The impact of chemotherapy-induced inner ear damage on quality of life in cancer survivors: a qualitative study

Purpose This study aimed to explore the burden of inner ear damage (ototoxicity) on adults living with and beyond cancer treated with chemotherapy and the impact on their quality of life (QoL). Furthermore, this study aimed to explore patient awareness surrounding chemotherapy-induced inner ear damage, known as ototoxicity, and assess what support they had been offered. Methods Participants were adults who had undergone chemotherapy, recruited from cancer clinics, charities and social media. Using semi-structured interviews and fieldnotes, an inductive thematic analysis was used to develop key themes surrounding this topic. Results Twenty participants from the UK were interviewed. Two key themes were developed from the thematic analysis, cancer-related QoL and ototoxicity-related QoL, with each one including 5 subthemes. Subthemes consisted of impact of ototoxicity, hearing, tinnitus, clinical experience, audiological assessments, and impact of treatment, cancer and chemotherapy, other toxicities, information and patient reflections. Conclusions Ototoxicity can have a negative impact on QoL, specifically on social life and the fear of hearing loss and/or tinnitus worsening. There are opportunities for increased awareness by patients and clinicians, including improved information sources, and hearing monitoring not only for those undergoing platinum-based chemotherapy but many others surviving after treatment for cancer. Implications for Cancer Survivors Better monitoring of hearing and information about ototoxicity during chemotherapy could potentially reduce the fear of the symptoms of ototoxicity worsening. Furthermore, hearing monitoring would facilitate the detection of hearing loss at early stages of survivorship, which would facilitate earlier access to clinical interventions and longer term counselling.

Monitoring Ototoxicity through Otoacoustic Emissions. Present, COVID-19, and Future Related Insights

The administration of certain drugs is directly related to inner ear damage. Due to the potential of these elements and their usage, more extensive monitoring of adverse effects should be implemented. That is why, baseline evaluation for ototoxicity must be adequately extensive and should embrace conventional PTA thresholds, HFA, immittance measurements, speech audiometry in quiet and in noise, and assessment of OAEs. Health care specialists have reasonably quested other test modalities for ototoxic monitoring, in their effort to eliminate behavioral – subjective testing and even more establishing further improvements in test efficacy. To iterate, drug induced ototoxicities typically are initially presented as OHC dysfunction, and the exact correlation between present OAEs and functional OHCs is fairly well demonstrated. This study provides recent evidence regarding OAEs’ strategic advantages as a part of an ototoxicity monitoring program, as they can detect earlier ototoxic induced thresholds shifts, do not need patient’s own cooperation and are substantially easy to perform and quick. This fact is particularly crucial during present COVID-19 pandemic where ototoxic agents such as chloroquine and hydroxychloroquine are routinely administered in many patients who may be too sick and haggard to perform adequately enough in conventional PTA or similar, behavioral based exams.

Protective Mechanisms of Avocado Oil Extract Against Ototoxicity

Despite the excellent antimicrobial activity of aminoglycoside antibiotics, permanent inner ear damage associated with the use of these drugs has resulted in the need to develop strategies to address the ototoxic risk given their widespread use. In a previous study, we showed that avocado oil protects ear hair cells from damage caused by neomycin. However, the detailed mechanism by which this protection occurs is still unclear. Here, we investigated the auditory cell-protective mechanism of enhanced functional avocado oil extract (DKB122). RNA sequencing followed by pathway analysis revealed that DKB122 has the potential to enhance the expression of detoxification and antioxidant genes associated with glutathione metabolism (Hmox4, Gsta4, Mgst1, and Abcc3) in HEI-OC1 cells. Additionally, DKB122 effectively decreased ROS levels, resulting in the inhibition of apoptosis in HEI-OC1 cells. The expression of the inflammatory genes that encode chemokines and interleukins was also downregulated by DKB122 treatment. Consistent with these results, DKB122 significantly inhibited p65 nuclear migration induced by TNF-α or LPS in HEI-OC1 cells and THP-1 cells and the expression of inflammatory chemokine and interleukin genes induced by TNF-α was significantly reduced. Moreover, DKB122 treatment increased LC3-II and decreased p62 in HEI-OC1 cells, suggesting that DKB122 increases autophagic flux. These results suggest that DKB122 has otoprotective effects attributable to its antioxidant activity, induction of antioxidant gene expression, anti-inflammatory activity, and autophagy activation.

Use of zebrafish larvae lateral line to study protection against cisplatin-induced ototoxicity: A scoping review

Aim: The present review aimed to consolidate and analyze the recent information about the use of zebrafish in studies concerning cisplatin-induced ototoxicity and otoprotection. Material and methods: The PubMed, Web of Science, and Scopus databanks were searched using the following MESH terms: zebrafish, cisplatin, ototoxicity. The identified publications were screened according to inclusion and exclusion criteria and the 26 qualifying manuscripts were included in the full-text analysis. The experimental protocols, including cisplatin concentrations, the exposure duration and the outcome measurements used in zebrafish larvae studies, were evaluated and the reported knowledge was summarized. Results: Twenty-six substances protecting from cisplatin-induced toxicity were identified with the use of zebrafish larvae. These substances include quinine, salvianolic acid B, berbamine 6, benzamil, quercetin, dexmedetomidine, dexamethsanone, quinoxaline, edaravone, apocynin, dimethyl sulfoxide, KR-22335, SRT1720, ORC-13661, 3-MA, D-methionine, mdivi-1, FUT-175, rapamycin, Z-LLF-CHO, ATX, NAC, CYM-5478, CHCP1, CHCP2 and leupeptin. The otoprotective effects of compounds were attributed to their anti-ROS, anti-apoptotic and cisplatin uptake-blocking properties. The broadest range of protection was achieved when the experimental flow used preconditioning with an otoprotective compound and later a co-incubation with cisplatin. Protection against a high concentration of cisplatin was observed only in protocols using short exposure times (4 and 6 h). Conclusions: The data extracted from the selected papers confirm that despite the differences between the human and the zebra fish hearing thresholds (as affected by cisplatin), the sensory cells of zebrafish and larval zebrafish are a valuable tool which could be used: (i) for the discovery of novel otoprotective substances and compounds; (ii) to screen their side effects and (iii) to extend the knowledge on the mechanisms of cisplatin-induced inner ear damage. For future studies, the development of a consensus experimental protocol is highly recommended.

Hearing Problems

The most common hearing problems after concussion are hypersensitivity to sound, tinnitus (ringing in the ears), and hearing loss. Excessive sensitivity to sound can be due to migraine, damage to the ear and auditory nerve, or neuropathic pain. Refer to ear, nose, and throat (ENT) specialist for an evaluation of the middle and inner ear. Consider trials of migraine abortive agents (e.g., triptans) and neuropathic pain agents (e.g., pregabalin). For tinnitus, if an audiogram reveals hearing loss, refer to ENT. Treatment from a specialized therapist team including an audiologist and psychologist may improve tinnitus outcomes. Assess for medications that adversely affect the inner ear and reduce them if possible. Test thyroid function. Consider a magnetic resonance imaging (MRI) scan of the brain to make sure that the concussion didn’t unmask another problem, such as a tumor or vascular malformation. A complaint of hearing loss can mean several things: true hearing loss due to middle or inner ear damage, attention deficit, or a language problem such as aphasia. Obtain an audiogram, and if it is abnormal, refer to ENT, assess for attention deficit, and test for receptive aphasia.

Circulating Serum miRNA-205 as a Diagnostic Biomarker for Ototoxicity in Mice Treated with Aminoglycoside Antibiotics

Background: To confirm levels and detection timing of circulating microRNAs (miRNAs) in the serum of a mouse model for diagnosis of ototoxicity, circulating miR-205 in the serum was evaluated to reflect damages in the cochlear microstructure and compared to a kidney injury model. Method: A microarray for miRNAs in the serum was performed to assess the ototoxic effects of kanamycin-furosemide. Changes in the levels for the selected miRNAs (miR-205, miR-183, and miR-103) were compared in the serum and microstructures of the cochlea (stria vascularis, organ of Corti, and modiolus) between the ototoxicity and normal mouse groups. An acute kidney injury (AKI) mouse model was used to assess changes in miR-205 levels in the kidney by ototoxic drugs. Results: In the mouse model for ototoxicity, the serum levels of circulating miR-205 peaked on day 3 and were sustained from days 7–14. Furthermore, miR-205 expression was highly expressed in the organ of Corti at day 5, continued to be expressed in the modiolus at high levels until day 14, and was finally also in the stria vascularis. The serum miR-205 in the AKI mice did not change significantly compared to the normal group. Conclusions Circulating miR-205 from the cochlea, after ototoxic damage, migrates through the blood vessels to organs, which is then finally found in blood. In conditions of hearing impairment with ototoxic medications, detection of circulating miR-205 in the blood can be used to determine the extent of hearing loss. In the future, inner ear damage can be identified by simply performing a blood test before the hearing impairment due to ototoxic drugs.