peaks and several other regions surpassing the significance threshold across almost all other chromosomes. We also identified important genes within the QTL regions, many of these genes are involved in tissue reparation, such as Mucin-16-like isoform X2 and Filamentous growth regulator 23-like isoform X1. The QTL region on ssa03 also contained cytoskeletal-modifying and immune response related genes such as Coronin 1A and Claudin. Our results confirm the highly polygenic architecture of sea lice load, but they also show that high experimental power can lead to the identification of candidate genes and thus to increased insight into the biology of sea lice resistance in Altantic salmon.
Oligodendrocyte precursor cells stop sensory axons regenerating into the spinal cord
Authors: Kim Hyukmin , Skuba Andy , Xia Jingsheng , Han Sung Baek , Zhai Jinbin , Hu Huijuan , Kang Shin H. , Son Young-Jin 
Published: October 2022

SUMMARYPrimary sensory axons stop regenerating as they re-enter the spinal cord, resulting in incurable sensory loss. What arrests them has remained unclear. We previously showed that axons stop by forming synaptic contacts with unknown non-neuronal cells. Here, we identified these cells in adult mice as oligodendrocyte precursor cells (OPCs). We also found that only a few axons stop regenerating by forming dystrophic endings, exclusively at the CNS:PNS borderline where OPCs are absent. Most axons stop in contacts with a dense network of OPC processes. Live imaging, immuno-EM and OPC-DRG co-culture additionally suggest that axons are rapidly immobilized by forming synapses with OPCs. Genetic OPC ablation enables many axons to continue regenerating deep into the spinal cord. We propose that sensory axons stop regenerating by encountering OPCs that induce presynaptic differentiation. Our findings identify OPCs as a major regenerative barrier that prevents intraspinal restoration of sensory circuits following spinal root injury.
Asynchronous haltere input drives specific wing and head movements inDrosophila
Authors: Rauscher Michael J , Fox Jessica L 
Published: October 2022

AbstractHalteres are multifunctional mechanosensory organs unique to the true flies (Diptera). A set of reduced hindwings, the halteres beat at the same frequency as the lift-generating forewings and sense inertial forces via mechanosensory campaniform sensilla. Though it is well-established that haltere ablation makes stable flight impossible, the specific role of wing-synchronous input has not been established. Using small iron filings attached to the halteres of tethered flies and an alternating electromagnetic field, we experimentally decoupled the wings and halteres of flyingDrosophilaand observed the resulting changes in wingbeat amplitude and head orientation. We find that asynchronous haltere input results in fast saccades in the wing but not the head. We also find that wing and gaze optomotor responses are disrupted differently by asynchronous input. These effects of wing-asynchronous haltere input show that specific sensory information is necessary for maintaining wing amplitude stability and adaptive gaze control.