Ex-vivo models of post-surgical residual disease in human glioblastoma [version 1; peer review: awaiting peer review]

Background Glioblastoma is a highly infiltrative, currently incurable brain cancer. To date, translation of novel therapies for glioblastoma from the laboratory into clinical trials has relied heavily on in vitro cell culture and murine (subcutaneous and orthotopic) xenograft models using cells derived from the main bulk of patient tumours. However, it is the residual cells left-behind after surgery that are responsible for disease progression and death in the clinic. A lack of substantial improvements in patient survival for decades suggests commonly used murine xenograft models, a key step before clinical trials, do not reflect the biology of residual disease in patients. Methods To address this, we have developed the ‘Sheffield Protocol’ to generate ex vivo models that reflect both resected, and post-surgical residual disease from the same patient. The protocol leverages parallel derivation of inherently treatment-resistant glioblastoma stem cells (GSCs) from ‘core’ and distant ‘edge’ regions through careful macrodissection of a large en bloc specimen, such as from a partial lobectomy for tumour, followed by tissue dissociation and propagation in serum-free media. Opportunistic en bloc specimen use can liberate the most distant infiltrative cells feasibly accessible from living patients. Results We provide an example illustrating that resected and residual disease models represent spatially divergent tumour subpopulations harbouring distinct transcriptomic and cancer stem cell marker expression profiles. We also introduce the ‘Sheffield Living Biobank’ of glioma models (SLB) that incorporates over 150 GSC lines from 60+ patients, including 44+ resected and residual models, which are available for academic use via MTA. Conclusions These models provide a novel tool to reduce animal xenograft usage by improving candidate drug triage in early preclinical studies and directly replacing animal studies for some therapies that are post-Phase 1+ clinical trial for other cancers/conditions to, ultimately, deliver more effective treatments for post-surgical residual disease in glioblastoma

The first Iraqi experience in sacral neuromodulation for patients with lower urinary tract dysfunction

Objectives: To present our experience, in Iraq, with sacral neuromodulation (SNM) in patients with refractory lower urinary tract dysfunction, with discussion of the factors that affect the response rate. Patients and methods: In this prospective, clinical, interventional study, 24 patients were evaluated and treated by a team comprised of a Urologist and a Neurosurgeon with SNM over a 1.5-year period. The gender, age, pathology, and clinical presentation, were all studied and evaluated. Successful clinical response was defined as achieving a ≥50% improvement in voiding diary variables. Results: The mean age of those that responded to SNM was 28 years, with females responding better than males (10 of 14 vs four of 10). The SNM response rate according to presentation was six of 10 in those with overactive bladder/urge urinary incontinence, six of nine of those with urinary retention, and two of five in those with a mixed presentation. The response rate in idiopathic voiding dysfunctions was 11 of 13, whilst for neurogenic dysfunctions it was three of 11. Other benefits such as in bowel motion, erectile function, menstruation, power of lower limbs, and quality of life (QoL), were also recorded. The complications were reasonable for this minimally invasive procedure. Conclusion: SNM offers a good and durable solution for some functional bladder problems, if patients are well selected. There may also be additional extra-urinary benefits that contribute to improvements in QoL. SNM was well tolerated by our patients with an encouraging response rate, especially in psychologically stable patients with idiopathic dysfunctions. Keywords: Lower urinary tract dysfunction, Overactive bladder, Urge urinary incontinence, Urinary retention, Neuromodulatio

A multilingual background for telecollaboration Practices and policies in European higher education

The Trans-Atlantic and Pacific Project (TAPP) is a telecollaboration network linking European university classes with classes in the US and beyond for nearly 20 years. Such collaborations have enabled students to participate in realistic projects, fostering transversal and language skills – including English as a lingua franca – which are highlighted in university policies at European, country/region and institutional levels. In turn, telecollaboration can support Internationalisation at Home, along with virtual mobility objectives, increasingly prominent in European higher education. Considering the grassroots nature of TAPP, whose instructors design their own partnerships and assignments, this contribution examines TAPP projects in light of language policies from a dual bottom-up/top-down perspective. Thus, considering the importance of language policies of several European countries involved in TAPP (Belgium, France, Italy, Spain), this paper analyses how TAPP teaching-learning practices align with such policies in terms of multilingualism and interculturality. Attention is paid to students’ roles – subject-matter experts, linguists/translators, project managers, usability experts – and their native languages. Emphasis is placed on how students relate to English from their various perspectives as native speakers, second-language speakers, language experts or language learners. Lessons derived from the analysis of such practices can inform policy makers as they make provisions for Internationalisation at Home, mainly in Europe, while also introducing comparisons between European and US perspectives.Peer ReviewedPostprint (published version

First report of a multicenter prospective registry of cranioplasty in the United Kingdom and Ireland

Background: There are many questions that remain unanswered regarding outcomes following cranioplasty including the timing of cranioplasty following craniectomy as well as the material used. Objective: To establish and evaluate 30-d outcomes for all cranial reconstruction procedures in the United Kingdom (UK) and Ireland through a prospective multicenter cohort study. Methods: Patients undergoing cranioplasty insertion or revision between June 1, 2019 and November 30, 2019 in 25 neurosurgical units were included. Data collected include demographics, craniectomy date and indication, cranioplasty material and date, and 30-d outcome. Results: In total, 313 operations were included, consisting of 255 new cranioplasty insertions and 58 revisions. Of the new insertions, the most common indications for craniectomy were traumatic brain injury (n = 110, 43), cerebral infarct (n = 38, 15), and aneurysmal subarachnoid hemorrhage (n = 30, 12). The most common material was titanium (n = 163, 64). Median time to cranioplasty was 244 d (interquartile range 144-385), with 37 new insertions (15) within or equal to 90 d. In 30-d follow-up, there were no mortalities. There were 14 readmissions, with 10 patients sustaining a wound infection within 30 d (4). Of the 58 revisions, the most common reason was due to infection (n = 33, 59) and skin breakdown (n = 13, 23). In 41 (71) cases, the plate was removed during the revision surgery. Conclusion: This study is the largest prospective study of cranioplasty representing the first results from the UK Cranial Reconstruction Registry, a first national registry focused on cranioplasty with the potential to address outstanding research questions for this procedure. © 2021 Congress of Neurological Surgeons 2021

Imaging timing after surgery for glioblastoma: an evaluation of practice in Great Britain and Ireland (INTERVAL-GB)- a multi-centre, cohort study

Purpose Post-operative MRI is used to assess extent of resection, monitor treatment response and detect progression in high-grade glioma. However, compliance with accepted guidelines for follow-up MRI, and impact on management/outcomes is unclear. Methods Multi-center, retrospective observational cohort study of patients with confirmed WHO grade 4 glioma (August 2018-February 2019) receiving oncological treatment. Primary objective: investigate follow-up MRI surveillance practice and compliance with recommendations from NICE (Post-operative scan < 72h, MRI every 3–6 months) and EANO (Post-operative scan < 48h, MRI every 3 months). Results There were 754 patients from 26 neuro-oncology centers with a median age of 63 years (IQR 54–70), yielding 10,100 (median, 12.5/person, IQR 5.2–19.4) person-months of follow-up. Of patients receiving debulking surgery, most patients had post-operative MRI within 72 h of surgery (78.0%, N = 407/522), and within 48 h of surgery (64.2%, N = 335/522). The median number of subsequent follow-up MRI scans was 1 (IQR 0–4). Compliance with NICE and EANO recommendations for follow-up MRI was 52.8% (N = 398/754) and 24.9% (N = 188/754), respectively. On multivariable Cox regression analysis, increased time spent in recommended follow-up according to NICE guidelines was associated with longer OS (HR 0.56, 95% CI 0.46–0.66, P < 0.001), but not PFS (HR 0.93, 95% CI 0.79–1.10, P = 0.349). Increased time spent in recommended follow-up according to EANO guidelines was associated with longer OS (HR 0.54, 95% CI 0.45–0.63, P < 0.001) but not PFS (HR 0.99, 95% CI 0.84–1.16, P = 0.874). Conclusion Regular surveillance follow-up for glioblastoma is associated with longer OS. Prospective trials are needed to determine whether regular or symptom-directed MRI influences outcomes