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European Annals of Otorhinolaryngology,... Feb 2018Sudden sensorineural hearing loss (SSNHL) is a common and alarming symptom that often prompts an urgent visit to an ENT specialist. Treatment of SSNHL remains one of the...
Sudden sensorineural hearing loss (SSNHL) is a common and alarming symptom that often prompts an urgent visit to an ENT specialist. Treatment of SSNHL remains one of the most problematic issues for contemporary otorhinolaryngology: although many meta-analyses and national guidelines have been issued, management is not standardized in terms of medical treatment, and duration and route of administration. We present several methodological suggestions for the study of treatments for SSNHL. These were developed from the existing level of evidence of the main treatments used in SSNHL by experts who convened at the IFOS 2017 ENT World Congress in Paris, France. All panelists agreed that one of the main limitations present in studies on SSNHL is related to the wide heterogeneity, which characterizes both the initial hearing deficit and the amount of hearing recovery. Although evidence of the efficacy of systemic steroids cannot be considered as strong enough to recommend their use, it is still the most widespread primary therapy and can be considered as the current standard of care. Therefore, systemic steroids stand as an adequate control for any innovative treatment. To reduce the number of subjects we suggest that the inclusion criteria should be restricted to moderate to profound levels of hearing loss. The efficacy of trans-tympanic steroids as a salvage therapy was suggested in several reports on small populations and needs to be confirmed with larger randomized controlled trials.
Topics: Hearing Loss, Sensorineural; Hearing Loss, Sudden; Humans; Internationality
PubMed: 29396226
DOI: 10.1016/j.anorl.2017.12.011 -
Frontiers in Neuroscience 2017The clinical uses of electrocochleography are reviewed with some technical notes on the apparatus needed to get clear recordings under different conditions.... (Review)
Review
The clinical uses of electrocochleography are reviewed with some technical notes on the apparatus needed to get clear recordings under different conditions. Electrocochleography can be used to estimate auditory thresholds in difficult to test children and a golf club electrode is described. The same electrode can be used to obtain electrical auditory brainstem responses (EABR). Diagnostic testing in the clinic can be performed with a transtympanic needle electrode, and a suitable disposable monopolar electrode is described. The use of tone bursts rather than click stimuli gives a better means of diagnosis of the presence of endolymphatic hydrops. Electrocochleography can be used to monitor the cochlear function during surgery and a long coaxial cable, which can be sterilized, is needed to avoid electrical artifacts. Recently electrocochleography has been used to monitor cochlear implant insertion and to record residual hearing using an electrode on the cochlear implant array as the non-inverting (active) electrode.
PubMed: 28634435
DOI: 10.3389/fnins.2017.00274 -
Pharmaceuticals (Basel, Switzerland) Sep 2022Hearing loss negatively impacts the well-being of millions of people worldwide. Systemic delivery of ototherapeutics has limited efficacy due to severe systemic side... (Review)
Review
Hearing loss negatively impacts the well-being of millions of people worldwide. Systemic delivery of ototherapeutics has limited efficacy due to severe systemic side effects and the presence of the blood-labyrinth barrier that selectively limits or enables transfer of molecules between plasma and inner ear tissues and fluids. Local drug delivery into the middle and inner ear would be preferable for many newly emerging classes of drugs. Although the cochlea is a challenging target for drug delivery, recent technologies could provide a safe and efficacious delivery of ototherapeutics. Local drug delivery routes include topical delivery via the external auditory meatus, retroauricular, transtympanic, and intracochlear delivery. Many new drug delivery systems specifically for the inner ear are under development or undergoing clinical studies. Future studies into these systems may provide a means for extended delivery of drugs to preserve or restore hearing in patients with hearing disorders. This review outlines the anatomy of the (inner) ear, describes the various local delivery systems and routes, and various quantification methodologies to determine the pharmacokinetics of the drugs in the inner ear.
PubMed: 36145336
DOI: 10.3390/ph15091115 -
Hearing, Balance and Communication 2020Current treatments for hearing loss offer some functional improvements in hearing, but do not restore normal hearing. The aim of this review is to highlight recent...
OBJECTIVES
Current treatments for hearing loss offer some functional improvements in hearing, but do not restore normal hearing. The aim of this review is to highlight recent advances in viral and non-viral vectors for gene therapy and to discuss approaches for overcoming barriers inherent to inner ear delivery of gene products.
DATA SOURCES
The databases used were Medline, EMBASE, Web of Science, and Google Scholar. Search terms were [("cochlea*" or "inner ear" or "transtympanic" or "intratympanic" or "intracochlear" or "hair cells" or "spiral ganglia" or "Organ of Corti") and ("gene therapy" or "gene delivery")]. The references section of resulting articles was also used to identify relevant studies.
RESULTS
Both viral and non-viral vectors play important roles in advancing gene delivery to the inner ear. The round window membrane is one significant barrier to gene delivery that intratympanic delivery methods attempt to overcome through diffusion and intracochlear delivery methods bypass completely.
CONCLUSIONS
Gene therapy for hearing loss is a promising treatment for restoring hearing function by addressing innate defects. Recent technological advances in inner ear drug delivery techniques pose exciting opportunities for progress in gene therapy.
PubMed: 33604229
DOI: 10.1080/21695717.2020.1807261 -
Frontiers in Immunology 2023Cisplatin is chemotherapy used for solid tumor treatment like lung, bladder, head and neck, ovarian and testicular cancers. However, cisplatin-induced ototoxicity limits...
Cisplatin is chemotherapy used for solid tumor treatment like lung, bladder, head and neck, ovarian and testicular cancers. However, cisplatin-induced ototoxicity limits the utility of this agent in cancer patients, especially when dose escalations are needed. Ototoxicity is associated with cochlear cell death through DNA damage, the generation of reactive oxygen species (ROS) and the consequent activation of caspase, glutamate excitotoxicity, inflammation, apoptosis and/or necrosis. Previous studies have demonstrated a role of CXC chemokines in cisplatin ototoxicity. In this study, we investigated the role of CXCL1, a cytokine which increased in the serum and cochlea by 24 h following cisplatin administration. Adult male Wistar rats treated with cisplatin demonstrated significant hearing loss, assessed by auditory brainstem responses (ABRs), hair cell loss and loss of ribbon synapse. Immunohistochemical studies evaluated the levels of CXCL1 along with increased presence of CD68 and CD45-positive immune cells in cochlea. Increases in CXCL1 was time-dependent in the spiral ganglion neurons and organ of Corti and was associated with progressive increases in CD45, CD68 and IBA1-positive immune cells. Trans-tympanic administration of SB225002, a chemical inhibitor of CXCR2 (receptor target for CXCL1) reduced immune cell migration, protected against cisplatin-induced hearing loss and preserved hair cell integrity. We show that SB225002 reduced the expression of , , , , and . Similarly, knockdown of by trans-tympanic administration of siRNA protected against hearing loss and loss of outer hair cells and reduced ribbon synapses. In addition, SB225002 reduced the expression of inflammatory mediators induced by cisplatin. These results implicate the CXCL1 chemokine as an early player in cisplatin ototoxicity, possibly by initiating the immune cascade, and indicate that CXCR2 is a relevant target for treating cisplatin ototoxicity.
Topics: Rats; Animals; Male; Cisplatin; Chemokine CXCL1; Ototoxicity; Rats, Wistar; NADPH Oxidases; Hearing Loss
PubMed: 37063917
DOI: 10.3389/fimmu.2023.1125948 -
Current Opinion in Otolaryngology &... Oct 2008Treatment of auditory and vestibular dysfunction has become increasingly dependent on inner ear drug delivery. Recent advances in molecular therapy and nanotechnology... (Review)
Review
PURPOSE OF REVIEW
Treatment of auditory and vestibular dysfunction has become increasingly dependent on inner ear drug delivery. Recent advances in molecular therapy and nanotechnology have pushed development of alternate delivery methodologies involving both transtympanic and direct intracochlear infusions. This review examines recent developments in the field relevant to both clinical and animal research environments.
RECENT FINDINGS
Transtympanic delivery of gentamicin and corticosteroids for the treatment of Meniere's disease and sudden sensorineural hearing loss continues to be clinically relevant, with understanding of pharmacokinetics becoming more closely studied. Stabilizing matrices placed on the round window membrane for sustained passive delivery of compounds offer more controlled dosing profiles than transtympanic injections. Nanoparticles are capable of traversing the round window membrane and cochlear membranous partitions, and may become useful gene delivery platforms. Cochlear and vestibular hair cell regeneration has been demonstrated by vector delivery to the inner ear, offering promise for future advanced therapies.
SUMMARY
Optimal methods of inner ear drug delivery will depend on toxicity, therapeutic dose range, and characteristics of the agent to be delivered. Advanced therapy development will likely require direct intracochlear delivery with detailed understanding of associated pharmacokinetics.
Topics: Adrenal Cortex Hormones; Animals; Cochlea; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Delivery Systems; Genetic Therapy; Gentamicins; Hearing Loss, Sudden; Humans; Injections, Intralesional; Meniere Disease; Nanoparticles; Sensitivity and Specificity; Tympanic Membrane
PubMed: 18797291
DOI: 10.1097/MOO.0b013e32830e20db -
Hearing Research Oct 2018The field of hearing and deafness research is about to enter an era where new cochlear drug delivery methodologies will become more innovative and plentiful. The present... (Review)
Review
The field of hearing and deafness research is about to enter an era where new cochlear drug delivery methodologies will become more innovative and plentiful. The present report provides a representative review of previous studies where efficacious results have been obtained with animal models, primarily rodents, for protection against acute hearing loss such as acoustic trauma due to noise overexposure, antibiotic use and cancer chemotherapies. These approaches were initiated using systemic injections or oral administrations of otoprotectants. Now, exciting new options for local drug delivery, which opens up the possibilities for utilization of novel otoprotective drugs or compounds that might not be suitable for systemic use, or might interfere with the efficacious actions of chemotherapeutic agents or antibiotics, are being developed. These include interesting use of nanoparticles (with or without magnetic field supplementation), hydrogels, cochlear micropumps, and new transtympanic injectable compounds, sometimes in combination with cochlear implants.
Topics: Animals; Cochlea; Drug Delivery Systems; Hearing; Hearing Loss; Labyrinth Diseases; Models, Animal; Pharmaceutical Preparations; Translational Research, Biomedical
PubMed: 29793764
DOI: 10.1016/j.heares.2018.05.002 -
Annals of the Royal College of Surgeons... Nov 2019Menière's disease (MD) is an uncommon cause of sudden profound vertigo. A variety of medical and surgical treatments have been used to manage this condition. This study...
INTRODUCTION
Menière's disease (MD) is an uncommon cause of sudden profound vertigo. A variety of medical and surgical treatments have been used to manage this condition. This study reviewed the outcomes of patients treated with grommet insertion and transtympanic steroid injection.
METHODS
Patients diagnosed with MD between 2007 and 2017 were identified, and case notes and audiological data were retrieved for those managed by grommet (ventilation tube) insertion with and without transtympanic steroid injection.
RESULTS
Thirty-three patients were identified as being diagnosed with MD. Grommet insertion resulted in cessation or improvement of attacks in 91% of cases. The mean follow-up duration was 33.8 months (median: 29 months). The mean hearing threshold across the low frequencies improved from 57.2dBHL to 49.4dBHL (=0.031). Following the intervention, improved tinnitus was reported in 80% of cases. Twelve patients (36%) reported aural fullness prior to grommet insertion; all reported improved symptoms following the procedure.
CONCLUSIONS
Early grommet insertion with transtympanic steroid injection, combined with customised vestibular physiotherapy, may provide an alternative first-line strategy for MD, preventing further true MD attacks. In some patients, it may significantly improve hearing thresholds.
Topics: Adult; Aged; Auditory Threshold; Combined Modality Therapy; Female; Glucocorticoids; Hearing Tests; Humans; Injections; Male; Meniere Disease; Methylprednisolone; Middle Aged; Middle Ear Ventilation; Retrospective Studies; Tinnitus; Vertigo
PubMed: 31508988
DOI: 10.1308/rcsann.2019.0099 -
Frontiers in Systems Neuroscience 2017Before 1964, electrocochleography (ECochG) was a surgical procedure carried out in the operating theatre. Currently, the newest application is also an intra-operative... (Review)
Review
Before 1964, electrocochleography (ECochG) was a surgical procedure carried out in the operating theatre. Currently, the newest application is also an intra-operative one, often carried out in conjunction with cochlear implant surgery. Starting in 1967, the recording methods became either minimal- or not-invasive, i.e., trans-tympanic (TT) or extra tympanic (ET), and included extensive studies of the arguments pro and con. I will review several valuable applications of ECochG, from a historical point of view, but covering all 75 years if applicable. The main topics will be: (1) comparing human and animal cochlear electrophysiology; (2) the use in objective audiometry involving tone pip stimulation-currently mostly pre cochlear implantation but otherwise replaced by auditory brainstem response (ABR) recordings; (3) attempts to diagnose Ménière's disease and the role of the summating potential (SP); (4) early use in diagnosing vestibular schwannomas-now taken over by ABR screening and MRI confirmation; (5) relating human electrophysiology to the effects of genes as in auditory neuropathy; and (6) intracochlear recording using the cochlear implant electrodes. The last two applications are the most recently added ones. The "historical aspects" of this review article will highlight the founding years prior to 1980 when relevant. A survey of articles on Pubmed shows several ups and downs in the clinical interest as reflected in the publication counts over the last 75 years.
PubMed: 28174524
DOI: 10.3389/fnsys.2017.00002 -
International Journal of Pediatric... Mar 2020To summarize recently published key articles on the topics of biomedical engineering, biotechnology and new models in relation to otitis media (OM). (Review)
Review
OBJECTIVE
To summarize recently published key articles on the topics of biomedical engineering, biotechnology and new models in relation to otitis media (OM).
DATA SOURCES
Electronic databases: PubMed, Ovid Medline, Cochrane Library and Clinical Evidence (BMJ Publishing).
REVIEW METHODS
Articles on biomedical engineering, biotechnology, material science, mechanical and animal models in OM published between May 2015 and May 2019 were identified and subjected to review. A total of 132 articles were ultimately included.
RESULTS
New imaging technologies for the tympanic membrane (TM) and the middle ear cavity are being developed to assess TM thickness, identify biofilms and differentiate types of middle ear effusions. Artificial intelligence (AI) has been applied to train software programs to diagnose OM with a high degree of certainty. Genetically modified mice models for OM have further investigated what predisposes some individuals to OM and consequent hearing loss. New vaccine candidates protecting against major otopathogens are being explored and developed, especially combined vaccines, targeting more than one pathogen. Transcutaneous vaccination against non-typeable Haemophilus influenzae has been successfully tried in a chinchilla model. In terms of treatment, novel technologies for trans-tympanic drug delivery are entering the clinical domain. Various growth factors and grafting materials aimed at improving healing of TM perforations show promising results in animal models.
CONCLUSION
New technologies and AI applications to improve the diagnosis of OM have shown promise in pre-clinical models and are gradually entering the clinical domain. So are novel vaccines and drug delivery approaches that may allow local treatment of OM.
IMPLICATIONS FOR PRACTICE
New diagnostic methods, potential vaccine candidates and the novel trans-tympanic drug delivery show promising results, but are not yet adapted to clinical use.
Topics: Animals; Artificial Intelligence; Biofilms; Biomedical Engineering; Biotechnology; Disease Models, Animal; Ear, Middle; Haemophilus Infections; Haemophilus Vaccines; Haemophilus influenzae; Humans; Otitis Media; Otitis Media with Effusion; Tympanic Membrane
PubMed: 31901291
DOI: 10.1016/j.ijporl.2019.109833