The mechanisms of this SNHL are postulated to involve alterations in the inner ear’s microenvironment mediated by the genetic cargo of VS-secreted extracellular vesicles (EVs). We aimed to identify the EV cargo associated with poor hearing and determine whether its delivery caused hearing loss and cochlear damage in a mouse model VS tissue was collected from routinely resected tumors of patients with good (VS-GH) or poor (VS-PH) pre-surgical hearing measured via pure-tone average and word recognition scores. Next-generation sequencing was performed on RNA isolated from cultured primary human VS cells and EVs from VS-conditioned media, stratified by patients’ hearing ability. microRNA expression levels were compared between VS-PH and VS-GH samples to identify differentially expressed candidates for packaging into a synthetic adeno-associated viral vector (Anc80L65). Viral vectors containing candidate microRNA were infused to the semicircular canals of mice to evaluate the effects on hearing, including after noise exposure.Differentially expressed microRNAs included hsa-miR-431-5p (enriched in VS-PH) and hsa-miR-192-5p (enriched in VS-GH). Newborn mice receiving intracochlear injection of viral vectors over-expressing hsa-miR-431-GFP, hsa-miR-192-GFP, or GFP only (control) had similar hearing 6 weeks post-injection. However, after acoustic trauma, the miR-431 group displayed significantly worse hearing, and greater loss of synaptic ribbons per inner hair cell in the acoustically traumatized cochlear region than the control group.Our results suggest that miR-431 contributes to VS-associated hearing loss following cochlear stress. Further investigation is needed to determine whether miR-431 is a potential therapeutic target for SNHL. AlthougThe etiology of VS-induced SNHL was long believed to be compression of the adjacent auditory nerve by the VS tumor, but multiple studies including diverse cohorts have failed to find a correlation between sporadic VS tumor size and the degree of a patient’s SNHL , and havThere is emerging evidence of differential gene expression and protein production in VS tumors from patients with preserved auditory function [good hearing (GH)] and those with severe-to-profound SNHL [poor hearing (PH)] . For exaA potential mechanism facilitating VSs’ negative impact to hearing is the secretion of exosomes, such as extracellular vesicles (EVs), which contain ototoxic cargo. EVs are lipid-membrane vesicles measuring ~30–200 nm and are released into the extracellular space by most cell types, including normal and neoplastic cells . They arin vitro, with varying effects depending on the hearing status of the VS donor , for candidate testing in mice to determine their effects on hearing sensitivity and cochlear cell integrity in vivo, including following noise exposure.Using a dual culture system, we have previously reported that EVs are produced by VSs and can be internalized by cochlear cells VS donor . SpecifiVS donor . These f2.2.1.N = 13). Patients’ age at resection, sex, tumor volume, and pre-surgical bilateral audiometric thresholds at six standard frequencies , and bilateral word recognition (WR) scores were recorded from patients’ medical files. Once the VS was removed, the specimen was transported from the operating room to the laboratory on ice. Primary culture was then performed as we have previously described (Patients presenting at Massachusetts Eye and Ear (MEE) in Boston, MA for VS resection between April 25, 2014 and October 10, 2014 were included in the study , purified by high-speed centrifugation to deplete EVs from the FBS. After 48 h, conditioned media were collected and centrifuged for 10 min at 300 g, then 10 min at 2000 g at 4°C. The supernatant was filtered through a 0.8 μm filter . EVs were pelleted by centrifugation at 100,000 g for 80 min at 4°C in a Type 70 Ti Rotor .The particle distributions (EVs) from the cells were measured using a Nanosight LM20 machine . A human NF2 VS-derived cell line (HEI-193) immortalized with human papilloma virus E6-7 genes was acquired from House Ear Institute   and used2.3.After centrifugation, the EV pellet was submerged in 4 μL of rDNAase 1  for 1 min and then incubated in 8 μL of Superasin  for 4 min at room temperature (RT) covered in paraffin. The pellet was resuspended in 700 μL of lysis buffer  by pipetting. After the Eppendorf tubes were left 3–5 min at RT, 140 μL chloroform was added and mixed by shaking for 15 s, and the phases were allowed to separate for 2–3 min at RT. This process was repeated twice. The tubes were centrifuged for 15 min at 12,000 g at 4°C. The upper aqueous phase was transferred to a new tube and the volume recorded; 1.5x volumes of 100% ethanol were added and mixed thoroughly by pipetting and vortexing. Approximately 500 μL of the sample was immediately transferred to Rneasy Mini spin columns  and centrifuged with serial applications of washing buffers according to the manufacturer’s instructions. The spin column was transferred to a new 1.5 mL collection tube and rinsed with 32 μL 95°C Rnase-free water for a final elution volume of 30 μL (minus the column volume). The sample was centrifuged for 1 min at 100 g to slowly allow the elution solvent to penetrate the column and then again at 8500 g for 1 min to elute the RNA. This process was repeated with an additional 32 μL 95°C Rnase-free water added to the spin column membrane, in the same collection tube.For the extraction of RNA from VS cells, after the medium was aspirated and the wells were washed with 1 mL of PBS, 200 μL of 0.25% Trypsin–EDTA  was added and allowed to sit for 5 min at 37°C. New media (800 μL/well) was added and mixed by pipetting, then transferred to 1.5 mL sterile Eppendorf tubes. The tubes were centrifuged at 300 g for 2 min at RT, the supernatant was aspirated, and 1 mL PBS was mixed with the pellet. Samples were centrifuged again at 300 g for 5 min at RT and supernatant removed. At this point, the procedures are the same as those described above, beginning with the application of QIAzol Lysis Reagent.2.4.The quantitative and qualitative analyses of the extracted RNA were performed using the NanoDrop spectrophotometer 2000 (Thermo-Scientific) and Agilent Bioanalyzer 2,100, using the RNA 6000 Pico kit  for RNA from EVs and the RNA 6000 Nano kit (Agilent) for cellular RNA.2.5.All samples were processed using the sRNAseq pipeline developed by the bcbio-nextgen project . Raw rea2.6.12 GC/mL) and stored at −80° C.Viral vectors were synthesized by the Gene Transfer Vector Core at MEE or the Boston Children’s Hospital Viral Core, as previously published . Vectors2.7.CBA/CaJ (strain #000654) breeding pairs were purchased from Jackson Laboratories  and bred at MEE. Neonatal pups were anesthetized by hypothermia and then kept on an ice pack during the procedure. A small incision was made in the left post-auricular region, and the sternocleidomastoid muscle identified. Muscle and soft tissue covering the posterior semicircular canal were gently removed with fine forceps. The semicircular canal wall was punctured with a beveled 35G Hamilton syringe , the tip was visualized in the canal, and 1.5 μL vector solution was slowly injected over 3 min. The syringe was removed, and the surgical incision closed with 7–0 Ethilon surgical suture . Animals were marked by paw tattoos, allowed to recover on a heating pad, and returned to their litter.2.8.Cochlear function was evaluated in the mice by measuring auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) 2–4 days before noise exposure at 6 weeks of age. Two weeks after noise exposure, cochlear function was re-assessed by ABR and DPOAE, the animals were sacrificed, and their cochleae were collected for histological analysis. ABR and DPOAE were recorded as previously described ; mice weABR responses to 5 ms tone pips were measured between subdermal electrodes , amplified 10,000 times, and filtered (0.3–3.0 kHz). For each frequency and sound level, 512 responses were recorded and averaged using custom LabVIEW data-acquisition software run on a PXI chassis . The ABR waveforms were stacked from lowest to highest SPL and visually inspected to define threshold as the first level at which a repeatable wave I was detected. ABR data were acquired in 5-dB intensity increments below threshold and at 5- to 10-dB increments above threshold.For DPOAE measurement, a custom acoustic system was used consisting of two miniature earphones serving as sound sources  and a microphone  coupled to a probe tube to measure sound pressure near the eardrum. DPOAEs were measured as ear canal pressure in response to two tones presented into the ear canal  at half octave steps, from f2 = 5.66–45.25 kHz, and in 5-dB intensity increments from 15 to 80 dB SPL.2.9.Mice were exposed to octave-band noise (8–16 kHz) for 2 h at 100 dB SPL in a reverberant, acoustically transparent wire box on a rotating platform. Animals were awake and unrestrained during noise exposure. The noise was created digitally using a fifth-order Butterworth filter, amplified through a power amplifier , and delivered by a loudspeaker  coupled to an exponential horn in the roof of the box. Exposure levels were measured in each cage with a 0.25-inch Brüel and Kjaer  condenser microphone.2.10.Two weeks after noise exposure, the mice were deeply anesthetized, intracardially perfused with 4% paraformaldehyde , and both cochleae were extracted. The round and oval window membranes were punctured and gently perfused with PFA. Cochleae were post-fixed for 2 h in 4% PFA and decalcified in 0.12 M EDTA  for 48–72 h. The cochleae were microdissected into 4 to 6 separate pieces to prepare whole mounts of the organ of Corti. Pieces were incubated in 30% sucrose for 15 min at room temperature and then frozen at −80° C to permeabilize the tissue. The pieces were blocked with 5% normal horse serum  and 1% Triton X-100  in PBS  for 30 min at RT.2.11.Cochlear samples were immunostained overnight at RT with rabbit anti-myosin 7A  to label hair cells and mouse (IgG1) anti-CtBP2  at 1:500  to label pre-synaptic ribbons, diluted in 1% NHS  and 0.3% Triton X-100. After washing in PBS three times, cochlear pieces were incubated in Alexa Fluor 647-conjugated goat anti-rabbit antibody at 1:1000  and Alexa Fluor 568-conjugated goat anti-mouse (IgG1) at 1:1000  twice for 1 hour. Nuclei were stained with Hoechst 33342 at 1:10000  and the specimen washed three times in PBS and mounted with VECTASHIELD mounting medium . A cochlear frequency map was created by imaging specimens at low magnification (10X objective) and then applying a custom ImageJ plug-in developed at MEE.2.12.Clinical data and samples were collected and used according to a protocol approved by the institutional review boards of MEE  and all procedures were in accordance with the Helsinki Declaration of 1975. All patients provided informed consent prior to study inclusion. Patients did not receive compensation for their participation in the study. The experimental procedures in mice were approved by the Institutional Animal Care and Use Committee of MEE (ACC# 15–003) and conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals.3.3.1.VS tumor samples from 13 people with sporadic VS were collected during indicated tumor resection surgeries . Patient3.2.The VS-GH and VS-PH specimens were separately cultured in EV-depleted culture media for 48 h to generate conditioned media as previously described . Primary3.3.Total RNA (including sRNA) was extracted from EVs isolated from VS cell-conditioned media and parent cells and the quality assessed with a Bioanalyzer (see example in 3.4.2 fold change [FC]: 2.39), hsa-miR-192-5p (log2 FC: −0.66), and hsa-miR-431-5p   (Illumina HiSeq2500 platform), and the miRNA dispersion plotted by the mean of the normalized counts and analyzed as described in the Methods . A total < 0.01) . No miRN3.5.in vivo, two AAV vectors associated with PH and GH, respectively, were constructed: hsa-miR-431-overexpressing AAV2/Anc80L65.AAP.U6.mir413.CMV.EGFP.SVPA and hsa-miR-192-overexpressing AAV2/Anc80L65.AAP.U6.mir192.CMV.EGFP.SVPA. An additional vector (AAV2/Anc80L65.CAG.GFP.WRPE) was constructed as a GFP-only control. Postnatal day (P) 1–2 CBA/CaJ mouse pups from four litters were randomly assigned to an AAV injection group: GFP-only control (n = 7), hsa-miR-192 (n = 6), or hsa-miR-431 (n = 6). The mice were injected intracochlearly via the semicircular canal with 1.5 μL vector solution over 3 min. At ~6 weeks of age (post-injection), baseline hearing was evaluated in the mice by measuring ABRs and DPOAEs, which reflect auditory evoked potentials and OHC function, respectively. Hearing was normal and there were no significant differences in hearing between the groups   2 to 4 days after assessment of their hearing function. At 2 weeks post-noise exposure, hearing was again assessed with ABR and DPOAE. Mice injected with the AAV overexpressing miR-431 had a 20 dB ABR threshold shift from baseline at 16 kHz that was significantly higher compared to the GFP-only control group ( < 0.01) . Mice in < 0.01) .p < 0.01)  and pre-synaptic ribbons (CtBP2-positive) (16 kHz region displayed in  < 0.01) . There w4.In this study, miR-431-5p was found to be significantly more abundant in VS tumor cells from patients with poor hearing than those with good hearing, pointing to a potential miRNA candidate contributing to VS-associated hearing loss. Although viral overexpression of miR-431 in the inner ear of mice produced no initial negative effects on hearing, following noise exposure, these mice exhibited significantly greater hearing loss, as well as greater loss of IHC synapses in the cochlear region most affected by the noise trauma. These results suggest that miR-431, enriched in the VS tumors of patients with poor hearing, may sensitize the cochlea to stress-induced trauma, including from noise, and the development of subsequent hearing loss. Our findings provide mechanistic insight into the clinical observation that patients with VS demonstrate increased susceptibility to acoustic trauma , and thaWhile there are two prior reports identifying a role for miR-431 in hearing function and dysfunction , 42, theEya4, with higher expression of miR-431 resulting in decreased production of the protein EYA4  of patients with VS and/or hearing loss are recommended to understand how it may circulate within the body to potentially impact hearing. Moreover, future large-scale epidemiologic studies should determine whether noise trauma is a modifiable risk factor for VS-induced hearing loss. The results of these studies, combined with the current results, may motivate future development of molecular therapeutics that inhibit miR-431 in order to prevent VS-induced hearing loss.https://stanfordmedicine.app.box.com/s/sq3nidp5l141qu27le3qvmx909wywsex.The data presented in this study are deposited in the Stankovic Lab website, accessible directly at: The studies involving humans were approved by the institutional review boards of Massachusetts Eye and Ear (#196424). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. The animal study was approved by Institutional Animal Care and Use Committee of Massachusetts Eye and Ear (ACC# 15-003). The study was conducted in accordance with the local legislation and institutional requirements.TF: Formal analysis, Methodology, Writing – original draft, Writing – review & editing, Data curation, Investigation, Validation, Visualization. RS: Formal Analysis, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing. S-YK: Methodology, Writing – review & editing, Validation. VS: Methodology, Writing – review & editing, Investigation. LP: Investigation, Methodology, Writing – review & editing, Formal analysis. RK: Formal analysis, Investigation, Methodology, Writing – review & editing. LL: Investigation, Methodology, Writing – review & editing. SB: Writing – review & editing, Visualization, Writing – original draft. KS: Writing – original draft, Writing – review & editing, Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Software, Supervision.


The development of the central auditory system, including the auditory cortex and other areas involved in processing sound, is shaped by genetic and environmental factors, enabling infants to learn how to speak. Before explaining hearing in humans, a short overview of auditory dysfunction is provided. Environmental factors such as exposure to sound and language can impact the development and function of the auditory system sound processing, including discerning in speech perception, singing, and language processing. Infants can hear before birth, and sound exposure sculpts their developing auditory system structure and functions. Exposing infants to singing and speaking can support their auditory and language development. In aging humans, the hippocampus and auditory nuclear centers are affected by neurodegenerative diseases such as Alzheimer’s, resulting in memory and auditory processing difficulties. As the disease progresses, overt auditory nuclear center damage occurs, leading to problems in processing auditory information. In conclusion, combined memory and auditory processing difficulties significantly impact people’s ability to communicate and engage with their societal essence. Previous work initiated with Merzenich, Kaas, Mishkin, and Rauschecker demonstrated that the auditory cortex (AC), particularly in monkeys and humans, receives input from the medial geniculate body (MGB) and shows the best frequency along the lateral sulcus . The audSpeech, pitch, loudness, timbre, rate, phrasing, and non-verbal vocalizations convey human sounds and emotions. The ability to receive and interpret this information is unique to humans ,6. The eMoreover, the whales’ brain–body size ratio is similar to humans, providing an objective measure for the singing space . DolphinNevertheless, the sound production mechanisms vary across mammals and birds ,13. LikeInterestingly, sound production may be controlled by similar motor neuronal input in fish, frogs, birds, and mammals ,19. The Fmr1 [Shank3 [Pten [Cntnap2 [Dyslexia is a polygenic developmental disorder characterized by a phonological and auditory deficit, often associated with changes in the micro-architecture in the temporal lobe ,22. ReceFmr1 ,25), SH3 [Shank3 ), phosphk3 [Pten ), contac[Cntnap2 ), among Pax6), T box brain transcription factor 1/2 (Tbr1/2), and forkhead box G1  receptor on the cell surface, leading to the activation of β-catenin that regulates the expression of various genes [LRP5/6), which is necessary to activate β-catenin. Thus, DKK-1 inhibits the proliferation of neural stem cells and promotes their differentiation into mature neurons [Pax6) deletion changes certain gene expressions, such as achaete-scute homolog1 (Ascl1), neurogenin 2 (Neurog2), neurogenic differentiation 1 (Neurod1), Tbr1, SRY-related HMG-box 5/9 , and hairy and enhancer of split 5 (Hes5), while other genes are near normal, including  and bone morphogenetic proteins , GS homeobox 2 (Gsx2), Sox2, and distal less homeobox-1/2/3 (Dlx1/2/3), among others, which are redirected in a different neuronal variation. Downstream of Pax6 is Neurog2, which regulates Neurod1 expression. Neurog2 and Neurod1 heterodimerize to control progenitor cell production and the amplification of granule neuron progenitors, and the generation of the granule neurons of the hippocampus, which is dependent on Neurod1 and lymphoid-enhancer-binding protein 1 . The. ThePax6ogenesis ,36. The  neurons . In addi neurons ,39,40. T neurons . Transcr neurons ,45,46,471 [Foxp2 ,49. Poss 1 Lef1 ,51,52,53,53Pax6, In mice, neurons are born between embryonic day E11.5–13.5; in humans, it happens much later , neurofibrillary tangle (t-tau), and brain atrophy, present themselves years before dementia ,108. TheIn summary, the hippocampus is involved with hearing but is not critical, while tau levels strongly correlate with ADs and the temporal gyri. Further work is needed to consolidate AD’s relation to degenerative processes in the AC (a common cause of ADs affects AC) and how AC degeneration affects hearing.Genetics play a role in the development of the auditory system, which allows infants to hear and process sounds. As they grow, they learn to speak and sing through exposure and practice, building upon their innate abilities. During the first 1.5 years of life, the auditory system rapidly develops, allowing infants to process and differentiate sounds, learn a language or more, and develop their speaking and singing abilities. However, their hearing abilities can decline as people age, leading to poor speech and language skills without proper care and support. The relationship between hearing loss and AD is still a topic of ongoing research and debate in the scientific community. The relationship between hearing loss and AD is likely complex and influenced by many factors, including genetics, lifestyle, and environmental factors. Further research is needed to understand the connection between hearing loss and AD and determine the best prevention and management methods.


The post hoc test results showed that the difference was significant between any two groups . In conclusion, this study elicited health utility of bilateral hearing impairment with different assistive devices using the VAS and TTO methods. The utility values obtained provide critical data for future cost–utility analysis and health technology assessment.Hearing loss is a common sensory disorder in newborns. Early intervention with assistive devices benefits children’s auditory and speech performance. This study aimed to measure the health utilities of children with bilateral severe-to-profound hearing impairment with different assistive devices. The descriptions of four hypothetical health states were developed, and their utility values were obtained from healthcare professionals via the visual analogue scale (VAS) and time trade-off (TTO) methods. Thirty-seven healthcare professionals completed the TTO interview and were included in the analysis. The mean utility scores obtained via VAS were 0.31 for no assistive devices, 0.41 for bilateral hearing aids, 0.63 for bimodal hearing, and 0.82 for bilateral cochlear implants. As for the utility scores obtained via TTO, mean values were 0.60, 0.69, 0.81, and 0.90, respectively. None of the four groups had the same VAS- or TTO-elicited utility ( Hearing loss, which is the most common sensory disorder in newborns, occurs in between 1 and 3 of every 1000 newborns ,3. In viAmong various hearing assistive devices, cochlear implant (CI) is of special concern from the socioeconomic perspective because of its relatively high cost and the need for a surgery to implant the device. Unlike hearing aids (HA), which work by amplifying sounds, CI is an implantable hearing device that directly transforms sounds into electrical impulses to stimulate functioning of the auditory nerve inside the cochlea. Accordingly, it brings benefits to people with severe-to-profound hearing loss who receive limited benefit from HAs. A CI consists of two parts: an external part and an internal part. The external part includes a microphone and a sound processor. The former works as the outer ear, which receives external sounds, while the processor transmits the sound signal to the subcutaneous signal receiver, i.e., the internal part. The receiver also plays the role of the basement membrane and hair cells. During the process, sound with different frequencies is decoded and separated. Finally, the signals stimulate the auditory nerves in different parts of the cochlea and are then interpreted by the brain. CIs can help patients with severe-to-profound sensorineural hearing loss, who have limited benefits from HAs, perceive the sensation of sound . PositivMeanwhile, bilateral cochlear implantation provides advantages including head shadow effect, binaural summation, and binaural squelch. The process of sound identification relies on the collaborative efforts of both ears. Individuals with unilateral hearing loss face challenges in localizing sound sources since all voices appear to originate from their unaffected ear, making it difficult to determine the actual source. People with unilateral hearing loss often turn their heads and rely on visual cues to locate the origin of sounds. For people with binaural hearing, when a sound originates from a particular direction, the ear that is positioned closer to the sound source is known as the leading ear, while the ear further away is referred to as the lagging ear. The discrepancy in volume perceived by each ear provides us with vital information for localizing the source of the sound. This phenomenon is commonly referred to as the head shadow effect. In addition to the advantage of sound localization conferred by binaural hearing, there are two other benefits: binaural summation and binaural squelch. Binaural summation refers to the phenomenon wherein the brain perceives sounds to be louder when heard with both ears compared to a single ear, even if the volume of sound remains the same. This enhancement in perceived loudness can be attributed as the way in which sound information is processed by both hemispheres of the brain. Although sound initially enters each ear and is processed by the opposite hemisphere, ultimately both hemispheres work together to process and interpret the sound. The brain’s integration of sound information from both ears results in increased sensitivity to sounds, enabling clearer perception. Another advantage of binaural hearing is binaural squelch. In addition to amplifying sound by integrating information from both ears, binaural processing allows the brain to effectively focus auditory attention and filter out background noise. This process enables individuals to listen more effortlessly in noisy environments and concentrate on the speech of interest. Binaural squelch capitalizes on the brain’s ability to separate the desired signal from surrounding noise based on differences in the timing and intensity of sound received by each ear. This separation enhances the signal-to-noise ratio (SNR) and improves the clarity of the message being conveyed. Past studies showed that bilateral CIs provide better speech perception under noise and sound localization over unilateral implantation .Pharmacoeconomics is the science of measuring costs and outcomes associated with the use of pharmaceuticals in healthcare services. Not limited to medication therapy, pharmacoeconomics can also be applied to other medical interventions, such as medical devices. Given finite resources, pharmacoeconomic studies are required to assist in decision-making in order to determine whether a drug or a medical device is cost-effective. These studies consider not only the direct costs of acquiring and administering medications or medical devices, but also their broader impact on overall healthcare expenditures and patient outcomes, such as quality of life. Health utilities are values that represent the strength of an individual’s preferences for specific health-related outcomes where higher values indicate better quality of life in those health states. The measurement of health utility is the key to calculating the health outcome measures in cost–utility analysis (CUA), which is a type of pharmacoeconomic evaluation that enables direct comparison between interventions in the same and different disease areas. Several studies measured health utilities for cochlear implantation ,12. A stAs the performance of CIs varies depending on language features , utilityThe present study aimed to use TTO to measure the health utilities of bilateral severe-to-profound hearing impairment with different assistive devices. To assess different devices’ impact on patients’ quality of life, four hypothetical health states were considered in the study: no assistive devices, bilateral HAs, bimodal hearing combines, and bilateral CIs.This study was a cross-sectional study using the visual analogue scale (VAS) and time trade-off (TTO) to measure the health utility values of four health states of interest. A flow chart of the study design is shown in This study aimed to measure health utilities for children with bilateral severe-to-profound hearing loss with different assistive devices, including HA and CI, and four health states were selected for utility elicitation: without any assistive devices (None), bilateral hearing aids (HA/HA), bimodal hearing using a cochlear implant on one ear and a hearing aid on the other (HA/CI), and bilateral cochlear implants (CI/CI). To draft the descriptions of the four health states, the literature review was conducted to obtain information about the impact of hearing loss, as well as the impact of using assistive devices on various aspects of health in children with severe hearing loss ,14,20,21The drafted health state descriptions were then examined by experts who had experience taking care of children with bilateral hearing loss, including 11 parents, 5 otolaryngologists, 4 audiologists, 2 social workers, and 1 teacher from a special education school. The experts were asked to respond to three prompts for each narrative: (1) whether the narrative conformed to the real-life situation of hearing-impaired children; (2) whether and how the narrative could be amended to enhance clarity and comprehension; and (3) the important narratives or health aspects had been left out regarding hearing loss or assistive devices. Minor revisions of the descriptions were made by incorporating the experts’ feedback.The participants in this study were recruited from three medical centers, three regional hospitals, and one hearing rehabilitation institute for children. Eligibility criteria were as follows: (1) being otolaryngologists, audiologists, or hearing-related healthcare professionals; (2) having CI-related working experience; and (3) having the ability to comprehend Chinese. The interviews were conducted from October 2021 to March 2022. Informed consent was obtained from all participants prior to the interviews. Eligible healthcare professionals who consented to participate were asked to complete a demographic questionnaire and then read the descriptions of the four hypothetical scenarios . The interview was conducted either face-to-face or online via webcam by a well-trained interviewer. The interview consisted of two parts: the VAS and the TTO. For the VAS, firstly, the respondents were provided with five cards representing the four assessed health states and the “dead” state. They were asked to place each card, according to their preferences, along the VAS scale, which was anchored using the worst imaginable health state as 0 and the best imaginable health state as 100, with a higher score indicating higher desirability for the health state. The intervals or spacing between placements corresponded to the differences in preference as perceived by the respondent . After aX: the raw score of the assessed health state, D: the raw score of the “dead” stateRespondents’ demographic characteristics were summarized via mean ± standard deviation (SD) for continuous variables and percentages for categorical variables. The calibration of the raw VAS scores was performed to transform the scores into utilities anchored at dead (=0) and perfect health (=1)  using thT: the indifferent point where the two options were equally preferable for the respondents.In the TTO interview, for example, if the respondent was willing to trade off two of the ten offered years in order to regain perfect health, it was suggested that eight years in perfect health had the same value as ten years with the impaired health states. The respondent perceived living in the impaired health states at a value of 0.8 relative to perfect health (=1) . AccordiT1, T2: time, the last two points with equal answers, thus indicating preference reversal.Orp-value of <0.05 was used to determine statistical significance.ANOVA, followed by Fisher’s Least Significant Difference (LSD) post hoc test, was used to find the differences in utility values among the four health states. All statistical analyses were conducted using IBM SPSS Statistics version 19. A From October 2021 to March 2022, a total of 39 healthcare professionals were recruited from three medical centers, three regional hospitals, and one hearing rehabilitation institute for children. Two respondents did not complete the TTO interview, resulting in a total of 37 respondents being included in the analysis. The respondents’ demographic characteristics are presented in p < 0.001). In addition, the results of the post hoc LSD pairwise comparisons showed that the difference was significant between any two groups .The utility scores of the four health states assessed are summarized in Despite the significant economic and quality of life-related impacts of CIs in children, few studies have been conducted in this field. As pharmacoeconomic research in Asia expands into new areas, collecting local health utility data is essential for economic evaluations. This study is one of the few in Asia that used TTO to measure the health utilities for bilateral severe hearing impairment with different assistive devices. The utility values elicited in this study enhance the understanding of the relative impact of these hearing-assistive devices. Moreover, the values can be used in future CUA that can inform decision-makers about healthcare resource allocation.Common measures for valuing health states include indirect questionnaire-based measures, such as the EuroQol five-dimensional questionnaire (EQ-5D), and direct valuation methods, such as standard gamble (SG) and TTO. Despite the convenience and popularity of the EQ-5D, however, it may not be appropriate for conditions affecting sensory functions, such as vision or hearing ,26,27. TThe utilities elicited in the present study via VAS and TTO were both lowest for the health state without any assistive devices, followed by HA/HA, HA/CI, and CI/CI. The observation that the greatest quality of life is associated with CI/CI is consistent with previous studies ,9,10,11,It was previously reported that the utility values obtained via TTO are generally higher than VAS-derived scores , which iThere are a few limitations to this study. Firstly, the sample size was relatively small, though the number of respondents needed for utility assessment studies was not determined and the number of participants enrolled in this study was close to that of previous studies ,14. SecoAn important implication of this study is the contribution of the utility values obtained to CUA, which assists policymakers in making informed decisions regarding resource allocation within the healthcare system. Since CUA plays a crucial role in determining the optimal allocation of public resources, it is essential to consider the perspectives of the general population. The health utilities derived from healthcare professionals may not be representative of societal perspectives. Future research is needed to expand the study population or generate experience-based utilities for patients’ individual health states.HAs and CIs demonstrated clinical benefits in children with severe hearing loss. Considering the long-term use and economic burden of these assistive devices, comparative evaluations are required to support health authorities’ policy decision making. The utility values obtained in the study provide critical data for future CUA and health technology assessment.This study used both VAS and TTO to measure the health utility values of bilateral severe-to-profound hearing loss with assistive devices. The results of this study showed that bilateral CIs had the greatest utility value, followed by bimodal hearing, bilateral HAs, and, finally, no use of any assistive devices. The elicited utility values can serve as essential data for the calculation of health outcome measures in future CUA research. CUA is a common analysis method in pharmacoeconomic evaluation that enables direct comparison of interventions in different areas. Since health utility is jointly affected by multiple dimensions, such as physiological function, psychological health, and social wellbeing, the health preferences of individuals with different cultural backgrounds can also vary. As such, local utility data are preferred for CUAs. Furthermore, the present study can help clinical experts clarify the extent to which bilateral assistive devices improve patients’ quality of life and hearing.


Tissue containment systems (TCS) are medical devices that may be used during morcellation procedures during minimally invasive laparoscopic surgery. TCS are not new devices but their use as a potential mitigation for the spread of occult malignancy during laparoscopic power morcellation of fibroids and/or the uterus has been the subject of interest following reports of upstaging of previously undetected sarcoma in women who underwent a laparoscopic hysterectomy. Development of standardized test methods and acceptance criteria to evaluate the safety and performance of these devices will speed development, allowing for more devices to benefit patients. As a part of this study, a series of preclinical experimental bench test methods were developed to evaluate the mechanical and leakage performance of TCS that may be used in power morcellation procedures. Experimental tests were developed to evaluate mechanical integrity, e.g., tensile, burst, puncture, and penetration strengths for the TCS, and leakage integrity, e.g., dye and microbiological leakage (both acting as surrogates for blood and cancer cells) through the TCS. In addition, to evaluate both mechanical integrity and leakage integrity as a combined methodology, partial puncture and dye leakage was conducted on the TCS to evaluate the potential for leakage due to partial damage caused by surgical tools. Samples from 7 different TCSs were subjected to preclinical bench testing to evaluate leakage and mechanical performance. The performance of the TCSs varied significantly between different brands. The leakage pressure of the TCS varied between 26 and > 1293 mmHg for the 7 TCS brands. Similarly, the tensile force to failure, burst pressure, and puncture force varied between 14 and 80 MPa, 2 and 78 psi, and 2.5 N and 47 N, respectively. The mechanical failure and leakage performance of the TCS were different for homogeneous and composite TCSs. The test methods reported in this study may facilitate the development and regulatory review of these devices, may help compare TCS performance between devices, and increase provider and patient accessibility to improved tissue containment technologies. Food and Drug Administration (FDA) issued a series of safety communications since 2014, highlighting the risk of unidentified uterine malignancy spreading to other organs during an uncontained power morcellation procedure5. Subsequently, to minimize the risk of spreading the cancerous cells during power morcellation, some studies have suggested the use of a tissue containment system (TCS) in patients11, which surrounds the power morcellator and the tissue to be excised and forms a barrier between them and the abdomen. As of April, 2022, the FDA has authorized marketing of two TCSs that are indicated for power morcellation for select patient populations through the De Novo classification process14 and one TCS via 510(k) process15.Laparoscopic power morcellators are medical devices used during minimally invasive hysterectomy and myomectomy procedures to facilitate the removal of uterine fibroids and/or uterine tissue and continue to carry the advantages of lower complication rates and quicker recovery times as compared to open procedures32. Some of these studies have reported evidence for damage and/or leakage (or spillage) during surgery30. The potential causes for containment system failures include, but are not limited to, permeable containment system material, puncture by surgical instrument, tear due to excessive pressure, etc. Mechanical and leakage integrity of the TCS material is critical to ensure that the TCS maintains its barrier properties throughout the surgical procedure.The TCSs typically made from polymer-based materials help to contain and prevent penetration of tissue cells through the containment system wall. Several clinical studies have evaluated the integrity and applicability of these containment systems during clinical procedures34 devices that outlines the type of mechanical and leakage integrity tests that were performed on the tissue containment system33. Full containment system immersion testing was done post-morcellation to ensure that the containment system remained intact and leak-proof after the surgical procedure. For establishing mechanical integrity, puncture and burst tests were performed to evaluate the forces required to cause physical damage to the containment system material during the surgical procedure. However, limited details about the test methodology, acceptance criteria, and test results were provided in the summaries.There are some open-access information available for the FDA-authorized35 developed a performance test method to measure the exertion force required to pull TCS from various sized incision ports ranging from 10 to 24 mm in diameter. Their results showed that the mechanical integrity was compromised for incision sizes less than 16 mm. Cohen et al.36 evaluated the leakage integrity of various containment systems by morcellating beef tongue stained with dye within a laparoscopic trainer. A visual evaluation was used to locate spilling and leakage of dye through the containment system’s material. Blue dye spill was noted in only one of 12 contained tissue extraction trials. Spillage was visualized from a seam in one of the 4 stitch-sealed rip-stop nylon containment systems before morcellation of the specimen. Similarly, Solima et al.29 performed visual examination of the containment system post-morcellation and used spillage of methylene blue as indicator for leakage. Rimbach et al.37 evaluated the presence of smooth muscle cells (from beef tongue) from washings in the peritoneal cavity as a measure for the containment system’s leakage integrity. In general, clinical studies used visual examination and dye spillage or peritoneal cavity washings as a measure for evaluating leakage integrity of the containment system. Van Den Haak et al.38 performed a Failure Mode and Effective Analysis (FMEA) for contained morcellation and identified ten causes most likely to cause spillage. Of them, two of the causes were TCS material related and could be eliminated by appropriate testing of the TCS materials.Apart from the De Novo and 510(k) summaries, few research studies have provided details about performance testing of tissue containment systems. For example, Anapolski et al.A priori systematic study of the integrity of the containment system is critical and fundamental to ensuring the device performs as intended and provides a mitigation for tissue spread during power morcellation procedures. There is a need for developing (1) a list of potential test methods for safety and performance evaluation, (2) detailed description of the test methodologies, and (3) appropriate acceptance criteria, if any, for those test methods.The objective of this study is to address these unmet needs by developing a series of preclinical test methods that will assess the mechanical and leakage integrity of the containment system material to mitigate the risk of spillage. The scope of this paper is limited to discussing the mechanical and leakage integrity of the TCS material and not the whole TCS as a device. Henceforth, any reference to TCS in this paper relates only to the TCS material and not the whole device.To evaluate the mechanical integrity, test-to failure experiments were conducted with the containment systems to evaluate the tensile, burst, and puncture strength of the TCS materials. Similarly, to evaluate the leakage integrity, test-to-failure experiments using dye and bacteriophage as cancer cell surrogates were designed to measure the maximum pressure when the TCS material may leak. Subsequently, materials from different TCS brands were evaluated using these test methods and assessed for correlation between leakage potential and physical characteristics and mechanical strength of the specific TCSs. The novelty of this study is that performance metrics have been compared from each test and correlated with the results of other tests to evaluate TCS material performance as a whole. Based on the test results, several considerations for assessing performance of TCS material during power morcellation are provided.A total of seven different brands of TCSs were evaluated experimentally using the test methods described below in Experimental Methods. Summary of the containment systems (with manufacturer information blinded) with material, and thickness details can be found in Table These TCSs are typically made of from either a homogeneous material such as polyurethane (PU) or from a combination of different materials such as rip-stock nylon and PU. Six of the TCSs chosen for testing were described in the literature for clinical use in insufflated contained tissue extractions. The seventh TCS, TC#7, is the only brand in the test samples that was authorized for marketing by FDA as a gynecologic laparoscopic power morcellation containment system.Table Evaluating the physical characteristics of the TCS material is critical to ensure that they meet the design requirements set forth by the manufacturers. Mechanical strength evaluation is critical to ensure that the material strength of the TCS is not compromised when they are subjected to tensile, radial, and puncture forces arising during the morcellation clinical procedure. Leakage integrity evaluation is critical to ensure that the TCS material, when subjected to clinically relevant forces, can still act as an effective barrier against penetration of tissue, blood and cancer cells. As part of this testing, leakage pressure of the TCS materials were obtained and compared to the pressures experienced during the power morcellation procedure. In addition, the resistance of the device to leakage may be related to its mechanical strength, the material composition, and the thickness.For each TCS brand, a total of atleast three specimens, each from different samples, were tested to obtain the mean and standard deviation for all quantities of interest for physical characteristics and mechanical strength evaluations as defined in Table The containment system material’s thickness was measured using a micrometer  which had a minimum resolution of 0.001 mm. The thickness measurements were repeated 5 times at different locations on cut specimens to obtain a mean and standard deviation for each containment system , and toughness  of each TCS material were estimated.The materials testing machine  shown in Fig. 42  cut out from TCS was used as a test specimen, attached to a circular specimen holder with an internal diameter of 57.3 mm using four screws and connected to an air-pressure chamber43. A small square coupon (108 mm length) was cut from the TCS and was used as a test specimen sandwiched to a circular specimen holder with an internal test diameter of 25 mm using four screws. The specimen holder was attached to the lower end of the Tabletop Instron . One of the two standard durometers pins, Type OO and Type D44 of tip radius 1.19 mm and 0.1 mm .The resistance to puncture for each containment system was obtained by measuring the force required to cause a standardized puncture pin to completely penetrate through the thickness of the specimen45. The sensitivity of the dye test method was validated using microbiological penetration testing.Dye penetration testing was performed using an ISO blood surrogate dye for determining leakage potential in terms of leakage pressure of different TCS brands  as a surrogate for detecting blood/tissue cell leakage based on its small size, spherical morphology, environmental stability, non-human infectivity, and rapid assayA combination of partial puncture followed by dye penetration testing was performed to estimate the tool pressure required to cause partial damage to the TCS material but significant enough to cause leakage of the contents. The test setup for puncture and dye penetration testing are the same as shown in Figs. puncture) using the Type D durometer pin as shown in Fig. 45.The flow chart outlining the partial puncture study is provided in Fig. puncture), the combination of partial puncture followed by dye penetration testing was repeated for incrementally higher partial puncture forces (at 5% increment) until all the TCS samples of the same brand leaked. However, if the TCS materials leaked at 0.5 × Fpuncture, the combination test was repeated at 0.1 × Fpuncture and incrementally increased by 5% until TCS samples showed evidence of leak. The force at which the TCS specimen showed first sign of leakage is referred to as the threshold partial puncture force causing leakage (Fleak-puncture).If the TCS specimen passed the dye penetration test and deemed to be leak-proof after partial puncture  values varied widely between the TCS materials and ranged from 2 to 78 psi  compared to composite ones (up to 78 psi). In comparison to TC#7, burst pressure was higher for TC#1, 2, 3, 5, and 6.Similar to the UTS and toughness values, the burst pressure (Ppuncture). After puncturing the TCS, the force drops suddenly as the pin’s tip is no longer in contact with the TCS. As the pin displaces further at a uniform speed, the tapered part of the pin’s tip contacts the TCS causing the tool force to increase with the displacement of the pin. The force keeps increasing until the distal part of the pin geometry penetrates completely through the TCS material, however, the forces post Fpuncture were not considered for further analysis. Instead of a single spike in the force curve seen for the homogeneous TCSs  for composite TCS materials.Figure CSs Fig. a, the coCSs Fig. b. The fipuncture was an order of magnitude more for Type OO blunt pin compared to Type D sharp pin. Fpuncture was higher for composite TCS materials (40 N–45 N) compared to homogeneous TCSs (2.5 N–35 N) for Type OO blunt pin. Same observation was made for Type D sharp pin . For the homogeneous TCSs made of the same material (PU), the Fpuncture increased proportionately with the TCS thickness. In comparison to TC#7, the force at puncture for both types of pins were higher for all other TCSs except TC#4.Figure 45. In summary, when exposed to an external pressure of 2 psi, all the TCS materials except TC#3 remained leak proof during both dye and microbiological penetration testing. For TC#3, ~ 89% and ~ 58% of the tested TCS specimens failed  the dye and microbiological penetration testing, respectively.The dye and microbiological penetration in different TCS materials were reported previously in Herman et al.leakage) performed previously when comparing the homogeneous and composite TCSs  and caused leakage of its content, was significantly lower in comparison to Fpuncture values .Preclinical testing requirements for TCSs include, but are not limited to, evaluating TCS’s material impermeability to tissues, cells, and fluids, and demonstrating device integrity when used with intended laparoscopic instruments and morcellators38, the TCS experience tensile stress when (1) it is pushed through the trocar into the pneumoperitoneum (i.e. distended abdomen), (2) when maneuvering the TCS in the pneumoperitoneum using graspers, (3) when pulling the TCS out of the abdominal cavity with blood or tissue remains inside it, etc. Similarly, the TCS is subjected to radial stress (1) during insufflation, and (2) during removal of TCS out of the cavity through the narrow incision if the insufflated CO2 is trapped inside it. The TCS is also subjected to puncture forces every time the grasper, tenaculum, or the morcellator contacts the device surface.As a part of this study, TCS materials were exposed to tensile, radial, and puncture forces to represent physiologically relevant loads anticipated during clinical use. For exampleOur results showed a clear distinction in mechanical performance between composite and homogeneous TCS materials. Overall, materials from composite TCSs showed superior performance for mechanical strength compared to homogenous TCSs, due to the fact that composite TCS materials had higher puncture and burst resistance than homogeneous TCSs Table . On the In comparison to TC#7, ultimate tensile strength was higher for TC#2, 3, 5, and 6. Similarly, the toughness was higher for TC#5 and 6 than for TC#7. Burst pressure was higher for TC#1, 2, 3, 5, and 6 than TC#7. The force at puncture for both types of pins was higher for TC#1, 2, 3, 5, and 6 than TC#7. Overall, the mechanical performance was very different for homogenous TCS material compared to composite TCS. Device manufacturers and testing laboratories should be cognizant of these distinctions while comparing the performance of TCS materials. Because of the underlying differences in mechanical performance, a homogenous TCS material may not be the best comparator if the device under evaluation is made of composite layers and vice versa.puncture, had the worst leakage pressure and Fleak-puncture  the dye and microbiological penetration testing, respectively. On one hand, the same TCS brand failed in both leakage integrity tests indicating the results of microbiological penetration test and dye penetration test may be similar. On the contrary, the sensitivity for leakage of the microbiological penetration test appears to be higher than the dye penetration test. The results may indicate that microbiological penetration test may be preferred over dye penetration test. Dye penetration testing alone was used in this study for evaluating leakage in partially punctured TCS material and results were compared to previously performed leakage integrity tests. Device manufacturers might benefit from primarily using dye penetration testing to verify leakage performance for different design variations of the TCS material to finalize the design, after which microbiological penetration testing may be performed for validation.Leakage integrity was evaluated using dye and microbiological penetration testing. From previous studies33. While evaluating the puncture resistance of various TCS materials, our studies showed a significant difference between the puncture force required to cause complete penetration through the device thickness (Fpuncture) being as high as two and half times the partial puncture force required to cause leakage (Fleak-puncture) for the composite materials. The puncture force required to cause complete penetration through the thickness and partial puncture to cause leakage were the same for all homogeneous TCSs indicating breach through the entire thickness of the TCS material in both cases. Consequently, these results showed that partial damage to composite TCS material due to contact with the surgical tools if not noticed could lead to catastrophic leakage of contents out of the TCS. This risk should be taken into consideration while establishing the acceptance criteria for tool forces exerted on the TCS. For this study, all the puncture testing was done using standardized durometer pins (Type OO and Type D in Fig. Inadvertent damage to TCS due to contact with surgical tools and morcellators during the surgical procedure is listed as one of the primary risks to patient health with the use of gynecologic laparoscopic power morcellationburst, Pleakage, Fpuncture and Fleak-puncture were established and measured. However, we did not come up with a set acceptance criterion for any of these metrics. The acceptance criteria tend to be device and material specific and could depend on several factors such as device design, indications for use, choice of comparator device, etc. However, it would be beneficial for the manufacturers to derive appropriate device safety factors45 by comparing the device’s test-to-failure metrics obtained after bench testing with clinically relevant forces encountered by the TCS material during actual surgical procedures. Previous studies have used force sensors to measure the force imparted by the clinicians on the surgical tools during medical procedures. The safety factors, if mentioned in product labeling, could help researchers and regulators understand the risk associated with the use of different TCS materials during power morcellation procedures.As a part of this study, several metrics for material performance such as UTS, PThe study has following limitations. This study outlined test methods to understand the performance of materials used to make TCSs. However, these protocols, as is, are not applicable to testing of the TCS bag as a whole. Additional test methods are needed to evaluate the mechanical and leakage integrity of the full TCS bag. Further more, additional test methods are needed to evaluate the ability of the device to allow for insertion and removal instruments while maintaining pneumoperitoneum, ability of the intended users to adequately deploy and use the device without compromising its integrity etc. These tests may necessitate the conduct of additional bench testing, clinical simulation, whole device TCS leakage testing, and animal studies to demonstrate performance.Currently, there is a clear need for developing standardized protocol to evaluate the mechanical performance and leakage potential of the TCS materials. Our study addressed this need my developing a series of bench tests that will be useful in evaluating performance of TCS materials for power morcellation procedures. Streamlining of preclinical testing will create efficiencies in bringing new tissue containment technologies to market, resulting in benefit to both patients and health care professionals.


The aim of the study was to verify the level of satisfaction of CI users with long periods of hearing deprivation, highlighting the positive and negative aspects of the use of the device and their quality of life.This is a analytical research, of the type observational cross-sectional study. The study was performed with 24 patients from a private Institute of Otorhinolaryngology. Three surveys were applied: Satisfaction with Amplification in Daily Life (SADL), International Outcome Inventory - Cochlear Implant (IOI - CI) to assess cochlear implant satisfaction and WHOQOL- bref to assess the quality of life. The results in the pre and post lingual groups were compared.The highest degree of satisfaction was reported with regard to personal image, positive effects, and how the users feel about their CI. The lowest degree of satisfaction was reported regarding the cost-benefit of the CI and the competitive noise. In the WHOQOL-bref assessment, the highest scores were found in physical, psychological and social relations domains. When comparing the results of the surveys, the pre and post-lingual groups showed no difference in relation to the achieved scores.The participants had a high level of satisfaction with the use of cochlear implants. The longer the sensory deprivation time, the greater the degree of satisfaction with the device. The use of the CI electronic device reflects on the individual's quality of life. It may be associated with social isolation, impairment of speech, psychological and professional development, as well as feelings of disability and inferiority. These factors can lead to emotional problems such as low self-esteem, loneliness, depression, and irritability. Study with adults with bilateral hearing loss (HL) related the difficulty in maintaining interpersonal relationships due to hearing impairment with low quality of life.Hearing loss (HL) can negatively impact the quality of life of adults.Part of individuals with HL who have partial functioning of the ear hair cells may acquire relevant gain with the use of hearing aids. While those who do not benefit from this may be indicated for cochlear implant (CI) surgery as an alternative form of treatment.The CI is an electronic device whose function is to partially replace the activities of Corti's organ, by means of electrical impulses that directly stimulate the remaining neural fibers of the cochlea. It consists of two parts. The internal part consists of a bundle of electrodes that are inserted into the cochlea and a stimulating receptor positioned surgically in the region of the temporal bone. The external part consists of a signal processor, a microphone and a transmitting antenna located in a retroauricular position that is responsible for capturing the sound that will be transmitted to the speech processor-8. There is general consensus in these publications about the candidacy of CI in adults: having severe-profound hearing loss, little gain with the use of hearing aids and evaluation by a multidisciplinary team.Several medical entities throughout the world have published recommendations for selecting candidates for cochlear implant.In Brazil, the availability of CI technology is a reality in both the private and public health sectors, and the number of CI users has been increasing over the years.CI is considered a well-established treatment for severe-profound sensorineural hearing loss. Despite this, there is little study on the satisfaction level in users of this technology in individuals who had had long periods of hearing deprivation. In addition to satisfaction, it is important to consider how improving hearing perception impacts the quality of life of users. It is suggested that quality of life and speech recognition in adults with prelingual deafness improved significantly after cochlear implantation,13. Contrary to expectations, these later studies revealed more benefit in the quality of life in users of cochlear implant with longer pre-implant hearing loss, suggesting that this result can be explained by the implication of reentering the world of hearing. The authors added, further, that the data currently available cannot fully explain this result.It is reported be significantly improves the quality of life after cochlear implantation; however, few studies relate these results in users with longer time of hearing loss before cochlear implantationThus, the aim of this study is to verify the level of satisfaction of CI users who had had long periods of hearing deprivation, highlighting the positive and negative aspects of the use of the electronic device and their overall quality of life.This is an analytical research, an observational cross-sectional study.This research was submitted to the Ethics Committee, approved with CAAE: 70324117.0.0000.5650. The sample consisted of patients from a Cochlear Implant Center. All participants signed the written informed consent., being over 18 years old, having had implant activation within a minimum period of 6 months, literate and capable of answering to the surveys.Inclusion criteria were: severe/profound, pre or postlingual sensorineural hearing loss with long sensory deprivation (ten years or more)Exclusion criteria were: Individuals with cognitive impairment or some other associated disability or those with shorter duration of hearing.The selected patients were in accordance with the guidelines “Cochlear Implant Indicator Criteria” elaborated by the consensus of the Brazilian Association of Otorhinolaryngology and Facial Cervical Surgery, Brazilian Society of Otology, Brazilian Society of Speech Therapy, Brazilian Academy of Audiology and Brazilian Society of Pediatrics. It is recommended cochlear implants for patients with bilateral profound sensorineural hearing loss with proven limited benefits with the hearing aids bilaterally.That is:Severe or profound bilateral sensorineural hearing loss;Result equal to or less than 50% of sentence recognition in open set with the use of hearing aids in both ears;Presence of language code established and adequately rehabilitated by the oral method;The adequate motivation of the patient for the use of cochlear implant and for the speech rehabilitation processThe implanted patients who met the study selection criteria were invited to participate in the research at the same time as their therapy and/or medical return visits. After the documented acceptance, they answered a case study, two inventories about satisfaction with the use of the CI, and an assessment about their quality of life.The sample of the present study was of convenience, being selected from the service's database the patients who met the research selection criteria and still had a connection with the service. Participants were invited to participate in the research, which was carried out before or after a routine visit to the institute.2 users. And the WHOQOL-bref assessment that evaluates the quality of life in predetermined aspects.The surveys were: International Outcome Inventory - Cochlear Implant (IOI - CI) and Satisfaction with Amplification in Daily Life (SADL), which were originally developed for users of hearing aids, but were adapted for CI.The IOI-CI inventory has seven questions to which the answer is a 5-point likert scale, where low values indicate worse results. It consists of two factors: factor 1 (4 questions) indicates the user's relationship with the use of their device  and factor 2 (3 questions) reflects the user's interaction with the social environment . As a global result, the sum of the scores of factors 1 and 2 is performed. The arithmetic mean of the scores obtained in each factor and in the global result was calculated, with the lowest possible score 1 and the highest 5. For data presentation, they were also dimensioned as suggested in a previous study as dissatisfied those whose score is below 2.5 and satisfied those whose score is above 2.5.The SADL research instrument consists of 15 questions, aiming to quantify the overall satisfaction with the use of CI. The aspects assessed by it are: Positive effects , service and costs (3 questions), negative factors  and personal image (3 questions), by characterizing the overall score and the four subscale scores. Each question has 7 possible answers ranging from “not at all” to “extremely”, with the lowest possible score 1 and the highest 7. For analysis, the sum of the constituent questions of each scale was performed to obtain their mean, and for the overall value, the average scores obtained in each of the 4 scales of the inventory were summed. Considering scores below 3.5 as dissatisfied and above 3.5 as satisfied.WHOQOL-bref has twenty-six questions to which the answer is a 5-point likert scale. Is subdivided into domains and facets, where questions 1 and 2 are classified as facets and the other questions in domains. Domain I corresponds to the physical aspects (seven questions), domain II represents the psychological aspects (six questions), domain III elucidates questions of social relations (three questions), and domain IV specifies the perceptions of the environment (eight questions). The arithmetic mean of each domain and facets was calculated, the results were classified, as specified in the inventory manual, as follows: need to improve (score from 1 to 2.9); regular (from 3 to 3.9); good (4 to 4.9) and very good (score 5)The application and completion of the pencil-and-paper inventories were performed in a room with the presence of a researcher. It has been given to each participant an explanation of the purpose of the inventories and any doubts on how to fill them up, being given the time necessary to fill them..The allocation of individuals in the pre and postlingual groups was carried out as follows: when a hearing loss occurs before 3 years of age, consider a prelingual hearing loss. After that age, a postlingual hearing loss is consideredρ shows that results close to -1 have a negative correlation, close to 0 have no correlation and close to 1 have a positive correlation. The level of significance of this analysis was 5% or 0.05 for both normality and correlation testsAll the variables were subjected to the normality tests of Shapiro-Wilk and Kolmogorov-Smirnovwhich. In order to statistically describe and compare the pre and postlingual groups, parametric tests were used when the distribution was Gaussian (Student's “T” test) and nonparametric tests (Mann Whitney) when the distribution was not Gausian. Spearman's nonparametric test was chosen for the correlation. Spearman's The MS-Excel spreadsheet, in its version of MS-Office 2013, was used to organize the data, and the GraphPadPrism statistical package, in its version 6.0, to obtain the results. The study participants were grouped into satisfied and dissatisfied for a better general understanding of the results except for the WHOQOL-bref assessment, where the percentage of answers obtained in each domain was rated.The sample consisted of 24 individuals, 75% female and 25% male, at the average age of 42.83 years and SD of 15.59. Regarding the moment of onset of deafness, 15 (62.5%) had postlingual hearing loss and 09 individuals (37.5%) had prelingual hearing loss. The other characteristics of the individuals are presented in Regarding the distribution between the sexes, it is observed that in the postlingual group the concentration of women is higher than that observed in the prelingual group, thirteen (86.7%) in the postlingual group and five (55.6%) in the prelingual group.Patients in the postlingual group were significantly older than the prelingual group (p = 0.001), with a mean age of 48.07 (range: 19 to 76) and SD of 17.21 compared with 34.11 (range: 26 to 45) and SD of 6.45 in the prelingual group.The age at which patients had had their cochlear implantation was significantly higher in the postlingual group (p = 0.020). The time of sensory deprivation was longer in the prelingual group, however, this difference was not statistically significant (p = 0.075). CI experience time was similar between the two groups (p = 0.26).Regarding the SADL and IOI-CI surveys the median score, as well as the minimum and maximum values found in the total sample, prelingual group and postlingual group and the significance value of the comparison between groups are described in In the SADL inventory, the highest satisfaction scores were found in the subscales referring to positive and personal image factors. The lowest satisfaction scores were found in the subscales referring to the negative and the service and cost factors.In the IOI-CI inventory, the highest satisfaction score was found in Factor 1 for the relationship between the user and their cochlear implant and the lowest satisfaction score was found in Factor 2 for the user 's relationship with their social environment.The most frequently reported negative factors were the cost-effective and competitive noise, observed in the negative factors and the services and costs of the SADL inventory.When compared to the scores of each of the surveys, the pre and postlingual groups did not present significant difference regarding cochlear implant satisfaction in all dimensions and factors of the SADL and IOI-CI inventory.The analysis of the degree of global satisfaction with the CI through the IOI-CI demonstrated that 100% of the users were satisfied with the device. Analyzing the SADL, 87.5% of the participants demonstrated to be satisfied with the device and 12.5% dissatisfied, with the degree of satisfaction in the prelingual group of 100% and in the postlingual group of 80%.No statistically significant difference was found between the proportion of satisfied and dissatisfied patients in the pre and postlingual group in IOI-CI, and a higher proportion of satisfied patients in the prelingual group in SADL was found.The results of the total sample regarding the quality of life analysis by the WHOQOL-bref assessment are presented in When comparing each constituent domain of the WHOQOL-bref assessment the pre and postlingual groups did not present significant differences.In the WHOQOL- bref assessment the results show us that users are satisfied with their quality of life. For a better understanding of the results, we present in The highest scores were obtained in domain I, which refers to the physical domain, and in domain II, which refers to the psychological domain. We had the lowest scores in domain IV regarding the environment.The analysis of the total sample, of the prelingual and postlingual groups showed that the older the patient  and the later the hearing loss  and the CI occurred , the greater the degree of satisfaction with the device observed through the SADL questionnaire. This correlation was not observed when analyzing the results of the IOI-CI.In the prelingual group, it was possible to correlate the time of hearing loss before CI with the degree of satisfaction with the CI through the SADL, which is a positive correlation (p=1.000). In the postlingual group, it was observed that the individuals who did post implant speech therapy had greater satisfaction with their device, observed in the IOI-CI (p=0.537).The activation time of the CI was negatively correlated with the degree of satisfaction with the device measured through the SADL (p=-0.617), analyzing the total sample.Although there was greater satisfaction with the device in specific groups in the sample, there was no better quality of life among these individuals compared to the others..Assessment of user satisfaction is provided for in the Ordinance of the General Guidelines for specialized care for people with hearing impairment in the Unified Health System (SUS), as part of the monitoring of CI patients. Knowing the positive and negative points regarding the use of CI is of paramount importance for enabling and rehabilitating individuals with HL,16. There have been efforts to develop different surveys in the seeking of quality of life in this specific population.The need for specific studies on quality of life in this population has recently been highlighted, as traditional speech recognition tests do not reflect this aspect,18.Studies already published show the effectiveness of CI as a treatment for individuals with severe to profound hearing loss, and that the degree of satisfaction stands out in relation to the dissatisfaction presented by CI usersselected according to the recommendations for selecting candidates for cochlear implant, patients with prelingual hearing loss benefit from the use of CI10. This fact deserves highlight in the present study because the individuals had a long duration of sensory deprivation. It is worth noting that the postoperative patients who underwent speech therapy had a higher degree of satisfaction with the device.Comparison between groups showed that even individuals with prelingual hearing loss had a high degree of satisfaction with CI. Previous studies agree that if ,19.Knowledge of the negative factors presented by CI users, as analyzed in the SADL, is perhaps one of the most relevant returns in the satisfaction survey. Considering that users' complaints, whether psychological or auditory, can influence and be a determining factor for treatment abandonment. Several studies have shown that at the public health level, CI is a cost-effective alternative in both high-income countries and developing countries,22. Factors such as unilateral or bilateral implantation and candidates receiving the device still remain a controversial subject.A significant number of dissatisfaction related to CI services and costs in general is observed. In IOI-CI the lowest satisfaction score was found in Factor 2 of the inventory, which refers to the user's relationship with their social environment. From the reports of users during data collection, it was observed that this result was influenced by the degree of difficulty they still encounter in competitive noise situations using cochlear implant.Despite the possibility that CI can provide in reaching high levels of understanding, research reveals that CI users are still experiencing considerable difficulty in noisy environments. Post-Hearing auditory training becomes essential; however, only a few studies address the perception of speech in a noisy environment as part of this training. Regarding this complaint, significant improvement has been demonstrated after five sessions of specific training.Hearing difficulty in noisy environments is associated with the ability of the auditory pathway to encode temporal envelope modulations due to the effect of degenerative processes associated with hearing loss.With the use of the device, adult users report considerable improvement in their hearing performance and communication difficulties, which allows the restoration of professional and social activities. Self-esteem, social relationships and independence are negatively affected in the lives of people with hearing loss. CI for these people can improve these factors and favor their personal, social, family relationships and autonomy,28.The last question of IOI-CI questionnaire asked, considering everything, how they thought their cochlear implant changed their joy of living or rejoice in life, the vast majority of respondents claimed that CI provided them with much more joy of living. These results are also proven by other authors.The use of the CI electronic device reflects directly on the individual's quality of life and may benefit him/her in social and family life aspects. A previous study has shown that even individuals well adapted to hearing aids demonstrate improved quality after performing the cochlear implant. It is important to point out that when comparing the quality of life of CI users with healthy adults, this group has significantly lower scores, demonstrating that the effects of hearing loss affect the quality of life even in implanted patients.Cochlear implant users demonstrated good quality of life, and it was even demonstrated in a study with the WHOQOL-bref that the CI user participants had scores very close to the maximum score that represents a satisfactory quality of life resembling the results found in the participants without hearing loss. Thus, studies have concentrated efforts on verifying the demographic and auditory factors that influence the individual's satisfaction with the cochlear implant, these factors still remain controversial.Traditionally, patients who use CI are evaluated using tests of speech recognition skills. These measures are poorly correlated with improvement in communication, social, emotional aspects and quality of life.The individual's age was related to greater satisfaction with the device in both the prelingual and postlingual groups. This data differs from that previously reported.Among the hearing factors, longer duration of hearing loss before CI was associated with greater satisfaction with the device in prelingual group. Perhaps this fact can be justified by the satisfaction generated by reentering the world of hearing after a long time. This greater satisfaction with the device, however, did not reflect a significant improvement in quality of life. As it differs from a previous study that reported the relationship between these data to be unexpected.When comparing the results of the three surveys applied in this research, the pre and postlingual groups showed no difference in relation to the achieved scores. This fact reiterates the option to perform cochlear implant surgery in prelingual patients even with a long time of sensory deprivation, provided that they meet the selection criteria for the use of a cochlear implant that includes speech therapy by the verbal auditory therapy and appropriate motivation for cochlear implantation and for the rehabilitation processThe participants had a high level of satisfaction with the use of cochlear implants. The longer the sensory deprivation time, the greater the degree of satisfaction with the device.The highest degree of satisfaction was reported with regard to personal image, positive effects, and how the users feel about their CI. The lowest degree of satisfaction was reported regarding the cost-benefit of the CI and the competitive noise.Sociodemographic and auditory factors interfere in the quality of life of these individuals and must be considered in their evaluation.The use of the CI electronic device reflects directly on the individual's quality of life. Pre and postlingual groups showed no difference in relation to the achieved scores.


Oxidative stress due to intermittent hypoxia is the main pathogenetic mechanism of damage. CPAP has no effects (positive or negative) on hearing function. More studies are needed, with the evaluation of extended high frequencies, the execution of vocal audiometry in noisy environments, and the evaluation of potential biomarkers due to oxidative stress.Introduction: OSAS is a disease that affects 2% of men and 4% of women of middle age. It is a major health public problem because untreated OSAS could lead to cardiovascular, metabolic, and cerebrovascular complications. The more accepted theory relates to oxidative stress due to intermittent hypoxia, which leads, after an intense inflammatory response through multiple pathways, to endothelial damage. The objective of this study is to demonstrate a correlation between OSAS and hearing loss, the effect of the CPAP on hearing function, and if oxidative stress is also involved in the damaging of the hearing system. Methods: A review of the literature has been executed. Eight articles have been found, where seven were about the correlation between OSAS and the hearing system, and only one was about the CPAP effects. It is noted that two of the eight articles explored the theory of oxidative stress due to intermittent hypoxia. Results: All studies showed a significant correlation between OSAS and hearing function ( Obstructive sleep apnea syndrome (OSAS) is a respiratory disease relating to sleep. It is characterized by five or more respiratory events , with a specific symptomatology. Every episode of apnea or hypopnea persists for at least 10 s, is associated with a loss of blood oxygenation of 3–4%, and ends with a short and unconscious awakening from sleep. A population of 2% of women and 4% of men older than 50 years old is often affected by this pathology . PhysicaA literature review has been conducted. PubMed research with keywords such as “OSAS”, “auditory”, “hearing”, “audiology”, “CPAP”, and “oxidative” has been performed. “OSAS and auditory” retrieved 18 articles, whereas no articles were found under “OSAS and auditory and oxidative”; “OSAS and hearing” retrieved 57 articles, and with “oxidative”, no results were retrieved; “OSAS and audiology” showed 42 results, but only one was found under “oxidative”. Lastly, “CPAP and oxidative” retrieved 206 articles, and 15 articles have been selected. All the published articles with pediatric patients have been excluded because this study is based only on adult patients. Furthermore, all the research that included all of the OSAS-related comorbidities, like cardiovascular and metabolic diseases, or every condition that could affect the auditory system, have not been considered. This is because in order to demonstrate the correlation between OSAS and hearing loss, it is necessary to exclude other causes of hearing damage that are pathology related. Similarly, all the articles with patients affected by ORL diseases, like otitis media, tubaric dysfunctions, and nasal obstruction, which can cause neurosensorial, conductive, or mixed hearing loss, have been excluded. Ultimately, all the studies involving lab animals, have been eliminated from the study because our research is focused only on human subjects. From this literature review, eleven articles were considered, and eight extensively evaluated OSAS effects on the auditory system and how this can be linked to microvascular damage of the tissues, and one focused on the effects of CPAP treatment .p > 0.05), both in terms of peak (I-III-V) and interpeak latencies. However, it has been found with speech-ABR that OSA patients had longer latency values than the control group, as regards the transient portion of speech-ABR. The statistical analysis results that were significant differences in the latencies between OSA and the control group for peak V, peak C, and peak O (p < 0.05). Another study compared 35 patients  affected by moderate and severe OSAS with a control group composed of 30 individuals  identified as having low-risk OSAS using the stop-bang questionnaire. With pure-tone audiometry, the hearing threshold of the OSAS group was significantly higher than the control group (p < 0.001). Even examining the frequencies separately, the hearing threshold of OSAS patients at 500, 1000, 2000, 4000, and 8000 Hz was significantly higher than the control group [p < 0.001, and left ear p < 0.05). Moreover, hearing thresholds and PSG data have been compared. No correlations between AHI, SpO2, TST, TST90, mean desaturation, and pure-tone audiometry data have been found. Spinosi et al. [p = 0.01). A total of 54 of these patients were affected by tinnitus, without significant difference in sex; 42 subjects affected by tinnitus were OSAS patients, while on the contrary, 12 were not OSAS patients (p = 0.004). A mild difference in the prevalence of hearing loss has been found with pure-tone audiometry (p = 0.23). A more significant hearing loss has been found in individuals affected by moderate and severe OSAS (p = 0.001). More specifically, all groups were characterized by a mean hearing threshold of 25 dB HL for the frequencies 250, 500, 1000, 2000, and 3000 Hz, and progressive hearing loss, with a peak of 60 dB HL for the frequencies 11.200, 12.500, 14.000 and 16.000 Hz in the case of moderate and severe OSAS. Overall, 45% of simple snoring and 24% of OSAS patients passed the test of TEOAe. Moreover, a significant difference between simple snoring and individuals affected by severe OSAS at the frequencies 3000 and 4000 Hz has been found. The analysis of ROM levels revealed a mean value of 323.29 ± 56.87 CARR U, with a significant difference (p = 0.004) between severe OSAS patients and simple snoring. Furthermore, a very higher level of ROM has been observed in individuals affected by tinnitus (p = 0.035). Casale et al. [2, mean age 38 years old), of which 18  was the severe OSAS group, and 21 , were the control group. The hearing threshold of the OSAS group was significantly higher than the control group (p < 0.01) at the pure-tone audiometry. Likewise, the values of the reproducibility test of the TEOAe of OSAS patients were lower than the control group (p < 0.01). The brainstem auditory evoked potentials (BAEPs) showed that in OSAS patients, there was a significantly prolonged peak latency in the wave I-III-V than simple snoring (p < 0.01). Moreover, analyzing the reproducibility of these waves, a significant difference between OSAS and the control group has been found. However, there was no correlation between AHI, mean SpO2, and auditory data as hearing threshold, TEOAe, and brainstem auditory evoked potential data. Wang et al. [p = 0.01). To study the auditory function, pure-tone audiometry, tympanogram, DPOAe, and click-ABR have been performed. Qiuyang Fu et al. [p < 0.05 has been obtained. Lastly, our review considered one article about the correlation between CPAP and its effects on hearing function. Deniz and Ersozlu [p > 0.05). Of these 22 patients, 16 were males, and 6 were females. A decrease in the hearing threshold > 10 dB in six ears of group A and in four ears of group B was detected. No change in hearing was found in 34 ears, and none showed an improvement in hearing ≥ 10 dB. According to the chi-square test for the examination of the relationship between a change in hearing and the two groups, no significant changes in hearing (75% group A and 80% group B) in many patients have been found (p > 0.05).From the literature, a few articles focusing articles underline the effect of OSAS on the auditory system. Quiyang fu et al.  analyzedi et al.  analyzede et al.  selectedg et al.  comparedu et al.  added sp Ersozlu  studied How can OSAS affect the auditory system? There are several hypotheses mainly associated with microvascular impairment and the damaging effects of reactive oxygen species (ROS). Steiner et al.  reportedMultiple pieces of evidence suggest that altered mitochondrial function and oxidative stress both in the OSAS and cochlea could play a pivotal role ,42,43,44Mitochondria are intracellular organelles that have the function of nutrient metabolization and ATP production, and they are involved in energy metabolism, the generation of free radicals, calcium homeostasis, cell survival, and death . They prOur body tries to adjust itself in this condition of hypoxia, by producing numerous molecules useful for cells survival in the condition of a lack of oxygen, like Hypoxia-Induced Factor 1-α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) . HIF-1α It also seems that some epigenetic alterations are involved in intermittent hypoxia and OSAS, involving the small non-coding-RNA as microRNA (miRNAs) . MiRNAs Intermittent hypoxia and oxidative stress activate an immune response by our organism, involving proinflammatory molecules, like TNF, CRP, and IL-6 and IL-8, with increased levels of NF-kB and TNF-α . IL-8 anRegarding the hearing system, the external ciliate cells of the cochlea, at its basal turn, are vulnerable to oxidative stress, probably because there is a minor activity of the antioxidant enzymes correlated with glutathione . It is iIn our opinion, high-frequency pure-tone audiometry could be a more cost-effective tool for the early diagnosis of hearing loss in OSAS patients. According to the tonotopic theory and to the pathophysiology of the possible auditory damage due to oxidative stress caused by intermittent hypoxia in OSAS patients, extended high frequencies might be impaired first by endothelial damage. High-frequency pure-tone audiometry is a tool used to evaluate hearing threshold in the frequency range of 8–20 kHz and detecting hearing loss before the involvement of medium and low frequencies and the impairment of hearing capacity .Antioxidants are molecules that inhibit ROS production and regulate oxidative stress. They can be endogenous, produced in vivo, and exogenous, taken from the outside. Endogenous antioxidants are the molecules we discussed early in this section. Exogenous antioxidants comprehend water and lipid-soluble molecules. Water-soluble antioxidants are methionine, vitamin C, carnitine, riboflavin, niacin, folic acid, polyphenols, and catechins. Methionine has the function to reduce cholesterol blood levels and to remove ROS . RiboflaOSAS is a disease characterized by chronic snoring, episodes of apnea, and episodes of hypopnea that lead to a reduction in blood oxygen levels and arousal. Sleep fragmentation decreases its quality. CPAP, giving positive pressure in the upper airways, overcomes the obstruction relating to the rhino- and oropharyngeal collapse, healing the symptoms relating to the pathology. Untreated OSAS can lead to cardiovascular, metabolic, and cerebrovascular complications, and one of the main mechanisms that leads to these comorbidities is oxidative stress due to intermittent hypoxia, which leads to an intense inflammatory response via multiple pathways. Untreated OSAS can affect the hearing system, and this is evident in the pure-tone audiometry (deficit for high frequencies), DPOAE, TEOAE, and in the brainstem auditory evoked potentials . Such modifications are evident in patients with severe OSAS, being more conspicuous. In individuals affected by mild OSAS, these modifications can be detectable only with speech-ABR, and it was suggested  that thi


Background and Objectives: This narrative review of the literature explores the effect of body temperature on hearing. In particular, its focus is on extended high frequency (EHF) hearing—the range beyond the standard audiometric limit of 8 kHz. Such high frequencies are the first to be affected by noise-induced hearing loss, and so monitoring them can provide an early warning sign of incipient damage. Materials and Methods: This review builds on a personal literature database of 216 references covering the general topic of EHF hearing; the procedure was to then identify papers related to whole-body or cochlear cooling. A starting point was the paper by Munjal et al. who in 2013 reported changes of up to 15–30 dB in the EHF thresholds of subjects who had undergone cardiopulmonary bypass (CBP) surgery, which typically involves mild to moderate hypothermia—cooling of the blood—to reduce cellular oxygen demand and minimise tissue damage. Results: Reviewing the surrounding literature, we find that although CBP surgery by itself can impair hearing thresholds, lower body and cochlear temperatures in general provide neuroprotective effects. A connection between hearing loss and CBP surgery has been periodically documented, but the mechanism behind it has yet to be conclusively identified. Conclusions: The observations reviewed here tend to confirm the otoprotective effects of cooling. We consider that the high sensitivity of EHF thresholds to temperature is a major factor that has not been sufficiently recognised, although it has important implications for otological research and practice. Two important inferences are that, first, monitoring EHF thresholds might have considerable value in audiology, and, second, that lowering temperature of the cochlea during cochlear implantation might provide substantially better hearing preservation, as some researchers have already suggested. Extended high frequency (EHF) hearing is concerned with hearing beyond the range encompassed by the traditional audiogram. While audiologists typically measure hearing thresholds from 0.125 to 8 kHz, human hearing continues up to 20 kHz or more. Measurement and calibration at frequencies between 8 and 20 kHz is more difficult, while speech discrimination is largely unaffected by losses in this band. Nevertheless, auditory researchers are now becoming aware that these frequencies are important, mainly because they are the first frequencies to be affected by hearing loss, which progressively moves to lower frequencies as it becomes worse )From a consideration of the above, we can see that there are two major factors at play. The first, and perhaps the easiest to establish, is that hypothermia generally reduces the amplitudes of OAEs . This isThe other important perspective is the indication that hypothermia is not just neuroprotective but otoprotective as well. Cryotherapy tends to increase tolerance to ischemia, reduce sensitivity to toxic chemicals, and reduce hearing loss in response to acoustic trauma. That is, following hypothermia, the cochlea will bounce back and will be more likely to regain its previous function than if the cooling was not applied, which is an important consideration for those undergoing cochlear implantation in which physical damage is apt to occur.However, the best way of cooling the cochlea is presently unknown. Clearly, localised cooling is the only practical option, as whole-body cooling is complicated and carries severe risks. Head and neck cooling, as used by Hato et al. , appearsThe focus of the Stanford work is to avoid damage to hearing due to ototoxic materials, primarily cisplatin and similar therapeutic chemicals used for cancer therapies. However, another promising field is that of cochlear implantation. It is now more common for those undergoing hearing related surgeries to have “partial hearing”, in which they require a cochlear implant for receiving high frequencies, but still have residual hearing at low frequencies (below 1 kHz) and can still use those frequencies for natural hearing  . Making Nevertheless, for all the positive indicators for the effectiveness of cooling, there are still many unknowns. Perhaps the most significant, as pointed out by Péus et al. , is thatThere are two useful conclusions from this narrative review. Firstly, that monitoring OAEs offers one way of keeping track of the temperature inside the cochlea. This applies particularly to OAEs in the extended high frequency region, which are particularly sensitive to temperature. The second is that hypothermia is otoprotective—that it protects the cochlea from mechanical insult and enables it to rebound to normal functioning after the hypothermia has been removed.Both these conclusions require careful validation in order for progress to be made, but there appears to be considerable potential for benefitting patients undergoing cochlear surgery, notably those receiving cochlear implants and who also have residual low-frequency hearing.