Hamartomas and midline anomalies in association with infantile hemangiomas, PHACE, and LUMBAR syndromes.

BACKGROUND/OBJECTIVE: The pathogenesis of infantile hemangiomas (IH), PHACE, and LUMBAR syndromes remains unknown. We aim to describe histopathologic features of midline anomalies associated with IH, including patients with PHACE and LUMBAR syndromes. METHODS: A multicenter retrospective chart review was performed to identify patients with IH, PHACE, and LUMBAR syndrome with histopathologic specimens from sternal or midline anomalies. A total of 18 midline lesions from 13 patients were included. Out of 18, 14 midline lesions underwent both histopathologic and clinical review. Three hamartoma-like chin plaques and one supraumbilical raphe underwent only clinical review. RESULTS: All 13 patients had midline lesions and IH. Histopathologic diagnoses were as follows: rhabdomyomatous mesenchymal hamartoma (3), folliculosebaceous cystic hamartoma (1), fibroepithelial polyp (1), verrucous epidermal hyperplasia with vascular proliferation and fibroplasia (1), congenital midline cervical cleft (1), pericardium with fibrosis (1), fibrous components with increased collagen (1), atrophic skin/membrane (3), angiolipomatous mass with neural components (1), and lipomatous mass (1). Due to the retrospective nature of this study, it was not possible to obtain pathology slides for all midline lesions that had previously been biopsied or resected. We show clinically and histopathologically a new association between PHACE syndrome and rhabdomyomatous mesenchymal hamartoma (RMH), in addition to demonstrating the association between PHACE syndrome and chin hamartomas. We also display histopathologic findings seen in midline lesions resected from LUMBAR patients. CONCLUSION: Rhabdomyomatous mesenchymal hamartoma is thought to be related to aberrations of mesenchymal cells during development; therefore, this may provide clues to the pathogenesis of IH and related syndromes.

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.

Congenital Cytomegalovirus Testing Outcomes From the ValEAR Trial.

OBJECTIVE: To determine the positivity rate of congenital cytomegalovirus (cCMV) testing among universal, hearing-targeted CMV testing (HT-cCMV) and delayed targeted dried blood spot (DBS) testing newborn screening programs, and to examine the characteristics of successful HT-cCMV testing programs. STUDY DESIGN: Prospective survey of birth hospitals performing early CMV testing. SETTING: Multiple institutions. METHODS: Birth hospitals participating in the National Institutes of Health ValEAR clinical trial were surveyed to determine the rates of cCMV positivity associated with 3 different testing approaches: universal testing, HT-cCMV, and DBS testing. A mixed methods model was created to determine associations between successful HT-cCMV screening and specific screening protocols. RESULTS: Eighty-two birth hospitals were surveyed from February 2019 to December 2021. Seven thousand six hundred seventy infants underwent universal screening, 9017 infants HT-cCMV and 535 infants delayed DBS testing. The rates of cCMV positivity were 0.5%, 1.5%, and 7.3%, respectively. The positivity rate for universal CMV screening was less during the COVID-19 pandemic than that reported prior to the pandemic. There were no statistically significant drops in positivity for any approach during the pandemic. For HT-cCMV testing, unique order sets and rigorous posttesting protocols were associated with successful screening programs. CONCLUSION: Rates of cCMV positivity differed among the 3 approaches. The rates are comparable to cohort studies reported in the literature. Universal CMV prevalence decreased during the pandemic but not significantly. Institutions with specific order set for CMV testing where the primary care physician orders the test and the nurse facilitates the testing process exhibited higher rates of HT-cCMV testing.

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.

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.

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.

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.

Laryngomalacia and Swallow Dysfunction.

OBJECTIVES: Laryngomalacia is an established cause of stridor and sleep-disordered breathing in children. However, the relationship between laryngomalacia and dysphagia has not been well characterized. The objectives of this study were to (1) describe the patient characteristics, symptoms, and prevalence of dysphagia in children with laryngomalacia and (2) examine the effectiveness of supraglottoplasty in improving feeding. METHODS: This was a retrospective study of patients with laryngomalacia who underwent a modified barium swallow study (MBSS) at a tertiary academic pediatric medical center between March 1, 2014, and March 1, 2018. Patients were excluded if they did not undergo a MBSS. Comorbidities, airway and feedings symptoms, MBSS results, and surgical history were recorded from each patient's electronic medical record. RESULTS: Forty-four children met inclusion/exclusion criteria. The median age at presentation was 96 days. There was a male predominance (66%). About one-third had a genetic or neuromuscular comorbidity. Most children had stridor (93%) and feeding difficulty (86%), while 50% had parent-reported poor weight gain. Fifty-seven percent of patients had evidence of penetration or aspiration on MBSS. All patients with a positive MBSS had dysphagia symptoms. Fifty-seven percent of patients underwent supraglottoplasty. Postoperatively, 92% reported improvement in dysphagia symptoms. CONCLUSION: Dysphagia is prevalent among a subset of children with laryngomalacia. Symptomatic children may benefit from a swallow evaluation to help determine the need for further intervention. Children who undergo supraglottoplasty for laryngomalacia have improved dysphagia at follow-up, though the amount of improvement directly attributable to surgery is unclear and warrants further investigation.

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.

Multicenter Interrater Reliability in the Endoscopic Assessment of Velopharyngeal Function Using a Video Instruction Tool.

OBJECTIVE: Assess interrater agreement of endoscopic assessment of velopharyngeal (VP) function before and after viewing the video instruction tool (VIT). We hypothesized improvement in interrater agreement using the Golding-Kushner scale (GKS) after viewing the VIT. STUDY DESIGN: Prospective study. SETTING: Multi-institutional. METHODS: Sixteen fellowship-trained pediatric otolaryngologists who treat velopharyngeal insufficiency (VPI) rated 50 video segments using the GKS before and after watching the VIT. Raters assessed gap size percentage and lateral pharyngeal wall (LPW), soft palate (SP), and posterior pharyngeal wall (PPW) movement. Intraclass correlation coefficient was estimated for these continuous measures. Raters also indicated the presence of a palatal notch, Passavant's ridge, and aberrant pulsations (categorical variables). Fleiss κ coefficient was used for categorical variables. Wilcoxon signed-rank test was performed on the difference between the pre/post individual video ratings. RESULTS: Reliability improved for all continuous variables after watching the instructional video. The improvement was significant for PPW (0.22-0.30, P < .001), SP (left: 0.63-0.68, P < .001 and right: 0.64-0.68, P = .001), and LPW (left: 0.49-0.54, P = .01 and right: 0.49-0.54, P = .09) but not significant for gap size (0.65-0.69, P = .36). Among categorical variables, agreement on Passavant's ridge significantly improved (0.30-0.36, P = .03). CONCLUSION: Exposure to a video instruction tool improves interrater agreement of endoscopic assessment of VP function. Significant improvement was observed in our primary end points, specifically posterior pharyngeal wall movement, soft palate movement, and lateral pharyngeal wall movement. There was less impact of the VIT on the interrater agreement of the categorical variables, palatal notch, Passavant's ridge, and aberrant pulsations.

Control of chronic otitis media and sensorineural hearing loss in C3H/HeJ mice: glucocorticoids vs mineralocorticoids.

OBJECTIVE: The impact of glucocorticoids and mineralocorticoids on chronic otitis media (COM) in toll-like receptor 4-deficient C3H/HeJ mice was investigated. STUDY DESIGN: To evaluate control of COM by steroids with differences in their anti-inflammatory (prednisolone, dexamethasone), and fluid absorption functions (fludrocortisone, aldosterone). A minimum sample size of five animals for each group was required based on power analysis calculations. Sample sizes ranged from 7 to 17 mice per treatment group. SUBJECTS AND METHODS: Auditory brain stem response (ABR) thresholds were performed at baseline, 2 weeks and 4 weeks. Histopathologic test results were evaluated on all mice ears at the end of the study. RESULTS: Analysis of variance (ANOVA) of ABR threshold change showed significant treatment effects (P < 0.05) by both steroid types at all time intervals and ABR frequencies except 4 weeks/8 kHz. Histologic assessment showed prednisolone-treated mice (62%) had a higher rate of clearance of middle and inner ear inflammation than control mice (4%). CONCLUSION: It was concluded that steroid treatments can improve the physiology of chronic middle and inner ear disease seen with COM.

Gram-negative pathogen Klebsiella oxytoca is associated with spontaneous chronic otitis media in Toll-like receptor 4-deficient C3H/HeJ mice.

CONCLUSION: This report confirms the presence of gram-negative Klebsiella bacteria in the middle ear of the C3H/HeJ mouse by culture, polymerase chain reaction (PCR), and electron microscopy. Identification of the bacterial pathogen supports the C3H/HeJ mouse as an excellent model for spontaneous chronic otitis media and its effects on the middle and inner ear. OBJECTIVES: The C3H/HeJ mouse has a single amino acid substitution in its Toll-like receptor 4, making it insensitive to endotoxin and suppressing initiation of the innate immune system. This study explored the bacteriology of the resultant middle ear infection by culture, PCR, histology, and electron microscopy. MATERIALS AND METHODS: Twelve-month-old C3H/ HeJ mice were screened positive for spontaneous otitis media. Tympanocentesis and blood cultures of mice were carried out under sedation. Middle ear aspirate material and blood samples were then sent for culture and PCR. Mice were then sacrificed for bright-field and electron microscopy analysis. RESULTS: All tympanocentesis and blood specimens grew gram-negative Klebsiella oxytoca, which was confirmed by PCR. Histopathology confirmed an intense inflammatory reaction and gram-negative bacteria in the middle and inner ears. Electron microscopy of the middle ears revealed abundant rod-shaped Klebsiella bacteria, both free and being engulfed by neutrophils.

Effect of gentamicin and levels of ambient sound on hearing screening outcomes in the neonatal intensive care unit: A pilot study.

OBJECTIVE: Hearing loss rates in infants admitted to neonatal intensive care units (NICU) run at 2-15%, compared to 0.3% in full-term births. The etiology of this difference remains poorly understood. We examined whether the level of ambient sound and/or cumulative gentamicin (an aminoglycoside) exposure affect NICU hearing screening results, as either exposure can cause acquired, permanent hearing loss. We hypothesized that higher levels of ambient sound in the NICU, and/or gentamicin dosing, increase the risk of referral on the distortion product otoacoustic emission (DPOAE) assessments and/or automated auditory brainstem response (AABR) screens. METHODS: This was a prospective pilot outcomes study of 82 infants (<37 weeks gestational age) admitted to the NICU at Oregon Health & Science University. An ER-200D sound pressure level dosimeter was used to collect daily sound exposure in the NICU for each neonate. Gentamicin dosing was also calculated for each infant, including the total daily dose based on body mass (mg/kg/day), as well as the total number of treatment days. DPOAE and AABR assessments were conducted prior to discharge to evaluate hearing status. Exclusion criteria included congenital infections associated with hearing loss, and congenital craniofacial or otologic abnormalities. RESULTS: The mean level of ambient sound was 62.9 dBA (range 51.8-70.6 dBA), greatly exceeding American Academy of Pediatrics (AAP) recommendation of <45.0 dBA. More than 80% of subjects received gentamicin treatment. The referral rate for (i) AABRs, (frequency range: ∼1000-4000 Hz), was 5%; (ii) DPOAEs with a broad F2 frequency range (2063-10031 Hz) was 39%; (iii) DPOAEs with a low-frequency F2 range (<4172 Hz) was 29%, and (iv) DPOAEs with a high-frequency F2 range (>4172 Hz) was 44%. DPOAE referrals were significantly greater for infants receiving >2 days of gentamicin dosing compared to fewer doses (p = 0.004). The effect of sound exposure and gentamicin treatment on hearing could not be determined due to the low number of NICU infants without gentamicin exposure (for control comparisons). CONCLUSION: All infants were exposed to higher levels of ambient sound that substantially exceed AAP guidelines. More referrals were generated by DPOAE assessments than with AABR screens, with significantly more DPOAE referrals with a high-frequency F2 range, consistent with sound- and/or gentamicin-induced cochlear dysfunction. Adding higher frequency DPOAE assessments to existing NICU hearing screening protocols could better identify infants at-risk for ototoxicity.

Evaluation of the mouse model for acute otitis media.

Various animal models have been employed for otitis media research. The mouse has been studied less, in spite of its many advantages. To better understand the suitability of the mouse for studies of otitis media, an evaluation was made of its middle ear inflammatory processes following inoculation with heat-killed Streptococcus pneumoniae (strain 6A), one of the three most common bacteria to cause otitis media in the human. A total of 94 BALB/c mice were injected transtympanically with three concentrations of heat-killed bacteria (10(4), 10(6), and 10(9) organisms per ml) and inflammation evaluated with both histologic examination and auditory brainstem response audiometry. Dose-related measures of the time course of inflammation showed it was maximal at 3 days. PBS-injected control mice also demonstrated some degree of middle ear inflammation. Therefore, inflammation measures from PBS injected mice were used as the threshold above which histologic inflammatory changes would be considered a response to bacteria. These quantitative comparisons of bacterial and PBS inoculations revealed the most significant middle ear measures of inflammation were amount of fluid in the middle ear, tympanic membrane thickness, and number of inflammatory cells. The induction of middle ear inflammation in the mouse demonstrated the applicability of this model for investigations of otitis media.

C3H/HeJ mouse model for spontaneous chronic otitis media.

OBJECTIVES/HYPOTHESIS: Chronic otitis media is a significant clinical problem. Understanding the mechanisms of chronic otitis media is critical for its control. However, little is known of these processes as a result of lack of animal models of spontaneous otitis media. The C3H/HeJ mouse has a single amino acid substitution in its toll-like receptor 4 (TLR4), making it insensitive to endotoxin. As a result, these mice cannot clear Gram-negative bacteria. The chronically inflamed middle ear in this animal provides us the opportunity to study spontaneous chronic otitis media. STUDY DESIGN AND METHODS: Otoscopy and auditory brain response (ABR) evaluation of C3H/HeJ mice at 3, 5, 7, 9, and 11 months were carried out under sedation. At 12 months of age, mice were killed and histologic analysis of the middle ear, inner ear, and eustachian tube was carried out. RESULTS: Tympanic membrane visualization and ABR thresholds in 7- to 8-month-old C3H/HeJ mice showed that approximately half developed middle and inner ear disease spontaneously. The significant elevation of thresholds suggested a sensorineural component in addition to the conductive loss. Middle and inner ear histology showed some degree of middle and inner ear inflammation in half the mice, paralleling the ABR data. CONCLUSIONS: The histopathologic changes reported here in the C3H/HeJ mouse model of chronic otitis media have been reported in human chronic otitis media. This spontaneous model of chronic otitis media will be valuable for the characterization of middle and inner ear inflammatory disease processes that are induced by middle ear infections.

Head and neck hemangiomas of infancy.

PURPOSE OF REVIEW: Hemangiomas are the most common benign tumor in infancy, affecting approximately 10% of infants. More than half of hemangiomas involve the head and neck. Increased understanding of hemangiomas has come about from identification of immunohistochemical markers, developmental defects associated with certain hemangiomas, and morphologic and classification schemes (focal versus segmental). RECENT FINDINGS: Immunohistochemical markers have been identified which are specific to hemangiomas in all phases of development and involution. Morphologic subtypes and anatomic locations have been identified that place an infant at higher risk for complications from the hemangioma. Hemangiomas associated with other developmental anomalies have been identified, which help guide the treating physician to tease out which infants will need more complete systemic investigations or imaging. Importantly for surgeons, studies have continued to identify which lesions may benefit from early intervention, either surgical or medical. SUMMARY: While full understanding of the mechanisms that turn on and turn off hemangiomas of infancy is not complete, progress has been made in identification of markers, subtypes at increased risk for complications, and in treatment. With continued work in these areas, we have increased knowledge of treatment options, optimal timing of surgical intervention, and ultimately, preventive options.