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Journal of Cancer Survivorship :... Feb 2023A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate... (Review)
Review
PURPOSE
A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate ototoxicity risk assessment would be useful for counseling, treatment planning, and survivorship follow-up in patients with cancer.
METHODS
This systematic review evaluated the literature on predictive models for estimating a patient's risk for chemotherapy-related auditory injury to accelerate development of computational approaches for the clinical management of ototoxicity in cancer patients. Of the 1195 articles identified in a PubMed search from 2010 forward, 15 studies met inclusion for the review.
CONCLUSIONS
All but 1 study used an abstraction of the audiogram as a modeled outcome; however, specific outcome measures varied. Consistently used predictors were age, baseline hearing, cumulative cisplatin dose, and radiation dose to the cochlea. Just 5 studies were judged to have an overall low risk of bias. Future studies should attempt to minimize bias by following statistical best practices including not selecting multivariate predictors based on univariate analysis, validation in independent cohorts, and clearly reporting the management of missing and censored data. Future modeling efforts should adopt a transdisciplinary approach to define a unified set of clinical, treatment, and/or genetic risk factors. Creating a flexible model that uses a common set of predictors to forecast the full post-treatment audiogram may accelerate work in this area. Such a model could be adapted for use in counseling, treatment planning, and follow-up by audiologists and oncologists and could be incorporated into ototoxicity genetic association studies as well as clinical trials investigating otoprotective agents.
IMPLICATIONS FOR CANCER SURVIVORS
Improvements in the ability to model post-treatment hearing loss can help to improve patient quality of life following cancer care. The improvements advocated for in this review should allow for the acceleration of advancements in modeling the auditory impact of these treatments to support treatment planning and patient counseling during and after care.
Topics: Child; Humans; Adult; Antineoplastic Agents; Prognosis; Ototoxicity; Quality of Life; Cancer Survivors; Neoplasms
PubMed: 36729346
DOI: 10.1007/s11764-022-01315-8 -
Clinical Pharmacology and Therapeutics Aug 2023Aminoglycoside antibiotic exposure can result in ototoxicity and irreversible hearing loss among individuals that harbor the m.1555A>G variant in the mitochondrial 12S...
Aminoglycoside antibiotic exposure can result in ototoxicity and irreversible hearing loss among individuals that harbor the m.1555A>G variant in the mitochondrial 12S rRNA gene, MT-RNR1. Importantly, pre-emptive m.1555A>G screening has been shown to reduce the prevalence of pediatric aminoglycoside-induced ototoxicity; however, professional guidelines to support and guide post-test pharmacogenomic counseling in this context are not currently available. This Perspective highlights key issues with delivering MT-RNR1 results, including longitudinal familial care considerations and communicating m.1555A>G heteroplasmy.
Topics: Child; Humans; Aminoglycosides; Anti-Bacterial Agents; DNA, Mitochondrial; Genes, rRNA; Mutation; Ototoxicity; Pharmacogenetics
PubMed: 37314952
DOI: 10.1002/cpt.2910 -
American Journal of Otolaryngology 2021Current clinical evidences do not support any specific treatment against SARS-CoV-2. Chloroquine (CQ) and hydroxychloroquine (HCQ) are typically used in the treatment of... (Review)
Review
INTRODUCTION
Current clinical evidences do not support any specific treatment against SARS-CoV-2. Chloroquine (CQ) and hydroxychloroquine (HCQ) are typically used in the treatment of rheumatoid arthritis, systemic lupus erythematosus and malaria; they have been considered for off-label and compassionate use in several countries against moderate to severe cases of COVID-19 and there's actually a massive demand of these two drugs. The aim of this paper is to briefly review the published literature, summarizing evidences about audiological implications after CQ and HCQ treatment.
METHODS
We conducted a review of the literature on Medline and Pubmed platforms from 27th May 2020 to 30 May 2020. We combined MeSH terms of "chloroquine", "hydroxychloroquine", "ototoxicity", "hearing loss", "tinnitus", "deafness" and "hearing". Publications with relevant data were included. Selected data (authors, country and year; sample size; study design; audiological side effects) were extracted and summarized in a table.
RESULTS
Of 45 initial studies, 14 met inclusion criteria. The authors found xix cases of HCQ ototoxicity; Tinnitus was reported in 2 cases, and it was found to be reversible or irreversible. Sensorineural hearing loss after HCQ use was reported in 7 patients; it was found to be irreversible or partially reversible after discontinuation of HCQ in 6 cases. Eight papers reporting CQ ototoxicity were; tinnitus was not reported by any authors. Sensorineural hearing loss after taking CQ was reported in 6 patients; it was found to be irreversible after discontinuation of CQ in 5 patients. One patient showed abnormal gait after a single intramuscular injection of CQ. Thirteen patients' Auditory Brainstem Response (ABR) were found to be abnormal, but they resolved after CQ discontinuation.
CONCLUSIONS
CQ and HCQ related ototoxicity is widely reported in the literature although the pathophysiological mechanism is not well known. Current data are not sufficient enough to support the use of CQ and HCQ as therapy for COVID-19, but considering the growing demand for these two drugs and the number of people around the world who have taken and will take CQ and HCQ, it must necessarily consider the clinical and social impact of long term audiological side effects.
Topics: Antirheumatic Agents; Humans; Hydroxychloroquine; Ototoxicity; COVID-19 Drug Treatment
PubMed: 33780902
DOI: 10.1016/j.amjoto.2020.102640 -
Otology & Neurotology : Official... Jan 2021Quinine, a cinchona bark-derived antimalarial alkaloid, is a known ototoxic. Isolated and named in 1820 by the French scientists Pierre-Joseph Pelletier and...
OBJECTIVES/HYPOTHESIS
Quinine, a cinchona bark-derived antimalarial alkaloid, is a known ototoxic. Isolated and named in 1820 by the French scientists Pierre-Joseph Pelletier and Joseph-Bienaimé Caventou, it has since been employed in the treatment of different maladies. Quinine was also recommended as a local anesthetic in surgical procedures in the early 20th century. This article aims to identify early ototoxicity reports regarding quinine and to investigate if quinine was previously used in otology as an anesthetic agent or as an actual therapy.
METHOD
Historical review of medical and pharmaceutical literature from the 19th and 20th centuries in databases (PubMed; Web of Science), as well as medical books on ototoxic drugs, quinine, and therapies in otology.
RESULTS
The first identified reference of quinine ototoxicity was from 1824. Quinine also had a therapeutic role in otology and neurotology and was employed for its analgesic properties. It was used in Menière's disease, vertigo, otalgia, purulent otitis media, neuralgia of the plexus tympani, furuncles in the auditory canal, and herpes zoster in the auricle.
CONCLUSION
Quinine was acknowledged as an ototoxic drug in the 19th century. Quinine was used in several otologic disorders, both as an analgesic (for herpes zoster, otalgia) and as a therapeutic agent (Menière's disease, vertigo, purulent otitis media, furuncles in the auditory canal). This research demonstrates that, analogously to gentamicin, quinine was used in Menière's disease specifically due to its ototoxic effects.
Topics: Gentamicins; Humans; Neurotology; Otolaryngology; Ototoxicity; Quinine
PubMed: 33301286
DOI: 10.1097/MAO.0000000000002809 -
The International Journal of... Sep 2019Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs). To...
Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs). To evaluate the prevalence of and risk factors for ADRs among patients with MDR- and extensively drug-resistant TB (XDR-TB). A retrospective chart review of patients initiating treatment for M/XDR-TB in 2010-2012 in Tbilisi, Georgia. Eighty (54%) and 38 (26%) of 147 patients developed nephrotoxicity per RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification and ototoxicity, respectively. Twenty-five (17%) patients required permanent interruption of injectables due to an ADR. Median hospital stay, total treatment duration and number of regimen changes were higher among those with nephrotoxicity and/or ototoxicity, compared to those without ( < 0.01). Multinomial logistic regression analysis identified increasing age (per year) as a risk factor for nephrotoxicity (aOR 1.08, 95%CI 1.03-1.12) and for both, nephro- and ototoxicity (aOR 1.11, 95%CI 1.05-1.17). Low baseline creatinine clearance (CrCl) was a significant risk factor for developing nephrotoxicity (aOR 1.05, 95%CI 1.02-1.07). Second-line injectable drug-related ADRs are common among M/XDR-TB patients. Patients with increasing age and low baseline CrCl should be monitored closely for injectable-related ADRs. Notably, our findings support WHO's latest recommendations on introduction of injectable free anti-TB treatment regimens.
Topics: Adolescent; Adult; Aged; Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Female; Georgia (Republic); Humans; Kidney Diseases; Male; Middle Aged; Ototoxicity; Prevalence; Retrospective Studies; Risk Factors; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 31615608
DOI: 10.5588/ijtld.18.0626 -
International Journal of... 2021To describe the audio-vestibular disorders related to the newly SARS-CoV-2 infection, including the possible ototoxicity side-effects related to the use of drugs...
To describe the audio-vestibular disorders related to the newly SARS-CoV-2 infection, including the possible ototoxicity side-effects related to the use of drugs included in the SARS-CoV-2 treatment protocols. A systematic review was performed according to the PRISMA protocol. The Medline and Embase databases were searched from March 1, 2020 to April 9, 2021. Initially the search yielded 400 manuscripts, which were reduced to 15, upon the application of inclusion criteria. Sensorineural hearing loss (SNHL) is the most frequent audio-vestibular symptom described, occurring alone or in association with tinnitus and vertigo. The etiopathogenesis of the inner ear disorders related to COVID-19 infection is still poorly understood. The number of reports of COVID-19 infections associated to audio-vestibular disorders is increasing; even if the quality of the studies available is often insufficient, audio-vestibular disorders should be considered as possible manifestations to be included among the symptoms of this infection.
Topics: COVID-19; Hearing Loss, Sensorineural; Humans; Ototoxicity; SARS-CoV-2; Vestibular Diseases
PubMed: 34142589
DOI: 10.1177/20587384211027373 -
Biochemical Pharmacology Feb 2024Puerarin (PUE), a flavonoid derivative with vasodilatory effects found in the traditional Chinese medicine kudzu, has anti-sensorineural hearing loss properties....
Puerarin (PUE), a flavonoid derivative with vasodilatory effects found in the traditional Chinese medicine kudzu, has anti-sensorineural hearing loss properties. However, the mechanism of its protective effect against ototoxicity is not well understood. In this study, we used in vitro and in vivo methods to investigate the protective mechanism of puerarin against cisplatin (CDDP)-induced ototoxicity. We established an ototoxicity model of CDDP in BALB/c mice and assessed the degree of hearing loss and cochlear cell damage. We used bioinformatics analysis, molecular docking, histological analysis, and biochemical and molecular biology to detect the expression of relevant factors. Our results show that puerarin improved CDDP-induced hearing loss and reduced hair cell loss. It also blocked CDDP-induced activation of TRPV1 and inhibited activation of IP3R1 to prevent intracellular calcium overload. Additionally, puerarin blocked CDDP-stimulated p65 activation, reduced excessive ROS production, and alleviated cochlear cell apoptosis. Our study provides new evidence and potential targets for the protective effect of puerarin against drug-induced hearing loss. Puerarin ameliorates cisplatin-induced ototoxicity and blocks cellular apoptosis by inhibiting CDDP activated TRPV1/IP3R1/p65 pathway, blocking induction of calcium overload and excessive ROS expression.
Topics: Animals; Mice; Antineoplastic Agents; Apoptosis; Calcium; Cell Line; Cisplatin; Hearing Loss; Isoflavones; Molecular Docking Simulation; Ototoxicity; Reactive Oxygen Species; TRPV Cation Channels
PubMed: 38043717
DOI: 10.1016/j.bcp.2023.115962 -
Clinical Imaging Oct 2020Ear malformations represent 50% of ear, nose and throat malformations. Ear malformations cause conductive hearing loss (CHL) and/or sensorineural hearing loss (SNHL)... (Review)
Review
Ear malformations represent 50% of ear, nose and throat malformations. Ear malformations cause conductive hearing loss (CHL) and/or sensorineural hearing loss (SNHL) with a significant childhood disability worldwide. Early accurate diagnosis and treatment are mandatory to enhance language and speech development. Understanding the embryology of the ear explains the outcome of ototoxic prenatal insult according to the affected gestational age and the incidence of association among inner, middle, and external ear malformations. Computed tomography (CT) and magnetic resonance imaging (MRI) examinations of the temporal bone are used in the evaluation of ear malformations. In this review article, the spectrum of ear malformations is discussed in detail with hints on the ear embryology, the ear radiological anatomy, and radiological determinant factors of operative reconstruction of ear anomalies.
Topics: Child; Ear, Inner; Female; Gestational Age; Hearing Loss, Sensorineural; Humans; Language; Magnetic Resonance Imaging; Male; Ototoxicity; Radiography; Radiologists; Radiology; Temporal Bone; Tomography, X-Ray Computed
PubMed: 32450482
DOI: 10.1016/j.clinimag.2020.04.022 -
Clinical Otolaryngology : Official... Jan 2024Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity... (Review)
Review
OBJECTIVES
Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients.
METHODS
Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales.
RESULTS
Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions.
CONCLUSIONS
Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.
Topics: Adult; Humans; Cisplatin; Antineoplastic Agents; Carboplatin; Ototoxicity; Hearing Loss; Neoplasms; Adrenal Cortex Hormones; Randomized Controlled Trials as Topic
PubMed: 37818931
DOI: 10.1111/coa.14106 -
Journal of Cystic Fibrosis : Official... Mar 2021Cystic fibrosis patients are often adminstered tobramycin to treat pulmonary infections. Unfortunately, a common side effect is hearing loss, which can fluctuate....
BACKGROUND
Cystic fibrosis patients are often adminstered tobramycin to treat pulmonary infections. Unfortunately, a common side effect is hearing loss, which can fluctuate. Ebselen has known anti-inflammatory properties and could reduce the incidence and severity of tobramycin-induced hearing loss.
METHODS
In vitro: neonatal cochlear cultures were treated with tobramycin or cotreated with tobramycin and ebselen for 3 days. In vivo: adult mice were injected with tobramycin or tobramycin and ebselen for 14 days. ABRs were collected in a repeated measures design until 56 days after treatments. ABR threshold shifts were analyzed and a novel cochleotoxic criteria applied to determine the incidence of ototoxicity. Cochlear immunohistology was analyzed for IHC and OHC loss.
RESULTS
Tobramycin leads to significant IHC and OHC loss in cochlear explant cultures. Ebselen co-treatment at 1:20 concentrations resulted in significant otoprotection. Tobramycin leads to significant ABR threshold shifts that are ameliorated by ebselen co-treatment. Hearing loss did not correlate with significant IHC or OHC loss.
CONCLUSIONS
This mouse model of tobramycin-induced ototoxicity is clinically relevant in that it results in an incidence and severity of hearing loss recently documented in clinic. The in vitro experiments show that tobramycin kills hair cells and that ebselen co-treatment can attenuate this ototoxicity. The in vivo model shows tobramycin-induced hearing loss is ameliorated by ebselen co-treatment, but this is not explained by concomitant hair cell loss. These preclinical data support the testing of ebselen in CF patients receiving tobramycin treatment.
Topics: Animals; Evoked Potentials, Auditory, Brain Stem; Hair Cells, Auditory, Outer; Hearing Loss; Isoindoles; Mice; Organoselenium Compounds; Ototoxicity; Tobramycin
PubMed: 32147183
DOI: 10.1016/j.jcf.2020.02.014