A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss.

Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change -0.87 dB; 95% CI -2.37 to 0.63; P = 0.252 and -0.46 dB; 95% CI -1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial's primary endpoint was not met.

Potential role of modulating autophagy levels in sensorineural hearing loss.

In recent years, extensive research has been conducted on the pathogenesis of sensorineural hearing loss (SNHL). Apoptosis and necrosis have been identified to play important roles in hearing loss, but they cannot account for all hearing loss. Autophagy, a cellular process responsible for cell self-degradation and reutilization, has emerged as a significant factor contributing to hearing loss, particularly in cases of autophagy deficiency. Autophagy plays a crucial role in maintaining cell health by exerting cytoprotective and metabolically homeostatic effects in organisms. Consequently, modulating autophagy levels can profoundly impact the survival, death, and regeneration of cells in the inner ear, including hair cells (HCs) and spiral ganglion neurons (SGNs). Abnormal mitochondrial autophagy has been demonstrated in animal models of SNHL. These findings indicate the profound significance of comprehending autophagy while suggesting that our perspective on this cellular process holds promise for advancing the treatment of SNHL. Thus, this review aims to clarify the pathogenic mechanisms of SNHL and the role of autophagy in the developmental processes of various cochlear structures, including the greater epithelial ridge (GER), SGNs, and the ribbon synapse. The pathogenic mechanisms of age-related hearing loss (ARHL), also known as presbycusis, and the latest research on autophagy are also discussed. Furthermore, we underscore recent findings on the modulation of autophagy in SNHL induced by ototoxic drugs. Additionally, we suggest further research that might illuminate the complete potential of autophagy in addressing SNHL, ultimately leading to the formulation of pioneering therapeutic strategies and approaches for the treatment of deafness.

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.

[Role of intratympanic glucocorticoid treatment in sudden hearing loss]. / Stellenwert der intratympanalen Glukokortikoidtherapie in der Behandlung des Hörsturzes.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is one of the most common diseases in otolaryngology. Its etiology remains unknown. Furthermore, there is only a low level of evidence for the efficacy of established treatment modalities. In addition to systemic glucocorticoids, intratympanic corticosteroid treatment (ICT) has become increasingly important for treatment of ISSNHL. Different application strategies and treatment regimens have been described; however, uniform standards do not yet exist. ICT may be used for primary treatment as well as salvage therapy. Current data from meta-analyses show no benefit of intratympanic versus systemic primary therapy for sudden hearing loss (moderate evidence) but suggest a benefit of intratympanic secondary treatment over no treatment or placebo (high effect size, low evidence). Regarding combination of systemic and local glucocorticoid therapy in primary treatment of hearing loss, there may be a small benefit over systemic treatment alone (low effect size, low evidence).

Clinical efficacy of intratympanic steroid injection for treating idiopathic sudden sensorineural hearing loss.

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) is an emergency that causes permanent hearing loss if timely treatment is not provided. However, the evidence supporting the effect of intratympanic steroid injection (ITSI) starting time on hearing outcome is limited. METHODS: We retrospectively enrolled 582 patients with ISSNHL who were treated with ITSIs and reviewed their clinical and audiological variables. The relationship between ITSI starting time and hearing recovery was analyzed. RESULTS: The mean starting time of ITSI was 13.17 ± 16.53 days. The overall hearing recovery rate was 55.15% (recovery = mean hearing level gain of ≥10 dB). The recovery rates were 79.2%, 67.4%, 50%, 36.6%, and 17.8% for the ITSI starting times of 1 to 3, 4 to 7, 8 to 14, 15 to 28, and ≥29 days, respectively. A multivariate analysis revealed that ITST starting time (odds ratio [OR] = 0.94, 95% CI, 0.92-0.96, p < 0.001) and salvage therapy (OR = 0.55, 95% CI, 0.35-0.86, p = 0.009) were independent poor prognostic factors for patients with ISSNHL. CONCLUSION: Earlier ITSI treatment is associated with a higher hearing recovery rate. Comorbidities and post-ITSI complications were nonsignificant independent risk factors.

N-Acetylcysteine combined with prednisolone treatment shows better hearing outcome than treatment with prednisolone alone for patients with idiopathic sudden sensorineural hearing loss: a retrospective observational study.

OBJECTIVES: Internationally, corticosteroids are still the mainstay treatment for patients with idiopathic sudden sensorineural hearing loss (ISSHL). This is a retrospective monocentric study investing the impact of adding N-acetylcysteine (NAC) to prednisolone treatment on patients with ISSHL at a tertiary university otorhinolaryngology department. METHODS: 793 patients (median age 60 years; 50.9% women) with a new diagnosis of ISSHL from 2009 to 2015 were included in the study. 663 patients received NAC administration in addition to standard tapered prednisolone treatment. Univariate and multivariable analysis were performed to identify independent factors regarding negative prognosis of hearing recovery. RESULTS: Mean initial ISSHL and hearing gain after treatment in 10-tone pure tone audiometry (PTA) were 54.8 ± 34.5 dB and 15.2 ± 21.2 dB, respectively. In univariate analysis, treatment with prednisolone and NAC was associated with a positive prognosis of hearing recovery in the Japan classification in 10-tone PTA. In multivariable analysis on Japan classification in 10-tone PTA including all significant factors from univariate analysis, negative prognosis of hearing recovery were age > median (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.139-2.385; p = 0.008), diseased opposite ear (OR 3.049; CI 2.157-4.310; p < 0.001), pantonal ISSHL (OR 1.891; CI 1.309-2.732; p = 0.001) and prednisolone alone without NAC treatment (OR 1.862; CI 1.200-2.887; p = 0.005). CONCLUSIONS: Prednisolone treatment combined with NAC resulted in better hearing outcomes in patients with ISSHL than treatment without NAC.

Batroxobin can improve the efficacy of combination therapy for profound sudden sensorineural hearing loss greater than but not less than 100 dB HL.

OBJECTIVE: To investigate the effects of combination therapy with and without batroxobin, and the frequency of batroxobin use on the prognosis of profound sudden sensorineural hearing loss. METHODS: Hearing recovery in the batroxobin group (231 patients) and non-batroxobin group (56 patients) was compared. The correlation between the number of times batroxobin was used and hearing recovery was analysed. RESULTS: The decrease in hearing threshold and overall improvement rate in the batroxobin group with hearing loss exceeding 100 dB HL was significantly higher than that in the non-batroxobin group. There was no linear correlation between the number of times batroxobin was used and the overall improvement rate. Using batroxobin two to three times achieved a therapeutic effectiveness plateau. CONCLUSION: Batroxobin can improve the efficacy of combination therapy for profound sudden sensorineural hearing loss exceeding 100 dB HL, and using batroxobin two to three times yields the maximum overall improvement rate.

Case report of scrub typhus with bilateral acute sensorineural hearing loss and cerebral salt-wasting disease.

Scrub typhus is a re-emerging and endemic disease in the Asia Pacific region caused by Orientia tsutsugamushi. We present a 65-year-old male from Sri Lanka who presented with fever, bilateral acute sensorineural hearing loss, and confusion. On examination, he was dehydrated. Significant orthostatic hypotension and an eschar were noted. Investigations revealed hyponatraemia with elevated urine sodium, reduced serum osmolality, and normal urine osmolality suggestive of cerebral salt wasting. After initial hydration with 0.9% NaCl, hyponatraemia was corrected with 3% NaCl. Oral doxycycline was prescribed, and he showed dramatic clinical improvement. A diagnosis of typhus must be considered in a patient presenting with a febrile illness and acute hearing loss. Cerebral salt-wasting disease should be considered in a patient with typhus who develops hyponatraemia with dehydration. Furthermore, acute sensorineural hearing loss in both ears is an important manifestation of the disease.

Efficacy of high dose systemic versus combined (systemic and intratympanic) corticosteroid therapy in idiopathic sudden sensorineural hearing loss: A prospective randomized trial and risk factor analysis.

The pathophysiology and the proper treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) are an ongoing subject of debate. Locally or systemic administered corticosteroids are the most accepted drugs of treatment in reference to ISSNHL (idiopathic sudden sensorineural hearing loss), however, no strong evidence nor guidelines regarding their effectiveness yet exists. In our prospective, randomized, controlled trial 78 participants were enrolled. Patients were randomly assigned based on the day of admission to two groups according to treatment: group SS (n = 43) received intravenous systemic methylprednisolone alone, and group CT (n = 35) received intratympanic dexamethasone + systemic methylprednisolone. The primary outcome was to compare the hearing outcomes between the treatment groups based on different, widely accepted categories (Siegel, Kanzaki, modified Siegel and PTA4 gain). In consideration of the secondary outcome, we examined the effect of the various risk factors on the hearing improvement. No differences were detected regarding hearing improvement between the two groups, based on any criteria [Siegel's criteria (p = 0.604); Kanzaki's criteria (p = 0.720); modified Siegel's criteria (p = 0.524) and PTA 4 gain (p = 0.569)]. However, several clinical factors such as vertigo (p = 0.039), or cardiovascular comorbidity (p = 0.02) and the severity of initial hearing loss (p = 0.033) were found to bear a significant impact upon the hearing outcome. To the best of our knowledge, this is the first randomized controlled trial comparing high dose systemic and combination corticosteroid therapy in ISSNHL patients. Our findings suggest coexisting cardiovascular comorbidity, vertigo and severity of the initial hearing loss may bear a significantly higher impact upon hearing improvement, than the additional intratympanic steroid administration. The presented trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (name: Combinated systemic and intratympanic steroid therapy in idiopathic sudden sensorineural hearing loss, No.: 2017-000658-20) and with the ethical approval of The National Institute of Pharmacy and Nutrition (OGYÉI) (protocol No.: 7621, on 2017.02.16.).

Efficacy of intratympanic steroid therapy for severe and profound sudden sensorineural hearing loss.

BACKGROUND: Intratympanic steroids (ITS) in treating sudden sensorineural hearing loss (SSNHL) have become more widespread. AIM: This study investigates whether ITS treatment provides additional benefits when combined with systemic steroids (SS) in patients with severe and profound SSNHL. MATERIALS AND METHODS: Patients diagnosed with severe and profound SSNHL were divided into two groups: SS group and SS combined with ITS group. Pure-tone audiometry was performed before and three months after treatment completion. The pure-tone average (PTA), frequency-specific hearing gains, and average values were compared between the groups. RESULTS: The study included 57 patients (27 SS, 30 ITS), with a mean age of 50.09 ± 15.56. Before treatment: SS PTA 84.40 ± 15 dB HL, ITS 87.50 ± 9.38 dB HL (p = 0.36). After treatment: SS 62.2 ± 23.13 dB HL, ITS 65.17 ± 12.19 dB HL (p = 0.55). Average hearing gain: SS 22.19 ± 13.81 dB HL, ITS 22.33 ± 12.24 dB HL (p = 0.96). Frequency-specific gains were similar (p > 0.05). SS group: 12 slight improvement, 10 no improvement, 3 partial, 2 complete recovery. ITS group: 23 slight improvement, 6 no improvement, 1 partial. CONCLUSION: In our study, combining ITS with SS treatment did not provide additional benefits in treating severe and profound SSNHL.

An Italian case series' description of thiamine responsive megaloblastic anemia syndrome: importance of early diagnosis and treatment.

BACKGROUND: Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations. CASES PRESENTATION: Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed. CONCLUSIONS: Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.

Pregnant Patients with Sudden Sensorineural Hearing Loss: Treatments and Efficacy.

BACKGROUND: The aim of this study was to study the safety and effectiveness of oral and tympanic hormone injection in the treatment of sudden sensorineural hearing loss during pregnancy. METHODS: Data were collected via prospective method. A total of 102 pregnant women with sensorineural hearing loss as experimental group and another 102 patients of sensorineural hearing loss without pregnancy as control group were simultaneously included in the study. Pure tone audiometry test was examined at pre- and posttreatment in 1 week, 2 weeks, and 12 weeks. The experimental group received oral and tympanic hormones, while the control group was treated with the Clinical Practice Guideline: Sudden Hearing Loss (2019) of USA. Recovery rate and hearing gain were assessed by the Clinical Practice Guidelines. RESULTS: After treatment, the effects of the experimental group and the control group were compared at the 1st, 2nd, and 12th week after treatment. It was found that at the 12th week after treatment, the curative effect of the experimental group was significantly different from that of the control group, and the difference was statistically significant. CONCLUSION: The pregnant women with sensorineural hearing loss were more serious than nonpregnant women, and the treatment efficacies were worse than control group. For pregnancy patients with sudden deafness, oral steroids and tympanic cavity injection is an effective, safe first-line treatment options.

Hearing results with combination steroid therapy for sudden sensorineural hearing loss.

BACKGROUND: Sudden Sensorineural Hearing Loss was described by Mc. Cabe in 1979 and, since then, many authors have tried to define, explain and correctly treat this disease. The National Institute on Deafness and Other Communication Disorders defines it as sudden sensorineural hearing loss of at least 30 dB in three contiguous audiometric frequencies in a period of 72 hours. Among the therapeutic strategies, corticosteroids have been shown to have the greatest benefit due to their anti-inflammatory and anti-cellular stress effects. OBJECTIVE: To determine the hearing results with combined steroid therapy in patients with sudden sensorineural hearing loss (SSHL), according to the Siegel recovery criteria scale. METHOD: Study carried out in the otorhinolaryngology and head and neck surgery service of the Centro Médico Naval, Ciudad de México, where 150 patients diagnosed with SSHL and who received combined therapy with intratympanic dexamethasone and systemic prednisone were included. RESULTS: Therapeutic effectiveness was demonstrated by correlating therapeutic success in 82% of cases and therapeutic failure in 18% of cases, by correlating it with the Siegel recovery criteria scale. When evaluating the general average of the pure tone average levels at the beginning and 6 weeks after treatment, a statistically significant difference was obtained (p = 0.001). The average of the speech audiometry at the beginning and 6 weeks later had a statistically significant difference (p = 0.001). CONCLUSIONS: Initial combined steroid treatment for SSHL has been shown to have beneficial results according to Siegel recovery criteria scale.

ANTECENDENTES: La Hipoacusia Neurosensorial Súbita Idiopática fue descrita por Mc. Cabe en 1979 y, desde entonces, muchos autores han tratado de definir, explicar y tratar correctamente esta enfermedad. El Nacional Institute on Deafness and Other Communication Disorders la define como pérdida auditiva neurosensorial brusca de al menos 30 dB en tres frecuencias audiométricas contiguas en un periodo de 72 horas. Entre las estrategias terapéuticas, los corticosteroides han demostrado tener mayor beneficio por sus efectos antiinflamatorios y antiestrés celular. OBJETIVO: Determinar los resultados auditivos con la terapia de esteroides combinados en pacientes con hipoacusia neurosensorial súbita idiopática (HNSI), de acuerdo a la escala de criterios de recuperación de Siegel. MÉTODO: Estudio realizado en el servicio de otorrinolaringología y cirugía de cabeza y cuello del Centro Médico Naval, en Ciudad de México, en el que se incluyeron 150 pacientes con diagnóstico de HNSI y que recibieron terapia combinada con dexametasona intratimpánica y prednisona sistémica. RESULTADOS: Se demostró una efectividad terapéutica al correlacionar el éxito terapéutico en el 82% de los casos y un fracaso terapéutico en el 18% de los casos según la escala de criterios de recuperación de Siegel. Al evaluar el promedio general de los niveles de promedio de tonos puros al inicio y 6 semanas posterior al tratamiento se obtuvo una diferencia estadísticamente significativa (p = 0.001). El promedio de las logoaudiometrías al inicio y 6 semanas posterior al tratamiento tuvo una diferencia estadísticamente significativa (p = 0.001). CONCLUSIONES: El tratamiento combinado con esteroides de manera inicial para la HNSI ha demostrado tener resultados benéficos de acuerdo con la escala de criterios de recuperación de Siegel.

Case Report: Leptospirosis Complicated by Persistent, Bilateral Sensorineural Hearing Loss.

The clinical manifestations of leptospirosis range from mild to life-threatening and can impact on multiple organ systems. A wide array of neurological manifestations of leptospirosis have been reported, although the pathophysiology of neuroleptospirosis remains incompletely understood. We present a case of leptospirosis complicated by bilateral sensorineural deafness, with nodular meningitis demonstrated in the internal auditory meatus on magnetic resonance imaging. The patient was treated with doxycycline, ceftriaxone, systemic and topical steroids, and hyperbaric oxygen therapy, with modest, but incomplete, improvement.

Paediatric Cogan Syndrome masquerading as IgA vasculitis.

Paediatric Cogan Syndrome is a rare and underrecognised autoimmune vasculitis characterised by ocular inflammation and sensorineural hearing loss. Its etiopathogenesis, diagnosis, and management are not well defined. We report a 12-year-old girl who initially presented with symptoms of IgA vasculitis formerly called Henoch Schoenlein Purpura (HSP) and eventually developed anterior uveitis and bilateral sensorineural hearing loss leading to the diagnosis of atypical Cogan Syndrome. The workup for infectious etiologies and other systemic rheumatologic disorders was negative. The management was multidisciplinary involving Rheumatology, Ophthalmology, Otorhinolaryngology, and Audiology. The anterior uveitis responded well to systemic glucocorticoids and Methotrexate, but the hearing loss was grossly progressive warranting a cochlear implant. We are not aware of Paediatric Cogan Syndrome being reported as a mimicker of IgA vasculitis previously in the literature. It is an important finding as IgA vasculitis is prevalent in the paediatric age group and new-onset ocular or vestibular symptoms after IgA vasculitis should alert the clinician to the possibility of Cogan Syndrome. In the absence of well-defined diagnostic criteria, it is crucial to recognise the clinical symptoms of Paediatric Cogan Syndrome for early diagnosis and treatment since the delay in diagnosis can lead to permanent disability.

The Effect of the Intra-Arterial Heparin Flushing (IAHF) Procedure on Hearing Threshold in Sensorineural Hearing Loss Patients.

Background: Sensorineural hearing loss (SNHL) is a frequent problem in Indonesia but its treatment is still limited. This type of hearing loss is related to oxidative stress and decreased vascularization, which can damage the hair cell. The intra-arterial heparin flushing (IAHF) is a procedure that can recover circulation and its agent, namely heparin, also has antioxidant activity. Therefore, the IAHF procedure has the potential to improve hearing function and can be considered an alternative therapy for SNHL. Objective: The study evaluates the effect of the IAHF on hearing improvement based on the difference in hearing threshold values before and after the procedure. Methods: This experimental study used a Pretest-Posttest One-Group Only design. A total of 17 patients with sensorineural hearing loss who met inclusion and exclusion criteria were subjected to pure tone audiometry tests before and 4 hours after the IAHF procedure. The mean difference in hearing threshold was analyzed using paired Students t-test for normally distributed data and Wilcoxon for non-normally distributed data. Results: There was a decrease in the means of hearing threshold in the right and left ear 4 hours after the IAHF procedure. However, based on the paired Students t-test, there was not a significant difference in hearing threshold before and after the procedure (p-value > 0.05). Conclusion: There was hearing threshold improvement 4 hours after the IAHF procedure. This study showed that the IAHF procedure can have a therapeutic effect on sensorineural hearing loss patients.

Preclinical prospects of investigational agents for hearing loss treatment.

INTRODUCTION: : Hearing loss has a high prevalence, with aging, noise exposure, ototoxic drug therapies, and genetic mutations being some of the leading causes of hearing loss. Health conditions such as cardiovascular disease and diabetes are associated with hearing loss, perhaps due to shared vascular pathology in the ear and in other tissues. AREAS COVERED: : Issues in the design of preclinical research preclude the ability to make comparisons regarding the relative efficacy of different drugs of interest for possible hearing loss prevention or hearing restoration. This has not slowed the advancement of candidate therapeutics into human clinical testing. There is a robust pipeline with drugs that have different mechanisms of action providing diverse candidate therapies and opportunities for combination therapies to be considered. EXPERT OPINION: : Much of the preclinical research literature lacks standard study design elements such as dose response testing, and lack of standardization of test protocols significantly limits conclusions regarding relative efficacy. Nonetheless, the many positive results to date have supported translation of preclinical efforts into clinical trials assessing potential human benefits. Approval of the first hearing loss prevention therapeutic is a major success, providing a pathway for other drugs to follow.

Experimental drugs for the prevention or treatment of sensorineural hearing loss.

INTRODUCTION: Sensorineural hearing loss results in irreversible loss of inner ear hair cells and spiral ganglion neurons. Reduced sound detection and speech discrimination can span all ages, and sensorineural hearing rehabilitation is limited to amplification with hearing aids or cochlear implants. Recent insights into experimental drug treatments for inner ear regeneration and otoprotection have paved the way for clinical trials in order to restore a more physiological hearing experience. Paired with the development of innovative minimally invasive approaches for drug delivery to the inner ear, new, emerging treatments for hearing protection and restoration are within reach. AREAS COVERED: This expert opinion provides an overview of the latest experimental drug therapies to protect from and to restore sensorineural hearing loss. EXPERT OPINION: The degree and type of cellular damage to the cochlea, the responsiveness of remaining, endogenous cells to regenerative treatments, and the duration of drug availability within cochlear fluids will determine the success of hearing protection or restoration.

The prognostic value of peripheral blood parameters on all-frequency sudden sensorineural hearing loss.

OBJECTIVE: To determine whether peripheral blood parameters have any predictive value for all-frequency Sudden Sensorineural Hearing Loss (SSNHL). METHODS: We chose 78 individuals with all-frequency SSNHL who had been admitted to our department. They were divided into two groups: the effective group and the ineffective group. In patients with all-frequency SSNHL, the prognostic variables, including peripheral blood tests and clinical traits, were examined by a logistic regression analysis. In addition, the predictive value was carried out. RESULTS: The effective rate of all-frequency SSNHL was 61.5%. Pre-treatment hearing level and the proportion of patients with diabetes were both significantly lower in the effective group than in the ineffective group (p = 0.024 and 0.000, respectively). The levels of fibrinogen and C-reactive protein were also significantly different between the two groups (p = 0.001 and 0.025, respectively). Pre-treatment hearing level and fibrinogen level both significantly impacted the prognosis of all-frequency SSNHL (p = 0.032 and 0.002, respectively), according to a logistic regression analysis. Furthermore, the prognosis was significantly predicted by both fibrinogen level and pre-treatment hearing level (p = 0.001 and 0.0002, respectively). The receiver operating characteristic curve showed that the fibrinogen level had a sensitivity of 85.4% and a specificity of 60.0% for predicting the prognosis of all-frequency SSNHL. CONCLUSION: For the prognosis of all-frequency SSNHL, the fibrinogen level can be regarded as a useful predictor. The level of C-reactive protein, however, does not have a significant prognostic effect on predicting all-frequency SSNHL. Therefore, more attention should be devoted to the level of fibrinogen in the acute period of all-frequency SSNHL.