Search

PURPOSE: This open-label, single-arm, phase II study evaluated the vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) rivoceranib in patients with recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC). PATIENTS AND METHODS: Eligible patients had confirmed disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) with ≥20% increase in radiologically or clinically measurable lesions or appearance of new lesions within the preceding 6 months. Patients received oral rivoceranib 700 mg once daily. Primary outcomes were objective response rate (ORR) by investigator review and by blinded independent review committee (BIRC). RESULTS: Eighty patients were enrolled and 72 were efficacy evaluable. Seventy-four patients had distant metastases and 49 received prior systemic treatment (14 received VEGFR TKIs). Per investigator and BIRC, respectively, ORR was 15.3% [95% confidence interval (95% CI), 7.9-25.7] and 9.7% (95% CI, 4.0-19.0); median duration of response was 14.9 months (95% CI, 4.9-17.3) and 7.2 months (95% CI, 3.5-8.4); and median progression-free survival was 9.0 months (95% CI, 7.3-11.5) and 9.0 months (95% CI, 7.7-11.5). Grade ≥3 treatment-related adverse events occurred in 56 patients (70.0%); the most common were hypertension (34, 42.5%) and stomatitis (6, 7.5%). Four grade 5 events occurred with one attributed to rivoceranib (epistaxis). Sixty-eight patients (85.0%) had ≥1 dose modifications and 16 patients (20.0%) discontinued rivoceranib for toxicity. CONCLUSIONS: In patients with progressing R/M ACC, rivoceranib demonstrated antitumor activity and a manageable safety profile consistent with other VEGFR TKIs.

Background Patients with severe-to-profound hearing loss may benefit from management with cochlear implants. These patients need a referral to a cochlear implant team for further assessment and possible surgery. The referral pathway may result in varied access to hearing healthcare. This study aimed to explore referral patterns and whether there were any socioeconomic or ethnic associations with the likelihood of referral. The primary outcome was to determine factors influencing referral for implant assessment. The secondary outcome was to identify factors impacting whether healthcare professionals had discussed the option of referral. Methods and findings A multicentre multidisciplinary observational study was conducted in secondary care Otolaryngology and Audiology units in Great Britain. Adults fulfilling NICE (2019) audiometric criteria for implant assessment were identified over a 6-month period between 1 July and 31 December 2021. Patient- and site-specific characteristics were extracted. Multivariable binary logistic regression was employed to compare a range of factors influencing the likelihood of implant discussion and referral including patient-specific (demographics, past medical history, and degree of hearing loss) and site-specific factors (cochlear implant champion and whether the hospital performed implants). Hospitals across all 4 devolved nations of the UK were invited to participate, with data submitted from 36 urban hospitals across England, Scotland, and Wales. Nine hospitals (25%) conducted cochlear implant assessments. The majority of patients lived in England (n = 5,587, 86.2%); the rest lived in Wales (n = 419, 6.5%) and Scotland (n = 233, 3.6%). The mean patient age was 72 ± 19 years (mean ± standard deviation); 54% were male, and 75·3% of participants were white, 6·3% were Asian, 1·5% were black, 0·05% were mixed, and 4·6% were self-defined as a different ethnicity. Of 6,482 submitted patients meeting pure tone audiometric thresholds for cochlear implantation, 311 already had a cochlear implant. Of the remaining 6,171, 35.7% were informed they were eligible for an implant, but only 9.7% were referred for assessment. When adjusted for site- and patient-specific factors, stand-out findings included that adults were less likely to be referred if they lived in more deprived area decile within Indices of Multiple Deprivation (4th (odds ratio (OR): 2·19; 95% confidence interval (CI): [1·31, 3·66]; p = 0·002), 5th (2·02; [1·21, 3·38]; p = 0·05), 6th (2·32; [1·41, 3·83]; p = 0.05), and 8th (2·07; [1·25, 3·42]; p = 0·004)), lived in London (0·40; [0·29, 0·57]; p < 0·001), were male (females 1·52; [1·27, 1·81]; p < 0·001), or were older (0·97; [0·96, 0·97]; p < 0·001). They were less likely to be informed of their potential eligibility if they lived in more deprived areas (4th (1·99; [1·49, 2·66]; p < 0·001), 5th (1·75; [1·31, 2·33], p < 0·001), 6th (1·85; [1·39, 2·45]; p < 0·001), 7th (1·66; [1·25, 2·21]; p < 0·001), and 8th (1·74; [1·31, 2·31]; p < 0·001) deciles), the North of England or London (North 0·74; [0·62, 0·89]; p = 0·001; London 0·44; [0·35, 0·56]; p < 0·001), were of Asian or black ethnic backgrounds compared to white patients (Asian 0·58; [0·43, 0·79]; p < 0·001; black 0·56; [0·34, 0·92]; p = 0·021), were male (females 1·46; [1·31, 1·62]; p < 0·001), or were older (0·98; [0·98, 0·98]; p < 0·001). The study methodology was limited by its observational nature, reliance on accurate documentation of the referring service, and potential underrepresentation of certain demographic groups. Conclusions The majority of adults meeting pure tone audiometric threshold criteria for cochlear implantation are currently not appropriately referred for assessment. There is scope to target underrepresented patient groups to improve referral rates. Future research should engage stakeholders to explore the reasons behind the disparities. Implementing straightforward measures, such as educational initiatives and automated pop-up tools for immediate identification, can help streamline the referral process., Author(s): Chloe Swords 1,2,3,*, Reshma Ghedia 3,4, Hannah Blanchford 3,5, James Arwyn-Jones 3,6, Elliot Heward 3,7, Kristijonas Milinis 3,8, John Hardman 3,9, Matthew E. Smith 1,2, Manohar Bance 1,2, Jameel [...]

Background/Objectives: Cochlear implantation (CI) is an effective intervention for individuals with severe to profound hearing loss; however, it may impact vestibular function due to its proximity to related anatomical structures. Vestibular evoked myogenic potentials (VEMPs) assess the function of the saccule and utricle, critical components of the vestibular system. This review examines CI's impact on air conduction (AC) and bone conduction (BC) VEMP responses. Methods: A scoping review was conducted following PRISMA guidelines, using databases such as Medline, Embase, Cochrane Library, Scopus, and ProQuest Dissertations. Studies reporting on AC and/or BC-VEMP in CI recipients were included. Data extraction focused on VEMP response rates, amplitudes, and latencies pre- and post-CI. Risk of bias/quality assessment was performed using the Newcastle–Ottawa Scale. Results: Out of 961 studies identified, 4 met the inclusion criteria, encompassing a total of 245 CI-implanted ears. Results indicated that AC-VEMP responses were often reduced or absent post-CI, reflecting the influence of surgical changes in the middle ear mechanics rather than otolith dysfunction. In contrast, BC-VEMP responses were more consistently preserved, suggesting that BC stimuli bypass the middle ear and more accurately delineate otolith function. Variations in VEMP outcomes were noted depending on the surgical approach and individual patient factors. Conclusions: CI impacts vestibular function as measured by VEMP, with AC-VEMP showing greater susceptibility to postoperative changes compared to BC-VEMP. The presence of preserved BC-VEMP alongside absent AC-VEMP underscores the need to differentiate between these measures in assessing vestibular function. [ABSTRACT FROM AUTHOR]

Background: Cochlear implantation (CI) has proven to be a highly effective method for rehabilitating individuals with severe to profound hearing loss. However, challenges persist, particularly in cases where CI failure necessitates re-implantation. This study aims to address the gap in understanding the knowledge and practices of audiologists in the UK regarding cochlear re-implantation through a comprehensive questionnaire survey. Methods: A bespoke questionnaire was distributed to audiologists working with CI across the UK. The survey, which included multiple-choice items, open-text responses, and visual analogue scales, was made accessible via an online link shared through professional bodies, email groups, and social media platforms. Results: The survey received 27 responses, predominantly from female audiologists (71.4%), with significant representation from London (28.6%) and the East of England (21.4%). A majority of respondents had over 16 years of CI experience (35.7%) and held a master's degree (60.7%). Key reasons for CI re-implantation included electrode failure (82.1%) and hermetic seal failure (60.7%). While respondents showed strong confidence in counselling (88.8%) and managing re-implanted devices (84.6%), there was a noted variation in opinions regarding the need for additional training in intraoperative measures. Conclusion: This survey highlights the current practices and training needs of UK audiologists in CI re-implantation. This underscores the importance of targeted training to fill knowledge gaps and improve clinical care during CI re-implantation, ultimately enhancing outcomes for both audiologists and CI recipients. [ABSTRACT FROM AUTHOR]

Background: Pharmacologic immunosuppression regimes are commonly employed in stem cell clinical trials to mitigate host immune rejection and promote survival and viability of transplanted cells. Immunosuppression and cell survival has been extensively studied in retinal and spinal tissues. The applicability of stem cell therapy is rapidly expanding to other sensory organs such as the ear and hearing. As regenerative therapy is directed to new areas, a greater understanding of immunosuppression strategies and their efficacy is required to facilitate translation to organ-specific biologic microenvironments. Objective: This systematic review appraises the current literature regarding immunosuppression strategies employed in stem cell trials of retinal and neural cells. Methods: This systematic review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included studies presenting data on neural or retinal cells as part of an in-human clinical trial that detailed the immunosuppression regime used. Exclusion criteria included non-English language studies, animal studies, review articles, case reports, editorials, and letters. The databases Medline, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to February 2024. Risk of bias was evaluated using the ROBINS-I tool. Results: Eighteen articles fit the inclusion criteria. Nine articles concerned retinal cells, 5 concerned spinal cord injury, and 4 concerned amyotrophic lateral sclerosis. A multi-drug and short-term immunosuppression regime were commonly employed in the identified studies. Detected immune responses in treated patients were rare. Common immunosuppression paradigms included tacrolimus, mycophenolate mofetil and tapering doses of steroids. Local immunosuppression with steroids was employed in some studies concerning retinal diseases. Discussion: A short-term course of systemic immunosuppression seemed efficacious for most included studies, with some showing grafted cells viable months to years after immunosuppression had stopped. Longer-term follow-up is required to see if this remains the case. Side effects related to immunosuppression were uncommon. [ABSTRACT FROM AUTHOR]

Purpose: This study is a systematic review of the literature which seeks to evaluate auditory and quality of life (QOL) outcomes of cochlear implantation in patients with Usher syndrome. Methods: Systematic review of studies indexed in Medline via PubMed, Ovid EMBASE, Web of Science, CENTRAL and clinicaltrials.gov was performed up to March 9th 2022, conducted in accordance with the PRISMA statement. Patient demographics, comorbidity, details of cochlear implantation, auditory, and QOL outcomes were extracted and summarized. Results: 33 studies reported over 217 cochlear implants in 187 patients with Usher syndrome, comprising subtypes 1 (56 patients), 2 (9 patients), 3 (23 patients), and not specified (99 patients). Auditory outcomes included improved sound detection, speech perception, and speech intelligibility. QOL outcomes were reported for 75 patients, with benefit reported in the majority. Conclusions: Many patients with Usher syndrome develop improved auditory outcomes after cochlear implantation with early implantation being an important factor. [ABSTRACT FROM AUTHOR]