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  • 1
    In: The Annals of Thoracic Surgery, Elsevier BV, Vol. 98, No. 4 ( 2014-10), p. 1246-1253
    Type of Medium: Online Resource
    ISSN: 0003-4975
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 1499869-5
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  • 2
    In: The Laryngoscope, Wiley, Vol. 132, No. 2 ( 2022-02), p. 470-477
    Abstract: Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute to persistent, viscous middle ear (ME) effusions, hearing loss, and potential for developmental delay. Extraesophageal reflux (EER), specifically pepsin, triggers inflammatory signaling in respiratory mucosa and is associated with OM. The objective of this study was to investigate the association of pepsin with ME inflammatory signaling and the outcomes and examine causality in vitro . Study Design Cross‐sectional study. Methods ME fluid (MEF) and preoperative audiometric data were collected from 30 pediatric subjects undergoing tympanostomy tube placement for recurrent OM or OM with effusion. MEF viscosity was characterized by the surgeon. Pepsin, inflammatory molecules, and mucin were assayed by enzyme‐linked immunosorbent assay (ELISA). ME epithelial primary culture was exposed to 0.1 to 1 mg/ml pepsin at pH 5, 6, and 7 for 30 minutes, and cytokine expression was assayed via qPCR. Results Pepsin was observed in the MEF of 77% of patients (range 71–2,734 ng/ml). Pepsin correlated with effusion viscosity, interleukins −6 and −8, neutrophil elastase, and mucin 5B ( P   〈  .05). Pepsin‐negative MEF was more frequently absent of interleukin 8 or mucin 5B ( P   〈  .05). Weak acid was generally insufficient to elicit cytokine expression in ME cells in vitro , however, pepsin induced IL6 , IL8 , and TNF at pH 7 ( P   〈  .05) and weak acid (pH 6) facilitated a response at lower pepsin concentration. Conclusions Pepsin may contribute to inflammatory signaling, persistent viscous effusion, and poorer OM outcomes. Level of Evidence 4 Laryngoscope , 132:470–477, 2022
    Type of Medium: Online Resource
    ISSN: 0023-852X , 1531-4995
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2026089-1
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  • 3
    In: The Laryngoscope, Wiley, Vol. 131, No. 11 ( 2021-11), p. 2590-2597
    Abstract: Otitis media (OM) is the most common pediatric diagnosis in the United States. However, our understanding of the molecular pathogenesis of OM remains relatively poor. Investigation of molecular pathways involved in OM may improve the understanding of this disease process and elucidate novel therapeutic targets. In this study, RNA sequencing (RNA‐Seq) was used to discern cellular changes associated with OME compared to healthy middle ear epithelium (MEE). Study Design Ex vivo case‐control translational. Methods Middle ear epithelia was collected from five pediatric patients diagnosed with OME undergoing tympanostomy tube placement and five otherwise healthy pediatric patients undergoing cochlear implantation. Specimens underwent RNA‐Seq and pathways analyses. Results A total of 1,292 genes exhibited differential expression in MEE from OME patients compared to controls including genes involved in inflammation, immune response to bacterial OM pathogens, mucociliary clearance, regulation of proliferation and transformation, and auditory cell differentiation. Top networks identified in OME were organismal injury and abnormalities, cell morphology, and auditory disease. Top Ingenuity canonical pathways identified were axonal guidance signaling, which contains genes associated with auditory development and disease and nicotine degradation II and III pathways. Associated upstream regulators included β‐estradiol, dexamethasone, and G‐protein‐coupled estrogen receptor‐1 (GPER1), which are associated with otoprotection or inflammation during insult. Conclusions RNA‐Seq demonstrates differential gene expression in MEE from patients with OME compared to healthy controls with important implications for infection susceptibility, hearing loss, and a role for tobacco exposure in the development and/or severity of OME in pediatric patients. Level of Evidence 4 Laryngoscope , 131:2590–2597, 2021
    Type of Medium: Online Resource
    ISSN: 0023-852X , 1531-4995
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2026089-1
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  • 4
    Online Resource
    Online Resource
    Elsevier BV ; 2011
    In:  International Journal of Pediatric Otorhinolaryngology Vol. 75, No. 10 ( 2011-10), p. 1271-1274
    In: International Journal of Pediatric Otorhinolaryngology, Elsevier BV, Vol. 75, No. 10 ( 2011-10), p. 1271-1274
    Type of Medium: Online Resource
    ISSN: 0165-5876
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 2224872-9
    detail.hit.zdb_id: 2009657-4
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  • 5
    Online Resource
    Online Resource
    Wiley ; 2011
    In:  Otolaryngology–Head and Neck Surgery Vol. 145, No. S2 ( 2011-08)
    In: Otolaryngology–Head and Neck Surgery, Wiley, Vol. 145, No. S2 ( 2011-08)
    Abstract: 1) Present outcomes of surgically treated infantile hemangioma, and describe changes in surgical management with the advent of changes in medical therapy. 2) Highlight the role of imaging in surgical planning. 3) Identify risk factors for surgical complications. Method Retrospective chart review of patients in a multidisciplinary clinic diagnosed with infantile hemangioma involving soft tissue and skin between 2008 and 2010. Data relating to demographics, indications for surgery, histopathology analysis, postoperative care, and complications were collected. Results Of 1050 subjects, 109 patients (10%) underwent surgical intervention, and 78% of the lesions were in the head and neck. Ulceration, bleeding, and deformity were the major surgical indications. Seven patients underwent staged excision. Magnetic resonance imaging was utilized in diagnostic workup and preoperative planning in 15 cases. Adjunctive medical therapy was safely used in 26% of the surgical cohort. Head and neck lesions were more likely to receive adjunctive therapy ( P =. 007) and had a higher complication rate. Overall complication rate was lower (6%) compared with our 2005‐2007 surgery cohort (1012 patients) with a complication rate of 17%. Conclusion Surgery continues to be a viable form of therapy for complicated infantile hemangiomas. Introduction of propanolol and vincrinstine for challenging lesions did not change the surgery rate but may partly explain the lower complication rate secondary to preoperative reduction of surgical bulk.
    Type of Medium: Online Resource
    ISSN: 0194-5998 , 1097-6817
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2008453-5
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  • 6
    In: The Laryngoscope, Wiley, Vol. 131, No. 2 ( 2021-02), p. 410-416
    Abstract: Cell culture models are valuable tools for investigation of the molecular pathogenesis of diseases including otitis media (OM). Previous study indicates that age‐, sex‐, and race‐associated differences in molecular signaling may impact disease pathophysiology. Currently, a singular immortalized middle ear epithelial (MEE) cell line exists, HMEEC‐1, derived from an adult without known middle ear disease. In this study, HMEEC‐1 and primary MEE cultures from pediatric patients with and without OM were stimulated with inflammatory cytokines or OM‐pathogenic bacterial lysates to examine differences in the response of molecules associated with OM pathogenesis. Study Design Case–control series. Methods MEE cultures were established from patients aged 〈 6 years: two with recurrent OM (ROM), two with OM with effusion (OME), and one patient without OM who was undergoing cochlear implant surgery control undergoing cochlear implantation (Peds CI). Primary MEE cultures and HMEEC‐1 cells were stimulated with tumor necrosis factor‐α, interleukin (IL)‐1β, or nontypeable Haemophilus influenzae lysate. TNFA, IL1B, IL6, IL8, IL10 , and MUC5B were assayed via quantitative polymerase chain reaction. IL‐8 was assayed by enzyme‐linked immunosorbent assay. Results Gene/protein target expressions were frequently higher in pediatric OM lines than in HMEEC‐1 and Peds CI. HMEEC‐1 cells were frequently less responsive to stimuli than all pediatric lines. OME lines were often more responsive than ROM lines. Conclusions OM may be associated with specific molecular phenotypes that are retained in primary cell culture. Adult‐derived HMEEC‐1 cells differ significantly in baseline expression and response of OM‐associated molecules relative to pediatric MEE cells. Work is underway to immortalize pediatric OM MEE cultures as improved tools for the OM research community. Level of Evidence 4 Laryngoscope , 131:410–416, 2021
    Type of Medium: Online Resource
    ISSN: 0023-852X , 1531-4995
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2026089-1
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  • 7
    In: The Laryngoscope, Wiley, Vol. 127, No. 10 ( 2017-10), p. 2413-2417
    Abstract: Laryngomalacia is a common cause of newborn stridor. Laryngopharyngeal reflux (LPR) has been associated with laryngomalacia. Although pepsin, a component of LPR, has been associated with inflammatory diseases of the aerodigestive tract, its presence in the airways of laryngomalacia patients is unknown. Study Design Prospective case‐control study comparing patients under age 3 years with laryngomalacia to children without laryngomalacia. Methods Children less than 3 years old undergoing supraglottoplasty for laryngomalacia or surgery unrelated to the airway, without a history of laryngomalacia, reflux, or respiratory disease, were offered enrollment. Supraglottic lavage samples (3 mL) were obtained from all subjects. Two‐millimeter arytenoid biopsies were collected from laryngomalacia patients. Pepsin Western blot and enzyme‐linked immunosorbent assay were performed. Results Ten laryngomalacia and five control subjects were enrolled. Pepsin was detected in lavages of laryngomalacia patients (8/10) but absent in controls (0/5; P = .007). Pepsin was observed more frequently in lavages (8/10) than biopsies (4/10; P = .046) of laryngomalacia subjects. Higher median pepsin concentration was observed in laryngomalacia than control lavages ( P = .025). Conclusions Pepsin in supraglottic specimens demonstrated an association with laryngomalacia, supporting a role for refluxed pepsin in laryngomalacia. These data corroborate previous work implicating pepsin in inflammatory diseases of the upper airways. Further studies are warranted to investigate the contribution of pepsin to the pathophysiology of laryngomalacia. Level of Evidence 3b. Laryngoscope , 127:2413–2417, 2017
    Type of Medium: Online Resource
    ISSN: 0023-852X , 1531-4995
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2026089-1
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  • 8
    In: Laryngoscope Investigative Otolaryngology, Wiley
    Abstract: Otitis media (OM) is among the most frequently diagnosed pediatric diseases in the US. Despite the significant public health burden of OM and the contribution research in culture models has made to understanding its pathobiology, a singular immortalized human middle ear epithelial (MEE) cell line exists (HMEEC‐1, adult‐derived). We previously developed MEE cultures from pediatric patients with non‐inflamed MEE (PCI), recurrent OM (ROM), or OM with effusion (OME) and demonstrated differences in their baseline inflammatory cytokine expression and response to stimulation with an OM‐relevant pathogen lysate and cytokines. Herein, we sought to immortalize these cultures and assess retention of their phenotypes. Methods MEE cultures were immortalized via lentivirus encoding temperature‐sensitive SV40 T antigen. Immortalized MEE lines and HMEEC‐1 grown in monolayer were stimulated with non‐typeable Haemophilus influenzae (NTHi) lysate. Gene expression ( TNFA , IL1B , IL6 , IL8 , MUC5AC , and MUC5B ) was assessed by qPCR. Results Similar to parental cultures, baseline cytokine expressions were higher in pediatric OM lines than in HMEEC‐1 and PCI, and HMEEC‐1 cells were less responsive to stimulation than pediatric lines. Conclusion Immortalized MEE lines retained the inflammatory expression and responsiveness of their tissues of origin and differences between non‐OM versus OM and pediatric versus adult cultures, supporting their value as novel in vitro culture models for OM.
    Type of Medium: Online Resource
    ISSN: 2378-8038 , 2378-8038
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2851702-7
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  • 9
    In: JAMA Otolaryngology–Head & Neck Surgery, American Medical Association (AMA), Vol. 143, No. 8 ( 2017-08-01), p. 810-
    Type of Medium: Online Resource
    ISSN: 2168-6181
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2017
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  • 10
    Online Resource
    Online Resource
    SAGE Publications ; 2016
    In:  Annals of Otology, Rhinology & Laryngology Vol. 125, No. 4 ( 2016-04), p. 273-276
    In: Annals of Otology, Rhinology & Laryngology, SAGE Publications, Vol. 125, No. 4 ( 2016-04), p. 273-276
    Abstract: Children with V3 cutaneous infantile hemangiomas (IH) and PHACE syndrome have a high incidence for airway hemangioma, 29% and 52%, respectively. Therefore, a clinical evaluation for these high-risk children is essential. We report our experience with in-office lower airway evaluation (OLAE) in these high-risk children. Results: Since 2003, 5 children with IH of the V3 cutaneous distribution and 3 children with PHACE syndrome underwent OLAE. Average age of presentation was 2.75 months. Two children had stridor at initial evaluation, and 1 child had subglottic hemangioma. This child was evaluated serially with OLAE to monitor disease progression and treatment response. A total of 10 upper tracheoscopies were performed on the 8 patients without respiratory complications. Conclusion: An airway evaluation is essential to evaluate and manage this high-risk population. Typically, operative endoscopy requires general anesthesia. However, in these high-risk children, we have performed OLAE without sedation to evaluate the trachea. High-speed recording and playback is essential in this method. Our series demonstrates that awake OLAE is possible and may be a safe technique to evaluate and monitor disease progression in these high-risk patients. These patients avoided general anesthesia and delay in diagnosis and did not incur any complications during or after OLAE.
    Type of Medium: Online Resource
    ISSN: 0003-4894 , 1943-572X
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2033055-8
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