Aren Bezdjian

Incidence of platinum-induced ototoxicity in pediatric patients in Quebec.

The antineoplastic agents cisplatin and carboplatin are widely‐used and highly‐effective against a variety of pediatric cancers. Unfortunately, ototoxicity is a frequently encountered side effect of platinum‐based chemotherapy. There is currently no treatment or prevention for platinum‐induced ototoxicity and development of hearing loss may lead to devastating consequences on the quality of life of pediatric cancer survivors. The objective of this study is to determine the incidence of platinum‐induced ototoxicity in a large series of pediatric patients and to evaluate the incidence of progression of ototoxicity after completion of treatment.

A Systematic Review on Complications of Tissue Preservation Surgical Techniques in Percutaneous Bone Conduction Hearing Devices.

Objective: To investigate skin-related postoperative complications from tissue preservation approaches in percutaneous bone conduction device (BCD) implantations. Data Sources: PubMed, Embase, and Cochrane Library. Study Selection: We identified studies on BCDs including the opted surgical technique and derived complications. Retrieved articles were screened using predefined inclusion criteria. Critical appraisal included directness of evidence and risk of bias. Studies that successfully passed critical appraisal were included. Data Extraction: Outcome measures included patient demographics, surgery time, follow-up time, and complications reported by Holgers classification. Data Synthesis: We selected 18 articles for data extraction; encompassing 381 BCDs implanted using non-skin thinning approaches. Four studies reported an implantation technique using the punch method (81 implants), 13 studies applied the linear incision technique without soft tissue reduction (288 implants) and one study used the Weber technique (12 implants). Holgers 3 was described in 2.5% following the punch technique, in 5.9% following the linear incision technique, and in no implants following the Weber technique. One patient was mentioned having Holgers 4, skin overgrowth was reported in 6 patients, and 10 studies compared their non-skin thinning technique with a skin-thinning technique. Overall, the soft tissue preservation technique had a similar or superior complication rate, shorter surgical time, and better and faster healing, compared with the soft tissue reduction technique. Conclusion: Tissue preservation surgical techniques for percutaneous BCDs have limited postoperative skin complication rates. Moreover, these techniques are suggested to have at least similar complications rates compared with skin-thinning techniques.

Association of Caffeine and Hearing Recovery After Acoustic Overstimulation Events in a Guinea Pig Model

IMPORTANCE Noise-induced hearing loss is an increasingly worrisome problem. Although caffeine intake is common in people involved in noise-related environments, the effect of caffeine on the recovery of hearing after a temporary threshold shift requires further understanding. OBJECTIVES To determine whether caffeine impairs hearing recovery in a guinea pig model exposed to acoustic overstimulation. DESIGN, SETTING, AND SUBJECTS This experiment at the McGill University Auditory Sciences Laboratory used 24 female albino guinea pigs (age, 6 months; weight, 500-600 g) divided randomly into 3 groups of 8 animals each. Group 1 was exposed to caffeine; group 2, acoustic overstimulation events (AOSEs); and group 3, both. Data were collected from July 1, 2013, to March 30, 2014, and analyzed from April 1 to August 1, 2014. INTERVENTIONS Daily caffeine dose for groups 1 and 3 consisted of 25 mg/kg administered intraperitoneally for 15 days. The AOSEs were administered on days 1 and 8 and consisted of 1 hour of 110-dB pure-tone sound. MAIN OUTCOMES AND MEASURES Serial auditory brainstem response (ABR) tests to determine the audiological threshold shift and recovery were obtained at baseline and on days 1 (1 hour after the first AOSE), 4, 8 (before and 1 hour after the second AOSE), 11, and 15. Scanning electron and light microscopy of the cochleas were performed to determine morphologic changes. RESULTS The day 1 post-AOSE measurement resulted in a similar threshold shift in all animals in groups 2 and 3 at all frequencies tested (8, 16, 20, and 25 kHz). The maximum threshold shift was at 16 kHz, with a mean of 66.12 dB. By day 8, the threshold shift in group 2 recovered completely at all frequencies except 20 kHz, where a mean threshold shift of 20.63 dB of sound pressure level (SPL) was present. Hearing impairment in group 3 persisted in 8-, 16-, and 25-kHz frequencies with thresholds of 21.88, 28.13, and 26.25 dB SPL, respectively (P = .001). After a second AOSE at day 8, similar threshold shift and outcome were recorded on day 15 compared with day 8, with a mean threshold shift at 20 kHz of 29.38 dB SPL in group 2 and mean threshold shifts at 8, 16, 20, and 25 kHz of 29.38, 35.63, 40.63, and 38.75 dB SPL, respectively, in group 3. The difference in ABR threshold recovery was in concordance with scanning electronic and light microscopy findings for each group. CONCLUSIONS AND RELEVANCE A daily dose of caffeine was found to impair the recovery of hearing after an AOSE.

What to do with medialized tympanostomy tubes? A survey of pediatric otolaryngologists

INTRODUCTION Tympanostomy tube placement is the most common surgical procedure performed in children. Medial migration of a tympanostomy tube is a rare occurrence where the tube migrates into the middle ear cavity as opposed to its normal extrusion into the external auditory canal. Whether medialized tympanostomy tubes should be surgically removed in asymptomatic patients is controversial. The objective of this study was to determine experience and management approach of medialized tympanostomy tubes among pediatric otolaryngologists. METHODS A 12-question cross-section survey was designed and distributed to the American Society of Pediatric Otolaryngology (ASPO) members. The survey study was granted McGill University institutional review board and ASPO research committee approval. The survey data were filtered and cross-tabulated. Descriptive statistics were generated. RESULTS 128 pediatric otolaryngologists completed the 12-question survey. The majority of respondents had experienced at least one case of medialized tympanostomy tube (90.6%). The majority of patients (82.0%) were asymptomatic. 74 out of 128 respondents (57.8%) indicated that they would not remove a medialized tube in an asymptomatic patient. However, 7.0% of those respondents clarified that they would proceed to surgical removal if the patient were undergoing general anesthesia for another surgery. 30.5% of respondents indicated that they would surgically remove the tube even if the patient were asymptomatic. 6.3% of respondents indicated that opted management in children would be based on a shared decision with parents. Most respondents (80.5%) did not experience complications with surgical removal nor with elected observation. CONCLUSION There is no consensus among pediatric otolaryngologists regarding the necessity of surgically removing a medialized tympanostomy tube in asymptomatic patients. The survey suggests that both options are acceptable. If observation is chosen, it is important that parents are well informed of the potential long-term sequelae of a medialized tube and advised to consult if symptoms occur.

The Effect of Radiotherapy on Gentamicin Ototoxicity An Animal Model

Objective Patients undergoing radiotherapy (RT) often present with serious bacterial infections requiring the use of antibiotic treatment. Gentamicin is a commonly used aminoglycoside antibiotic, whose ototoxicity remains a major problem in clinical use. The objective of this study was to determine whether radiation exposure can influence gentamicin-induced ototoxicity. Study Design Prospective animal study. Setting Animal care facilities of the Montreal Children’s Hospital Research Institute. Methods Sixteen guinea pigs received low-dose RT unilaterally for 4 weeks (total: 48 Gy). Animals then received low or high doses of gentamicin (40 mg/kg/d and 80 mg/kg/d) for 10 days. The ears were divided into 4 groups: gentamicin 40 mg, gentamicin 80 mg, gentamicin 40 mg + RT, and gentamicin 80 + RT. Auditory brainstem responses and distortion products otoacoustic emissions were assessed at baseline and before and after gentamicin treatment. Cochlear morphology using light and scanning electron microscopy were evaluated. Results High-dose gentamicin caused significant auditory brainstem response threshold shifts (P = .020), with greater hearing loss in the irradiated ear (difference of 23.6 + 7.5 dB). All animals exposed to high-dose gentamicin had head tilts toward the radiated side. Cochlear morphology revealed the greatest hair cell damage in the gentamicin 80 + RT group followed by gentamicin 80. Conclusion Results suggest that radiation can exacerbate the ototoxicity of gentamicin at high doses.

Sialendoscopy in treating pediatric salivary gland disorders: a systematic review

ObjectiveThe primary aim of this study is to conduct a systematic review in order to evaluate the use of sialendoscopy in treating pediatric salivary gland disorders.MethodsEligible articles were identified through a comprehensive search of electronic databases. Using predefined inclusion criteria, published articles on sialendoscopy in children were selected and reviewed.Results17 articles including 323 pediatric patients and 424 salivary glands managed by sialendoscopy were identified. The most common salivary gland disorder affected was the parotid (83% of cases), followed by the submandibular gland (16.5% of cases). Juvenile recurrent parotitis (68.9%) was the most frequent diagnosis followed by sialolithiasis (14.7%). The most common complication was ductal perforation. During a pooled mean follow-up time of 18.3 months, recurrences were reported in 14.5% of patients mostly in patients diagnosed with juvenile recurrent parotitis.ConclusionSialendoscopy is a minimally invasive diagnostic and therapeutic tool for inflammatory salivary gland disorders in pediatric patients. Based on the current review, sialendoscopy can be successfully implemented in cases of pediatric salivary gland disorders.

Preliminary audiologic and peri-operative outcomes of the Sophono™ transcutaneous bone conduction device: A systematic review

OBJECTIVE To delineate the auditory functional improvement and peri-operative outcomes of the Sophono™ transcutaneous bone conduction device. METHODS Eligible articles presenting patients implanted with the Sophono™ were identified through a comprehensive search of PubMed and Embase electronic databases. All relevant articles were reviewed to justify inclusion independently by 2 authors. Studies that successfully passed critical appraisal for directness of evidence and risk of bias were included. RESULTS From a total of 125 articles, 8 studies encompassing 86 patients using 99 implants were selected. Most patients (79.1%) were children. Ear atresia (67.5%) was the most frequently reported indication for Sophono™ implantation. Overall pure tone average auditory improvement was 31.10 (±8.29) decibel. During a mean follow-up time of 12.48 months, 25 patients (29%) presented with post-operative complications from which 3 were deemed as serious implant-related adverse events (3.5%). CONCLUSIONS The Sophono™ transcutaneous bone conduction device shows promising functional improvement, no intra-operative complications and minor post-operative skin related complications. If suitable, the device could be a proposed solution for the rehabilitation of hearing in children meeting eligibility criteria. A wearing schedule must be implemented in order to reduce magnet-related skin complications.

Towards Clinical Application of Neurotrophic Factors to the Auditory Nerve; Assessment of Safety and Efficacy by a Systematic Review of Neurotrophic Treatments in Humans

Animal studies have evidenced protection of the auditory nerve by exogenous neurotrophic factors. In order to assess clinical applicability of neurotrophic treatment of the auditory nerve, the safety and efficacy of neurotrophic therapies in various human disorders were systematically reviewed. Outcomes of our literature search included disorder, neurotrophic factor, administration route, therapeutic outcome, and adverse event. From 2103 articles retrieved, 20 randomized controlled trials including 3974 patients were selected. Amyotrophic lateral sclerosis (53%) was the most frequently reported indication for neurotrophic therapy followed by diabetic polyneuropathy (28%). Ciliary neurotrophic factor (50%), nerve growth factor (24%) and insulin-like growth factor (21%) were most often used. Injection site reaction was a frequently occurring adverse event (61%) followed by asthenia (24%) and gastrointestinal disturbances (20%). Eighteen out of 20 trials deemed neurotrophic therapy to be safe, and six out of 17 studies concluded the neurotrophic therapy to be effective. Positive outcomes were generally small or contradicted by other studies. Most non-neurodegenerative diseases treated by targeted deliveries of neurotrophic factors were considered safe and effective. Hence, since local delivery to the cochlea is feasible, translation from animal studies to human trials in treating auditory nerve degeneration seems promising.

Assessment of ototoxicity of intratympanic administration of Auralgan in a chinchilla animal model

Auralgan (benzocaine and antipyrine) is an over‐the‐counter otic drug commonly used for otalgia. Nevertheless, there is limited evidence about the effects of the drug on hearing function and cochlear morphology in the presence of a tympanic membrane perforation. The aim of the present study was to assess the cytotoxicity of Auralgan using cultured auditory cells (HEI‐OC1) and to examine its effects on hearing function and cochlear morphology after intratympanic administration in a chinchilla model.

Quality of reporting of otorhinolaryngology articles using animal models with the ARRIVE statement

Research involving animal models is crucial for the advancement of science, provided that experiments are designed, performed, interpreted, and reported well. In order to investigate the quality of reporting of articles in otorhinolaryngology research using animal models, a PubMed database search was conducted to retrieve eligible articles. The checklist of the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines was used to assess the quality of reporting of articles published in ear, nose and throat (ENT) and multidisciplinary journals. Two authors screened titles, abstracts, and full texts to select articles reporting otorhinolaryngology research using in vivo animal models. ENT journals (n = 35) reported a mean of 57.1% adequately scored ARRIVE items (median: 58.3%; 95% confidence interval [CI; 53.4–60.9%]), while articles published in multidisciplinary journals (n = 36) reported a mean of 49.1% adequately scored items (median: 50.0; 95% CI [46.2–52.0%]). Articles published in ENT journals showed better quality of reporting of animal studies based on the ARRIVE guidelines (P < 0.05). However, adherence to the ARRIVE guidelines is generally poor in otorhinolaryngology research using in vivo animal models. The endorsement of the ARRIVE guidelines by authors, research and academic institutes, editorial offices and funding agencies is recommended for improved reporting of scientific research using animal models.