Tissue expression of miR-449a as risk factor for occult neck metastasis in patients with cT3-T4 N0 laryngeal cancer. A pilot study.

OBJECTIVE: To explore the potential role of miR-449a as biomarker for laryngeal squamous cell carcinoma (LSCC), especially in the decision strategy of neck dissection (ND). METHODS: Each patient underwent total laryngectomy and bilateral ND (levels II-IV); during surgery, tissue samples of around 1 × 0.5 cm were extracted from both healthy tissue adjacent to the tumor and the visibly affected tumor tissue. The extraction of total RNA, encompassing miRNA, was performed using a mirVana PARIS kit. To detect miR449a, cDNA was synthesized from 200 ng of RNA using a TaqMan miRNA reverse transcription kit. RESULTS: The study group was formed of 66 patients (62 males, and 4 females) with LSCC, aged between 39 and 77 years (mean 60 + 14.56 yr). MiR-449a was up-regulated in twenty-eight tumors (42%), while it was down-regulated in 38 samples (58%). In the present study, there was a statistical relevance for miR-449a tissue expression for pN staging (p = 0.017), and PNI (p = 0.005). Eight tumors (12%) cN0 became pN + showing occult cervical lymph node metastases at the final histopathological examination, and all of these patients showed miR-449a downregulation. CONCLUSION: Super-selective ND (sparing the sub evels IIb and IV) might be the approach to cT3-T4 N0 LSCCs with upregulation of miR-449a; on the other hand, to ensure and effective control of occult neck metastases it would be appropriate to reserve elective ND (including sublevels IIb and IV) for cT3-T4 N0 LSCCs with miR-449a downregulation. Although promising, due to the small size of the cohort, the results of this work can be considered preliminary and need to be confirmed by prospective and larger studies.

Sarcomatoid larynx carcinoma differential clinical evolution, on field statistical considerations.

Spindle cell larynx carcinoma (SpCC) represents around 3% of laryngeal cancers. It is originated by a single cancer stem cell undergoing epithelial to mesenchymal transition. This explains the aggressiveness, the peculiar resistance to conventional therapy and the frequent relapses. We focused on this particular cancer subset characteristics in patients, in early and advanced stages primarily aiming to define and highlight the differences with Laryngeal Squamous Cell Carcinoma (LSCC) focusing on clinical features, treatments, follow-up and survival in a patient's cohort composed by comparable cases from two subgroups.

Effect of liposomes, vitamins A and E nasal spray in reducing the healing time after septoplasty with concurrent turbinate surgery in adolescents.

BACKGROUND: This study evaluates endoscopic and quality of life (QoL) outcomes in two groups, composed by both allergic (A) and non-allergic (N-A) adolescents undergoing septoplasty with concurrent turbinate surgery by radiofrequency treated after surgery with nasal spray containing liposomes and vitamins A and E. METHODS: This double-blind randomized study was carried out on 40 patients (22 males, 18 females, mean age 15.5±1.0 years) undergoing septoplasty and volumetric tissue reduction of inferior turbinates by radiofrequency for post-traumatic deformities and severe nasal obstruction. We enrolled 20 subjects with positive skin prick tests and 20 with negative skin prick tests (SPT) to aeroallergens. All subjects underwent the Visual Analogue Scale (VAS) questionnaire and the nasal endoscopy score by Lund and Kennedy (LK) at baseline before surgery (T0) and 15 days (T15) and 21 days (T21) after treatment. After surgery, the nose was not packed and the day after surgery all subjects were randomized into two groups, experimental arm group I (GI) and control arm group II (GII) and given the treatment, nasal spray containing liposomes composed of phospholipids, fatty acids, and vitamin A and E for group I and saline solution (sodium chloride 0.9%) for group II. RESULTS: After therapy, the VAS and LK scores were better (P<0.05) in the investigational than in the control arm in both sub-groups (A and N-A). CONCLUSIONS: Our findings suggested that liposomal, vitamins A and E nasal spray improves the QoL in the early postoperative period, both in A and N-A sub-groups.

The Role of Quantic Molecular Resonance (QMR) in the Treatment of Inferior Turbinate Hypertrophy (ITH): Our Experience With Long-Term Follow-Up in Allergic and Nonallergic Rhinitis Refractory to Medical Therapy. Preliminary Results.

OBJECTIVE: The aim of this study was to assess the long-term effectiveness of quantic molecular resonance (QMR) in the treatment of inferior turbinate hypertrophy (ITH) in allergic and nonallergic rhinitis refractory to medical therapy. METHODS: This study enrolled 281 patients, 160 males (56.9%) and 121 females (43.1%), mean age 37.8 ± 4.1 years, range 18 to 71. Fifty-four patients have been lost to follow up and have been therefore excluded from the final analysis. Based on skin prick test results, 69 patients were considered allergic (group A) and 158 nonallergic (group B). All subjects underwent before surgery (T0) and 3 (T1), 12 (T2), 24 (T3), and 36 months (T4) after QMR treatment to: 4-phase rhinomanometric examination, nasal endoscopy evaluation, and visual analogue scale to quantify the subjective feelings about nasal obstruction. RESULTS: Subjective and objective parameters showed statistically significant improvement in both groups. Group B parameters not changed during follow-up, while group A showed significant worsening between T1 and subsequent assessments. T4 outcome indicates a better result in nonallergic patients. CONCLUSIONS: In accordance with the literature, our preliminary data validate QMR treatment as a successful therapeutic option for nasal obstruction due to ITH. Nonallergic patients had a very good T4 outcome. Allergic patients showed a worsening trend after 1 year probably due to other causes.

Deep Neck Infections: Decisional Algorithm for Patients with Multiple Spaces Involvement.

BACKGROUND: Deep Neck Infections (DNIs) spread along fascial planes and involve neck spaces. Recently, their incidence has decreased due to the introduction of antibiotics; nevertheless, complications related to DNIs are often life-threatening. OBJECTIVE: The purpose of this article is focused on the identification of predisposing factors of these complications, as well as on the development of a reliable therapeutic algorithm. METHODS: Sixty patients with DNIs were enrolled from 2006 to 2019 for a retrospective study. The exclusion criteria for the present study were cellulitis, small abscesses responding to empiric or specific antibiotic therapy, or involvement of only one deep neck space. During the analysis, the following parameters of interest have been evaluated: gender, age, site of origin, pathways of spread, comorbidities, clinical features, bacteriology data, type of surgical approach required, complications, duration of hospitalization and mortality rate. On admission, microbial swab analysis was performed. RESULTS: Diabetes Mellitus (DM), Chronic Obstructive Pulmonary Disease (COPD), iron deficiency anemia and the involvement of multiple spaces have been associated with a significantly higher risk of developing complications. Most of our patients had polymicrobial infections. All patients underwent surgical drainage. The complication rate had occurred in 56.6% of patients, while death in 18.3%. CONCLUSION: DNIs represent a medical and surgical emergency with potentially serious complications; thus, avoidance of diagnostic delay is mandatory. Our preliminary data suggest the importance of evaluating the extent of infections because the involvement of multiple spaces requires timely surgery due to the higher risk of complications and mortality.

Comparison between overlay and underlay primary myringoplasty: retrospective analysis on anatomical and functional results in 497 adult patients

PURPOSE: Retro-auricular approach using an autologous graft is the main surgical method for myringoplasty (MPL). Endaural and transcanal or endoscopic approaches are also used. There is no definitive consensus on the best MPL surgical technique. The aim of this study is to compare the two most used technique, over and underlay MPL, to evaluate the difference in anatomical and functional outcomes. MATERIALS AND METHODS: We made a retrospective analysis of 497 adult patients who underwent underlay or overlay primary MPL, between 2010 and 2018, and evaluated the difference in anatomical and functional outcomes. RESULTS: Successful functional results, evaluated 18 months after surgery, were obtained in 380 patients (76,4%); the underlay MPL obtained a successful result in 85% of patients, while the overlay technique in the 68%. We observed anatomical failure in 13.4% patients, in detail 9,8% of underlay MPL and 17,2% of overlay MPL had an anatomical failure. CONCLUSION: Our results show less complications related to the underlay technique. We believe that this remains the technique to prefer, except in subtotal or wide anterior perforations that could be better managed using the overlay technique.

MicroRNAs' Crucial Role in Salivary Gland Cancers' Onset and Prognosis.

Salivary gland cancer (SGC) is an uncommon and heterogeneous disease that accounts for around 8.5% of all head and neck cancers. MicroRNAs (miRNAs) consist of a class of highly conserved, short, single-stranded segments (18-25 nucleotides) of noncoding RNA that represent key gene-transcription regulators in physiological and pathological human conditions. However, their role in SGC development and progression is not completely clear. This review aims to compile and summarize the recent findings on the topic, focusing on the prognostic and diagnostic value of the major modulated and validated microRNAs in SGC. Their differential expression could possibly aid the clinician in delivering an early diagnosis, therapeutic strategy and precision medicine.

Anomaly of digastric muscle: an alarm bell for head and neck surgeon.

Objectives: Here follows the discussion of a case of hypoplasia of both bellies of digastric muscle and the difficult during neck dissection, because of his surgical importance like a pivotal landmark. METHODS: We reported a case report concerning digastric muscle abnormalities, accidentally discovered during neck dissection due to surgical excision of a glottic squamous cell carcinoma staged as cT3N0. A brief literature review was done to compare and research similar cases. RESULTS: Literature counts several reports of digastric muscle abnormalities, namely involving the anterior belly. Little has been written about hypoplasia of digastric muscle. CONCLUSION: Digastric muscle abnormalities are rare, which can be absent or, more frequently, duplicated. Albeit its anomalies are anecdotal, it is advisable to give due consideration to the hypoplasia of both bellies of the digastric muscle during the analysis of radiological imaging, in order to prevent the risk of operative complications. According to our knowledge, this is the first and singular case of digastric muscle's hypoplasia.

Covid-19 laryngectomized patients care, on field experience, and considerations.

Laryngectomized patients showed an unconventional response to SARS-CoV-2 viral infection. Here, we describe five different patient cases along with our interpretation of the phenomena and suggestions for their safe management.

Sudden Sensorineural Hearing Loss in Mild COVID-19: Case Series and Analysis of the Literature.

BACKGROUND: There is growing evidence of otoneurological involvement of SARS-CoV-2, such as tinnitus and balance disorders and smell and taste disorders, but HL in COVID-19 patients has still been marginally studied. Investigating the role of SARS-CoV-2 as an aetiological factor of Sudden Sensorineural Hearing Loss (SSNHL) may offer the opportunity to address treatment strategies to maximize clinical recovery and avoid side effects. METHODS AND RESULTS: For this purpose, we will present case studies of five patients who experienced SSNHL during COVID-19. Patients were selected from COVID-19 positive adult subjects with mild clinical presentation, admitted to the outpatient Ear Nose and Throat Department of Cardarelli Hospital due to the onset of SSNHL during the infection. All underwent a complete audio-vestibular investigation before and after SSNHL treatment protocol. Each patient is described with a detailed analysis. CONCLUSIONS: SSNHL could be an occasional symptom of COVID-19, even in mild manifestations of the disease. Our experience leads us to underline the value of promptly recognizing and addressing this and other uncommon symptoms, giving patients the opportunity to receive early treatment.

Our Experience on Temporal Bone Fractures: Retrospective Analysis of 141 Cases.

Temporal bone fractures are a common lesion of the base of the skull. The diagnosis and management of temporal bone fractures require a multidisciplinary approach. Variable clinical presentations may arise from such fractures, ranging from an asymptomatic course to very serious consequences. The aim of this study was to report our experience with a series of patients with temporal bone fractures and to propose a diagnostic/therapeutic algorithm. This study enrolled 141 patients, 96 (68.1%) males and 45 (31.9%) females, ranging in age from 20 to 60 (average age: 39 ± 4.1 years), with temporal bone fractures who were referred to Cardarelli Hospital between 2006 and 2018. The present paper presents a classification of temporal bone fractures and typical clinical sequelae and provides an illustration of their prognosis and treatment.

Diagnosis of benign paroxysmal positional vertigo in Emergency Department: Our experience.

The Benign Paroxysmal Positional Vertigo (BPPV) represents the first cause of peripheral vertigo in populations and it is determined by a displacement of otoconial fragments within the semicircular canals. Following the patient's head movements, these fragments, moving by inertia, incorrectly stimulate the canals generating vertigo. The BPPV is diagnosable by observing the nystagmus that is generated in the patient following the Dix-Hallpike maneuver used for BPPV diagnosis of vertical semi-circular canal, and, following the supine head yaw test used for lateral semi-circular canal. Correctly identifying the origin of this specific peripheral vertigo, would mean to obtain a faster diagnosis and an immediate resolution of the problem for the patient. In this context, this study aims to identify precise training activities, aimed at the application of specific diagnostic maneuverers for algorithm decisions in support of medical personnel. The evaluations reported in this study refer to the data collected in the Emergency Department of the Cardarelli Hospital of Naples. The results obtained, over a six-month observation period, highlighted the advantages of the proposed procedures in terms of costs, time and number of BPPV diagnoses.

Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion.

Laryngeal cancer (LCa), a neoplasm of the head and neck region, is a leading cause of death worldwide. Surgical intervention remains the mainstay of LCa treatment, but a crucial point is represented by the possible nodal involvement. Therefore, it is urgently needed to develop biomarkers and therapeutic tools able to drive treatment approaches for LCa. In this study, we investigated deregulated microRNAs (miRNAs) in tissues from LCa patients with either lymph node metastases (N+) or not (N-). miRNA expression profiling was performed by a comprehensive PCR array and subsequent validation by RT-qPCR. Results showed a significant decrease of miR-449a expression in N+ compared to N- patients, and miR-133b down-modulation in LCa tissues compared to paired normal ones. Receiver operating characteristic (ROC) curve analysis revealed the potential diagnostic power of miR-133b for LCa detection. According to the validation results, we selected miR-449a for further in vitro studies. Ectopic miR-449a expression in the LCa cell line Hep-2 inhibited invasion and motility in vitro, slowed cell proliferation, and induced the downregulation of Notch1 and Notch2 as direct targets of miR-449a. Collectively, this study provides new promising biomarkers for LCa diagnosis and a new opportunity to use miR-449a for the treatment of nodal metastases in LCa patients.

Adenoid cystic carcinoma of the larynx in a 70-year-old patient: A case report.

Adenoid cystic carcinoma (ACC) is a relatively rare tumor that accounts for <1% of all head and neck malignancies. Laryngeal localization of ACC, which is most commonly hypoglottic, is relatively rare, occurring in 0.07-0.25% of all laryngeal tumors. ACC is characterized as a slow-growing tumor with a high recurrence rate, which often causes dyspnea and hoarseness. ACC exhibits a propensity for perineural invasion and thus, patients may experience pain as a late symptom of the disease. Distant metastasis occurs in 35-50% of cases and the lungs are the most common site of metastasis. Tumors are usually diagnosed by physical examination with fiberoscopy and computed tomography of the neck and chest, due to the high rate of lung metastases. The standard therapy for ACC is surgery followed by radiotherapy. In this study, a 70-year-old patient presented with laryngeal ACC, who underwent total laryngectomy with bilateral neck dissection and adjuvant radiotherapy, is presented. Follow-up examination performed 2 years after surgery revealed no evidence of locoregional recurrence or distant metastases. Previously published literature regarding ACC of the larynx was also reviewed.

Aggressiveness pattern and second primary tumor risk associated with basaloid squamous cell carcinoma of the larynx.

Basaloid squamous cell carcinoma (BSCC) is a rare, aggressive and distinct variant of squamous cell carcinoma (SCC) of the upper respiratory and digestive tract. We have evaluated disease specific survival (DSS) and overall survival (OS) through Kaplan-Meier method and mortality risk through univariate statistical analysis of Cox in 42 cases of BSCC and other 42 of laryngeal SCC (LSCC) matched for both age and sex. We demonstrated that laryngeal BSCC is a more aggressive tumor than LSCC as is associated to higher nodal recurrence of pathology (5 vs 2 patients, overall risk, OR 2.7), a reduced survival (median survival 34 vs 40 months, OR 3.2 for mortality); in addition, basaloid patients have a higher risk to be affected by second primary tumors (13 vs 3 patients, OR 5.8) and a higher probability to die for this second tumor (Hazard Risk, HR 4.4). The analysis of survival shows an increased mortality risk concurrent with the parameters assessed by univariate analyses that assume a predictive and statistical significance in second tumor and grading in basaloid LSSC.

Temporal bone meningioma involving the middle ear: A case report.

Meningioma is a common intracranial tumor involving the meninges. The localization of this type of tumor is rarely extracranial due to its typically low invasive properties. Furthermore, invasion of the middle ear is exceptional. The present study reported a case of meningioma extending into the middle ear from the middle cranial fossa through the tegmen tympani. The clinical and pathological characteristics, as well as the outcome of the patient, were described.

¿Influye el consumo de comidas ricas en proteínas y grasas en la glucemia postprandial de pacientes con diabetes tipo 1 que realizan conteo de hidratos de carbono? / Does the consumption of meals rich in proteins and fats influence on the postprandial glucemia of patients with diabetes type 1 that follow carbohydrate counting?

Introducción: el tratamiento de la diabetes tipo 1 (DM1) requiere de la administración de insulina exógena; dentro de las variables a tener en cuenta para calcular la dosis se encuentra el contenido de hidratos de carbono (HC) de la comida a ingerir. Este macronutriente es considerado, desde hace varios años, el responsable del aumento de la glucemia postprandial (GPP). El conteo de hidratos de carbono (CHC) es el método más aceptado y utilizado actualmente en el tratamiento nutricional, aunque cada vez existe más evidencia de que hay otros macronutrientes, como las proteínas y las grasas, que pueden influir en la variación de la GPP. Objetivo: el objetivo de esta revisión bibliográfica es reunir los resultados de publicaciones científicas que analizaron la respuesta glucémica (RG) al consumo de comidas con alto contenido de proteínas y grasas y hacer un análisis de las diferentes intervenciones. Materiales y método: búsqueda bibliográfica en PUBMED, inicialmente 196 artículos. Luego de aplicar los criterios de inclusión y exclusión se seleccionaron 26 artículos realizados en personas con DM1 de los últimos 10 años (2007-2017) referidos al consumo de comidas altas en proteínas y grasas. Resultados: hay una significativa variación interpersonal en los requerimientos de insulina en respuesta a las grasas y proteínas dietarias, que puede fluctuar en un 65% ± 10%. En los estudios randomizados se logró determinar que en las comidas altas en grasas el pico de GPP fue demorado y la sensibilidad a la insulina fue menor. Uno de los estudios logró demostrar que el 100% de las comidas altas en grasa se asociaron con hiperglucemia tardía. En relación a las dos revisiones sistemáticas encontradas, se hace hincapié en la búsqueda de datos para mejorar el tratamiento intensificado de la DM1, siendo el control de la GPP el indicador principal, ponderando la importancia de considerar la ingesta proteica y grasa de manera adicional al CHC. Conclusión: se concluye que el efecto de una comida con un alto contenido en proteínas y grasas sobre la glucemia suele presentarse entre las 3 a 6 hs de consumidas, siempre teniendo en cuenta la respuesta individual y el modo de administrar la insulina. La tarea del equipo interdisciplinario es fundamental para conocer la respuesta individual en el paciente con DM1 ante el consumo de comidas altas en proteínas y grasas, pudiendo así orientar la toma de decisión(AU).

Introduction: the treatment of type 1 diabetes (DM1) requires the administration of exogenous insulin, being the carbohydrate (HC) content of the meal to be ingested one of the variables to be considered to calculate the insulin dose. For several years, this macronutrient has been considered responsible for the increase in postprandial glycemia (PPG). Carbohydrate Counting (CHC) is the most accepted and currently used method in the nutritional treatment, although there is enough evidence that other macronutrients, such as protein and fat, can influence on the variation of PPG. Objective: to gather the results of scientific publications which analysed the glycemic response (GR) to the consumption of high-protein and high-fat meals and to analyse de different interventions. After applying the inclusion and exclusion criteria, 24 articles were selected including those with individuals with DM1 from the past 10 years (with the exception of one) referring to the consumption of high-protein and high-fat meals. Results: there is a significant interpersonal variation in insulin requirements in response to dietary fat and protein, which can fluctuate by 65% +/- 10%. Randomized studies showed that in the high-fat meals, the peak of PPG was delayed and insulin sensitivity was lower. One of the studies showed that 100% of high-fat meals were associated with late hyperglycemia. Both systematic reviews emphasize the need to search for data to improve the intensive treatment of DM1, with the control of PPG being the main indicator, considering protein and fat intake, in addition to CHC. Conclusion: the effect on blood glucose of high-protein and high-fat meals usually occurs between 3 to 6 hours after being consumed, always considering the individual response and the insulin administration method. The task of the interdisciplinary team is essential to know the individual response in the DM1 patient to the consumption of high-protein and high-fat meals, thus being able to guide the decision-making process(AU).

Consumo de bebidas endulzadas artificialmente con edulcorantes no nutritivos y su relación con el desarrollo de síndrome metabólico y diabetes tipo 2 / Consumption of artificially sweetened beverages (BEA)with non-nutritive sweeteners and its relationship to the development of metabolic syndrome and type 2 diabetes

Introducción: En Argentina un 37,1% de la población padece sobrepeso, un 20,8% obesidad y un 9,8% diabetes. La prevalencia de síndrome metabólico oscila entre el 20 y 25%. Según el estudio HIDRATAR, el consumo promedio de agua, bebidas e infusiones era de 2.050 ml/día, de los cuales un 29% correspondió a bebidas endulzadas artificialmente (BEA). No existe consenso de los organismos internacionales para su consumo. Metodología: Se llevó a cabo una búsqueda bibliográfica en PubMed, Scielo y Cochrane, de artículos publicados a partir del año 2005, con el objetivo de conocer la relación entre el consumo de BEA y el riesgo de desarrollo de síndrome metabólico y diabetes mellitus tipo 2. Resultados: Se encontraron 12 trabajos que señalan los efectos adversos de las BEA. Los mismos representan una mayor población en estudio, seguida durante más tiempo. Es un tema controvertido con mucha disparidad en la obtención de la información, teniendo en cuenta además que, en el caso de estudios con humanos, son muchos los componentes del plan alimentario que hay que considerar. Conclusiones: Ha quedado demostrado que los edulcorantes no nutritivos no son sustancias metabólicamente inertes y hay evidencia que sugiere que las BEA no son completamente inocuas, siendo primordial y necesaria la educación para limitar su consumo y promover la ingesta de agua.

Audiometria de altas frequências no diagnóstico complementar em audiologia: uma revisão da literatura nacional / High-frequency audiometry in audiological complementary diagnosis: a revision of the national literature

A audiometria de altas frequências (AAF) é um exame audiológico importante na detecção precoce de perdas auditivas por lesões na base do ducto coclear. Nos últimos anos, a sua utilização foi facilitada pelo fato de os audiômetros comercializados passarem a incorporar frequências superiores a 8 kHz. Porém, existem diferenças relacionadas aos equipamentos utilizados, às metodologias empregadas e/ou aos resultados e interpretação. Assim, o objetivo deste artigo foi analisar a produção científica nacional sobre a aplicação clínica com AAF, para compreender sua utilização atual. Foram pesquisados textos publicados e indexados nas bases de dados LILACS, SciELO e Medline, num período de tempo de dez anos, utilizando como descritor audiometria de altas frequências/high-frequency audiometry. Encontraram-se 24 artigos científicos nacionais utilizando AAF, cuja população avaliada, em sua maioria, apresentava de 18 a 50 anos de idade; 13 dos estudos determinaram os limiares utilizando como referência decibel nível de audição (dBNA); alguns estudos realizaram a comparação dos limiares auditivos tonais entre grupos para definir a normalidade; os autores relataram diferenças significativas nos limiares auditivos de altas frequências entre as idades. A AAF é utilizada na clínica audiológica para identificação precoce de alterações auditivas e no acompanhamento da audição de sujeitos expostos a drogas ototóxicas e/ou agentes otoagressores.

High-frequency audiometry (HFA) is an important audiological test for early detection of hearing losses caused by leasions in the base of the cochlear duct. In recent years, its use was facilitated because audiometers began to identify frequencies higher than 8 kHz. However, there are differences related to the equipment used, the methodologies followed, and/or to the results and their interpretation. Therefore, the aim of this study was to analyze the national scientific production regarding HFA clinical application, to better understand its current use. Articles published and indexed in LILACS, SciELO and Medline databases in the last ten years were researched, using as keyword audiometria de alta frequência/high-frequency audiometry. Twenty-four Brazilian scientific papers using HFA were found; most studies evaluated participants with ages ranging from 18 to 50 years; 13 studies used decibel hearing level (dBHL) to determine the thresholds; a few studies compared tonal auditory thresholds between groups to define normality; the authors reported significant differences in high frequency auditory thresholds among age ranges. HFA is used in audiological clinic for early identification of auditory alterations and in the auditory follow-up of subjects exposed to ototoxic drugs and/or otoagressive agents.