Pop-rock musicians are at risk of developing hearing loss and other symptoms related to amplified music.The aim of the present study was to assess the satisfaction provided by the use of hearing protection in pop-rock musicians. Study design: Contemporary cohort study.A study of 23 male pop-rock musicians, aged between 25 to 45 years. After audiological evaluation  hearing protective devices were provided to be used for three months. After that musicians answered a satisfaction assessment questionnaire.The prevalence of hearing loss was of 21.7%. The most common complaints about the hearing protectors were: autophonia, pressure in the ears, interference in high frequencies perception and full time use of the hearing protector during concerts. There was a positive correlation between a reduction in tinnitus after the use of the HPD with the following complaints: tinnitus after beginning the career (p= 0.044), discomfort with the sound intensity in the work place (p= 0.009) and intolerance to loud sound (p= 0.029).There was a high prevalence of hearing loss and a positive tendency towards the use of the ear protector device among the sample population. Since the 1960s several authors have asked whether sound levels from amplification systems used by pop rock and rock and roll bands are harmful to hearing and could permanently damage the auditory apparatus. Studies haves hown that the prevalence of hearing loss among musicians ranges from 5% to 52%.6,Aside from the auditory effects that electronically amplified music may cause, other studies have reported non-auditory findings that affect the quality of life of music professionals. These include tinnitus, dizziness, hyperacusis, sound distortion, fullness in the ear, altered cardiovascular, gastric and muscular systems, changes in humor, stress, and irritability.The main feature of hearing protectors for musicians is to have uniform attenuation, never attenuating more the higher frequencies relative to middle and low frequencies, as happens with common hearing protectors. They are named high fidelity hearing protectors because the original quality of music is preserved, but at a lower sound level. Custom models may reduce sound by 9dB, 13A study showed that musicians who used hearing protectors assiduously were those that presented some hearing complaints, comprising about 20% of a sample of 196 musicians. They had started using hearing protectors after perceiving initial hearing symptoms of any type. The most common types used in this group were custom insert (47%) and premolded (25%) hearing protectors. The author concluded that the presence of hearing complaints could positively affect the decision of using a hearing protector.A survey of young pop-rock musicians assessed the acceptance of musician-specific hearing protectors. Although these protectors were specifically made for musicians, a few sound quality issues were noted, such as occlusion effects and altered perception of high frequencies. There was a negative trend relative to the use of hearing protectors throughout shows. Nevertheless, a qualitative analysis of hearing protectors generally revealed a positive receptivity among musicians.In this context, it is necessary to assess the effects that exposure to amplified music generate to health in general and hearing in these professionals, and to prevent such losses by the use of individual hearing protectors that do not distort music quality.The purpose of this study was to assess the satisfaction level of hearing protector use among pop rock bands.This study consisted of a contemporary cohort investigation of pop-rock musicians from June to November 2007.Prior to the study, participants were informed about the procedures and signed a free informed consent form. The institutional review board of the institution approved the study (numbers 009/2007 and 002/2007).,,Fifty musicians belonging to several pop rock bands were invited to participate. Only 24 of them accepted the invitation and underwent the study procedures. Others stated that they were interested, but presented the following reasons for not participating: fear of discovering hearing loss; too many commitments; a full agenda; lack of interest or rejection about using hearing protectors. Similar difficulties have been reported in other studies of musicians.Subjects with any of the following were excluded from the sample: age over 50 years; presence of conductive or mixed hearing loss; altered tympanometric curve in acoustic immittance testing; and presence of preexisting diseases and other neurological or degenerative diseases. Thus, of 24 subjects, one was excluded because of a left type B tympanometric curve.The study sample therefore consisted of 23 male subjects who had been musicians of pop rock bands for at least one year. These bands comprised 3 to 5 members, and each participant was characterized according to his or musical instrument, as follows: voice (8), electric guitar (7), bass guitar (4), double bass (4), guitar (4), drums (4), and keyboards (1). It should be noted that some of them played more than one musical instrument.Ages ranged from 25 to 45 years; the mean age was 32.4 years, and the standard deviation was 4.5 years. The time spent at work ranged from 3 to 21 years; the mean was 13.4 years, and the standard deviation was 4.7 years. The exposure time to sound in hours per week ranged from 1.5 to 20 hours; the mean was 10 hours per week, and the standard deviation was 5.5 hours per week. Thus, the sample mostly comprised musicians aged from 25 to 35 years (82.6%), who had spent from 6 to 15 years working (78.3%), and who were exposed to music during shows from 6 to 10 hours per week (47.8%).,,After passing the selection criteria, subjects answered a questionnaire adapted from those applied in previous studies.Visual inspection of the outer ear canal was done before audiological testing to check for any obstruction that might preclude further testing. If this was the case, these subjects were excluded from the study and referred for an otorhinolaryngological evaluation.Next, the following hearing tests were applied: pure tone audiometry, acoustic immittance testing, transient-evoked otoacoustic emissions testing (TEOAE) and distortion product otoacoustic emissions testing (DPOAE). An auditory rest of at least 14 hours was given between tests.After audiological testing, each musician was given a pair of E.A.R. ER 20 high-fidelity hearing protectors, which is a premolded single size silicone three-flange earplug. The manufacturer informs that this hearing protector provides a linear sound level frequency decrease and does not distort voice or music. Its noise reduction rating is 12 dB.The reasons for choosing this hearing protector were: uniform attenuation preserving the fidelity of the original sound signal; a single size not requiring experts to make a mold; lower cost, and adequate attenuation for the needs of the study group.,Musicians were given instructions about the placement and hygiene of the hearing protector. They were asked to use the hearing protectors in their shows for the next three months.After this period they were asked to fill in a standard questionnaireThe SPSS  version 13.0 software was used for the statistical analysis. The Mann-Whitney test was applied for studying the parametric values. The chi-square and Fisher's exact test were applied to study non-parametric variables. The significance level throughout was 5% (α=0.050).The most frequent hearing complaints of musicians upon entering their profession and just after a show were tinnitus  and intolerance to loud sounds (34.8% upon entering the profession and 30.4% after a show). The most common extra-auditory complaints were insomnia (26.1%) and memory problems (26.1%).Pure tone audiometry revealed that the highest mean audiometric threshold values occurred at 3000, 4000 and 6000 Hz in both ears. Classifying the audiograms based on Fiorini (1994)TEOAE revealed a higher occurrence of positive responses bilaterally (52.2%). The sum of unilateral and bilateral absent responses comprised 47.8% of subjects, similar to one ear only. DPOAE showed absent responses in 56.5% of cases, especially in the bilateral condition (34.8%).Of 23 musicians, 18 (78.3%) scored over 30 points, showing that the hearing protector satisfactorily met user expectations and needs. When asked about the score (from 0 to 10) given to demonstrate satisfaction with using the hearing protector, six musicians (26.1%) scored 6 or less, seven musicians (30.4%) score 7, and ten musicians (43.5%) scores 8 and 9. Thus, 73.9% of scores were between 7 and 9, which reveals a positive trend in favor of satisfaction with the use of the HiFi ER 20 hearing protector.Questionnaire statements were divided into three categories:15 quality of sound reception, comfort, and ease of use. The mean values resulted from the sum of scores for each agreement/disagreement intervals indicated by musicians (from 0 to 5).The fist category concerned the quality of sound reception, where the mean values were: quality perception of band instruments (3.7), perception of the timbre of band instruments (4.0), perception of high frequency sounds (3.1), perception of low frequency sounds (3.9), and clear perception of the vocalist's voice (3.7). The lowest mean values were found in the statement about interference in perceiving high frequency sounds.The second category was related to comfort when using the hearing protector, where the mean value was 3.3 for comfort while using the protector and 3.4 for its esthetics.The third category, ease of use, yielded the following mean values: ease of placing the hearing protector (4.4), using the protector full time during rehearsals (3.6), and using the protector full time during shows (2.9).The most frequent negative sensations while using the hearing protector were dampened voice (43.5%), and pressure on the ears (39.1%) . The occFischer's exact test found positive correlations between the perception of decreased tinnitus after using the HiFi ER 20 hearing protector and the following variables: presence of a complaint of tinnitus after entering the profession (p=0.044), reports of feeling bothered with the sound level at the worksite (p= 0.009), and complaints of intolerance to loud sounds (p= 0.029).•Presence of a complaint of tinnitus and sensation of the HiFi ER 20 hearing protector interfering with the quality of music (p=0.028),•Presence of tinnitus and a sensation of decreased tinnitus after using the hearing protector (p=0.031),•Presence of a complaint of intolerance to loud sounds and a sensation of decreased tinnitus after using the hearing protector (p=0.015),•Presence of feeling bothered with the sound intensity to which one is exposed, and an assessment that the hearing protector had a positive influence on performance (p=0.042),•Presence of feeling bothered with the sound intensity to which one is exposed and the sensation of decreased tinnitus after using the hearing protector (p=0.006), and•Prior use of any type of hearing protector and an assessment that the protection provided by the HiFi ER 20 model was satisfactory (p=0.041).The Mann-Whitney test related hearing complaints with satisfaction indicators with use of the HiFi ER 20 hearing protector; the results were statistically significant for the following conditions:,,,,25The main hearing complaints reported by pop-rock musicians in this study were tinnitus (39.1%) and intolerance to loud sound 34.8%). These findings corroborate several national and international studies that have confirmed these problems as the most frequent in musicians. In these studies, the frequency of the complaint tinnitus ranged from 37.5% to 45%, and the complaint intolerance to loud sound ranged from 19% to 48%.%. These ,,The same complaints were also reported after shows; tinnitus in this situation may be related to a temporary change in hearing thresholds as a result of exposure to highly amplified music, even for short time periods. It should be noted that the average daily exposure was three hours and the average weekly exposure was ten hours, which are lower than a regular workday (8h/day or 40h/ week). The weekly average exposure time was similar to that in other studies.Early studies in 1967 and 1974 on the prevalence of hearing loss in musicians showed rates of around 8%.Also note that this prevalence of NIHL-suggesting audiograms is similar to that in steel mills, notwithstanding exposure to different sound sources and time spent in the noisy environment.,,,,,Absent otoacoustic emissions test responses (OAE) were frequent in this study; 78.3% of musicians had audiometric thresholds within normal limits. This result may reflect the fact that OAE are a measurement of cochlear motor activity due to outer hair cell action. Because hearing loss caused by high sound pressure levels starts with outer hair cell damage,Responses in the questionnaire on satisfaction with the HiFi ER 20 hearing protector were concentrated in the “agree” and “fully agree” groups, indicating a positive attitude towards using hearing protectors. Two questions were exceptions: clear perception of high frequency sounds, and full-time use of the ER 20 hearing protector during shows. For the first question, 39.1% “disagreed” and “strongly disagreed,” suggesting that, even with uniform attenuation, the hearing protector alters the perception of high-frequency sounds. For the latter question, 43.5% of responses to full-time use of hearing protectors during shows were “disagree” and “strongly disagree,” which indicates resistance to hearing protector use.A study of young pop-rock musicians has also found that the worst evaluation scores refer to similar aspects.Musicians that had no interest in using the hearing protector full time during shows commented in the questionnaire that compliance was low for specific performance reasons, namely that there was interference with sound fidelity and referential normal hearing. These findings were similar to those observed in a study of instrumental band musicians; it assessed compliance with the same type of hearing protector.The most important point favoring the use of hearing protectors in a study of opera and classical musicians was perception of the sonority of the instrument itself, that is, whether use of hearing protectors did or did not generate sound distortion of instruments.The most frequent negative sensations due to protectors were dampened voice (43.5%) and pressure in the ear (39.1%). Only 4.3% of musicians said they had no negative sensations with protectors.,,Some authors have attributed sensations of pressure and dampened voice to an occlusion effect.Pressure in the ears may also be explained by the relative size of the hearing protector.Negative feelings observed in this study were similar to those in a study of workers exposed to occupational noise designed to assess comfort with hearing protector use. The authors reported that interference with comfort was due to difficulties in conversation (53.4%) and pressure in the ears (39.4%). Only 5% of the sample reported absence of discomfort.Our findings differed from those of a study of orchestra musicians,,,A significant positive correlation was found between hearing complaints  and perception of decreased sensation of tinnitus after using hearing protectors. It is known that tinnitus is among the effects of exposure to excessive sound pressure levels, annoyance with exposure to noise and intolerance to loud sounds. Exposure levels are attenuated when using hearing protectors; it is therefore possible to perceive its benefits.,,A relation between the presence of hearing complaints (tinnitus and intolerance to loud sound) and variables considered as indicators of the degree of satisfaction with hearing protectors was found. The results corroborate research findings showing that hearing complaints interfere in the evaluation and use of hearing protectors.According to survey data, more hearing complaints relate to increased concern by musicians about their hearing; they are consequently more aware of the perception of discomfort with noise exposure at work. In such cases there is more acceptance of hearing protectors and its use in rehearsals and performances becomes more frequent.After using hearing protectors for three months, 73.9% of the sample gave a score over 7.0 for satisfaction with use. Furthermore, 78.3% of the questionnaires had scores above 30 points. These findings suggest that hearing protectors satisfactorily met the needs and expectations of users and indicate a positive trend for accepting hearing protectors.The overall results of the evaluation HiFi ER 20 hearing protectors raised two hypotheses; we considered that few participants reported full-time use during presentations. Firstly, pop-rock musicians resist using earplug type hearing protectors, because they affect some aspects of music quality or their visual aspect. Secondly, this type of hearing protector, although providing uniform attenuation, is not the most recommended model for this profession. Therefore, it may be interesting to use custom hearing protectors to assure comfort and esthetics, despite a higher cost; it is also possible to adapt different attenuation filters.A recent study of opera and classical music musicians revealed that 82.6% of the sample already knew about custom hearing protectors; this was the most frequently used model among this group, especially among percussionists.It is worth noting that not using hearing protectors may contribute significantly to the onset of hearing loss. A study of 42 non-professional pop-rock musicians compared audiological results of musicians that used and did not use hearing protectors; controls were a group of 20 normal hearing subjects. Differences were statistically significant in a comparison of audiometric means between musicians that did not use hearing protectors (8.2 dB) and those that did (2.4 dB). The authors concluded that hearing loss in musicians that used hearing protectors was very similar to the control group. Hearing loss, however, was significantly more pronounced in those who never used hearing protectors. Thus, musicians that did not use hearing protectors were at a higher risk of developing hearing loss.Further studies with pop-rock musicians could evaluate acceptance of personal hearing protectors with custom filters or individual monitors to ascertain which would be the most appropriate model for this style of music.,,,,As suggested in other studies,Regarding the use of hearing protectors, musicians need to be re-educated by motivation and training, first to adjust for the presence of an object in the ear canal, and second to listen to music and instruments with properly placed hearing protectors.There is also the possibility of acoustic treatment of venues. This may be difficult to achieve in the short term due to the high costs of such modifications and the fact that bands do not present at only one place. Moreover, even if environmental issues are dealt with, they are limited because the sound source (instrument) is close to the musician, especially in the case of drummers.Simple measures may be adopted, such as placing the stage as further away as possible from loudspeakers to decrease the level of noise exposure . Return speakers may be placed close to musicians, and rest intervals during shows may provide periods of auditory rest.For such changes to happen, it would be necessary to know the particularities of each musical style and to create educational activities to foster cultural and behavioral changes in professional musicians, since hearing is their primary instrument.Finally, regulations for safe levels of noise exposure among musicians would be appropriate, together with recommended effective preventive measures as a means of establishing safer work practices.•The worst satisfaction evaluation scores about using the HiFi ER 20 hearing protector concerned interference by the protector of high frequency sound perception and full time use of the hearing protector during shows;•The most common negative sensations while using the hearing protector were dampened voice and pressure in the ears;•There was a positive correlation between the presence of hearing complaints and the sensation of decreased tinnitus after using the hearing protector;•73.9% of musicians scored over 7 to reflect their satisfaction with using the HiFi ER 20 hearing protector, which suggests a favorable tendency towards accepting this device.


Lawsonia intracellularis is the aetiological agent of proliferative enteropathy, an enteric disease endemic in swine. Survival in its intracellular niche of the ileum epithelial lining requires the capacity to subvert, repress or exploit the host immune response to create an environment conducive to bacterial propagation. To better understand how L. intracellularis survives in its intracellular niche, we have performed an investigation into the dynamic relationship between infection and the host autophagy response by immunohistochemistry in experimentally infected porcine ileum samples.L. intracellularis residence. Detecting microtubule-associated protein light chain 3 (LC3) is used as a method for monitoring autophagy progression as it associates with mature autophagosomes. For LC3 there was no notable change in signal intensity between crypts with characteristic L. intracellularis infection and healthy crypts of uninfected pigs. Finally, as p62 is degraded with the internal substrate of an autophagosome it was used to measure autophagic flux. There was no observed reduction or redistribution of p62.Beclin1, a protein required early in the autophagy pathway was observed to be distributed with a basal to apical concentration gradient in the crypts of healthy piglets, whilst infected piglets were observed to have no gradient of distribution and an increase in the presence of Beclin1 in crypts with histological characteristics of L. intracellularis affects autophagy. This disruption to host ileum homeostasis may provide a mechanism that assists in bacterial propagation and contributes to pathogenesis.These preliminary results of the autophagy response in the ileum suggest that  Proliferative Enteropathy (PE) is principally a porcine disease with clinical manifestations most commonly observed in juveniles post-weaning   and quantitation of fluorescence. The two samples selected for this study were two of the most highly infected available piglets from Roerink et al, L. intracellularis.Briefly, paraffin blocks from ileum tissues of pigs 21 days post challenge and infection were empirically assessed by staining for the presence of L. intracellularis (VPM53) staining, all slides underwent heat-mediated antigen retrieval in citrate buffer, pH6, using a Histo5 Rapid Microwave Histoprocessor  under high pressure at 110 °C for 5 min. For VPM53 tissue samples were incubated in proteinase K (DAKO UK Ltd.) for 20 min at room temperature followed by two washes in phosphate buffered saline (PBS). Cells were permeabilised with 0.1% Triton-X (Sigma-Aldrich) in PBS for 10 min at room temperature followed by two further PBS washes. Samples were blocked with 5% skim milk powder (SMP) in PBS at room temperature for 1 h, before incubation at 4 °C overnight with the primary antibody , LC3  and p62 ) in 5% SMP in PBS. Slides were washed in PBS before incubation with secondary antibodies  at a concentration of 1:1000 for 1 h at room temperature. Samples were counter-stained with 6-diamidino-2-phenylindone (DAPI) before a coverslip was mounted with LabVision PermaFluor (ThermoFisher Scientific).Tissue Sects. (4 µM thick) used were from sequential ileum. From the uninfected and infected cohorts 2 pigs were selected for investigation for all staining experiments, excepting LC3 which had only a single control pig stained. Except for Intestinal alkaline phosphatase (IAP) was monitored with Vector® Red Alkaline Phosphatase Substrate (Vector Laboratories) according to manufacturer instructions  and imaged using Zen Black Software (Carl Zeiss). Only regions of the ileum sectioned to show entire longitudinal crypts were selected in the optical field for imaging. Because Fluorescence intensity was quantified using FIJI . Samples from 2 uninfected and 2 experimentally infected piglets were used for each condition, with at least 9 discrete regions of the ileum imaged per section. Regions of interest (ROI) were manually outlined, the spectrally opposite colour of interest was selected, and global thresholding was set at 60 & 255 to highlight the marker and account for background fluorescence. For crypts and epithelial lining measurements, signal intensity was normalised to the area of the entire field. Villus epithelial lining was selected using the line tool on a thickness of ten. The mean area:signal ratio of the ROI as determined using ImageJ was used to consider crypt size and localisation of proteins.L. intracellularis-infected piglets. The presence of L. intracellularis in epithelial cells in the ileum was confirmed in the infected samples  is conjugated to phosphatidylethanolamine to form LC3-II before joining the autophagosome as the penultimate protein for maturation. Cytosolic puncta of LC3-II are therefore utilised as a marker for mature autophagosome formation (He et al. on Table , Fig. 2BL. intracellularis had no observable difference in distribution of p62 when compared to the uninfected piglets (Table L. intracellularis infected crypts of infected pigs compared to uninfected pigs (Pankiv et al. p62 contains a ubiquitin binding domain and a domain that binds specifically to the LC3-II isoform, thus acting as a mediator between the ubiquitin detection innate immune response and the formation of the mature autophagosome (Pankiv et al. ts Table , Fig. 2CL. intracellularis is in a constant arms race with its unobliging host to create a niche conducive to its replication and survival. It had been suggested earlier that L. intracellularis did not exploit the autophagosome as an intracellular niche, and thus a mechanism of escape or repression of autophagy was likely to exist (McOrist et al. L. intracellularis. This limited data set provides preliminary data to suggest that the relationship between L. intracellularis and autophagy could be contributing to the clinical manifestation and transmission of PE.As an intracellular pathogen, L. intracellularis to further understand how it survives and replicates in its intracellular niche of epithelial cells in the ileum. Beclin1 had a distinct gradient in uninfected samples, with levels decreasing going up the villi. Although less pronounced, the LC3 gradient augments the Beclin1 observations of autophagy occurring at a higher level closer to the base in crypts of uninfected porcine ileum, augmenting results previously reported in the murine jejunum (Asano et al. Using immunohistochemistry, we investigated the distribution of autophagy pathway proteins in ileum samples infected with L. intracellularis may evade autophagy before p62 inclusion in the pathway and that L. intracellularis does not rely on the maturation of an autophagy-associated vacuole to support survival and replication. The methods required with our VPM53 antibody for L. intracellularis are unfortunately not amenable to being used concurrently with other antibodies, meaning co-localisation of L. intracellularis with the autophagy markers was unable to confirmed in this study, however the distinctive inflammation and loss of cell differentiation characteristic of PE was used to determine L. intracelllularis infected regions.As a mediating protein between ubiquitin and LC3, the degradation of p62 can be used as a proxy for autophagy turnover (Pankiv et al. Autophagy is recognised as being critical to the regulation of the cell cycle. It regulates cellular proliferation, which is the principal driving force of cell migration from crypts to villi and intestinal stem cell differentiation (Parker et al. L. intracellularis.It should be taken into account that the number of cells present in hyperplastic regions will be far greater than in healthy crypts, and therefore the increase in cell number could be accounting for some of the increase in signal intensity detected. However, as only Beclin1 was observed to increase in signal intensity, either the presence of LC3 and p62 is reduced relative to this cell number increase and Beclin1 remains more stable, or Beclin1 increases and LC3 and p62 do not. This consideration emphasises the need for future work to be performed with co-localisation of autophagy markers and L. intracellularis invasion, however more investigations are required to better understand the molecular mechanisms at play.With a contiguous presence on the brush border of healthy porcine villi, Beclin1 may have a role in early detection of bacterial invasion, orchestrating the autophagic response against bacteria capable of penetrating the mucous lining (Benjamin et al. L. intracellularis during PE. These novel insights into L. intracellularis and autophagy provides a framework from which to begin future studies, progressing towards the overarching goal of developing more effective control methods of L. intracellularis to reduce the burden of PE in swine herds and the financial impact it has on farmers.The results from this study have made initial steps into characterising the molecular interactions between the innate immune response of autophagy and


Aim: to study the incidence of hearing alterations in patients with vitiligo. Method: prospective audiological evaluation, transient-evoked otoacoustic emission recordings and study the effects of suppression in 24 patients with vitiligo. Their ages ranged from 15 to 45 years. Results: 21 patients (87.5%) had normal audiometry; 2 had unilateral hearing loss in the high frequencies and 1 had cochlear moderate hearing loss in the left ear. Of these 21 subjects, 66.7% had no otoacoustic emissions, suggesting cochlear dysfunction. Only 7 patients had otoacoustic emissions present in all frequencies (29.2%) and 17 (70.8%) did not have them, and the highest rate of no otoacoustic emissions happened in the right ear of males. Regarding the suppression study, 6 subjects failed, all of them were females, and their left ears were the most affected. Conclusion: the findings show that patients with vitiligo, particularly males, have a greater predisposition to cochlear dysfunction, especially in the right ear. As far as the suppression effect was concerned, there was a greater alteration in the female efferent system, particularly in the left ear. Hearing alterations did not vary as far as age is concerned, type of vitiligo and time of disease progression.Vitiligo is a skin disease characterized by absence of melanin due to melanocytes destruction.  Vitiligo is an idiopathic acquired skin disease characterized by pearl-white patches of diverse shapes and sizes, caused by a loss of melanocytes (cells that synthesize melanin). It affects 1% of the general population, of which about 30% have a family history. It affects every race, and has no sex prevalence. The initial manifestations usually start at an age between 20 and 30 years, although the onset may occur in early infancy.21)auto-immunity - due to frequent associations with other auto-immune disease such as thyroiditis and type I diabetes, the presence of anti-melanocyte antibodies, and a response to immunosuppressant therapy;2)cytotoxicity - the possibility that metabolites formed during melanin synthesis may destroy melanocytes;3)neural - chemical mediators released at nerve endings might destroy melanocytes or inhibit melanin production;4)free radicals - excess free radicals might be toxic for melanocytes;5)convergent - a combination of these theories.The etiology is unknown, but some theories have been used to explain the disease:Alphonse Corti 1831) was the first researcher to mention the presence of pigment cells in the inner ear.1 was theThe inner ear contains many melanocytes, particularly in the basal area of the cochlea, which is responsible for high sound frequencies, those that are affected earlier by ototoxic drugs and intense noise exposure.Carvalho (2004) found that otoacoustic emissions and the high frequency sensitivity auditory function was affected negatively in patients with pigment disorders, such as vitiligo.Recent studies have suggested a direct relation between cochlear dysfunction and decreased amounts of melanin. It is thus thought that melanin has a protective role against harmful agents in the inner ear.The clinical uses of research on otoacoustic emissions and the suppression effect of contralateral noise have grown in importance. These are early detection methods of changes in cochlear function, even before these changes manifest themselves in hearing; they are also fast and non-invasive methods. Additionally, Guedes et al. (2002)The purpose of this study was to verify whether fewer melanocytes altered cochlear function, by measuring and analyzing TOAE, and to verify the function of the medial olivocochlear efferent system, by studying the effect of TOAE suppression in subjects with pigment disorders such as vitiligo.The Research Ethics Committee approved this study (number 1065/06), which was undertaken at the outpatient unit of the Disciplina de Distúrbios de Audição (Hearing Disorders Discipline), Departamento de Fonoaudiologia (Speech Therapy Department), Universidade Federal de Sao Paulo .All participants signed a free informed consent form. The sample in this study consisted of 24 subjects with vitiligo referred to the dermatology department of a university hospital. There were 15 female subjects  and 9 male subjects . The age ranged from 15 to 45 years (mean age - 31.29 years), and the mean duration of the disease was 9.23 years. The inclusion criteria were as follows: no history of otological diseases, no tinnitus, no having been subjected to intense noise, no past use of ototoxic drugs, and no family history of hearing loss. All patients were being treated dermatologically.The clinical history was taken from each participant to establish the inclusion criteria; the external acoustic meatus was inspected to check for conditions that might interfere with the tests and the full audiological assessment. Testing comprised pure tone audiometry (MAICO 41 audiometer with TDH 39 earphones and an MX 41 pad - ANSI-69 standard) at 250 Hz, 500 Hz, 1 KHz, 2 KHz, 3 KHz, 4 KHz, 6 KHz, and 8 KHz in an acoustically treated test suite; normalcy was based on the criteria of the American Speech-language-hearing Association Acoustic immittance tests consisted of tympanometry and investigation of the contralateral stapedian reflex ; normal criteria were an A-type curve and contralateral stapedian muscle reflexes present and with intensities of 70 to 90 dBHL over the threshold.Finally, patients underwent otoacoustic emissions testing  with a non-linear click at 80 microsecond regular pulses (duration of stimulus), a 50 cycle-per-second repetition frequency, and an 80 dBpeSPL  with 3 dBSPL, at a 6 000 Hz bandwidth and a 20 millisecond window. A series of 260 stimuli in blocks of four clicks in each test were presented. Contralateral acoustic stimulation was done with continuous white noise transmitted at an intensity of 50 dBSPL by a TDH 39 earphone to check for the absence or presence of otoacoustic emissions suppression.The following order of tests was used in this study: TOAE in the right ear with no noise; TOAE in the right ear with contralateral noise; TOAE in the left ear with no noise; TOAE in the left ear with contralateral noise.The normalcy criterion was the presence of TOAE 3 dB over noise in each frequency range  with reproducibility equal to or over 70% and probe stability equal to or higher than 70%.The suppression value of the olivocochlear system is given by the difference between values gathered with and with no contralateral stimulation for each ear; this value defines whether there is suppression of the amplitude of emissions or not.14The significance value (p) was 5% (0.050) for the statistical tests and data analysis. The Fisher’s statistics adjusted chi-square test was applied to verify possible differences among categories in each case.Twenty-one (87.5%) of 24 patients with vitiligo  had normal pure tone audiometries, two had unilateral hearing loss (one in the right ear and one in the left ear) between 3 000 Hz and 8 000 Hz, and one had moderate cochlear loss in the left ear; thus, 12.5% of patients had hearing loss. Fourteen (66.7%) of 21 patients with normal audiometries presented partial (at 4 KHz) or absent TOAE, suggesting cochlear dysfunction. There were no sex-related statistically significant differences in conventional audiometry. Emissions were present at all frequencies in only seven patients (29.2%), and absent in 17 patients (70.8%), as shown in Eleven (64.7%) of 17 patients in which TOAE were absent had bilateral failure, and six (35.2%) had unilateral failure. Four (36.3%) of 11 subjects with bilateral failure presented these failures at all frequency bands, and seven subjects (63.6%) had failure only at high frequencies (3 KHz and 4 KHz). Two female patients of six subjects with unilateral failure presented failure at all frequency bands in the left ear, and four patients had failure only at 4 000 Hz, of which three failed in the left ear.There were no statistically significant differences in conventional audiometry as related to the type of vitiligo (p=0.566).Altered emissions were more frequent in males compared to females (77.8% in which TOAE were absent), a difference that was statistically significant only in the right ear (p=0.035).There were no statistically significant differences in the occurrence of TOAE in relation to the type of vitiligo (p=0.648), the duration of disease (p=0.406), or age (p=0.510), as shown in Suppression was investigated in 18 cases with bilateral emissions of the 24 sample subjects. There was bilateral suppression in 12 cases (66.6%), and absence of suppression in six cases (33.3%); all of these patients were female, with a statistically significant difference compared to males (p=0.034).The two cases with unilateral TOAE (right ear only) were also taken into account in the assessment of the suppression effect per ear. The findings revealed that the left ear was more harmed; this difference in the occurrence of suppression relative to the side was statistically significant (p=0.024). Occurrence in the left ear (66.7%) was lower compared to the right ear (95%). The type of vitiligo did not affect the occurrence of suppression.We found in this study that there was a 12.5% hearing loss percentage in conventional pure tone audiometry. In studies on this theme, the evaluation of hearing revealed similar results (decreased hearing).Tosti et al. (1987)Sharma et al. (2004)Aydogan et al. (2005)Carvalho M. (2004)Ardic et al. (1998)Our findings in the present study (hearing loss in 12.5% of subjects) are similar to other published results.Our findings also show that TOAE are a sensitive test for detecting cochlear dysfunction before symptoms become manifest, as TOAE were absent in 66.7% of subjects with normal audiometries. Carvalho M. (2004) concluded that emissions  and high frequency audiometry are sensitive tests for identifying cochlear dysfunction in vitiligo subjects.Additionally in our study, we found increased auditory vulnerability in male subjects, as demonstrated by absent TOAE; this finding is similar to Ardic et al.’s results (1998).We found no published papers on the use of TOAE and the suppression effect in vitiligo.There were no statistically significant differences in the present study related to the duration of vitiligo, or to age. Other published papers have also found no statistically significant differences related to the duration of the disease or age, compared to controls.Patients with suspected retrocochlear dysfunction due to lack of suppression were referred to an Otorhinolaryngologist and for brainstem audiometry.We believe that all vitiligo patients required routine monitoring and audiological assessments by specialists for early identification and monitoring of changes as the disease progresses.Vitiligo patients appear to be more predisposed to cochlear dysfunction, as shown by the absence of otoacoustic emissions, although pure tone audiometry was within normal limits in most of the sample; this group was also more likely to develop changes in the medial olivocochlear efferent system.


Auditory Steady-State Responses (ASSR) are being recognized as a promising technique in the assessment of hearing in children.To investigate the agreement level between results obtained from ASSR and click-ABR in a group of children with sensorineural hearing loss, in order to study the clinical applicability of this technique to evaluate the hearing status in young children.clinical prospective with a cross-sectional cohort.15 children aged between two and 36 months and with diagnosis of sensorineural hearing loss. The correlation between the responses of the two tests was evaluated by intraclass correlation coefficient and McNemar test comparing the probability of responses in both tests.The correlation coefficients were: 0.70; 0.64; 0.49; 0.69; 0.63 and 0.68 respectively for frequencies of 1, 2, 4, 1–2, 2–4 and 1–2-4kHz. In McNemar test p = 0.000, indicating that the probability of obtaining responses in both tests was not equal, but greater for the ASSR.we found good agreement between the techniques among the four frequencies evaluated, suggesting that both tests may be complementary. However, the ASSR was able to obtain additional information in cases of severe and profound hearing losses, adding important data to the management of these children, providing greater accuracy to the audiological diagnosis. With the neonatal hearing screening, aiming at improving the negative aspects associated with congenital hearing loss, there is the need to do an accurate diagnosis of the child's hearing status, in order to start to fit hearing aids and proceed with the necessary interventions. Studies show that the proper sound amplification followed by speech and hearing therapy in the first six months of life maximizes speech and hearing development potential in children with all levels of hearing loss.Nonetheless, to establish the audiometric profile in children in their first months of life is a rather complex task; having seen that it is not possible to obtain reliable results which depend on the behavioral responses from these patients. In this population, the audiologic diagnosis is then based on electroacoustics tests and, mainly, electrophysiological - which assess the integrity of the auditory pathways, enabling an estimate of the child's hearing.It is with such aim that the Brainstem Evoked Response Audiometry (BERA) obtained from the click stimuli (Click BERA) has been broadly used in recent decades. The click is considered more efficient to evoke electrophysiological responses since it stimulates a larger region of the cochlea, resulting in a good neural synchrony through the joint action of a larger number of nervous fibers. Nonetheless, since it is a broad band stimulus, the click is not frequency specific and has its concentration on the higher frequencies (2 to 4 kHz), in such as way that it does not provide information on the hearing loss configuration.In the clinical setting, the specific frequency brainstem evoked potentials (SF-BERA) has been used to estimate the hearing loss configuration. In such technique, the study is done as it is with the click-BERA; however the stimuli used are tonebursts, usually in the frequencies of 0.5, 1, 2 and 4 kHz; or even, 0.5, 1.5 and 4 kHz. Each frequency is studied alone and unilaterally, which extends considerably the test duration.The Stable State Evoked Auditory Potentials (SSEAP) brought about the promise of solving some of the click-BERA and SF-BERA limitations. The use of specific stimuli, introduced simultaneously, enables the assessment of four frequencies at the same time, making the recording of these potentials faster and more specific. The response detection provided by statistical methods brings about a reduction in the risks created by the subjective interpretation; and also the possibility of studying intensity thresholds stronger than the click-BERA and SF-BERA; also enabling the further assessment of the residual hearing in cases of profound hearing loss.7Studies have compared BERA and click-BERA responses showing reasonable correlations among the techniques.In this paper we will discuss the first clinical experiences with the SSEAP in a highly complex hearing health service in São Paulo. The experimental inclusion of the SSEAP among the electrophysiological tests enabled the comparison with the protocol previously established, in other words, the click-BERA. The present study aimed at investigating the level of agreement among the SSEAP and click-BERA tests in a group of children with sensorineural hearing loss, thus studying the clinical applicability of this technique in the audiological evaluation of children.This study was held at the “Audição na Criança” Center – CeAC, serviço da DERDIC – Studies and Rehabilitation of Communication Disorders Division Pontifícia Universidade Católica de São Paulo - PUC/SP, and was approved by the Ethics Committee (protocol # 113/2008). All the guardians of the subjects of the study signed the “Free and Informed Consent Form”, thus consenting with the study and the disclosure of the results, according to Resolution 196/96.We had 15 children with sensorineural hearing loss in the age range between 02 and 36 months  enrolled in the study, adding up to a total of 30 ears. In order to confirm the hearing loss, we held the following procedures, according to the protocol established by the institution's diagnostic team: otolaryngological exam, behavioral audiologic evaluation, immittance measures, transient stimulus and distortion product otoacoustic emission recordings and electrophysiological tests (click-BERA and SSEAP) at the end of the tests, a new otolaryngological consultation is carried out in order to conclude each case studied.The equipment used was the “SmartEP”, from Intelligent Hearing Systems (IHS). The tests were held under natural sleep, and the reference electrodes were placed on the right (A2) and left (A1) mastoids, and the active (Fz) and ground (Fpz) electrodes on the forehead.In order to record the click-BERA we used the rarefaction polarity clicks with 100 μs duration in the repetition rate of 27.7/s. The analysis window was of 20 ms and filters were those of 100 and 3000 Hz. The responses were recorded at 10 dB steps and the maximum intensity used was 90 dBnHL. The criterion used to establish the presence of the response was the visual identification of wave V and its reproducibility.Each stimulus used was made up of the simultaneous combination of 4 tonepipes with the frequencies of 0.5, 1, 2 and 4 kHz, in the modulation frequencies of approximately 77, 85, 93 and 101 Hz on the left ear and of 79, 87, 95 and 103 Hz on the right ear, respectively.We studied the minimum response level (MRL) found for the frequencies of 0.5, 1, 2 and 4 kHz simultaneously in both ears. The MRL were studied at 10 dB steps. As the responses were observed, with electrical noise below 0.05 μV, the test was interrupted and these frequencies were removed. The test in the remaining frequencies was then restarted, in the same intensity. Each simultaneous stimulus was presented bilaterally through ER-3A insertion phones. When it was not possible to do the bilateral test, it was done unilaterally. The initial intensity was deemed audible by the subject based on the behavioral evaluation and did not go beyond 110 dBSPL.The maximum number of stimuli was adjusted for 400 with 1.024s duration each, broken down in 20 scans. The EEG samples after the scanning were filtered with 30–3000 Hz filters, and amplified with a 1,000.0 K gain, and were then processed using an A/D 20 kHz conversion rate. After each scanning, the Fourier Fast Transformation (FFT) was automatically carried out by the software, showing the result obtained in a polar batch and in a frequency spectrum. The F test calculated that the response amplitude likelihood would be significantly different from the modulation frequency background mean amplitude, as well as the background noise mean amplitude in the adjacent frequencies. If the signal/noise ratio was higher than 6.13 dB (p = 0.05) in both conditions, the sign was considered a response.The SSEAP results were transformed from dBSPL to dBHL according to the ISO 389-2 standard for insertion phones, with the corrections −6, −0, −3 and −6 dB respectively, for tones 0.5, 1, 2 and 4 kHz, a criterion already used in a study15 which used the same equipment.The agreement between the SSEAP and click-BERA results was analyzed through the interclass correlation coefficientThe click-BERA responses were compared to the SSEAP ones in the frequencies of 1, 2 and 4 kHz; and also with the mean values of 1–2, 1–4 and 1–2-4 kHz. The frequencies of 1, 2 and 4 kHz of the SSEAP were selected because the click-Bera result, in many cases, can correspond to the best response between 1 and 4 kHz.We carried out twelve comparisons between the pairs. The interclass correlation coefficients found between the SSEAP and the click-BERA are presented on When the two tests were compared in terms of their response likelihood, the SSEAP presented a higher probability than the click-BERA. Results are shown on In order to exemplify the interpretation of this table, we considered the 1 kHz frequence. Of the 30 ears, one (3.3%) did not present an answer in the SSEAP and in the click-BERA; seventeen (56.7%) presented an answer in the SSEAP and no answer in the click-BERA, and twelve (40%), a response present in both tests. We observed the table marginal values, in the click-BERA the response was absent in eighteen ears (60%) and present in twelve (40%); in the SSEAP the response was absent in one ear (3.3%) and present in 27 (96.7%).Below each session in the table we have the p-value obtained in the McNemar test, which compares the probabilities of presence in the two tests, considering that both are applied to the same ears. In the three frequencies we obtained a p=0.000, indicating that the likelihood of a response happening in the two tests is not the same, and the SSEAP probability was higher than in the click-BERA.The coefficients found point to a good agreement between the two techniques in the high frequencies, as already reported by studies which compared the click-BERA with SSEAP in the frequencies of 2 and 4 kHz;The best correlation between click-BERA and SSEAP happened in the frequency of 1 kHz (0.70), followed by the mean value of 1–2 kHz (0.69) and the mean value of 1-2-4 kHz (0.68). The worst correlation was with the frequency of 4 kHz (0.49). These results are similar to the group with the sensorineural hearing loss.The coefficients found in previous studies varied between 0.77 and 0.958,The variability between the coefficients obtained in the different studies can be assigned to the different methodologies employed, as well as the hearing loss configurations which made up the samples. Since the click-BERA can correspond to the best response between 1 and 4 kHz, a sample made up of a larger number of hearing loss with descending configurations, for instance, may present a better correlation with the SSEAP for the frequency of 1 kHz.Swanepoel and EbrahimIn general, the click has its power concentrated between 2 and 4 kHz, indicating hearing loss for the high frequencies; however, in cases of descending hearing loss, its broad band nature may represent the low frequencies.It is still worth stressing that, although the click-BERA is broadly used in the clinical routine in order to estimate hearing thresholds, its relation with the behavioral thresholds is not always exact. Studies from the 70′s and 80′s already reported correlations varying between 0.40 and 0.75 between the results of the click-BERA and the behavioral thresholds.Cone-Wesson et al.When the SSEAP and the SF-BERA were compared as to the probability of response occurrence, the SSEAP presented a much higher probability. Studies have pointed to a SSEAP advantage in estimating the residual hearing in profound hearing loss which will not show responses in the click-BERA.In our findings, the SSEAP indicated a residual hearing in the absence of click-BERA recordings, as in the cases illustrated on It is a consensus that click-BERA recordings are limited to the study of strong intensities. The maximum intensity value available in most of the equipment is 90 to 100 dBnHL, which is not enough to properly measure the profound hearing loss.The continuous stimuli used in the SSEAP recordings enabled us to better study the stronger intensity hearing thresholds when compared to the click-BERA. Nonetheless, there are reports of artifacts and the supposed presence of vestibular responses when the SSEAP are presented in strong intensities.So far, there is no report of any artifact in strong intensities with the system used in this study. Nonetheless, because of the very impossibility of performing a VRA with the insertion phones in many cases, one can not rule out the likelihood of artifacts present, such as in cases 8 and 9 illustrated on Fig.2, in which the VRA was not carried out, or in cases 12 and 13, in which there are responses present in the SSEAP when VRA is not present.It is clear, however, that the cases in which the click-BERA were absent, the SSEAP responses indicated better residual hearing, as in the cases illustrated on Fig.1.The advantages of estimating hearing by frequency specificity and determining residual hearing in the cases of profound hearing loss shown at the SSEAP when compared to the click-BERA are well reported in the literature.However, the click-BERA, also presented advantages which must be considered when one discusses the applicability of the tests in clinical practice, since it adds information which can not be obtained by means of the SSEAP. This information is related to the type of hearing loss, if conductive or sensorineural, and those necessary for the differential diagnosis of the hearing neuropathy.For this reason, we deemed important to use the click-BERA and the SSEAP together, in such a way that one completes and confirms the information of the other; by the same token, logoaudiometry is used to confirm pure tone thresholds, as suggested by Cone-Wesson et al.We must also stress that some studies have suggested that the decisions about referring a patient to cochlear implant are reinforced with the SSEAP, as well as the decision about which ear will be implanted.In fact, although the SSEAP were not routinely done in clinical practice, and even considering that this study is experimental, these potentials add important information. Interpreted together with the other procedures, they enabled the referral of five cases for cochlear implant. In all the cases, the VRA could not be carried out with insertion phones, which differentiates the hearing status of each ear separately.The comparison between the click-BERA and the SSEAP responses in the 1, 2 and 4 kHz frequencies in 15 children with sensorineural hearing loss led to the conclusion that there is a good agreement between the responses of both techniques in the frequencies evaluated. Moreover, the SSEAP brought about additional information in the cases of severe and profound hearing loss. The results obtained from the click-BERA, and the SSEAP recordings tend to add important hearing data, especially when it is not possible to obtain reliable behavioral responses - adding data to the battery of tests with children with hearing loss and providing for an audiological diagnosis and a more accurate hearing aid fitting.


Cochlear Implant is a sensory prosthesis capable of restoring hearing in patients with severe or profound bilateral sensorineural hearing loss.To evaluate if there is a better side to be implanted in post-lingual patients.Retrospective longitudinal study. Participants were 40 subjects, of both sex, mean age of 47 years, with post-lingual hearing loss, users of unilateral cochlear implant for more than 12 months and less than 24 months, with asymmetric auditor reserve between the ears , divided into two groups. Group A was composed of individuals with cochlear implant in the ear with better auditory reserve and Group B with auditory reserve lower in relation to the contralateral side.There was no statistical difference for the tonal auditory threshold before and after cochlear implant. A better speech perception in pre-cochlear implant tests was present in B (20%), but the final results are similar in both groups.The cochlear implant in the ear with the worst auditory residue favors a bimodal hearing, which would allow the binaural summation, without compromising the improvement of the audiometric threshold and the speech perception. A Cochlear Implant (CI) is a sensory prosthesis to restore hearing in bilateral severe-to-profound hearing loss if no Hearing Aid Devices (HAD) is effective. CI indications have been expanded to other types of losses due to technological advances related to software, devices and electrodes, and rehabilitation process.For the indication of CI surgery, a multidisciplinary assessment is necessary, including audiological and imaging tests and etiological diagnosis. These tests are important to predict auditory responses after the speech processor is turned on.CI may be indicated for pre-lingual children with bilateral severe-to-profound sensorineural hearing loss or for post-lingual adults and children.Among the individuals with post-lingual deafness, some have audiometry with asymmetrical curves due to better hearing in one ear in comparison to the other and/or received higher asymmetrical hearing stimulus. After Computed Tomography (CT) image analysis and Magnetic Resonance Imaging (MRI) of the inner ear, excluding the indication of the best ear with good anatomical conditions, it is necessary to choose the side to the CI surgery in order to reach the best audiological results.Some studies indicate the CI device on the best hearing side with the best “hearing reserve” that represents more spiral ganglion cells surviving.Despite the increased possibility of surgical success on the side with better hearing reserve, it is known that unilateral CI provides monaural hearing, without the possibility of stimulation by a hearing device in the other side, limiting the location and sound discrimination in noisy environments.Aiming to offer the patient a possibility for binaural hearing, with bimodal adaptation, hearing aid stimulation in one ear and CI in the other one, was recommended by the International Consensus on cochlear implants in 2005 and some surgeons have chosen the side of poor hearing reserve for CI surgery in an attempt to provide hearing with binaural summation.10Binaural hearing eliminates the shadow effect of the head, which is the obstruction of the head to the arrival of the sound stimulus when it is presented to one ear only; it provides the squelch effect, which is the ability of the auditory system to use the information from both ears when speech and noise are separated spatially and provides binaural summation as a result of central auditory processing to integrate and use the hearing of both ears.The aim of this study is to assess whether there is an indication for the best side for cochlear implants in post-lingual deafness patients.The study was approved by the Ethics Committee under number 56931916.8.0000.5440.A retrospective longitudinal study was conducted using the review of medical records of post-lingual deafness patients undergoing cochlear implant surgery between 2004 and 2014 to evaluate the best audiological response variables such as age at the time of implant, gender, hearing loss time, stimulus time in each ear with hearing aids, sound deprivation time and audiological characteristics of each patient before and after CI were analyzed. To obtain the post-cochlear implant results, audiological results were standardized at the period from 1 to 2 years post-CI.Unilateral CI users with at least one full year using the device, who presented severe to profound asymmetric post-lingual hearing loss and who were 18 years old or older were included in this study. We excluded bilateral CI users, patients with severe to profound hearing loss with pre-lingual hearing loss, younger than 18 years, neuro-psychomotor disorders or meningitis etiology with central nervous system impairment.Patients were divided into two Groups (A and B) according to the implanted side, that is, Group A with patients implanted on the side with the best auditory reserve and Group B, with patients implanted on the side with the worst auditory reserve. Both groups were subdivided for analysis according to the time of hearing deprivation, with time of deprivation below or equal to 10 years and with time of hearing deprivation over 10 years. The auditory deprivation time criterion for dividing the groups was based on reports obtained in the literature.13Group A was composed of patients implanted at the best hearing reserve side, whose pure tone audiometry thresholds at 500 Hz were greater or equal than 10 dB and they reported better hearing at the implanted side. Group B was composed of patients with CI at the worst hearing reserve side, whose pure tone audiometry thresholds at 500 Hz were lower than 10 dB and they reported worse hearing at the implanted side.Data were compared through the non-parametric Mann–Whitney statistical test, in independent samples (between groups) and through Wilcoxon Signed-Rank Sum Test, in paired samples (pre vs. post), as the data did not follow the normal distribution. Therefore, the JMP SAS software, version 10.0  was used.p = 0.2201, Chi square test) and age .Group A was composed of 19 patients implanted in the best hearing side, average age of 49 years (48.6 ± 15.3), 9 men and 10 women. Group B was composed of 21 patients implanted in the worst hearing side, average age of 45 years (45.4 ± 15.1), 6 men and 15 women. There was no difference between the groups regarding gender (p = 0.601). The same occurred with time of hearing deprivation, Group A (10.5 ± 10.2 years) and Group B (10.7 ± 14.0 years) .The time of hearing loss did not differ between Groups A (20.1 ± 11.6 years) and B (22.1 ± 12.4 years) .There was a significant gain in hearing thresholds after CI for both Groups A and B, but when the groups were compared, there was no significant difference in pure tone audiometry at 500 Hz before and after CI or audiometric gain between the two groups  and no difference in audiological gain between the two groups (p = 0.455). For each individual group, gain before and after CI surgery was significant (p < 0.0001 for Groups A and B – Wilcoxon test).By analyzing average hearing level  before and after CI, there was no statistical difference between the Groups A and B . After one year of using the speech processor, there are no significant differences in both groups (p = 0.974). As for each individual group, statistical difference was observed in pre- and post-CI situation  and .Regarding the speech perception tests pre-CI (% accuracy for trisyllable), a better percentage was observed in Group B before CI surgery, but no significant difference in both groups (p = 0.7525 and p = 0.2962), which was also observed in speech perception tests before and after CI (p = 0.0585 and p = 0.2051). We observed statistical difference in the speech perception gain comparing the time of sound deprivation (p = 0.0125) (At 500 Hz in Group A (best side), there was no difference between deprivation time below or equal to 10 years or over 10 years in the pre- and post-CI ( 0.0125) .Table 2Ap = 0.1393 and p = 0.0784) and in the speech perception tests pre-CI (p = 0.2038) or speech perception gain (p = 1.0000) (p = 0.0130)  . When sp 0.0130) .Table 3Ap = 0.0352) (p = 0.4751)  , which d 0.4751) .Table 4AThe electronic device in CI is the most effective prosthesis in the medical history and is a unique sensory prosthesis to restore sensorial deprivation. CI indications have undergone evolutionary times and have depended on the technological development, on the improvement of surgical techniques and the training and qualification of interdisciplinary teams involved with all stages of the implantation process, which have allowed this technology to benefit people with varying degrees of hearing loss at different hearing deprivation times.By comparing Groups A and B in pre-CI, we observed no difference in the pre- and post-CI average values at 500 Hz; but we observed better performance in the perception test pre-CI (trisyllable) in Group B (Group A – 9% and Group B – 20%).This finding may be explained by the fact that most individuals in Group A presented profound bilateral hearing loss, when frequencies from 500 to 8000 Hz were taken into consideration and these patients have been implanted in situation of worse bilateral reserve than in Group B. Despite the difference in the audiometric threshold, no statistical difference was found when the preoperative Speech Perception Test (SPT) results between the two groups were compared. Individuals from both groups performed well in the postoperative SPT , in line with the findings of Boisvert et al.This similar SPT results for both post-CI groups may be attributed to the fact that implanting the CI device in the patients’ worst hearing side – the worst hearing reserve side – allowed them to use the hearing aid device in the CI-contralateral side after the surgery, allowing bimodal hearing over at least one year after CI. This would allow a better perception or understanding of words that prove CI-unilaterally favoring central binaural stimulation of mechanisms that facilitate the best hearing performance for the worst ear, even if analyzed separately. Another aspect is that in our sample we assume that patients had the same hearing rehabilitation, which cannot be assured because this aspect cannot be completely controlled in a retrospective sample. The results presented in Unlike Firszt et al.,p = 0.0125) and on Group B, we observed better performance on post-CI SPT in the group with shorter sound deprivation time (p = 0.0130), indicating that the greater the sound deprivation time, the worst negative correlation in postoperative SPT, as demonstrated by Portmann et al.By comparing Groups A and B regarding time of sound deprivation, we observed an improvement in speech gain for the shorter sound deprivation time on Group A . They showed a worse sound in postoperative audiometric average.These results show that the choice for the best hearing reserve or worse reserve does not interfere with audiological results presented in the post-operative when the patient is below 10 years of sound deprivation and shows what can actually interfere with post-CI result, even in post-lingual individuals, is hearing deprivation time over 10 years, and allows us to assume that the stimulation of the central auditory pathways is dependent only on the presence of sound stimulus and not its laterality.Articles with level evidence 2a, 2b and 2c show that the benefit post-CI for speech perception seems to be more positively correlated to the integrity of the auditory central nervous system pathways than the functional status of the inner ear and auditory nerve. In patients with asymmetric hearing loss, when only one ear will be implanted, the best choice for the cochlear implant is the ear with worse hearing threshold.It is worth highlighting the need for further studies in this area, with a larger number of subjects in order to ensure better understanding of the contribution of the contralateral ear to the CI in the obtained results.There was no statistical evidence when comparing Groups A and B in relation to the (better or worse) side with CI implant, in relation to the average values of the obtained auditory thresholds and the perception and speech test.There was a significant difference between the studied groups when the time of hearing deprivation was compared.The choice of implanting the internal IC device in the ear with worse auditory reserve and shorter time of sound deprivation may favor bimodal hearing, which would allow binaural summation without impairing the audiometric threshold improvement and speech perception.The authors declare no conflicts of interest.


We present the case of a patient treated as affected by conductive hearing loss due to recurrent otitis, then as a juvenile otosclerosis, who was finally diagnosed as affected by bilateral ossicular chain fixation and enlarged vestibular aqueduct by means of cone-beam CT. Conductive hearing loss is an extremely frequent condition during childhood, especially in the first years of life, when anatomical, immunological, and social conditions favor the high incidence of recurrent otitis media .This condition typically causes a conductive hearing loss that might have a tremendous impact on the child’s development since an impaired hearing function can cause delays in speech development and mid-to-long-term consequences on the child’s quality of life .The extremely high prevalence of this condition in the first years of life makes the correct characterization of congenital hearing loss very challenging, especially in complex and fragile patients . Indeed, the occurrence of the combination of different rare conditions might mimic this extremely frequent pathology, and only patient performance in behavioral audiological tests is sometimes able to produce a correct diagnosis of hearing loss.All of the conditions that might cause conductive or mixed hearing loss frequently require multiple examinations to reach a good characterization of the hearing deficit. The audiological evaluation is frequently followed by radiological imaging and, in some cases, by genetic testing. Only the collection of all these data can lead to an accurate final diagnosis.Herein, we report the case of a patient diagnosed and treated first as affected by recurrent otitis media, then as affected by otosclerosis. In the end, it was recognized to be a case of congenital ossicular chain fixation and concomitant enlarged vestibular aqueduct (EVA).A 13-year-old boy presented to our tertiary referral center with mixed mild–moderate bilateral hearing loss, worse on the left side .Clinical history indicated previous surgeries for lingual frenectomy and multiple tympanostomic tubes. He also underwent speech rehabilitation for speech delay. Apart from borderline cognitive function, no other major diseases were reported.Upon clinical ENT examination, otoscopy was negative for inflammatory or infectious middle ear pathologies.The information concerning previous audiological examinations was scattered. In different centers, the bilateral hearing loss was deemed to be conductive in the first years of life, but as the boy grew up, the better-characterized mixed hearing loss was interpreted as juvenile otosclerosis, and stapedotomy was performed on his right side. Air conductive hearing aids were suggested, although the patient, especially after surgery, preferred to use it only on his left ear.At this point, the patient was referred to our center to obtain a second opinion, given the unsatisfactory hearing improvement after surgery. A cone beam computed tomography (CBCT) of the temporal bone was performed, revealing bilateral enlarged vestibular aqueducts (EVAs) associated with a malformation of the ossicular chain, which appeared bilaterally fixed to the upper lateral wall of the middle ear . The vesOtitis media, with its recurrent course in most patients, is the most frequent cause of conductive hearing loss in the first years of life: it is estimated that in the post-pneumococcal conjugate vaccine era, about 60% of children aged less than 4 years have ≥1 episode of acute otitis media [Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis [In the acute phase of the disease, the most common symptoms are very non-specific and may include fever, otalgia, headache, irritability, cough, rhinitis, listlessness, anorexia, vomiting, diarrhea, and pulling at the ears . These, arrhalis , and antarrhalis . For recarrhalis , even ifarrhalis . Moreovearrhalis . In factarrhalis , mastoidarrhalis .In children with persistent hearing loss following tympanostomy tube placement, an accurate characterization of the type and the side of the hypoacusis should be made: if bilateral hearing loss is present, imaging and genetic testing should be considered (such as what happened regarding our patient), to identify a possible syndrome. Patients with mixed hearing loss should be evaluated for middle/inner ear anomalies .The difficulty in addressing the possible hearing loss in children is that multiple non-disease-related factors can impair pediatric audiological evaluation . Some patients might also be affected by specific conditions that impair the diagnostic process: those factors could be represented by other comorbidities that need to be addressed before the hearing management or by the presence of cognitive and behavioral issues which might impair the audiological evaluation.Based on the age of the patient, the diagnosis of hearing loss might be reached using different techniques: for infants under the age of 6 months, auditory brainstem response or otoacoustic emissions; for children up to two years of age, behavioral audiometry, and after this, conditioned play audiometry . AlthougWhen the first-line treatments continue to fail in treating conductive hearing loss, an in-depth evaluation should be performed, adding both objective audiological tests  and radiological imaging .It is recommended to perform computed tomography (CT) using both the Axial and the coronal planes because they are complementary in visualizing all of the different ear structures . The mosIf we are talking about rare causes of conductive congenital hearing loss, congenital middle ear anomalies, defined as malformations of the auditory ossicles of any type, should be considered. The ossicular chain has an embryological origin from the branchial arches  , and malClass 1: ears with congenital isolated stapes ankylosis.Class 2: ears with congenital stapes ankylosis and a congenital anomaly of the ossicular chain.Class 3: ears with congenital anomalies of the ossicular chain and at least a mobile stapes footplate.Class 4: ears with aplasia or severe dysplasia of the oval window or round window.Usually, class 3 anomalies comprise the majority of middle ear anomalies, while class 4 is the one with the worse post-surgical hearing outcomes . Our patOther causes of juvenile hearing loss identifiable with CT are progressive diseases of the middle ear that can cause fixation, decalcification, or fractures of the ossicles . These conditions cause mixed hearing loss when combined with inner-ear-derived sensorineural hearing loss, but in some cases, the progression of the abovementioned pathologies within the otic capsule, such as a chronic infection/inflammation or cholesteatoma, can cause a mixed hearing loss with a single etiology. CT can also visualize the presence of otosclerosis, characterized by osteo-rarefaction and otospongiosis at the fissula ante fenestram with frequent inner ear involvement .Additionally, some inner ear malformations may cause mixed hearing loss. It is crucial to identify these anomalies because the management and course of hearing loss may be extremely different among these conditions. For example, incomplete partition type 2, incomplete partition type 3, or cochlear hypoplasia may show similar audiological characteristics, but the anatomical features are extremely different.In our patient, a concomitant EVA was revealed by CT examination.EVA is the most commonly identified malformation of the temporal bone, and it is reported to be the most common inner ear malformation associated with congenital hearing loss . EVA canThe diagnosis of EVA is based on high-resolution, fine-section CT scans of the temporal bone. According to Valvassori and Clemi’s criteria, EVA can be diagnosed if the diameter of the aqueduct is ≥ 1.5 mm at the midpoint or ≥ 2 mm at the operculum, as in our case . In someAlthough an EVA could be observed alone, it may also be associated with cochlear and modiolar defects , even if the literature is scarce regarding its association with middle ear defects, such as the case of our patient .Moreover, clinically speaking, EVA can be an isolated finding, or it can be associated with specific syndromes, such as Pendred, Waardenburg, or branchio-oto-renal syndrome .The course of hearing loss is often progressive, starting from normal/almost normal hearing thresholds and worsening over time towards a conductive/mixed type, ranging from mild to profound. Hearing loss can be conductive , sensorineural , or mixed (due to combined causes) .Vestibular symptoms are often present in these patients, although infrequently investigated, because they are subjectively less relevant than the cochlear ones . UnilateEven if imaging is not sufficient to explain still open questions about the above-mentioned conditions (i.e. the pathophysiology of EVA), in our opinion, it should have been performed earlier in this patient.The conductive component of hearing loss cannot be resolved by stapes surgery, which may still be reasonable for stapes fixation and ossicular anomalies (without concomitant inner ear pathologies). In the literature, satisfactory outcomes are reported if incus continuity and mobility are preserved . UnfortuIn general, patients with EVA are expected to show mixed hearing loss due to inner ear mechanisms, and middle ear surgeries probably can only provide a temporary benefit. Indeed, a great number of patients with EVA present fluctuating hearing loss worsening over time, which requires air-conduction hearing aids or even cochlear implantation.The previously described functional and anatomical data are crucial for the management of these patients and for the choice among surgical options among different types of hearing rehabilitation.The patient is currently living a normal life, fully integrated into society. He is scheduled for regular audiological evaluations, with seriate vocal and tonal audiometry, to early detect a possible worsening in his hearing function.The combination of a malformation of the ossicular chain along with enlarged vestibular aqueduct (EVA) is an extremely rare condition. Our patient was treated for a long time as though affected by simple conductive hearing loss due to recurrent otitis media, and imaging was performed very late in his clinical history. Indeed, the results of the cone beam computed tomography (CBCT) scan would have been crucial for the improvement of overall clinical management, saving time and unnecessary procedures.This case demonstrates that clinicians should be aware that a combination of rare conditions might occur, and we should also expect the unexpected.


Although most patients diagnosed with early‐stage cutaneous melanoma (CM) have excellent outcomes, because of the large number diagnosed each year, many will experience recurrence or death. Prognostic testing for CM using the 31‐gene expression profile (31‐GEP) test can benefit patients by helping guide risk‐appropriate treatment and surveillance plans. We sought to evaluate patients' attitudes toward prognostic testing with the 31‐GEP and assess whether patients experience decision regret about having 31‐GEP testing.A 43‐question survey was distributed by the Melanoma Research Foundation in June–August 2021 to CM patients enrolled in their database. Patients were asked questions regarding their decision to undergo 31‐GEP testing and the extent to which they experienced decision regret using a validated set of Decision Regret Scale questions.n  = 120). Of these, 28 had received 31‐GEP testing. Most respondents  desired prognostic information when diagnosed. Of those who received 31‐GEP testing, most felt the results were useful (n  = 22 out of 24) and had regret scores significantly less than neutral regret, regardless of their test results . Further, decision regret scores were not significantly different between patients who received a Class 1 31‐GEP result and those who received a Class 2 result .We analyzed responses from patients diagnosed in 2014 or later (Most newly diagnosed CM patients desired prognostic information about their tumors. Patients who received 31‐GEP testing felt it was useful and did not regret their decision to undergo 31‐GEP testing. Prognostic testing for CM using the 31‐gene expression profile (31‐GEP) test can benefit patients by helping guide risk‐appropriate treatment and surveillance plans. A 43‐question survey regarding their decision to undergo 31‐GEP testing and the extent to which they experienced decision regret was distributed by the Melanoma Research Foundation to CM patients. Most newly diagnosed CM patients desired prognostic information about their tumors. Patients who received 31‐GEP testing felt it was useful and did not regret their decision to undergo 31‐GEP testing. It is important to incorporate more accurate prognostic testing methods to identify patients at high risk of poor outcomes, particularly because planned imaging studies are effective at identifying metastatic spread early and there are now effective adjuvant therapies available for patients with CM. Similarly, patients with a low risk of poor outcomes can avoid an unnecessary sentinel lymph node biopsy surgical procedure.It has been suggested that a poor prognosis could potentially cause patients to regret their decision to undergo prognostic testing; however, few studies have formally assessed decision regret levels after prognostic testing for CM.Molecular‐based technologies for predicting CM outcomes have been of recent interest. The validated 31‐gene expression profile test (31‐GEP)  that analyzes differential gene expression of a validated panel of 31 gene targetsThe objective of the present study was to understand patients' attitudes toward prognostic testing generally and with 31‐GEP testing specifically, and to assess whether patients who had 31‐GEP testing experienced regret about their decision.22.1A 43‐question online survey Appendix  was distn = 120), at which time 31‐GEP prognostic testing became available, or if the respondent reported that they had received 31‐GEP testing and reported a test result.The 31‐GEP test was made clinically available in 2013. To capture the first full year of clinical use, we only analyzed those responses in which participants self‐reported a melanoma diagnosis in or after 2014 . Participant demographics are shown in Table We included all responses for patients diagnosed in 2014 and later in our analyses  . Few patients reported that their provider had discussed 31‐GEP testing with them at the time of their diagnosis, including 11 patients who received 31‐GEP testing and five who did not receive 31‐GEP testing. Of respondents who did not have 31‐GEP testing, 53.8% wished they had been offered the option of 31‐GEP testing, 37.5% did not know, and 8.8% did not wish they had been offered testing (data not shown).Most respondents desired prognostic information about their tumors at diagnosis n = 08, 90% . Of those who had concerns, they included cost , accuracy , impact of poor prognosis on mental/emotional health , and having sufficient tumor material available for other tests  (data not shown).When asked what factors impacted their decision to get 31‐GEP testing, respondents stated they wanted all the information they could have about their tumor (76.9%), their healthcare provider recommended it (69.2%), they thought it would better inform their treatment decisions (46.2%), and they wanted to better understand their future (30.8%) .To assess survivorship bias in the survey results, we compared the results of patients diagnosed at least 3 years previously (before 2019) with those diagnosed recently (between 2019 and 2021). These time frames were selected because adjuvant therapies and increased surveillance for CM often continue 2–3 years post‐diagnosis, and we wanted to reflect this in our comparison. Chi‐square analysis did not find significant differences between patient concerns for those diagnosed recently versus more than 3 years ago (p = 0.30).Respondents generally felt that the test results were easy to understand; 22 out of 24 respondents stated the results were very or somewhat easy to understand, while 2 out of 24 stated the results were difficult or very difficult to understand . None of the respondents answered that they had increased (decision regret score of 4) or high (decision regret score of 5) levels of regret to any of the questions. Average individual decision regret scores were not significantly different between respondents who received Class 1 or Class 2 GEP test results  , demonstrating that none of the respondents regretted their decision to undergo 31‐GEP testing. Because so few patients reported receiving a Class 2 result, we could not statistically analyze their responses for survivorship bias. However, we found no statistically significant differences in decision regret scores between patients diagnosed before 2019 and those diagnosed in 2019–2021 who received Class 1 results (p = 0.54) (data not shown).Twenty‐one respondents who received 31‐GEP testing answered the questions related to decision regret , which is not surprising given that women are more likely to complete surveys than males.4.2Our data suggest that patients are generally satisfied with their decision to get 31‐GEP testing, even when their result indicates a high risk of developing metastases. Indeed, respondents indicated that the results provided relief from uncertainty about the future and additional information relevant to life planning decisions, similar to patients who undergo genetic testing to assess the risk of familial melanoma or prognostic testing for uveal melanoma.5Patients diagnosed with CM desire prognostic information about their tumors. Patients who received 31‐GEP testing felt that the 31‐GEP test relieved them of uncertainty, provided them important information to help with management‐ and treatment‐related decision‐making and planning for the future, and they did not regret their decision.Kelli Ahmed, Jennifer J. Siegel, and Kyleigh LiPira conceptualized the study; designed the survey, and collected survey data; Jennifer J. Siegel provided statistical support and data analysis; Sonia K. Morgan‐Linnell and Jennifer J. Siegel analyzed study data; Sonia K. Morgan‐Linnell wrote the original draft of the manuscript; and all authors critically reviewed and edited the manuscript. All authors have read and agreed to the published version of the manuscript.This study was funded by Castle Biosciences, Inc.Kelli Ahmed, Jennifer J. Siegel, and Sonia K. Morgan‐Linnell are employees and options holders at Castle Biosciences, Inc. Kyleigh LiPira has no conflicts of interest to declare.The study received exemption from Institutional Review Board review by Advarra IRB .The study was considered exempt from written informed consent and IRB review by the Advarra IRB.Appendix S1Click here for additional data file.