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1.
Hum Genet ; 141(3-4): 853-863, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34424407

RESUMO

Pathogenic variations in the OTOF gene are a common cause of hearing loss. To refine the natural history and genotype-phenotype correlations of OTOF-related auditory neuropathy spectrum disorders (ANSD), audiograms and distortion product otoacoustic emissions (DPOAEs) were collected from a diverse cohort of individuals diagnosed with OTOF-related ANSD by comprehensive genetic testing and also reported in the literature. Comparative analysis was undertaken to define genotype-phenotype relationships using a Monte Carlo algorithm. 67 audiograms and 25 DPOAEs from 49 unique individuals positive for OTOF-related ANSD were collected. 51 unique OTOF pathogenic variants were identified of which 21 were missense and 30 were loss of function (LoF; nonsense, splice-site, copy number variants, and indels). There was a statistically significant difference in low, middle, and high frequency hearing thresholds between missense/missense and LoF/missense genotypes as compared to LoF/LoF genotypes (average hearing threshold for low, middle and high frequencies 70.9, 76.0, and 73.4 dB vs 88.5, 95.6, and 94.7 dB) via Tukey's test with age as a co-variate (P = 0.0180, 0.0327, and 0.0347, respectively). Hearing declined during adolescence with missense/missense and LoF/missense genotypes, with an annual mid-frequency threshold deterioration of 0.87 dB/year and 1.87 dB/year, respectively. 8.5% of frequencies measured via DPOAE were lost per year in individuals with serial tests. Audioprofiling of OTOF-related ANSD suggests significantly worse hearing with LoF/LoF genotypes. The unique pattern of variably progressive OTOF-related autosomal recessive ANSD may be amenable to gene therapy in selected clinical scenarios.


Assuntos
Surdez , Perda Auditiva Central , Perda Auditiva Central/diagnóstico , Perda Auditiva Central/genética , Humanos , Proteínas de Membrana/genética , Mutação
2.
Hum Mutat ; 40(8): 1156-1171, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31009165

RESUMO

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media.


Assuntos
Regulação para Baixo , Perfilação da Expressão Gênica/métodos , Mutação , Otite Média/genética , Análise de Sequência de DNA/métodos , alfa-Macroglobulinas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Finlândia , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Paquistão , Linhagem , Filipinas , Análise de Sequência de RNA , Transdução de Sinais , Estados Unidos , Adulto Jovem
4.
Am J Otolaryngol ; 39(2): 101-106, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29395279

RESUMO

PURPOSE: Otorrhea frequently follows tympanostomy tube (TT) placement. We evaluated otorrhea following single 6mg OTO-201 (OTIPRIO®, ciprofloxacin otic suspension 6%) intraoperative injection into each middle ear in a variety of effusion types and concurrent procedures in children undergoing TT placement. SECONDARY OBJECTIVE: Efficacy based on Medicaid status and safety. BASIC PROCEDURES: In this prospective, 8-week, multicenter, open-label study, 501 patients were enrolled: mean age 2.9years, male (56.9%), wet/wet ears (66.9%), wet/dry (16.8%), dry/dry (16.3%), and Medicaid-insured (32.9%). MAIN FINDINGS: In per-protocol population (n=410), otorrhea rate through Day 15 were 8.8% (CI:5.7%-12.8%), 6.6% (CI:2.2%-14.7%), 3.3% (CI:0.4%-11.3%) in wet/wet, wet/dry, and dry/dry ears, respectively. For Medicaid patients through Day 15, Week 4 and Week 8, otorrhea rates were 8.1% (CI:4.1%-14.1%), 17.0% (CI:11.1%-24.5%), and 17.8% (CI:11.7%-25.3%) compared with those non-Medicaid insured: 7.3% (CI:4.5%-11.0%), 14.5% (CI:10.6%-19.3%), and 21.8% (CI:17.1%-27.2%), respectively. Safety was similar to previous Phase 3 trials. PRINCIPAL CONCLUSIONS: OTO-201 demonstrated otorrhea rates consistent with Phase 3 trials in a broader, real-world, ENT practice-based pediatric population. Outcomes were similar in Medicaid- and non-Medicaid insured patients. OTO-201 was well-tolerated.


Assuntos
Ciprofloxacina/administração & dosagem , Ventilação da Orelha Média/métodos , Otite Média com Derrame/terapia , Adolescente , Antibacterianos/administração & dosagem , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Injeção Intratimpânica , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
5.
Am J Otolaryngol ; 35(5): 655-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25085633

RESUMO

Pediatric cervical masses can present a diagnostic dilemma given their broad differential diagnosis. We present a 3-year-old girl with a midline anterior neck mass found to have histopathologic findings consistent with a bronchogenic cyst. Although rare, bronchogenic cysts should be considered in the differential diagnosis in both lateral and anterior pediatric cervical masses as their pathophysiology and embryogenesis differ considerably from more common cervical masses. Imaging is an important aspect in the pre-operative work-up, although diagnosis is only made after histopathologic analysis. Complete surgical excision is the definitive treatment.


Assuntos
Cisto Broncogênico/diagnóstico por imagem , Cisto Broncogênico/cirurgia , Pescoço , Cisto Broncogênico/patologia , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Ultrassonografia
6.
Laryngoscope ; 134(1): 40-46, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37341501

RESUMO

OBJECTIVE: Our goal was to identify the early pioneering women surgeons in the United States who devoted their career or the majority of their practice to the care of otolaryngologic disorders in children. We sought to share their stories, recognize their contributions to the surgical subspecialty now known as pediatric otolaryngology, and acknowledge their vision and leadership. DATA SOURCES: Primary sources include books, published articles in the medical literature, newspaper articles, memorials/obituaries in both the medical literature and lay press, web logs, the John Q Adams Center for the History of Otolaryngology to include the Women in Otolaryngology, a number of otolaryngology departments, and children's hospitals nationwide. Interviews were conducted with former colleagues and senior pediatric otolaryngologists. REVIEW METHODS: Following review of all available information, women surgeons were included in this study if there was documentation of a clinical practice involving the otolaryngologic care of children in the United States before 1985 with demonstration of the education of others in this discipline. RESULTS: Six women surgeons were identified: Drs. Alice G Bryant, Margaret F. Butler, Ellen James Patterson, Emily Lois Van Loon, LaVonne Bernadene Bergstrom, and Joyce A. Schild. CONCLUSION: Six pioneering women surgeons in the United States have been identified who devoted their practice to the care of otolaryngologic disorders in children and mentored or trained other health care providers. The stories of their lives, their contributions to the care of otolaryngologic disorders in children, and their work as mentors or educators have been described. Laryngoscope, 134:40-46, 2024.


Assuntos
Otolaringologia , Otorrinolaringopatias , Cirurgiões , Humanos , Criança , Feminino , Estados Unidos , Otorrinolaringologistas , Hospitais Pediátricos
7.
Int J Pediatr Otorhinolaryngol ; 176: 111799, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38081110

RESUMO

OBJECTIVE: Postviral olfactory dysfunction (OD) including corona 2019 viral disease (COVID-19) OD occurs in both adults and children. Despite limited reports of efficacy in treating adult postviral including COVID-19 OD with olfactory training (OT), its effects on children in general, and post-COVID-19 in specific, is unknown. The study aimed at evaluating the effects of OT in a COVID-19 OD pediatric cohort. METHODS: A single-arm prospective study of pediatric COVID-19 OD subjects confirmed by the University of Pennsylvania Smell Identification Test (UPSIT), was conducted. All subjects underwent OT by sniffing 4 odorants (lavender, orange, peppermint, and eucalyptus) for 1 min twice a day for 3 months. Subjects underwent an odorant identification test (OIT) of the 4 odorants each visit. A repeat UPSIT was administered at the 4th visit. RESULTS: The study enrolled a total of 37 subjects [11 males/26 females with mean age/standard deviation (std) of 15.6(2.1) years]. The time interval between COVID-19 and entry was 5.3(2.4) months. The mean pre/post study UPSIT score improvement was 2.3(4.7), p = .09. OIT scores between entry and 3 subsequent visits showed a mean improvement of 1.8(1.5), 1.8(1.9) and 2.3(1.9) odorants, respectively, with P < .001 for all 3 comparisons. CONCLUSIONS: OT subjects were predominantly female teens with substantial OD lasting greater than 5 months. OT did not affect OD as measured by UPSIT but OIT scores improved during OT. We postulate that OT likely has a role in pediatric post-COVID OD recovery, but UPSIT likely is too rigid to detect disparate odorant improvement.


Assuntos
COVID-19 , Transtornos do Olfato , Adulto , Masculino , Adolescente , Humanos , Feminino , Criança , Olfato , Estudos Prospectivos , Treinamento Olfativo , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Transtornos do Olfato/terapia , Odorantes
8.
J Pediatr ; 162(3): 635-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23219244

RESUMO

Cervical ribs may cause thoracic outlet syndrome in adults, but symptoms are poorly described in children. In our series, 88.8% of the 322 children were asymptomatic. The most common symptoms were neck mass and pain. Useful diagnostic tools were cervical spine and chest radiographs. Differential diagnosis of a supraclavicular mass includes cervical ribs.


Assuntos
Síndrome da Costela Cervical/diagnóstico , Costela Cervical/diagnóstico por imagem , Vértebras Cervicais/diagnóstico por imagem , Adolescente , Síndrome da Costela Cervical/diagnóstico por imagem , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Cervicalgia/diagnóstico , Cervicalgia/etiologia , Radiografia Torácica , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
Clin Pediatr (Phila) ; : 99228231211155, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932925

RESUMO

Tinnitus and misophonia are important "sound annoyance" disorders in pediatric otolaryngology and audiology practices. There is scant published literature to suggest increased anxiety and depression symptoms in these disorders. This study aimed at assessing the clinical characteristics of these 2 disorders and their prevalence in mental health-related symptoms in a 2-year retrospective chart review of a multi-disciplinary (otolaryngology, audiology, and psychology) clinic cohort. Analyses were based on 54 (tinnitus = 33 and misophonia = 21) children consisting of 19 males and 35 females with a mean age (standard deviation) of 14.3 (3.0) years. The entire cohort was negatively affected by diagnosis-based symptom severity instruments as assessed by Tinnitus Functional Index and Amsterdam Misophonia Scale. Both subgroups exhibited elevated anxiety and depression symptoms in psychometric instruments as assessed by Screen for Child Anxiety Related Emotional Disorders and Short Mood and Feelings Questionnaire. Evidence-based management of these disorders is lacking, and clinical trials are needed.

10.
Genet Test Mol Biomarkers ; 27(7): 221-228, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37522794

RESUMO

Background: Otitis media (OM) is defined as middle ear (ME) inflammation that is usually due to infection. Globally, OM is a leading cause of hearing loss and is the most frequently diagnosed disease in young children. For OM, pediatric patients with Down syndrome (DS) demonstrate higher incidence rates, greater severity, and poorer outcomes. However, to date, no studies have investigated the bacterial profiles of children with DS and OM. Method: We aimed to determine if there are differences in composition of bacterial profiles or the relative abundance of individual taxa within the ME and nasopharyngeal (NP) microbiotas of pediatric OM patients with DS (n = 11) compared with those without DS (n = 84). We sequenced the 16S rRNA genes and analyzed the sequence data for diversity indices and relative abundance of individual taxa. Results: Individuals with DS demonstrated increased biodiversity in their ME and NP microbiotas. In children with OM, DS was associated with increased biodiversity and higher relative abundance of specific taxa in the ME. Conclusion: Our findings suggest that dysbioses in the NP of DS children contributes to their increased susceptibility to OM compared with controls. These findings suggest that DS influences regulation of the mucosal microbiota and contributes to OM pathology.


Assuntos
Síndrome de Down , Microbiota , Otite Média , Criança , Humanos , Pré-Escolar , RNA Ribossômico 16S/genética , Síndrome de Down/genética , Otite Média/genética , Orelha Média/microbiologia , Orelha Média/patologia , Microbiota/genética
11.
Int J Pediatr Otorhinolaryngol ; 141: 110563, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360407

RESUMO

OBJECTIVE: To provide guidance for home care tracheostomy management in the pediatric population. The mission of the IPOG is to develop expertise-based recommendations for the management of pediatric otolaryngologic disorders with the goal of improving patient care. METHODS: Survey of expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). RESULTS: Survey results provide guidance for caregiver teaching, the reuse of tracheostomies and suction catheters while inpatient and following discharge, acceptable sterilization practices for tracheostomies, tracheitis workup and management, and outpatient follow-up practices. CONCLUSION: This presentation of common home tracheostomy care practices are aimed at improving patient-centered care in the pediatric population.


Assuntos
Serviços de Assistência Domiciliar , Otolaringologia , Criança , Humanos , Assistência Centrada no Paciente , Inquéritos e Questionários , Traqueostomia/efeitos adversos
12.
Front Cell Infect Microbiol ; 11: 798246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35096646

RESUMO

Otitis media (OM) is a leading cause of childhood hearing loss. Variants in FUT2, which encodes alpha-(1,2)-fucosyltransferase, were identified to increase susceptibility to OM, potentially through shifts in the middle ear (ME) or nasopharyngeal (NP) microbiotas as mediated by transcriptional changes. Greater knowledge of differences in relative abundance of otopathogens in carriers of pathogenic variants can help determine risk for OM in patients. In order to determine the downstream effects of FUT2 variation, we examined gene expression in relation to carriage of a common pathogenic FUT2 c.461G>A (p.Trp154*) variant using RNA-sequence data from saliva samples from 28 patients with OM. Differential gene expression was also examined in bulk mRNA and single-cell RNA-sequence data from wildtype mouse ME mucosa after inoculation with non-typeable Haemophilus influenzae (NTHi). In addition, microbiotas were profiled from ME and NP samples of 65 OM patients using 16S rRNA gene sequencing. In human carriers of the FUT2 variant, FN1, KMT2D, MUC16 and NBPF20 were downregulated while MTAP was upregulated. Post-infectious expression in the mouse ME recapitulated these transcriptional differences, with the exception of Fn1 upregulation after NTHi-inoculation. In the NP, Candidate Division TM7 was associated with wildtype genotype (FDR-adj-p=0.009). Overall, the FUT2 c.461G>A variant was associated with transcriptional changes in processes related to response to infection and with increased load of potential otopathogens in the ME and decreased commensals in the NP. These findings provide increased understanding of how FUT2 variants influence gene transcription and the mucosal microbiota, and thus contribute to the pathology of OM.


Assuntos
Fucosiltransferases , Infecções por Haemophilus , Microbiota , Nasofaringe , Otite Média , Animais , Orelha Média , Fucosiltransferases/genética , Infecções por Haemophilus/metabolismo , Haemophilus influenzae/genética , Humanos , Camundongos , Microbiota/genética , Nasofaringe/microbiologia , Otite Média/genética , Otite Média/metabolismo , RNA Ribossômico 16S/genética , Galactosídeo 2-alfa-L-Fucosiltransferase
13.
J Mol Med (Berl) ; 99(11): 1571-1583, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34322716

RESUMO

Otitis media (OM) is common in young children and can cause hearing loss and speech, language, and developmental delays. OM has high heritability; however, little is known about OM-related molecular and genetic processes. CDHR3 was previously identified as a locus for OM susceptibility, but to date, studies have focused on how the CDHR3 p.Cys529Tyr variant increases epithelial binding of rhinovirus-C and risk for lung or sinus pathology. In order to further delineate a role for CDHR3 in OM, we performed the following: exome sequencing using DNA samples from OM-affected individuals from 257 multi-ethnic families; Sanger sequencing, logistic regression and transmission disequilibrium tests for 407 US trios or probands with OM; 16S rRNA sequencing and analysis for middle ear and nasopharyngeal samples; and single-cell RNA sequencing and differential expression analyses for mouse middle ear. From exome sequence data, we identified a novel pathogenic CDHR3 splice variant that co-segregates with OM in US and Finnish families. Additionally, a frameshift and six missense rare or low-frequency variants were identified in Finnish probands. In US probands, the CDHR3 p.Cys529Tyr variant was associated with the absence of middle ear fluid at surgery and also with increased relative abundance of Lysobacter in the nasopharynx and Streptomyces in the middle ear. Consistent with published data on airway epithelial cells and our RNA-sequence data from human middle ear tissues, Cdhr3 expression is restricted to ciliated epithelial cells of the middle ear and is downregulated after acute OM. Overall, these findings suggest a critical role for CDHR3 in OM susceptibility. KEY MESSAGES: • Novel rare or low-frequency CDHR3 variants putatively confer risk for otitis media. • Pathogenic variant CDHR3 c.1653 + 3G > A was found in nine families with otitis media. • CDHR3 p.Cys529Tyr was associated with lack of effusion and bacterial otopathogens. • Cdhr3 expression was limited to ciliated epithelial cells in mouse middle ear. • Cdhr3 was downregulated 3 h after infection of mouse middle ear.


Assuntos
Proteínas Relacionadas a Caderinas/genética , Proteínas de Membrana/genética , Otite Média/genética , Animais , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Camundongos Endogâmicos C57BL , Microbiota/genética , Mutação , Otite Média/microbiologia , RNA Ribossômico 16S , Transcriptoma
14.
Otol Neurotol ; 41(7): 978-985, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32658404

RESUMO

OBJECTIVES: To investigate novel variants in hearing loss genes and clinical factors affecting audiometric outcomes of cochlear implant (CI) patients. BACKGROUND: Approximately 50% of hearing loss has a genetic etiology, with certain genetic variants more prevalent in specific ethnic groups. Different variants and some clinical variables including inner ear malformations result in different prognoses or clinical outcomes after CI. METHODS: Medical and genetic testing records of pediatric CI patients were reviewed for clinical variables. Minor allele frequencies of variants were obtained from Genome Aggregation Database (gnomAD) and variants were classified for pathogenicity. Standard statistical testing was done using Fisher's exact, Wilcoxon, and Spearman correlation tests. RESULTS: Eighteen CI patients with genetic test results had pathogenic variants, including six patients with syndromic hearing loss and six patients with known GJB2 variants. Novel pathogenic variants were noted in CHD7, ADGRV1, and ARID1B, with variants in the latter two genes identified in Hispanic patients. Overall, carriage of genetic variants was associated with better pre-CI audiometric thresholds at 2000 Hz (p = 0.048). On the other hand, post-CI thresholds were significantly worse in patients with inner ear malformations, particularly in patients with atretic cochlear nerve canals. CONCLUSION: Four novel pathogenic variants were identified, which contributes to knowledge of allelic spectrum for hearing loss especially in Hispanic patients. In this cohort, carriage of pathogenic variants particularly of GJB2 variants was associated with better pre-CI audiometric thresholds, while patients with inner ear malformations had worse post-CI audiometric thresholds.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva , Criança , Etnicidade/genética , Perda Auditiva/cirurgia , Humanos
15.
Otol Neurotol ; 41(3): 345-351, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31851066

RESUMO

OBJECTIVE: To provide recommendations to otolaryngologists and allied physicians for the comprehensive management of children who present with signs and symptoms of congenital cholesteatoma. METHODS: A two-iterative Delphi method questionnaire was used to establish expert recommendations by the members of the International Pediatric Otolaryngology Group, on the preoperative work-up, the perioperative considerations, and follow-up. RESULTS: Twenty-two members completed the survey, in 14 tertiary-care center departments representing 5 countries. The main consensual recommendations were: a precise otoscopic description of the quadrants involved, extensive audiological workup (bilateral tonal, vocal audiometry, and BERA), and a CT scan are required. Facial nerve monitoring and a combination of microscope and telescope are recommended for surgical removal. Clinical and audiological follow-up should be pursued yearly for at least 5 years. First MRI follow-up should be done at 18 months postoperatively if the removal violated the matrix. MRI follow-up duration depends on the initial extent of the cholesteatoma. CONCLUSION: The goal of preoperative and follow-up consensus from International Pediatric Otolaryngology Group participants is to help manage infants and children with congenital cholesteatoma. The operative techniques may vary, and experienced surgeons must perform these procedures.


Assuntos
Colesteatoma da Orelha Média , Colesteatoma , Otolaringologia , Criança , Colesteatoma/diagnóstico por imagem , Colesteatoma/cirurgia , Colesteatoma da Orelha Média/diagnóstico por imagem , Colesteatoma da Orelha Média/cirurgia , Consenso , Humanos , Lactente , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X
16.
Sci Rep ; 10(1): 15035, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929111

RESUMO

Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.


Assuntos
Mutação de Sentido Incorreto , Otite Média/genética , Plasminogênio/genética , Animais , Orelha Média/metabolismo , Orelha Média/microbiologia , Feminino , Genômica/métodos , Humanos , Masculino , Camundongos , Microbiota , Otite Média/microbiologia , Otite Média/patologia , Linhagem , Plasminogênio/metabolismo , Polimorfismo de Nucleotídeo Único , Saliva/metabolismo
17.
Int J Pediatr Otorhinolaryngol ; 129: 109770, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31733596

RESUMO

INTRODUCTION: Advanced practice providers (APPs), including nurse practitioners and physician assistants, have been deployed in children's hospital-based academic pediatric otolaryngology practices for many years. However, this relationship in terms of prevalence, roles, financial consequences and satisfaction has not been examined. The objective of this study is to explore how APPs impact healthcare delivery in this setting. METHODS: Pediatric otolaryngology chiefs of all academic children's hospitals in the US were electronically surveyed about the ways APPs intersected clinically and financially in their respective practice. RESULTS: A total of 29 of 36 children's hospital-based pediatric otolaryngology practices completed the survey, of which 26 practices (90%) utilized APP. There were large variances within the APP practice cohort in faculty size (mean/median/range = 9.4/8.5/3-29); annual patient visits (mean/median = 18,373/17,600); number of practice site (mean/median/range = 4.3/4/2-9) and number of outpatient APP (mean/median/range = 6.3/5/1-30). No factors (faculty size, annual visits and number of practice sites) differentiated between the APP and non-APP practices. Among APP practices, significant correlation (p<.00001) was observed between size of APP cohort to faculty size and annual visits. 69% of the practices did not differentiate job functions of nurse practitioners and physician assistants. 85% of the practices utilized APPs in all practice sites and 19% utilized APPs in the operating room. 77% of APPs billed independently and 46% had on-site supervision. The most prevalent APP salary bracket based on 0-5, 6-10 and > 11 years of tenure were $76-100K (65%), $100-150K (77%) and $100-150K (86%), respectively. In 46% of the practices, APPs were able to generate enough revenue to cover more than 75% of their salary and 23% of practices generated a profit. 81% of the chiefs ranked the effectiveness of APPs as high (4 and 5) on a 5-point Likert scale. DISCUSSION: The majority of academic pediatric otolaryngology practices employed APPs. Despite the diversity seen in practice complexity, APP functionality and financial impact, most found the APP model to be beneficial in improving patient care, patient access and faculty productivity.


Assuntos
Profissionais de Enfermagem/estatística & dados numéricos , Otolaringologia/organização & administração , Otolaringologia/estatística & dados numéricos , Assistentes Médicos/estatística & dados numéricos , Papel Profissional , Docentes de Medicina/estatística & dados numéricos , Hospitais Pediátricos , Humanos , Renda/estatística & dados numéricos , Profissionais de Enfermagem/organização & administração , Otolaringologia/economia , Otolaringologia/educação , Assistentes Médicos/organização & administração , Inquéritos e Questionários
18.
J Pediatr ; 154(5): 754-8, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19159906

RESUMO

OBJECTIVE: Previous investigation demonstrated predominantly lymphocytic inflammation in sinus mucosa of young children with chronic rhinosinusitis (CRS) rather than eosinophilic inflammation typical of adult CRS. Immunohistopathological study was undertaken to define further the cellular response in pediatric CRS. STUDY DESIGN: Maxillary mucosal biopsies from children and adults with CRS were stained for CD3 (T lymphocytes), CD4 (helper T lymphocytes), CD8 (cytotoxic T lymphocytes), CD20 (B lymphocytes), CD68 (monocytes/macrophages), CD56 (natural killer cells), kappa and lambda (plasma cells), and myeloperoxidase (MPO; neutrophils). RESULTS: Nineteen children with CRS (median age, 3.0 years; range, 1.4-8.2 years) had more CD8+, MPO+, and CD68+ cells (P < or = .03) and a trend toward more CD3+ and CD4+ cells (P = .06) in their epithelium and more CD20+, kappa+ and lambda+, MPO+, and CD68+ cells (P < or = .05) and a trend toward more CD4+ cells (P = .06) in their submucosa compared with adult control subjects. Immunostains from children with positive sinus cultures were similar to those with negative cultures except for more MPO+ cells in the submucosa (P = .04). CONCLUSION: The inflammatory response of young children with CRS is characterized by a mixed lymphocyte population, macrophages, and neutrophils. Differences between pediatric and adult CRS suggest differing pathogenic mechanisms or progression in the inflammatory response with protracted disease.


Assuntos
Mucosa Nasal/imunologia , Rinite/imunologia , Sinusite/imunologia , Adulto , Antígenos CD/imunologia , Linfócitos B/imunologia , Biópsia , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença Crônica , Humanos , Lactente , Macrófagos/imunologia , Seio Maxilar/imunologia , Seio Maxilar/metabolismo , Mucosa Nasal/metabolismo , Células T Matadoras Naturais/imunologia , Neutrófilos/enzimologia , Neutrófilos/imunologia , Peroxidase/metabolismo , Plasmócitos/imunologia , Coloração e Rotulagem , Linfócitos T/imunologia
19.
Otolaryngol Head Neck Surg ; 161(5): 877-880, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31500503

RESUMO

OBJECTIVES: Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by abnormal respiratory cilia ultrastructure and/or function causing defective mucociliary clearance. We investigated the extent and severity of rhinosinusitis in a large cohort of children with PCD and explored associations among risk factors, including genotype and sinus disease. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic children's hospital. SUBJECTS AND METHODS: A review was conducted with a patient registry at the PCD Foundation Center at our institution. Demographic, imaging, clinical, and operative data were reviewed through the institutional electronic health record system. RESULTS: Fifty-four subjects were identified with mean and median age at diagnosis of 5.2 and 4.0 years. The male:female ratio was 35%:65%. Sinus symptoms were present in 46 (85%) subjects, 22 of whom had chronic rhinosinusitis. Nineteen (35%) subjects underwent operative intervention, consisting of endoscopic sinus surgery (ESS; 16 patients) and maxillary lavage (3 patients). Nineteen subjects underwent adenoidectomy for PCD-related indications. Five sinus-related admissions in 3 subjects were noted during the study period, and no complication of rhinosinusitis occurred in the cohort. Genetic test results were available in 27 subjects, in whom 23 (85%) had biallelic mutations in a PCD gene. Demographic factors, Lund-Mackay score, and PCD genotype were not found to be predictors for ESS or hospitalization in our cohort. CONCLUSION: While rhinosinusitis was common in our PCD cohort, most patients did not require ESS. Since complications of rhinosinusitis were uncommon, we recommend judicious surgical management tailored to the patient's symptoms.


Assuntos
Transtornos da Motilidade Ciliar/complicações , Rinite/epidemiologia , Sinusite/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Transtornos da Motilidade Ciliar/diagnóstico , Transtornos da Motilidade Ciliar/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Rinite/diagnóstico , Rinite/cirurgia , Fatores de Risco , Índice de Gravidade de Doença , Sinusite/diagnóstico , Sinusite/cirurgia
20.
Int J Pediatr Otorhinolaryngol ; 117: 148-152, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30579070

RESUMO

OBJECTIVE: Large-scale otoscopic and audiometric assessment of populations is difficult due to logistic impracticalities, particularly in low- and middle-income countries (LMIC). We report a novel assessment methodology based on training local field workers, advances in audiometric testing equipment and cloud-based technology. METHODS: Prospective observational study in Bohol, Philippines. A U.S. otolaryngologist/audiologist team trained 5 local nurses on all procedures in a didactic and hands-on process. An operating otoscope (Welch-AllynR) was used to clear cerumen and view the tympanic membrane, images of which were recorded using a video otoscope (JedMedR). Subjects underwent tympanometry and distortion product otoacoustic emission (DPOAE) (Path SentieroR), and underwent screening audiometry using noise cancelling headphones and a handheld Android device (HearScreenR). Sound-booth audiometry was reserved for failed subjects. Data were uploaded to a REDCap database. Teenage children previously enrolled in a 2000-2004 Phase 3 pneumococcal conjugate vaccine trial, were the subjects of the trainees. RESULTS: During 4 days of training, 47 Filipino children (M/F = 28/19; mean/median age = 14.6/14.6 years) were the subjects of the trainee nurses. After the training, all nurses could perform all procedures independently. Otoscopic findings by ears included: normal (N = 77), otitis media with effusion (N = 2), myringosclerosis (N = 5), healed perforation (N = 6), perforation (N = 2) and retraction pocket/cholesteatoma (N = 2). Abnormal audiometric findings included: tympanogram (N = 4), DPOAE (N = 4) and screening audiometry (N = 0). CONCLUSION: Training of local nurses has been shown to be robust and this methodology overcomes challenges of distant large-scale population otologic/audiometric assessment.


Assuntos
Testes de Impedância Acústica , Audiometria , Colesteatoma/diagnóstico , Países em Desenvolvimento , Otopatias/diagnóstico , Educação Continuada em Enfermagem/métodos , Papel do Profissional de Enfermagem , Otoscopia , Adolescente , Feminino , Perda Auditiva/diagnóstico , Humanos , Masculino , Miringoesclerose/diagnóstico , Otite Média/diagnóstico , Filipinas , Projetos Piloto , Estudos Prospectivos , Perfuração da Membrana Timpânica/diagnóstico por imagem
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