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1.
Bull World Health Organ ; 100(12): 789-796A, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36466201

RESUMO

Following the efforts of patient advocates, the World Health Organization published updated guidelines for management of multidrug-resistant tuberculosis in 2018 that advised against the routine use of ototoxic second-line injectable drugs (amikacin, capreomycin and kanamycin). Although hearing loss is no longer considered an unavoidable harm for patients with multidrug-resistant tuberculosis, ototoxic medications continue to be used for several infectious and oncological disorders around the world. These drugs contribute to more than a half a million cases of hearing loss worldwide annually. Currently, there are no international standards for preventing and managing hearing loss associated with ototoxic medications. We present recent data on the prevention and management of hearing loss related to these drugs and highlight the variability in care across settings. More importantly, we aim to provide an evidence-based framework for evaluating, screening and preventing ototoxicity. Finally, we identify avenues for future research so that patients no longer have to choose between hearing loss and a disease cure. There remain significant gaps in our understanding about optimal screening and treatment of ototoxic hearing loss. Here we aim to inspire future international guidelines to address gaps in ototoxicity care and establish research agendas for eliminating ototoxic medications.


Sous l'impulsion des défenseurs des droits des patients, l'Organisation mondiale de la Santé a publié une version actualisée des lignes directrices relatives à la prise en charge de la tuberculose multirésistante en 2018, qui déconseille l'usage systématique de médicaments ototoxiques injectables de deuxième intention (amikacine, capréomycine et kanamycine). Bien que la perte auditive ne soit plus considérée comme un risque inévitable chez les patients atteints de tuberculose multirésistante, les médicaments ototoxiques continuent à être largement employés pour traiter de nombreuses maladies infectieuses et oncologiques à travers le monde. Ces médicaments sont impliqués chaque année dans plus de la moitié des cas de déficience auditive dans le monde. Il n'existe actuellement aucune norme internationale consacrée à la prévention et à la prise en charge de la perte auditive causée par des médicaments ototoxiques. Dans le présent document, nous exposons les données récentes à ce propos et soulignons la variabilité des soins prodigués d'une région à l'autre. Nous tentons surtout d'établir, à partir d'éléments concrets, un cadre dédié à l'évaluation, au dépistage et à la prévention de l'ototoxicité. Enfin, nous dégageons des pistes pour de futures études, afin que les patients n'aient plus à choisir entre une perte auditive et un remède. D'importantes lacunes subsistent dans notre compréhension du dépistage et du traitement de la perte auditive d'origine ototoxique. Nous espérons inspirer de futures lignes directrices internationales afin d'y remédier et de développer des programmes de recherche pour supprimer les médicaments ototoxiques.


Tras los esfuerzos de los defensores de pacientes, la Organización Mundial de la Salud publicó en 2018 unas directrices actualizadas para el tratamiento de la tuberculosis multirresistente en las que se desaconsejaba el uso rutinario de medicamentos inyectables de segunda línea ototóxicos (amikacina, capreomicina y kanamicina). Aunque la pérdida de audición ya no se considera un daño inevitable para los pacientes con tuberculosis multirresistente, los medicamentos ototóxicos se siguen administrando para varios trastornos infecciosos y oncológicos en todo el mundo. Estos fármacos contribuyen a más de medio millón de casos de pérdida de audición en todo el mundo cada año. En la actualidad, no existen estándares internacionales para prevenir y tratar la pérdida de audición asociada a los medicamentos ototóxicos. En este documento, se presentan datos recientes sobre la prevención y el tratamiento de la pérdida de audición relacionada con estos fármacos y se destaca la variabilidad de la atención en los distintos entornos. Además, se pretende ofrecer un marco basado en la evidencia para evaluar, detectar y prevenir la ototoxicidad. Por último, se identifican las vías de investigación futura para que los pacientes no tengan que elegir entre la pérdida de audición y la cura de la enfermedad. Siguen existiendo importantes deficiencias en el conocimiento del cribado y el tratamiento óptimos de la pérdida de audición ototóxica. En este sentido, se pretende inspirar futuras directrices internacionales para abordar las deficiencias en la atención a la ototoxicidad y establecer programas de investigación para eliminar los medicamentos ototóxicos.


Assuntos
Surdez , Perda Auditiva , Ototoxicidade , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Ototoxicidade/etiologia , Ototoxicidade/prevenção & controle , Perda Auditiva/induzido quimicamente , Perda Auditiva/prevenção & controle , Organização Mundial da Saúde
2.
Artigo em Inglês | MEDLINE | ID: mdl-31844012

RESUMO

Staphylococcus aureus is a major human pathogen that causes a wide range of infections by producing an arsenal of cytotoxins. We found that passive immunization with either a monoclonal antibody (MAb) neutralizing alpha-hemolysin or a broadly cross-reactive MAb neutralizing Panton-Valentine leukocidin, leukocidin ED, and gamma-hemolysins HlgAB and HlgCB conferred only partial protection, whereas the combination of those two MAbs conferred significant protection in a rabbit model of necrotizing pneumonia caused by the USA300 methicillin-resistant S. aureus epidemic clone.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Proteínas Hemolisinas/imunologia , Leucocidinas/uso terapêutico , Pneumonia Necrosante/tratamento farmacológico , Pneumonia Necrosante/imunologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/microbiologia , Animais , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Coelhos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade
3.
Bioconjug Chem ; 29(4): 1240-1250, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29485861

RESUMO

Hearing loss affects more than two-thirds of the elderly population, and more than 17% of all adults in the U.S. Sensorineural hearing loss related to noise exposure or aging is associated with loss of inner ear sensory hair cells (HCs), cochlear spiral ganglion neurons (SGNs), and ribbon synapses between HCs and SGNs, stimulating intense interest in therapies to regenerate synaptic function. 7,8-Dihydroxyflavone (DHF) is a selective and potent agonist of tropomyosin receptor kinase B (TrkB) and protects the neuron from apoptosis. Despite evidence that TrkB agonists can promote survival of SGNs, local delivery of drugs such as DHF to the inner ear remains a challenge. We previously demonstrated in an animal model that a fluorescently labeled bisphosphonate, 6-FAM-Zol, administered to the round window membrane penetrated the membrane and diffused throughout the cochlea. Given their affinity for bone mineral, including cochlear bone, bisphosphonates offer an intriguing modality for targeted delivery of neurotrophic agents to the SGNs to promote survival, neurite outgrowth, and, potentially, regeneration of synapses between HCs and SGNs. The design and synthesis of a bisphosphonate conjugate of DHF (Ris-DHF) is presented, with a preliminary evaluation of its neurotrophic activity. Ris-DHF increases neurite outgrowth in vitro, maintains this ability after binding to hydroxyapatite, and regenerates synapses in kainic acid-damaged cochlear organ of Corti explants dissected in vitro with attached SGNs. The results suggest that bisphosphonate-TrkB agonist conjugates have promise as a novel approach to targeted delivery of drugs to treat sensorineural hearing loss.


Assuntos
Cóclea/efeitos dos fármacos , Difosfonatos/química , Difosfonatos/farmacologia , Perda Auditiva/tratamento farmacológico , Glicoproteínas de Membrana/agonistas , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Receptor trkB/agonistas , Animais , Cóclea/citologia , Cóclea/metabolismo , Difosfonatos/administração & dosagem , Sistemas de Liberação de Medicamentos , Perda Auditiva/metabolismo , Humanos , Glicoproteínas de Membrana/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neurogênese/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Receptor trkB/metabolismo , Gânglio Espiral da Cóclea/citologia , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/metabolismo
4.
Am J Otolaryngol ; 39(3): 338-344, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29506762

RESUMO

OBJECTIVE: While hearing loss following temporal bone fracture is a well-described phenomenon, few data exist on auditory dysfunction in patients with traumatic brain injury (TBI) without temporal bone fracture. Herein, we aim to systematically review hearing loss after TBI without bony fracture and describe its etiologies. DATA SOURCES: Pubmed, Embase, Cochrane databases. REVIEW METHODS: A systematic review of the literature from 1966 to January 2017 was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations. Data were obtained from studies that investigated hearing loss in TBI without skull fracture according to an a priori protocol with inclusion and exclusion criteria. Variables included type and severity of hearing loss, as well as pathophysiology of hearing loss. RESULTS: There were 13 studies with 773 patients that met study criteria. Overall, there was one prospective cohort study, four retrospective cohort studies, two case-control studies, and six case reports. The studies with the highest level of evidence report a change in hearing of at least 10-15 dB across a range of frequencies in as many as 58% percent of TBI patients without bony fracture, which was transient or chronic. The mechanism/severity of injury may impact the rate of hearing loss. CONCLUSIONS: Hearing loss after TBI in the absence of bony injury appears to be a clinically significant but poorly characterized phenomenon.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Perda Auditiva/diagnóstico , Perda Auditiva/etiologia , Audiometria/métodos , Estudos de Coortes , Feminino , Fraturas Ósseas/diagnóstico por imagem , Humanos , Escala de Gravidade do Ferimento , Imageamento por Ressonância Magnética/métodos , Masculino , Avaliação das Necessidades , Prognóstico , Estudos Retrospectivos , Osso Temporal/diagnóstico por imagem , Osso Temporal/lesões
5.
Ann Otol Rhinol Laryngol ; 125(1): 20-4, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26195577

RESUMO

The association of sensorineural hearing loss and vertigo with inflammatory eye disease, usually interstitial keratitis, has been called Cogan's syndrome. The pathogenesis of Cogan's syndrome is unknown, but it has been assumed to be an immune mediated disorder with vasculitis. The histopathology of the inner ear in Cogan's syndrome has been described in 6 case reports. Although common pathologic findings in these reports include degeneration of the auditory and vestibular neuroepithelium, endolymphatic hydrops, fibrosis, and new bone formation, direct pathologic evidence of a vasculitis has not been published. A possible reason for this failure to identify vasculitis was a substantial delay (range, 4-40 years) between the onset of symptoms and examination of the otopathology. In the current case report, the patient had both auditory and vestibular symptoms and interstitial keratitis with a time delay of only 2 to 4 weeks between symptoms and death. Evidence of a vasculitis as a possible underlying etiology included H&E histopathology and anti-CD45 immunostaining of vessels both in the auditory and vestibular systems, supporting the hypothesis of a vasculitis as a mechanism in this disorder.


Assuntos
Síndrome de Cogan/patologia , Orelha Interna/patologia , Vasculite/patologia , Idoso , Síndrome de Cogan/complicações , Orelha Interna/irrigação sanguínea , Feminino , Humanos , Vasculite/complicações
6.
Artigo em Inglês | MEDLINE | ID: mdl-38360789

RESUMO

BACKGROUND: Neoplasms derived from the sinonasal epithelium are a rare finding in the temporal bone, and their origins are controversial. PURPOSE: To review the characteristics of sinonasal epithelial (previously known as Schneiderian) tumors occurring in the temporal bone. DATA SOURCE: This was a 2-center case series and systematic review of MEDLINE, EMBASE, and the Web of Science through May 2021. STUDY SELECTION: Patients with clinicopathologic evidence of temporal bone involvement by neoplasms of sinonasal epithelial origin were selected, with or without a history of prior primary sinonasal epithelial tumors. DATA ANALYSIS: Clinical, radiologic, and pathologic data were extracted. DATA SYNTHESIS: The systematic review included 56 studies and our 8 unpublished cases, totaling 76 cases of papillomas or squamous cell carcinomas in the temporal bone. Of these, 51% occurred secondary to sinonasal tumors, and 49% occurred primarily. Secondary tumors were usually metachronous (77%), with a median delay of 1 year from sinonasal-to-temporal bone tumor diagnosis. Most cases were unilateral (90%); bilateral temporal bone involvement occurred only as secondary ("trilateral") tumors. Unilateral secondary tumors had ipsilateral (81%) or bilateral (19%) sinonasal counterparts. Secondary tumors were more likely to be malignant (OR, 6.7, P < .001). LIMITATIONS: The review was based on case reports and small case series, which are subject to reporting bias. CONCLUSIONS: The observed tumor patterns support the hypothesis that the Eustachian tube facilitates the spread of sinonasal epithelium-derived neoplasms from the sinonasal cavity to the temporal bone. Transtubal spread of sinonasal epithelium-derived neoplasms should be considered among the rare causes of middle ear masses.

8.
Expert Opin Investig Drugs ; 32(7): 643-654, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37598357

RESUMO

INTRODUCTION: Sensorineural hearing loss results in irreversible loss of inner ear hair cells and spiral ganglion neurons. Reduced sound detection and speech discrimination can span all ages, and sensorineural hearing rehabilitation is limited to amplification with hearing aids or cochlear implants. Recent insights into experimental drug treatments for inner ear regeneration and otoprotection have paved the way for clinical trials in order to restore a more physiological hearing experience. Paired with the development of innovative minimally invasive approaches for drug delivery to the inner ear, new, emerging treatments for hearing protection and restoration are within reach. AREAS COVERED: This expert opinion provides an overview of the latest experimental drug therapies to protect from and to restore sensorineural hearing loss. EXPERT OPINION: The degree and type of cellular damage to the cochlea, the responsiveness of remaining, endogenous cells to regenerative treatments, and the duration of drug availability within cochlear fluids will determine the success of hearing protection or restoration.


Assuntos
Perda Auditiva Neurossensorial , Humanos , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/prevenção & controle , Células Ciliadas Auditivas Internas/fisiologia , Gânglio Espiral da Cóclea , Preparações Farmacêuticas , Drogas em Investigação
9.
Sci Rep ; 13(1): 19870, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036538

RESUMO

Tinnitus, reduced sound-level tolerance, and difficulties hearing in noisy environments are the most common complaints associated with sensorineural hearing loss in adult populations. This study aims to clarify if cochlear neural degeneration estimated in a large pool of participants with normal audiograms is associated with self-report of tinnitus using a test battery probing the different stages of the auditory processing from hair cell responses to the auditory reflexes of the brainstem. Self-report of chronic tinnitus was significantly associated with (1) reduced cochlear nerve responses, (2) weaker middle-ear muscle reflexes, (3) stronger medial olivocochlear efferent reflexes and (4) hyperactivity in the central auditory pathways. These results support the model of tinnitus generation whereby decreased neural activity from a damaged cochlea can elicit hyperactivity from decreased inhibition in the central nervous system.


Assuntos
Zumbido , Doenças do Nervo Vestibulococlear , Adulto , Humanos , Limiar Auditivo/fisiologia , Audição/fisiologia , Cóclea/inervação , Percepção Auditiva
10.
Front Cell Infect Microbiol ; 13: 1297281, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149013

RESUMO

Background: New drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa, have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections. Methods: We report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with Pseudomonas aeruginosa by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression. Results: In a rabbit model of non-ventilated pneumonia, endobronchial challenge with live P. aeruginosa strain 6206, but not with UV-killed Pa6206, caused acute respiratory distress syndrome, as evidenced by acute lung inflammation, pulmonary edema, hemorrhage, severe hypoxemia, hyperlactatemia, neutropenia, thrombocytopenia, and hypoglycemia, which preceded respiratory failure and death. Pa6206 increased >100-fold in the lungs and then disseminated from there to infect distal organs, including spleen and kidneys. At 5 h post-infection, 67% of Pa6206-challenged rabbits had PaO2 <60 mmHg, corresponding to a clinical cut-off when oxygen therapy would be required. When administered at 5 h post-infection, humanized dosing regimens of tobramycin and meropenem reduced mortality to 17-33%, compared to 100% for saline-treated rabbits (P<0.001 by log-rank tests). For meropenem which exhibits time-dependent bactericidal activity, rabbits treated with a humanized meropenem dosing regimen of 80 mg/kg q2h for 24 h achieved 100% T>MIC, resulting in 75% microbiological clearance rate of Pa6206 from the lungs. For tobramycin which exhibits concentration-dependent killing, rabbits treated with a humanized tobramycin dosing regimen of 8 mg/kg q8h for 24 h achieved Cmax/MIC of 9.8 ± 1.4 at 60 min post-dose, resulting in 50% lung microbiological clearance rate. In contrast, rabbits treated with a single tobramycin dose of 2.5 mg/kg had Cmax/MIC of 7.8 ± 0.8 and 8% (1/12) microbiological clearance rate, indicating that this rabbit model can detect dose-response effects. Conclusion: The rabbit model may be used to help predict clinical efficacy of new antibacterial drugs for the treatment of non-ventilated P. aeruginosa pneumonia.


Assuntos
Pneumonia , Infecções por Pseudomonas , Humanos , Animais , Coelhos , Meropeném/uso terapêutico , Pseudomonas aeruginosa , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Tobramicina/farmacologia , Tobramicina/uso terapêutico , Pneumonia/tratamento farmacológico , Desenvolvimento de Medicamentos
11.
OTO Open ; 6(2): 2473974X221104663, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35769917

RESUMO

Surgical residents may have limited experience with grant writing even though it is an important skill for academic physicians. We describe a novel curriculum on the conduct of research and grant literacy delivered at a single otolaryngology training program over 5 years. This workshop series included preparing a draft grant and conducting a mock grant review committee. In a survey of past participants (71% response rate), 91% found the workshops useful for grant writing or reviewing, and many used or planned to use the draft grants for real grant applications. The average number of American Academy of Otolaryngology-Head and Neck Surgery Foundation CORE grants submitted and successfully funded increased among residents at this program in the 4 years after the introduction of the workshop series as compared with the 4 years before. Further improvements continue to be made to the curriculum based on resident feedback.

12.
Otol Neurotol ; 43(3): 376-384, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35020686

RESUMO

OBJECTIVE: Vestibular schwannomas (VS) commonly undergo magnetic resonance imaging (MRI) surveillance, but long-term data to support the ideal frequency is limited. Herein, we aim to investigate intracanalicular VS growth predictors and long-term growth rates (GR). STUDY DESIGN: Retrospective chart review. SETTING: Two tertiary care centers. PATIENTS: Sporadic intracanalicular VS with initial conservative management and at least two sequential MRIs. INTERVENTION: Serial MRI. MAIN OUTCOME MEASURES: VS were categorized by baseline internal auditory canal tertile sublocalization (fundus, midpoint, porus) and size (≤100, 100-200, >200 mm3). Throughout follow-up, volumetric GR (mm3/yr) were determined (baseline-3 yrs, 3-5 yrs, 5-10 yrs) and treatment rates were assessed. RESULTS: Ninety-nine intracanalicular VS were identified (mean follow-up of 6.1 ±â€Š4.5 yrs). Mean GR before 5-year follow-up were comparable for baseline tertile involvement and size. After 5-year follow-up, mean GR of VS involving the fundus at baseline were lower than those involving the midpoint and fundus (6.17 ±â€Š21.16 and 119.74 ±â€Š117.57 mm3/yr, respectively; p = 0.034). Mean GR of VS with less than or equal to 100 mm3 at baseline (-7.29 ±â€Š25.44 mm3/yr) were lower than those with 100 to 200 mm3 (86.55 ±â€Š103.99 mm3/yr; p = 0.011) and more than 200 mm3 (45.70 ±â€Š35.71 mm3/yr; p = 0.031). Vestibular schwannomas involving the midpoint and fundus had greater treatment rates compared with VS involving only the fundus (p < 0.001). CONCLUSIONS: Baseline tertile involvement and size may predict long-term intracanalicular VS growth where fundal tumors or those less than or equal to 100 mm3 exhibit little long-term growth. Extending surveillance after 5-year follow-up may be reasonable for fundal VS.


Assuntos
Orelha Interna , Neuroma Acústico , Orelha Interna/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroma Acústico/complicações , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/patologia , Estudos Retrospectivos
13.
Otol Neurotol ; 43(2): e153-e164, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35015749

RESUMO

OBJECTIVE: We aim to assess the histopathology of human temporal bones (TBs) with evidence of cochlear implantation (CI) electrode scalar translocation. STUDY DESIGN: Otopathology study. SETTING: Otopathology laboratory. PATIENTS: TBs from patients who had a history of CI and histopathological evidence of interscalar translocation. Specimens with electrode placed entirely within the ST served as controls. INTERVENTION: Histopathological assessment of human TBs. MAIN OUTCOME MEASURES: TBs from each patient were harvested postmortem and histologically analyzed for intracochlear changes in the context of CI electrode translocation and compared to controls. Intracochlear new fibro-ossification, and spiral ganglion neuron (SGN) counts were assessed. Postoperative word recognition scores (WRS) were also compared. RESULTS: Nineteen human TBs with electrode translocation and eight controls were identified. The most common site of translocation was the ascending limb of the basal turn (n = 14 TBs). The average angle of insertion at the point of translocation was 159°â€Š±â€Š79°. Eighteen translocated cases presented moderate fibroosseous changes in the basal region of the cochlea, extending to the translocation point and/or throughout the electrode track in 42%. Lower SGN counts were more pronounced in translocated cases compared to controls, with a significant difference for segment II (p = 0.019). Although final postoperative hearing outcomes were similar between groups, translocated cases had slower rate of improvement in WRS (p = 0.021). CONCLUSIONS: Cochlear implant electrode translocation was associated with greater fibroosseous formation and lower SGN population. Our findings suggest that scalar translocations may slow the rate of improvement in WRS overtime as compared to atraumatic electrode insertions.Level of evidence: IV.


Assuntos
Implante Coclear , Implantes Cocleares , Cóclea/cirurgia , Humanos , Osteogênese , Osso Temporal/patologia , Osso Temporal/cirurgia
14.
Otol Neurotol ; 43(10): e1094-e1099, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36201555

RESUMO

OBJECTIVES: In 2020, Advanced Bionics (AB) announced a recall of two cochlear implant (CI) models, the "HiRes Ultra" and "HiRes Ultra 3D", because of reports of hearing degradation. The present study examines clinical parameters and patient features in cases of device failure and evaluates outcomes after reimplantation. MATERIALS AND METHODS: A series of 52 patients implanted with the recalled devices experienced suspected device failure and subsequently underwent revision CI placement at a tertiary academic medical center between December 2019 and November 2021. RESULTS: Consonant-nucleus-consonant scores and individual phonemes increased significantly between patients' preoperative evaluation and primary cochlear implantation. Performance declined significantly before revision and recovered after revision CI placement. Similarly, pure-tone average thresholds improved between preoperative and primary CI, fell before revision surgery, and were corrected with revision implantation. As a group, patients reached their peak hearing performance significantly faster after revision CI (mean ± standard deviation, 53.4 ± 51.8 d) compared with their primary CI (mean ± standard deviation, 260.6 ± 245.9 d). Electrical field imaging performed by AB and device impedance measurements were found to be abnormal in the basally positioned electrodes (electrodes 9-16). CONCLUSION: Hearing performance degradation is significant in AB Ultra device failures and seems to be linked to the basal-most electrodes in the array. Revision outcomes have been robust, necessitating continued monitoring of affected patients and support for reimplantation procedures. LEVEL OF EVIDENCE: IV.


Assuntos
Implante Coclear , Implantes Cocleares , Percepção da Fala , Humanos , Biônica , Testes Auditivos , Reoperação , Estudos Retrospectivos
15.
Mol Ther Methods Clin Dev ; 26: 169-180, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-35846573

RESUMO

Loss of function of the neurofibromatosis type 2 (NF2) tumor suppressor gene leads to the formation of schwannomas, meningiomas, and ependymomas, comprising ∼50% of all sporadic cases of primary nervous system tumors. NF2 syndrome is an autosomal dominant condition, with bi-allelic inactivation of germline and somatic alleles resulting in loss of function of the encoded protein merlin and activation of mammalian target of rapamycin (mTOR) pathway signaling in NF2-deficient cells. Here we describe a gene replacement approach through direct intratumoral injection of an adeno-associated virus vector expressing merlin in a novel human schwannoma model in nude mice. In culture, the introduction of an AAV1 vector encoding merlin into CRISPR-modified human NF2-null arachnoidal cells (ACs) or Schwann cells (SCs) was associated with decreased size and mTORC1 pathway activation consistent with restored merlin activity. In vivo, a single injection of AAV1-merlin directly into human NF2-null SC-derived tumors growing in the sciatic nerve of nude mice led to regression of tumors over a 10-week period, associated with a decrease in dividing cells and an increase in apoptosis, in comparison with vehicle. These studies establish that merlin re-expression via gene replacement in NF2-null schwannomas is sufficient to cause tumor regression, thereby potentially providing an effective treatment for NF2.

16.
Otol Neurotol ; 42(2): 285-289, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33273305

RESUMO

OBJECTIVE: This report describes a case of development of radiologic superior semicircular canal dehiscence and reviews the literature for pertinent clinical and radiologic findings in patients with superior semicircular canal dehiscence syndrome (SCDS). PATIENT: A 28-year-old man presented with auditory and vestibular symptoms of SCDS and underwent a high-resolution temporal bone computed tomography scan that showed frank dehiscence of the right superior semicircular canal. Diagnosis of SCDS was further verified with audiometric and cervical vestibular-evoked myogenic potential (cVEMP) thresholds. The patient had previously undergone a computed tomography scan 12 years prior for work-up of sudden sensorineural hearing loss that showed no evidence of superior semicircular canal dehiscence bilaterally. INTERVENTIONS: A combination of diagnostic and therapeutic interventions was conducted consisting of preoperative audiometric and cVEMP thresholds, followed by middle fossa craniotomy for surgical repair of the dehiscence. MAIN OUTCOME MEASURE: Postoperative audiometric and cVEMP thresholds and symptomatic improvement of SCDS after surgical repair of the dehiscence. RESULTS: The patient reported resolution of his clinical symptoms after surgical repair of the dehiscence. Postoperative cVEMP thresholds improved to the normal range and the mild low-frequency conductive hearing loss resolved. CONCLUSIONS: To our knowledge, this case report is the first description of radiologically proven new development of superior canal dehiscence. Further prospective studies that include serial imaging examinations may help with visualizing and understanding the temporal evolution of superior canal dehiscence, and better elucidate the relationship between development/ progression of superior canal dehiscence and onset of clinical symptoms.


Assuntos
Deiscência do Canal Semicircular , Potenciais Evocados Miogênicos Vestibulares , Adulto , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Canais Semicirculares/diagnóstico por imagem , Canais Semicirculares/cirurgia
17.
Otolaryngol Head Neck Surg ; 165(1): 163-165, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33228476

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic resulted in widespread unprecedented changes to the health care system. Herein, we sought to assess the impact of the viral outbreak on clinical presentations of sudden sensorineural hearing loss (SSNHL) at a single academic center. Our results demonstrate a decrease in the absolute number of patients presenting with SSNHL to our institution during the initial onset of the COVID-19 pandemic compared to an analogous time frame 1 year prior. However, the ratio of patients with SSNHL compared to total patients evaluated was largely similar during the 2 time periods. Based on data from our institution, the COVID-19 virus does not appear to confer a significantly increased risk for the development of SSNHL.


Assuntos
COVID-19 , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Súbita/epidemiologia , Humanos , Estudos Retrospectivos
18.
Front Cell Neurosci ; 15: 666706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335184

RESUMO

Sensorineural hearing loss is irreversible and is associated with the loss of spiral ganglion neurons (SGNs) and sensory hair cells within the inner ear. Improving spiral ganglion neuron (SGN) survival, neurite outgrowth, and synaptogenesis could lead to significant gains for hearing-impaired patients. There has therefore been intense interest in the use of neurotrophic factors in the inner ear to promote both survival of SGNs and re-wiring of sensory hair cells by surviving SGNs. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) represent the primary neurotrophins in the inner ear during development and throughout adulthood, and have demonstrated potential for SGN survival and neurite outgrowth. We have pioneered a hybrid molecule approach to maximize SGN stimulation in vivo, in which small molecule analogues of neurotrophins are linked to bisphosphonates, which in turn bind to cochlear bone. We have previously shown that a small molecule BDNF analogue coupled to risedronate binds to bone matrix and promotes SGN neurite outgrowth and synaptogenesis in vitro. Because NT-3 has been shown in a variety of contexts to have a greater regenerative capacity in the cochlea than BDNF, we sought to develop a similar approach for NT-3. 1Aa is a small molecule analogue of NT-3 that has been shown to activate cells through TrkC, the NT-3 receptor, although its activity on SGNs has not previously been described. Herein we describe the design and synthesis of 1Aa and a covalent conjugate of 1Aa with risedronate, Ris-1Aa. We demonstrate that both 1Aa and Ris-1Aa stimulate neurite outgrowth in SGN cultures at a significantly higher level compared to controls. Ris-1Aa maintained its neurotrophic activity when bound to hydroxyapatite, the primary mineral component of bone. Both 1Aa and Ris-1Aa promote significant synaptic regeneration in cochlear explant cultures, and both 1Aa and Ris-1Aa appear to act at least partly through TrkC. Our results provide the first evidence that a small molecule analogue of NT-3 can stimulate SGNs and promote regeneration of synapses between SGNs and inner hair cells. Our findings support the promise of hydroxyapatite-targeting bisphosphonate conjugation as a novel strategy to deliver neurotrophic agents to SGNs encased within cochlear bone.

19.
Otolaryngol Head Neck Surg ; 164(1): 67-73, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32660367

RESUMO

OBJECTIVE: To investigate small-particle aerosolization from mastoidectomy relevant to potential viral transmission and to test source-control mitigation strategies. STUDY DESIGN: Cadaveric simulation. SETTING: Surgical simulation laboratory. METHODS: An optical particle size spectrometer was used to quantify 1- to 10-µm aerosols 30 cm from mastoid cortex drilling. Two barrier drapes were evaluated: OtoTent1, a drape sheet affixed to the microscope; OtoTent2, a custom-structured drape that enclosed the surgical field with specialized ports. RESULTS: Mastoid drilling without a barrier drape, with or without an aerosol-scavenging second suction, generated large amounts of 1- to 10-µm particulate. Drilling under OtoTent1 generated a high density of particles when compared with baseline environmental levels (P < .001, U = 107). By contrast, when drilling was conducted under OtoTent2, mean particle density remained at baseline. Adding a second suction inside OtoTent1 or OtoTent2 kept particle density at baseline levels. Significant aerosols were released upon removal of OtoTent1 or OtoTent2 despite a 60-second pause before drape removal after drilling (P < .001, U = 0, n = 10, 12; P < .001, U = 2, n = 12, 12, respectively). However, particle density did not increase above baseline when a second suction and a pause before removal were both employed. CONCLUSIONS: Mastoidectomy without a barrier, even when a second suction was added, generated substantial 1- to 10-µm aerosols. During drilling, large amounts of aerosols above baseline levels were detected with OtoTent1 but not OtoTent2. For both drapes, a second suction was an effective mitigation strategy during drilling. Last, the combination of a second suction and a pause before removal prevented aerosol escape during the removal of either drape.


Assuntos
Aerossóis/efeitos adversos , COVID-19/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Otopatias/cirurgia , Mastoidectomia/métodos , Procedimentos Cirúrgicos Otológicos/normas , Equipamento de Proteção Individual , Cadáver , Comorbidade , Otopatias/epidemiologia , Humanos , Processo Mastoide/cirurgia , Procedimentos Cirúrgicos Otológicos/métodos , SARS-CoV-2
20.
Otolaryngol Head Neck Surg ; 162(2): 211-214, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31842677

RESUMO

Vestibular schwannomas (VSs) were proposed to arise from the glial-Schwann cell junction within the internal auditory canal (IAC). However, otopathology studies indicate that VS may arise anywhere along the course of the vestibular nerve. Recent studies suggested that the majority of tumors are located centrally within the IAC with an equal distribution near the porus acusticus and the fundus. However, these studies analyzed tumors of all sizes, obscuring their precise origin. Herein, we aim to quantify the position of small intracanalicular tumors (<5 mm), assessing hearing outcomes and growth patterns in relation to tumor position. Of the 38 small intracanalicular tumors analyzed, 61% originated closest to the fundus, 34% at the midpoint, and only 5% closest to the porus acusticus. Tumors were observed with serial magnetic resonance imaging for 3.37 ± 2.65 years (mean ± SD) without intervention. Our findings indicate a lateral predominance of small VS within the IAC, an independence between tumor location and hearing outcomes, and further support the slow natural progression of VS.


Assuntos
Perda Auditiva/diagnóstico , Audição/fisiologia , Imageamento por Ressonância Magnética/métodos , Neuroma Acústico/diagnóstico , Nervo Vestibular/patologia , Idoso , Audiometria de Tons Puros , Feminino , Perda Auditiva/etiologia , Perda Auditiva/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/complicações , Neuroma Acústico/fisiopatologia , Estudos Retrospectivos , Nervo Vestibular/fisiopatologia
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