OAEs and Meniere Disease

Otoacoustic emissions (OAEs) are responses originating from the inner ear. Clinically they are evoked by different families of acoustic stimuli, such as transient acoustic clicks, tone pips, and pure tones. Upon stimulation, the acoustic energy is transformed in the middle ear at acoustic pressure acting upon the stapes footplate. The pressure wave inside the cochlea stimulates the OAE generators and a reverse acoustic energy (the OAE response) propagates from the inner ear, through the stapes and the middle ear structures, to the tympanic membrane. Considering that the acoustic energy has to cross the middle ear structures twice, the functional status of the middle ear can influence or attenuate considerably the OAE response. In this context, any vestibular alteration can influence the middle ear mechanics (mainly the middle ear impedance) and consequently the OAE response characteristics. The data in the literature indicate that OAEs are very sensitive to changes in the intracranial pressure. These pressure alterations during the Meniere’s hydrops phase are expressed as changes in the intralabyrinthine pressure. Other studies have presented data supporting the assumption that OAEs can adequately monitor middle ear changes induced by the presentation of the glycerol test. The data in the literature suggest that OAEs can monitor the progress of Meniere’s disease using reliable indices

Genetic Polymorphisms in Sudden Sensorineural Hearing Loss: An Update

Objective: To investigate the association between genetic polymorphisms and sudden sensorineural hearing loss (SSNHL). Most of the SSNHL cases still remain idiopathic, and several etiopathogenetic hypotheses, including a genetic predisposition, have been proposed. Methods: A literature review was conducted using different databases: Medline/PubMed, EMBASE, and CINAHL, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All databases have been searched from May 2016 to April 2020. Results: Genetic susceptibility could represent a key element in the pathogenesis of SSNHL. A number of genetic polymorphisms related to (1) inner ear microvascular disease and endothelial dysfunction and (2) to inner ear oxidative stress and inflammation have been addressed in the current literature. Conclusions: The potential identification of a genetic profile related to SSNHL could provide a more accurate prognostic evidence of idiopathic SSNHL (ISSNHL), offering to the patients not only early-prevention strategies but eventually information on various inheritance modalities. © The Author(s) 2020

SARS-CoV-2 (COVID-19) and audio-vestibular disorders

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

Non-Syndromic Sensorineural Prelingual and Postlingual Hearing Loss due to COL11A1 Gene Mutation

This paper aims to present a third world case of Non-Syndromic sensorineural hearing loss (NSHL) due to a novel missense variant in COL11A1 gene, defined as DFNA37 non-syndromic hearing loss. The clinical features of a 6-year-old boy affected by a bilateral moderate to severe down-sloping sensorineural hearing loss are presented, as well as the genetic analysis, the latter identifying a heterozygous missense variation in the COL11A1 gene. In addition, in families with autosomal dominant transmission, COL11A1 gene should be considered in the genetic workup of the NSHL with prelingual onset

Don't forget ototoxicity during the SARS-CoV-2 (Covid-19) pandemic!

Aim of this communication is to remind clinical professionals to be aware of ototoxic side effects of several specific drugs proposed for the treatment of the new virus SARS-CoV-2 (Covid-19). In particular, chloroquine and hydroxychloroquine, azithromycin, as well as antiviral drugs such as remdesivir, favipiravir and lopinavir can all present potential ototoxic side effects. The data in the literature do not offer specific information on their potential synergetic effects nor on their interactions

EVALUATION OF INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR, TYPE 3 EXPRESSION AND ACTIVITY PROFILE IN THE CONTEXT OF COLON AND HEAD AND NECK CANCER

Colon adenocarcinoma and head and neck (H&N) squamous cell carcinoma (SCC) are different tumoral diseases, both in histology and epidemiology. Nonetheless, these anatomical sites are parts of the digestive tract and, consequently, could share possible common tumorigenic processes. Chemotherapy remains to date an important treatment for both tumours, especially in advanced stages. Nonetheless, cancer shows different degrees of chemoresistance, meaning the tumour is not susceptible to the apoptotic stimulus induced by the chosen drug. Apoptosis is a fine-tuned mechanism in which calcium (Ca2+) signalling is one of the main actors. In fact, a slow but continuous entry of Ca2+ inside the mitochondria is responsible for the activation of the apoptotic cascade. In this scenario, the family of inositol 1,4,5-trisphosphate receptors (IP3Rs), namely Ca2+ channels that reside at the endoplasmic reticulum membrane, play a pivotal role. In particular, the isoform 3 (IP3R3) is found to be enriched in regions of the endoplasmic reticulum membrane that are close to mitochondria, known as mitochondrial-associated membranes, where it allows the quasi-synaptic Ca2+ transfer from these two organelles. These findings highlight the IP3R3 as a key regulator of apoptosis. Coherently, alterations in IP3R3 expression and/or function were found in many different tumours and proposed to be a key in oncogenesis and chemotherapy resistance. Based on this hypothesis, the present study aimed to assess the IP3R3 expression levels in tumour tissue, assuming that its alteration could be involved in chemoresistance development. Accordingly, the main purpose of this thesis was to evaluate the expression of IP3R3 in colon adenocarcinoma and H&N SCC biopsies and compare it with its expression levels in the isogenic healthy mucosa. IP3R3 was investigated both at the protein level by western blot analysis and immunohistochemistry (IHC). Furthermore, upon IP3R3 detection in the tumour, the receptor functionality was assessed by ex vivo Ca2+ mobility assay. The results of the present study indicate that IP3R3 expression is significantly downregulated in the tumoral context compared to isogenic healthy mucosa, both in the colon and H&N tumours. Interestingly, as the risk class increases, the IP3R3 expression becomes more comparable between the healthy mucosa and the tumoral tissue. According to these data, it is possible to speculate a progressive degeneration of the healthy mucosa, with a progressive reduction of IP3R3 expression leading to a greater tumour predisposition. In fact, the decreased expression of IP3R3 in tumour tissue suggests the role of IP3R3 as a tumour suppressor, which is degraded or inhibited during the carcinogenesis process. This hypothesis is further supported by the functional studies, which indicate that when detected in the tumour tissue IP3R3 is not functional. Thus, it could be assumed that the produced protein could be unfunctional due to ITPR3 alterations or that IP3R3 undergoes post-translational modifications by its regulatory proteins that affect the activity of the Ca2+ channel. In conclusion, these results suggest that IP3R3 is a key tumour suppressor, and its reduced expression may represent a predisposing factor for tumour development, becoming a promising therapeutical target.I tumori del colon e del distretto cervico-cefalico rappresentano due entità tumorali differenti, sia nell’aspetto istologico, sia nell’entità epidemiologica. Ciononostante, questi tumori originano da parti diverse dell’apparato digerente e, di conseguenza, potrebbero condividere processi tumorigenici comuni. La chemioterapia rimane ancora oggi un pilastro della terapia oncologica. Tuttavia, ad oggi, l’entità dei tumori che mostra chemioresistenza è in continuo aumento e in questo caso i tumori non sono suscettibili allo stimolo apoptotico indotto dal chemioterapico. L’apoptosi è un meccanismo di morte cellulare programmata finemente regolato in cui lo ione calcio (Ca2+) riveste un ruolo importante di modulazione. Infatti, l’incremento protratto nel tempo della concentrazione di Ca2+ a livello mitocondriale è responsabile dell’innesco del processo apoptotico. In questo contesto, l’isoforma 3 dei recettori dell’inositolo 1,4,5-trifosfato (IP3R3), ovvero un canale permeabile al Ca2+ localizzato a livello delle MAM (mitochondria-associated endoplasmic reticulum membranes), gioca un ruolo centrale, determinando un flusso di Ca2+ “quasi-sinaptico” tra i due organelli. Queste evidenze hanno permesso di identificare IP3R3 come un fattore chiave di regolazione dell’apoptosi e, di conseguenza, di oncogenesi e di chemioresistenza. Il presente studio trae origine dall’idea che la chemioresistenza possa essere dovuta a una riduzione dei livelli di IP3R3 nel tumore. L’obiettivo dello studio è quello di valutare i livelli di espressione di IP3R3 nelle biopsie di adenocarcinoma del colon e del carcinoma squamocellulare cervico-cefalico e nelle mucose sane isogeniche. IP3R3 è stato valutato a livello proteico mediante tecnica western blot e analisi immunoistochimica; inoltre, laddove sia stata identificata la presenza del recettore, è stato eseguito uno studio ex vivo del flusso di Ca2+ mediante microscopia a fluorescenza. I risultati del presente studio indicano che IP3R3 è downregolato in maniera significativa nel tessuto tumorale rispetto alla mucosa sana. Inoltre, il livello di espressione di IP3R3 tra la mucosa sana e il tessuto tumorale risulta sempre più comparabile all’incrementare della classe di rischio tumorale. Secondo questa osservazione, si potrebbe ipotizzare che vi sia una progressiva degenerazione della mucosa sana, con una progressiva riduzione di IP3R3, che di conseguenza comporti una maggiore predisposizione allo sviluppo tumorale. Infatti, la riduzione dei livelli di espressione di IP3R3 nel tessuto tumorale fa supporre che tale recettore rappresenti un oncosoppressore, in quanto degradato o inibito durante la carcinogenesi. Questa ipotesi è inoltre supportata dagli studi di funzionalità, poiché nel tessuto tumorale che esprime IP3R3 il recettore è risultato non funzionale. Pertanto, si potrebbe ipotizzare che il recettore possa essere non funzionale a causa di alterazioni geniche di ITPR3 oppure a seguito di modifiche post-traduzionali da parte delle proteine deputate alla regolazione di IP3R3. In conclusione, i risultati di questo studio suggeriscono che IP3R3 possa svolgere un ruolo di oncosoppressore e che la sua ridotta espressione possa comportare una predisposizione allo sviluppo tumorale, rappresentando potenzialmente un promettente target terapeutico

Late relapse in the neck: considerations from a case of seminoma and review of the literature

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Autoimmune inner ear disease (AIED): A diagnostic challenge

Autoimmune inner ear disease (AIED) has been defined as a condition of bilateral sensorineural hearing loss (SNHL), caused by an 'uncontrolled' immune system response. The inner ear can be the direct target of the immune response, but it can be additionally damaged by a deposition of circulating immune complexes or by systemic immune-mediated diseases. The clinical expression of immune-mediated inner ear disease shows a progressive bilateral and asymmetric SNHL profile, which typically benefits from a steroid and immunosuppressive therapy. The onset of AIED is between 3 and 90 days. Cochlear symptoms can be associated with vestibular disorders and in 15%-30% of cases, AIED occurs in the contest of a systemic autoimmune disease. Currently, the onset of immune-mediated SNHL is not a well-understood process and the pathogenetic mechanisms of AIED remain unclear. Furthermore, there are no standardized diagnostic criteria or reliable diagnostic tests for the diagnosis of AIED. Hence, the definition of immune-mediated cochleovestibular disorders is a challenging diagnosis based on exclusion. A close collaboration between otolaryngologists, audiologists and rheumatologists is recommended, in order to achieve the multidisciplinary management of this rare entity, since an early AIED identification and a prompt medical treatment might result in acceptable hearing outcomes. The paper describes the clinical features of AIED and offers a diagnostic flow-chart to use in the clinical assessment of this condition

Facial nerve paralysis in children

Facial nerve palsy is a condition with several implications, particularly when occurring in childhood. It represents a serious clinical problem as it causes significant concerns in doctors because of its etiology, its treatment options and its outcome, as well as in little patients and their parents, because of functional and aesthetic outcomes. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective,inflammatory, neoplastic, traumatic or iatrogenic causes). Nonetheless, in approximately 40%-75% of the cases, the cause of unilateral facial paralysis still remains idiopathic. A careful diagnostic workout and differential diagnosis are particularly recommended in case of pediatric facial nerve palsy, in order to establish the most appropriate treatment, as the therapeutic approach differs in relation to the etiology

Tapia's Syndrome: keep it in mind!

Introduction: The aim of this study was to revise the etiologic features about Tapia's Syndrome (TS), a condition to particularly consider in the era of the COVID-19 pandemic. Evidence acquisition: A systematic review was performed according to the PRISMA criteria. The Medline and Embase databases were searched from January 1, 1990, to December 31, 2020. Initially the search yielded 399 manuscripts, which were reduced to 50, upon the application of inclusion criteria. Evidence synthesis: A total of 65 patients were included in the present review. Mean age was 44±17.5 (DS) years (15-95); M:F ratio was 2.3:1. TS involved mainly the left side (3:2) and was rarely bilateral. Only 2 TS reported cases were due to central causes. Peripheral causes were mainly due to postintubation edema (77%), extrinsic compression (15%), vascular disease (3%), other/not defined (5%). Conclusions: TS is a rare syndrome that has been related to a combined cranial nerve palsy; while TS due to central causes is very rare, it is mainly related to peripheral causes. A particular attention to TS should be given during the SARS-CoV-2 pandemic, either since the correlation between Tapia's syndrome, airway management and anesthetic procedures, since the possible implication of the viral infection itself