Perda auditiva em pacientes oncológicos usuários de AASI: impacto no reconhecimento de fala e na qualidade de vida / Hearing loss in cancer patients who use IHAs: Impact on speech recognition and on Quality of Life

INTRODUÇÃO: Tanto o câncer quanto a perda auditiva (PA) podem interferir na qualidade de vida, o primeiro por alterar a rotina e envolver um tratamento muitas vezes agressivo, e a segunda por interferir na comunicação interpessoal, podendo levar ao isolamento ou privação social. OBJETIVO: Analisar o impacto da PA na qualidade de vida e no reconhecimento de fala em pacientes submetidos a tratamento oncológico, usuários de aparelho de amplificação sonora individual (AASI). METODOLOGIA: Estudo prospectivo de corte transversal aprovado pelo comitê de ética da Instituição. Foram selecionados usuários de AASI acompanhados no Serviço Ambulatorial de Saúde Auditiva da Univali ­ SASA/Univali. Os participantes com registro de diagnóstico e tratamento de câncer foram alocados no grupo estudo (GE) e, aqueles sem histórico de câncer, pareados por idade e grau da PA, foram alocados no grupo controle (GC). Os dados quanto ao histórico do câncer, limiares audiométricos e uso do AASI foram coletados em prontuário. A aplicação de questionários de qualidade de vida e autoavaliação (SF-36, HHIA/HHIES e IOI-HA) e do teste de reconhecimento de sentenças no silêncio e no ruído foram coletados em visita de rotina para acompanhamento no serviço no período de setembro de 2019 a janeiro de 2022. Os dados coletados foram analisados no software SPSS v.25, sendo a comparação entre os grupos realizada por meio dos testes paramétricos e não paramétricos como Qui-quadrado, teste de Fisher, teste t para igualdade de médias ou U de Mann-Whitney para amostras independentes, adotando-se nível de significância de 5%. A correlação entre as variáveis foi analisada pelo teste de Spearman. RESULTADOS: A amostra contou com 30 participantes ­ 15 alocados no GE e 15 no GC. A idade média foi de 62,4 anos no GE e de 61,4 anos no GC, com distribuição semelhante quanto ao sexo. No GE todos os participantes apresentaram histórico de câncer prévio, sendo o tratamento predominante a quimio associada à radioterapia. Nos dois grupos predominou PA neurossensorial de grau moderado e configuração descendente, porém com diferença significante para o grau da PA à esquerda (p = 0,025). Não foram observadas diferenças significantes no reconhecimento de sentenças no silêncio e no ruído entre os grupos. A qualidade de vida mostrou diferença significante no Domínio aspectos sociais, sendo o grupo com pior desempenho o GE. O impacto da PA e o desempenho com o uso do AASI avaliados pelos questionários HHIA/HHIE-S e IOI-HA foi semelhante entre os grupos. Ao analisar a correlação entre as variáveis estudadas observou-se correlação positiva para o reconhecimento de fala no silêncio, handicap auditivo e fator 1 do questionário IOI-HA ("eu e meu AASI"), bem como houve correlação positiva para os Domínios capacidade funcional, dor, vitalidade e Índice do SF-36 com o questionário IOI-HA (fator 1 ou fator 2 ­ "eu e o resto do mundo"). CONCLUSÃO: Os dois grupos estudados apresentaram desempenhos semelhantes no reconhecimento de fala, na autopercepção do handicap auditivo e na qualidade de vida, salvo no Domínio aspectos sociais do questionário SF-36, que revelou maior impacto quando a díade câncer e perda auditiva estavam associadas (GE)

INTRODUCTION: Both cancer and hearing loss (HL) can interfere in Quality of Life: the former for changing the routine and often involving aggressive treatments and the latter for interfering in interpersonal communication, with the possibility of leading to social isolation or deprivation. OBJECTIVE: To analyze the impact of HL on Quality of Life and on speech recognition in patients undergoing cancer treatments and who use hearing aids (HAs). METHODOLOGY: Prospective and cross-sectional study approved by the Ethical committee of the Institution. Hearing aid users followed up at Univali Hearing Health Outpatient Service ­ SASA/Univali were selected. Participants with a record of cancer diagnosis and treatment were allocated to the study group (SG) and those without a history of cancer, matched by age and degree of HL, were allocated to the control group (CG). Data regarding cancer history, audiometric thresholds and HA use were collected from medical records. Quality of Life and self-assessment questionnaires (SF-36, HHIA/HHIES and IOI-HA) scores and sentences recognition in quiet and in noise were assessed in the routine monitoring visits at SASA/Univali. Data were analyzed in the SPSS software (version 25), initially testing data normality and comparing groups by means of the following parametric and non-parametric tests: Chi-square, Fisher's and t test for equality of means or through the Mann-Whitney U test for independent samples. The correlation between the variables was analyzed through Spearman's test, adopting a 5% significance level for all tests. RESULTS: The sample was composed by 30 participants, 15 allocated to the SG and 15 to the CG. Mean age in the SG and CG was 62.4 and 61.4 years old, respectively, with similar distribution regarding gender. All the SG participants had a previous cancer history, with combined chemotherapy and radiotherapy as predominant treatment. Sensorineural HL of moderate degree and descending configuration predominated in both groups, although with a statistically significant difference for HL degree in the left ear (p = 0.025). No statistically significant differences were observed in sentences recognition in quiet or noise. Quality of Life showed a statistically significant difference in the Social Aspects domain, with the SG presenting worse performance. The impact of HL and performance with IHA use evaluated through the HHIA/HHIE-S and IOIHA questionnaires were similar between the groups. When analyzing the correlation between the variables studied, a positive correlation was observed for speech recognition in the midst of silence, auditory handicap and factor 1 of the IOI-IHA questionnaire ("Me and my HA"), as well as a positive correlation for the Functional Ability, Pain and Vitality domains and the SF36 Index with the IOI-HA questionnaire (factor 1 or factor 2 ­ "Me and the rest of the world"). CONCLUSION: Both groups in this sample presented similar performance in speech recognition, self-perception of the auditory handicap and Quality of Life, except in the Social Aspects domain of the SF-36 questionnaire, suggesting higher impact when cancer and hearing loss were associated (SG).

Effects of Toluene on the Development of the Inner Ear and Lateral Line Sensory System of Zebrafish / 生物医学与环境科学（英文）

Objective@#The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.@*Methods@#Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.@*Results@#The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml @*Conclusion@#This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.

Ototoxic effects of hydroxychloroquine

SUMMARY OBJECTIVE To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine (HCQ). METHODS The studies were selected using a combination based on the Medical Subject Headings (MeSH). The databases searched were MEDLINE (PubMed), LILACS, SciELO, and BIREME, encompassing articles from January 2010 to May 2020, with no restrictions of language and place of publication. RESULTS A total of 148 articles with the potential to be included were retrieved. Of these, two answered the research question, which consisted of seeking evidence of the ototoxic effects of hydroxychloroquine. These studies scored 11 in their quality assessment with the modified protocol by Pithon et al.13. CONCLUSIONS The studies reported possible ototoxicity of HCQ. Audiovestibular changes, such as hearing loss, peripheral vestibular syndrome, and tinnitus were evidenced in patients submitted to HCQ. The improvement in the audiological examinations and the regression in the vestibular syndrome after stopping the treatment with HCQ are strong arguments in favor of the ototoxicity caused by this medication. However, there are still divergences about the relationship between ototoxic effects and the use of HCQ.

Ototoxicity of cypermethrin in Wistar rats / Ototoxicidade da cipermetrina em ratos Wistar

Abstract Introduction: This study presents the effect of cypermethrin on the cochlear function in Wistar rats post-subchronic inhalation exposure. Worldwide several pesticides are described as causing health disorders. Cypermethrin is currently one of the most commonly used, however, little is known about its harmful effects, especially related to hearing. Human studies have associated pesticides with hearing disorders, but they present limited conclusions due to the multiple factors to which the population is exposed, such as noise. Objective: Mimic human exposure to cypermethrin and to verify the effects on cochlear function. Methods: It is a subchronic inhalation animal study (6 weeks, 4 hours/day), using 36 male Wistar aged 60 day. Rats were randomly assigned into three groups: Control (12 rats exposed to inhalation of water); Positive Control for auditory lesion (12 rats administrated with 24 mg/kg intraperitoneal cisplatin); Experimental (12 rats exposed to inhalation of cypermethrin - 0.25 mg/L). Animals were evaluated by distortion product otoacoustic emissions pre- and post-exposure. Results: The frequencies of 8, 10 and 12 kHz in both ears (right p = 0.003; 0.004; 0.008 and left 0.003; 0.016; 0.005 respectively) and at frequencies 4 and 6 in the right ear (p = 0.007 and 0.015, respectively) in the animals exposed to cypermethrin resulted in reduction. Conclusion: Subchronic inhalation exposure to cypermethrin provided ototoxicity in rats.

Resumo Introdução: Este estudo apresenta o efeito da cipermetrina sobre a função coclear em ratos Wistar após exposição por inalação subcrônica. Em todo o mundo, vários pesticidas são descritos como causadores de distúrbios de saúde. A cipermetrina é atualmente um dos mais utilizados, porém pouco se conhece sobre seus efeitos deletérios, principalmente relacionados à audição. Estudos em humanos associaram pesticidas a alterações auditivas, mas apresentaram conclusões limitadas devido aos múltiplos fatores aos quais a população está exposta, como, por exemplo, o ruído. Objetivo: Mimetizar a exposição humana à cipermetrina e verificar os seus efeitos na função coclear. Método: Estudo de inalação subcrônica em animais (6 semanas, 4 horas/dia), 36 ratos machos Wistar com 60 dias. Os ratos foram distribuídos aleatoriamente em três grupos: controle (12 ratos expostos à inalação de água); controle positivo para lesão auditiva (12 ratos com administração de 24 mg/kg de cisplatina intraperitoneal); e experimental (12 ratos expostos a inalação de cipermetrina - 0,25 mg/L). Os animais foram avaliados por emissões otoacústicas por produto de distorção, pré e pós-exposição. Resultados: As frequências de 8, 10 e 12 kHz em ambas as orelhas (direita p = 0,003; 0,004; 0,008 e esquerda 0,003; 0,016; 0,005 respectivamente) e frequências 4 e 6 na orelha direita (p = 0,007 e 0,015, respectivamente) apresentaram redução nos animais expostos à cipermetrina. Conclusão: A exposição subcrônica por inalação à cipermetrina resultou em ototoxicidade em ratos.

Protective effect of N-acetylcysteine against cisplatin ototoxicity in rats: a study with hearing tests and scanning electron microscopy / Efeito protetor da N-acetilcisteína na ototoxicidade por cisplatina em ratos: um estudo com testes auditivos e microscopia eletrônica de varredura

Abstract Introduction Ototoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea. Objectives The possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy. Methods This study was conducted on 21 Wistar Albino rats in four groups. 1 mL/kg/day three times in total intraperitoneal (i.p.) Saline (n = 5), 500 mg/kg/day i.p. three times in total N-acetylcysteine (n = 5), i.p. 15 mg/kg cisplatin alone (single dose) (n = 5) and i.p. 15 mg/kg cisplatin plus 500 mg/kg/day N-acetylcysteine (n = 6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy. Results Auditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin + N-acetylcysteine group. Conclusion Cisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4 h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.

Resumo Introdução A ototoxicidade é um problema que pode ocorrer após certos tipos de tratamentos para condições graves de saúde. Às vezes é inevitável quando o tratamento da doença é necessário. A cisplatina é um agente antineoplásico cujo uso em pesquisas anteriores demonstrou aumentar os radicais livres de nitrogênio e espécies reativas de oxigênio que danificam as células ciliadas e resultam em ototoxicidade. Por outro lado, a N-acetilcisteína, que já demonstrou diminuir a ototoxicidade causada por diferentes agentes, é conhecida por ser um potente antioxidante in vitro. Provavelmente a N-acetilcisteína, além de seu efeito antioxidante, bloqueia uma cascata onde espécies reativas de oxigênio resultam em apoptose na cóclea. Objetivos Estudar o possível efeito preventivo da N-acetilcisteína na ototoxicidade por cisplatina por meio de potencial evocado auditivo de tronco encefálico, emissões otoacústicas e investigação histopatológica da cóclea por microscopia eletrônica de varredura. Método Este estudo foi realizado em 21 ratos albinos Wistar, separados em quatro grupos. Foram administrados: 1 mL/kg/dia intraperitoneal (i.p.) de solução salina (n = 5), três vezes no total; 500 mg/kg/dia i.p. de N-acetilcisteína (n = 5), três vezes no total; 15 mg/kg i.p. (dose única) somente de cisplatina (n = 5) e 15 mg/kg i.p. de cisplatina e 500 mg/kg/dia i.p. de N-acetilcisteína (n = 6). Os ratos foram anestesiados para estudo dos testes auditivos antes e depois do experimento. Os ratos foram sacrificados para investigação da cóclea por microscopia eletrônica de varredura. Resultados Os potenciais evocados auditivos de tronco encefálico e os valores das emissões otoacústicas estavam atenuados no grupo cisplatina. O grupo que recebeu N-acetilcisteína além da cisplatina apresentou melhores limiares de respostas auditivas do tronco encefálico e emissões otoacústicas. As amostras obtidas do grupo cisplatina apresentaram irregularidades de superfície, áreas de degeneração, com perdas graves totais ou parciais de estereocílios. As alterações foram mais leves no grupo cisplatina + N-acetilcisteína. Conclusão A ototoxicidade por cisplatina pode ser detectada por meio de potenciais evocados auditivos de tronco encefálico e pelo teste de emissões otoacústicas em ratos. A N-acetilcisteína pode proteger as células cocleares contra alterações histopatológicas. Concluímos que a N-acetilcisteína administrada 4 horas após a injeção de cisplatina tem potencial efeito otoprotetor contra a ototoxicidade por cisplatina e pode ser utilizada em ensaios clínicos.

Ototoxicidad inducida por quimio-radioterapia basada en platinos: una revisión / Ototoxicity induced by platinum compounds-based chemoradiotherapy: a review

RESUMEN Los análogos del platino, como el cisplatino, y la radioterapia son usados de forma individual y en conjunto para el tratamiento de diversas neoplasias en población adulta y pediátrica. Sin embargo, el uso de estos tratamientos puede generar ototoxicidad, especialmente cuando son usados de forma combinada para neoplasias que comprometen cabeza y cuello, manifestándose principalmente como una hipoacusia progresiva e irreversible que compromete la calidad de vida. Diversos mecanismos han sido propuestos para explicar el daño en las estructuras auditivas generado por estos tratamientos, incluyendo la producción de especies reactivas del oxígeno y la inflamación, desencadenando muerte celular. Si bien distintas estrategias otoprotectoras han sido probadas en humanos, es aún incierta su efectividad y seguridad en combinación con los tratamientos oncológicos. El objetivo de la siguiente revisión es proporcionar una visión general y actualizada de la ototoxicidad inducida por quimio-radioterapia basada en platinos, discutiendo sus bases, características clínicas, potenciales tratamientos y estrategias preventivas que se han desarrollado en los últimos años.

ABSTRACT Platinum analogues, such as cisplatin, and radiotherapy are used separately or in combination to treat several neoplasms in pediatric and adult populations. Nonetheless, the use of these treatments may lead to ototoxicity, especially when these treatments are concomitantly used to treat head and neck cancers, which can manifest as progressive and irreversible hearing loss that decreases quality of life. Several mechanisms have been proposed in order to explain the damage to the auditory structures induced by these treatment modalities, including: reactive oxygen species production and inflammation, leading to cell death. Although several otoprotective strategies have been attempted in humans, their effectiveness and security are unclear. The objective of this review is to provide an updated and general overview on platinum-based chemoradio-therapy induced ototoxicity, discussing its basis, clinical features, potential treatments and preventive strategies developed in recent years.

A review on medicinal plants used for treating ototoxicity and acoustic trauma induced hearing loss

Hearing loss induced by chemotherapy and acoustic trauma is mainly associated with two factors, free radical formation and apoptosis pathway activation. Despite numerous efforts on reducing the effects of these factors, no definite strategy is still determined to interfere with and control these processes. In recent studies, various protective agents, including antioxidants have been used on animal models, to inhibit the formation of free radicals thus improving hearing loss.In this review article we will discuss the role of traditional herbal medicine in treatment of noise/drug induced hearing loss, focusing on medicinal plants' active substances,as well as their mechanisms of action in reducing or preventing the formation of free radicals thus increasing the rate of survival of cochlea cells. Data have been gathered since year 2000, from scientific publications including the following keywords: deafness, drug toxicity, acute trauma, medicinal herbs and oxidative stress. The study includes all herbs and medicinal plants that have been experimentally used in studies on animal models and clinical trials. The results from these studies indicate the effectiveness of most of these herbs and their active substances through their antioxidative properties. Medicinal plants reported in this review can thus be considered as effective remedies intreating noise/drug induced hearing loss,yet further studies need to be done.

Efectos ototóxicos del cisplatino y su relación con la aparición de hipoacusia en pacientes con cáncer de cuello uterino / Ototoxic effects of cisplatin and its relationship with the appearance of hypoacusia in patients with cervical cancer

Con el objetivo de determinar los efectos ototóxicos del cisplatino y su relación con la aparición de hipoacusia en pacientes con cáncer de cuello uterino que asistieron al Servicio Autónomo de Oncología del estado Lara durante el lapso octubre 2017-febrero 2018, se realizó un estudio descriptivo transversal en 16 pacientes siendo las más afectadas el grupo de edad entre 36-45 años (43,2%). Los síntomas auditivos antes de iniciar el tratamiento fueron pérdida de la audición (6,2%); después del primero y segundo ciclo de quimioterapia se reportaron acúfenos (62,5% y 68,7%, respectivamente) siendo en la mayoría del tipo agudo (60% y 81,8% respectivamente) y pérdida de la audición (37,5% y 31,2% respectivamente). Los valores audiométricos al inicio fueron hipoacusia superficial para 25db (31,2%) y 30db (25%) en cambio, después del primero y segundo ciclo, fue hipoacusia superficial de tipo neurosensorial a predominio de frecuencias agudas con valores de 35db (31,2%) y de 40db (31,2%), respectivamente. Los hallazgos audiométricos mostraron que 56,2% de las pacientes presentaban hipoacusia superficial al inicio; pero luego se reportó 50% de pacientes con hipoacusia superficial de tipo neurosensorial a predominio de frecuencias agudas, posterior a ambos ciclos. Los resultados obtenidos permiten identificar de forma temprana las pacientes susceptibles de desarrollar hipoacusia posterior al tratamiento adyuvante con cisplatino(AU)

With the objective of determining the ototoxic effects of cisplatin and its relationship with the onset of hearing loss in patients with cervical cancer who attended the Autonomous Oncology Service of Lara state, during the period October 2017-February 2018; A cross-sectional descriptive study was conducted, obtaining 16 patients, being the most affected the age group between 36-45 years (43.25%), and the ranges of 25-35 years and 46-55 years (25%, respectively) . Hearing symptoms before starting treatment were hearing loss (6.25%); After the first and second cycle, tinnitus was reported (62.5% and 68.75%), being most of the acute type (60% and 81.81%) and hearing loss (37.5% and 31%). 25%). The audiometric values at the beginning were superficial hypoacusis for 25db (31.25%) and 30db (25%); however, after the first and second cycle was hearing loss Surface-type neurosensory with a curve suggestive of grade I acoustic trauma with values of 35db (31.25%) and 40db (31.25%), respectively. The audiometric findings showed that 56.25% had superficial hearing loss at baseline; but, then, 50% were reported with superficial sensorineural hearing loss with a curve suggestive of grade I acoustic trauma, after both cycles. The results obtained allow the early identification of patients susceptible to developing hearing loss after adjuvant treatment with cisplatin(AU)