Subsequent Hearing Loss Research Articles

The Medicare annual wellness visit: An opportunity to improve health system identification of hearing loss?

Hearing loss is prevalent and consequential but under-diagnosed and managed. The Medicare Annual Wellness Visit (AWV) health risk assessment elicits patient-reported hearing concerns but whether such information affects documentation, diagnosis, or referral is unknown. We use 5 years of electronic medical record (EMR) data (2017-2022) for a sample of 13,776 older primary care patients. We identify the first (index) AWV indication of hearing concerns and existing and subsequent hearing loss EMR diagnoses (visit diagnoses or problem list diagnoses) and audiology referrals. For a 20% random sample of AWV notes (n = 474) we compared hearing loss EMR diagnoses to documentation of (1) hearing concerns, (2) hearing loss/aid use, and (3) referrals for hearing care. Of 3845 (27.9%) older adults who identified hearing concerns (mean age 79.1 years, 57% female, 75% white) 24% had an existing hearing diagnosis recorded. Among 474 patients with AWV clinical notes reviewed, 90 (19%) had an existing hearing loss diagnosis. Clinicians were more likely to document hearing concerns or hearing loss/aid use for those with (vs. without) an existing EMR diagnosis (50.6% vs. 35.9%, p = 0.01; 68.9% vs. 37.5%, p < 0.001, respectively). EMR diagnoses of hearing loss were recorded for no more than 40% of those with indicated hearing concerns. Among those without prior diagnosis 38 (9.9%) received a hearing care referral within 1 month. Subgroup analysis suggest greater likelihood of documenting hearing concerns for patients age 80+ (OR:1.51, 95% confidence interval [CI]: 1.03, 2.19) and decreased likelihood of documenting known hearing loss among patients with more chronic conditions (OR: 0.49, 95% CI: 0.27, 0.9), with no differences observed by race. Documentation of hearing loss in EMR and AWV clinical notes is limited among older adults with subjective hearing concerns. Systematic support and incorporation of hearing into EMR and clinical notes may increase hearing loss visibility by care teams.

Intracranial malignant peripheral nerve sheath tumor: A case report and comprehensive literature review.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare malignant soft-tissue sarcomas arising from peripheral nerves. Little data exist regarding MPNST originating intracranially. Here, we present a 7th/8th nerve complex MPNST, discuss the treatment strategy and patient outcome, and provide a comprehensive review of existing literature. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed and crossed references were queried, yielding 37 publications from 1952 to the present. Fifty-three cases of primary intracranial and extra-axial MPNST were identified. We additionally report a 40-year-old female presented with acute onset dizziness and subsequent hearing loss with associated right-sided facial numbness. Magnetic resonance imaging revealed a 0.5 cm × 1.7 cm enhancing lesion within the right internal auditory canal extending into the cerebellopontine angle. The patient was initially treated with retro sigmoid craniotomy for tumor resection followed by a trans labyrinth approach for residual tumor resection. She completed adjuvant fractionated radiation therapy and underwent facial nerve transfer to restore complete hemifacial paralysis. The most common cranial nerves involved were V and VIII (43.4% each), with 66% of patients male and 34% female. The average age was 43.4 ± 17.4 years. The mean survival time for reported non-survivors after tissue diagnosis was 15 ± 4 months. Two-year survival for patients receiving gross total resection was 33.3% versus 22.8% with subtotal resection. MPNSTs comprise a group of highly aggressive neoplasms that rarely arise intracranially. Gross total surgical resection should be pursued when feasible.

Underestimated Subsequent Sensorineural Hearing Loss after Septicemia.

Background and Objectives: Hearing loss after septicemia has been found in mice; the long-term risk increased 50-fold in young adults in a previous study. Hearing loss after septicemia has not received much attention. The aim of this study was to assess the relationship between septicemia and subsequent hearing loss. Materials and Methods: Inpatient data were obtained from the Taiwan Insurance Database. We defined patients with sensorineural hearing loss and excluded patients under 18 years of age. Patients without hearing loss were selected as controls at a frequency of 1:5. The date of admission was defined as the date of diagnosis. Comorbidities in the 3 years preceding the date of diagnosis were retrieved retrospectively. Associations with hearing loss were established by multiple logistic regression and forward stepwise selection. Results: The odds ratio (OR) for the association between sepsis and hearing loss was 3.052 (95% CI: 1.583-5.884). Autoimmune disease (OR: 5.828 (95% CI: 1.906-17.816)), brain injury (OR: 2.264 (95% CI: 1.212-4.229)) and ischemic stroke (OR: 1.47 (95% CI: 1.087-1.988)) were associated with hearing loss. Conclusions: Our study shows that hearing loss occurred after septicemia. Apoptosis caused by sepsis and ischemia can lead to hair cell damage, leading to hearing loss. Clinicians should be aware of possible subsequent complications of septicemia and provide appropriate treatment and prevention strategies for complications.

Potential role of Bcl2 in lipid metabolism and synaptic dysfunction of age-related hearing loss

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.

Modulation of auditory processing by non-auditory brain areas: Effects of acoustic trauma

Acoustic trauma (AT) induced hearing loss elicits plasticity in the form of altered spontaneous firing throughout the central auditory pathway, including at the level of the medial geniculate nucleus (MGN). Non-auditory areas such as the prefrontal cortex (PFC) and amygdala are thought to modulate auditory processing in the MGN, which may play a role in sensory gating. In our laboratory, we investigated the functionality of inputs from the PFC and amygdala on MGN activity in different animal models (rat and guinea pig) both without and with AT. The effects of AT on auditory thresholds were investigated using auditory brainstem response (ABR) recordings or compound action potential recordings of the auditory nerve. To test circuitry functionality, we used single neuron recordings in the MGN combined with electrical stimulation of the PFC or amygdala. Our data showed, first, that electrical stimulation of either the PFC or amygdala resulted in a variety of effects within the MGN (facilitation, inhibition, or no effect) and, second, that AT and subsequent hearing loss significantly increased the magnitude of inhibition. This change in inhibition may represent a compensatory mechanism in response to the increased spontaneous activity in the central auditory pathway known to occur following hearing loss.

Acoustic trauma increases inhibitory effects of amygdala electrical stimulation on thalamic neurons in a rat model

Acoustic trauma (AT) induced hearing loss elicits plasticity throughout the central auditory pathway, including at the level of the medial geniculate nucleus (MGN). Hearing loss also results in altered neuronal responses in the amygdala, which is involved in sensory gating at the level of the MGN. However, whether these altered responses in the amygdala affect sensory gating at the level of the MGN requires further evaluation. The current study aimed to investigate the effects of AT-induced hearing loss on the functional connectivity between the amygdala and the MGN. Male Sprague–Dawley rats were exposed to either sham (n = 5; no sound) or AT (n = 6; 16 kHz, 1 h, 124 dB SPL) under full anaesthesia. Auditory brainstem response (ABR) recordings were made to determine hearing thresholds. Two weeks post-exposure, extracellular recordings were used to assess the effect of electrical stimulation of the amygdala on tone-evoked (sham n = 22; AT n = 30) and spontaneous (sham n = 21; AT n = 29) activity of single neurons in the MGN. AT caused a large temporary and small permanent ABR threshold shift. Electrical stimulation of the amygdala induced differential effects (excitatory, inhibitory, or no effect) on both tone-evoked and spontaneous activity. In tone-evoked activity, electrical stimulation at 300 µA, maximum current, caused a significantly larger reduction in firing rate in AT animals compared to sham, due to an increase in the magnitude of inhibitory effects. In spontaneous activity, there was also a significantly larger magnitude of inhibitory effects following AT. The findings confirm that activation of the amygdala results in changes in MGN neuronal activity, and suggest the functional connectivity between the amygdala and the MGN is significantly altered following AT and subsequent hearing loss.

Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction

Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin βA. We demonstrate that activin A, a homodimer of inhibin βA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin βA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target.

Identifying Clinical Criteria for an Expanded Targeted Approach to Screening for Congenital Cytomegalovirus Infection-A Retrospective Study.

Targeted screening for congenital CMV infection (cCMV), which entails CMV testing of infants who fail newborn hearing screening (NBHS), has become common practice. However, this strategy misses nearly all infected infants with normal hearing at birth who are nonetheless at high risk of subsequent hearing loss and would benefit from timely cCMV diagnosis. The objective of this study was to identify expanded criteria predictive of cCMV to increase the scope and utility of targeted newborn CMV screening. In this retrospective study, 465 newborns were tested for cCMV at a single tertiary care center with a targeted screening program between 2014 and 2018. Twenty-two infants were diagnosed with cCMV, representing 0.2% of the 12,189 births over this period and 4.7% of the infants tested. The highest prevalence of cCMV infection was among infants tested because of primary maternal CMV infection (8/42, 19%), followed by failed initial NBHS (10/88, 11.4%), maternal HIV infection (3/137, 2.2%), and clinical suspicion alone (5/232, 2.2%). The symptoms with the highest prevalence of infection among all infants tested included an enlarged liver and/or spleen (33.3%) (3/9), followed by petechiae (33.3%), microcephaly (9.4%), direct hyperbilirubinemia (7.7%), thrombocytopenia (6%), and growth impairment (4.3%). In addition to CMV screening of newborns who fail the NBHS, these data suggest that certain clinical signs of cCMV-in particular: thrombocytopenia, growth impairment, and HIV exposure in pregnancy-should be additional criteria for expanded targeted newborn CMV screening, where universal screening is not yet the standard of care.

Genetic variants and altered expression of SERPINF1 confer disease susceptibility in patients with otosclerosis.

Otosclerosis (OTSC) is a focal and diffuse bone disorder of the human middle ear characterized by abnormal bone growth and deposition at the stapes' footplate. This hinders the transmission of acoustic waves to the inner ear leading to subsequent conductive hearing loss. The plausible convections for the disease are genetic and environmental factors with yet an unraveled root cause. Recently, exome sequencing of European individuals with OTSCrevealed rare pathogenic variants in the Serpin Peptidase Inhibitor, Clade F (SERPINF1)gene. Here, we sought to investigate the causal variants of SERPINF1 in the Indian population. The gene and protein expression was also evaluated in otosclerotic stapes to ameliorate our understanding of the potential effect of this gene in OTSC. A total of 230 OTSC patients and 230 healthy controls were genotyped by single-strand conformational polymorphism and Sanger sequencing methods. Bycomparing the case controls, we identified five rare variants (c.72 C > T, c.151 G > A, c.242 C > G, c.823 A > T, and c.826 T > A) only in patients. Four variants c.390 T > C (p = 0.048), c.440-39 C > T (p = 0.007), c.643 + 9 G > A (p = 0.035), and c.643 + 82 T > C (p = 0.005) were found to be significantly associated with the disease. Down-regulation of SERPINF1 transcript level in otosclerotic stapes was quantified by qRT-PCR, ddPCR and further validated by in situ hybridization. Similarly, reduced protein expression was observed by immunohistochemistry and immunofluorescence in otosclerotic stapes that corroborate with immunoblotting of patients' plasma samples. Our findings identified that SERPINF1 variants are associated with the disease. Furthermore, reduced expression of SERPINF1 in otosclerotic stapes might contribute to OTSC pathophysiology.

Monoallelic loss of the F-actin-binding protein radixin facilitates startle reactivity and pre-pulse inhibition in mice.

Hearing impairment is one of the most common disorders with a global burden and increasing prevalence in an ever-aging population. Previous research has largely focused on peripheral sensory perception, while the brain circuits of auditory processing and integration remain poorly understood. Mutations in the rdx gene, encoding the F-actin binding protein radixin (Rdx), can induce hearing loss in human patients and homozygous depletion of Rdx causes deafness in mice. However, the precise physiological function of Rdx in hearing and auditory information processing is still ill-defined. Here, we investigated consequences of rdx monoallelic loss in the mouse. Unlike the homozygous (-/-) rdx knockout, which is characterized by the degeneration of actin-based stereocilia and subsequent hearing loss, our analysis of heterozygous (+/-) mutants has revealed a different phenotype. Specifically, monoallelic loss of rdx potentiated the startle reflex in response to acoustic stimulation of increasing intensities, suggesting a gain of function relative to wildtype littermates. The monoallelic loss of the rdx gene also facilitated pre-pulse inhibition of the acoustic startle reflex induced by weak auditory pre-pulse stimuli, indicating a modification to the circuit underlying sensorimotor gating of auditory input. However, the auditory brainstem response (ABR)-based hearing thresholds revealed a mild impairment in peripheral sound perception in rdx (+/-) mice, suggesting minor aberration of stereocilia structural integrity. Taken together, our data suggest a critical role of Rdx in the top-down processing and/or integration of auditory signals, and therefore a novel perspective to uncover further Rdx-mediated mechanisms in central auditory information processing.

Reduced BDNF expression in the auditory cortex contributed to neonatal pain-induced hearing impairment and dendritic pruning deficiency in mice

IntroductionProcedural pain in neonates is associated with impaired neurodevelopment. Whether hearing development is impaired, however, remains unknown. This study examined potential cause-and-effect relationship between neonatal pain and subsequent hearing loss...

RIPOR2-mediated autophagy dysfunction is critical for aminoglycoside-induced hearing loss.

Aminoglycosides (AGs) are potent antibiotics that are capable of treating a wide variety of life-threatening infections; however, they are ototoxic and cause irreversible damage to cochlear hair cells. Despite substantial progress, little is known about the molecular pathways critical for hair cell function and survival that are affected by AG exposure. We demonstrate here that gentamicin, a representative AG antibiotic, binds to and within minutes triggers translocation of RIPOR2 in murine hair cells from stereocilia to the pericuticular area. Then, by interacting with a central autophagy component, GABARAP, RIPOR2 affects autophagy activation. Reducing the expression of RIPOR2 or GABARAP completely prevents AG-induced hair cell death and subsequent hearing loss in mice. Additionally, abolishing the expression of PINK1 or Parkin, two key mitochondrial autophagy proteins, prevents hair cell death and subsequent hearing loss caused by AG. In summary, our study demonstrates that RIPOR2-mediated autophagic dysfunction is essential for AG-induced hearing loss.

Dync1li1 is required for the survival of mammalian cochlear hair cells by regulating the transportation of autophagosomes.

Dync1li1, a subunit of cytoplasmic dynein 1, is reported to play important roles in intracellular retrograde transport in many tissues. However, the roles of Dync1li1 in the mammalian cochlea remain uninvestigated. Here we first studied the expression pattern of Dync1li1 in the mouse cochlea and found that Dync1li1 is highly expressed in hair cells (HCs) in both neonatal and adult mice cochlea. Next, we used Dync1li1 knockout (KO) mice to investigate its effects on hearing and found that deletion of Dync1li1 leads to early onset of progressive HC loss via apoptosis and to subsequent hearing loss. Further studies revealed that loss of Dync1li1 destabilizes dynein and alters the normal function of dynein. In addition, Dync1li1 KO results in a thinner Golgi apparatus and the accumulation of LC3+ autophagic vacuoles, which triggers HC apoptosis. We also knocked down Dync1li1 in the OC1 cells and found that the number of autophagosomes were significantly increased while the number of autolysosomes were decreased, which suggested that Dync1li1 knockdown leads to impaired transportation of autophagosomes to lysosomes and therefore the accumulation of autophagosomes results in HC apoptosis. Our findings demonstrate that Dync1li1 plays important roles in HC survival through the regulation of autophagosome transportation.

Increased mitophagy protects cochlear hair cells from aminoglycoside-induced damage

ABSTRACT Aminoglycosides exhibit ototoxicity by damaging mitochondria, which in turn generate reactive oxygen species that induce hair cell death and subsequent hearing loss. It is well known that damaged mitochondria are degraded by mitophagy, an important mitochondrial quality control system that maintains mitochondrial homeostasis and ensures cell survival. However, it is unclear whether dysregulation of mitophagy contributes to aminoglycoside-induced hair cell injury. In the current study, we found that PINK1-PRKN-mediated mitophagy was impaired in neomycin-treated hair cells. Our data suggested that mitochondrial recruitment of PRKN and phagophore recognition of damaged mitochondria during mitophagy were blocked following neomycin treatment. In addition, the degradation of damaged mitochondria by lysosomes was significantly decreased as indicated by the mitophagic flux reporter mt-mKeima. Moreover, we demonstrated that neomycin disrupted mitophagy through transcriptional inhibition of Pink1 expression, the key initiator of mitophagy. Moreover, we found that neomycin impaired mitophagy by inducing ATF3 expression. Importantly, treatment with a mitophagy activator could rescue neomycin-treated hair cells by increasing mitophagy, indicating that genetic modulation or drug intervention in mitophagy may have therapeutic potential for aminoglycoside-induced hearing loss. Abbreviations: AAV: adeno-associated virus; ABR: auditory brainstem response; ATF3: activating transcription factor 3; ATOH1/MATH1: atonal bHLH transcription factor 1; BafA1: bafilomycin A1; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; COX4I1/COXIV: cytochrome c oxidase subunit 4I1; CTBP2/RIBEYE: C-terminal binding protein 2; DFP: deferiprone; EGFP: enhanced green fluorescent protein; FOXO3: forkhead box O3; GRIA2/GLUR2: glutamate receptor, ionotropic, AMPA2 (alpha 2); HC: hair cell; HSPD1/HSP60: heat shock protein 1 (chaperonin); IHC: inner hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MYO7A: myosin VIIA; OPTN: optineurin; OMM: outer mitochondrial membrane; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; RT-qPCR: real-time quantitative polymerase chain reaction; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling; USP30: ubiquitin specific peptidase 30; XBP1: X-box binding protein 1.

Transient Receptor Potential Channels and Auditory Functions.

Significance: Transient receptor potential (TRP) channels are cation-gated channels that serve as detectors of various sensory modalities, such as pain, heat, cold, and taste. These channels are expressed in the inner ear, suggesting that they could also contribute to the perception of sound. This review provides more details on the different types of TRP channels that have been identified in the cochlea to date, focusing on their cochlear distribution, regulation, and potential contributions to auditory functions. Recent Advances: To date, the effect of TRP channels on normal cochlear physiology in mammals is still unclear. These channels contribute, to a limited extent, to normal cochlear physiology such as the hair cell mechanoelectrical transduction channel and strial functions. More detailed information on a number of these channels in the cochlea awaits future studies. Several laboratories focusing on TRPV1 channels have shown that they are responsive to cochlear stressors, such as ototoxic drugs and noise, and regulate cytoprotective and/or cell death pathways. TRPV1 expression in the cochlea is under control of oxidative stress (produced primarily by NOX3 NADPH oxidase) as well as STAT1 and STAT3 transcription factors, which differentially modulate inflammatory and apoptotic signals in the cochlea. Inhibition of oxidative stress or inflammation reduces the expression of TRPV1 channels and protects against cochlear damage and hearing loss. Critical Issues: TRPV1 channels are activated by both capsaicin and cisplatin, which produce differential effects on the inner ear. How these differential actions are produced is yet to be determined. It is clear that TRPV1 is an essential component of cisplatin ototoxicity as knockdown of these channels protects against hearing loss. In contrast, activation of TRPV1 by capsaicin protected against subsequent hearing loss induced by cisplatin. The cellular targets that are influenced by these two drugs to account for their differential profiles need to be fully elucidated. Furthermore, the potential involvement of different TRP channels present in the cochlea in regulating cisplatin ototoxicity needs to be determined. Future Directions: TRPV1 has been shown to mediate the entry of aminoglycosides into the hair cells. Thus, novel otoprotective strategies could involve designing drugs to inhibit entry of aminoglycosides and possibly other ototoxins into cochlear hair cells. TRP channels, including TRPV1, are expressed on circulating and resident immune cells. These receptors modulate immune cell functions. However, whether they are activated by cochlear stressors to initiate cochlear inflammation and ototoxicity needs to be determined. A better understanding of the function and regulation of these TRP channels in the cochlea could enable development of novel treatments for treating hearing loss. Antioxid. Redox Signal. 36, 1158-1170.

Hearing Loss Risk in Pediatric Patients Treated with Cranial Irradiation and Cisplatin-Based Chemotherapy.

Cranial radiation therapy (RT) and cisplatin-based chemotherapy are essential to treating many pediatric cancers but cause significant ototoxicity. The objective of this study is to determine the relationship between the RT dose and the risk of subsequent hearing loss in pediatric patients treated with cisplatin. This retrospective study of cisplatin-treated pediatric patients examined ototoxicity from cranial RT. Ototoxicity was graded for each ear according to the International Society of Pediatric Oncology (SIOP) consensus ototoxicity scale. The RT dose to the cochlea was calculated using the mean, median, maximum, and minimum dose received to determine the most predictive parameter for hearing loss. Multivariable logistic regression models then examined risk factors for hearing loss. In 96 children (161 ears) treated with RT + cisplatin, the minimum cochlear RT dose was most predictive of hearing loss. A higher cochlear RT dose was associated with increased hearing loss (odds ratio per 10 Gy dose increase = 1.64; P = .043), with an added risk in those receiving an autologous bone marrow transplantation (hazard ratio = 10.47; P < .001). This research supports further testing of the minimum cochlear RT dose as a more predictive dose parameter for risk of ototoxicity. The cochlear RT dose was additive to the risk of hearing loss from underlying cisplatin-based chemotherapy. Exposure to autologous bone marrow transplantation was the strongest predictor of developing hearing loss, placing these children at particularly high risk for hearing loss across all cochlear doses. Future prospective studies are crucial to further inform RT dose thresholds and minimize the risk of hearing loss in childhood cancer survivors.

Cost-effectiveness of implementing routine hearing screening using a tablet audiometer for pediatric cystic fibrosis patients receiving high-dose IV aminoglycosides.

BACKGROUND: Cystic fibrosis (CF) patients who receive high-dose aminoglycosides can acquire inner ear damage and subsequent hearing loss. There is no current standard protocol for assessing ototoxicity in CF centers in the United States. OBJECTIVE: To evaluate the cost-effectiveness of a pharmacist-implemented routine hearing screening for ototoxicity among pediatric patients using a clinically validated tablet audiometer to allow for earlier detection of hearing loss in an exploratory analysis. METHODS: A Markov decision-analytic model was developed to assess the cost-effectiveness of implementing routine screening with monthly cycles over a 3-year time horizon. The model measured the difference in promptly detected hearing loss, delayed detected hearing loss, and undetected hearing loss, compared with current screening practices. Model inputs were obtained through a comprehensive literature review. Primary model outcomes included total health care costs and quality-adjusted life-years (QALYs) gained with a 3% yearly discount. One-way, two-way, and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. RESULTS: In a hypothetical cohort of 100 patients, routine screening using a tablet audiometer increased promptly detected hearing loss by 8 patients. There was an incremental gain of 3.2 QALYs at an increased cost of $333,826 compared with current screening practices. This resulted in an incremental cost-effectiveness ratio (ICER) of $103,771 per QALY. In the 1-way sensitivity analysis, the ICER ranged between $64,345 and $258,830 per QALY. CONCLUSIONS: Using a tablet audiometer for routine hearing screening appears to be a cost-effective option at a $150,000 per QALY willingness-to-pay threshold when only considering the immediate benefits gained. This analysis did not examine the long-term effects of early detection in language development for pediatric patients. DISCLOSURES: Huang reports funding from the University of North Carolina and GlaxoSmithKline Health Outcomes Fellowship. GlaxoSmithKline had no involvement in the study creation, analysis, or manuscript composition. The other authors have nothing to disclose.

Measurement of the Intracochlear Hypothermia Distribution Utilizing Tympanic Cavity Hypothermic Rinsing Technique in a Cochlea Hypothermia Model.

Introduction: Cochlea implants can cause severe trauma leading to intracochlear apoptosis, fibrosis, and eventually to loss of residual hearing. Mild hypothermia has been shown to reduce toxic or mechanical noxious effects, which can result in inflammation and subsequent hearing loss. This paper evaluates the usability of standard surgical otologic rinsing as cooling medium during cochlea implantation as a potential hearing preservation technique.Material and Methods: Three human temporal bones were prepared following standard mastoidectomy and posterior tympanotomy. Applying a retrocochlear approach leaving the mastoidectomy side intact, temperature probes were placed into the basal turn (n = 4), the middle turn (n = 2), the helicotrema, and the modiolus. Temperature probe positions were visualized by microcomputed tomography (μCT) imaging and manually segmented using Amira® 7.6. Through the posterior tympanotomy, the tympanic cavity was rinsed at 37°C in the control group, at room temperature (in the range between 22 and 24°C), and at iced water conditions. Temperature changes were measured in the preheated temporal bone. In each temperature model, rinsing was done for 20 min at the pre-specified temperatures measured in 0.5-s intervals. At least five repetitions were performed. Data were statistically analyzed using pairwise t-tests with Bonferroni correction.Results: Steady-state conditions achieved in all three different temperature ranges were compared in periods between 150 and 300 s. Temperature in the inner ear started dropping within the initial 150 s. Temperature probes placed at basal turn, the helicotrema, and middle turn detected statistically significant fall in temperature levels following body temperature rinses. Irrigation at iced conditions lead to the most significant temperature drops. The curves during all measurements remained stable with 37°C rinses.Conclusion: Therapeutic hypothermia is achieved with standard surgical irrigation fluid, and temperature gradients are seen along the cochlea. Rinsing of 120 s duration results in a therapeutic local hypothermia throughout the cochlea. This otoprotective procedure can be easily realized in clinical practice.

A case report of Adult Onset Still’s Disease and Kikuchi Fujimoto lymphadenitis-challenges and learning points

Background: Adult Onset Stills Disease (AOSD) and Kikuchi Fujimoto Lymphadenitis (KFL) are both rare Rheumatological diseases. Co-occurrence is very rare. Case Presentation: This is a case of AOSD and KFL co-occurrence presenting with polyarthritis, rash, and B Symptoms. Elevated serum lactate dehydrogenase and ferritin with anemia and lymphadenopathy raised suspicions of lymphoma. Histology confirmed KFL and clinical features, and raised ferritin confirmed AOSD. After starting sulfasalazine, the patient was admitted to the hospital with ‘Drug Reaction with Eosinophilia and Systemic Symptoms’ (DRESS) Syndrome. Prior to sepsis exclusion, Gentamicin was given and subsequent hearing loss was noted. Sustained remission was achieved with Tocilizumab and azathioprine. Tocilizumab was stopped during pregnancy. Conclusion: The diagnostic challenges of two rare overlapping Rheumatological diseases are highlighted. An early distinction of disease flares or drug reactions from sepsis is difficult. Risk-benefit ratio consideration of continuing successful treatments in pregnancy is acknowledged.

Disruption of Atg7-dependent autophagy causes electromotility disturbances, outer hair cell loss, and deafness in mice

Atg7 is an indispensable factor that plays a role in canonical nonselective autophagy. Here we show that genetic ablation of Atg7 in outer hair cells (OHCs) in mice caused stereocilium damage, somatic electromotility disturbances, and presynaptic ribbon degeneration over time, which led to the gradual wholesale loss of OHCs and subsequent early-onset profound hearing loss. Impaired autophagy disrupted OHC mitochondrial function and triggered the accumulation of dysfunctional mitochondria that would otherwise be eliminated in a timely manner. Atg7-independent autophagy/mitophagy processes could not compensate for Atg7 deficiency and failed to rescue the terminally differentiated, non-proliferating OHCs. Our results show that OHCs orchestrate intricate nonselective and selective autophagic/mitophagy pathways working in concert to maintain cellular homeostasis. Overall, our results demonstrate that Atg7-dependent autophagy plays a pivotal cytoprotective role in preserving OHCs and maintaining hearing function.