bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying novel molecular differences between WHO grade I and II meningiomas
Authors: Sofela Agbolahan (Boh) , Hanemann Oliver 
Published: October 2019

Abstract

Background
With the increasing emphases on the integrated histo-pheno-genotypical diagnoses of central nervous system (CNS) tumours, there is a pressing need for the identification of biomarkers to aid in the clinical management, diagnosis, prognosis and follow-up of meningiomas too. WHO grade II meningiomas remain a very controversial group of CNS tumours to diagnose/treat, compared to the more prevalent and extensively researched grade I tumours.
Typical clinical scenarios include; the serum diagnosis of conservatively managed tumours, follow-up of surgically managed patients and prognostication, for predicting grade progression. We herein describe the identification of novel biomolecular differences between grade I and II meningiomas.

Aim
To identify biomarkers unique to grade II meningiomas (versus grade I) and describe their potential use in typical clinical scenarios.

Methods
Unbiased global proteomic analyses of four grade I & II primary-meningioma cells were carried out to identify proteins differentially expressed between both grades.
Differential expression and statistical analyses were performed using Perseus and Microsoft Excel.
The significantly differentially expressed proteins were validated by Western blot, IHC and ELISA, using tumour tissue and primary cells.

Results
We identified 3553 proteins commonly expressed in both meningioma grades. Further analysis revealed that 86 of these were significantly differentially up/down-regulated.
Initial validation studies on some of the most promising candidates have confirmed these patterns of expressions between the two tumour grades.

Conclusion
There is a need for the identification of grade II biomarkers. The initial findings of this study have identified novel biomolecular differences between grade I/II meningiomas that can potentially aid in the aforementioned typical clinical scenarios.
Defining the Speech and Language Therapist role in palliative care of neuro-oncology patients: A qualitative research study.
Authors: Evans Rachel , Longo Mirella , Nelson Annmarie 
Published: October 2019

Abstract
Speech and language therapists (SLTs) are experts in the management of swallowing and communication disorders. Although there is increasing recognition of SLTs in palliative care, evidence specifically supporting their role with primary malignant gliomas (PMG) patients is lacking, despite the prevalence of swallowing and communication difficulties in this non-curable disease. This study aimed to explore the contribution of SLT to PMG, as perceived by SLTs themselves and by members of the regional neuro-oncology multidisciplinary team (MDT).
Following ethical approval, semi-structured one-to-one interviews were conducted with ten SLTs working with PMG in outpatients and community settings across South East Wales. In addition, five members of the regional neuro-oncology MDT were interviewed. Thematic analysis was used to analyse the data and to identify and pinpoint salient themes.
The findings indicate that despite lack of professional guidance and previous evidence, SLTs provided evidence to suggest that they contribute beyond swallowing and communication management, to areas such as shared decision-making, key-working, patient advocacy, advanced care planning and support for psychological wellbeing. However, these extended roles are inconsistently recognised by the MDT. Five barriers were identified which hampered SLT contributions: a perceived identity crisis affecting PMG patients, lack of confidence from SLTs, inconsistent MDT integration, reduced resources and strategic direction. The study suggests that SLTs need to promote and educate the MDT in order to achieve routine integration and enhance patient-centred and holistic care. The profession may also benefit from capturing the value of their involvement with PMG to drive service developments.
A service improvement project exploring the extent of need for allied health care professionals within neuro-oncology in Velindre Cancer Centre.
Authors: Evans Rachel , Williams Hayley , Love-Gould Lisa , Tilsley Owen , Powell James , Burke Rhian , Sahar Iqbal Najmus , Johnson Karen , Pearce Siobhan , Williams Rhiannon , Halon Elizabeth , Evans Callum 
Published: October 2019

Abstract
Given the highly complex and holistic needs of neuro-oncology patients, gold standard guidelines recommend that support is best served by a coordinated multi-disciplinary team (MDT) to provide seamless care from diagnosis to end of life (NICE 2018). Allied Healthcare Professionals (AHPs) including occupational therapy (OT), physiotherapy (PT), speech and language therapy (SLT) and dietitians (DT) are recognised as key professions within the MDT. As there is no designated AHP team at Velindre Cancer Centre, input can be reactive and fragmented with limited opportunity for patient education or service developments.
The aim of the project was to scope and evaluate the level of AHP need the neuro-oncology population attending Velindre Cancer Centre. A service improvement grant funded a Band 4 Therapies support worker to conduct the project. The project involved a number of elements including the implementation of a revised neuro-oncology screening tool, strategic effort to improve patient education and self-management and engaging patients and staff to guide future service developments. The mixed methods approach yielded rich quantitative and qualitative data.
The results demonstrated that whilst AHP input was beneficial to patient care, significant unmet needs were highlighted and demands for services exceeded the teams’ capacity. Therefore a designated neuro-oncology therapies team should be a central consideration for future care to enable timely, responsive, equitable and seamless MDT working. Greater AHP resource would also enable greater AHP involvement in research and education to revolutionise care in order to fully meet the needs of this vulnerable and complex patient group.
Ketogenic diets as an adjuvant therapy in glioblastoma (KEATING): A mixed methods randomised feasibility study
Authors: Martin-McGill Kirsty , Cherry Gemma , Marson Anthony , Tudur Smith Catrin , Young Bridget , Jenkinson Michael 
Published: October 2019

Abstract

Background
There is increasing interest in the use of ketogenic diets (KD) as adjuvant therapy for glioblastoma (GBM). Trial aims: i) investigate protocol feasibility; ii) assess patient/carer acceptability; iii) explore the decision-making of patients’ invited to participate in KEATING; and iv) inform phase III trial design.

Methods
Prospective, feasibility study, with embedded qualitative design randomised 12 newly-diagnosed GBM patients to three months of medium chain triglyceride ketogenic diet (MCTKD) or the modified ketogenic diet (MKD) during chemoradiotherapy. Primary outcome was retention; secondary outcomes included recruitment rate, dietary acceptability, progression free survival (PFS) and overall survival (OS). Semi-structured interviews were conducted with a representative sample of patients and relatives (n=15).

Results
Recruitment targets were achieved, but recruitment rate was low (28.6%). Retention was poor; only 4 of 12 completed the three-month diet (MCTKD n=3; MKD n=1). Median duration until discontinuing was 5.2 weeks (0–7 weeks; n=8). Participants made instantaneous decisions without deliberation: relatives supported diet implementation. Decliners made considered decisions factoring diet burden and quality of life. A three-month diet was undesirable to these patients. Median PFS was 11.4 weeks and OS was 67.3 weeks.

Conclusion
Recruitment to a ketogenic-glioblastoma trial is possible. To assess effectiveness in a phase III clinical trial, a six week intervention period is proposed. Future trials should optimise and adequately support the decision-making of patients. The role of relatives should not be underestimated.
Single centre, retrospective review of gamma-knife stereotactic radiosurgery and other therapies on prevalence of seizures in patients with brain metastases
Authors: De Boisanger James , Mackay Katherine , Tancu Cornel , Fersht Naomi , Kitchen Neil , Rees Jeremy 
Published: October 2019

Abstract

Background
An increasing number of patients with brain metastases (BM) are having stereotactic radiosurgery (SRS), but it is not known whether this causes epilepsy.

Methods
We carried out a retrospective review of patients surviving one-year post gamma-knife SRS at the National Hospital for Neurology and Neurosurgery (NHNN) between February 2012 and April 2017.
Data on seizures during the pre- and post-SRS periods were collected along with information about the primary tumour, metastasis location and previous treatments, including whole brain radiotherapy (WBRT) and surgery.

Results
61 patients were treated with SRS. 6 patients had incomplete records and were excluded. Of the remaining 55, 21 had a seizure at some point. 4 had seizures both pre- and post-SRS, 7 had seizures pre-SRS but not post and 10 patients had de-novo seizures post-SRS. 34 did not have a documented seizure at any point.
Of the 14 patients who had seizures post-SRS, 4 also had both WBRT and surgery, 2 had WBRT and 4 had surgery. 100% (4/4) who had WBRT, surgery and SRS went on to have a seizure. Seizures occurred in 11/25 patients who had previous surgery and 7/11 who had previous WBRT.
The primary tumour and metastasis location had no obvious impact on seizure incidence.

Conclusions
The incidence of new seizures post-SRS is low (18%). Previous surgery and/or WBRT may increase seizure incidence post-SRS. The data is currently being reviewed for effect of tumour/ treatment volume, dose delivered, presence of significant oedema and radionecrosis. A larger prospective study is also underway.
Wireless Bioelectronics Towards Treatment of Glioblastoma Multiforme
Authors: Shaw Andie , Sanjuan-Alberte Paola , Hague Richard , Rahman Ruman , Rawson Frankie 
Published: October 2019

Abstract
‘Bioelectronic therapies’ are defined as treatments that provide therapy via electrical stimulation. As electrochemical signalling is a key communication pathway of the human body, learning and modulating these signals could allow us to regenerate lost functions and restore health where previously regarded impossible. Bioelectronics do not yet fully exploit this possibility as they lack resolution and plasticity to fully merge with biology. We aim to negate these problems by pioneering the development of wireless bioelectronics. One exciting area we hope this can be applied is that of tumour treating fields (TTFs).
TTFs apply electric fields to a tumour region, providing a non-invasive anti-mitotic treatment modality. This anti-mitotic behaviour arises due to dipole alignment and di-electrophoresis. However, an understanding of the exact mode of action has not yet been reached. We aim to improve this knowledge by analysing how healthy astrocytes vs glioblastoma cells behave in various electrical systems: comparing ionic currents with electric fields.
Furthermore, we hope to improve targeting of TTFs through the in-situ growth of conductive structures, via wireless electrochemistry.
Proof of concept has been achieved by wirelessly growing silver micro-wires in the presence of U251 glioblastoma cells. Wire growth has been optimised without the presence of cells, allowing controlled growth direction via electrode geometry. Wires range from 2–9µm in diameter and have been shown to be conductive through the completion of a circuit lighting an LED. Such structures could ultimately be grown in the region of a tumour, therefore therapeutically targeting the electric field to that site.
Diffuse Low Grade Glioma - A 10-year single institution case series
Authors: Acharya Shami , Sekhon Priya , Pedro Lavrador Jose , Visagan Ravindran , Narbad Vijay , Jung Josephine , Gullan Richard , Vergani Francesco , Bhangoo Ranj , Ashkan Keymours 
Published: October 2019

Abstract

Objectives
To study clinical features and treatment options between 2007–2018 in a population of diffuse low grade glioma (DLGG) patients (WHO Grade2).

Methods
Single centre retrospective cohort study. Variables reviewed: demographics, extent of resection (biopsy – Bx, subtotal resection – STR, gross total resection – GTR), molecular genetics and outcome.

Results
N=104.M=61 F=43, average age, 41.8 yrs. For their first surgery, 40.4% underwent a Bx, 32.7% STR, 26.9% GTR. 50.9% of patients had a second procedure due to clinical progression (13.8% Bx, 38.85% STR, 47.2% GTR). We were more surgically aggressive at the second sitting (p=0.0021). After 2014, we were more aggressive in terms of achieving a resection over a biopsy alone (pre 2013: 26 Bx, 24 resection, post 2013: 15 Bx, 28 resection). 35% had 1p19q co-deletion, 70% had 1DH1 mutation and 44.6% with MGMT methylated. There was no difference in survival and extent of resection in 1p19 co-deletions (HR 0.35), however there was in the IDH 1 group (HR 1.25. Post operatively, 37.9% patients had chemotherapy and 57.3 % radiotherapy. 80.5% (Bx 65,9% alive, resection 95% alive) of patients are still alive (longest survival 11.6 yrs). Amongst those who died, the mean overall survival was 4.0 (range 0–7 - 5 years): Of these 14% had undergone a Bx and 6% STR/GTR. The adjusted analysis revealed that EOR is the only revelant factor for survival in the population when adjusted for IDH, 1p19q, tumour volume, age, gender and surgery year (p=0.44).

Conclusion
Our data emphasises the importance of achieving maximal resection when possible.
Primary lumbar paraganglioma: A single-centre UK experience over 21 years
Authors: Fiorini Francesco , Lavrador José Pedro , Vergani Francesco , Bhangoo Ranjeev , Gullan Richard , Ashkan Keyoumars 
Published: October 2019

Abstract

Objectives
Paragangliomas are rare neuro-endocrine neoplasms which may occur at multiple anatomical sites, typically the adrenal glands. In the CNS, they can affect the head and neck, and more rarely the lumbar region. Primary lumbar paragangliomas are prominently vascularised lesions which can present variably and pose both diagnostic and surgical challenges.

Methods
We identified and analysed all cases of lumbar paraganglioma confirmed both surgically and histologically, treated at our regional neurosurgical centre. We collected retrospective clinical, radiological, surgical and histological data.

Results
We treated 25 patients with confirmed paraganglioma between 1997–2018. This included 19 primary tumours, of which 13 cases of primary lumbar paraganglioma (8 males (61.5%); mean age 51.3 years, range 33.2 – 68.9).
Patients presented most frequently with a recent worsening of long-standing lower back pain and sciatica. 7 patients were admitted as emergency cases, including 3 with cauda equina syndrome. The average Ki67 mitotic index was 5.7% (range 1 – 10%).

Conclusion
We present one of the largest case series of primary lumbar paragangliomas to date to the best of our knowledge. Defining these clinical, radiological, surgical and histological features may be of assistance in recognising and managing this surgical disease.
Redo-Surgery for Recurrent Glioblastoma: A 10-year single-institution series
Authors: Lavrador José , Ghimire Prajwal , Acharya Shami , Swampillai Angela , Glendenning Jennifer , Brazil Lucy , Alsahib Omar , Gullan Richard , Vergani Francesco , Bhangoo Ranjeev , Ashkan Keyoumars 
Published: October 2019

Abstract

Introduction
Multiple surgeries for recurrent / progressive glioblastomas is a matter of debate within the neuro-oncology community reflecting the higher risk of complications and the limited adjuvant treatment options for patients who recurred after initial treatment. Therefore it is crucial to identify who may benefit of a more aggressive approach and if the neurosurgical practice has changed in the last years.

Methods
Single-Neuro-Oncology Surgical Centre (1 neurosurgical and 2 medical neuro-oncology units) retrospective cohort study of patients with more than one surgery for intracranial Glioblastoma Multiforme (GBM). All patient diagnised with GBM at the time of the first surgery in the period between 2009–2018. Second surgery within 2-months time following initial biopsy or surgical complication or prior to chemo-radiotherapy were excluded. Demographic and clinical data was collected from the medical records.

Results
96 patients underwent second surgery (63 males, 33 females, mean age of 52.6) met criteria for surgery at progression. At the time of the first surgery, the extent of resection (EOR) was: 15 biopsy, 17 subtotal rescetion (STR) and 35 gross total resection (GTR) – 29 missing data. With regards to the molecular markers, 26 were IDH mutant, 73 were MGMT methylated. All of the patients recieved adjuvant chemoradiotherapy following the STUPP protocol prior.

Conclusion
Our data corresponds to the data in the current literature. Further qualitative study will provide an insight into the effectiveness and aggressive approach to the recurrent GBMs.
Delayed heamatoma after melanoma metastasis resection upon restart of Immunotherapy: Case Report and Review of the Literature
Authors: Elhag Ali , Lavrador José , Frantzias Joseph , Kailaya-Vasan Ahilan , Gullan Richard , Ghimire Prajwal , Vergani Francesco , Ashkan Keyoumars , Bhangoo Ranjeev 
Published: October 2019

Abstract

Background
Supratentorial Metastatic Melanomas are common and increasingly treated with immunotherapy. While improving the outcome, the immunotherapy potentially increases the risks of the intracranial surgical procedures, particularly bleeding. However, scarce reports address this complications.

Case Description
A 52-year old male with a history of right upper limb excised skin lesion resected with wide local excision 6 months prior to admission, who presented with a three weeks history of progressive headaches, vomiting, odd behaviours, forgetfulness, and left lower sided weakness. Brain imaging showed a right frontal lesion with evidence of haemorrhage within it with midline shift and mass effect. He underwent craniotomy and resection of the lesion with no post-operative complication, resolution of left sided hemiparesis and post-operative imaging documenting complete resection and no post-operative complications. The histopathology confirmed metastatic melanoma and he received adjuvant immunotherapy (Nivolumab), however he represented 4 weeks post operatively with sudden onset headache with vomiting with no neurological deficit, brain imaging showed a delayed hematoma in the surgical site.

Conclusions
This case report highlights the risk of post-operative bleeding with the immunotherapy and paves the way for further studies with regards to the safety of immunotherapy after intracranial procedures
Endoscopic Evacuation of Intracerebral Hematoma Utilizing a Side-Cutting Aspiration Device
Authors: Shao Jianning , Witek Alex , Borghei-Razavi Hamid , Bain Mark , Recinos Pablo F 
Published: October 2019

Abstract

BACKGROUND
Intracerebral hemorrhage (ICH) is associated with a significant mortality of up to 50%, with almost all survivors suffering from debilitating functional compromise. In most cases, open craniotomy has failed to yield significant survival benefit. However, emerging evidence suggests that minimally invasive surgery (MIS) may yield clinically significant improvements in patient survival and quality of life in cases where open craniotomy has not shown benefit.

CASE PRESENTATION
We report the first documented usage of a side-cutting-aspiration device via an endoscopic approach for the evacuation of a 56cc hematoma, which was a technical modification on previous MIS techniques. The patient is a 50-yr-old female who was transferred emergently to our center with a National Institutes of Health Stroke Scale score of 27 and found to have a large hematoma involving her left basal ganglia. A minimally-invasive approach was elected due to evidence on the risks and suboptimal outcomes of open craniotomy in ICH evacuation. Neuronavigation was used to plan the surgical trajectory for ICH access. Evacuation took place in three main steps: 1) beginning at the center of the clot to remove bulk; 2) mobilizing clots from parenchymal walls to a safe zone via aspiration, followed by clot homogenization; and 3) re-expansion of the cavity via continuous irrigation to allow visualization of further clots. A final inspection was performed to ensure removal of all clots that could be safely removed. The dual functionalities of the device, namely, suction only and suction plus side-cutting functions, enabled key maneuvers, such as clot homogenization and controlled aspiration strength, to be safely performed. A near-total evacuation of the hematoma was achieved without damage to surrounding parenchyma. The patient experienced a rapid clinical course from comatose to discharge-ready in 5 d. At 30-d follow-up, the patient had residual expressive aphasia and was able to ambulate with the assistance of a quad cane. There are no radiographical signs of recurrent hemorrhage or parenchymal injury. Clinical follow-up with this patient is ongoing.

CONCLUSION
This is the first ICH evacuation with a side-cutting-aspiration device via an endoscopic approach. In our patient, this technique proved to be safe and efficacious, suggesting that this technique may be a promising addition to the armamentarium of MIS for ICH evacuation.
Disrupted Autophagy and Neuronal Dysfunction in C. elegans Knock-in Models of FUS Amyotrophic Lateral Sclerosis
Authors: Baskoylu Saba N. , Chapkis Natalie , Unsal Burak , Lins Jeremy , Schuch Kelsey , Simon Jonah , Hart Anne C. 
Published: October 2019

AbstractIt remains unclear how mutations in FUS, a ribonucleoprotein, lead to neuronal dysfunction in Amyotrophic Lateral Sclerosis (ALS) patients. To examine mechanisms underlying ALS FUS dysfunction, we generated the first C. elegans knock-in models using CRISPR/Cas9-mediated genome editing, creating R524S and P525L ALS FUS models. Although FUS inclusions were not detected, ALS FUS animals showed defective neuromuscular function, as well as stress-induced locomotion defects. Unlike C. elegans lacking the endogenous FUS ortholog, ALS FUS animals had impaired neuronal autophagy and increased SQST-1 accumulation in ALS FUS motor neurons. Loss of sqst-1, the C. elegans ortholog for ALS-linked, autophagy adaptor protein SQSTM1/p62, suppressed both neuromuscular and stress-induced locomotion defects in ALS FUS animals, but did not suppress neuronal autophagy defects. Therefore, autophagy dysfunction is upstream of, and not dependent on, SQSTM1 function in ALS FUS pathogenesis. Combined, our findings demonstrate that autophagy dysfunction likely contributes to protein homeostasis and neuromuscular defects in ALS FUS knock-in animals.