scholarly journals Nuclear Factor Erythroid 2-Related Factor 2-Histone Deacetylase 2 Pathway in the Pathogenesis of Refractory Sudden Sensorineural Hearing Loss and Glucocorticoid Resistance

ORL ◽  
2021 ◽  
pp. 1-7
Author(s):  
Hui Qi ◽  
Zi-Wen Gao ◽  
Jie Hou ◽  
Qiongqiong Zhou ◽  
Wei Ma ◽  
...  

<b><i>Introduction:</i></b> A significant number of sensorineural hearing loss (SSNHL) patients had no noticeable hearing improvement after glucocorticoid (GC) treatment. In the present study, we examined expression of the nuclear factor erythroid 2-related factor 2 (NRF2) and histone deacetylase 2 (HDAC2) in peripheral blood mononuclear cells (PBMCs) of refractory SSNHL patients to study the role of NRF2-HDAC2 pathway in GC insensitivity hearing improvement after GC treatment, which is usually referred to as refractory SSNHL or GC insensitivity. <b><i>Materials and Methods:</i></b> Forty-four refractory SSNHL patients were treated by intratympanic GC infusion. Hearing was tested in all patients before and after treatment by pure tone hearing test. NRF2/HDAC2 mRNA and protein levels were examined in PBMCs of refractory SSNHL patients before and after treatment. PBMCs from healthy volunteers were used as normal controls. <b><i>Results:</i></b> According to the hearing improvement after treatment, patients were assigned into 2 groups: the intratympanic GC sensitive (IGCS) group (hearing recovery ≥15 dB HL) and the intratympanic GC insensitive (IGCI) group (hearing recovery &#x3c;15 dB HL). Before treatment, the NRF2 mRNA level was lower in all patients than the normal control group. After treatment, NRF2 and HDAC2 mRNA and protein levels were increased in the IGCS group, while no significant change was observed in the IGCI group. <b><i>Conclusion:</i></b> Low response of NRF2/HDAC2 proteins is associated with GC insensitivity in SSNHL. We speculate that the NRF2-HDAC2 pathway affects GC sensitivity in SSNHL patients.

2021 ◽  
pp. 1-10
Author(s):  
Alexandros Andrianakis ◽  
Ulrich Moser ◽  
Axel Wolf ◽  
Peter Kiss ◽  
Clemens Holzmeister ◽  
...  

<b><i>Introduction:</i></b> Intratympanic steroid (ITS) injections represent an increasingly used salvage treatment option for patients with idiopathic sudden sensorineural hearing loss ­(ISSHL) after systemic treatment. The most effective corticosteroid for this treatment modality still remains unclear. Triamcinolone acetonide has been used for ITS treatment in various clinical settings. However, there are limited clinical data of its usage in the therapeutic management of ISSHL. The aim of this study was to determine the efficacy of intratympanic triamcinolone acetonide injections as a salvage treatment for ISSHL. <b><i>Methods:</i></b> We conducted a retrospective chart review on patients affected by ISSHL with insufficient hearing recovery after primary systemic corticosteroid therapy and who were treated with intratympanic triamcinolone acetonide as a salvage therapy between January 2014 and August 2019. The patients were divided into groups according to their degree of hearing recovery, and we evaluated potential predictors of hearing recovery. Audiometric results were then compared to historic studies using dexamethasone or methylprednisolone. <b><i>Results:</i></b> One-hundred and fifty-two patients received up to 3 intratympanic injections with triamcinolone acetonide at 1-week intervals. The mean hearing improvement due to ITS salvage treatment was 15.9 ± 18.9 dB. Complete hearing recovery was noted in 15 patients (9.9%), while 73 patients (48%) obtained partial recovery, and 64 patients (42.1%) had no recovery. Primary systemic treatment delay, hearing improvement by primary systemic treatment, and severity of initial hearing loss were identified as significant predictors of hearing improvement. The first of the 3 injections resulted in the greatest hearing improvement. <b><i>Conclusion:</i></b> The use of triamcinolone acetonide in ITS salvage treatment resulted in similar hearing improvements as the use of the commonly used corticosteroids, namely, dexamethasone and methylprednisolone. Longer treatment delays, lower hearing improvement by primary systemic treatment, and higher initial hearing loss are associated with poorer prognoses of hearing recovery.


2020 ◽  
Vol 63 (10) ◽  
pp. 448-457
Author(s):  
Hyun Min Lee ◽  
Da Hee Park ◽  
Dong Jo Kim ◽  
Sung Won Choi ◽  
Se Joon Oh ◽  
...  

Background and Objectives The combined intratympanic and oral steroid treatment has been accepted as effective treatment strategy for idiopathic sudden sensorineural hearing loss (ISSNHL). However, the treatment protocol of combined treatment for ISSNHL has not been established. In this study, we investigated whether hearing outcome differed according to different starting timing of intratympanic steroid injection (ITSI) in combined treatment for ISSNHL.Subjects and Method Tertiary academic referral center-based retrospective medical records of idiopathic 144 ISSNHL patients who received combined treatment from January 2015 to April 2018 were reviewed. All patients underwent a 2-week oral systemic steroid treatment and multiple ITSI. The hearing results of 3 months after treatment were compared according to the timing of ITSI.Results The mean pure tone audiogram gain was 24.3±23.6 dB. When Siegel’s criteria was applied, the overall rate of hearing improvement was 63.9% (92/144). The rate of hearing improvement was significantly higher in women (p=0.043) statistically, and there was a statistically significant lower rate of recovery in the former history of hearing loss (p<0.01) or otitis media (p<0.01). Moreover, the shorter the delay between symptom onset and initial ITSI, greater the statistical significance of hearing recovery rate became (p<0.01).Conclusion The result of this study suggests that early ITSI during combined intratympanic and oral steroid treatment increases the chance of hearing recovery.


2018 ◽  
Vol 132 (11) ◽  
pp. 1039-1041 ◽  
Author(s):  
J Suzuki ◽  
Y Takanashi ◽  
A Koyama ◽  
Y Katori

AbstractObjectivesSodium bromate is a strong oxidant, and bromate intoxication can cause irreversible severe-to-profound sensorineural hearing loss. This paper reports the first case in the English literature of bromate-induced hearing loss with hearing recovery measured by formal audiological assessment.Case reportA 72-year-old woman was admitted to hospital with complaints of profound hearing loss, nausea, diarrhoea and anuria after bromate ingestion in a suicide attempt. On admission, pure tone audiometry and auditory brainstem responses showed profound bilateral deafness. Under the diagnosis of bromate-induced acute renal failure and sensorineural hearing loss, continuous haemodiafiltration was performed. When dialysis was discontinued, pure tone audiometry and auditory brainstem responses showed partial threshold recovery from profound deafness.ConclusionSevere-to-profound sensorineural hearing loss is a common symptom of bromate intoxication. Bromate-induced hearing loss may be partially treated, and early application of continuous haemodiafiltration might be useful as a treatment for this intractable condition.


2010 ◽  
Vol 2 (2) ◽  
pp. 143-149
Author(s):  
Ashutosh G Pusalkar

Abstract Till about 15 years ago, the only choice of hearing improvement for moderate sensorineural hearing loss with severe speech discrimination defect was a hearing aid. It was only after Mr. Geoff Ball, an electronic engineer who was suffering from a similar defect, started thinking of an alternative to the conventional hearing aid that the Vibrant Soundbridge came into existence, and with the passage of time the indications for the use of the same have increased.


Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 96
Author(s):  
Magdalena B. Skarżyńska ◽  
Aleksandra Kołodziejak ◽  
Elżbieta Gos ◽  
Milaine Dominici Sanfis ◽  
Piotr H. Skarżyński

(1) Background: A retrospective clinical study was conducted to compare the effectiveness of different pharmacological and non-pharmacological regimens for treating sudden sensorineural hearing loss (SSNHL). (2) Methods: Adult patients (n = 130) diagnosed with sudden sensorineural hearing loss (SSNHL) and hospitalized between 2015 and 2020 were enrolled in this study. Depending on the treatment regimen applied, patients were divided into five groups. Inclusion criteria were as follows: (i) hearing loss of sudden onset; (ii) hearing loss of at least 30 dB at three consecutive frequencies; (iii) unilateral hearing loss; (iv) age above 18 years. Exclusion criteria were as follows: (i) no follow-up audiogram; (ii) bilateral hearing loss; (iii) recognized alternative diagnosis such as tumor, disorder of inner ear fluids, infection or inflammation, autoimmune disease, malformation, hematological disease, dialysis-dependent renal failure, postdural puncture syndrome, gene-related syndrome, mitochondrial disease; and (iv) age below 18 years. (3) Results: Complete recovery was found in 14% of patients (18/130) and marked improvement was found in 6% (8/130), giving an overall success rate of 20%. The best results were obtained in the second group (i.e., patients given intratympanic glucocorticoid + prolonged orally administered glucocorticoid) where the success rate was 28%. In general, the older the patient, the smaller the improvement in hearing, a correlation that was statistically significant. (4) Conclusions: In treating SSNHL, the highest rate of hearing recovery—28%—was in the group of patients given intratympanic corticoid plus prolonged treatment with orally administered glucocorticoid.


2021 ◽  
pp. 159101992110568
Author(s):  
Yang Cui ◽  
Wenzhao Liang ◽  
Mengxue Li ◽  
Zhongyu Zhao ◽  
Xinzhao Jiang ◽  
...  

Background and Purpose Cochlear vascular micro-thrombosis has been hypothesized as one of the pathogenic mechanisms for sudden sensorineural hearing loss (SSNHL) refractory to regular management. This study aimed to evaluate the feasibility and safety of intra-arterial pulsed-injection urokinase (IAPU) as a salvage therapy for SSNHL after the failure of conventional therapy. Methods We retrospectively reviewed our patient database to identify refractory SSNHL patients between November 2017 and July 2020. Study outcomes before and after the IAPU therapy were compared between IAPU and conventional therapy groups. Results Sixty-seven moderate-profound SSNHL patients (29 in IAUP group, 38 in control group) were included in this study. Compared to the control group, patients in the IAPU group showed more significant improvement in pure tone average (PTA) (34.2 ± 23.5 vs. 10.7 ± 13.1, p < 0.001) and degree of hearing recovery (total: 20.7% vs. 5.3%, partial: 24.1% vs. 10.5%, mild: 27.6% vs. 13.2% and non: 27.6% vs. 71.1%) 2 weeks after admission. In the IAPU group, a significant improvement of PTA (86.6 ± 11.5 vs. 54.6 ± 20.1 dB, p < 0.005) was observed on the first day after IAPU treatment. Conclusion In carefully selected SSNHL cases with a highly suspected vascular origin, IAPU is a safe and effective therapy when conventional treatments have failed. Despite the encouraging findings of our work, large studies are needed to better investigate the strengths and limitations of this salvage therapy.


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