When is pre-operative imaging required for craniofacial dermoid cysts/sinuses? A review.

OBJECTIVES: Dermoid cysts/sinuses (DCS) are congenital masses occurring along lines of embryonic fusion. Midline DCS carry a risk of intracranial extension. Pre-operative computed tomography (CT) or magnetic resonance imaging (MRI) are the primary imaging modalities used and based on the results, the need to involve a neurosurgical team in the resection is determined. Although less so, non-midline locations are also at risk for intracranial communication. This study aims to quantify our institutional experience with both midline and lateral DCS for intracranial extension and discuss potential need for preoperative imaging in all DCS cases. METHODS: Institutional Review Board approval was obtained. Pediatric patients ages 0-18 years with DCS presenting to the pediatric otolaryngology, plastic surgery, and neurosurgery clinics from 2005 to 2020 were retrospectively reviewed. Data collected included patient demographics, imaging modality, location, size, complications, and presence/absence of intracranial extension. DCS location included nasoethmoidal (NE), periorbital, frontotemporal (FT), and scalp. Lesions were further classified as midline and non-midline. RESULTS: 205 patients with surgically removed DCS were included for analysis. Mean age at surgery was 3 years. MRI was the most common imaging modality used (60.5%), followed by US (18%), CT (18%) and plain films (1%). Locations were: NE (69, 34%), periorbital (67, 33%), FT (28, 14%), and scalp (41, 20%). 105 DCS were midline: NE (69), periorbital (7), and scalp (29). Of these, 29 (28%) had intracranial extension: NE (8), scalp (21). 100 DCS were non-midline: periorbital (60), FT (28) and scalp (12). Of these, 7 (7%) had intracranial extension: periorbital (3), FT (3) and scalp (1). CONCLUSION: The risk of intracranial extension of midline craniofacial DCS is well established. We have shown that there is a percentage of lateral DCS which carry a risk for intracranial extension, and for which the involvement of a neurosurgical team may be required. Given the potential benefit, pre-operative imaging of all lateral head and neck DCS may be prudent to screen for intracranial extension.

A Systematic Review and Meta-Analysis: Timing of Elective Removal of Tympanostomy Tubes.

OBJECTIVE(S): Tympanostomy tube (TT) placement is the most common surgical procedure in children. Less than 10% of TT do not self-extrude. This study is a systematic review (SR) on elective TT removal in the pediatric population: timing, perforation rates, and role of simultaneous repair. A PICOTS (population, intervention, comparison, outcome, timing, setting) question was formulated: In pediatric patients who have retained TT, what is the preferred time to elective removal of such tubes, and what are the outcomes in terms of perforation rates? Does an intervention at the time of TT removal improve perforation rates? STUDY DESIGN: Systematic review and meta-analysis. METHODS: We searched four major electronic databases: EMBASE, MEDLINE, CDSR, CCRCT for articles published prior to 02/19/20. EndNote® was used to gather references, review abstracts, and obtain full text articles. Inclusion criteria were studies reporting patients aged 0 to 18 years undergoing elective TT removal with follow-up greater than 3 months. Exclusion criteria included patients >18 years, duplicate patient series, or case series with fewer than five patients. Articles that were not available in English, not available in full text, and those that only addressed long-acting TT were excluded. Data were pooled and meta-analysis was conducted to examine how timing of TT removal, patching of the tympanic membrane, or any TM intervention at TT removal affected outcomes. RESULTS: A total of 1,064 references were found. We identified 63 unique studies for full text review. Of these, 17 were selected for SR. MINORS (Methodological Index for Nonrandomized Studies) scores were low-revealing high bias among the studies. Reported perforation rates after elective TT removal ranged from 0% to 57%. Four studies had data suitable for comparative meta-analysis, which showed a significant increase in perforation rates after elective removal of TT after 3 years compared to removal prior to 3 years (OR 2.89; CI 1.78-4.69). No difference in perforation rates were identified when TM intervention vs. no intervention at time of TT removal was performed (six studies: OR 1.21; CI 0.71-2.07). No difference in perforation rates was identified when the type of TM intervention was compared, including freshening of TM edges, to patching with various materials (paper, fat, gelfoam®/gelfilm®, Trichloroacetic acid) (three studies: OR 1.07; CI 0.52-2.19). CONCLUSION: From the data reviewed in this SR and meta-analysis, elective TT removal at or prior to 3 years' retention showed decreased perforation rates. However, TM intervention at the time of TT removal was not shown to lower perforation rates. In the absence of tube complications such as granuloma formation, nonfunctional tube, or chronic tube otorrhea, it may be reasonable to wait up to 3 years to electively remove a retained TT. Laryngoscope, 132:2063-2070, 2022.

Drug-Induced Sleep Endoscopy Findings in Children With Obstructive Sleep Apnea With vs Without Obesity or Down Syndrome.

Importance: Persistent obstructive sleep apnea after adenotonsillectomy is common in children with Down syndrome or obesity. Drug-induced sleep endoscopy could help to identify anatomic differences in these patients that might affect surgical decision-making. Objective: To assess drug-induced sleep endoscopy findings in surgically naive children with obstructive sleep apnea with obesity or Down syndrome and compare these findings with children without obesity or Down syndrome. Design, Setting, and Participants: This cross-sectional analysis of data from a prospective cohort study of patients enrolled between May 1, 2015, and December 31, 2019, was conducted at an academic tertiary care children's hospital and included a consecutive sample of surgically naive children (age 2-18 years) who underwent drug-induced sleep endoscopy at the time of adenotonsillectomy for sleep-disordered breathing. Indications for sleep endoscopy included severe sleep apnea, age older than 7 years, obesity, African American race, and Down syndrome. Exposures: Drug-induced sleep endoscopy. Main Outcomes and Measures: Sleep endoscopy findings were scored according to the Sleep Endoscopy Rating Scale. Ratings at 6 anatomic levels for children with obesity and those with Down syndrome were compared with controls without obesity or Down syndrome using several measures of effect size (Cohen d, Cramer V, and η2). Results: A total of 317 children (158 girls [50%]; 219 [69%] White, 20 [6%] Black, and 103 [34%] Hispanic; mean [95% CI] age, 9.6 [9.2-10.0] years) were included, of whom 115 (36%) were controls without obesity or Down syndrome, 179 (56%) had obesity without Down syndrome, and 23 (7%) had Down syndrome. The mean apnea-hypopnea index was 16 (95% CI, 13-19), and the mean minimum O2 saturation was 83% (95% CI, 81%-85%). Compared with controls without obesity or Down syndrome, children with Down syndrome demonstrated greater overall obstruction (mean sleep endoscopy rating scale total score of 5.6 vs 4.8; Cohen d, 0.46), and greater tonsillar (percentage of complete obstruction: 65% vs 54%), tongue base (percentage of complete obstruction: 26% vs 12%), and arytenoid obstruction (percentage of at least partial obstruction, 35% vs 6%). Children with obesity had greater tonsillar (percentage of complete obstruction, 74% vs 54%) and less base of tongue obstruction (percentage of complete obstruction, 2% vs 12%) compared with controls. Conclusions and Relevance: In this cohort study, surgically naive children with obesity with obstructive sleep apnea had predominantly tonsillar obstruction, whereas children with Down syndrome demonstrated greater obstruction of the tonsils, tongue base, and arytenoids compared with controls. Routine drug-induced sleep endoscopy should be considered in surgically naive children with Down syndrome to help inform the surgical plan.

Endoscopic ear surgery in children with down syndrome.

INTRODUCTION: Children with Down syndrome (DS) have a high incidence of chronic middle ear disease. Surgery to manage this disease is challenging due to the severity of illness and narrow ear canal dimensions. Endoscopic ear surgery is used to manage tympanic membrane and middle ear disease with the advantages of improved visualization and avoidance of post-auricular incisions. However, its application in children with DS has not been reported. We aim to compare the outcomes of endoscopic versus microscopic ear surgery in children with DS. METHODS: All patients with DS who underwent tympanoplasty without mastoidectomy between 2012 and 2018 were identified, and their charts retrospectively reviewed. Rate of residual perforation, hearing, surgical time, and surgical details were recorded. RESULTS: 37 surgeries in 26 patients were identified that met inclusion criteria. Two subgroups were analyzed. The first included 14 cases that were done using traditional microscopic visualization (MV). The second included 17 cases that had substantial or exclusive use of endoscopic visualization (EES). Due to a learning curve, the number of cases done endoscopically increased over time. The average age in MV was 13.9 years vs 11.0 in EES. The MV cases included 2 with cholesteatoma vs 4 in EES. In cases with adequate follow up, residual perforations were found in 1/13 MV, and 4/17 EES. All of the residual perforation cases in EES used acellular porcine submucosa grafts. None of the cases in MV used this material. Average air bone gap reduction was seen in both groups; 4.2 dB in MV, 9.8 dB in EES. Average surgical time was similar between groups; 124 min in MV, 115 min in EES. All cases in MV required a post-auricular incision and approach to the middle ear. Only four cases in EES required this approach. Six cases in EES did not require any incision outside of the ear canal for either graft harvest or middle ear approach. CONCLUSION: Endoscopic and microscopic ear surgery in children with DS have similar outcomes. There were no statistical differences in hearing results, surgical times, or residual tympanic membrane perforations, although the rate of perforations in the endoscopic group trended higher. Most endoscopic cases did not require conversion to a post-auricular approach. Endoscopic surgery allows some DS patients to avoid any incision outside of the ear canal.

Advanced practice providers and children's hospital-based pediatric otolarynology practices.

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.

Intratympanically Delivered Steroids Impact Thousands More Inner Ear Genes Than Systemic Delivery.

OBJECTIVES: Glucocorticoids are given for sensorineural hearing loss, but little is known of their molecular impact on the inner ear. Furthermore, in spite of claims of improved hearing recovery with intratympanic delivery of steroids, no studies have actually documented the inner ear molecular functions that are enhanced with this delivery method. METHODS: To assess steroid-driven processes in the inner ear, gene chip analyses were conducted on mice treated systemically with the glucocorticoids prednisolone or dexamethasone or the mineralocorticoid aldosterone. Other mice were given the same steroids intratympanically. Inner ears were harvested at 6 hours and processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34 000 genes. Results were statistically analyzed for up or down expression of each gene against control (untreated) mice. RESULTS: Analyses showed approximately 17 500 genes are normally expressed in the inner ear and steroids alter expression of 55% to 82% of these. Dexamethasone changed expression of 9424 (53.9%) inner ear genes following systemic injection but 14 899 ear genes (85%) if given intratympanically. A similar pattern was seen with prednisolone, as 7560 genes were impacted by oral delivery and 11 164 genes (63.8%) when given intratympanically. The mineralocorticoid aldosterone changed expression of only 268 inner ear genes if given orally, but this increased to 10 124 genes (57.9%) if injected intratympanically. Furthermore, the glucocorticoids given actually impacted more inner ear genes via the mineralocorticoid receptor than the glucocorticoid receptor. CONCLUSIONS: Thousands of inner ear genes were affected by steroids, and this number increased significantly if steroids were delivered intratympanically. Also, the impact of glucocorticoids on inner ear mineralocorticoid functions is more substantial than previously known. Thus, the application of therapeutic steroids for hearing loss needs to be reassessed in light of their more comprehensive impact on inner ear genes. Furthermore, simply ascribing the efficacy of steroids to immunosuppression no longer appears to be warranted.

Simultaneous intra-operative sclerotherapy and surgical resection of cervicofacial venous malformations.

OBJECTIVES: To review simultaneous intra-operative sclerotherapy (IOS) with immediate surgical resection for the treatment of cervicofacial venous malformations (VMs) at a single institution. While pre-operative sclerotherapy (POS) has been reported in the literature, simultaneous intra-operative sclerotherapy and surgery in the operating room has not. METHODS: The database from the Hemangioma and Vascular Birthmarks Clinic was reviewed. All patients in both groups had biopsy-proven VMs. RESULTS: IOS was used in 11 surgical patients with average age 17 years. Sclerotherapy was performed with sodium tetradecyl sulfate 3%, absolute alcohol or bleomycin. Immediately after IOS, and under the same anesthetic, all patients had either complete resection or debulking of the VMs. Eight patients had complete resolution of their VM and 3 had improvement. Average duration of the combined procedures done under a single anesthetic was 121 min. The POS approach was used for 6 surgical patients with average age 7 years. Sclerotherapy agents used were absolute alcohol or sodium tetradecyl sulfate 3%. All patients underwent complete resection of the VM 24-72 h after sclerotherapy under a separate surgical session. Five patients experienced complete resolution of their VM and one has had further sclerotherapy for recurrent disease. Interventional Radiology suite sclerotherapy times were on average 70 min. Surgical times were on average 142 min. Total combined anesthesia times for the two procedures added together were 212 min. Treatment time was significantly shorter in the IOS group (p = 0.0015). CONCLUSIONS: Simultaneous IOS at the time of surgical resection has been successful in our hands. IOS has the advantage of a single procedure and decreased cost to the patient. In the era of reducing pediatric exposure to anesthesia, this approach is especially attractive in the pediatric population. As well, at approximately $100/minute cost to the patient to be in either the Interventional Radiology Suite or in the operating room, the reduced length of the procedures seen in the IOS approach results in lower overall cost to the patient.

Is Routine Electrocardiography Necessary Before Initiation of Propranolol for Treatment of Infantile Hemangiomas?

BACKGROUND: In recent years propranolol has become the treatment of choice for infantile hemangiomas (IHs). There is broad variation in the approach to propranolol initiation in clinical practice. This retrospective study explored the effectiveness of routine pre-treatment ECG in screening infants being considered for systemic treatment with propranolol. METHODS: All patients seen in the outpatient pediatric dermatology clinics at Oregon Health and Sciences University (OHSU) and The Mayo Clinic Rochester (MCR), as well as those seen in multidisciplinary vascular anomalies clinics, who had ECGs obtained prior to planned initiation of propranolol for treatment of IH from 2008 to 2013, were identified. A total of 162 patients were included in the study. RESULTS: We found that 43% (69) of routine ECGs were read as abnormal, leading to 28 formal consultation appointments with pediatric cardiologists. After either formal consultation or informal discussion with cardiology, no patients with initially "abnormal" ECGs were ultimately excluded from treatment with propranolol based on routine ECG findings. Additionally no patients in our cohort experienced an adverse effect during treatment that could have been predicted or prevented by ECG prior to initiation of the propranolol. CONCLUSION: Our findings suggest that routine ECG may not be necessary or helpful in the vast majority of patients treated with propranolol for IHs.

Quality of life improvement after pressure equalization tube placement in Down syndrome: A prospective study.

OBJECTIVE: To evaluate quality-of-life changes after bilateral pressure equalization tube placement with or without adenoidectomy for the treatment of chronic otitis media with effusion or recurrent acute otitis media in a pediatric Down syndrome population compared to controls. STUDY DESIGN: Prospective case-control observational study. METHODS: The OM Outcome Survey (OMO-22) was administered to both patients with Down syndrome and controls before bilateral tube placement with or without adenoidectomy and at an average of 6-7 months postoperatively. Thirty-one patients with Down syndrome and 34 controls were recruited. Both pre-operative and post-operative between-group and within-group score comparisons were conducted for the Physical, Hearing/Balance, Speech, Emotional, and Social domains of the OMO-22. RESULTS: Both groups experienced improvement of mean symptom scores post-operatively. Patients with Down syndrome reported significant post-operative improvement in mean Physical and Hearing domain item scores while control patients reported significant improvement in Physical, Hearing, and Emotional domain item scores. All four symptom scores in the Speech domain, both pre-operatively and post-operatively, were significantly worse for Down syndrome patients compared to controls (p ≤ 0.008). CONCLUSIONS: Surgical placement of pressure equalizing tubes results in significant quality of life improvements in patients with Down syndrome and controls. Problems related to speech and balance are reported at a higher rate and persist despite intervention in the Down syndrome population. It is possible that longer follow up periods and/or more sensitive tools are required to measure speech improvements in the Down syndrome population after pressure equalizing tube placement ± adenoidectomy.

Use of intravenous propranolol for control of a large cervicofacial hemangioma in a critically ill neonate.

Cervicofacial segmental infantile hemangiomas (IH) may result in airway obstruction requiring use of propranolol to induce hemangioma regression and reestablish the airway. We present the first case using intravenous (IV) propranolol for control of airway obstruction and rapid expansion of cervicofacial IH in the setting of necrotizing enterocolitis (NEC) impaired gastrointestinal function. Intravenous dosing of propranolol was tolerated well in a critically ill neonate with multisystem complications of prematurity.

Implementation of a Pediatric Posttonsillectomy Pain Protocol in a Large Group Practice.

OBJECTIVE: In response to the increased risk of respiratory failure and death after tonsillectomy related to codeine use, Kaiser Permanente Northwest restricted use of opioids in patients <7 years old via electronic health record (EHR). However, opioids could be prescribed at physician discretion by overriding the EHR. This study aims to examine protocol compliance in a large group practice using EHR order sets and complication rates as compared with historical data. STUDY DESIGN: Case series with chart review. SETTING: Ambulatory care within a health maintenance organization. SUBJECTS AND METHODS: Procedural codes were used to identify children <7 years old who underwent tonsillectomy or adenotonsillectomy approximately 1.5 years before and after implementation of EHR protocol (n = 437). Primary outcome was opioid pain prescriptions received by patients. Secondary outcomes were emergency or urgent care utilization, postoperative bleeding, nausea, vomiting, dehydration, death, and reasons for prescribing opioid pain medication after EHR protocol implementation. Chi-square analysis and Fischer's exact testing were used to compare differences in event rates. RESULTS: Implementation of an age-based narcotic protocol significantly decreased physician narcotic prescribing from 82.2% to 15.4% (P < .0001). The most common reason for narcotic prescription after the intervention was the report of inadequate pain control by phone call (35%). There was no significant difference in rate of emergency or urgent care utilization between pre- and postimplementation groups (4% vs 6%, P = .29). CONCLUSIONS: Implementation of an age-based narcotic restriction for posttonsillectomy patients using an EHR order set is an effective and safe way to influence physician prescription practices.

Assessment of pediatric obstructive sleep apnea using a drug-induced sleep endoscopy rating scale.

OBJECTIVES/HYPOTHESIS: Assess the reliability of a Sleep Endoscopy Rating Scale (SERS) and its relationship with pediatric obstructive sleep apnea (OSA) severity. STUDY DESIGN: Retrospective case series of pediatric patients who underwent drug-induced sleep endoscopy (DISE) at the time of surgery for OSA from January 1, 2013 to May 1, 2014. METHODS: Three blinded otolaryngologists scored obstruction on DISE recordings as absent (0), partial (+1), or complete (+2) at six anatomic levels: nasal airway, nasopharynx, velopharynx, oropharynx, hypopharynx, and arytenoids. Ratings were summed for a SERS total score (range, 0-12). Reliability was calculated using a κ statistic with linear weighting. SERS ratings and obstructive apnea-hypopnea index (OAHI) were compared using Spearman correlation. A receiver operating characteristic (ROC) analysis determined the ability of the SERS total score to predict severe OSA (OAHI >10). RESULTS: Thirty-nine patients were included (mean age, 8.3 ± 5.1 years; 36% obese; mean OAHI, 19.1 ± 23.7). Intrarater and inter-rater reliability was substantial-to-excellent (κ = 0.61-0.83) and fair-to-substantial (κ = 0.33-0.76), respectively. Ratings correlated best with OAHI for the oropharynx (r = 0.54, P = .02), hypopharynx (r = 0.48, P = .04), and SERS total score (r = 0.75, P = .002). In ROC analysis, a SERS total score ≥6 demonstrated sensitivity/specificity of 81.8%/87.5%, respectively, and correctly classified 84% of patients. CONCLUSIONS: The SERS can be applied reliably in children undergoing DISE for OSA. Ratings of the oropharynx, hypopharynx, and SERS total score demonstrated significant correlation with OSA severity. A SERS total score ≥6 was an accurate predictor of severe OSA. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1492-1498, 2016.

Propranolol-responsive cranial nerve palsies in a patient with PHACES syndrome.

PHACES syndrome is a neurocutaneous disorder characterized by the presence of segmental hemangiomas with associated anomalies of the posterior fossa, cerebral vasculature, cardiovascular system, eyes, and ventral or midline structures. We present the first case of propranolol-responsive congenital trigeminal and facial nerve palsies secondary to an intracranial hemangioma in a patient with PHACES syndrome.

Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus.

BACKGROUND: Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts. METHODS: We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls. RESULTS: In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNFα secretion in myeloid dendritic cells. CONCLUSIONS: The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM.

Correlative mRNA and protein expression of middle and inner ear inflammatory cytokines during mouse acute otitis media.

Although the inner ear has long been reported to be susceptible to middle ear disease, little is known of the inflammatory mechanisms that might cause permanent sensorineural hearing loss. Recent studies have shown inner ear tissues are capable of expressing inflammatory cytokines during otitis media. However, little quantitative information is available concerning cytokine gene expression in the inner ear and the protein products that result. Therefore, this study was conducted of mouse middle and inner ear during acute otitis media to measure the relationship between inflammatory cytokine genes and their protein products with quantitative RT-PCR and ELISA, respectively. Balb/c mice were inoculated transtympanically with heat-killed Haemophilus influenzae and middle and inner ear tissues collected for either quantitative RT-PCR microarrays or ELISA multiplex arrays. mRNA for several cytokine genes was significantly increased in both the middle and inner ear at 6 h. In the inner ear, these included MIP-2 (448 fold), IL-6 (126 fold), IL-1ß (7.8 fold), IL-10 (10.7 fold), TNFα (1.8 fold), and IL-1α (1.5 fold). The 24 h samples showed a similar pattern of gene expression, although generally at lower levels. In parallel, the ELISA showed the related cytokines were present in the inner ear at concentrations higher by 2-122 fold higher at 18 h, declining slightly from there at 24 h. Immunohistochemistry with antibodies to a number of these cytokines demonstrated they occurred in greater amounts in the inner ear tissues. These findings demonstrate considerable inflammatory gene expression and gene products in the inner ear following acute otitis media. These higher cytokine levels suggest one potential mechanism for the permanent hearing loss seen in some cases of acute and chronic otitis media.

Control of middle ear inflammatory and ion homeostasis genes by transtympanic glucocorticoid and mineralocorticoid treatments.

HYPOTHESIS: Transtympanic steroid treatment will induce changes in ion homeostasis and inflammatory gene expression to decrease middle ear inflammation due to bacterial inoculation. BACKGROUND: Otitis media is common, but treatment options are limited to systemic antibiotic therapy or surgical intervention. Systemic glucocorticoid treatment of mice decreases inflammation and improves fluid clearance. However, transtympanic delivery of glucocorticoids or mineralocorticoid has not been explored to determine if direct steroid application is beneficial. METHODS: Balb/c mice received transtympanic inoculation of heat-killed Haemophilus influenzae (H flu), followed by transtympanic treatment with either prednisolone or aldosterone. Mice given PBS instead of steroid and untreated mice were used as controls. Four hours after steroid treatment, middle ears were harvested for mRNA extraction and 24 hours after inoculation middle ears were harvested and examined for measures of inflammation. RESULTS: H flu inoculation caused the increased expression of nearly all inflammatory cytokine genes and induced changes in expression of several genes related to cellular junctions and transport channels. Both steroids generally reversed the expression of inflammatory genes and caused ion and water regulatory genes to return to normal or near normal levels. Histologic evaluation of middle ears showed improved fluid and inflammatory cell clearance. CONCLUSION: Improvement in middle ear inflammation was noted with both the glucocorticoid prednisolone and the mineralocorticoid aldosterone. This was due to reversal of inflammation-induced changes in middle ear cytokine genes, as well as those involved in ion and water homeostasis. Because glucocorticoids bind to the mineralocorticoid receptor, but not the reverse, it is concluded that much of the reduction of fluid and other inflammation measures was due to these steroids impact on ion and water transport channels. Further research is necessary to determine if this alternative mineralocorticoid treatment for otitis media will be clinically effective with fewer side effects than glucocorticoids.

Outcomes of tympanostomy tube placement in children with Down syndrome--a retrospective review.

OBJECTIVES: Tympanostomy tubes are commonly used for treatment of chronic otitis media with effusion (COME) or recurrent acute otitis media (RAOM) in patients with Down syndrome, but hearing outcomes in this population have been mixed, and complications appear to be common. We aim to characterize outcomes and complications associated with tympanostomy tube placement in this population. METHODS: Retrospective review. All patients with Down syndrome presenting to a tertiary academic pediatric otolaryngology practice over a ten year period from 2002 to 2012 who received tympanostomy tubes for COME, RAOM, or hearing loss were reviewed. RESULTS: Long term follow up data was obtained in 102 patients, with average follow up 4.7 years. COME was the primary indication for tube placement in 100/102 (98%). Less than half of these patients (44%) initially failed their newborn hearing screen. Post operative hearing was found to be normal or near normal for the better hearing ear in 85/99 (85.9%), and normal to near normal in bilateral ears in 71/99 (71%). A majority (63.7%) of patients required two or more sets of tubes during the follow up period. Long term complications were common and were significantly increased if the patient required three or more sets of tubes, including chronic perforation (36.6% vs 8.2%, p<0.001), atelectasis (29.3% vs 1.6%, p<0.0001), and cholesteatoma (14.6% vs 0%, p=0.003). CONCLUSIONS: COME is a frequent problem in Down syndrome, and the majority of patients will require two or more sets of tubes during their childhood and achieve normal postoperative hearing. Long term complications of otitis media appear to be more common in this population and appear to correlate with increasing number of tubes placed. More investigation is required to determine optimal treatment strategies for COME in patients with Down syndrome.

Genetic susceptibility to chronic otitis media with effusion: candidate gene single nucleotide polymorphisms.

OBJECTIVES/HYPOTHESIS: The genetic factors leading to a predisposition to otitis media are not well understood. The objective of the current study was to develop a tag-single nucleotide polymorphism (SNP) panel to determine if there is an association between candidate gene polymorphisms and the development of chronic otitis media with effusion. STUDY DESIGN: A 1:1 case/control design of 100 cases and 100 controls was used. The study was limited to the chronic otitis media with effusion phenotype to increase the population homogeneity. METHODS: A panel of 192 tag-SNPs was selected. Saliva for DNA extraction was collected from 100 chronic otitis media with effusion cases and 100 controls. After quality control, 100 case and 79 control samples were available for hybridization. Genomic DNA from each subject was hybridized to the SNP probes, and genotypes were generated. Quality control across all samples and SNPs reduced the final SNPs used for analysis to 170. Each SNP was then analyzed for statistical association with chronic otitis media with effusion. RESULTS: Eight SNPs from four genes had an unadjusted P value of <.05 for association with the chronic otitis media with effusion phenotype (TLR4, MUC5B, SMAD2, SMAD4); five of these polymorphisms were in the TLR4 gene. CONCLUSIONS: Even though these results need to be replicated in a novel population, the presence of five SNPs in the TLR4 gene having association with chronic otitis media with effusion in our study population lends evidence for the possible role of this gene in the susceptibility to otitis media.

Otitis media impacts hundreds of mouse middle and inner ear genes.

OBJECTIVE: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition. METHODS: To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes. RESULTS: Statistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear. CONCLUSION: Whole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media.

Inner ear tissue remodeling and ion homeostasis gene alteration in murine chronic otitis media.

HYPOTHESIS: Studies were designed to ascertain the impact of chronic middle ear infection on the numerous ion and water channels, transporters, and tissue remodeling genes in the inner and middle ear. BACKGROUND: Permanent sensorineural hearing loss is a significant problem resulting from chronic middle ear disease, although the inner ear processes involved are poorly defined. Maintaining a balanced ionic composition of endolymph in the inner ear is crucial for hearing; thus, it was hypothesized that this may be at risk with inflammation. METHODS: Inner and middle ear RNA collected separately from 6-month-old C3H/HeJ mice with prolonged middle ear disease were subjected to qRT-PCR for 8 common inflammatory cytokine genes, 24 genes for channels controlling ion (sodium, potassium, and chloride) and water (aquaporin) transport, tight junction claudins, and gap junction connexins, and 32 tissue remodeling genes. Uninfected Balb/c mice were used as controls. RESULTS: Significant increase in inner ear inflammatory and ion homeostasis (claudin, aquaporin, and gap junction) gene expression, and both upregulation and downregulation of tissue remodeling gene expression occurred. Alteration in middle ear ion homeostasis and tissue remodeling gene expression was noted in the setting of uniform upregulation of cytokine genes. CONCLUSION: Chronic inflammatory middle ear disease can impact inner ear ion and water transport functions and induce tissue remodeling. Recognizing these inner ear mechanisms at risk may identify potential therapeutic targets to maintain hearing during prolonged otitis media.