Sofia Waissbluth

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

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.

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

OBJECTIVE To conduct an updated systematic review on the outcome of Bells 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.

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

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.

Auditory risk of hyperbilirubinemia in term newborns: A systematic review

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.

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

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.

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

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.

Protective Effect of Erdosteine against Cisplatin-Induced Ototoxicity in a Guinea Pig Model

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.

Review of pediatric head and neck pilomatrixoma

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.

Long term platinum-induced ototoxicity in pediatric patients

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.

RNA preservation in decalcified cochlear samples.

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.