Protocol for a multicentre randomised controlled trial of STeroid Administration Routes For Idiopathic Sudden sensorineural Hearing loss: The STARFISH trial.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is the rapid onset of reduced hearing due to loss of function of the inner ear or hearing nerve of unknown aetiology. Evidence supports improved hearing recovery with early steroid treatment, via oral, intravenous, intratympanic or a combination of routes. The STARFISH trial aims to identify the most clinically and cost-effective route of administration of steroids as first-line treatment for ISSNHL. STARFISH is a pragmatic, multicentre, assessor-blinded, three-arm intervention, superiority randomised controlled trial (1:1:1) with an internal pilot (ISRCTN10535105, IRAS 1004878). 525 participants with ISSNHL will be recruited from approximately 75 UK Ear, Nose and Throat units. STARFISH will recruit adults with sensorineural hearing loss averaging 30dBHL or greater across three contiguous frequencies (confirmed via pure tone audiogram), with onset over a ≤3-day period, within four weeks of randomisation. Participants will be randomised to 1) oral prednisolone 1mg/Kg/day up to 60mg/day for 7 days; 2) intratympanic dexamethasone: three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart; or 3) combined oral and intratympanic steroids. The primary outcome will be absolute improvement in pure tone audiogram average at 12-weeks following randomisation (0.5, 1.0, 2.0 and 4.0kHz). Secondary outcomes at 6 and 12 weeks will include: Speech, Spatial and Qualities of hearing scale, high frequency pure tone average thresholds (4.0, 6.0 and 8.0kHz), Arthur Boothroyd speech test, Vestibular Rehabilitation Benefit Questionnaire, Tinnitus Functional Index, adverse events and optional weekly online speech and pure tone hearing tests. A health economic assessment will be performed, and presented in terms of incremental cost effectiveness ratios, and cost per quality-adjusted life-year. Primary analyses will be by intention-to-treat. Oral prednisolone will be the reference. For the primary outcome, the difference between group means and 97.5% confidence intervals at each time-point will be estimated via a repeated measures mixed-effects linear regression model.

Nanocatalysts as fast and powerful medical intervention: Bridging cochlear implant therapies and advanced modelling using Hidden Markov Models (HMMs) for effective treatment of inner ear infections.

As human population growth and waste from technologically advanced industries threaten to destabilise our delicate ecological equilibrium, the global spotlight intensifies on environmental contamination and climate-related changes. These challenges extend beyond our external environment and have significant effects on our internal ecosystems. The inner ear, which is responsible for balance and auditory perception, is a prime example. When these sensory mechanisms are impaired, disorders such as deafness can develop. Traditional treatment methods, including systemic antibiotics, are frequently ineffective due to inadequate inner ear penetration. Conventional techniques for administering substances to the inner ear fail to obtain adequate concentrations as well. In this context, cochlear implants laden with nanocatalysts emerge as a promising strategy for the targeted treatment of inner ear infections. Coated with biocompatible nanoparticles containing specific nanocatalysts, these implants can degrade or neutralise contaminants linked to inner ear infections. This method enables the controlled release of nanocatalysts directly at the infection site, thereby maximising therapeutic efficacy and minimising adverse effects. In vivo and in vitro studies have demonstrated that these implants are effective at eliminating infections, reducing inflammation, and fostering tissue regeneration in the ear. This study investigates the application of hidden Markov models (HMMs) to nanocatalyst-loaded cochlear implants. The HMM is trained on surgical phases in order to accurately identify the various phases associated with implant utilisation. This facilitates the precision placement of surgical instruments within the ear, with a location accuracy between 91% and 95% and a standard deviation between 1% and 5% for both sites. In conclusion, nanocatalysts serve as potent medicinal instruments, bridging cochlear implant therapies and advanced modelling utilising hidden Markov models for the effective treatment of inner ear infections. Cochlear implants loaded with nanocatalysts offer a promising method to combat inner ear infections and enhance patient outcomes by addressing the limitations of conventional treatments.

Behavioral and functional assessment of mice inner ear after chronic exposure to an ultrahigh B0 field of 11.7 T or 17.2 T.

PURPOSE: Assess short-term and long-term effects of chronic exposure to an ultrahigh static magnetic (B0 ) field on mice inner ear in the context of MR safety of human scanning at 11.7 T. METHODS: Mice were chronically exposed to a B0 field of 11.7 T or 17.2 T during ten 2-h exposure sessions evenly distributed over a period of 5 weeks, resulting in a total of 20 h of exposure per mouse. During exposure sessions, mice were anesthetized and positioned either parallel or antiparallel to B0 . Before, during, and 2 weeks after the magnetic-field exposure period, mice performed behavioral tests (balance beam, rotarod, and swim tests) to evaluate their short-term and long-term motor coordination and balance. An auditory brainstem response (ABR) test was finally performed to assess the functional integrity of mice cochlea, 2 weeks after the last exposure. RESULTS: After awaking from anesthesia following B0 exposures at 11.7 Tor 17.2 T, mice displayed a transient (<5 min) rotating behavior. The behavioral tests did not show any difference between the exposed and the control mice at any time point. Determination of ABR thresholds did not reveal an impairment of cochlea hair cells resulting from chronic B0 exposure. CONCLUSION: Despite the transient disturbance of mice vestibular system observed immediately after B0 exposure, no short-term nor long-term alteration was detected with behavioral and ABR tests.

Application of CNN and ANN in assessment the effect of chemical components of biological nanomaterials in treatment of infection of inner ear and environmental sustainability.

Nanoparticles (NPs) are a promising alternative to antibiotics for targeting microorganisms, especially in the case of difficult-to-treat bacterial illnesses. Antibacterial coatings for medical equipment, materials for infection prevention and healing, bacterial detection systems for medical diagnostics, and antibacterial immunizations are potential applications of nanotechnology. Infections in the ear, which can result in hearing loss, are extremely difficult to cure. The use of nanoparticles to enhance the efficacy of antimicrobial medicines is a potential option. Various types of inorganic, lipid-based, and polymeric nanoparticles have been produced and shown beneficial for the controlled administration of medication. This article focuses on the use of polymeric nanoparticles to treat frequent bacterial diseases in the human body. Using machine learning models such as artificial neural networks (ANNs) and convolutional neural networks (CNNs), this 28-day study evaluates the efficacy of nanoparticle therapy. An innovative application of advanced CNNs, such as Dense Net, for the automatic detection of middle ear infections is reported. Three thousand oto-endoscopic images (OEIs) were categorized as normal, chronic otitis media (COM), and otitis media with effusion (OME). Comparing middle ear effusions to OEIs, CNN models achieved a classification accuracy of 95%, indicating great promise for the automated identification of middle ear infections. The hybrid CNN-ANN model attained an overall accuracy of more than 0.90 percent, with a sensitivity of 95 percent and a specificity of 100 percent in distinguishing earwax from illness, and provided nearly perfect measures of 0.99 percent. Nanoparticles are a promising treatment for difficult-to-treat bacterial diseases, such as ear infections. The application of machine learning models, such as ANNs and CNNs, can improve the efficacy of nanoparticle therapy, especially for the automated detection of middle ear infections. Polymeric nanoparticles, in particular, have shown efficacy in treating common bacterial infections in children, indicating great promise for future treatments.

Novel Multiportal Approach to the Internal Auditory Canal for Hearing-Preserving Surgery: Feasibility Assessment in Dissections.

OBJECTIVE: State-of-the-art, minimally invasive endoscopic transcanal surgery of the internal auditory canal (IAC) sacrifices the cochlea with complete hearing loss. With a combination of the transcanal infracochlear and transmastoid retrolabyrinthine approaches, we aim to preserve hearing and enable minimally invasive surgical treatment of vestibular schwannoma. In this study, we investigate the anatomical indications and the feasibility of both approaches in dissections, in human whole head specimens. METHODS: We operated whole head anatomical specimens with a four-handed technique, using the retrolabyrinthine approach as the main surgical corridor and the infracochlear approach for endoscopic visualization. We tested 4 different powered surgical systems. We collected intraoperative data on the size of the access windows, the surgical freedom, and the exposed area of the IAC. Finally, we evaluated the outcome in postoperative computed tomography scans. RESULTS: Six out of 14 sides were anatomically suitable and qualified for the surgery based on preoperative computed tomography. In all attempted sides, the IAC could be reached and opened, leaving the ossicular chain and the labyrinth intact. 51%-75% of the length and 22%-40% of the circumference of the IAC could be exposed. All tested instruments were beneficial at different stages of the surgery. The four-handed technique enabled good maneuverability of the instruments. CONCLUSIONS: The combined multiportal approach to the IAC is feasible with a good surgical exposure and full anatomical preservation of hearing. State-of-the-art surgical instruments in specimens with suitable anatomy are sufficient to perform this approach.

Assessment of prestin level changes as an inner-ear biomarker in patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE: To assess the correlation of serum prestin level and audiological findings in adults with idiopathic sudden sensorineural hearing loss. METHODS: Audiometry and serum prestin measurements were performed at study entry (T0), at day 14 (end of treatment, T1) and at day 30 (T2). RESULTS: A total of 25 idiopathic sudden sensorineural hearing loss patients and 25 healthy adults were included. The geometric mean prestin level in the case and control groups at T0 was 227.7 pg/ml and 130.5 pg/ml, respectively. The geometric mean prestin level in the case group demonstrated a downward trend at T1 and T2 (214.0 pg/ml and 180.1 pg/ml, respectively; p < 0.001). Of 17 patients with high baseline prestin levels (over 150 pg/ml), prestin levels tended to decrease in 11 patients, and 5 of them (45.5 per cent) showed good recovery. CONCLUSION: The prestin concentrations increased in two-thirds of patients with idiopathic sudden sensorineural hearing loss. Future work is recommended to determine the location of injury.

Hearing-related quality of life assessment of pediatric cochlear implant users with inner ear malformations.

OBJECTIVES: To assess the quality of life (QoL) in child and adolescent cochlear implant users with inner ear malformations (IEM) and to compare their outcomes to their cochlear implant using peers with normal inner ear structures. METHODS: The present sample consisted of 100 children (45 with IEM, 55 without IEM) and 100 adolescents (46 with IEM, 54 without IEM). The following QoL questionnaires were used to assess the hearing-related QoL: The Hearing Environments and Reflection on Quality of Life 26 (HEAR-QL-26 for children between 7 and 12 years of age) and HEAR-QL-28 (for adolescents between 13 and 18 years of age). Both questionnaires were based on a 5-points Likert scale from 0 to 4, with higher scores indicating a better perception of QoL. The scores were converted to percentage values (never = 100, almost never = 75, sometimes = 50, often = 25, almost always = 0). RESULTS: For the patients with IEM, mean scores from the HEAR-QL-26 and HEAR-QL-28 were 50.4 (SD = 18.9) and 54.5 (SD = 19.6), respectively. For the patients without IEM, mean scores from the HEAR-QL-26 and HEAR-QL-28 were 72.7 (SD = 18.0) and 65.0 (SD = 19.1), respectively. For both child and adolescent subgroups, statistically significant differences were observed between QoL scores from patients with and without IEM (p < 0.001). There were no statistically significant effects of the malformation type on the QoL findings (p ≥ 0.05). CONCLUSION: Child and adolescent cochlear implant users with IEM had significantly lower scores on validated HEAR-QL versions in comparison to their implanted peers without IEM.

Hearing-Preserving Approaches to the Internal Auditory Canal: Feasibility Assessment from the Perspective of an Endoscope.

OBJECTIVE: Minimally invasive transcanal transpromontorial endoscopic approaches to the internal auditory canal sacrifice the cochlea. Two hearing-preserving approaches, the exclusively endoscopic transcanal infracochlear approach and the endoscope-assisted transmastoid retrolabyrinthine approach, have been controversially discussed in the literature. In this study, we examine the feasibility of these 2 approaches by means of three-dimensional surface models, a population-based analysis of the available surgical space, and dissections in human whole-head specimens. METHODS: We reconstructed three-dimensional surface models based on clinical high-resolution computed tomography scans of 53 adult temporal bones. For both approaches, we measured the maximal extensions and the area of the surgical access windows located between landmarks on the surrounding anatomic structures. We then identified the limiting extensions and derived the cumulative distribution to describe the available surgical space. Dissections were performed to validate the corridors and landmark selection. RESULTS: The limiting extension for the infrachochlear approach is 7.0 ± 2.7 mm from the round window to the dome of the jugular bulb. The limiting extension for the retrolabyrinthine approach is 6.4 ± 1.5 mm from the dura of the posterior fossa to the facial nerve. The cumulative distribution shows that 80% of the cohort have access window extensions ≥3 mm for both approaches. CONCLUSIONS: This study shows that in a high percentage of the measured cohort, the access windows are sufficiently large for endoscopic approaches to the internal auditory canal. With appropriate instrumentation, these hearing-preserving minimally invasive approaches may evolve into alternatives to surgical treatment.

Construction of an MRI-based decision tree to differentiate autoimmune and autoinflammatory inner ear disease from chronic otitis media with sensorineural hearing loss.

Autoimmune and autoinflammatory inner ear diseases (AIED/AID) are characterized by the symptom of sensorineural hearing loss (SNHL). To date, standardized diagnostic tools for AIED/AID are lacking, and clinically differentiating AIED/AID from chronic otitis media (COM) with SNHL is challenging. This retrospective study aimed to construct a magnetic resonance imaging (MRI)-based decision tree using classification and regression tree (CART) analysis to distinguish AIED/AID from COM. In total, 67 patients were enrolled between January 2004 and October 2019, comprising AIED/AID (n = 18), COM (n = 24), and control groups (n = 25). All patients underwent 3 T temporal bone MRI, including post-contrast T1-weighted images (postT1WI) and post-contrast FLAIR images (postFLAIR). Two radiologists evaluated the presence of otomastoid effusion and inner ear contrast-enhancement on MRI. A CART decision tree model was constructed using MRI features to differentiate AIED/AID from COM and control groups, and diagnostic performance was analyzed. High-intensity bilateral effusion (61.1%) and inner ear enhancement (postFLAIR, 93.8%; postT1WI, 61.1%) were the most common findings in the AIED/AID group. We constructed two CART decision tree models; the first used effusion amount as the first partitioning node and postT1WI-inner ear enhancement as the second node, whereas the second comprised two partitioning nodes with the degree of postFLAIR-enhancement of the inner ear. The first and second models enabled distinction of AIED/AID from COM with high specificity (100% and 94.3%, respectively). The amount of effusion and the degree of inner ear enhancement on MRI may facilitate the distinction between AIED/AID and COM with SNHL using decision tree models, thereby contributing to early diagnosis and intervention.

Preoperative Differences in Intracranial Facial Versus Vestibular Schwannomas: A Four Nerve Assessment.

OBJECTIVES: Assesses whether preoperative functional testing can distinguish vestibular schwannomas from facial nerve schwannomas medial to the labyrinthine segment. STUDY DESIGN: Retrospective cohort. METHODS: Retrospectively review surgically managed intracranial facial and vestibular schwannomas between January 2015 and December 2019 at two tertiary care centers. Patients with neurofibromatosis 2 and surgery for recurrence were excluded. Preoperative functional testing to include House-Brackmann scores, electroneuronography (ENoG), cervical vestibular evoked myogenic potentials (cVEMP), caloric testing, acoustic brainstem responses (ABRs), acoustic reflexes, and audiograms was compared between the two groups of schwannomas. RESULTS: Twelve facial and 128 vestibular schwannomas met inclusion criteria. In only one case was a facial schwannoma diagnosed preoperatively from imaging. No statistically significant difference was found in preoperative House-Brackmann scores, ENoG, cVEMP, caloric testing, ABRs, or acoustic reflexes. Pure tone average was worse in the vestibular schwannoma group (63 dB [95% CI: 58-68 dB] vs. 46 dB [95% CI: 34-58 dB], P = .01), and the difference was more apparent in the lower frequencies. Word recognition score was better in the facial schwannoma group (66% [95% CI: 45-86%] vs. 41% [95% CI: 34-47%], P = .02). CONCLUSION: Specialized preoperative functional evaluation of the nerves of the internal auditory canal cannot reliably predict the presence of an intracranial facial schwannoma. Hearing is better in facial schwannomas, particularly in the lower frequencies. This should raise the index of suspicion for an intracranial facial schwannoma, especially in candidates for hearing preservation vestibular schwannoma surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2098-2105, 2021.

Comparative assessment of Fgf's diverse roles in inner ear development: A zebrafish perspective.

Progress in understanding mechanisms of inner ear development has been remarkably rapid in recent years. The research community has benefited from the availability of several diverse model organisms, including zebrafish, chick, and mouse. The complexity of the inner ear has proven to be a challenge, and the complexity of the mammalian cochlea in particular has been the subject of intense scrutiny. Zebrafish lack a cochlea and exhibit a number of other differences from amniote species, hence they are sometimes seen as less relevant for inner ear studies. However, accumulating evidence shows that underlying cellular and molecular mechanisms are often highly conserved. As a case in point, consideration of the diverse functions of Fgf and its downstream effectors reveals many similarities between vertebrate species, allowing meaningful comparisons the can benefit the entire research community. In this review, I will discuss mechanisms by which Fgf controls key events in early otic development in zebrafish and provide direct comparisons with chick and mouse.

Assessment of the Membranous Labyrinth in Infants Using a Heavily T2-weighted 3D FLAIR Sequence without Contrast Agent Administration.

BACKGROUND AND PURPOSE: Imaging is fundamental to assessing the acoustic pathway in infants with congenital deafness. We describe our depiction of the membranous labyrinth in infants using the heavily T2-weighted 3D FLAIR sequence without a contrast agent. MATERIALS AND METHODS: We retrospectively reviewed 10 infants (20 ears) (median term equivalent age: 2 weeks; IQR: 1-5 weeks) who had undergone brain MR imaging including a noncontrast heavily T2-weighted 3D FLAIR scan of the temporal bone. For each ear, 3 observers analyzed, in consensus, the saccule, the utricle, and the 3 ampullae, assessing the visibility (score 0, not appreciable; score 1, visible without well-defined boundaries; score 2, visible with well-defined boundaries) and morphology ("expected" or "unexpected" compared with adults). The heavily T2-weighted 3D FLAIR sequence was scored for overall quality (score 0, inadequate; score 1, adequate but with the presence of image degradation; score 2, adequate). RESULTS: Six (60%) MR examinations were considered adequate (score 1 or 2). The saccule was visible in 10 ears (83.3%) with an expected morphology in 9 ears (90%). In 1 ear of an infant with congenital deafness, the saccule showed an unexpected morphology. The utricle was visible as expected in 12 ears (100%). The lateral ampulla was visible in 5 ears (41.6%), the superior ampulla was visible in 6 ears (50.0%), and the posterior ampulla was visible in 6 ears (50.0%), always with expected morphology (100%). CONCLUSIONS: MR imaging can depict the membranous labyrinth in infants using heavily T2-weighted 3D FLAIR without an injected contrast agent, but the sequence acquisition time reduces its feasibility in infants undergoing MR studies during natural sleep.

Investigating the Potential of Phosphatidylcholine-Based Nano-Sized Carriers in Boosting the Oto-Topical Delivery of Caroverine: in vitro Characterization, Stability Assessment and ex vivo Transport Studies.

PURPOSE: Drug delivery into the inner ear across the intact tympanic membrane (TM) has been a challenge in the treatment of inner ear disorders. In this study, nano-sized carriers were formulated for improving the non- invasive oto-topical delivery of caroverine for the treatment of tinnitus. METHODS: Caroverine was loaded into two types of phospholipid-containing systems, namely, nano elastic vesicles (EVs) and phosphatidylcholine-based liquid crystalline nano-particles (PC-LCNPs). The prepared formulations were characterized for their drug loading, particle size, polydispersity index, zeta potential, morphological features by transmission electron microscopy (TEM), and physicochemical stability. In addition, comparative ex vivo transport study was carried out using rabbits' TM for both types of formulations. RESULTS: The findings show a significant superiority of PC-LCNPs over the EVs formulations in the drug payload (1% and 0.25%, respectively), physical stability and the efficiency of permeation across rabbits' TM. The results showed a more than twofold increase in the cumulative drug flux values of PC-LCNPs (699.58 ± 100 µg/cm2) compared to the EVs (250 ± 45 µg/cm2) across the TM. CONCLUSION: The current study revealed the smart physicochemical properties of PC-LCNPs demonstrating the potential of this carrier as a new attractive candidate for improving the non-invasive oto-topical delivery of caroverine.

Auditory Brainstem Implantation for Adults With Neurofibromatosis 2 or Severe Inner Ear Abnormalities: A Health Technology Assessment.

BACKGROUND: Neurofibromatosis 2 (NF2) is a rare genetic disorder that causes vestibular schwannomas to develop in both eighth cranial nerves. Almost all people with NF2 eventually become completely deaf as a result of progressive tumour enlargement or following surgical or radiotherapy treatment. Other rare abnormal conditions in the inner ears can also cause complete deafness. For people with either indication who are not candidates for cochlear implantation, auditory brainstem implantation is the only treatment option to restore some functional hearing. We conducted a health technology assessment of auditory brainstem implantation for adults with NF2 and severe inner ear abnormalities, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding auditory brainstem implantation, and patient preferences and values. METHODS: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search. We did not conduct a primary economic evaluation because the outcomes identified in our clinical evidence review were difficult to translate into measures appropriate for health economic modelling. We also analyzed the net budget impact of publicly funding auditory brainstem implantation over the next 5 years in Ontario, including the device, presurgical assessment, surgical procedure, and postsurgical rehabilitation. To contextualize the potential value of auditory brainstem implants, we spoke with six people with lived experience of NF2 and severe inner ear abnormalities. RESULTS: We included 22 publications (16 in NF2, five in severe inner ear abnormalities, and one in complications of auditory brainstem implantation) in the clinical evidence review. In adults with NF2, auditory brainstem implantation when compared with no intervention allows any degree of improvement in sound recognition (GRADE: High), allows any degree of improvement in speech perception when used in conjunction with lip-reading (GRADE: High), and provides subjective benefits of hearing (GRADE: High). It likely allows any degree of improvement in speech perception when using the implant alone (GRADE: Moderate) and may improve quality of life (GRADE: Low). In adults with severe inner ear abnormalities, auditory brainstem implantation when compared with no intervention likely allows any degree of improvement in sound recognition (GRADE: Moderate) and in any speech perception when using the implant alone (GRADE: Moderate). It may allow any degree of improvement in speech perception when used in conjunction with lip-reading (GRADE: Low), provide subjective benefits of hearing (GRADE: Low), and improve quality of life (GRADE: Low).We did not identify any economic studies on auditory brainstem implantation for adults with NF2 or adults with deafness due to severe inner ear abnormalities. We estimated that the annual net budget impact of publicly funding auditory brainstem implantation in Ontario over the next 5 years would range from about $130,000 in year 1 for two procedures to about $260,000 in year 5 for four procedures.People with whom we spoke who had received an auditory brainstem implant reported that it restored some hearing ability and improved their quality of life, though they also reported ongoing challenges in using the device or side effects from the procedure. CONCLUSIONS: When compared with no intervention, auditory brainstem implantation provides some benefit for completely deaf adults with NF2 or severe inner ear abnormalities who are not candidates for cochlear implantation. Based on evidence of moderate to high quality, auditory brainstem implants allow any degree of improvement in sound recognition and in speech perception when used in conjunction with lip-reading for people with NF2. The quality of evidence on these outcomes was low to moderate for people with severe inner ear abnormalities. These functional outcomes lead to subjective benefits of hearing which are consistently reported in the literature and in interviews with patients. We were unable to determine the cost-effectiveness of this treatment. We estimate that publicly funding auditory brainstem implantation in Ontario would result in additional costs of about $130,000 to $260,000 annually over the next 5 years.

Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN): assessment of potential otoprotective effects.

BACKGROUND: Ototoxicity is one of the major side effects of platinum-based chemotherapy, especially cisplatin therapy. To date, no FDA approved agents to alleviate or prevent this ototoxicity are available. However, ototoxicity is generally believed to be produced by excessive generation of reactive oxygen species (ROS) in the inner ear, thus leading to the development of various antioxidants, which act as otoprotective agents. Astaxanthin (ATX) is an interesting candidate in the development of new therapies for preventing and treating oxidative stress-related pathologies, owing to its unique antioxidant capacity. METHODS AND RESULTS: In this study, we aimed to evaluate the potential antioxidant properties of ATX in the inner ear by using the HEI-OC1 cell line, zebrafish, and guinea pigs. Because ATX has poor solubility and cannot pass through round window membranes (RWM), we established lipid-polymer hybrid nanoparticles (LPN) for loading ATX. The LPN enabled ATX to penetrate RWM and maintain concentrations in the perilymph in the inner ear for 24 h after a single injection. ATX-LPN were found to have favorable biocompatibility and to strongly affect cisplatin-induced generation of ROS, on the basis of DCFHDA staining in HEI-OC1 cells. JC-1 and MitoTracker Green staining suggested that ATX-LPN successfully reversed the decrease in mitochondrial membrane potential induced by cisplatin in vitro and rescued cells from early stages of apoptosis, as demonstrated by FACS stained with Annexin V-FITC/PI. Moreover, ATX-LPN successfully attenuated OHC losses in cultured organ of Corti and animal models (zebrafish and guinea pigs) in vivo. In investigating the protective mechanism of ATX-LPN, we found that ATX-LPN decreased the expression of pro-apoptotic proteins (caspase 3/9 and cytochrome-c) and increased expression of the anti-apoptotic protein Bcl-2. In addition, the activation of JNK induced by CDDP was up-regulated and then decreased after the administration of ATX-LPN, while P38 stayed unchanged. CONCLUSIONS: To best of our knowledge, this is first study concluded that ATX-LPN as a new therapeutic agent for the prevention of cisplatin-induced ototoxicity.

Hearing Protection, Restoration, and Regeneration: An Overview of Emerging Therapeutics for Inner Ear and Central Hearing Disorders.

OBJECTIVE: To provide an overview of biotechnology and pharmaceutical companies active in the field of inner ear and central hearing disorders and their therapeutic approaches. METHODS: Scientific and grey literature was searched using broad search terms to identify companies and their hearing-related therapeutic approaches. For each approach its lead indication, product, therapeutic modality, target, mechanism of action and current phase of clinical development was collated. RESULTS: A total of 43 biotechnology and pharmaceutical companies have been identified that are developing therapeutics for inner ear and central hearing disorders. Their therapeutics include drug-, cell- and gene-based approaches to prevent hearing loss or its progression, restore hearing, and regenerate the inner ear. Their therapeutic targets and specific mechanisms of action are wide-ranging, reflecting the complexity of the hearing pathways and the diversity of mechanisms underlying inner ear disorders. While none of the novel products under investigation have yet made it to the clinical market, and a large proportion are still at preclinical phase, many therapeutics have already entered clinical testing with more expected to do so in the next few years. CONCLUSION: A wide range of novel therapeutics targeting different hearing, balance and tinnitus pathways, and patient populations are approaching the clinical domain. It is important that clinicians involved in the care of patients with hearing loss prepare for what may become a radically different approach to the management of hearing disorders, and develop a true understanding of the new therapies' mechanisms of action, applications, and indications.

Incidental mastoiditis on magnetic resonance imaging scans: clinical relevance and cost implications.

OBJECTIVES: To determine: (1) the incidence of incidental 'mastoiditis' reported on magnetic resonance imaging scans performed in patients with asymmetrical sensorineural hearing loss and/or unilateral tinnitus; (2) how many of those patients have actual otological pathology and/or require treatment; and (3) the financial implications of such a reporting practice. METHOD: Retrospective case series. RESULTS: Between October 2015 and November 2016, 500 patients underwent magnetic resonance imaging of the internal auditory meatus to rule out cerebellopontine angle lesions. There was an incidental finding of increased mastoid signalling in 5.8 per cent (n = 29), of which 20.7 per cent (6 of 29) were reported as bilateral cases. The diagnosis of 'mastoiditis' was found in 39.7 per cent (29 of 73). None of these patients had any pathology identified clinically. Other significant pathology was identified in a further 8.8 per cent (n = 44). CONCLUSION: The diagnosis of mastoiditis is primarily clinical. An incidental finding of high signalling in the mastoid region on magnetic resonance imaging is highly unlikely to represent actual clinical disease. In patients who are scanned for other reasons and who do not complain of otological symptoms, such findings are unlikely to require otolaryngology input.

Flat Panel Angiography in the Cross-Sectional Imaging of the Temporal Bone: Assessment of Image Quality and Radiation Dose Compared with a 64-Section Multisection CT Scanner.

BACKGROUND AND PURPOSE: Cross-sectional imaging of the temporal bone is challenging because of the complexity and small dimensions of the anatomic structures. We evaluated the role of flat panel angiography in the cross-sectional imaging of the temporal bone by comparing its image quality and radiation dose with a 64-section multisection CT scanner. MATERIALS AND METHODS: We retrospectively collected 29 multisection CT and 29 flat panel angiography images of normal whole-head temporal bones. Image quality was assessed by 2 neuroradiologists, who rated the visualization of 30 anatomic structures with a 3-point ordinal scale. The radiation dose was assessed with an anthropomorphic phantom. RESULTS: Flat panel angiography showed better image quality than multisection CT in depicting the anterior and posterior crura of the stapes, the footplate of the stapes, the stapedius muscle, and the anterior ligament of the malleus (P < .05). In contrast, multisection CT showed better image quality than flat panel angiography in assessing the tympanic membrane, the bone marrow of the malleus and incus, the tendon of the tensor tympani, the interscalar septum, and the modiolus of the cochlea (P < .05). Flat panel angiography had a significantly higher overall image quality rating than multisection CT (P = .035). A reduction of the effective dose of approximately 40% was demonstrated for flat panel angiography compared with multisection CT. CONCLUSIONS: Flat panel angiography shows strengths and weaknesses compared with multisection CT. It is more susceptible to artifacts, but due to the higher spatial resolution, it shows equal or higher image quality in assessing some bony structures of diagnostic interest. The lower radiation dose is an additional advantage of flat panel angiography.

Assessment of the cochlear nerve to facial nerve size ratio using MR multiplanar reconstruction of the internal auditory canal in patients presenting with acquired long-standing hearing loss.

OBJECTIVE: To test using the facial nerve as a reference for assessment of the cochlear nerve size in patients with acquired long-standing sensorineural hearing loss (SNHL) using MRI multiplanar reconstruction. METHODS: The study was retrospectively performed on 86 patients. Group 1 (study group, n = 53) with bilateral long-standing SNHL. Group 2 (control group, n = 33) without hearing loss. The nerve size was measured by drawing a region of interest around the cross-sectional circumference of the nerve in multiplanar reconstruction images. RESULTS: No significant correlation was noted between the cochlear nerve and facial nerve size, and the patient's age, gender and weight (p > 0.05). In Group 1, the mean ratio of the cochlear to facial nerve size was 0.99 ± 0.30 (range: 0.52-1.86) and 1.12 ± 0.35 (range: 0.34-2.3) for the right and left sides, respectively. In Group 2, it was 1.18 ± 0.23 (range: 0.78-1.71) and 1.25 ± 0.25 (range: 0.85-1.94) for the right and left sides, respectively. The cochlear nerve size was statistically (p = 0.0004) smaller in Group 1 than in Group 2. CONCLUSION: The cochlear nerve size and the cochlear to facial nerve size ratio are significantly smaller in patients with acquired long-standing SNHL. Advances in knowledge: The facial nerve can be used as a reference for assessment of the cochlear nerve in patients with acquired long-standing SNHL.