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Article ; Online: Investigating centrifugal filtration of serum-based FTIR spectroscopy for the stratification of brain tumours.

Ashton G Theakstone / Paul M Brennan / Michael D Jenkinson / Royston Goodacre / Matthew J Baker

PLoS ONE, Vol 18, Iss 2, p e

2023 Volume 0279669

Abstract: Discrimination of brain cancer versus non-cancer patients using serum-based attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy diagnostics was first developed by Hands et al with a reported sensitivity of 92.8% and specificity ...

Abstract	Discrimination of brain cancer versus non-cancer patients using serum-based attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy diagnostics was first developed by Hands et al with a reported sensitivity of 92.8% and specificity of 91.5%. Cameron et al. then went on to stratifying between specific brain tumour types: glioblastoma multiforme (GBM) vs. primary cerebral lymphoma with a sensitivity of 90.1% and specificity of 86.3%. Expanding on these studies, 30 GBM, 30 lymphoma and 30 non-cancer patients were selected to investigate the influence on test performance by focusing on specific molecular weight regions of the patient serum. Membrane filters with molecular weight cut offs of 100 kDa, 50 kDa, 30 kDa, 10 kDa and 3 kDa were purchased in order to remove the most abundant high molecular weight components. Three groups were classified using both partial least squares-discriminate analysis (PLS-DA) and random forest (RF) machine learning algorithms; GBM versus non-cancer, lymphoma versus non-cancer and GBM versus lymphoma. For all groups, once the serum was filtered the sensitivity, specificity and overall balanced accuracies decreased. This illustrates that the high molecular weight components are required for discrimination between cancer and non-cancer as well as between tumour types. From a clinical application point of view, this is preferable as less sample preparation is required.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Neurosurgical CSF Diversion in Idiopathic Intracranial Hypertension

Geraint J. Sunderland / Michael D. Jenkinson / Elizabeth J. Conroy / Carrol Gamble / Conor L. Mallucci

Life, Vol 11, Iss 393, p

A Narrative Review

2021 Volume 393

Abstract: The prevalence of idiopathic intracranial hypertension (IIH), a complex disorder, is increasing globally in association with obesity. The IIH syndrome occurs as the result of elevated intracranial pressure, which can cause permanent visual impairment and ...

Abstract	The prevalence of idiopathic intracranial hypertension (IIH), a complex disorder, is increasing globally in association with obesity. The IIH syndrome occurs as the result of elevated intracranial pressure, which can cause permanent visual impairment and loss if not adequately managed. CSF diversion via ventriculoperitoneal and lumboperitoneal shunts is a well-established strategy to protect vision in medically refractory cases. Success of CSF diversion is compromised by high rates of complication; including over-drainage, obstruction, and infection. This review outlines currently used techniques and technologies in the management of IIH. Neurosurgical CSF diversion is a vital component of the multidisciplinary management of IIH.
Keywords	idiopathic intracranial hypertension ; pseudotumour cerebri ; cerebrospinal fluid ; ventriculoperitoneal shunt ; lumboperitoneal shunt ; programmable valve ; Science ; Q
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Refining the Intraoperative Identification of Suspected High-Grade Glioma Using a Surgical Fluorescence Biomarker

Colin Watts / Alimu Dayimu / Tomasz Matys / Keyoumars Ashkan / Stephen Price / Michael D. Jenkinson / Gail Doughton / Claire Mather / Gemma Young / Wendi Qian / Kathreena M. Kurian

Journal of Personalized Medicine, Vol 13, Iss 514, p

GALA BIDD Study Report

2023 Volume 514

Abstract: Background. Improving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling. Methods. We designed a multicentre, prospective ... ...

Abstract	Background. Improving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling. Methods. We designed a multicentre, prospective surgical cohort study (GALA-BIDD) to validate the presence of visible fluorescence as a pragmatic intraoperative surgical biomarker of suspected high-grade disease within a tumour mass in patients undergoing 5-aminolevulinic acid (5-ALA) fluorescence-guided cytoreductive surgery. Results. A total of 106 patients with a suspected high-grade glioma or malignant transformation of a low-grade glioma were enrolled. Among the 99 patients who received 5-ALA, 89 patients were eligible to assess the correlation of fluorescence with diagnosis as per protocol. Of these 89, 81 patients had visible fluorescence at surgery, and 8 patients had no fluorescence. A total of 80 out of 81 fluorescent patients were diagnosed as high-grade gliomas on postoperative central review with 1 low-grade glioma case. Among the eight patients given 5-ALA who did not show any visible fluorescence, none were high-grade gliomas, and all were low-grade gliomas. Of the seven patients suspected radiologically of malignant transformation of low-grade gliomas and with visible fluorescence at surgery, six were diagnosed with high-grade gliomas, and one had no tissue collected. Conclusion. In patients where there is clinical suspicion, visible 5-ALA fluorescence has clinical utility as an intraoperative surgical biomarker of high-grade gliomas and can aid surgical decision-making and sampling. Further studies assessing the use of 5-ALA to assess malignant transformation in all diffuse gliomas may be valuable.
Keywords	5ALA ; intraoperative biomarker ; fluorescence ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Current preoperative antisepsis in neurosurgery: an example of the challenges in implementing evidence-based medicine to surgical practice.

Bobby, Sachdev / Michael D, Jenkinson / Hiren, Patel / Benjamin, Davies

Annals of the Royal College of Surgeons of England

2018 Volume 101, Issue 4, Page(s) 279–284

Abstract: Introduction: Surgical site infection is associated with significant morbidity and mortality. Effective preoperative skin decolonisation is an important preventative strategy. The National Institute for Health and Care Excellence clinical guidelines ... ...

Abstract	Introduction: Surgical site infection is associated with significant morbidity and mortality. Effective preoperative skin decolonisation is an important preventative strategy. The National Institute for Health and Care Excellence clinical guidelines recommend decolonisation using chlorhexidine gluconate (CHG) or povidone iodine (PVI). Current evidence indicates that CHG is more effective, while the combination of CHG and PVI is greater still. This study describes current practice among neurosurgeons in the UK, including differences between trainees and consultants, to review compliance with the latest evidence. Materials and methods: A Society of British Neurosurgical Surgeons approved national, multicentre questionnaire was circulated online. A total of 74 complete responses were obtained from 27 trainees and 47 consultants, representing 28 of 37 neurosurgical centres. Results: Of the total responding centres, 36 (49%) used a single agent and 38 (51%) used a dual-agent preparation. One respondent used Tisept®. Seventy (95%) used alcohol in some form and none used aqueous CHG. Trainees were more likely to use a dual-agent preparation (P = 0.025). Forty-seven (63%) prepared the skin three or more times, with trainees preparing the skin more times than consultants (P = 0.002). Conclusion: Neurosurgical practice adheres to national clinical guidelines but not the latest evidence from the literature. Given the weighting placed on randomised controlled trials, such a trial may be required to standardise practice that is likely to reduce surgical site infection.
MeSH term(s)	Anti-Infective Agents, Local/therapeutic use ; Antisepsis/methods ; Evidence-Based Medicine/methods ; Humans ; Neurosurgical Procedures/methods ; Practice Patterns, Physicians'/statistics & numerical data ; Preoperative Care/methods ; Surveys and Questionnaires ; United Kingdom
Chemical Substances	Anti-Infective Agents, Local
Language	English
Publishing date	2018-10-24
Publishing country	England
Document type	Journal Article
ZDB-ID	80044-2
ISSN	1478-7083 ; 0035-8843
ISSN (online)	1478-7083
ISSN	0035-8843
DOI	10.1308/rcsann.2018.0174
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cell cycle progression in glioblastoma cells is unaffected by pathophysiological levels of hypoxia

Rosalie Richards / Michael D. Jenkinson / Brian J. Haylock / Violaine See

PeerJ, Vol 4, p e

2016 Volume 1755

Abstract: Hypoxia is associated with the increased malignancy of a broad range of solid tumours. While very severe hypoxia has been widely shown to induce cell cycle arrest, the impact of pathophysiological hypoxia on tumour cell proliferation is poorly understood. ...

Abstract	Hypoxia is associated with the increased malignancy of a broad range of solid tumours. While very severe hypoxia has been widely shown to induce cell cycle arrest, the impact of pathophysiological hypoxia on tumour cell proliferation is poorly understood. The aim of this study was to investigate the effect of different oxygen levels on glioblastoma (GBM) cell proliferation and survival. GBM is an extremely aggressive brain tumour with a heterogeneous oxygenation pattern. The effects of a range of oxygen tensions on GBM cell lines and primary cells were assessed using flow cytometry. Results indicate that cell cycle distribution and viability are unaffected by long term exposure (24–96 h) to pathophysiological levels of oxygen (1–8% O2). Both transient cell cycle arrest and small amounts of cell death could only be detected when cells were exposed to severe hypoxia (0.1% O2). No significant changes in p21 protein expression levels were detected. These findings reinforce the importance of using physiologically relevant oxygen tensions when investigating tumour hypoxia, and help to explain how solid tumours can be both hypoxic and highly proliferative, as is the case with GBM.
Keywords	Hypoxia ; Cell cycle ; HIF ; Glioblastoma ; Cell death ; Tumour microenvironment ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2016-03-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ketogenic diets as an adjuvant therapy in glioblastoma (the KEATING trial)

Kirsty J. Martin-McGill / Anthony G. Marson / Catrin Tudur Smith / Michael D. Jenkinson

Pilot and Feasibility Studies, Vol 3, Iss 1, Pp 1-

study protocol for a randomised pilot study

2017 Volume 11

Abstract: Abstract Background Glioblastoma is the commonest form of malignant brain tumour in adults, affecting 2–3 people per 100,000 per year. Despite current treatment options including surgical resection, radiotherapy and temozolomide chemotherapy, overall ... ...

Abstract	Abstract Background Glioblastoma is the commonest form of malignant brain tumour in adults, affecting 2–3 people per 100,000 per year. Despite current treatment options including surgical resection, radiotherapy and temozolomide chemotherapy, overall survival at 2 years is approximately 27%, with a median survival of 12–14 months. The ketogenic diet (KD) is postulated to work by simulating the metabolic response to fasting by promoting the utilisation of ketones as a primary energy source, and depriving the glycolytic pathways utilised by malignant glioma cells for growth. At present, there is no consensus as to which KD is preferable, with previous case series using different KDs, at different points in the treatment pathway. The aim of this randomised pilot study is to investigate protocol feasibility, tolerability and the impact on patient health and quality of life of two different KDs within an NHS setting. The results of this pilot study will inform which KD will be most deliverable and adhered to by patients in order to test for effectiveness in future trials. Methods A prospective, non-blinded, randomised, pilot study will be undertaken in 12 patients with newly diagnosed glioblastoma treated by surgical resection. Patients will be randomised in a ratio of 1:1, using a permuted block randomisation method to one of two diets; the modified ketogenic diet and the medium chain triglyceride ketogenic diet. Primary data collection will take place 12 weeks after starting the diet and secondary data collection after 12 months. Feasibility will be assessed by retention and recruitment rates, ability to enrol patients prior to starting chemoradiotherapy, dietary compliance and adjustments, ketone levels, glucose levels and intervention time. Patient impact will be assessed through quality of life and food acceptability questionnaires, gastrointestinal side effects and changes to biochemical markers and anthropometric measures, assessed at regular intervals. Discussion The results of this pilot study will be used ...
Keywords	Ketogenic diet ; Modified ketogenic diet ; Medium chain triglyceride diet ; Glioblastoma ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fibulin-2

Agbolahan A. Sofela / David A. Hilton / Sylwia Ammoun / Daniele Baiz / Claire L. Adams / Emanuela Ercolano / Michael D. Jenkinson / Kathreena M. Kurian / Mario Teo / Peter C. Whitfield / Felix Sahm / C. Oliver Hanemann

International Journal of Molecular Sciences, Vol 22, Iss 2, p

A Novel Biomarker for Differentiating Grade II from Grade I Meningiomas

2021 Volume 560

Abstract: There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas. There is currently no consensus on the optimum management of WHO grade II meningiomas. In this study, we ... ...

Abstract	There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas. There is currently no consensus on the optimum management of WHO grade II meningiomas. In this study, we identified the calcium binding extracellular matrix glycoprotein, Fibulin-2, via mass-spectrometry-based proteomics, assessed its expression in grade I and II meningiomas and explored its potential as a grade II biomarker. A total of 87 grade I and 91 grade II different meningioma cells, tissue and plasma samples were used for the various experimental techniques employed to assess Fibulin-2 expression. The tumours were reviewed and classified according to the 2016 edition of the Classification of the Tumours of the central nervous system (CNS). Mass spectrometry proteomic analysis identified Fibulin-2 as a differentially expressed protein between grade I and II meningioma cell cultures. Fibulin-2 levels were further evaluated in meningioma cells using Western blotting and Real-time Quantitative Polymerase Chain Reaction (RT-qPCR); in meningioma tissues via immunohistochemistry and RT-qPCR; and in plasma via Enzyme-Linked Immunosorbent Assay (ELISA). Proteomic analyses ( p < 0.05), Western blotting ( p < 0.05) and RT-qPCR ( p < 0.01) confirmed significantly higher Fibulin-2 (FBLN2) expression levels in grade II meningiomas compared to grade I. Fibulin-2 blood plasma levels were also significantly higher in grade II meningioma patients compared to grade I patients. This study suggests that elevated Fibulin-2 might be a novel grade II meningioma biomarker, when differentiating them from the grade I tumours. The trend of Fibulin-2 expression observed in plasma may serve as a useful non-invasive biomarker.
Keywords	meningioma ; atypical ; benign ; biomarker ; plasma ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The Modified Ketogenic Diet in Adults with Glioblastoma: An Evaluation of Feasibility and Deliverability within the National Health Service

Martin-McGill, Kirsty J / Anthony G. Marson / Catrin Tudur Smith / Michael D. Jenkinson

Nutrition and cancer. 2018 May 19, v. 70, no. 4

2018

Abstract: There is an increasing interest in the use of the ketogenic diet (KD) as an adjuvant therapy for glioma patients. We assessed the tolerability and feasibility of a modified ketogenic diet (MKD) in patients with glioma, along with willingness of patients ... ...

Abstract	There is an increasing interest in the use of the ketogenic diet (KD) as an adjuvant therapy for glioma patients. We assessed the tolerability and feasibility of a modified ketogenic diet (MKD) in patients with glioma, along with willingness of patients to participate in future randomized controlled trials. The study was undertaken in two parts; a patient questionnaire and evaluation of the diet. One hundred and seventy-two questionnaires were completed; 69% (n = 119) of the population reported MKD should be offered to patients with glioma and 73% (n = 125) would be willing to try MKD for 3 months. Six male patients with high grade gliomas tried the diet; 4 completed the 3-month feasibility period. Ketosis was achieved in all patients. The only gastrointestinal side effect was constipation (n = 2). Minimal changes were observed in weight, body mass index, fat mass and cholesterol profiles. MKD was well tolerated, with few side effects and is deliverable within a financially viable, NHS service. There is a high level of interest in the diet within the glioma patient community to ensure adequate recruitment for a clinical trial. Further studies are required to demonstrate efficacy and patient benefit before implementing a service.
Keywords	adjuvants ; adults ; adverse effects ; body mass index ; cholesterol ; constipation ; gastrointestinal system ; health services ; ketogenic diet ; ketosis ; males ; patients ; questionnaires ; randomized clinical trials ; therapeutics
Language	English
Dates of publication	2018-0519
Size	p. 643-649.
Publishing place	Taylor & Francis
Document type	Article
ZDB-ID	2025822-7
ISSN	1532-7914 ; 0163-5581
ISSN (online)	1532-7914
ISSN	0163-5581
DOI	10.1080/01635581.2018.1460677
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Does the application of diffusion weighted imaging improve the prediction of survival in patients with resected brain metastases? A retrospective multicenter study

Rasheed Zakaria / Yin Jie Chen / David M. Hughes / Sumei Wang / Sanjeev Chawla / Harish Poptani / Anna S. Berghoff / Matthias Preusser / Michael D. Jenkinson / Suyash Mohan

Cancer Imaging, Vol 20, Iss 1, Pp 1-

2020 Volume 7

Abstract: Abstract Background Brain metastases are common in clinical practice. Many clinical scales exist for predicting survival and hence deciding on best treatment but none are individualised and none use quantitative imaging parameters. A multicenter study ... ...

Abstract	Abstract Background Brain metastases are common in clinical practice. Many clinical scales exist for predicting survival and hence deciding on best treatment but none are individualised and none use quantitative imaging parameters. A multicenter study was carried out to evaluate the prognostic utility of a simple diffusion weighted MRI parameter, tumor apparent diffusion coefficient (ADC). Methods A retrospective analysis of imaging and clinical data was performed on a cohort of 223 adult patients over a ten-year period 2002–2012 pooled from three institutions. All patients underwent surgical resection with histologically confirmed brain metastases and received adjuvant whole brain radiotherapy and/or chemotherapy. Survival was modelled using standard clinical variables and statistically compared with and without the addition of tumor ADC. Results The median overall survival was 9.6 months (95% CI 7.5–11.7) for this cohort. Greater age (p = 0.002), worse performance status (p < 0.0001) and uncontrolled extracranial disease (p < 0.0001) were all significantly associated with shorter survival in univariate analysis. Adjuvant whole brain radiotherapy (p = 0.007) and higher tumor ADC (p < 0.001) were associated with prolonged survival. Combining values of tumor ADC with conventional clinical scoring systems such as the Graded Prognostic Assessment (GPA) score significantly improved the modelling of survival (e.g. concordance increased from 0.5956 to 0.6277 with Akaike’s Information Criterion reduced from 1335 to 1324). Conclusions Combining advanced MRI readings such as tumor ADC with clinical scoring systems is a potentially simple method for improving and individualising the estimation of survival in patients having surgery for brain metastases.
Keywords	Brain metastasis ; Cerebral metastasis ; Diffusion MRI ; DWI ; Biomarkers ; Survival modelling ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	610 ; 616
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Development of high-throughput ATR-FTIR technology for rapid triage of brain cancer

Holly J. Butler / Paul M. Brennan / James M. Cameron / Duncan Finlayson / Mark G. Hegarty / Michael D. Jenkinson / David S. Palmer / Benjamin R. Smith / Matthew J. Baker

Nature Communications, Vol 10, Iss 1, Pp 1-

2019 Volume 9

Abstract: Diagnosing brain cancer is frequently difficult and requires specialist equipment. Here, the authors develop their previous attenuated total reflectance-Fourier transform infrared spectroscopy method and incoporate the use of disposable silicon wafers ... ...

Abstract	Diagnosing brain cancer is frequently difficult and requires specialist equipment. Here, the authors develop their previous attenuated total reflectance-Fourier transform infrared spectroscopy method and incoporate the use of disposable silicon wafers for diagnosing brain cancer using serum samples.
Keywords	Science ; Q
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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