RESUMO
Autoimmune Inner Ear Disease (AIED) is characterized by bilateral, fluctuating sensorineural hearing loss with periods of hearing decline triggered by unknown stimuli. Here we examined whether an environmental exposure to mold in these AIED patients is sufficient to generate a pro-inflammatory response that may, in part, explain periods of acute exacerbation of disease. We hypothesized that molds may stimulate an aberrant immune response in these patients as both several Aspergillus species and penecillium share homology with the LCCL domain of the inner ear protein, cochlin. We showed the presence of higher levels of anti-mold IgG in plasma of AIED patients at dilution of 1:256 (p = 0.032) and anti-cochlin IgG 1:256 (p = 0.0094 and at 1:512 p = 0.024) as compared with controls. Exposure of peripheral blood mononuclear cells (PBMC) of AIED patients to mold resulted in an up-regulation of IL-1ß mRNA expression, enhanced IL-1ß and IL-6 secretion, and generation of IL-17 expressing cells in mold-sensitive AIED patients, suggesting mold acts as a PAMP in a subset of these patients. Naïve B cells secreted IgM when stimulated with conditioned supernatant from AIED patients' monocytes treated with mold extract. In conclusion, the present studies indicate that fungal exposure can trigger autoimmunity in a subset of susceptible AIED patients.
Assuntos
Aspergilose/imunologia , Aspergillus/imunologia , Doenças Autoimunes/imunologia , Doenças do Labirinto/imunologia , Leucócitos Mononucleares/imunologia , Adulto , Idoso , Anticorpos Antifúngicos/sangue , Antígenos de Fungos/imunologia , Células Cultivadas , Reações Cruzadas , Citocinas/genética , Citocinas/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Humanos , Imunidade Inata , Imunoglobulina G/sangue , Leucócitos Mononucleares/microbiologia , Masculino , Pessoa de Meia-Idade , Homologia de Sequência de AminoácidosRESUMO
Autoimmune inner ear disease is an enigmatic disorder characterized by recurring episodes of sudden or progressive sensorineural hearing loss. Hearing loss can be improved by timely corticosteroid administration, but only half of those treated respond, and for many responders, that response is lost over time. The mechanisms that control corticosteroid responsiveness in this disorder are largely uncharacterized. We have previously identified that the induction by dexamethasone of IL-1R type II (IL-1R2) expression in PBMC predicts corticosteroid responsiveness in this disorder. In this study, we asked whether IL-1ß was overexpressed, and whether clinical corticosteroid responders differentially regulated IL-1ß expression or release in response to dexamethasone, as compared with nonresponders. IL-1ß has been reported to induce matrix metalloproteinase-9 (MMP-9) expression. Given that metalloproteinases can cleave IL-1R2, we also asked whether MMP-9 expression was altered in this disorder. In this study, we demonstrate that corticosteroid nonresponders have elevated plasma levels of IL-1ß and MMP-9 as compared with clinically responsive patients (p = 0.0008 and p = 0.037, respectively). Increasing MMP-9 expression correlated with increasing IL-1ß concentration, suggesting that IL-1ß expression regulates MMP-9 expression. As expected, monocytes were the predominant producers of IL-1ß. In vitro exposure of PBMC to dexamethasone from clinical corticosteroid responders suppressed IL-1ß release. PBMC of corticosteroid nonresponders have substantially higher release of IL-1ß into the conditioned media, and when exposed to dexamethasone, failed to repress IL-1ß release (p = 0.05). Treatment of PBMC from clinical corticosteroid nonresponders with anakinra resulted in repression of IL-1ß release, suggesting that IL-1ß blockade may be a viable therapy for these patients.
Assuntos
Doenças Autoimunes/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Glucocorticoides/uso terapêutico , Interleucina-1beta/biossíntese , Administração Oral , Adulto , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/genética , Células Cultivadas , Implante Coclear , Dexametasona/farmacologia , Feminino , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/imunologia , Perda Auditiva Neurossensorial/metabolismo , Humanos , Imunossupressores/uso terapêutico , Interleucina-1beta/sangue , Interleucina-1beta/genética , Masculino , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/sangue , Inibidores de Metaloproteinases de Matriz , Prednisona/uso terapêutico , Estudos ProspectivosRESUMO
Meniere's disease (MD) is a chronic disease that causes episodic vertigo, fluctuating hearing loss, and aural fullness, initially managed by dietary salt reduction, and use of diuretics. Our prior research in autoimmune inner ear disease (AIED) demonstrated that in peripheral blood mononuclear cell (PBMC) from corticosteroid-resistant AIED patients, increased production, processing and release of interleukin-1ß (IL-1ß) is observed and hearing could be improved with use of anakinra, an interleukin-1 receptor antagonist. We have further identified that in these AIED patients, IL-1ß is uniquely processed to a 28 kDa pro-inflammatory product by caspase-7. In the present study, we characterize the production, processing and release of the pro-inflammatory cytokines IL-1ß and IL-6 from PBMC of MD (n = 14) patients in response to sodium chloride (NaCl), and determined the effect of the diuretic triamterene-hydrocholothiazide (T-HCTZ), or anakinra in these patients. We observed that PBMC cultured with NaCl from MD patients show processing of IL-1ß to the 28 kDa product, and that this product is abrogated with T-HCTZ. Our observations are consistent with other autoimmune diseases where high concentrations of NaCl caused release of pro-inflammatory cytokines and may provide further insight as to the mechanism of disease progression in MD patients.
Assuntos
Doenças Autoimunes , Doença de Meniere , Citocinas/metabolismo , Humanos , Hidroclorotiazida/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1beta/farmacologia , Leucócitos Mononucleares/metabolismo , Doença de Meniere/tratamento farmacológico , Cloreto de Sódio/farmacologiaRESUMO
A case series with chart review of pediatric patients with immune-mediated sensorineural hearing loss, including sudden sensorineural hearing loss and autoimmune-mediated hearing loss, was performed. Ninety-eight patients with sensorineural hearing loss were reviewed, and 41 patients met the inclusion criteria, which included corticosteroid therapy for a decline in sensorineural hearing. The primary outcome was the corticosteroid response rate: 61% of patients responded. The secondary outcome was a sustained response following multiple courses of corticosteroids for additional hearing loss, which correlated with timely corticosteroid treatment: 57% showed sustained response with multiple treatments, but as anticipated, patients were more likely to respond when treated promptly. Sustained responses fell over time with multiple treatments. These data demonstrate pediatric immune-mediated sensorineural hearing loss is corticosteroid responsive in at a rate similar to their adult counterparts and should be considered for similar treatment approaches.
Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Corticosteroides/uso terapêutico , Adulto , Criança , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/tratamento farmacológico , Testes Auditivos , HumanosRESUMO
OBJECTIVE: Since the introduction of neural response telemetry (NRT) for the Nucleus 24 cochlear implant (CI24), researchers and clinicians have investigated the feasibility of using the electrically evoked compound action potential (ECAP) threshold to objectively predict psychophysical measurements that are used in the programming of the speech processor. The ability to substitute objective for behavioral measurements, particularly measurements made at the time of surgery, would greatly facilitate programming the MAP for young children and other individuals who are not able to provide reliable behavioral data required for MAP programming. There have been a number of studies that have examined characteristics of the ECAP measured at the time of surgery and postoperatively; however, all the available published data are based on the CI24. With the introduction of the Nucleus Freedom device, an automated NRT (AutoNRT) program became available, which was capable of measuring ECAP thresholds at lower levels than was previously possible with NRT software associated with the CI24 device. It was hypothesized that the enhancements to the NRT program may improve the predictability of postoperative measurements from intraoperatively recorded ECAP thresholds. The purpose of this study was to track ECAP thresholds obtained using AutoNRT as a function of time and electrode position. DESIGN: ECAP thresholds were recorded from 71 children and adults implanted with the Nucleus Freedom device using the AutoNRT test protocol. ECAP thresholds were obtained at the time of surgery, at initial stimulation, and 3 mos poststimulation. Five electrodes located at basal, middle, and apical positions in the cochlea were tested at each time interval and thresholds were compared. RESULTS: Significant differences were found in ECAP thresholds measured with AutoNRT as a function of both time and electrode position. Basal electrodes had higher ECAP thresholds than apical electrodes and that relationship was consistent for each time period. Thresholds for all electrodes decreased between surgery and initial stimulation and remained relatively stable at 3 mos poststimulation. ECAP thresholds were consistently lower for children compared with adults at each time point. Mid-array electrodes (11 and 16) showed the least amount of change over time. CONCLUSIONS: AutoNRT thresholds demonstrated significant change over time, limiting the ability to use intraoperatively recorded ECAP thresholds to predict postoperative measurements. In this study, electrodes 11 and 16 showed the least amount of change in ECAP threshold over time and therefore would be the best choices for estimating postoperative ECAP thresholds. Although not an ideal solution, mid-array ECAP thresholds obtained intraoperatively may prove to be helpful in creating a first MAP when no other behavioral or electrophysiological data are available.
Assuntos
Audiometria de Resposta Evocada/instrumentação , Limiar Auditivo/fisiologia , Implantes Cocleares , Surdez/reabilitação , Potenciais Evocados Auditivos , Sistemas Inteligentes/instrumentação , Software , Telemetria/instrumentação , Algoritmos , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de PróteseRESUMO
Immune-mediated hearing losses include autoimmune inner ear disease, sudden sensorineural hearing loss, and Meniere's disease. Standard therapy for an acute decline in hearing is timely use of corticosteroids. Although 60% to 70% of patients are initially corticosteroid-responsive, that responsiveness is lost over time. In corticosteroid-resistant patients, increased expression of interleukin (IL)-1 is observed, and these patients may benefit from IL-1 inhibition. Autoinflammatory diseases are characterized by dysregulation of the innate immune response, clinically include sensorineural hearing loss, and benefit from IL-1 inhibition, thereby further establishing the relationship of IL-1 with immune-mediated sensorineural hearing loss.
Assuntos
Doenças Autoimunes , Produtos Biológicos , Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Doença de Meniere , Perda Auditiva Neurossensorial/tratamento farmacológico , HumanosRESUMO
HYPOTHESIS: Autoimmune inner ear disease (AIED) patients will differentially express interleukin (IL)-6 based on corticosteroid responsiveness. BACKGROUND: AIED is characterized by periods of acute sensorineural hearing loss (SNHL). In a majority of patients corticosteroid responsiveness is lost over time. The mechanisms that control corticosteroid responsiveness have not been fully elucidated. METHODS: Thirty-five AIED patients and 13 age-matched control subjects were enrolled in this study. Steroid responsive (nâ=â15) and steroid nonresponsive AIED patients (nâ=â20) were characterized based on audiometry before and after treatment for acute SNHL. Plasma and peripheral blood mononuclear cells (PBMC) were obtained at the time of acute SNHL to quantify plasma IL-6, soluble IL-6 receptor (sIL-6R), and C-C Motif Chemokine Ligand 3 (CCL3). PBMCs were stimulated with dexamethasone and release of soluble IL-6, sIL-6R, and CCL3 protein into conditioned supernatants was measured. Plasma IL-6 was also correlated to serum c-reactive protein (CRP), cardiac CRP, erythrocyte sedimentation rate. RESULTS: Statistically significant differences were observed in the plasma IL-6 between AIED patients and controls (2.37 versus 2.03âpg/ml, pâ<â0.01), plasma IL-6, and CCL3 between responders and nonresponders (0.136 versus 3.84âpg/ml, pâ<â0.005; 30.5 versus 32.4, pâ<â0.05) and released IL-6 from dexamethasone stimulated PBMC in AIED patients compared with controls (0.54 versus 1.12âpg/ml, pâ<â0.001). There was a correlation between plasma IL-6 levels of AIED patients to both serum CRP and cardiac CRP (R2â=â0.83, R2â=â0.88). CONCLUSIONS: We observed AIED patients, specifically nonresponders expressed greater levels of IL-6. Elevated IL-6 levels in AIED patients correlated with CRP levels, providing a commonly available laboratory test that may aid in rapid clinical decision-making in these patients.
Assuntos
Doenças Autoimunes , Interleucina-6/sangue , Labirintite , Corticosteroides/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Estudos de Casos e Controles , Humanos , Leucócitos MononuclearesRESUMO
BACKGROUND: COVID-19 is a pandemic respiratory and vascular disease caused by SARS-CoV-2 virus. There is a growing number of sensory deficits associated with COVID-19 and molecular mechanisms underlying these deficits are incompletely understood. METHODS: We report a series of ten COVID-19 patients with audiovestibular symptoms such as hearing loss, vestibular dysfunction and tinnitus. To investigate the causal relationship between SARS-CoV-2 and audiovestibular dysfunction, we examine human inner ear tissue, human inner ear in vitro cellular models, and mouse inner ear tissue. RESULTS: We demonstrate that adult human inner ear tissue co-expresses the angiotensin-converting enzyme 2 (ACE2) receptor for SARS-CoV-2 virus, and the transmembrane protease serine 2 (TMPRSS2) and FURIN cofactors required for virus entry. Furthermore, hair cells and Schwann cells in explanted human vestibular tissue can be infected by SARS-CoV-2, as demonstrated by confocal microscopy. We establish three human induced pluripotent stem cell (hiPSC)-derived in vitro models of the inner ear for infection: two-dimensional otic prosensory cells (OPCs) and Schwann cell precursors (SCPs), and three-dimensional inner ear organoids. Both OPCs and SCPs express ACE2, TMPRSS2, and FURIN, with lower ACE2 and FURIN expression in SCPs. OPCs are permissive to SARS-CoV-2 infection; lower infection rates exist in isogenic SCPs. The inner ear organoids show that hair cells express ACE2 and are targets for SARS-CoV-2. CONCLUSIONS: Our results provide mechanistic explanations of audiovestibular dysfunction in COVID-19 patients and introduce hiPSC-derived systems for studying infectious human otologic disease.
RESUMO
Interleukin-1ß (IL-1ß) is a key proinflammatory cytokine involved in the progression of many autoinflammatory and autoimmune diseases, including autoimmune inner ear disease (AIED). IL-1ß inhibition has been shown to result in clinical hearing improvement in a small cohort of corticosteroid-resistant patients with AIED. Canonical processing of pro-IL-1ß by caspase-1 generates an active 17-kDa fragment, capable of instigating a proinflammatory microenvironment. However, in response to LPS, PBMCs from patients with AIED uniquely express a 28-kDa IL-1ß fragment, as compared with PBMCs from control subjects. We synthesized and compared the biologic activity of the 28-kDa fragment to the 17-kDa IL-1ß product and the pro-IL-1 31-kDa protein. The 28-kDa IL-1ß fragment induces IL-6, TNF-α, and CCL3 in PBMCs. Uniquely, only caspase-7 treatment showed a dose- and time-dependent increase in 28-kDa band generation. Mass spectrometry confirmed the putative caspase-7 cleavage site of pro-IL-1ß, which was used to generate the 28-kDa fragment used for PBMC stimulation studies. Collectively, these results provide insight into the function of a poorly understood, processed 28-kDa form of IL-1ß in patients with AIED that is uniquely generated by caspase-7 and is capable of activating further downstream proinflammatory cytokines. Further investigation may provide novel pharmacologic targets for the treatment of this rare disease.
Assuntos
Doenças Autoimunes/metabolismo , Caspase 7/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Doenças do Labirinto/metabolismo , Citocinas/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , ProteóliseRESUMO
Implantable auditory devices (IADs) are a viable hearing restoration option for patients with hearing loss. Conditions such as chronic otitis externa, congenital aural atresia, and chronic otitis media can be treated with a variety of implants. Progressive disease are also amenable to restoration with IADs, providing stabilized hearing. When considering the best rehabilitative options, the patient's preference, ease of surgery, ease of device use, quality of life, and the traditional alternatives (such as ossiculoplasty, hearing aids, and cochlear implants) need to be considered. Patients with conductive, mixed, and sensorineural losses, mild to severe in nature, can be candidates for IADs.
Assuntos
Perda Auditiva/reabilitação , Prótese Ossicular , Pessoas com Deficiência Auditiva/reabilitação , Implantes Cocleares , Auxiliares de Audição , Perda Auditiva/etiologia , Perda Auditiva/cirurgia , Humanos , Preferência do Paciente , Desenho de Prótese , Ajuste de Prótese , Qualidade de VidaRESUMO
OBJECTIVE: To define the rate and characterize the type of newborn hearing screening failures in multigestational births. METHODS: Retrospective chart review of all multigestational births that occurred in a 10-year period (2002-2012) in which at least one newborn failed newborn hearing screening at two tertiary care hospitals in the Northwell Health System. RESULTS: Out of 125,405 total births, we identified 2961 multigestational births, of which 59 (2.0%) newborns failed newborn hearing screening. None of their 66 twin/triplet siblings failed their newborn hearing screens. Of 43 newborns that returned for follow-up, 56.0% (24/43) had confirmed hearing loss, resulting in an overall rate of 0.81% in all multigestational newborns with hearing loss. Of 19 infants that passed repeat testing, two were judged to need myringotomy tube placement. Twenty-four infants had a confirmed hearing loss, 11 of which had sensorineural hearing loss (0.37%), and 13 with a conductive or mixed hearing loss (0.44%). CONCLUSIONS: We identified a greater than expected risk of conductive hearing loss, not attributable to otitis media, than sensorineural hearing loss in this population. These observations are consistent with the increased risk of birth defects in multigestational births.
Assuntos
Perda Auditiva/epidemiologia , Testes Auditivos/estatística & dados numéricos , Triagem Neonatal/métodos , Gravidez Múltipla/estatística & dados numéricos , Feminino , Perda Auditiva/diagnóstico , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: Given ongoing debate about the suggested association, the primary objective was to determine if idiopathic sudden sensorineural hearing loss (ISSNHL) was a sentinel event for acute myocardial infarction (AMI) in adults. STUDY DESIGN: Case-control study. SETTING: United States MarketScan administrative health claims database. PATIENTS: Aged 18 years or older, had a diagnosis of ISSNHL on or after January 1st, 2011 and had sufficient follow-up data available to assess for AMI occurrence. INTERVENTION: N/A. MAIN OUTCOME MEASURES: Incidence rates (per 1,000 patient years) of AMI for cases and controls were computed. Adjusted and unadjusted Cox proportional hazards models were created to explore possible associations between ISSNHL and initial AMI. RESULTS: A total of 10,749 ISSNHL cases and 10,749 matched controls were included. There were no significant differences in the incidence rate of AMI between ISSNHL cases (8.29âevents/1,000 person-years) and controls (9.25âevents/1,000 person-years), nor were there differences within age groups, sex, or comorbidity status (overall incidence rate ratio 0.90; 95% confidence interval [CI] 0.70-1.15 pâ=â0.39). The unadjusted and adjusted Cox proportional hazards models did not demonstrate an association between ISSNHL and initial AMI (hazard ratio [HR]: 0.90, 95% CI: 0.70-1.15; HR: 0.86, 95% CI: 0.67-1.10, respectively). CONCLUSIONS: ISSNHL is not a predictor of an initial AMI in adult patients from the United States. Considerable inconsistencies in associations between cardiovascular risk factors and ISSNHL exist in the literature. Further work is needed to confirm or refute direct associations between cardiovascular disease risk factors and ISSNHL before definitive mechanistic conclusions can be made.
Assuntos
Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Súbita/epidemiologia , Infarto do Miocárdio/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos ProporcionaisRESUMO
Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a protein implicated in the control of inflammation in a number of autoimmune diseases. We hypothesized that the balance of TIMP-1 and matrix metalloproteinase-9 (MMP-9) may influence the control or perpetuation of inflammation in corticosteroid-responsive (RES) and corticosteroid-resistant (NR) autoimmune inner ear disease (AIED) patients. In the present study, we observed that plasma from AIED patients exhibited greater levels of TIMP-1 values compared with normal healthy controls. TIMP-1 abrogates lipopolysaccharide-mediated interleukin (IL)-1ß release from peripheral blood mononuclear cells in a dose-dependent manner. RES AIED patients have higher basal TIMP-1 levels and produce more TIMP-1 in response to IL-1ß. Conversely, consistent with our previous studies, we found that NR patients have higher basal MMP-9 levels and produce more MMP-9 levels in response to IL-1ß.
Assuntos
Doenças Autoimunes/metabolismo , Doenças do Labirinto/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Corticosteroides/uso terapêutico , Adulto , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/tratamento farmacológico , Microambiente Celular , Feminino , Humanos , Inflamação/patologia , Interleucina-1beta/sangue , Doenças do Labirinto/sangue , Doenças do Labirinto/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/sangueRESUMO
Objectives (1) Describe national patterns of chronic rhinosinusitis (CRS) care across academic and community practices. (2) Determine the prevalence of comorbid disorders in CRS patients, including nasal polyposis, allergic rhinitis, asthma, and cystic fibrosis. (3) Identify demographic, clinical, and practice type factors associated with endoscopic sinus surgery (ESS). Study Design Multisite cross-sectional study. Setting Otolaryngology's national research network CHEER (Creating Healthcare Excellence through Education and Research). Subjects and Methods A total of 17,828 adult patients with CRS were identified, of which 10,434 were seen at community practices (59%, n = 8 sites) and 7394 at academic practices (41%, n = 10 sites). Multivariate logistic regression was used to evaluate the association between demographic, practice type, and clinical factors and the odds of a patient undergoing ESS. Results The average age was 50.4 years; 59.5% of patients were female; and 88.3% were Caucasian. The prevalence of comorbid diseases was as follows: allergic rhinitis (35.1%), nasal polyposis (13.3%), asthma (4.4%), and cystic fibrosis (0.2%). In addition, 24.8% of patients at academic centers underwent ESS, as compared with 12.3% at community sites. In multivariate analyses, nasal polyposis (odds ratio [OR], 4.28), cystic fibrosis (OR, 2.42), and academic site type (OR, 1.86) were associated with ESS ( P < .001), while adjusting for other factors. Conclusions We describe practice patterns of CRS care, as well as demographic and clinical factors associated with ESS. This is the first study of practice patterns in CRS utilizing the CHEER network and may be used to guide future research.
Assuntos
Padrões de Prática Médica , Rinite/cirurgia , Sinusite/cirurgia , Adulto , Idoso , Doença Crônica , Comorbidade , Estudos Transversais , Fibrose Cística/complicações , Endoscopia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Razão de Chances , Otolaringologia , Seios Paranasais/cirurgia , Rinite/complicações , Rinite Alérgica/complicações , Sinusite/complicações , Estados UnidosRESUMO
OBJECTIVES: Autoinflammatory diseases are a family of immune-mediated, rare diseases, some of which, exhibit sensorineural hearing loss (SNHL), suggesting potentially similar mechanisms of molecular pathogenesis between autoinflammatory-mediated hearing loss and autoimmune inner ear disease (AIED) may exist. The purpose of this review is to compare the clinical features of autoimmune and autoinflammatory diseases that affect hearing, discuss the limitations of our knowledge, and highlight potential new disease mechanisms and therapeutics. DATA SOURCES: Pubmed Literature Review; Google Scholar Literature review. REVIEW METHODS: A focused comparison of AIED with a number of autoinflammatory diseases that manifest with sensorineural hearing loss was performed. The pathogenesis of these diseases is reviewed in the context of the innate and adaptive immune system, cytokine expression and genetic polymorphisms. RESULTS: AIED, since first described by Cogan and Lehnhardt and first clinically characterized by McCabe, has remained an enigmatic disease, with limited advances in both new diagnostics and new therapeutics. Since the discovery of autoinflammatory diseases, a number of systemic autoimmune diseases have either been re-classed as autoinflammatory diseases or identified to have features of autoinflammatory disease. CONCLUSION: AIED has clinical features of both autoimmune and autoinflammatory disease. It is critical that autoinflammatory diseases be correctly identified, as failure to do so may result in systemic amyloidosis and kidney damage.
RESUMO
We present a 3-year old boy with Leopard syndrome. His clinical manifestations included a congenital bilateral sensorineural hearing loss. He underwent cochlear implantation on the right side at age 1 year and on the left side at age 1.5 years. The patient is doing very well and mainstreamed in a regular pre-school program with a teacher of the deaf and home based speech therapy. Bilateral cochlear implantation in the case of a child with Leopard syndrome can be successful.
Assuntos
Implante Coclear , Perda Auditiva Bilateral/reabilitação , Perda Auditiva Neurossensorial/reabilitação , Síndrome LEOPARD/reabilitação , Pré-Escolar , Implantes Cocleares , Perda Auditiva Bilateral/etiologia , Perda Auditiva Neurossensorial/etiologia , Humanos , Síndrome LEOPARD/complicações , Inclusão Escolar , Masculino , Pessoas com Deficiência Auditiva , Fala , Percepção da Fala , FonoterapiaRESUMO
OBJECTIVES: (1) Describe thyroid-related diagnoses and procedures in Creating Healthcare Excellence through Education and Research (CHEER) across academic and community sites. (2) Compare management of malignant thyroid disease across these sites. (3) Provide practice-based data related to flexible laryngoscopy vocal fold assessment before and after thyroid surgery based on the American Academy of Otolaryngology-Head and Neck Surgery Foundation's clinical practice guidelines. STUDY DESIGN: Review of retrospective data collection (RDC) database of the CHEER network using ICD-9 and CPT codes related to thyroid conditions. SETTING: Multisite practice-based network. SUBJECTS AND METHODS: There were 3807 thyroid patients (1392 malignant, 2415 benign) with 10,160 unique visits identified from 1 year of patient data in the RDC. Analysis was performed for identified cohort of patients using demographics, site characteristics, and diagnostic and procedural distribution. RESULTS: Mean number of patients with thyroid disease per site was 238 (range, 23-715). In community practices, 19% of patients with thyroid disease had cancer versus 45% in the academic setting (P < .001). While academic sites manage more cancer patients, community sites are also surgically treating thyroid cancer and performed more procedures per cancer patient (4.2 vs 3.5, P < .001). Vocal fold function was assessed by flexible laryngoscopy in 34.0% of preoperative patients and in 3.7% postoperatively. CONCLUSION: This is the first overview of malignant and benign thyroid disease through CHEER. It shows how the RDC can be used alone and with national guidelines to inform of clinical practice patterns in academic and community sites. This demonstrates the potential for future thyroid-related studies utilizing the otolaryngology-head and neck surgery practice-based research network.
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Padrões de Prática Médica/estatística & dados numéricos , Doenças da Glândula Tireoide/cirurgia , Adulto , Bases de Dados Factuais , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Classificação Internacional de Doenças , Laringoscopia , Masculino , Pessoa de Meia-Idade , Otolaringologia/organização & administração , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Doenças da Glândula Tireoide/epidemiologia , Tireoidectomia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: (1) Integrate practice-based patient encounters using the Dartmouth Atlas Medicare database to understand practice treatments for Ménière's disease (MD). (2) Describe differences in the practice patterns between academic and community providers for MD. STUDY DESIGN: Practice-based research database review. SETTING: CHEER (Creating Healthcare Excellence through Education and Research) network academic and community providers. SUBJECTS AND METHODS: MD patient data were identified with ICD-9 and CPT codes. Demographics, unique visits, and procedures per patient were tabulated. The Dartmouth Atlas of Health Care was used to reference regional health care utilization. Statistical analysis included 1-way analyses of variance, bivariate linear regression, and Student's t tests, with significance set at P < .05. RESULTS: A total of 2071 unique patients with MD were identified from 8 academic and 10 community otolaryngology-head and neck surgery provider centers nationally. Average age was 56.5 years; 63.9% were female; and 91.4% self-reported white ethnicity. There was an average of 3.2 visits per patient. Western providers had the highest average visits per patient. Midwest providers had the highest average procedures per patient. Community providers had more visits per site and per patient than did academic providers. Academic providers had significantly more operative procedures per site (P = .0002) when compared with community providers. Health care service areas with higher total Medicare reimbursements per enrollee did not report significantly more operative procedures being performed. CONCLUSION: This is the first practice-based clinical research database study to describe MD practice patterns. We demonstrate that academic otolaryngology-head and neck surgery providers perform significantly more operative procedures than do community providers for MD, and we validate these data with an independent Medicare spending database.
Assuntos
Doença de Meniere/terapia , Padrões de Prática Médica/estatística & dados numéricos , Bases de Dados Factuais , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Classificação Internacional de Doenças , Masculino , Medicare , Doença de Meniere/epidemiologia , Pessoa de Meia-Idade , Otolaringologia/organização & administração , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: (1) Compare postoperative bleeding in the CHEER network (Creating Healthcare Excellence through Education and Research) among age groups, diagnoses, and practice types. (2) Report the incidence of bleeding by individual CHEER practice site based on practice guidelines. STUDY DESIGN: Retrospective data collection database review of the CHEER network based on ICD-9 and CPT codes related to tonsillectomy patients. SETTING: Multisite practice-based network. SUBJECTS AND METHODS: A total of 8347 subjects underwent tonsillectomy as determined by procedure code within the retrospective data collection database, and 107 had postoperative hemorrhage. These subjects had demographic information and related diagnoses based on the CPT and ICD-9 codes collected. Postoperative ICD-9 and CPT codes were used to identify patients who also had postoperative bleed. Variables included age (<12 vs ≥12 years), diagnoses (infectious vs noninfectious), and practice type (community vs academic). Statistical analysis included multivariate logistic regression variables predictive of postoperative bleeding, with P < .05 considered significant. RESULTS: Thirteen sites contributed data to the study (7 academic, 6 community). There was postoperative bleeding for an overall bleed rate of 1.3%. Patients ≥12 years old had a significantly increased bleed rate when compared with the younger group (odds ratio, 5.98; 95% confidence interval: 3.79-9.44; P < .0001). There was no significant difference in bleed rates when practices or diagnoses were compared. CONCLUSION: A site descriptor database built to expedite clinical research can be used for practice assessment and quality improvement. These data were also useful to identify patient risk factors for posttonsillectomy bleed.