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.

A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression.

Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains, and greater morphological diversity. Here, we report that RNA-level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination. We show that RNLTR12-int-encoded RNA binds to the transcription factor SOX10 to regulate transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. RNLTR12-int-like sequences (which we name RetroMyelin) are found in all jawed vertebrates, and we further demonstrate their function in regulating myelination in two different vertebrate classes (zebrafish and frogs). Our study therefore suggests that retroviral endogenization played a prominent role in the emergence of vertebrate myelin.

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.

Can accelerated ageing models inform us on age-related tauopathies?

Ageing is the greatest risk factor of late-onset neurodegenerative diseases. In the realm of sporadic tauopathies, modelling the process of biological ageing in experimental animals forms the foundation of searching for the molecular origin of pathogenic tau and developing potential therapeutic interventions. Although prior research into transgenic tau models offers valuable lessons for studying how tau mutations and overexpression can drive tau pathologies, the underlying mechanisms by which ageing leads to abnormal tau accumulation remains poorly understood. Mutations associated with human progeroid syndromes have been proposed to be able to mimic an aged environment in animal models. Here, we summarise recent attempts in modelling ageing in relation to tauopathies using animal models that carry mutations associated with human progeroid syndromes, or genetic elements unrelated to human progeroid syndromes, or have exceptional natural lifespans, or a remarkable resistance to ageing-related disorders.

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.