bluuebunny/crossref_metadata_2025 huggingface dataset:
Gliocova: Predictors of Post-Operative Complications, 30 Day Mortality and Readmission After First Surgical Intervention in Brain Tumour Patients in England Between 2013-2018
Authors: Mauricaite Radvile , Le Calvez Kerlann , Brodbelt Andrew , Bottle Alex , Gregory Jonathan , Booth Thomas , Williams Matt
Published: October 2022

AIMS

The Gliocova dataset uses linked English national cancer data on all 51,775 adult primary brain tumour patients diagnosed between 2013-2018. Here we investigate patient safety and post-operative complications after first surgical intervention.

METHOD

We identified patients undergoing first surgical intervention (surgical debulking or biopsy) and used a modified Delphi approach to identify diagnosis codes indicating potential post-surgical complications. We calculated Elixhauer Comorbidity Index (ECI) weights based on our data and developed regression models to link patient characteristics and ECI with 30-day mortality, readmission and chance of complication.

RESULTS

29,258 out of 51,775 patients underwent a surgical intervention (28,173 surgical debulking; and 1,207 biopsy). 11,959 (40.9\%) patients had at least one comorbidity during first intervention admission. In hospital mortality was 0.99\% (N = 289), 30-day mortality was 2.3\% (N = 677) and 30-day readmission was 12.7\% (N = 3,725). 13,137 patients (44.9\%) had at least one complication code from our defined list, either during their first surgical intervention or during a 30-day readmission. Predictors of 30-day mortality, readmission, and risk of complications included age, ECI score, number of complications, type of intervention (biopsy vs surgical debulking), income quintile, and tumour type (i.e., Glioblastoma versus other types of brain tumours).

CONCLUSION

To our knowledge this is the first study in England to assess post-surgical complications in a large brain tumour patient cohort. Our further work will focus on variation in outcomes between different centres/ centre volumes/ regions and the cost of complications. More information: https://blogs.imperial.ac.uk/gliocova/about-gliocova/.
MR Electrical Properties Tomography (MREPT) at 9.4T to Assess Treatment Response of Choline Kinase Inhibition on GL261 Glioblastoma
Authors: Alrashidi Tareq , Nooradean Ahmed , Bhaduri Sourav , Mukherjee Soham , Poptani Harish
Published: October 2022

AIMS

To monitor changes in tissue-conductivity based MR parameter in response to JAS239 treatment in preclinical glioblastoma model.

METHOD

C57BL/6 mice were injected intracranially with 5x105 GL261 glioblastoma cells and tumours were observed on T2 weighted MRI. Mice were imaged on day 0 (baseline), day 3 , 6 of treatment and post-treatment day 10. For MREPT, multi-slice-multi-echo sequence was used. Laplacian algorithm was employed to obtain the phase-based MREPT image reconstruction.

RESULTS

Saline treated mice showed a greater increase in tumour volume compared to JAS239 treated animals with respect to baseline. Percentage changes in conductivity values with respect to baseline from saline treated mice were compared to JAS239 treated animals. JAS239 group showed a slight increase in mean conductivity on day 3 and 6 compared to saline group. There were no statistically (p> 0.05) significant differences between the two groups. 4 days after treatment completion (Day10), the mean of conductivity values of JAS239 treated animals compared to saline treated animals showed no statistically (p> 0.05) significant differences. These results may indicate that GL261 tumour model is treatment resistant. Our findings agree with a study conducted by Bhaduri et al, where tumours were treated with JAS239.

CONCLUSION

EPT technique provides unique data on tissue conductivity which can be used to improve the assessment of treatment response in glioblastoma. MREPT parameter might be insensitive to evaluate choline kinase inhibitor. For future work, this technique can be incorporated into multiparametric MRI to complement diffusion and perfusion-weighted imaging of assessing treatment response in glioblastoma.
Survival Outcomes of Stereotactic Radiotherapy for Ten or More Brain Metastases
Authors: Rozati Hamoun , Williams Matt
Published: October 2022

AIMS

Discrepancies exist in the use of stereotactic radiotherapy (SRT) for patients with 10 or more brain metastases. Concerns include multiple metastases being associated with poor survival and the lack of prospective data. We analysed survival outcomes of these patients in a multi-centre cohort.

METHOD

We performed a retrospective cohort study of 511 consecutive patients from three SRT centres treated for brain metastases between January 2010 - August 2021, censored in January 2022. We assessed survival post-SRT of patients with ≥10 metastases against a matched group of 5-9 and 1-4 metastases using the logrank test for statistical testing. We used a multivariate Cox model to assess the relationship between overall survival and: number of metastases; total volume; primary malignancy; use of systemic anti-cancer therapies with intracranial penetrance; controlled extracranial disease. Results with p-values <0.05 were considered significant.

RESULTS

Survival data was available for all patients, and for 85-100% of factors in multivariate analysis. 63 patients had ≥10 metastases (median 19). Median survival was 13.3 months, compared with 15.1 and 19.0 months for the 5-9 and 1-4 metastasis groups respectively. Differences were not statistically significant (p-value 0.14). Increasing volume of disease (HR 1.05 [1.01-1.09], p-value: 0.01), non-small cell lung cancer (HR 3.5 [1.35-9.09] p-value: 0.01) and use of systemic anti-cancer therapy with intracranial penetrance (HR 0.239 [0.105-0.547] p-value: <0.01) had a statistically significant effect on survival in multivariate analysis.

CONCLUSION

Carefully selected patients with multiple metastases have acceptable survival outcomes following SRT and this approach should be more widely considered.
Clinical Evaluation of Gamma Knife Stereotactic Radiosurgery for Metastatic Disease in Elderly Patients
Authors: Bishr Mai , Tancu Cornel , Fersht Naomi , Kitchen Neil , Kosmin Michael
Published: October 2022

AIMS

Gamma Knife Stereotactic Radiosurgery (GK-SRS) is an effective treatment option for limited brain metastases (BM); however, there is a paucity of data about its use in the elderly. Our aim is to explore the clinical outcomes of elderly cancer patients treated for BM with GK-SRS at our institution.

METHOD

We identified cancer patients aged ≥80 years at the time of receiving GK-SRS to BM between July 2017 and August 2021 from our electronic institutional database. Descriptive statistics and Kaplan–Meier analysis were performed using SPSS v.22.

RESULTS

A total of 24 patients were identified, with a median age of 83 years (range 80.1-89.9). The most common primary tumours were melanoma (58.4%) and lung (20.8%). In 14 patients (58%), multiple BM were treated simultaneously with a median of 2 lesions (range 2-15). The median target volume was 1.34cc (range 0.03-15.06). Prescribed doses ranged from 18Gy – 25Gy, prescribed to the 41-97% isodose line. After a median follow-up of

6.9 months (range 1.9-49.4 months), the local control rate (LCR) was 91.3% and the median post-GK-SRS overall survival was 9.8 months (95%CI 5.4-14.3). This compares to our previously published data from our wider GK-SRS-treated BM patient cohort, which showed a median survival of 15.6 months and LCR of 94.6%.

CONCLUSION

GK-SRS is an effective treatment modality for selected cancer patients with BM, including those over 80 years of age. Multi-institutional prospective studies are warranted to further explore the safety and functional outcomes of GK-SRS in elderly cancer patients.
The Usefulness of Pre-Operative Extra-Cranial Imaging in Radiologically Suspicious Glioblastoma Multiforme in the West of Scotland: and a Proposal of an Imaging Diagnostic Pathway
Authors: Lammy Simon , McPartlin Rebecca , Bridgman Elsie , Bouttell Janet , Brown Jennifer
Published: October 2022

AIMS

Objective: a CT chest, abdomen and pelvis (CT CAP) is probably unnecessary if a glioblastoma multiforme (GBM) is detected on initial CT brain (CTB) prior to definitive MRI. We audited its frequency to develop a management pathway

METHOD

Methods: 12-month retrospective case series from 2018 of patients having an initial CTB suspicious for GBM. We dichotomised patients into two groups a) tissue proven and b) non-tissue proven, due to these representing distinct patient profiles. We quantified frequencies of plain and contrast CTBs, CT CAPs and extra-cranial malignancy.

RESULTS

Results: Group 1 (total n=84 [mean age 59 years]): 64% had a CT CAP. Plain CTB occurred in 24% and contrast CTB in 76%. Extra-cranial malignancy was 8% and 12%. Group 2 (total n=47 [mean age 73 years]): 85% had a CT CAP. Plain CTB occurred in 22% and contrast CTB in 78%. Extra-cranial malignancy was 33% and 23%. Negative CT CAPs in ~88% of CTBs in Group 1 and ~75% of CTBs in Group 2.

CONCLUSION

Conclusions: patients having a contrast CTB as their initial imaging modality, being suggestive of GBM, prior to definitive MRI, and managed surgically, having no history of extra-cranial malignancy, do not need a CT CAP unless MRI is non-diagnostic.
Evaluation of a Panel of 105 Cytokines from Human Glioblastoma (GBM) Tissue Maintained, and Treated, on a Unique Microfluidic Platform
Authors: Moursi Amr , Barry Antonia , Achawal Shailendra , Rajaraman Chittoor , Feugere Lauric , Beltran-Alvarez Pedro , Greenman John
Published: October 2022

AIMS

The first aim was to measure the changes in the levels of 105 cytokines potentially released by GBM tissue maintained on-chip. The second aim was to compare the cytokine profiles from control GBM tissue and tissue treated with anti-GBM drugs {temozolomide (TMZ) at 1 and 10μM both with 1μM arginine methylation inhibitors}.

METHOD

Intra-operative tissue biopsies were taken from the tumour and transferred immediately from the operating theatre to Hull University laboratories (< 1 hour). Tissue samples were maintained in a viable state in a bespoke chip device for eight days. The biopsy was perfused (3μl/min) with culture medium, with or without drug treatment. Eﬄuents from the biopsies were collected at 24h intervals. Cytokines levels were measured using the Proteome Profiler Human XL Cytokine Array Kit (R&D Systems), each membrane is spotted with 105 different cytokine antibodies in duplicate.

RESULTS

Six GBM diagnosed patients (five negative for MGMT) were recruited and studied. Eleven cytokines showed consistent, high level, release from GBM tissue either in control or treated samples: Chitinase3-like1, IL8(CXCL8) ,MCP-1(CCL2 ),MIF(Macrophage migration inhibitory factor), MMP-9(Matrix metallopeptidase 9), Osteopontin(OPN), Serpin E1, VEGF(Vascular endothelial growth factor) ,Apolipoprotein A-I, Angiogenin and Emmprin. Multivariate analysis (PERMANOVA) did not show evidence for differential cytokine release profiles with time (P=0.113), treatment (P=0.629), , nor the combined interaction (P=0.936).

CONCLUSION

GBM biopsies remained viable on the microfluidic platform, shown by sustained cytokine production cytokines. We have also shown that treatment with TMZ plus arginine methylation inhibitors does not significantly affect cytokine release over an eight day period.
CONSENT - A Randomised Controlled Trial of Enhanced Informed Consent Compared to Standard Informed Consent to Improve Patient Understanding of Early Phase Oncology Clinical Trials – GBM Cohort (Nonrandomised) Analysis
Authors: Pal Abhijit , Daly Robert , Mohamedkhan Shybi , Grochot Rafael , Stapleton Sarah , Yap Christina , Magkos Dimitrios , Baikady Bindumalini Rao , Minchom Anna , Banerji Udai , De Bono Johann , Karikios Deme , Boyle Frances , Lopez Juanita
Published: October 2022

AIMS

Early phase cancer clinical trials have become more complicated and patients often misunderstand their nature and purpose. CONSENT (NCT04407676) is a randomised controlled trial testing whether enhanced informed consent for patient education can improve comprehension – since patients with glioblastoma multiforme (GBM) have a higher rate of baseline cognitive impairment, we studied this group separately.

METHOD

GBM patients (from the ICE-CAP Phase 1 study - NCT03673787), underwent the schedule for the standard CONSENT arm - full length trial PIS, Quality of Informed Consent Questionnaire Parts A and B (QuIC-A and QuIC-B), experimental intervention (2 page study aid and 10 educational videos), and a repeat QuIC-A and QuIC-B. The primary endpoint for this subgroup was the difference in QuIC-A scores before and after the intervention using a paired t-test.

RESULTS

6 patients with GBM were recruited - 3 did not complete any study questionnaires. The three pre intervention QuIC-A scores were 70, 81, 88, with a mean of 75 (unit reference 76). The three pre intervention QuIC-B scores were 69, 62, 75 with a mean of 69 (unit reference is 91). Only one patient completed the post intervention questionnaire - their QuIC-A score moved from 88 to 100.

CONCLUSION

This study demonstrates the significant difficulties in studying comprehension in patients with GBM considering early phase trials. There is a need for creative multi-modality solutions to provide information to GBM patients considering clinical trials, and novel tools to assess the effectiveness of these solutions.
Patient Information on Awake Craniotomy: A Video Leaflet
Authors: Wall Gemma , Cooke Gill , Albanese Erminia , Merron Stephen , Chan Huan , Craker Lloyd , Owen Michael
Published: October 2022

AIMS

An Awake Craniotomy is a neuro-surgical procedure where the patient remains awake for all or part of their surgery to allow a lesion to be maximally resected without damaging healthy brain functioning. An annual audit of our Patient Satisfaction Survey demonstrated that ‘Receiving Written Information’ was scoring below standard. A new leaflet was designed to address this and it was developed into a ‘Video Leaflet’ comprising a 10 minute audio-visual production, accessed by QR code.

METHOD

The team created a scripted description of the patient Awake Craniotomy experience. The script was coded into: audio narration, written information or video content. The areas covered were: consultations with the team; pre and intra-operative testing; fMRI scanning; hospital environments; and follow-up. The script was filmed with written consent from all involved and then collated by the Communications Department. There were several revisions made based on feedback from all involved resulting in the final product.

RESULTS

The Video Leaflet is ready to be demonstrated to and evaluated by patients using a structured questionnaire. The annual audit of Satisfaction Surveys will be compared prior to and post the introduction of the Video Leaflet to determine whether ratings for ‘Receiving Written Information’ have improved. Questionnaire results which are available by the conference date will be presented as preliminary findings.

CONCLUSION

It is anticipated that the Video Leaflet will further optimise patient preparation, facilitate informed consent and contribute to maximising coping and engagement from a patient perspective to improve patient experience for a complex and daunting procedure.
Management of Low-Grade Gliomas – Extent of Resection Matters But Not All Tumours Are Amenable to Surgery
Authors: Sokratous Giannis , Sokratous Jill , Bakhsh Ali , Brodbelt Andrew , Chavredakis Emmanuel , Lawson David , Farah Jibril , Shenoy Aditya , May Chloe , Jenkinson Michael , Mehta Shaveta
Published: October 2022

AIMS

To present and review our experience in the management of low-grade gliomas.

METHOD

Retrospective case note review of all patients with WHO grade 2 glioma from 2011 to 2018 (based on WHO criteria at time of diagnosis). Data collected on demographics, presentation, location, initial management, histology, treatment, progression free (PFS) and overall survival (OS).

RESULTS

130 eligible patients. Median follow 4.6 years (up to 10.5). Median age 40 years (range: 18-83). There were 70 (53.8%) astrocytomas, 44 (33.8%) oligodenrogliomas, 16 (12.3%) oligoastrocytomas. 66%(n=86) presented with seizures, 10.7%(n=14) with sensory symptoms, 8.5%(n=11) with speech disturbance, 5.3%(n=4) with motor symptoms and 12.3%(n=16) were identified incidentally. 50.1%(n=65) were frontal, 27.7%(n=36) temporal and 9.2%(n=12) parietal. 1st line treatment was resection in 70.7%(n=92), biopsy in 23.8%(n=31) and observation in 4.6%(n=6). 15.4%(n=20) received adjuvant radiotherapy alone and 6.1%(n=8) received adjuvant radiotherapy followed by chemotherapy . At first recurrence, 31.6%(n=12) received further surgery and 95%(n=38) received radiotherapy and/or chemotherapy . Median PFS from 1st line treatment 66, 44 and 33 months for gross total resection (GRT), subtotal resection (STR), and biopsy respectively. Overall survival was 95.1%, 79.3% and 69.% for GTR, STR and biopsy respectively.

CONCLUSION

Management of low-grade gliomas remains challenging. Extent of resection impacts prognosis but not all patients have gliomas amenable to surgery. The effects of chemoradiotherapy will be presented in future meetings as this is an ongoing project.
Survival and Prognostic Factors in Melanoma Brain Metastasis (MBM) Treated With Stereotactic Radiosurgery (SRS)
Authors: Fitzpatrick Amanda , Bartram Alex , Rockall Louise , Mitchell Adam , Palmer Kieran , Crusz Shanthini , Plowman Nick , Lewis Rachel
Published: October 2022

AIMS

Brain metastasis is a frequent complication in melanoma, ultimately affecting 40–60% of patients with metastatic disease1. In the era of immune checkpoint and small molecule inhibitor therapy, there is a need to identify patient, tumour and treatment characteristics which may predict an improved prognosis in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM).

METHOD

Retrospective casenote review was carried out for all patients receiving SRS, including gammaknife and cyberknife, for MBM between 2014 – 2020 at Barts Cancer Centre. Overall survival (OS) was calculated using the Kaplan-Meier method. Differences between groups were assessed using the Log-rank (Mantel-Cox) test.

RESULTS

93 patients were treated with SRS for MBM, with a median of 15 patients treated per year. The median age at treatment decision was 60 years (range 26 – 90): 59% were male; 41% female. Median number of lesions treated was 2 (range 1 – 15). Survival data was available for 74 patients: median overall survival for all patients was 9.5 months, with no significant survival difference by gender nor treatment year (pre-2017 vs. post-2017). However, treatment of 1-2 brain lesions carried a better prognosis compared to 3 or more lesions (median 12.2 vs. 5.7 months, p = 0.0292).

CONCLUSION

Initial analysis reveals an improved overall survival when fewer MBM are present. Further analyses will examine the impact of the following factors on patient survival: status of extracranial metastases, symptomatic vs. asymptomatic brain metastasis, intratumoral haemorrhage, systemic therapy pre- and post-SRS, and corticosteroid use during and after SRS.
CyberKnife Stereotactic Radiosurgery for Spinal Haemangioblastoma: A Single Centre Experience
Authors: Palmer Kieran , Whitelaw Gemma , Krishnan Anant , Dean Chris , De Luna Paolo Jose , Mitchell Adam , Plowman Nick , Lewis Rachel
Published: October 2022

AIMS

‘CyberKnife’ stereotactic radiosurgery (SRS) is increasingly being used as a treatment for spinal haemangioblastoma to avoid complex surgery, especially in patients with multi-focal tumours associated with von Hippel-Lindau syndrome (VHL). Here we present the outcomes of patients treated in our centre.

METHOD

Retrospective review of patients treated at St Bartholomew’s Hospital, London. Assessment of radiological response was based upon RECIST criteria. The development of a symptomatic new or worsening cyst was included in the definition of progression when determining overall tumour control. Solid and overall tumour control rates were calculated using the Kaplan-Meier method.

RESULTS

14 tumours in 10 patients were included. 70% of patients were male and 90% had VHL. 9 (64%) tumours had an associated cyst. The median (IQR) age at treatment was 45.5 (43.5 – 53). The median gross tumour volume was 0.355cc. Patients received a mean marginal prescribed dose of 9.6Gy in a single fraction (mean central dose 14Gy) – dose constrained by spinal cord tolerance. Mean follow up was 15.4 months. 7 patients’ symptoms improved or were stable and 3 worsened. Radiologically, 11 (78.6%) of tumours were stable or regressed, and 3 (21.4%) progressed. The 1-year solid tumour and overall tumour control rates were 92.3% and 75.7% respectively. All patients were alive at most recent follow up. 2 patients developed grade 1 adverse related events.

CONCLUSION

SRS is a safe and effective treatment modality for spinal haemangioblastoma. Further prospective randomised trials with longer follow up are required to determine the optimum management strategy.
The Measurement and Reporting of Outcomes in Clinical Studies of Incidental and Untreated Meningioma Are Heterogeneous and Prevent Knowledge Progress: A Systematic Review
Authors: Millward Christopher , Islim Abdurrahman , Keshwara Sumirat , Srikandarajah Nisaharan , Brodbelt Andrew , Marson Anthony , Williamson Paula , Jenkinson Michael
Published: October 2022

AIMS

There is increasing interest in the clinical management of patients with incidental and untreated intracranial meningioma. Determining balance between observation and intervention is a key research priority. However, heterogeneity of outcome measurement and reporting has hampered knowledge progress. This systematic review aimed to summarise the outcomes measured and reported in such studies.

METHOD

A systematic literature search was performed to identify published full-texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma. Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Deduplication, grouping, and classification of verbatim outcomes was performed to identify unique outcomes reported in the literature.

RESULTS

Thirty-three published articles and one ongoing study were included, describing 32 unique studies: retrospective n=27, cross-sectional n=3, prospective n=2. 271 verbatim outcomes were reported, of which 90 were defined. Following deduplication, 181 unique verbatim outcomes remained and were grouped into 53 unique ‘non-verbatim’ outcomes. Those reported most frequently included: volume of tumor n=18, growth of tumor n=30, absolute growth rate n=18, relative growth rate n=17, need for surgery n=21, and progression-free survival n=11.

CONCLUSION

Harmonisation of outcome measurement and reporting across clinical studies of incidental and untreated intracranial meningioma could facilitate knowledge progress for this priority research area. The unique outcomes identified from this systematic literature review will be prioritised through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a Core Outcome Set (COS) for use in future clinical studies.
Assessment of the Efficacy of an Alternative Regimen of Lomustine in Recurrent GBM – A Single Centre Experience
Authors: Tan Chevonne , Wong Helen , Flint Helen , May Chloe , Shenoy Aditya , Eswar Chinnamani , Mehta Shaveta
Published: October 2022

AIMS

Lomustine (CCNU) based regimens are frequently used for recurrent glioblastoma multiforme (GBM). The usual CCNU regimen is 100-130mg/m2, day 1 x 6-weekly cycle for up to 6 cycles. Efficacy is limited, with median progression-free survival (PFS) approximating 1.0-3.0 months with higher haematological toxicities, particularly thrombocytopenia around 13-25%. The Clatterbridge Cancer Centre, UK, has adopted the regimen of 40mg once a day over 4 days x 4-weekly for up to 6 cycles. This study aims to identify the efficacy and toxicity profile of this regimen in recurrent GBM.

METHOD

A retrospective analysis on 113 recurrent GBM patients, treated with single-agent CCNU as a second-line, between June 2016 and January 2020. Kaplan-Meier survival estimates identified PFS, PFS at 6 months (PFS6) and Overall Survival (OS) using SPSS v.27. Overall Responses were based on imaging or clinical assessment in patients with at least 2 CCNU cycles. SACT assessments and blood test records, using CTCAE v5.0 grading, identified clinical adverse events.

RESULTS

We observed an 18.8% overall response rate with 2.4% partial response and 16.5% stable disease. There was a CCNU-specific 8-month median OS, 4-month median PFS, and 20.4%% PFS6. This regimen was well-tolerated. The most common toxicity was grade 1 fatigue (38.9%). The Grade 3 or 4 haematological toxicity was low with 12% thrombocytopenia and 2.7% neutropenia rates in patients.

CONCLUSION

This study suggests a reasonable alternative to the usual regimen, offering improved tolerance, lower toxicity rates, and equivalent efficacy. We propose prospective studies comparing differing CCNU regimens to mitigate retrospective studies’ limitations.
Neurosurgery Database for Brain Tumour Patients
Authors: De Luna Paolo Jose , McKintosh Edward , Scandura Glenda , Hilling Molly , Ghosh Arnab
Published: October 2022

AIMS

We develop an electronic database system for brain tumour patients. This aims to provide accessible and comprehensive data in a unified database for all neuro-oncology patients at Barts Health NHS Trust.

METHOD

The database was created using Microsoft Access with data categorised using forms and tables. Initially, patients were added retrospectively using the neuropathology list and the neuro-oncology multi-disciplinary team patient lists. Once creation and validation was complete, patients were added prospectively. Queries on neuro-oncology patients can be launched to produce datasets which can be copied to Microsoft Excel spreadsheets for sorting, calculation, and graph creation.

RESULTS

At the time of writing, records of 1171 neuro-oncology patients who were accepted for MDT discussion at Barts Health NHS Trust are included in the database. It is used to routinely run data queries more efficiently and complete in a shorter time. Queries include post-operative complications, overall survival, histological diagnosis, and average surgery waiting time. These queries have already been used to publish audit-based research papers and will be used increasingly as part of routine clinical governance.

CONCLUSION

The database yields data about treatment of our brain tumour patients with increased completeness and significant reduction in time to return queries, compared to using standard data management. The database has been used to produce data, including tumour types, seizure incidence, and post-operative complications. We have been successful in producing published research, although low absolute complication numbers in the current dataset have not yet allowed comparison of complications rates at individual clinician and team level.
Clinical Outcome of Glioblastoma Treated in North Wales Cancer Treatment Centre Between 2014 and 2018
Authors: Ghosal Niladri , Burford Pauline , Showkat Mehrine , Abbasi Ehsaan Ullah , Sirelkhatim Mazin , Kodavatiganti Ravi , Hind Ann , Soe Win
Published: October 2022

AIMS

Glioblastoma (GBM) is the most common primary brain tumour in adults and has a very poor clinical outcome. An audit of the clinical outcomes of patients with glioblastoma at our centre was conducted and compare with the results reported nationally in the National Cancer Registration Service and Hospital Episode Statistics 2007– 2011.[1] ) as well as international standards.

METHOD

Patients with GBM in North Wales Cancer Treatment Centre from October 2014 to September 2018 were identified using Canisc databases. We censored 2 patients because of no further follow up due to transferred to other centres. Treatment and outcome data was retrospectively collected using electronic record systems and the case notes.

RESULTS

The total 117 patients with GBM were identified. The craniotomy and Debulking surgery was done in 67, Biopsy only in 29 and no surgery in 21 patients. Median OS of all patients was 9.2 months. The median OS in the patient group of under 70 years treated with Concurrent chemo-radiotherapy (60 Gy) followed by adjuvant chemotherapy was 16.9 months. Median OS of patients aged 70 years and above who had “radiotherapy” or “no radiotherapy” were 6.5 months versus 1.9 months respectively.

CONCLUSION

Our results are comparable to the national outcomes. We would be reporting further on the differential survivals of different age groups and with results of genetic biomarker stratifications.
Predictors of Improved Outcomes in the Management of Newly Diagnosed Glioblastoma Multiforme – Retrospective Review of a Single Centre Experience
Authors: Ziff Charlotte , Price Louise , Elmasry Abdelfattah , Giridharan Selvaraj
Published: October 2022

AIMS

To assess the benefit of combining maximal resection, Gliadel wafer insertion, CCRT and 4 or more cycles of adjuvant TMZ.

METHOD

We retrospectively reviewed a cohort of 110 patients who had undergone neurosurgery followed by chemo-radiotherapy (CRT) 60 Gray in 30 fractions and had at least one cycle of adjuvant TMZ from 2007 to 2016. Minimum follow up period 5 years.

RESULTS

Patients who had maximal safe debulking plus Gliadel wafer insertion, median OS was 19.5 months (95% confidence interval 14-30) those without wafers median OS was 16 months (95% confidence interval 14 – 21), P=0.06; significant on cox regression modelling. (P-value 0.008). Those continuing to receive at least 4 cycles of adjuvant TMZ median OS improved by 10 months compared to those unable to complete 4 cycles (10 vs 20 months). On cox analysis the number of adjuvant cycles of TMZ significantly affects OS, P-value 0.0003. Of these significant predictors of OS when combined (n=12) median OS was 18 months. Compared to 16 months for those who did not receive Glidel wafers and could not complete 4 cycles of TMZ following CRT. OS log-rank test P-value 0.4

CONCLUSION

We were not able to demonstrate a statistically significant improved OS for those undergoing wafer insertion and completing at least 4 cycles of TMZ. Data may be inconclusive due to the small numbers, we conclude standard of care should still remain maximal safe debulking followed by CCRT and TMZ.
Evaluation of Bebtelovimab for Treatment of Covid-19 During the SARS-CoV-2 Omicron Variant Era
Authors: McCreary Erin K , Kip Kevin E , Collins Kevin , Minnier Tami E , Snyder Graham M , Steiner Ashley , Meyers Russell , Borneman Tina , Adam Michelle , Thurau Lauren , Yealy Donald M , Huang David T , Bariola J Ryan , Schmidhofer Mark , Wadas Richard J , Angus Derek C , Kip Paula L , Marroquin Oscar C
Published: October 2022

Background

Monoclonal antibody (mAb) treatment is associated with decreased risk of hospitalization and death in high-risk outpatients with mild to moderate coronavirus disease 2019 (COVID-19) caused by early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Bebtelovimab exhibits in vitro activity against the Omicron variant and its sublineages; however, clinical data are lacking.

Methods

A retrospective cohort study was conducted comparing bebtelovimab-treated patients with propensity score–adjusted and matched nontreated control groups. Participants included high-risk outpatients eligible for bebtelovimab treatment under Emergency Use Authorization with a positive SARS-CoV-2 test from March 30 to May 28, 2022. Treated patients received single-dose intravenous treatment with bebtelovimab. The primary outcome was hospitalization or death over 28 days.

Results

Before matching/statistical adjustment, mAb-treated patients were, on average, 10 years older than nontreated patients (61.6 vs 51.3 years) and had higher prevalence of obstructive sleep apnea, hypertension, chronic kidney disease, cancer, organ or cell transplant, and immunocompromised status (standardized mean differences ≥0.20). The adjusted odds ratio (OR) of hospitalization or death comparing 1006 treated with 2023 nontreated patients was 0.50 (95% CI, 0.31–0.80). Among 930 treated and 930 propensity score–matched nontreated patients, the incidence of hospitalization or death was 3.1% vs 5.5%, respectively (conditional OR, 0.53; 95% CI, 0.32–0.86). The lower odds ratio of hospitalization or death associated with bebtelovimab treatment was most evident in older patients, those with immunocompromised status, and fully vaccinated patients.

Conclusions

Monoclonal antibody treatment with bebtelovimab among COVID-19 outpatients is associated with lower odds of hospitalization or death, particularly among immunocompromised and older patients.
Degendering the Law Through Stereotype Theory
Authors: Bornstein Stephanie
Published: October 2022

The development of gender stereotype theory in feminism and in the law reflects three interrelated ideas: uprooting women’s subordination, promoting individual liberty, and dismantling the gender binary. In early cases, legal advocates pursued an anticlassification strategy to challenge “separate spheres” ideology, while laying the groundwork for antisubordination approaches. In later cases, advocates used social science on bias to challenge the structural nature of gender stereotypes and framed discrimination because of sexual orientation or gender identity as an unlawful penalty for gender nonconformity. Gender stereotyping has become a primary concept in antidiscrimination law, helping expand what constitutes discrimination “because of sex” and the types of proof that may support discrimination claims. Yet while gender stereotyping arguments have advanced formal equality goals, they have been less successful in achieving substantive equality, redressing intersectional discrimination for women of color, or reaching beyond the gender binary. As with feminist legal theory, then, gender stereotype theory continues to evolve.
Applying International Feminist Insights to Gendered Violence in the United States
Authors: Higgins Tracy E.
Published: October 2022

This chapter explores practical and theoretical insights gained from international human rights work on gender equality and their potential application to persistent problems of gender-motivated violence in the United States. Beyond simply asserting the relevance and application of international human rights instruments to domestic law in the United States, the chapter focuses on various ways that international human rights theorists have conceptualized the role of the state in committing, tolerating, and supporting gendered violence. Because international human rights law necessarily foregrounds the state, it offers feminist theorists working on domestic law new ways to consider both the advantages and the risks of invoking state power as a means of disrupting patriarchy.
Pacification in Asia since the End of the Cold War
Authors: Brenner David
Published: October 2022

Peacebuilding scholars have highlighted the illiberal nature of pacification practices in Asia, often in juxtaposition to the supposedly liberal character of Western peacebuilding approaches. This binary between Western “liberal” and Eastern “illiberal” peacebuilding however seems problematic. The dichotomy does not account for the authoritarian tenets of Western “liberal peacebuilding” and, consequently, fails to specify the political condition of pacification in Asia. To offer a better understanding of the politics of peacebuilding in Asia, this chapter historicizes conflict and pacification in the region. Doing so highlights the role of ethnicity and nationalism in driving protracted conflict between the postcolonial nation-state and ethnic minority populations in the region. It also provides for an alternative understanding of contemporary peacemaking efforts in Asia, which often unfold within the trajectory of ethnocratic statebuilding. As this approach to pacification seeks to align the state container with a national body, it has often fueld resistance and conflict rather than peace.
Elihu Burritt
Authors: Howlett Charles F.
Published: October 2022

Elihu Burritt (1810–1879) was a self-taught blacksmith by trade who mastered some forty languages while growing up in New England. A publicist at heart and an idealist in temperament, Burritt singlehandedly founded the most famous nonsectarian peace organization of his century, League of Universal Brotherhood. His organization linked the American cause to sympathetic counterparts on the British Isles and the European continent. Reaching out primarily to the laboring masses in the United States and abroad, he carried his message of peace through his short-lived weekly newspaper (Christian Citizen), his “Friendly Addresses” filled with signatures on both sides of the Atlantic that he personally delivered to officials in Washington DC, and his “The Olive Leaf Mission” through which peace messages were inserted in some forty continental newspapers and in presses in the United States. At the time of his death in 1879, he was considered the most popular peace figure in nineteenth-century America.
Sérgio Vieira de Mello
Authors: Hartwell Leon
Published: October 2022

Sérgio Vieira de Mello (1948–2003) was a legendary United Nations diplomat and quintessential negotiator. Throughout his career he served in a variety of hotspots where he rubbed shoulders with some of the world’s most objectionable characters, including génocidaires, mass murderers, and war criminals. His friends joked that his memoirs should be entitled My Friends: The War Criminals, while some individuals were deeply uncomfortable with Vieira de Mello’s undertakings. This chapter focuses on some of Vieira de Mello’s ventures in Cambodia and the former Yugoslavia. It is argued that he left behind important lessons as to why, if, and how one should bargain with the devil.
Introduction
Authors: Peterson Christian Philip , Howlett Charles F. , Buffton Deborah D. , Hostetter David L.
Published: October 2022

This introductory chapter seeks to explore how peace historians affirm that the pursuit of peace is as significant as military conflict in explaining the past. The task of historians who explore the dynamics of peacemaking is to examine how people, across time and place, have striven to create diverse cultures of peace and applied strategies for change. Such exploration reveals that people can effectively challenge a violent status quo by describing the ways that peace advocates have resisted militarism, nationalism, xenophobia, and oppression. Greater understanding of the many methods of peacemaking also provides examples of legitimate civic systems capable of reducing and preventing violent conflicts. As part of a broader, interdisciplinary inquiry, peace history evaluates efforts to cultivate practices of peace aimed at mitigating violence and preventing major state wars in an increasingly dangerous world. What is peace history? What have peace historians done so far? What are the strengths and limits of peace history, and what can it offer for the future? What is the relationship between peace history and other related fields, such as peace and conflict studies, conflict resolution, and so on? These issues are addressed from a chronological and topical approach tied to a global outlook.
تعزيز استجابة الشرطة لـ كوفيد- 19 مع المشاركة الإعلامية: تجربة الإمارات العربية المتحدة
Authors: علم إدريس
Published: October 2022

الملخص

صَنّفت التقييماتُ العالمية المستخلصة للاستجابة لجائحة كوفيد- 19 والممارسة السريرية العالمية (وهي شبكة تتكون من 12942 طبيباً من 151 دولة) الاستجابةَ العالميةَ لأمراض العدوى في الإمارات العربية المتحدة باستمرار على أنها واحدة من أكثر الدول فعالية في الاستجابات الطبية لجائحة كوفيد- 19. بالتوازي مع ذلك، فإنه وفقًا لمقياس إيدلمان للثقة لعام 2020، فقد بلغت ثقة الجمهور في حكومة الإمارات العربية المتحدة 81٪ - وهي نتيجة رائدة في الشرق الأوسط. وفي حين لوحظ انتشار شائعات حول سوء الفهم على نطاق واسع ونقص التنسيق في المراحل الأولى من كوفيد- 19 على مستوى العالم، أظهرت حالة الإمارات العربية المتحدة نهجًا وتجربة إيجابية شاملة. يهدف البحث الوارد في هذه الورقة إلى فهم دور الإعلام في استجابة الشرطة فيما يتعلق بإدارة مخاطر كوفيد- 19 في الإمارات العربية المتحدة. تم إجراء تحليل محتوى الوثائق ومصادر البيانات من مصادر البيانات الوصفية العامة المتعلقة بـ كوفيد- 19. تشير النتائج إلى أن البنية التشريعية والمؤسسية المواتية المحددة مسبقًا، والكفاءة المهنية لوسائل الإعلام والشرطة، والأساليب التعاونية بين الهيئات المنفذة ساهمت في نجاح المرحلة المبكرة من إدارة مخاطر كوفيد- 19 في الإمارات العربية المتحدة. يساهم هذا البحث في تكوين مجموعة المعرفة في إدارة مخاطر الجائحات والوباء المعلوماتي من خلال تحليل تجربة الإمارات العربية المتحدة.
الشرطة الذكية: مبادرة شرطة أبو ظبي القائمة على الذكاء الاصطناعي والنظام العالمي لتحديد المواقع (جي بي اس) لخفض مخالفات سائقي المركبات الثقيلة
Authors: ديفيس أماندا , الشامسي أحمد سرور
Published: October 2022

المخلص

واحدة من نتائج مجتمع القرن الحادي والعشرين الذي يتطور بسرعة كبيرة هو إدارة حركة المرور عالميا. تُعَدّ حوادث الاصطدام الناجمة عن حركة المرور من أكثر الحوادث شيوعا مما يتطلب استجابة الشرطة. يناقش البحث في هذا المقال استراتيجية التدخل التي طورتها وطبقتها شرطة أبو ظبي لتقليل تأثير مخالفات سائقي المركبات الثقيلة والآثار المصاحبة للاصطدام والوفيات والإصابات خلال 5 سنوات حتى أبريل 2020. تقدم هذه المقالة النتائج المستخلصة من تقييم تأثير نظام أذونات الشاحنات لمركز المرور الذكي التابع لشرطة أبو ظبي والذي يدعمه نظام تعقب مركبات ذكي معقد متعدد الأبعاد قائم على التكنولوجيا إلى جانب عملية عقوبة انتهاك السائق. ويشير تحليل البيانات إلى حدوث انخفاض إيجابي في الحوادث الناجمة عن الشاحنات والوفيات والإصابات الناجمة عنها خلال فترة ما بعد التدخل. يشير البحث إلى أن استراتيجيات الشرطة الفعالة التي تتضمن قدرات التكنولوجيا الذكية لديها القدرة على التحسين المستمر لإدارة حركة المرور على الطرق وعن طريق الارتباط بالأثر على الاستدامة الإنسانية والاقتصادية للمجتمع والشعب.
Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study
Authors: Grumet Martin , Sherman Jason , Dorf Barry S
Published: October 2022

Patients with severe COVID-19 experience cytokine storm, an uncontrolled upregulation of pro-inflammatory cytokines, which if unresolved leads to acute respiratory distress syndrome (ARDS), organ damage, and death. Treatments with mesenchymal stromal cells (MSC) [Viswanathan S, Shi Y, Galipeau J, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy. 2019;21:1019-1024] appear to be effective in reducing morbidity and mortality. MSC respond to pro-inflammatory cytokines by releasing anti-inflammatory factors and mobilizing immune cells. We analyzed 82 COVID-19 clinical trials registered at ClinicalTrials.gov to determine MSC dosing, routes of administration, and outcome measures. Nearly all trials described the use of intravenous delivery with most doses ranging between 50 and 125 million MSC/treatment, which overlaps with a minimal effective dose range that we described previously. We also searched the literature to analyze clinical trial reports that used MSC to treat COVID-19. MSC were found to improve survival and oxygenation, increase discharge from intensive care units and hospitals, and reduce levels of pro-inflammatory markers. We report on a 91-year-old man with severe COVID-19 who responded rapidly to MSC treatment with transient reductions in several pro-inflammatory markers and delayed improvement in oxygenation. The results suggest that frequent monitoring of pro-inflammatory markers for severe COVID-19 will provide improved treatment guidelines by determining relationships between cytokine storms and ARDS. We propose that markers for cytokine storm are leading indicators for ARDS and that measurement of cytokines will indicate earlier treatment with MSC than is performed now for ARDS in severe COVID-19.
Patching Up the Permeability: The Role of Stem Cells in Lessening Neurovascular Damage in Amyotrophic Lateral Sclerosis
Authors: Monsour Molly , Garbuzova-Davis Svitlana , Borlongan Cesario V
Published: October 2022

Amyotrophic lateral sclerosis (ALS) is a debilitating disease with poor prognosis. The pathophysiology of ALS is commonly debated, with theories involving inflammation, glutamate excitotoxity, oxidative stress, mitochondria malfunction, neurofilament accumulation, inadequate nutrients or growth factors, and changes in glial support predominating. These underlying pathological mechanisms, however, act together to weaken the blood brain barrier and blood spinal cord barrier, collectively considered as the blood central nervous system barrier (BCNSB). Altering the impermeability of the BCNSB impairs the neurovascular unit, or interdependent relationship between the brain and advances the concept that ALS is has a significant neurovascular component contributing to its degenerative presentation. This unique categorization of ALS opens a variety of treatment options targeting the reestablishment of BCNSB integrity. This review will critically assess the evidence implicating the significant neurovascular components of ALS pathophysiology, while also offering an in-depth discussion regarding the use of stem cells to repair these pathological changes within the neurovascular unit.
Effects of spring- versus fall-calving on perinatal nutrient availability and neonatal vigor in beef cattle
Authors: Wichman Lindsey G , Redifer Colby A , Rathert-Williams Abigail R , Duncan Natalie B , Payne Craig A , Meyer Allison M
Published: October 2022

To determine the effect of calving season on perinatal nutrient availability and neonatal beef calf vigor, data were collected from 4 spring- (average calving date: February 14; n = 203 total) and 4 fall- (average calving date: September 20; n = 179 total) calving experiments. Time to stand was determined as minutes from birth to standing for 5 s. After birth, calf weight and size (length, heart and abdominal girth, and cannon circumference) were recorded. Jugular blood samples and rectal temperatures were obtained at 0, 6, 12, and 24 h postnatally in 6 experiments and at 48 h postnatally in Exp. 2 to 8. Data were analyzed with fixed effects of season (single point) or season, hour, and their interaction (over time, using repeated measures). Experiment was a random effect; calf sex was included when P ≤ 0.25. Within calving season, correlations were determined between calf size, vigor, and 48-h serum total protein. Fall-born calves tended to have lighter (P = 0.09) birth weight and faster (P = 0.05) time to stand than spring-born calves. Season did not affect (P ≥ 0.18) gestation length, other calf size measures, or 48-h serum total protein. Fall-born calves had greater (P ≤ 0.003) rectal temperature at 0, 24, and 48 h postnatal. Spring-born calves had greater (P ≤ 0.009) circulating glucose at 0 h, serum non-esterified fatty acids at 0 and 6 h, and plasma triglycerides at 0, 6, 12, and 48 h. Fall-born calves had greater (P ≤ 0.03) sodium from 6 to 48 h and magnesium from 0 to 24 h of age. Phosphorus was greater (P ≤ 0.02) at 6 and 12 h of age in spring-born calves. Spring-born calves had greater (P ≤ 0.04) aspartate aminotransferase at 12 and 24 h and creatine kinase at 0 and 12 h of age. Fall-born calves had greater (P ≤ 0.03) albumin, calcium, and chloride, had lower (P ≤ 0.03) bicarbonate and direct bilirubin, and tended to have greater (P = 0.10) anion gap (all main effects of calving season). Calf birth weight had a weak positive relationship (P ≤ 0.03) with 48-h serum total protein and time to stand in fall-born, but not spring-born, calves. Overall, fetal growth was restricted and neonatal dehydration was increased by warm conditions for fall-born calves, but vigor and metabolism were negatively affected by cold conditions in spring-born calves. These data suggest that calving season influences perinatal nutrient availability, which may impact the transition of beef calves to postnatal life.