Publications by authors named "Sofia Waissbluth"

23 Publications

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The impact of COVID-19 preventive lockdowns on the prevalence of benign paroxysmal positional vertigo.

Medwave 2021 Apr 27;21(3):e8174. Epub 2021 Apr 27.

Departamento Otorrinolaringología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. ORCID: 0000-0002-8428-5095.

Introduction: The implementation of preventive lockdowns worldwide due to the COVID-19 pandemic has radically altered our daily lives. We have observed an increase in vertigo consultations during this period, mainly benign paroxysmal positional vertigo.

Objective: To determine the impact of preventive lockdown on the prevalence and characteristics of benign paroxysmal positional vertigo.

Methods: We did a retrospective study. All patients with benign paroxysmal positional vertigo during July and August 2020 who visited the clinic in Red de Salud UC Christus, Santiago, Chile, were included. Demographic data, clinical characteristics, need for repositioning maneuvers, and medical history was compared with patients seen in July and August 2019. Cases secondary to trauma and with incomplete records were excluded.

Results: During July and August 2020, 99 patients consulted with a medical history compatible with benign paroxysmal positional vertigo, average age 54.5 years, 68.9% were female. Repositioning maneuvers were required in 40.2% of cases. Of 28 patients with vitamin D levels, 27 showed deficiency/insufficiency. In 2019, for July and August, 54 patients were seen in the clinic with an average age of 61.7 years, and 83.3% were female. Repositioning maneuvers were required in 79.6%, and of the nine patients with vitamin D levels, seven presented deficiency/insufficiency. Statistically significant differences were observed regarding age, sex, and need for repositioning maneuvers.

Conclusions: A high prevalence of benign paroxysmal positional vertigo was observed during preventive lockdown for COVID-19 in our clinic. Patients were generally younger, and although it was more frequent in women, the incidence by sex was not as striking as in the previous year.
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http://dx.doi.org/10.5867/medwave.2021.03.8174DOI Listing
April 2021

Observed Frequency and Characteristics of Hearing Loss in Osteogenesis Imperfecta.

Rev Med Chil 2020 Dec;148(12):1781-1786

Department of Pediatric Endocrinology, UC Christus Health Center, Pontificia Universidad Católica de Chile, Chile.

Background: Osteogenesis imperfecta (OI) is a rare group of genetic disorders affecting connective tissue, with consequent bone fragility, frequent fractures and skeletal deformity. Depending on the type, patients can have blue sclera, dentinogenesis imperfecta, and hearing loss.

Aim: To determine the frequency, type and audiometric characteristics of hearing loss in a group of patients with OI.

Material And Methods: A prospective cohort study was completed. A clinical and diagnostic hearing evaluation with tympanometry, acoustic stapedial reflex, pure-tone and speech audiometry were performed.

Results: Thirty patients completed the study; mean age of 22 years (range 6-63 years). Sixty seven percent had a type I OI. Overall, nine (30%) patients had hearing loss (15/60 ears). Of these, six had bilateral hearing loss. Of the 15 affected ears, six showed conductive hearing loss, five sensorineural hearing loss, and four mixed hearing loss. Patients with hearing loss were older than patients with normal hearing. Only one pediatric patient developed hearing loss. Of the ears without hearing loss, 13% did not have an acoustic stapedial reflex.

Conclusions: In this group of patients with OI, 30% had hearing loss and among those ears with normal hearing, 13% did not have an acoustic stapedial reflex. Patients with OI should be monitored for hearing loss.
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http://dx.doi.org/10.4067/S0034-98872020001201781DOI Listing
December 2020

How the COVID-19 pandemic affects specialty training: An analysis of a nationwide survey among otolaryngology residents in Chile.

Medwave 2021 Jan 8;21(1):e8098. Epub 2021 Jan 8.

Departamento Otorrinolaringología, Facultad de Medicina, Universidad de Católica del Norte, Coquimbo, Chile. ORCID: 000-0002-1775-0057.

Introduction: Coronavirus disease 2019, or COVID-19, has become a global pandemic. Given that the highest viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in the airway, otolaryngologists are at high risk of infection. As a result, multiple recommendations have emerged regarding protective measures for surgical teams, including suspending non-urgent procedures and surgeries.

Objectives: To evaluate the impact of the COVID-19 pandemic on otolaryngology residency training programs nationwide.

Methods: A cross-sectional survey-based study was completed in April 2020. The participants were recruited through an online survey, sent by email to all Chilean otolaryngology residents. Demographics, clinical activities, on-call shifts, COVID-19 infection status, exposure to COVID-19 patients, deployment to other specialties, diagnostic/therapeutic procedures, and surgeries performed were analyzed. Self-reported surgical data logs from previous years were used to compare results.

Results: Forty-seven residents completed the survey (84% response rate); 64% of residents refer seeing patients ten days or less during April 2020. Commonly performed procedures such as flexible nasolaryngoscopy, rigid nasal endoscopy, and peritonsillar abscess drainage were not performed by over 40% of the residents in that month. Only 38% participated in surgeries, with an average of 0.6 surgeries as a first surgeon, a dramatic decrease in surgical exposure when comparing the data logs from previous years. Most residents refer the following measures taken by their residency program to improve residency training: bibliographic videoconferences (87%), online clinical case seminars (60%), weekly journal clubs (38%), among others.

Conclusions: Clinical and surgical opportunities decreased dramatically during April 2020. Adjustments to the regular academic curricula should be considered to decrease the negative impact of this pandemic on residency training.
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http://dx.doi.org/10.5867/medwave.2021.01.8097DOI Listing
January 2021

The Skull Vibration-induced Nystagmus Test (SVINT) for Vestibular Disorders: A Systematic Review.

Otol Neurotol 2021 06;42(5):646-658

Department of Otolaryngology, Pontificia Universidad Católica de Chile, Santiago, Chile.

Objective: To determine the specificity and sensitivity of the skull vibration-induced nystagmus test (SVINT) for detecting vestibular hypofunction.

Databases Reviewed: The Cochrane Library, MEDLINE, PubMed, EMBASE, and SciELO.

Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Databases were searched using a comprehensive search strategy including the terms "Vibration-induced nystagmus" or "SVINT" or "skull vibration-induced nystagmus test" or "skull vibration-induced nystagmus" from inception to May 2020.

Results: A total of 79 articles were identified, and 16 studies met the inclusion criteria. The methodology for performing the SVINT and determining positivity is varied. Most authors refer to reproducibility, sustained response, ending with withdrawal of stimulus, nondirection changing, and response in more than one point of stimulation, as necessary for a positive test. Only seven studies included a slow phase velocity of 2 degrees/s or 2.5 degrees/s as a criterion. Most studies employed 100 Hz stimulus for 10 seconds, while longer duration is suggested for pediatric patients. For partial and total unilateral vestibular loss, positivity varied from 58 to 60%, and 93 to 100%, respectively. Sensitivity ranged from 50 to 100%, and specificity from 62 to 100%. Importantly, the SVINT may decrease with time but does not usually disappear, hence, can provide information of past/compensated vestibular events.

Conclusions: The SVINT can be used in pediatric and adult patients. It provides information regarding unilateral vestibular loss, acute, or compensated. It is a quick, safe, and noninvasive test, and is complementary to the dynamic vestibular and positional tests.
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http://dx.doi.org/10.1097/MAO.0000000000003022DOI Listing
June 2021

Is Cyclosporine Ototoxic?

Authors:
Sofia Waissbluth

Front Neurol 2020 22;11:593917. Epub 2020 Oct 22.

Department of Otolaryngology, Pontificia Universidad Católica de Chile, Santiago, Chile.

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http://dx.doi.org/10.3389/fneur.2020.593917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642242PMC
October 2020

Clinical trials evaluating transtympanic otoprotectants for cisplatin-induced ototoxicity: what do we know so far?

Authors:
Sofia Waissbluth

Eur Arch Otorhinolaryngol 2020 Sep 1;277(9):2413-2422. Epub 2020 May 1.

Department of Otolaryngology, Pontificia Universidad Católica de Chile, Santiago, Chile.

Background: Cisplatin (CDDP) chemotherapy can cause serious side effects including irreversible and progressive hearing loss. Studies have aimed to assess potential protective strategies; however, systemic treatments have presented variable results, and potential interactions with CDDP have limited clinical trials.

Methods: A review of the literature was performed in order to evaluate clinical trials that have studied a transtympanic approach as an otoprotectant strategy.

Results: Six clinical trials were included. While a transtympanic approach can limit side effects and avoid interactions with CDDP, recurrent issues have been expressed including which otoprotectant to test, time delays between CDDP treatment and transtympanic injections, side effects such as pain and dizziness, concentrations, and number of injections. Clinical trials have used sodium thiosulfate, N-acetylcysteine and dexamethasone.

Conclusions: While a transtympanic approach seems like an attractive strategy, further research is needed to clarify which is the optimal otoprotectant, its dosage, and the number of injections.
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http://dx.doi.org/10.1007/s00405-020-06003-wDOI Listing
September 2020

Characteristics of children with refractory acute otitis media treated at the pediatric emergency department.

Int J Pediatr Otorhinolaryngol 2019 Jan 31;116:173-176. Epub 2018 Oct 31.

Department of Pediatric Otolaryngology - Head and Neck Surgery, Université de Montréal, Centre Hospitalier Universitaire Sainte-Justine, 3175 Côte Sainte-Catherine, Montréal, Québec, H3T 1C5, Canada.

Introduction: Refractory acute otitis media (rAOM) is defined as the persistence of signs and symptoms of AOM for more than 48 to 72 hours after the initiation of antibiotic treatment. These patients are often referred to the pediatric emergency department (PED). We sought to study rAOM cases referred to our PED, and to evaluate their clinical characteristics and response to our local management guidelines.

Methods: A retrospective chart review of all children treated for rAOM between 1/2012-3/2014 was performed. Data recorded included demographics, clinical presentation, antibiotic treatments, need for surgery, and culture results.

Results: A total of 255 patients were included with a mean age of 19 months. Prior to admission, all the children had received at least one course of antibiotics. Amoxicillin was the most common first-line antibiotic prescribed while amoxicillin-clavulanic acid was the most common second and third-line antibiotic given. Intravenous ceftriaxone was the treatment administered at the PED. Myringotomy and pressure equalizing tube (PET) insertion were required in 60% of cases. Middle ear cultures (55 ears) were positive for Streptococcus pneumoniae in two, and Moraxella catarrhalis in only one culture. There were no differences between the mean age of children who had PET insertion and those who did not with regards to fever, rhinorrhea, and preschool or school attendance. Children presenting with otorrhea were less likely to undergo surgery (P = 0.013).

Conclusions: This is the first study evaluating the established local practice guideline with regards to clinical characteristics and need for surgical management. We showed that myringotomy and PET insertion due to antibiotic failure is commonly performed for cases of rAOM. The majority of the middle ear cultures were sterile.
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http://dx.doi.org/10.1016/j.ijporl.2018.10.045DOI Listing
January 2019

Incidence and associated risk factors for platinum-induced ototoxicity in pediatric patients.

Int J Pediatr Otorhinolaryngol 2018 Aug 12;111:174-179. Epub 2018 Jun 12.

Department of Pediatric Hematology-Oncology, Complejo Asistencial Dr. Sotero Del Rio, Santiago, Chile.

Objectives: Platinum-based chemotherapy is effective against a variety of pediatric malignancies. Unfortunately, the use of cisplatin and carboplatin can lead to permanent and progressive sensorineural hearing loss which can affect the quality of life of cancer survivors. The objectives of this study were to evaluate the incidence of platinum-induced ototoxicity in children and analyze potential risk factors.

Methods: Prospective cohort study. All pediatric patients receiving chemotherapy with cisplatin and/or carboplatin from 01/2012 until 10/2017 were included. Hearing evaluations were performed before every chemotherapy cycle, and following the end of chemotherapy, with auditory brainstem response, otoacoustic emissions and/or audiometry. Demographics, cumulative doses, cranial irradiation and exposure to other ototoxic agents were analyzed.

Results: Twenty-eight patients were included, with a mean age of 7.2 years at the beginning of chemotherapy (range 5 months-15 years 2 months); twenty-one patients received cisplatin, four received carboplatin, and three received both agents. Twelve patients had cranial irradiation and seven received another ototoxic medication. The most frequent malignancies were germ cell tumors, medulloblastoma and gliomas. Sensorineural hearing loss occurred in 28.6% of the patients with a mean follow-up period of 21.5 months (range: 1-53 months). All patients evaluated with audiometry had ≥ Chang 2b ototoxicity. Risk factors include age less than 5 years, cranial irradiation, and cisplatin cumulative dose greater than 400 mg/m.

Conclusion: Sensorineural hearing loss is a potential side effect of platinum-based chemotherapy. Pediatric patients receiving cisplatin chemotherapy with a cumulative dose exceeding 400 mg/m, cranial irradiation as well as patients younger than 5 years are at greater risk of developing hearing loss.
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http://dx.doi.org/10.1016/j.ijporl.2018.06.021DOI Listing
August 2018

Long term platinum-induced ototoxicity in pediatric patients.

Int J Pediatr Otorhinolaryngol 2018 Apr 31;107:75-79. Epub 2018 Jan 31.

Department of Pediatric Hematology-Oncology, Complejo Asistencial Dr. Sotero Del Rio, Santiago, Chile.

Objectives: Platinum-based chemotherapy treatments are effective against a variety of pediatric malignancies. However, its use can lead to permanent hearing loss. The aim of this study was to evaluate the long-term effect of platinum chemotherapy on hearing and evaluate its progression.

Methods: Prospective cohort study. All records of pediatric patients receiving platinum-based chemotherapy between 2001 and 2006 were reviewed. Demographics and audiograms performed before, during, and following chemotherapy were analyzed. An updated audiogram and a video head impulse test were performed. A hearing ability questionnaire was also completed.

Results: Thirty-nine patients met the inclusion criteria. Of these, 12 patients were included in the study; 14 were deceased, 8 had incomplete data and 5 were excluded for other reasons. Median age at chemotherapy was 4.3 years (range 10 months-14.2 years). Seven patients had received cisplatin, two received carboplatin and three received both agents. Five had also received cranial irradiation. With a median follow-up time of 11.9 years, 58.3% had developed hearing loss and two patients wore bilateral hearing aids; 67% of the patients with hearing loss had worsening of their hearing in the long-term. All patients referred difficulties in various subscales measured by the questionnaire. Three patients had decreased vestibulo-ocular reflex gains.

Conclusion: Platinum-induced hearing loss in pediatric patients can be progressive and debilitating. A long term audiometric follow-up of at least 10 years is suggested for these patients.
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http://dx.doi.org/10.1016/j.ijporl.2018.01.028DOI Listing
April 2018

The impact of erdosteine on cisplatin-induced ototoxicity: a proteomics approach.

Eur Arch Otorhinolaryngol 2017 Mar 23;274(3):1365-1374. Epub 2016 Nov 23.

Department of Otolaryngology-Head and Neck Surgery, Montreal Children's Hospital, McGill University, 1001 Boulevard Décarie, Montreal, QC, H4A 3J1, Canada.

Cisplatin is a commonly used chemotherapeutic agent and causes serious side effects, including progressive and irreversible hearing loss. No treatment is currently available for cisplatin-induced ototoxicity. We have previously demonstrated that erdosteine, a potent antioxidant, partially protected the cochlea against cisplatin toxicity in vivo. The aims of this study were to (1) evaluate the protein profiles of the cochlea following cisplatin administration and (2) evaluate the impact of erdosteine on the protein profile using a proteomics-based approach. Thirty Sprague-Dawley rats were injected intraperitoneally with saline (n = 10), cisplatin (n = 10) or with cisplatin and erdosteine (n = 10). The cisplatin dosage was 14 mg/kg and for erdosteine, 500 mg/kg. Following euthanasia, protein lysates were obtained from fresh-frozen cochleae and were processed for mass spectrometry and western blotting. We detected 445 proteins that exhibited a twofold change or greater in the cisplatin group as compared to the control group. Of these, 18 proteins showed a fourfold or greater change in expression associated with cisplatin administration, including ras-related protein Rab-2A, Rab-6A, cd81, ribosomal protein S5, and myelin basic protein, which were downregulated, while Ba1-647 and fibrinogen (alpha chain), amongst others, were upregulated. Co-administration of erdosteine revealed a reversal of these changes in the expression of ras-related protein Rab-2A, ribosomal protein S5, myelin basic protein, and fibrinogen (alpha chain); erdosteine also upregulated glutathione reductase. In this study, we identified various proteins that may play a role in cisplatin-induced ototoxicity. We also observed the changes resulting from co-treatment with an antioxidant.
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http://dx.doi.org/10.1007/s00405-016-4399-1DOI Listing
March 2017

Platinum-induced ototoxicity: a review of prevailing ototoxicity criteria.

Eur Arch Otorhinolaryngol 2017 Mar 31;274(3):1187-1196. Epub 2016 May 31.

Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, QC, Canada.

The antineoplastic agent's cisplatin and carboplatin are widely used as they are highly effective. Unfortunately, ototoxicity is a frequently encountered side effect of platinum-based chemotherapy. Clinically, patients generally develop a progressive, bilateral, and irreversible sensorineural hearing loss. With rising cancer survival rates, a greater proportion of patients are living with the side effects of their chemotherapy treatments. Consequently, the quality of life of cancer survivors has now become a major concern for clinicians. Various classification systems are currently available to grade side effects and provide a guideline for subsequent treatments. An extensive review of the literature revealed that a variety of criteria are used worldwide for grading platinum-induced hearing loss in children and adults, including the National Cancer Institute criteria, Brock's grading system, the American Speech-Hearing-Language Association criteria, the World Health Organization criteria, the Pediatric Oncology Group criteria, and the Muenster classification. Less commonly used criteria include the Chang classification, the Functional Hearing Loss scale, the HIT system (German Hirntumor study grading system), and most recently, the International Society of Pediatric Oncology Boston ototoxicity grading scale. The objective of this review is to evaluate the commonly used ototoxicity criteria and discuss their benefits and limitations.
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http://dx.doi.org/10.1007/s00405-016-4117-zDOI Listing
March 2017

Review of pediatric head and neck pilomatrixoma.

Int J Pediatr Otorhinolaryngol 2016 Jun 28;85:148-53. Epub 2016 Mar 28.

Department of Otolaryngology-Head and Neck Surgery, The Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada. Electronic address:

Introduction: Pilomatrixoma is a benign skin tumor, which is commonly found in the head and neck region. It usually presents as an isolated lesion and rarely undergoes malignant transformation. It is not uncommon for these tumors to be misdiagnosed.

Objective: To review the clinical characteristics of head and neck pilomatrixomas in the pediatric population.

Methods: A systematic review was completed by searching ten databases to identify studies reporting findings on pilomatrixoma in the pediatric population. Eligible articles were independently assessed for quality by two authors.

Results: A total of 17 studies met the inclusion criteria totaling 318 pediatric patients. The age of diagnosis ranged from 3 months to 17 years of age. The female to male ratio was 1.65:1. In 14 articles, in which pilomatrixoma was located in the head and neck region, 76 (25%) lesions were found in the neck while 229 (75%) were present in the head region. Three articles exclusively described ophthalmologic pilomatrixoma. Even though pilomatrixoma presents with classical features, the clinical diagnostic accuracy when confronting this lesion averaged 43%. The definitive treatment was surgical excision with a very low recurrence rate.

Conclusion: Head and neck pilomatrixoma in the pediatric population has a typical presentation with a low clinical diagnostic accuracy. Awareness of this lesion and its clinical appearance can improve its diagnosis. We hereby suggest a management algorithm for suspected pilomatrixoma.
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http://dx.doi.org/10.1016/j.ijporl.2016.03.026DOI Listing
June 2016

Attenuation of cisplatin ototoxicity by otoprotective effects of nanoencapsulated curcumin and dexamethasone in a guinea pig model.

Otol Neurotol 2014 Aug;35(7):1131-9

*McGill Auditory Sciences Laboratory, †Montreal Children's Hospital Research Institute, Cancer and Angiogenesis Laboratory, McGill University; and ‡Department of Otolaryngology, The Montreal Children's Hospital, Montreal, Quebec, Canada.

Objectives: Cisplatin, one of the most effective and widely used chemotherapeutic agents in the treatment of head and neck malignancies, has severe dose-limiting side effects including ototoxicity. This study evaluates the effectiveness of nanoencapsulated curcumin and dexamethasone in preventing degenerative changes in inner ear cells caused by cisplatin.

Study Design: Prospective study, animal experiment.

Methods: Cultured auditory cells [House Ear Institute Organ of Corti-1 (HEI-OC1)] and a guinea pig model were used for in vitro and in vivo experiments, respectively. Cell viability assays were conducted to compare the direct toxicity of cisplatin against auditory cells in the presence or absence of pretreatment with nanoencapsulated curcumin and dexamethasone. To recapitulate these effects in vivo, 68 guinea pigs received cisplatin either alone, or along with dexamethasone, nanoencapsulated curcumin, or the combination of both products. Outcome measures included auditory brainstem response, cochlear morphology under both light and scanning electron microscopy, and antioxidant enzyme assays.

Results: Pretreatment of auditory cells with naonoencapsulated curcumin and dexamethasone resulted in significant attenuation of cisplatin toxicity. Similarly, in the corresponding animal model (guinea pig), cisplatin caused an average hearing loss of 50 dB, which was attenuated by nanoencapsulated curcumin and dexamethasone across all of the hearing frequencies. There was also greater preservation of histologic structures in this group. Superoxide dismutase and catalase activities were increased in cisplatin-treated animals, whereas the nanoencapsulated curcumin with dexamethasone led to a diminution of this effect.

Conclusion: Nanoencapsulated curcumin administered in combination with dexamethasone provides a partial but marked protection against cisplatin-induced hearing loss, likely because of reduced toxic damage to auditory cells.
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http://dx.doi.org/10.1097/MAO.0000000000000403DOI Listing
August 2014

Histopathologic changes in the cochlea associated with diabetes mellitus--a review.

Otol Neurotol 2014 Jun;35(5):764-74

*McGill Auditory Sciences Laboratory, McGill University; and †Department of Otolaryngology-Head and Neck Surgery, The Montreal Children's Hospital, Montreal, Quebec, Canada.

Background: The pathologic changes that occur as a result of diabetic microangiopathy have been well described for the kidneys and the eyes. Although many studies suggest an association between diabetes mellitus and hearing loss, the pathologic changes in the cochlea in association with the diabetic state remain to be clarified.

Aim/objective: The aim of this review is to determine the effects of diabetes mellitus on cochlear morphology.

Method: A comprehensive search for relevant articles was carried out on electronic databases of Ovid Medline, Ovid Medline in Process, PubMed, Ovid Embase,or Biosis Preview, The Cochrane Library, ISI Web of Science, and Scopus. Articles published in English between 1940 and June 2010 were eligible to be reviewed. Using predefined inclusion criteria, published articles on histologic changes occurring in the cochlea due to diabetes mellitus were selected and reviewed, and their findings were synthesized.

Results: Changes were observed in the basement membrane of the capillaries of the stria vascularis and in the basilar membrane, which was remarkably thickened, giving rise to diabetic microangiopathy. Loss of spiral ganglion neurons, organ of Corti cells, and atrophic changes in the stria vascularis were varied and infrequent.

Conclusion: There seems to be variable vulnerability of different cochlear cell types to the DM state. Further studies are required to determine the factors responsible for the differences in the histopathologic observations of cochlear tissues.
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http://dx.doi.org/10.1097/MAO.0000000000000293DOI Listing
June 2014

Earigate™ for softening ear wax: is it safe when the eardrum is perforated?

Int J Pediatr Otorhinolaryngol 2014 Jan 14;78(1):88-90. Epub 2013 Nov 14.

McGill Auditory Sciences Laboratory, Montreal Children's Hospital, Montreal, Quebec, Canada; Department of Otolaryngology, Head and Neck Surgery, McGill University, Montreal Children's Hospital, Montreal, Quebec, Canada. Electronic address:

Objective: To determine the safety of Earigate™ as an ear wax softening product.

Study Design: Prospective, controlled animal study.

Methods: Bilateral wide myringotomies were performed in eleven chinchillas. In each animal, Earigate™ was delivered to a randomly selected experimental ear canal as 2 puffs twice a day. Auditory brainstem response (ABR) was used to assess the hearing of the animals before, 3 days and 10 days following the local application of Earigate™. The ABR threshold shifts were compared for both experimental and control ears.

Results: The mean hearing threshold shifts in the experimental animals were comparable at all frequencies and at days 3 and 10. No statistically significant differences were observed in the mean threshold shifts for all of the frequencies evaluated, between the control and experimental ears.

Conclusions: The administration of Earigate™ to the middle ear of chinchillas did not cause any ototoxicity as assessed by ABR.
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http://dx.doi.org/10.1016/j.ijporl.2013.07.034DOI Listing
January 2014

Auditory risk of hyperbilirubinemia in term newborns: a systematic review.

Int J Pediatr Otorhinolaryngol 2013 Jun 30;77(6):898-905. Epub 2013 Apr 30.

McGill Auditory Sciences Laboratory, McGill University, Montreal, QC, Canada.

Objectives: High levels of unconjugated bilirubin have been associated with neuronal damage. The auditory brain nuclei and the inferior colliculi are often the first part of the brainstem to be involved, often leading to hearing abnormalities. A systematic review of clinical studies was conducted to evaluate the effect of hyperbilirubinemia on hearing in term newborns, to show the relationship between hearing function and bilirubin levels as well as the effect of treatment.

Methods: Eligible studies were identified through searches of electronic databases Ovid MEDLINE, Ovid MEDLINE In-Process, Embase, PubMed and The Cochrane Library. Articles obtained were independently reviewed by 2 authors using inclusion criteria to identify eligible studies. The search was restricted to articles written in English, French and Spanish and published between 1970 and 2010. Data extracted included study type, number of patients, bilirubin levels, hyperbilirubinemia criteria, hearing assessment methods, time of hearing assessment and outcome measures.

Results: The nineteen articles included showed heterogeneity regarding the time of hearing test and hyperbilirubinemia criteria. The incidence of hearing loss at initial testing ranged between 13.2-83.3% and 6.7-14.3% at 3 months follow-up. Five studies showed a rising incidence of hearing loss with increasing levels of serum bilirubin.

Conclusions: Hyperbilirubinemia resulted in abnormal hearing assessment in up to 83.3% of term newborns. Greater hearing abnormalities were observed with rising serum bilirubin levels. Treatment of hyperbilirubinemia led to a considerable decrease in the incidence of hearing loss.
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http://dx.doi.org/10.1016/j.ijporl.2013.03.029DOI Listing
June 2013

Cisplatin-induced ototoxicity: transporters playing a role in cisplatin toxicity.

Hear Res 2013 May 1;299:37-45. Epub 2013 Mar 1.

Department of Otolaryngology, The Montreal Children's Hospital, Quebec, Canada.

Cisplatin is a potent antineoplastic agent widely used for a variety of cancer types. Unfortunately, its use leads to dose limiting side effects such as ototoxicity. Up to 93% of patients receiving cisplatin chemotherapy will develop progressive and irreversible sensorineural hearing loss which leads to a decreased quality of life in cancer survivors. No treatment is currently available for cisplatin-induced ototoxicity. It appears that cisplatin causes apoptosis by binding DNA, activating the inflammatory cascade as well as generating oxidative stress in the cell. Various studies have aimed to assess the potential protective effects of compounds such as antioxidants, anti-inflammatories, caspase inhibitors, anti-apoptotic agents and calcium channel blockers against the toxicity caused by cisplatin in the inner ear with variable degrees of protection. Nevertheless, the pathophysiology of cisplatin-induced ototoxicity remains unclear. This review summarizes all of the known transporters that could play a role in cisplatin influx, leading to cisplatin-induced ototoxicity. The following were evaluated: copper transporters, organic cation transporters, the transient receptor potential channel family, calcium channels, multidrug resistance associated proteins, mechanotransduction channels and chloride channels.
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http://dx.doi.org/10.1016/j.heares.2013.02.002DOI Listing
May 2013

Characteristics of radiation-induced sensorineural hearing loss in head and neck cancer: a systematic review.

Head Neck 2013 Nov 22;35(11):1662-8. Epub 2012 Dec 22.

Division of Otolaryngology-Head and Neck Surgery, The Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.

Background: Patients receiving radiotherapy (RT) for head and neck tumors are at risk of developing sensorineural hearing loss. The objective of this study was to analyze the literature regarding sensorineural hearing loss after RT for head and neck cancer.

Methods: Seven databases were searched to identify eligible studies. Eligible articles were independently assessed for quality by 2 authors.

Results: Fourteen articles were evaluated. There was considerable heterogeneity among studies. The reported incidence of sensorineural hearing loss (SNHL) varied from 0% to 85% for the speech frequencies and from 27% to 95% for high frequencies. As the follow-up increased, an increase in the incidence of SNHL was observed. The minimum cochlear dose reported to be a risk factor for SNHL was 45 Gy.

Conclusions: High quality literature in the topic is lacking. Radiation-induced SNHL is progressive, permanent, and dose-dependent. Total dose and follow-up time are important factors affecting incidence rates.
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http://dx.doi.org/10.1002/hed.23201DOI Listing
November 2013

RNA preservation in decalcified cochlear samples.

Otol Neurotol 2013 Feb;34(2):331-7

Department of Surgical Research, McGill University, Montreal, Quebec, Canada.

Hypothesis: Decalcification of cochlear samples in Morse's solution after methacarn fixation provides greater RNA quantification and morphologic preservation of cochlear structures as compared with EDTA and formic acid decalcifying solutions after methacarn fixation.

Background: A variety of fixatives and decalcifying agents can fragment or chemically alter RNA in samples inhibiting their isolation and quantification. Morphologic alterations can also be observed in light microscopy analyses. The cochlea is embedded in the bone; hence, fixation and decalcification steps are mandatory to obtain histologic sections and preserve the cochlea for morphologic evaluation.

Methods: Cochlear samples obtained in a RNase-free environment were processed in 4 combinations of decalcifying agents in combination with methacarn fixation. Samples in Protocols 1, 2, and 3 were fixed in methacarn for 4 hours at 4°C, followed by decalcification at 4°C with Morse's solution, 10% ethylenediaminetetraacetic acid, and 5% formic acid solution, respectively. Samples processed with protocol 4 were decalcified in Morse's solution at 4°C followed by fixation for 4 hours at 4°C. Real-time PCR analysis was performed on total RNA extracted. Histology sections were evaluated for morphology preservation of cochlear structures.

Results: RNA was isolated in all samples. Relative expression levels were greatest with Protocol 1 and lowest with Protocol 3. Morphology preservation was adequate with Protocols 1, 2, and 3.

Conclusion: Of the 4 protocols evaluated, methacarn fixation followed by decalcification in Morse's solution provided the greatest genetic expression levels as well as the best tissue morphology preservation in the cochlea.
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http://dx.doi.org/10.1097/MAO.0b013e318278bf1aDOI Listing
February 2013

Systemic dexamethasone for the prevention of cisplatin-induced ototoxicity.

Eur Arch Otorhinolaryngol 2013 May 21;270(5):1597-605. Epub 2012 Aug 21.

Department of Surgical Research, McGill University, Montreal, QC, Canada.

Ototoxicity is a common side effect of cisplatin chemotherapy. This study was undertaken to determine the potential protective effects of a systemic administration of dexamethasone against cisplatin-induced ototoxicity. A prospective controlled trial conducted in an animal model. The setting was Animal care research facilities of the Montreal Children's Hospital Research Institute. An experimental guinea pig model was used. The animals were divided as follows: group 1 (n = 10): 12 mg/kg intraperitoneal (IP) cisplatin, group 2 (n = 14): 15 mg/kg/day dexamethasone IP for 2 days followed by cisplatin 12 mg/kg IP, group 3 (n = 14): 10 mg/kg/day dexamethasone IP for 2 days, on day 3, they received cisplatin 12 mg/kg IP followed by 20 mg/kg/day dexamethasone for 2 days and group 4 (n = 5): 10 ml of saline IP twice a day for 3 days. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (8, 16, 20 and 25 kHz) for groups 1, 2 and 3. Histological changes in the organ of Corti, the stria vascularis, the spiral ligament and the spiral ganglion neurons as well as scanning electron microscopy for outer hair cells were completed. Immunohistochemistry for tumour necrosis factor-alpha (TNF-α) was performed. ABR threshold shifts were similar in all groups. Histological and scanning electron findings demonstrate that dexamethasone has greater protective effect on the stria vascularis. Systemic dexamethasone administration in a guinea pig model did not provide significant protection against cisplatin-induced ototoxicity. Dexamethasone may be useful in future applications as a complementary treatment.
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http://dx.doi.org/10.1007/s00405-012-2150-0DOI Listing
May 2013

Do children with Bell's palsy benefit from steroid treatment? A systematic review.

Int J Pediatr Otorhinolaryngol 2012 Jul 13;76(7):921-6. Epub 2012 Apr 13.

Division of Otolaryngology-Head and Neck Surgery, The Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.

Objective: To conduct an updated systematic review on the outcome of Bell's palsy (BP) in children following steroid treatment.

Data Sources: MEDLINE, EMBASE, Cochrane Library and BIOSIS Previews electronic databases were searched obtaining articles published between 2000 and 2010 without any language restriction.

Review Methods: Articles describing children aged 0-18 years with BP treated solely with corticosteroids were included. In studies including various etiologies for facial palsy; cases of BP treated with steroids were selected and when available, untreated patients as well for comparison. The outcome measure was facial movements following steroidal treatment based on different clinical scales. Controlled clinical trials, prospective and historical cohort studies, cross sectional studies and case series were included.

Results: A total of 2293 papers were initially identified. Following review by two authors, 68 papers were analyzed in a hard-copy format. Finally, 6 studies were eligible to be included in the systematic review. Four of the studies included children with BP exclusively while the remaining studies described various etiologies of facial palsy. Type of steroid and duration of treatment were inconsistently specified. Outcome measures used include the House-Brackmann scale, Yanagihara grading system and clinical evaluation. Studies analyzed were retrospective cohorts or case-series and were categorized as level 4 of evidence.

Conclusion: There were no controlled trials and level 4 publications predominate. Therefore, the role of steroid treatment for BP in children is still inconclusive. Further studies are required.
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http://dx.doi.org/10.1016/j.ijporl.2012.02.044DOI Listing
July 2012

Gene therapy for cisplatin-induced ototoxicity: a systematic review of in vitro and experimental animal studies.

Otol Neurotol 2012 Apr;33(3):302-10

McGill Auditory Sciences Laboratory, McGill University, Montreal, Quebec, Canada.

Objective: Ototoxicity is a frequent adverse event of cisplatin treatment. No therapy is currently available for cisplatin-induced ototoxicity. A systematic review of experimental animal studies and in vitro experiments was conducted to evaluate gene therapy as a potential future therapeutic option.

Data Sources: Eligible studies were identified through searches of electronic databases Ovid MEDLINE, Ovid MEDLINE In-Process, Embase, PubMed, Biosis Previews, Scopus, ISI Web of Science, and The Cochrane Library.

Study Selection: Articles obtained from the search were independently reviewed by 2 authors using specific criteria to identify experimental animal studies and in vitro experiments conducted to evaluate gene therapy for cisplatin-induced ototoxicity. No restriction was applied to publication dates or languages.

Data Extraction: Data extracted included experiment type, cell type, species, targeted gene, gene expression, method, administration, inner ear site evaluated, outcome measures for cytotoxicity, and significant results.

Results: Fourteen articles were included in this review. In vitro and in vivo experiments have been performed to evaluate the potential of gene expression manipulation for cisplatin-induced ototoxicity. Twelve different genes were targeted including NTF3, GDNF, HO-1, XIAP, Trpv1, BCL2, Otos, Nfe2l2, Nox1, Nox3, Nox4, and Ctr1. All of the included articles demonstrated a benefit of gene therapy on cytotoxicity caused by cisplatin.

Conclusion: Experimental animal studies and in vitro experiments have demonstrated the efficacy of gene therapy for cisplatin-induced ototoxicity. However, further investigation regarding safety, immunogenicity, and consequences of genetic manipulation in the inner ear tissues must be completed to develop future therapeutic options.
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http://dx.doi.org/10.1097/MAO.0b013e318248ee66DOI Listing
April 2012

Protective effect of erdosteine against cisplatin-induced ototoxicity in a guinea pig model.

Otolaryngol Head Neck Surg 2012 Apr 3;146(4):627-32. Epub 2011 Nov 3.

McGill University, Montreal, Quebec, Canada.

Objective: Cisplatin is a commonly used chemotherapeutic agent. One of its major dose-limiting side effects is ototoxicity. No treatment has yet been approved for this condition. The objective of this study was to determine the potential protective effect of a systemic administration of erdosteine against cisplatin-induced ototoxicity.

Study Design: A prospective controlled trial conducted in an animal model.

Setting: Animal care research facilities of The Montreal Children's Hospital Research Institute.

Subjects And Methods: A total of 27 guinea pigs were assigned to 4 groups, each receiving a different concentration of intraperitoneal erdosteine: group 1 (control group; n = 9) did not receive erdosteine, group 2 (n = 6) received 100 mg/kg/d, group 3 (n = 6) received 200 mg/kg/d, and group 4 (n = 6) received 500 mg/kg/d. The animals in the experimental groups received the erdosteine injection daily for 4 days. All of the animals received 12 mg/kg of intraperitoneal cisplatin. Auditory brainstem response threshold shifts were measured at 4 frequencies (8, 16, 20, and 25 kHz) for all groups. Scanning electron microscopy and outer hair cell counts were performed to assess the protective effect of erdosteine.

Results: Significant protection was observed in groups 3 and 4 at 25 kHz. These findings are supported by outer hair cell counts by scanning electron microscopy.

Conclusion: A systemic administration of erdosteine appears to provide an otoprotective effect at high frequencies for cisplatin-induced ototoxicity.
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http://dx.doi.org/10.1177/0194599811426261DOI Listing
April 2012
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