Search

Background Most schwannomas are isolated tumours occurring in otherwise healthy people. However, bilateral vestibular schwannomas (BVS) or multiple nonvestibular schwannomas indicate an underlying genetic predisposition. This is most commonly NF2-related schwannomatosis (SWN), but when BVS are absent, this can also indicate SMARCB1-related or LZTR1-related SWN. Methods We assessed the variant detection rates for the three major SWN genes (NF2, LZTR1 and SMARCB1) in 154 people, from 150 families, who had at least one non-vestibular schwannoma, but who did not meet clinical criteria for NF2-related SWN at the time of genetic testing. Results We found that 17 (11%) people from 13 families had a germline SMARCB1 variant and 19 (12%) unrelated individuals had a germline LZTR1 variant. 19 people had an NF2 variant, but 18 of these were mosaic and 17 were only detected when 2 tumours were available for testing. The overall detection rate was 25% using blood alone, but increased to 36% when tumour analysis was included. Another 12 people had a germline variant of uncertain significance (VUS). Conclusions There were similar proportions of LZTR1, SMARCB1 or mosaic NF2. However, since an NF2 variant was detected in tumours from 103 people, it is likely that further cases of mosaicism would be detected if more people had additional tumours available for analysis. In addition, if further evidence becomes available to show that the VUSs are pathogenic, this would significantly increase the proportion of people with a genetic diagnosis. Our results indicate the importance of comprehensive genetic testing and improved variant classification. [ABSTRACT FROM AUTHOR]

Objectives New diagnostic criteria for NF2- related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated in accordance with these, with an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted in genetic counselling). The distribution of variant types among de novo and familial NF2 cases was also assessed. Methods The UK National NF2 database identifies patients meeting updated NF2 criteria from a highly ascertained population cared for by England's specialised service. Diagnostic prevalence was assessed on 1 February 2023. Molecular analysis of blood and, where possible, tumour specimens for NF2, LZTR1 and SMARCB1 was performed. Results 1084 living NF2 patients were identified on prevalence day (equivalent to 1 in 61 332). The proportion with NF2 inherited from an affected parent was only 23% in England. If people without a confirmed molecular diagnosis or bilateral vestibular schwannoma are excluded, the frequency of de novo NF2 remains high (72%). Of the identified de novo cases, almost half were mosaic. The most common variant type was nonsense variants, accounting for 173/697 (24.8%) of people with an established variant, but only 18/235 (7.7%) with an inherited NF2 pathogenic variant (p<0.0001). Missense variants had the highest proportion of familial association (56%). The prevalence of LZTR1- related schwannomatosis and SMARCB1- related schwannomatosis was 1 in 527 000 and 1 in 1.1M, respectively, 8.4--18.4 times lower than NF2. Conclusions This work confirms a much higher rate of de novo NF2 than previously reported and highlights the benefits of maintaining patient databases for accurate counselling [ABSTRACT FROM AUTHOR]

The increasing complexity and diversity of a typical portfolio of research awards coupled with advancing technology makes successful implementation and delivery of system benefits more challenging than ever. Moreover, the role of systems in knowledge management is a fundamental issue faced by all research active organizations. One of the principal drivers for introducing better systems should be to serve the academic mission and make life easier for researchers; yet most appear to perform conversely, perhaps sacrificing potential benefits to meet the requirements of administration. The principal challenge thus is to deliver a system that meets the needs of both academic and administrative communities. This paper provides a commentary on the experience gained within a research office following implementation of two systems (one pre-award, the other post-award) and identifies key elements for successful delivery. The paper contains suggestions, based on our experience, of best practices and techniques that research administrators might adopt to ensure a well-managed project and its implementation. It concludes how, post implementation, users may begin to derive maximum benefit from systems and points to the advantages that high-quality knowledge management can offer a range of stakeholders. (Contains 1 table and 1 figure.)

Objective: Translabyrinthine excision of a vestibular schwannoma is associated with acute vestibular failure. Preoperative intratympanic gentamicin (ITG) injections can improve objective balance function after surgery but its clinical benefits remain to be established. Methods: Adult patients undergoing translabyrinthine removal of a vestibular schwannoma between January 2014 and February 2018 underwent preoperative vestibular function testing. Patients were divided in to 3 groups, those with vestibular function (VF) who received ITG injections, those with VF but did not receive ITG and those with no VF. Groups were compared according to degree of vertigo, length of stay, time to unassisted mobilization, and postoperative anti‐emetic consumption. Results: Forty six patients had ITG injections (Group 1), 7 had residual VF but refused treatment (Group 2), 21 had no VF (Group 3). Group 1 had a significant improvement in vertigo over time whereas groups 2 and 3 did not. There was a statistically significant 70% decrease in time to independent mobilization between Group 1 and other groups and a 19% decrease in length of stay in Group 1 compared to other groups although this did not reach statistical significance. Two patients had injection‐related complications. Group 1 used less anti‐emetics than other groups but this was not statistically significant. Conclusion: Preoperative intratympanic gentamicin injection with vestibular rehabilitation exercises is associated with less postoperative vertigo and earlier postoperative mobilization. There was reduced duration of hospitalization and decreased consumption of anti‐emetic but not significantly so possibly because of low numbers of patients in the no treatment group. Level of Evidence: 2 Laryngoscope, 134:3316–3322, 2024 [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess degree of audiovestibular handicap in patients with vestibular schwannoma. Methods: Audiovestibular handicap was assessed using the Hearing Handicap Inventory, Tinnitus Handicap Inventory and Dizziness Handicap Inventory. Patients completed questionnaires at presentation and at least one year following treatment with microsurgery, stereotactic radiosurgery or observation. Changes in audiovestibular handicap and factors affecting audiovestibular handicap were assessed. Results: All handicap scores increased at follow up, but not significantly. The Tinnitus Handicap Inventory and Dizziness Handicap Inventory scores predicted tinnitus and dizziness respectively. The Hearing Handicap Inventory was not predictive of hearing loss. Age predicted Tinnitus Handicap Inventory score and microsurgery was associated with a deterioration in Dizziness Handicap Inventory score. Conclusion: Audiovestibular handicap is common in patients with vestibular schwannoma, with 75 per cent having some degree of handicap in at least one inventory. The overall burden of handicap was, however, low. The increased audiovestibular handicap over time was not statistically significant, irrespective of treatment modality. [ABSTRACT FROM AUTHOR]

The authors recognise that there is no "one-size-fits-all" approach to implementing business intelligence strategy within universities. Elements of best practice have been taken from a case study of Imperial College, which may be applied across other institutions. The process starts with implementing and developing systems that capture robust data and provide a platform for enhanced reporting capabilities. Once this platform has been established, people, process and systems need to be harmonised with each other. Systems need to capture the information in fine detail, which can then be used to underpin reporting at other levels within the organisational hierarchy. By doing this the same information can be circulated throughout the organisation at different levels of granularity, and consistency of understanding can be achieved about how analysis has been carried out and how decision-making has been informed. As the organisation's business intelligence strategy develops over time it is crucial to establish mechanisms to revisit and appraise success and/or limitations. Universities do not exist in a vacuum and must continually adapt and respond to the environment they inhabit. Reporting needs are likely to change and the organisation must develop system capabilities and regularly engage with users of management information to ensure relevance and buy-in. However, the guiding principles discussed in this paper of consistent data, stakeholder participation and information policy frameworks are likely to remain significant factors for those leading business intelligence initiatives. (Contains 13 figures.)

Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2 -related and LZTR1 -related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants. To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 × 10−13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A/B , also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis. [ABSTRACT FROM AUTHOR]