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MPZL2-related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty-five previously reported patients had biallelic truncating variants in MPZL2, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed MPZL2-related hearing loss. A rare missense likely pathogenic variant [NM_005797.4(MPZL2):c.280C>T,p.(Arg94Trp)] located in exon 3 was confirmed to be in trans with a recurrent pathogenic truncating variant that segregated with hearing loss in three of the patients from two unrelated families. This is the first recurrent likely pathogenic missense variant identified in MPZL2. Apparently milder or later-onset hearing loss associated with rare missense variants in MPZL2 indicates that some missense variants in this gene may cause a milder phenotype than that resulting from homozygous or compound heterozygous truncating variants. This study, along with the identification of truncating loss of function and missense MPZL2 variants in several diverse populations, suggests that MPZL2-related hearing loss may be more common than previously appreciated and demonstrates the need for MPZL2 inclusion in hearing loss testing panels., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Objective: To provide recommendations for a comprehensive management approach for infants and children presenting with symptoms or signs of aspiration., Methods: Three rounds of surveys were sent to authors from 23 institutions worldwide. The threshold for the critical level of agreement among respondents was set at 80 %. To develop the definition of "intractable aspiration," each author was first asked to define the condition. Second, each author was asked to complete a 5-point Likert scale to specify the level of agreement with the definition derived in the first step., Results: Recommendations by the authors regarding the clinical presentation, diagnostic considerations, and medical and surgical management options for aspiration in children., Conclusion: Approach to pediatric aspiration is best achieved by implementing a multidisciplinary approach with a comprehensive investigation strategy and different treatment options., Competing Interests: Declaration of competing interest None declared, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Aerodigestive disorders encompass various pathological conditions affecting the lungs, upper airway, and gastrointestinal tract in children. While advanced care has primarily occurred in specialty centers, many children first present to general pediatric gastroenterologists with aerodigestive symptoms necessitating awareness of these conditions. At the 2021 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the aerodigestive Special Interest Group held a full-day symposium entitled, Pediatric Aerodigestive Medicine: Advancing Collaborative Care of Children with Aerodigestive Disorders. The symposium aimed to underline the significance of a multidisciplinary approach to achieve better outcomes for these complex patients., Methods: The symposium brought together leading experts to highlight the growing aerodigestive field, promote new scientific and therapeutic strategies, share the structure and benefits of a multidisciplinary approach in diagnosing common and rare aerodigestive disorders, and foster multidisciplinary discussion of complex cases while highlighting the range of therapeutic and diagnostic options. In this article, we showcase the diagnostic and therapeutic approach to oropharyngeal dysphagia (OPD), one of the most common aerodigestive conditions, emphasizing the role of a collaborative model., Conclusions: The aerodigestive field has made significant progress and continues to grow due to a unique multidisciplinary, collaborative model of care for these conditions. Despite diagnostic and therapeutic challenges, the multidisciplinary approach has enabled and greatly improved efficient, high-quality, and evidence-based care for patients, including those with OPD., Competing Interests: Dr Friedlander is the Chief Medical Officer and Co-Founder of EvoEndo, Inc. He is an employee, stockholder, and on the board of directors of EvoEndo, Inc. He is co-inventor on several University of Colorado and EvoEndo, Inc patents and patent pendings related to virtual reality, endoscope design, endoscopic methods, endoscopic training methods, and its associated technologies. Dr Prager is a cofounder of EvoEndo, Inc. The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Lectins are important biological tools for binding glycans, but recombinant protein expression poses challenges for some lectin classes, limiting the pace of discovery and characterization. To discover and engineer lectins with new functions, workflows amenable to rapid expression and subsequent characterization are needed. Here, we present bacterial cell-free expression as a means for efficient, small-scale expression of multivalent, disulfide bond-rich, rhamnose-binding lectins. Furthermore, we demonstrate that the cell-free expressed lectins can be directly coupled with bio-layer interferometry analysis, either in solution or immobilized on the sensor, to measure interaction with carbohydrate ligands without purification. This workflow enables the determination of lectin substrate specificity and estimation of binding affinity. Overall, we believe that this method will enable high-throughput expression, screening, and characterization of new and engineered multivalent lectins for applications in synthetic glycobiology., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Ketorolac-refractory pain behavior following bilateral myringotomy and pressure equalization tube placement (BMT) is associated with the absence of middle ear fluid. Intraoperative fentanyl/ketorolac affords more reliable pain control than ketorolac alone. We hypothesized that middle ear condition would correlate with postoperative pain despite such combination therapy. We further sought to demonstrate seasonal variation in ear condition and its influence on pain., Methods: We conducted a single-institution retrospective cohort study of healthy children (9 months-7 years), who underwent BMT by a single surgeon from 2015 to 2020. Anesthetic care included sevoflurane/nitrous oxide/oxygen/air by mask and intramuscular fentanyl/ketorolac. Left/right middle ear fluid status was recorded at the time of BMT, and ear condition (primary exposure) was dichotomized as bilateral infected (mucoid or purulent) or normal/unilateral infected. The primary outcome was maximum postanesthesia care unit Face, Legs, Activity, Cry, and Consolability (FLACC) score: 4-10 (moderate-to-severe pain) versus 0-3 (no-to-low pain). Rescue oxycodone, acetaminophen administration, and emergence agitation were secondary outcomes. Statistical analysis incorporated generalized linear mixed-effect models (GLMMs) with random intercepts to account for clustering by anesthesia provider. A year-over-year monthly time-series analysis was conducted using an autoregressive integrated moving average (ARIMA) regression model., Results: Excluding recurrent cases, 1149 unique evaluable subjects remained. Bilateral infection prevalence was 39.8% (457/1149; 95% confidence interval [CI], 37.0-42.6). Probability of moderate-to-severe pain behavior was 23.5% (270/1149; 95% CI, 21.1-26.0) overall. Compared to patients with bilateral infected middle ears, those with normal/unilateral infected ears were more likely to have a FLACC score ≥4 (26.7% [185/692] versus 18.6% [85/457]; odds ratio [95% CI], 1.7 [1.2-2.3]; P = .002). Variability in pain outcome explained by the multivariable GLMM was 4.7%. Fentanyl dose response was evidenced by oxycodone administration differences ( P ≤ 0.002). Moderate-to-severe pain and emergence agitation were more likely with reduced fentanyl dosing. Bilateral infection prevalence exhibited seasonality, peaking in March and nadiring in July. However, pain outcomes did not vary by season., Conclusions: Normal/unilateral infected ears at time of pediatric BMT are associated with higher incidence of moderate-to-severe postoperative pain following intraoperative fentanyl/ketorolac administration, but the predictive value of ear condition on pain is limited. Infections were less common in the summer., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Enterotoxigenic Escherichia coli (ETEC) is the primary etiologic agent of traveler's diarrhea and a major cause of diarrheal disease and death worldwide, especially in infants and young children. Despite significant efforts over the past several decades, an affordable vaccine that appreciably decreases mortality and morbidity associated with ETEC infection among children under the age of 5 years remains an unmet aspirational goal. Here, we describe robust, cost-effective biosynthetic routes that leverage glycoengineered strains of non-pathogenic E. coli or their cell-free extracts for producing conjugate vaccine candidates against two of the most prevalent O serogroups of ETEC, O148 and O78. Specifically, we demonstrate site-specific installation of O-antigen polysaccharides (O-PS) corresponding to these serogroups onto licensed carrier proteins using the oligosaccharyltransferase PglB from Campylobacter jejuni. The resulting conjugates stimulate strong O-PS-specific humoral responses in mice and elicit IgG antibodies that possess bactericidal activity against the cognate pathogens. We also show that one of the prototype conjugates decorated with serogroup O148 O-PS reduces ETEC colonization in mice, providing evidence of vaccine-induced mucosal protection. We anticipate that our bacterial cell-based and cell-free platforms will enable creation of multivalent formulations with the potential for broad ETEC serogroup protection and increased access through low-cost biomanufacturing., Competing Interests: MD and MJ have financial interests in Gauntlet, Inc. and Resilience, Inc. MD has financial interests in Glycobia, Inc, MacImmune, Inc, UbiquiTx, Inc, and Versatope Therapeutics, Inc. MD’s and MJ’s interests are reviewed and managed by Cornell University and Northwestern University, respectively, in accordance with their conflict-of-interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Williams, Warfel, Desai, Li, Lee, Wong, Nguyen, Qin, Sobol, Jewett, Chang and DeLisa.)

Cell-free protein synthesis systems that can be lyophilized for long-term, non-refrigerated storage and transportation have the potential to enable decentralized biomanufacturing. However, increased thermostability and decreased reaction cost are necessary for further technology adoption. Here, we identify maltodextrin as an additive to cell-free reactions that can act as both a lyoprotectant to increase thermostability and a low-cost energy substrate. As a model, we apply optimized formulations to produce conjugate vaccines for ∼$0.50 per dose after storage at room temperature (∼22 °C) or 37 °C for up to 4 weeks, and ∼$1.00 per dose after storage at 50 °C for up to 4 weeks, with costs based on raw materials purchased at the laboratory scale. We show that these conjugate vaccines generate bactericidal antibodies against enterotoxigenic Escherichia coli (ETEC) O78 O-polysaccharide, a pathogen responsible for diarrheal disease, in immunized mice. We anticipate that our low-cost, thermostable cell-free glycoprotein synthesis system will enable new models of medicine biosynthesis and distribution that bypass cold-chain requirements.

Objectives: Tracheocutaneous fistula (TCF) is a common occurrence after pediatric tracheostomy decannulation. However, the persistence of TCF after staged reconstruction of the pediatric airway is not well-described. The primary objective was to determine the rate of persistent TCF after successful decannulation in children with staged open airway reconstruction., Methods: A case series with chart review of children who underwent decannulation after double-stage laryngotracheal reconstruction between 2017 and 2019., Results: A total of 26 children were included. The most common open airway procedure was anterior and posterior costal cartilage grafting (84.6%, 22/26). Median age at decannulation was 3.4 years (IQR: 2.8-4.3) and occurred 7.0 months (IQR: 4.3-10.4) after airway reconstruction. TCF persisted in 84.6% (22/26) of children while 15.4% (4/26) of stomas closed spontaneously. All closures were identified by the one-month follow-up visit. There was no difference in age at tracheostomy ( P  = .86), age at decannulation ( P  = .97), duration of tracheostomy ( P  = .43), or gestational age ( P  = .23) between stomas that persisted or closed. Median diameter of stent used at reconstruction was larger in TCFs that persisted (7.0 mm vs 6.5 mm, P  = .03). Tracheostomy tube diameter ( P  = .02) and stent size ( P  < .01) correlated with persistence of TCF on multivariable logistic regression analysis. There were 16 surgical closure procedures, which occurred at a median of 14.4 months (IQR: 11.4-15.4) after decannulation. Techniques included 56.3% (9/16) by primary closure, 18.8% (3/16) by secondary intention and 25% (4/16) by cartilage tracheoplasty. The overall success of closure was 93.8% (15/16) at latest follow-up., Conclusions: Persistent TCF occurs in 85% of children who are successfully decannulated after staged open airway reconstruction. Spontaneous closure could be identified by 1 month after decannulation and was more likely when smaller stents and tracheostomy tubes were utilized. Surgeons should counsel families on the frequency of TCF and the potential for additional procedures needed for closure.

Objectives/hypothesis: Create a competency-based assessment tool for pediatric esophagoscopy with foreign body removal., Study Design: Blinded modified Delphi consensus process., Setting: Tertiary care center., Methods: A list of 25 potential items was sent via the Research Electronic Data Capture database to 66 expert surgeons who perform pediatric esophagoscopy. In the first round, items were rated as "keep" or "remove" and comments were incorporated. In the second round, experts rated the importance of each item on a seven-point Likert scale. Consensus was determined with a goal of 7 to 25 final items., Results: The response rate was 38/64 (59.4%) in the first round and returned questionnaires were 100% complete. Experts wanted to "keep" all items and 172 comments were incorporated. Twenty-four task-specific and 7 previously-validated global rating items were distributed in the second round, and the response rate was 53/64 (82.8%) with questionnaires returned 97.5% complete. Of the task-specific items, 9 reached consensus, 7 were near consensus, and 8 did not achieve consensus. For global rating items that were previously validated, 6 reached consensus and 1 was near consensus., Conclusions: It is possible to reach consensus about the important steps involved in rigid esophagoscopy with foreign body removal using a modified Delphi consensus technique. These items can now be considered when evaluating trainees during this procedure. This tool may allow trainees to focus on important steps of the procedure and help training programs standardize how trainees are evaluated., Level of Evidence: 5. Laryngoscope, 131:1168-1174, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objective: The first pediatric tracheostomy tube change often occurs within 7 days after placement; however, the optimal timing is not known. The primary objective was to determine the rate of adverse events of an early tube change. Secondary objectives compared rates of significant peristomal wounds, sedation requirements, and expedited intensive care discharges., Study Design: Prospective randomized controlled trial., Setting: Tertiary children's hospital between October 2018 and April 2020., Methods: A randomized controlled trial enrolled children under 24 months to early (day 4) or late (day 7) first tracheostomy tube changes., Results: Sixteen children were enrolled with 10 randomized to an early change. Median age was 5.9 months (interquartile range, 5.4-8.3), and 86.7% required tracheostomy for respiratory failure. All tracheostomy tube changes were performed without adverse events. There were no accidental decannulations. Significant wounds developed in 10% of children with early tracheostomy tube changes and 83.3% of children with late tracheostomy tube changes (odds ratio [OR], 45.0; 95% CI, 2.3-885.6; P = .01). This significant reduction in wound complications justified concluding trial enrollment. Hours of dexmedetomidine sedation ( P = .11) and boluses of midazolam during the first 7 days ( P = .08) were no different between groups. After the first change, 90% of the early group were discharged from intensive care within 5 weeks compared to 33.3% of patients in the late group (OR, 18.0; 95% CI, 1.2-260.9; P = .03)., Conclusion: The first tracheostomy tube change in children can occur without adverse events on day 4, resulting in fewer significant peristomal wounds and earlier intensive care discharge.

Although the majority of attention to the health care impact of COVID-19 has focused on adult first responders and critical care providers, the pandemic has had a profound effect on the entire health care industry, including the pediatric otolaryngology community. This article highlights the unique ramifications of COVID-19 on pediatric otolaryngology, with a focus on the immediate and potential long-term shifts in practice. Specifically, the article is divided into 3 sections (care for the patient, care for the practitioner, and care for the practice) and details the unique effects of the pandemic on the pediatric otolaryngology specialty., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: An airway assessment often occurs prior to tracheocutaneous fistula (TCF) closure in children. Bronchoscopy (MLB) with or without fistula-occluded polysomnography (PSG) helps determine candidacy and localize potential obstruction. To date, little has been published on MLB or PSG findings in children before surgically closing a TCF., Methods: A case series with chart review of children between 2017 and 2020 who underwent repair of a TCF after tracheostomy decannulation., Results: Thirty-six children were included for review. Mean age was 5.9 years (95% CI: 4.5-7.3), 58.3% were male, and 50% had chronic lung disease. Surgery occurred 13.3 months (95% CI: 11.9-14.8) after decannulation, with 80.6% by primary closure and 19.4% by secondary intention. There was one unsuccessful closure and two patients (5.6%) presented with a postoperative complication. An MLB was performed in 97.2% of children, where 22.9% identified supraglottic pathology, 11.4% had grade 2 subglottic stenosis, and 11.4% had difficult exposure of the larynx. Further, one child had a non-obstructing subglottic cyst, one had a supraglottoplasty for redundant arytenoid mucosa, and two children had suprastomal granulomas requiring removal. A PSG was obtained in 36.1%, with a mean Apnea-Hypopnea Index of 2.4 events/hour (95% CI: 0.9-3.9), nadir Oxygen saturation of 90.5% (95% CI: 87.9-93.0), and peak end-tidal CO 2 of 46.1 mmHg (95% CI: 43.7-48.5)., Conclusion: The selection of candidates for pediatric TCF closure requires careful evaluation of the airway. Surgeons should be familiar with the potential findings on MLB and PSG prior to closure., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives/hypothesis: Create a competency-based assessment tool for pediatric tracheotomy., Study Design: Blinded, modified, Delphi consensus process., Methods: Using the REDCap database, a list of 31 potential items was circulated to 65 expert surgeons who perform pediatric tracheotomy. In the first round, items were rated as "keep" or "remove," and comments were incorporated. In the second round, experts were asked to rate the importance of each item on a seven-point Likert scale. Consensus criteria were determined a priori with a goal of 7 to 25 final items., Results: The first round achieved a response rate of 39/65 (60.0%), and returned questionnaires were 99.5% complete. All items were rated as "keep," and 137 comments were incorporated. In the second round, 30 task-specific and seven previously validated global rating items were distributed, and the response rate was 44/65 (67.7%), with returned questionnaires being 99.3% complete. Of the Task-Specific Items, 13 reached consensus, 10 were near consensus, and 7 did not achieve consensus. For the 7 previously validated global rating items, 5 reached consensus and two were near consensus., Conclusions: It is feasible to reach consensus on the important steps involved in pediatric tracheotomy using a modified Delphi consensus process. These items can now be considered to create a competency-based assessment tool for pediatric tracheotomy. Such a tool will hopefully allow trainees to focus on the important aspects of this procedure and help teaching programs standardize how they evaluate trainees during this procedure., Level of Evidence: 5 Laryngoscope, 130:2700-2707, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Many infants in the neonatal intensive care unit (NICU) require prolonged periods of respiratory support. Microlaryngoscopy and bronchoscopy (MLB) is performed to evaluate for airway pathology and facilitate decision-making regarding further airway interventions or tracheostomy. The objectives of this study are to describe the operative findings of MLB performed on infants in the NICU and determine which pre-operative characteristics or operative findings are predictive of the need for tracheostomy., Methods: The medical records of preterm inpatients in the NICU at a single tertiary care hospital who underwent MLB between January 1, 2013 and January 7, 2016 were reviewed. Baseline and demographic characteristics and intra-operative findings were compared between patients who underwent tracheostomy and those who were successfully weaned from respiratory support., Results: Seventy-three preterm patients underwent MLB for respiratory failure, of whom 41 (56.2%) underwent tracheostomy. Patients who underwent tracheostomy had lower mean gestational age (27.4 vs. 30.5 weeks), higher prevalence of bronchopulmonary dysplasia (73.2% vs. 37.5%), lower mean birth weight (1.1 kg vs. 1.6 kg), and a greater number of extubation events (5.2 vs. 3.0) than those who weaned from respiratory support. Abnormal MLB findings were common in both groups, though no single MLB finding differed significantly between groups., Conclusions: Preterm infants in the NICU with gestational age ≤30 weeks, birth weight <1.5 kg, severe pulmonary disease, and who have failed more than 3 extubation attempts are more likely to require tracheostomy., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Determine preoperative comorbidities and intraoperative parameters associated with adverse postoperative outcomes., Methods: Retrospective case series at a single tertiary care children's hospital from 2010 through 2017., Results: Twenty-six patients with median age of 6 months and median weight of 7.1 kg underwent slide tracheoplasty. Median time to extubation, length of intensive care unit admission, and length of hospitalization were 7, 27, and 30 days, respectively. Twenty-two (85%) required no additional intervention. Overall success was 87%. One (4%) patient required open revision, and 3 (11%) required tracheostomy. Concomitant cardiac surgery was associated with postoperative tracheostomy (p = 0.04). Age and weight at surgery were inversely correlated with length of intubation (p = 0.03) and length of hospital stay (p = 0.001, p = 0.002) respectively. Hospital stay was 2.2 times longer if preoperative mechanical ventilation was required (p = 0.01) and 39% longer for every 1 mm decrease in airway diameter at the narrowest portion of the stenosis (p = 0.005). There were no deaths related to persistent tracheal stenosis with a median follow-up of 24 months., Conclusion: Slide tracheoplasty is safe and effective. Concomitant cardiac surgery was associated with postoperative tracheostomy. Lower age and weight at surgery were correlated with longer length of intubation and hospital stay. Preoperative mechanical ventilation and smaller airway diameter were associated with longer hospital stay. This information may be helpful in counseling families and planning future prospective studies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Recurrent Respiratory Papillomatosis (RRP) is a rare disease characterized by the growth of papillomas in the airway and especially the larynx. The clinical course is highly variable among individuals and there is poor understanding of the factors that drive an aggressive vs an indolent course., Methods: A convenience cohort of 339 affected subjects with papillomas positive for only HPV6 or HPV11 and clinical course data available for 1 year or more, from a large multicenter international study were included. Exploratory data analysis was conducted followed by inferential analyses with frequentist and Bayesian statistics., Results: We examined 339 subjects: 82% were diagnosed prior to the age of 18 years, 65% were infected with HPV6, and 69% had an aggressive clinical course. When comparing age at diagnosis with clinical course, the probability of aggressiveness is high for children under five years of age then drops rapidly. For patients diagnosed after the age of 10 years, an indolent course is more common. After accounting for confounding between HPV11 and young age, HPV type was minimally associated with aggressiveness. Fast and Frugal Trees (FFTs) were utilized to determine which algorithms yield the highest accuracy to classify patients as having an indolent or aggressive clinical course and consistently created a branch for diagnostic age at ~5 years old. There was no reliable strong association between clinical course and socioeconomic or parental factors., Conclusion: In the largest cohort of its type, we have identified a critical age at diagnosis which demarcates a more aggressive from less aggressive clinical course., Competing Interests: The authors have declared that no competing interests exist.

Laryngotracheoesophageal cleft (LTEC) is a rare anatomic cause of aspiration in the newborn and infant. The clinical presentation of infants with LTEC is variable and will usually vary with the degree of anatomic communication between the airway and esophagus. The diagnosis of LTEC is often challenging, particularly in cases where the presentation and pathology are more subtle. Management of LTEC depends upon the clinical presentation, degree of aspiration, and anatomic depth of the cleft. The goal of this review is to present the clinician with a practical approach to diagnosis and management of this rare but challenging congenital airway anomaly., (Copyright © 2018 Mosby, Inc. All rights reserved.)

Importance: There is controversy over whether a critical period in the development of olfaction exists, as there is in hearing and vision, whereby early stimulation of the olfactory nerve is necessary for normal olfactory performance later in life. Children who undergo tracheotomy early in life are deprived of airflow through the nasal cavity during a critical period of development. Persistent olfactory dysfunction in this patient group after decannulation would provide evidence that postnatal stimulation of the olfactory nerve is critical to normal development., Objective: To determine whether children who undergo early tracheotomy have persistent olfactory dysfunction following decannulation and to validate a prior study showing olfactory deficits in cannulated patients., Design, Setting, and Participants: This was a cross-sectional study of smell function in pediatric patients with either long-term tracheostomy (cannulated), decannulated patients after long-term tracheostomy, and healthy age- and sex-matched controls, conducted in a tertiary care academic referral center, using data that were collected between 2013 and 2015. All patients were without coexisting nasal abnormalities or developmental delay that would prevent completion of testing., Interventions: Administration of a validated pediatric smell test to all 3 patient groups., Main Outcomes and Measures: Mean percentage correct on a validated pediatric smell test., Results: In 18 patients ages 6 to 18 years, there was a statistically significant difference (P = .007) in mean percentage of correct responses on the smell test between cannulated (67%; 95% CI, 54%-79%, N = 6), decannulated (61%; 95% CI, 42%-80%, N = 6), and age-matched controls (94%; 95% CI, 90%-99%, N = 6). Analysis between groups showed statistically significant differences between both control and cannulated patients (P = .002) and between control and decannulated patients (P = .006). There was no significant difference between scores in the cannulated and decannulated groups (P = .64)., Conclusions and Relevance: This pilot study suggests that olfactory deficits from early chronic tracheostomy persist following decannulation and provides early data suggestive of a critical period in the postnatal development and neuroplasticity of olfaction.

Objective: To determine the need for postoperative admission following airway foreign body retrieval by examining the preoperative presentation, operative details, and postoperative recovery., Introduction: Inpatient admission following foreign body removal is common, however little evidence supports this practice. In the era of cost containment and prudent utilization of hospital resources, careful examination of the postoperative course following airway foreign body removal is required., Methods: A retrospective review of cases over a four year period from a pediatric tertiary care pediatric hospital was performed. All children presenting with concerns for airway foreign bodies were included. Children without identification of an airway foreign body during bronchoscopy were excluded. Microlaryngoscopy and bronchoscopy with airway foreign body extraction was performed. Details concerning demographics, operative findings, and pre and postoperative course including pulse oximetry were collected. All respiratory events, intubations, and persistent oxygen requirements were investigated., Results: Thirty five children underwent successful airway foreign body removal. The mean age was 3.2±2.6 years with a preponderance of males (68.6%). The retrieved items included: nuts (31.4%), popcorn (14.3%), seeds (8.6%), and inorganic materials (34.3%). Mean operative time was 29.7±25.6min. The mean length of stay following surgery was 1.3±1.9 days. Most patients (31/35) (88.6%) were extubated prior to transfer to recovery. 30/35 (85.7%) patients required no supplemental oxygen without desaturations following post anesthesia care unit (PACU) recovery. One patient developed laryngospasm requiring reintubation within 15min of surgery. Two patients were intubated prior to transfer for respiratory distress and remained intubated following surgery. Two patients breathing spontaneously prior to surgery were left intubated following surgery secondary to prolonged pneumonia treatment or multifocal foreign bodies with airway edema. All patients subsequently extubated without complication. In total, 30/31 (96.7%) of patients extubated in the operating room returned to room air oxygenation within 2h of surgery., Conclusions: PACU observation and discharge is feasible in select children following airway foreign body extraction. Patients carefully monitored in the recovery unit without oxygen requirement are candidates for discharge. Inpatient monitoring is advised in 'children with preoperative respiratory distress or a complicated operative course., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Importance: The incidence and timing patterns of decannulation failure in children are unknown. There is substantial variability in the duration of inpatient hospitalization for patients undergoing decannulation, which represents an opportunity for improved resource use., Objective: To determine the incidence and timing patterns of elective decannulation failure in the pediatric population and to determine an appropriate interval of inpatient observation following decannulation that optimizes both patient safety and resource use., Design, Setting, and Participants: Retrospective review of medical records of consecutive patients 18 years or younger hospitalized for elective, inpatient decannulation between January 1, 2012, and October 31, 2013, at a quaternary care pediatric hospital., Main Outcomes and Measures: Duration of decannulation hospitalization, failure of elective decannulation (decision not to decannulate or reinsertion of tracheostomy tube after decannulation), time interval from decannulation to failure., Results: Forty-six patients completed 50 elective decannulation hospitalizations during the study period. The median duration of hospitalization for decannulation was 3.0 days. The hospitalization-specific failure rate was 16% (8 of 50), and the overall failure rate was 9% (4 of 46). Four patients were not able to tolerate capping of the tracheostomy tube and were discharged with their original tracheostomy tubes in place. Three of these patients were decannulated at a later hospitalization. In 4 patients, decannulation failed and they had to have their tracheostomy tubes replaced prior to discharge. Patients who did not tolerate decannulation were younger (mean [SD] age, 45.7 [17.0] months) than patients whose decannulation was successful (68.2 [48.0] months). All patients with unsuccessful decannulation attempts were symptomatic during capping. The longest interval from decannulation to tracheostomy reinsertion was 11 hours., Conclusions and Relevance: Elective decannulation failure occurred in 9% of this population and may be more common in younger patients and those with a diagnosis of vocal fold paralysis. Patients who are symptomatic during predecannulation capping are at high risk for decannulation failure. Inpatient observation for a 24-hour asymptomatic interval after decannulation may be sufficient because late failures were not observed in this sample.

Objectives: Based on an interpretation of a recent Joint Commission protocol to sterilize instruments coming into contact with mucous membranes, there has been institutional interest in sterile packaging of cerumen curettes used for manual cerumen removal. To date, there are no studies that have assessed the risk of otitis externa (OE) following cerumen removal and the utility of sterile packaging is questionable. The objective of this study is to assess the incidence of OE following cerumen disimpaction prior to the implementation of sterile packaging at our institution., Methods: This was a retrospective chart review. Over a I-year period, 1457 episodes of manual cerumen removal took place in the otolaryngology clinic. Charts were assessed for signs or symptoms of OE within 2 weeks of the procedure through follow-up phone calls and clinic visits in the otolaryngology division., Results: There were no patients who followed up with symptoms or signs suggestive of OE in the 2-week postprocedure period., Conclusion: There is no evidence that OE is a complication of manual cerumen removal when performed by otolaryngologists using clean technique. Unnecessary sterilization of tools leads to increased cost and time for this common outpatient procedure performed by the otolaryngologist.

Memory is a hallmark of adaptive immunity, wherein lymphocytes mount a superior response to a previously encountered antigen. It has been speculated that epigenetic alterations in memory lymphocytes contribute to their functional distinction from their naive counterparts. However, the nature and extent of epigenetic alterations in memory compartments remain poorly characterized. Here we profile the DNA methylome and the transcriptome of B-lymphocyte subsets representing stages of the humoral immune response before and after antigen exposure in vivo from multiple humans. A significant percentage of activation-induced losses of DNA methylation mapped to transcription factor binding sites. An additional class of demethylated loci mapped to Alu elements across the genome and accompanied repression of DNA methyltransferase 3A. The activation-dependent DNA methylation changes were largely retained in the progeny of activated B cells, generating a similar epigenetic signature in downstream memory B cells and plasma cells with distinct transcriptional programs. These findings provide insights into the methylation dynamics of the genome during cellular differentiation in an immune response.

Objectives: We review and stage a series of congenital lymphatic malformations (LMs) that caused laryngeal obstruction according to a proposed staging system, review the treatment modalities utilized, and correlate the stage of disease with clinical outcomes and tracheotomy statuses., Methods: We present a detailed description of the clinical presentation, management approach, and clinical outcome and tracheotomy status of a series of patients with laryngeal obstruction by LMs. A 4-part staging system (stages I to IV) for congenital LMs obstructing the larynx, based upon our clinical experience, is proposed. The patients were retrospectively reviewed and staged according to the proposed system, and clinical management and outcomes were correlated with the stage of disease., Results: We identified 16 patients with laryngeal obstruction by LMs. Eighty-one percent (13 of 16) received sclerotherapy, and 50% (8 of 16) underwent operative excision or debridement. Forty percent (2 of 5) of stage I lesions, 75% (3 of 4) of stage II lesions, 100% (4 of 4) of stage III lesions, and 100% (3 of 3) of stage IV lesions were in patients who required tracheotomy. All patients who had stage I and II lesions and required tracheotomy have been decannulated, whereas only 2 of the 4 patients with stage III lesions and no patients with stage IV lesions have been successfully decannulated., Conclusions: Lymphatic malformations obstructing the larynx require a careful and often staged management approach. A proposed staging system helps to predict the need for tracheotomy and the likelihood of long-term tracheotomy dependence.

Objectives/hypothesis: To analyze the microbiological origins of deep neck space infections requiring surgical intervention in a pediatric population., Study Design: Retrospective cohort study., Methods: The study population (N = 136) included all pediatric patients surgically treated for deep neck space abscesses in a metropolitan tertiary care children's hospital over the course of 5 years (September 2004-August 2009). Demographic and clinical information was compared with microbiological isolate data., Results: Microbiological analysis of 118 bacterial isolates demonstrated 49 (42%) methicillin-resistant Staphylococcus aureus (MRSA), 35 (30%) methicillin-sensitive S. aureus, and 34 (28%) non-S. aureus (N-SA) isolates. The median age was 16 months (range, 1 month-13years). Patients <16 months of age were 10 times more likely to have an S. aureus (SA) infection versus N-SA (P <.0001). MRSA comprised the majority of all SA isolates (58%). Eighty percent of all SA abscesses were located in the lateral neck. African American pediatric patients accounted for 70% of all deep neck space infections, and 86% of all MRSA infections. Clindamycin resistance was noted in 8% (4/49) of all community-acquired MRSA isolates., Conclusions: Children younger than 16 months and/or with lateral neck abscesses are at a significantly increased risk of having an SA infection, the majority being MRSA.

Aberrant DNA methylation commonly occurs in cancer cells where it has been implicated in the epigenetic silencing of tumor suppressor genes. Additional roles for DNA methylation, such as transcriptional activation, have been predicted but have yet to be clearly demonstrated. The BCL6 oncogene is implicated in the pathogenesis of germinal center-derived B cell lymphomas. We demonstrate that the intragenic CpG islands within the first intron of the human BCL6 locus were hypermethylated in lymphoma cells that expressed high amounts of BCL6 messenger RNA (mRNA). Inhibition of DNA methyltransferases decreased BCL6 mRNA abundance, suggesting a role for these methylated CpGs in positively regulating BCL6 transcription. The enhancer-blocking transcription factor CTCF bound to this intronic region in a methylation-sensitive manner. Depletion of CTCF by short hairpin RNA in neoplastic plasma cells that do not express BCL6 resulted in up-regulation of BCL6 transcription. These data indicate that BCL6 expression is maintained during lymphomagenesis in part through DNA methylation that prevents CTCF-mediated silencing.

Objective: Little information is available concerning the treatment of pediatric head and neck infections caused by methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to antimicrobial agents such as cephalosporins. The objective of this investigation is to describe clinical characteristics of pediatric MRSA head and neck infections in the United States and how they are treated., Design: National survey., Setting: United States., Methods: Practicing members of the American Academy of Otolaryngology-Head and Neck Surgery were surveyed regarding patients aged < 18 years with MRSA head and neck infections during 2006., Main Outcome Measures: Clinical characteristics and treatment of pediatric MRSA infections., Results: Of 701 surveys sent, 201 were completed (adjusted response rate 30%). Otolaryngologists responding to the survey reported treating a total of 1123 pediatric MRSA head and neck infections in 2006. Forty-seven percent reported treating pediatric patients with MRSA infections in the otologic region, 39% in the oropharyngeal/neck region, and 17% in the sinonasal region. The antimicrobials most frequently used to treat these infections were clindamycin, trimethoprim-sulfamethoxazole, and vancomycin. Cephalosporins and fluoroquinolones were also commonly prescribed., Conclusions: Otolaryngologists in the United States reported treating a broad range of MRSA head and neck infections in pediatric patients. Although most were treated with appropriate antimicrobials, some were treated with agents not active against MRSA.

We conducted a prospective analysis to independently observe the initial opinion of: (1) consulting pediatric residents (postgraduate year 2 [PGY-2]), (2) corresponding consulting attending physicians (general pediatric or pediatric emergency medicine), and (3) consulting otolaryngology PGY-2 residents when assessing patients for "noisy breathing." Each was asked to define the type of noisy breathing present and to formulate a diagnosis based on a limited set of choices. The final diagnosis was determined by a single attending pediatric otolaryngologist (S.E.S.) at the completion of the diagnostic workup. The accuracy for characterization of breath sounds for the pediatric residents, attending pediatricians, and otolaryngology residents were 26.1%, 23.5%, and 98.6%, respectively. The positive predictive values for the determination of diagnosis were 71.6%, 69.4%, and 76.6%, respectively. These findings indicate that pediatric residents and attending pediatricians may be deficient in their ability to characterize the breath sounds commonly seen in patients with noisy breathing. Further education of pediatricians may lead to a more accurate diagnostic evaluation of a child with noisy breathing.

Objectives: To evaluate the epidemiologic manifestations of pediatric Staphylococcus aureus head and neck infections nationwide and to identify possible trends in the antibiotic drug susceptibility of S aureus during a 6-year period., Design: Retrospective review of microbiologic data from a peer-reviewed national database., Setting: More than 300 hospitals nationwide., Patients: All pediatric patients with head and neck infections involving S aureus., Main Outcome Measures: Anatomic sites were divided into oropharynx/neck, sinonasal, and otologic infection categories. Demographic and antimicrobial drug susceptibility patterns were reviewed., Results: A total of 21,009 pediatric head and neck S aureus infections that occurred between January 2001 and December 31, 2006 were gathered from the database. Predominance was observed in the oropharyngeal/neck category (60.3%). For all sites, the mean patient age was 6.7 years (range, 0-18 years), with a 51.7% male predominance. There was a high occurrence in the North East Central region of the United States. Overall, methicillin-resistant S aureus was seen in 21.6% of all patient isolates (n = 4534), with rates of 11.8%, 12.5%, 18.1%, 27.2%, 25.5%, and 28.1% for 2001 through 2006, respectively. This represents a 16.3% increase in methicillin-resistant S aureus during these 6 years for all pediatric head and neck S aureus infections., Conclusions: There is an alarming nationwide increase in the prevalence of pediatric methicillin-resistant S aureus head and neck infections. Disparities in the treatment of various head and neck infections nationwide may contribute to the regional differences in the prevalence of such infections. Judicious use of antibiotic agents and increased effectiveness in diagnosis and treatment are warranted to reduce further antimicrobial drug resistance in pediatric head and neck infections.

Objective: To evaluate the postoperative results of patients treated with and without the use of stents at the time of initial surgical treatment of choanal atresia (CA). Surgical treatment of CA in the neonatal period is complicated by postoperative stenosis, often necessitating multiple revision surgical procedures., Design: Retrospective medical record review., Setting: Tertiary care academic center., Patients: The medical records of 9 patients treated for bilateral CA during the neonatal period were reviewed. All patients were treated with an endoscopic approach. Outcomes were compared for patients with and without stent use at the initial operation., Main Outcome Measures: Medical records were analyzed for diagnostic modality, clinical symptoms, age at surgery, sex, surgical repair, placement of stents, reoccurrence of atresia, follow-up time, and postoperative outcomes., Results: The mean age at initial surgery was 8 days (range, 5-15 days). Four patients had endotracheal tube stents placed at the time of initial surgery for a duration of 4 to 6 weeks. All patients required at least 1 additional surgery (mean, 2.6 procedures), and 3 (75%) had restenosis during infancy. The mean follow-up time for this group was 7.5 months. Five patients did not have stents placed at the time of initial surgery. None of these patients required additional surgical procedures during infancy, and none developed restenosis. The follow-up time for this group was 2.5 months., Conclusions: This study suggests that the placement of stents for bilateral CA repair during the neonatal period results in a high rate of restenosis as well as the need for multiple subsequent procedures during infancy. The use of an endoscopic approach without stent placement appears to result in superior healing without the need for revision surgery.

Infections of the upper airways are a frequent cause of morbidity in children. Viral laryngotracheobronchitis (croup) is the most common cause of stridor in children and usually has a self-limited course with occasional relapses in early childhood. Epiglottitis has become rare in developed countries with the advent of universal vaccinations against Haemophilus influenzae. It can be rapidly fatal, however, if not promptly recognized and appropriately managed. This article reviews the pathogenesis, epidemiology, clinical presentation, diagnosis, and management of these pediatric upper airway infections.

Background: RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV) 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course., Methodology/principal Findings: Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with at least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher than that of patients with HPV 6 (Fisher's exact p = 0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p = 0.014). Both by multiple linear regression and by multiple logistic regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. CONCLUSIONS/SIGNIFICANCE ABSTRACT: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course.

Objective: To determine the sensitivity and specificity of airway fluoroscopy in the diagnosis of pediatric laryngotracheal abnormalities., Design: Retrospective chart review., Setting: Tertiary care children's hospital., Patients: Thirty-nine children, with a mean age of 18 months at the time of evaluation, were evaluated for stridor., Main Outcome Measures: Diagnoses made by airway fluoroscopy and endoscopy. The medical records of patients who had undergone both airway fluoroscopy and airway endoscopy for the evaluation of stridor over a 5-year period were reviewed. The sensitivity, specificity, and positive and negative predictive values of airway fluoroscopy in the diagnosis of laryngomalacia, tracheomalacia, airway stenosis at any level, and airway mass lesions were determined using endoscopic evaluation as the "gold standard.", Results: Twenty-three of 39 patients (59%) received a different diagnosis by airway endoscopy than by airway fluoroscopy. The sensitivity of airway fluoroscopy in the diagnosis of laryngomalacia, tracheomalacia, airway stenosis, and an airway mass was 27%, 20%, 69%, and 43%, respectively. The specificity for the same diagnoses was 100%, 94%, 100%, and 100%, respectively., Conclusions: Airway fluoroscopy appears to be reliable in the diagnosis of laryngomalacia, tracheomalacia, airway stenosis, and airway masses because of its high specificity. However, its sensitivity in detecting these common causes of stridor is poor. Negative fluoroscopic study results require further diagnostic evaluation if the clinical indication exists; therefore, the value of fluoroscopy as a screening tool remains uncertain.

Recurrent laryngeal papillomatosis (RLP), a chronic disease associated with human papilloma virus (HPV), requires serial surgical procedures for debulking, resulting in debilitating long-term dysphonia, laryngeal scarring, and rarely malignant degeneration. Human papilloma virus 11 tumors have been widely accepted as more aggressive than HPV 6 tumors; however, the clinical course has been difficult to predict at disease onset, and the biologic mediators of proliferation have not been well characterized. A retrospective case review of 43 patients (4 months to 10 years at diagnosis) was performed on children treated for recurrent laryngeal papillomatosis. Patient charts were reviewed for demographic information, age at RLP diagnosis, approximate frequency of surgical intervention, and absolute number of surgical procedures performed. Human papilloma virus subtyping was performed. Expression analysis of the HPV-encoded E6 and E7 oncogenes was performed by reverse-transcriptase polymerase chain reaction. Fourteen patients had subtype 11 (33%) and 29 patients had subtype 6 (67%). As expected, HPV 11 patients showed a more aggressive clinical course than HPV 6 patients. However, 38% of patients with subtype 6 (11 patients) followed a clinical course that mirrored the more severe subtype 11 patients. These patients expressed the disease at a younger age (P < 0.0002) and showed higher levels of E6 and E7 oncogenes compared to the patients with the more indolent course. Although HPV subtype and early onset of RLP are well characterized prognostic factors, our study documents the significance of E6 and E7 oncogene expression as potential biologic mediators of proliferation and thereby clinical behavior.

Background: Thyroglossal duct cysts (TGDCs) are the most common form of congenital neck cyst, accounting for up to 70% of such lesions. There has been no consensus on which factors predict outcome of thyroglossal duct cyst excision. The objective of the current study is to evaluate the relevance of symptomatology and age at presentation with outcome of TGDCs., Methods: Retrospective review of patients with TGDC at a tertiary care children's hospital. Data collected included patient's age, gender, clinical presentation, presence or absence of preoperative infection, imaging modality, type of procedure performed, size and location of the lesion, postoperative infection, complications, and recurrence of disease., Results: Twenty-nine patients were identified (59% female, 41% male). Age of presentation was bimodal and ranged from 18 months to 14 years. The most common presenting symptom was the presence of an asymptomatic midline neck mass (76%). A history of preoperative TGDC infection was present in 22% of patients /=5 years of age. Recurrence rate after the Sistrunk procedure was 3.4%., Conclusions: The finding of a midline neck mass is the most common presentation of TGDCs in toddlers, whereas infection is the most common presenting symptoms in school-aged children. The incidence of preoperative infection was 41% in our series, much higher than previously reported. Independent of presenting age and symptomatology, recurrence of TGDC remains low when the Sistrunk procedure is employed.

Objective: To present our experience with balloon laryngoplasty (BL) as a means of establishing control of the compromised airway and as a definitive alternative to open surgery in infants with acquired subglottic stenosis (SGS)., Design: The medical charts of 10 consecutive infants diagnosed as having acquired SGS secondary to a history of intubation and treated initially with BL were reviewed., Setting: Academic tertiary care children's hospital., Patients: A total of 10 patients (3 girls and 7 boys), with a mean age of 4.8 months (range, 2-12 months), met the inclusion criteria for the study., Main Outcome Measures: The medical charts were assessed for the patients' demographics, clinical presentation, and outcomes, which were defined by postoperative symptomatology, endoscopic grading of residual SGS, complications, and the need for subsequent interventions to control SGS., Results: All 10 patients presented with biphasic stridor, and 8 had significant retractions noted on examination. In all patients, control of the airway was established with BL followed by intubation. Four patients were completely asymptomatic after the initial BL. An additional 3 patients had recurrent stridor during the postoperative period and required a second BL before having complete, persistent resolution of symptoms. Balloon laryngoplasty failed in 3 patients, of whom 2 went on to undergo single-staged laryngotracheal reconstruction and 1 required a tracheotomy., Conclusions: Balloon laryngoplasty is a safe means of establishing the airway in infants with obstruction secondary to acquired SGS. It was an effective, stand-alone procedure for the management of SGS in 7 of our 10 patients, obviating the need for tracheotomy or cricoid split.

Background: Parotitis is a well recognized entity in the adult population, however there are very few studies concerning the clinical presentation and management of this condition in children., Objectives: To characterize pediatric parotitis in a tertiary care setting, with the goal of clarifying management recommendations and outcomes., Methods: The charts of all pediatric patients with a diagnosis of parotitis treated at a tertiary care academic institution from 1999 to 2004 were reviewed. The management of inpatients and outpatients were characterized to define differences in presentation and care., Results: Twenty-one children (6 months-15 years) with a diagnosis of parotitis were identified. Thirteen (62%) children were treated as inpatients, of which seven (54%), had significant medical co-morbidities. The most common clinical presentations of the inpatient group included dehydration (46%), fever (38%) and leukocytosis (46%). Two inpatients (15%) required surgical drainage due to abscess formation. Eight children (38%) were treated as outpatients, none with associated co-morbidity, fever, leukocytosis, or complication due to infection. All outpatients were treated with oral antibiotics or conservative therapy with eventual resolution., Conclusions: Parotitis in the pediatric population is uncommon. The presence of a significant co-morbidity, fever, or leukocytosis may require inpatient therapy and imaging if patients fail to improve with medical therapy. Other than abscess drainage, surgery for parotitis in children is not routinely recommended.

Objective: To compare the effects of 3 commonly used ototopical corticosteroid-antibiotic agents, currently available for use in the treatment of inflammatory conditions of the external and middle ear, on granulation tissue in an established murine model of wound healing., Subjects: Twelve C57/BL6J mice., Design: Eight-millimeter wounds, created bilaterally on the dorsum of the mice, were treated with combinations of 0.3% ciprofloxacin and 0.1% dexamethasone (CiproDex), 0.3% tobramycin and 0.1% dexamethasone (TobraDex), 0.2% ciprofloxacin hydrochloride and 1% hydrocortisone (Cipro HC), or phosphate-buffered saline (n = 6 each) for 3 days (days 4-6) and then harvested on day 7. Wound sections were stained with hematoxylin-eosin, Gomori trichrome, and CD31. Extracellular matrix deposition was graded from 1-4, and neovascularization was assessed by counting the number of endothelial-lined vessel lumens per high-power field (HPF)., Results: The mean +/- SEM grade of extracellular matrix deposition was lower in CiproDex- (1.7 +/- 0.2) and TobraDex- (2.0 +/- 0.2) but not Cipro HC-(2.9 +/- 0.3) treated wounds compared with control wounds (2.9 +/- 0.2) (P<.01). The mean +/- SEM number of vessel lumens per HPF was lower in CiproDex- (0.9 +/- 0.2 lumens/HPF), TobraDex- (1.5 +/- 0.3 lumens/HPF) and Cipro HC-(0.9 +/- 0.3 lumens/HPF) treated wounds compared with controls (3.3 +/- 0.5 lumens/HPF) (P<.01)., Conclusions: All 3 ototopical corticosteroid-antibiotic agents studied were equally effective at reducing neovascularization, although dexamethasone-based products were more effective at reducing extracellular matrix deposition. The results of this study suggest that ototopical agents containing dexamethasone may be more effective for the treatment of granulation tissue resulting from external and middle ear inflammatory conditions.

Background: The management of chronic sinusitis (CS) in children has yet to be fully elucidated. The objective of this study is to assess practice trends within the pediatric otolaryngology community for the management of children with CS., Methods: A multiple choice survey of the members of the American Society of Pediatric Otolaryngology (ASPO) was performed to assess for various factors related to the management of CS in children., Results: A total of 175 ASPO members responded to the survey. The majority of respondents initially treat patients medically with oral antibiotics (95%), topical steroids (90%), and nasal saline sprays (68%). Fifty-five percent performed adenoidectomy as part of the treatment of CS, with 81% performing the operation before endoscopic sinus surgery (ESS). Compared with 3 years before the survey, 47% of respondents performed approximately the same number of ESS cases, whereas 35% reported doing fewer cases annually. Seventy-two percent of practitioners do not routinely perform a second-look surgery., Conclusions: The majority of pediatric otolaryngologists use oral antibiotics, nasal steroids, and saline lavage, and will perform adenoidectomy when managing patients with CS. More than a third of pediatric otolaryngologists are using more stringent criteria for surgery and performing less extensive surgery than 3 years before the survey. Surgical outcomes for CS do not appear to have changed over the past 3 years.

Objective: To examine the developmental time course of the mutant phenotype and cellular mechanisms that result in malformations of the superior semicircular canal (SSCC) in Brn4 knockout mice. Mutations in the Brn4/Pou3f4 gene result in characteristic inner ear abnormalities in mutant mouse pedigrees, and the findings in these mice are similar to those in human X-linked deafness type III., Design: Mutant and control mice were killed at various neonatal time points to assess the development of the SSCC. Measurements of SSCC diameter were made on paint-perfused specimens at postnatal day (P) 0, P7, P10, and P14. Histologic evaluation of the SSCC was made on hematoxylin-eosin-stained sections at P10., Results: A dysmorphic constriction of the superior arc of the SSCC in Brn4 knockout mice was initially detectable at P14. Interestingly, the mutant SSCC is indistinguishable from control mice at earlier neonatal time points. In mutant neonates, there is persistence of immature woven bone with high cellularity surrounding the perilymphatic space of the SSCC. These findings are not present in control animal specimens, which demonstrate appropriate lamellar bony architecture., Conclusions: In Brn4 knockout mice, constriction of the SSCC with narrowing of the bony labyrinth develops in the postnatal period at approximately P14. The persistence of immature bone in affected mice indicates that signaling abnormalities disrupt normal mesenchymal differentiation in the SSCC.

Background: Otitis media with effusion (OME) occurs in the setting of eustachian tube (ET) dysfunction. Previous studies have demonstrated a predominance of T helper 2 (Th2) mediators in the middle ear effusions (MEEs) of atopic children, suggesting that allergy plays a role in the pathogenesis of OME. Given that the middle ear is contiguous with the upper airway, the allergic inflammation seen in the middle ear of atopic patients with OME may also have been observed in the nasopharynx., Objective: We hypothesize that atopic children have different cellular and cytokine profiles in MEE compared with nonatopic patients and that this allergic inflammation occurs in both the middle ear and the nasopharynx., Methods: Forty-five patients undergoing both ventilation tube placement for OME and adenoidectomy for adenoid hypertrophy were recruited. The atopic status was determined for each patient using standard skin testing. The cellular and cytokine profiles of the MEEs and the torus tubarius and adenoid tissues were investigated using immunocytochemistry and in situ hybridization., Results: Our results indicate that, within the atopic patient, there is a similar cellular and cytokine profile within the three regions sampled, with a predominant expression of interleukin-4 (a Th2 cytokine) and an increased infiltration of eosinophils compared with the nonatopic patient., Conclusion: These findings confirm the association of allergy with MEE and support the hypothesis that the middle ear may be an integral part of the United Airway Concept.

Background: Otitis media with effusion (OME) is a chronic inflammatory disease of the middle ear space characterized by the accumulation of fluid. Previous investigations have suggested that the immunopathologic mechanism underlying the development of middle ear effusion in patients with allergy is largely due to the effects of T(H)2 mediators. The composition of the inflammatory substrate in the effusions of allergic otitis media is similar to the late-phase allergic response seen elsewhere in the respiratory tract, such as in asthma and in allergic rhinitis., Objective: To determine whether the middle ear compartment may be a component of the united airways in allergic disease by comparing the inflammatory profiles of the middle ear to the upper airway., Methods: Middle ear effusions, torus tubaris (Eustachian tube mucosa at the nasopharyngeal orifice), and adenoidal tissue biopsies were obtained from 45 patients undergoing simultaneous tympanostomy tube placement for OME and adenoidectomy for adenoid hypertrophy. The cellular and cytokine profiles of each site were investigated by using immunocytochemistry (elastase, CD3, major basic protein) and in situ hybridization (IL-4, IL-5, IFN-gamma mRNA). Atopic status was determined for each patient by using skin prick testing., Results: Eleven of the 45 patients with OME (24%) were atopic. The middle ear effusions of atopic patients had significantly higher levels of eosinophils, T lymphocytes, and IL-4 mRNA + cells ( P < .01) and significantly lower levels of neutrophils and IFN-gamma mRNA + cells ( P < .01) compared with nonatopic patients. The nasopharyngeal tissue biopsies revealed similar cellular and cytokine profiles., Conclusion: In atopic patients with OME, the allergic inflammation occurs on both sides of the Eustachian tube, both in the middle ear and in the nasopharynx. The results of this study support the concept that the middle ear may be part of the united airway in atopic individuals.