Immunosuppression in stem cell clinical trials of neural and retinal cell types: A systematic review.

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.

Outcomes following cochlear implantation with eluting electrodes: A systematic review.

Objectives: To establish audiological and other outcomes following cochlear implantation in humans and animals with eluting electrodes. Methods: Systematic review and narrative synthesis. Databases searched (April 2023): MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and Web of Science. Studies reporting outcomes in either humans or animals following cochlear implantation with a drug-eluting electrode were included. No limits were placed on language or year of publication. Risk of bias assessment was performed on all included studies using either the Brazzelli or Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) assessment tools. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Results: Searches identified 146 abstracts and 108 full texts. Of these, 18 studies met the inclusion criteria, reporting outcomes in 523 animals (17 studies) and 24 humans (1 study). Eluting electrodes included dexamethasone (16 studies), aracytine (1 study), nicotinamide adenine dinucleotide (1 study), the growth factors insulin-like growth factor 1 (IGF1) and hepatocyte growth factor (HGF) (1 study), and neurotrophin-3 (1 study). All included studies compare outcomes following implantation with an eluting electrode with a control non-eluting electrode. In the majority of studies, audiological outcomes (e.g., auditory brainstem response threshold) were superior following implantation with an eluting electrode compared with a standard electrode. Most studies which investigated post-implantation impedance reported lower impedance following implantation with an eluting electrode. The influence of eluting electrodes on other reported outcomes (including post-implantation cochlear fibrosis and the survival of hair cells and spiral ganglion neurons) was more varied across the included studies. Conclusions: Eluting electrodes have shown promise in animal studies in preserving residual hearing following cochlear implantation and in reducing impedance, though data from human studies remain lacking. Further in-human studies will be required to determine the clinical usefulness of drug-eluting cochlear implants as a future treatment for sensorineural hearing loss.

Temporal bone management in external and middle ear carcinoma.

PURPOSE OF REVIEW: The purpose of this review is to outline the temporal bone management of external and middle ear carcinoma. The review will outline the current evidence involved in deciding which surgical approach to take, as well as new advances in auditory rehabilitation and immunotherapy. RECENT FINDINGS: Traditional surgical approaches include lateral temporal bone resection, subtotal temporal bone resection and total temporal bone resection. They can also involve parotidectomy and neck dissection depending on extension of disease into these areas. Options for auditory rehabilitation include osseointegrated hearing aids, transcutaneous bone-conduction implants, and active middle ear implants. Recent advances in immunotherapy have included the use of anti-PD-1 monoclonal antibodies. SUMMARY: The mainstay of management of temporal bone disease involves surgical resection. Early-stage tumours classified according to the Pittsburgh staging tool can often be treated with lateral temporal bone resection, whereas late-stage tumours might need subtotal or total temporal bone resection. Parotidectomy and neck dissection might also be indicated if there is a risk of occult regional disease. Recent advances in immunotherapy have been promising, particularly around anti-PD-1 inhibitors. However, larger clinical trials will be required to test the extent of efficacy, particularly around combination use with surgery.

Meningitis Risk in Patients with Inner Ear Malformations after Cochlear Implants: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this study is to determine the rate of postoperative meningitis after cochlear implantation in those with inner ear malformations (IEMs) via meta-analysis. DATA SOURCES: Medline, EMBASE, and the Cochrane Library. METHODS: This study was reported following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Proportion meta-analysis was conducted through an inverse variance random-effect model based on arcsin transformation and presented as forest plots. Quality assessment of the included studies was performed through the National Institutes of Health Quality Assessment Tool. RESULTS: Overall, 38 of 2966 studies met the inclusion criteria and were included in the analysis. There were 10 cases of meningitis after cochlear implantation in 1300 malformed ears. The overall rate of meningitis after cochlear implantation in IEMs was 0.12% (95% confidence interval, 0.006-0.380%; I2 = 0%). Cases occurred in incomplete partition (n = 5), Mondini deformity (n = 2), common cavity (n = 2), and enlarged internal auditory canal (n = 1). Six of 10 cases of postoperative meningitis occurred with an intraoperative cerebrospinal fluid leak. CONCLUSION: In those with IEMs, the risk of meningitis after cochlear implantation is very low.

The Risk of Meningitis After Cochlear Implantation: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to estimate the rate of postoperative meningitis (both immediate and long-term) in patients following cochlear implants (CIs). It aims to do so through a systematic review and meta-analysis of published studies tracking complications after CIs. DATA SOURCES: MEDLINE, Embase, and Cochrane Library. REVIEW METHODS: This review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies tracking complications following CIs in patients were included. Exclusion criteria included non-English language studies and case series reporting <10 patients. Bias risk was evaluated using the Newcastle-Ottawa Scale. Meta-analysis was performed through DerSimonian and Laird random-effects models. RESULTS: A total of 116/1931 studies met the inclusion criteria and were included in the meta-analysis. Overall, there were 112 cases of meningitis in 58,940 patients after CIs. Meta-analysis estimated an overall rate of postoperative meningitis of 0.07% (95% confidence interval [CIs], 0.03%-0.1%; I2 = 55%). Subgroup meta-analysis showed this rate had 95% CIs crossing 0% in implanted patients who received the pneumococcal vaccine, antibiotic prophylaxis, those with postoperative acute otitis media (AOM), and those implanted less than 5 years. CONCLUSION: Meningitis is a rare complication following CIs. Our estimated rates of meningitis after CIs appear lower than prior estimates based on epidemiological studies in the early 2000s. However, the rate still appears higher than the baseline rate in the general population. The risk was very low in implanted patients who received the pneumococcal vaccine, antibiotic prophylaxis, received unilateral or bilateral implantations, developed AOM, those implanted with a round window or cochleostomy techniques, and those under 5 years.

Intrathyroidal parathyroid adenomas: Scoping review on clinical presentation, preoperative localization, and surgical treatment.

Intrathyroidal parathyroid adenomas (IPAs) are a rare cause of primary hyperparathyroidism. They are often difficult to localize preoperatively and intraoperatively, making diagnosis and treatment challenging. Current data on IPAs are sparse and fragmented in the literature. This makes it difficult to compare the effectiveness of different imaging and surgical techniques. To address this issue, this scoping review maps the literature on IPAs, focusing on four domains: clinical presentation, current localization methods, different surgical techniques, and histopathological features. A search of MEDLINE, Embase, and the Cochrane Library was conducted, with 19 studies meeting the inclusion criteria. The characteristics of IPAs on ultrasound, fine-needle aspiration, CT, MRI, sestamibi-based techniques, and selective venous sampling are summarized. Emerging imaging modalities, including autofluorescence, are introduced. Surgical methods and intraoperative factors that correlate with high success rates for removal are highlighted. This review also identifies gaps in knowledge to guide further research into this area.

Assessment of the cochlear implant pathway for newborn hearing screening referrals.

OBJECTIVE: To evaluate the cochlear implant (CI) assessment pathway for children referred through the newborn hearing screening programme (NHSP) and identify potential reasons for delay in CI surgery at a large UK centre. METHODS: Retrospective analysis of electronic notes of children referred through NHSP from 2016 to 2019. Key points in the assessment pathway from referral to switch-on were assessed. RESULTS: Of the 46 referrals, 44 went on to have CI surgery. Median age at CI surgery was 15 months (interquartile range (IQR) 13 to 17 months). Only 5% of referrals were implanted before the age of 12 months. Delayed referral and the presence of otitis media with effusion (OME) were associated with delayed implantation. The median period of monitoring for OME was 48 days (IQR 20 to 93 days), with a natural resolution rate of only 11%. The median time from surgery to switch-on was 5 weeks (IQR 4.1 to 5.4 weeks). CONCLUSION: Achieving implantation prior to the age of 12 months for NHSP referrals can be challenging for a variety of reasons. The delays in the system and the steps that our implant programme has taken to address these will be highlighted.