PEPITA: Parallelized High-Throughput Quantification of Ototoxicity and Otoprotection in Zebrafish Larvae.

Drug-induced hearing injury (ototoxicity) is a common, debilitating side effect of many antibiotic regimens that can be worsened by adverse drug interactions. Such adverse drug interactions are often not detected until after drugs are already on the market because of the difficulty of measuring all possible drug combinations. While in vivo mammalian assays to screen for ototoxic damage exist, they are currently time-consuming, costly, and limited in throughput, which limits their utility in assessing drug interaction outcomes.

screening for toxicity-modulating drug interactions identifies antagonism that protects against ototoxicity in zebrafish.

Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug-drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury.

screening for toxicity-modulating drug interactions identifies antagonism that protects against ototoxicity in zebrafish.

Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury.

Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes.

Importance: In the US, most childhood-onset bilateral sensorineural hearing loss is genetic, with more than 120 genes and thousands of different alleles known. Primary treatments are hearing aids and cochlear implants. Genetic diagnosis can inform progression of hearing loss, indicate potential syndromic features, and suggest best timing for individualized treatment.

Educational Environments and Secondary School Outcomes Among Students Who Are D/deaf and Hard of Hearing in Special Education.

Purpose: The purpose of this study is to provide updated national estimates on the annual number, educational environments, and secondary school outcomes of students who are D/deaf and hard of hearing (D/HH) receiving special education (SpEd) and related services in the United States.

Method: We performed a retrospective cross-sectional descriptive analysis of Individuals with Disabilities Education Act, Part B, Section 618 data from 2012 to 2018. Participants included students 6-21 years old in SpEd with "hearing impairment" reported as their primary disability.

Impact of Eliminating Local Anesthesia on Immediate Postoperative Analgesia in Pediatric Ambulatory Adenotonsillectomy.

Unlabelled: Our goal was to standardize intraoperative analgesic regimens for pediatric ambulatory tonsillectomy by eliminating local anesthetic use and to determine its impact on postoperative pain measures, while controlling for other factors.

Methods: We assembled a quality improvement team at an ambulatory surgery center. They introduced a standardized anesthetic protocol, involving American Society of Anesthesiologists Classification 1 and 2 patients undergoing adenotonsillectomy.

Reliability of Measuring Insertion Depth in Cochlear Implanted Infants and Children Using Cochlear View Radiography.

Objectives: Cochlear implant depth of insertion affects audiologic outcomes and can be measured in adults using plain films obtained in the "cochlear view." The objective of this study was to assess interrater and intrarater reliability of measuring depth of insertion using cochlear view radiography.

Study Design: Prospective, observational.

Defining Essential Services for Deaf and Hard of Hearing Children during the COVID-19 Pandemic.

COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of "social distancing," reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered "elective," balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers.

Pediatric Otolaryngology Divisional and Institutional Preparatory Response at Seattle Children's Hospital after COVID-19 Regional Exposure.

Coronavirus disease 2019 (COVID-19) is a novel coronavirus resulting in high mortality in the adult population but low mortality in the pediatric population. The role children and adolescents play in COVID-19 transmission is unclear, and it is possible that healthy pediatric patients serve as a reservoir for the virus. This article serves as a summary of a single pediatric institution's response to COVID-19 with the goal of protecting both patients and health care providers while providing ongoing care to critically ill patients who require urgent interventions.

Unilateral Hearing Loss in Youth: Development of Candidate Items for a Condition-Specific Validated Instrument.

Objective: This study interviewed youth with unilateral hearing, utilizing their responses to generate candidate items for a condition-specific patient-reported instrument.

Study Design: Mixed methods, cross-sectional.

Setting: Tertiary care children's hospital.

Comparison of MRI in pediatric cochlear implant recipients with and without retained magnet.

Objective: To report and compare medical, radiological, and audiological outcomes in pediatric cochlear implant recipients who underwent 1.5 and 3 Tesla strength MRI with and without retained magnet.

Methods: Retrospective chart review at a tertiary care pediatric hospital and review of literature.

Mitochondrial calcium uptake underlies ROS generation during aminoglycoside-induced hair cell death.

Exposure to aminoglycoside antibiotics can lead to the generation of toxic levels of reactive oxygen species (ROS) within mechanosensory hair cells of the inner ear that have been implicated in hearing and balance disorders. Better understanding of the origin of aminoglycoside-induced ROS could focus the development of therapies aimed at preventing this event. In this work, we used the zebrafish lateral line system to monitor the dynamic behavior of mitochondrial and cytoplasmic oxidation occurring within the same dying hair cell following exposure to aminoglycosides.

Canertinib induces ototoxicity in three preclinical models.

Neuregulin-1 (NRG1) ligand and its epidermal growth factor receptor (EGFR)/ERBB family regulate normal cellular proliferation and differentiation in many tissues including the cochlea. Aberrant NRG1 and ERBB signaling cause significant hearing impairment in mice. Dysregulation of the same signaling pathway in humans is involved in certain types of cancers such as breast cancer or non-small cell lung cancer (NSCLC).

Identification of small molecule inhibitors of cisplatin-induced hair cell death: results of a 10,000 compound screen in the zebrafish lateral line.

Hypothesis: The zebrafish lateral line can be used to identify small molecules that protect against cisplatin-induced hair cell death.

Background: Cisplatin is a commonly used chemotherapeutic agent, which causes hearing loss by damaging hair cells of the inner ear. There are currently no FDA-approved pharmacologic strategies for preventing this side effect.

Upper aerodigestive magnetic foreign bodies in children.

Objectives/hypothesis: Small, powerful magnets are increasingly available in toys and other products, and are responsible for increasing numbers of foreign body injuries in children. Small, spherical, neodymium magnets available since 2008 are of particular concern. We aimed to identify all cases of upper aerodigestive foreign bodies at our institution over 15.

Fish in a Dish: Drug Discovery for Hearing Habilitation.

The majority of hearing loss is caused by the permanent loss of inner ear hair cells. The identification of drugs that modulate the susceptibility to hair cell loss or spur their regeneration is often hampered by the difficulties of assaying for such complex phenomena in mammalian models. The zebrafish has emerged as a powerful animal model for chemical screening in many contexts.

Functional mechanotransduction is required for cisplatin-induced hair cell death in the zebrafish lateral line.

Cisplatin, one of the most commonly used anticancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death.

"In-bone" utricle cultures--a simplified, atraumatic technique for in situ cultures of the adult mouse (Mus musculus) utricle.

Hypothesis: The "in-bone" method of culturing utricles described here is a reliable and atraumatic technique for culturing mature mouse hair cells and studying hair cell death and protection.

Background: The current in vitro technique for studying hair cells of the mature mouse utricle involves removal from the temporal bone and free floating culture in media. This technique can be problematic because of variability in the preservation of the sensory epithelium and a steep learning curve that results in injury of the sensory epithelium in less experienced hands.

Quinoline ring derivatives protect against aminoglycoside-induced hair cell death in the zebrafish lateral line.

We have previously published results from a screen of 1,040 FDA-approved drugs and bioactives (NINDS Custom Collection) for drugs that protect against neomycin-induced hair cell death (Ou et al., J Assoc Res Otolaryngol 10:191-203, 2009). Further evaluation of this drug library identified eight protective drugs that shared a common quinoline scaffold.

Screening for chemicals that affect hair cell death and survival in the zebrafish lateral line.

The zebrafish lateral line is an efficient model system for the evaluation of chemicals that protect and damage hair cells. Located on the surface of the body, lateral line hair cells are accessible for manipulation and visualization. The zebrafish lateral line system allows rapid screens of large chemical libraries, as well as subsequent thorough evaluation of interesting compounds.

Transoral approach for direct and complete excision of vallecular cysts in children.

Objective: To review the presentation, evaluation, and treatment of children with vallecular cysts and introduce a new technique of transoral excision for this entity.

Methods: Retrospective case series of children diagnosed with vallecular cyst between 2001 and 2008 at a single tertiary care children's hospital. Data collected, including age at diagnosis, presenting symptoms, additional diagnoses, diagnostic modality, prior and subsequent surgical therapy, length of hospital stay, length of follow-up, and recurrence were analyzed with descriptive statistics.

Hair cell toxicity in anti-cancer drugs: evaluating an anti-cancer drug library for independent and synergistic toxic effects on hair cells using the zebrafish lateral line.

Inner ear hair cell loss is the most common pathology seen after ototoxic drug injury. While certain drugs such as aminoglycosides and cisplatin are well-known to have dramatic ototoxic effects, it is probable that there are other drugs that cause occult degrees of hair cell loss and lesser degrees of hearing loss. Anti-cancer drugs are particularly strong candidates due to their general cytotoxicity.

Assessing the immunization status of pediatric cochlear implant recipients using a state-maintained immunization registry.

Objective: To demonstrate the use of a state-maintained database (CHILD Profile) to monitor immunization status of pediatric cochlear implant recipients, and to assess compliance with current vaccination recommendations for cochlear implant users managed at Seattle Children's Hospital.

Study Design: Cross-sectional study.

Setting: Tertiary academic pediatric hospital.