Management of Pediatric Persistent Asymptomatic Cervical Lymphadenopathy.

OBJECTIVE: Persistent asymptomatic cervical lymphadenopathy (PACL) is a common outpatient referral diagnosis for pediatric otolaryngologists. Historically, excisional biopsy under general anesthesia has been the gold standard for diagnosis but is associated with some risks. Current literature provides little guidance on less invasive monitoring. Our hypothesis is that the majority of children who present with PACL can be safely monitored with ultrasound and avoid the risks of excisional biopsy. STUDY DESIGN: A retrospective review was performed of patients <18 years of age, referred to a tertiary care children's hospital for PACL who also underwent at least 1 neck ultrasound from 2007 to 2021. Patients with acute neck infections, congenital masses, or known rheumatologic, immunologic, or malignant conditions were excluded. A multivariate logistic regression model was used to determine patient and nodal factors associated with the decision for operative management. SETTING: University of California, San Francisco Pediatric Otolaryngology Department. RESULTS: Among the 197 patients meeting inclusion criteria, 30 (15.2%) underwent surgical biopsy. Overall, 26% underwent repeat ultrasound with a mean interval of 6.6 months, and a mean decrease in nodal size of 0.34 cm. Of the 30 surgical cases, 27 (90%) patients had benign pathology. Multivariate regression analysis revealed pain (p = .04), firmness (p < .001), and lack of a normal fatty hilum on ultrasound (p = .04) as statistically significantly correlated with decisions for surgical management. CONCLUSION: The majority of pediatric PACL is benign and does not require an excisional biopsy to rule out lymphoma. Serial clinical follow-up with neck ultrasound can be used to safely monitor patients.

Airway Hemangiomas in PHACE Syndrome: A Multicenter Experience.

OBJECTIVE: To describe the prevalence and clinical characteristics of airway findings in a multi-institutional cohort of PHACE patients. STUDY DESIGN: Multicenter retrospective case series. SETTING: Multidisciplinary vascular anomalies clinics at 2 institutions. METHODS: Data were collected from the electronic medical record, including clinical presentation, airway findings, treatment, and outcomes. RESULTS: Of 55 PHACE patients, 22 (40%) had airway hemangiomas. Patients with airway involvement were more commonly female (P = .034, odds ratio [OR] 23, 95% confidence interval [CI] 1.3-410) and of Caucasian ethnicity (P = .020, OR 5.3, 95% CI 1.3-21). Anatomically, patients with bilateral S3 involvement had higher rates of airway disease (P = .0012, OR 15, 95% CI 2.9-77). Most patients with airway hemangiomas had stridor (68%). Of the patients managed in the propranolol era (2008 or later, n = 35), 14 had airway involvement. All 14 were treated with propranolol, whereas 13 (62%) of 21 nonairway patients were treated with propranolol. The average treatment duration was longer in the airway patients (22.1 vs 16.7 months). All patients who underwent tracheostomy (n = 4) did so before 2008. CONCLUSION: Risk factors for airway involvement in PHACE include female gender, Caucasian ethnicity, and stridor. Since the widespread use of propranolol, fewer patients have required surgical management of their airway disease. Given the high prevalence of airway involvement even in patients without stridor, assessment of the airway is a crucial component of a comprehensive PHACE workup.

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.

Cryoprobe retrieval of an airway foreign body: A case report and literature review.

We report a case of a 7-year-old boy with clinical and radiographic evidence of foreign body (FB) aspiration with a 2-week delay in diagnosis. The retrieval of the pushpin with traditional bronchoscopic instrumentation was made difficult by granulation tissue formation. A cryoprobe through a flexible bronchoscope was used to successfully remove the FB. To our knowledge, this is the first report of interventional bronchoscopy with a cryoprobe to remove a pushpin in a child under suspension laryngoscopy and spontaneous ventilation. A high index of suspicion is crucial for identifying FBs early and minimizing granulation tissue development which complicates FB removal.

Hearing loss in PHACE syndrome: clinical and radiologic findings.

PURPOSE: To characterize the types of hearing loss, auditory-related imaging findings, and hemangioma characteristics in patients with Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and abnormalities of the Eye (PHACE) syndrome. METHODS: Retrospective medical records, audiologic data, and imaging review of all patients presenting to a tertiary care children's hospital with a proven diagnosis of PHACE syndrome from 2005 to 2016. RESULTS: Twelve patients were identified with hearing and imaging data. 5/12 had hearing loss, 1 had unilateral severe sensorineural loss with minor conductive component, 1 had unilateral moderate sensorineural loss with minor conductive component, 1 had mild bilateral conductive loss, 1 had bilateral hearing loss (left severe mixed and right severe sensorineural), and 1 had moderate bilateral conductive loss. All patients passed their newborn hearing screening. Of the 5 patients with hearing loss, 3 had IAC hemangiomas (1 bilateral), 3 had enlarged IACs with prominent posterior petrous bones (1 bilateral), 2 had dysgenesis of the cerebellar vermis and hemispheres, there was 1 patient each with a deformed pinna and middle ear and mastoid effusions, and 1 patient had no abnormal auditory-related imaging findings. Patients with hearing loss were more likely to have more areas of cutaneous hemangioma involvement (mean 6.4 vs 3.1, p = .05). Laterality of hearing impairment correlated with the side of cutaneous hemangioma in all patients with hearing loss. Treatment with systemic propranolol did not improve hearing. CONCLUSIONS: Patients with PHACE are at risk for hearing loss and may demonstrate radiologic abnormalities within the ear structures, although the type of hearing loss, imaging findings, and their respective correlation vary. While our results are limited by our small sample size, comprehensive audiology evaluations (as opposed to newborn screening testing only) should be considered for PHACE patients who have extensive cutaneous hemangioma or auditory-related imaging abnormalities, such as internal auditory canal hemangiomas.

Genetic engineering in primary human B cells with CRISPR-Cas9 ribonucleoproteins.

Genome editing in human cells with targeted nucleases now enables diverse experimental and therapeutic genome engineering applications, but extension to primary human B cells remains limited. Here we report a method for targeted genetic engineering in primary human B cells, utilizing electroporation of CRISPR-Cas9 ribonucleoproteins (RNPs) to introduce gene knockout mutations at protein-coding loci with high efficiencies that in some cases exceeded 80%. Further, we demonstrate knock-in editing of targeted nucleotides with efficiency exceeding 10% through co-delivery of oligonucleotide templates for homology directed repair. We delivered Cas9 RNPs in two distinct in vitro culture systems to achieve editing in both undifferentiated B cells and activated B cells undergoing differentiation, reflecting utility in diverse experimental conditions. In summary, we demonstrate a powerful and scalable research tool for functional genetic studies of human B cell biology that may have further applications in engineered B cell therapeutics.

Sirolimus for management of complex vascular anomalies - A proposed dosing regimen for very young infants.

Neonates with vascular anomalies causing airway compromise and other complications require early initiation of medical therapy. Sirolimus has emerged as a safe and effective treatment, but standard recommendations for dosing start at seven months. Guidelines are needed for dosing in very young infants, who have reduced hepatic metabolism of sirolimus. We present our experience treating six neonates (mean age 14.8 days) with complicated vascular anomalies. Standard dosing caused supratherapeutic levels in this population. Our modified dosing regimen has resulted in safe therapeutic concentrations. Properly dosed, sirolimus is a viable and potentially lifesaving option for neonates with severe morbidity from vascular anomalies.

Sleep-disordered breathing in pediatric head and neck vascular malformations.

OBJECTIVES: To determine the prevalence of sleep-disordered breathing (SDB) symptoms among children with head and neck vascular malformations and to compare obstructive sleep apnea (OSA)-18 scores between children with head and neck vascular malformations and children with non-head and neck vascular malformations. STUDY DESIGN: Retrospective cohort and prospective cross-sectional studies METHODS: Forty-three pediatric subjects with head and neck vascular malformations evaluated at a tertiary-care multidisciplinary vascular anomalies center were included in a retrospective cohort study. Eighty-three consecutive pediatric subjects with vascular malformations evaluated at the same center were included in the prospective cross-sectional study. RESULTS: In the retrospective cohort study, 20 (47%) subjects with head and neck malformations had documented SDB symptoms. Of those with SDB symptoms, five (25%) required long-term tracheotomy. The children with SDB symptoms had greater vascular malformation size, more extensive pharyngeal involvement, greater vascular malformation mass effect on airway, and closer proximity of malformation to airway when compared to children without SDB symptoms. For the prospective cross-sectional study, 23% of pediatric subjects had malformations of the head and neck. Those with head and neck malformations had a higher OSA-18 score and a lower overall quality of life (QOL) score when compared to subjects with non-head and neck malformations. CONCLUSION: Nearly half of children with head and neck vascular malformations have SDB symptoms. Children with head and neck vascular malformations have a higher OSA-18 score and lower overall QOL score when compared to children with non-head and neck vascular malformations. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2159-2164, 2017.

Pediatric sialendoscopy indications and outcomes.

PURPOSE OF REVIEW: Chronic sialadenitis can affect patients of all age ranges and typically presents as recurrent or chronic painful swelling of the salivary glands. In children, the most common cause of sialadenitis is juvenile recurrent parotitis. Salivary stones, or sialolithiasis, are a much less common cause. Historically, for patients with chronic sialadenitis who failed conservative management, salivary gland removal was the standard treatment option. Recently, however, sialendoscopy has emerged as an effective gland-preserving procedure for sialadenitis evaluation and treatment in adults and children. The aim of this review is to discuss pediatric sialadenitis evaluation and treatment, including sialendoscopy indications, technique, and outcomes. RECENT FINDINGS: Sialendoscopy is a well tolerated and effective treatment for sialadenitis Sialendoscopy and salivary duct irrigation have been shown to improve frequency and severity of sialadenitis episodes in patients with juvenile recurrent parotitis. Salivary stones are managed successfully with endoscopic and combined endoscopic-assisted open approaches. Minimally invasive approaches with sialendoscopy have improved the ability to preserve salivary glands in patients with recurrent sialadenitis. SUMMARY: Sialendoscopy is a well tolerated and effective procedure for recurrent sialadenitis in children.

Pneumothorax after tracheostomy closure with successful nonsurgical management.

A 3-year-old girl presented for routine closure of her tracheostomy site. She was intubated easily for the procedure, and the wound was closed with a drain in place. In recovery, the mother noticed fullness in the patient's submandibular region, and on examination, the girl had subcutaneous emphysema in the neck bilaterally. She returned to the operating room for exploration, and air was released from the surgical site. The wound was again closed with a drain in place, and the patient was extubated uneventfully. After arriving to the pediatric intensive care unit for monitoring, the patient acutely developed respiratory distress and was found to have pneumomediastinum and pneumothorax and was emergently intubated. She was observed closely, and the following day, the pneumothorax improved, and she successfully extubated without further complication.

Airway response to sirolimus therapy for the treatment of complex pediatric lymphatic malformations.

Head and neck lymphatic malformations can create airway management challenges requiring tracheotomy. Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), may inhibit growth of lymphatic malformations. We describe two patients born with large lymphatic malformations with improved airway symptoms following sirolimus therapy. Patient #1 underwent tracheotomy and multi-modal therapy including sirolimus with reduction in airway involvement but regrowth after discontinuation of sirolimus. Patient #2 also experienced a significant response to sirolimus allowing for extubation and discharge without tracheotomy. Early initiation of sirolimus therapy should be considered as a means to avoid tracheotomy in complex head and neck lymphatic malformations.

MRI phenotypes of localized intravascular coagulopathy in venous malformations.

BACKGROUND: The incidence of localized intravascular coagulopathy (LIC) in venous malformations varies with lesion size and location, as well as the presence of palpable phleboliths. The development of LIC can cause pain and hemorrhage and can progress to disseminated intravascular coagulopathy (DIC) and thromboembolic disease resulting in death in some cases. Early recognition of LIC can relieve symptoms and prevent progression to life-threatening complications. OBJECTIVE: The aim of this work was to identify MRI features of venous malformation associated with LIC. We hypothesized that venous malformations with larger capacitance, slower flow and less physiological compression (greater stasis) were more likely to be associated with LIC. MATERIALS AND METHODS: In this HIPAA-compliant and IRB-approved study, we retrospectively reviewed clinical records and MRI for consecutive patients undergoing evaluation of venous malformations at our multidisciplinary Birthmarks and Vascular Anomalies Center between 2003 and 2013. Inclusion required consensus diagnosis of venous malformation and availability of laboratory data and MRI; patients on anticoagulation or those previously undergoing surgical or endovascular treatment were excluded. LIC was diagnosed when D-dimer exceeded 1,000 ng/mL and/or fibrinogen was less than 200 mg/dL. Two board-certified radiologists assessed the following MRI features for each lesion: morphology (spongiform vs. phlebectatic), presence of phleboliths, size, location (truncal vs. extremity), and tissue type(s) involved (subcutis, muscle, bone and viscera). Univariate logistic regression analyses were used to test associations between LIC and MRI findings, and stepwise regression was applied to assess the significance of the individual imaging predictors. RESULTS: Seventy patients, 37 with LIC, met inclusion criteria during the 10-year study period (age: 14.5 +/- 13.6 years [mean +/- standard deviation]; 30 male, 40 female). Both elevated D-dimer and low fibrinogen were associated with the presence of phleboliths, larger lesion sizes and visceral involvement on MRI (all P < 0.05). In stepwise regressions, lesion size (P < 0.001), the presence of phleboliths (P = 0.005) and lesion morphology (P = 0.006) were all significant predictors of LIC. CONCLUSION: LIC is associated with larger lesion size, visualized phleboliths, truncal location and spongiform morphology on MRI in venous malformations, suggesting that lesions with larger capacitance, slower flow and less physiological compression are more likely to be associated with coagulopathy.

Effectiveness and costs of sialendoscopy in pediatric patients with salivary gland disorders.

OBJECTIVES/HYPOTHESIS: This study aimed to characterize the common salivary gland disorders presenting in the pediatric population and to describe the diagnostic and therapeutic outcomes of sialendoscopy in this population. STUDY DESIGN: Retrospective observational study in a tertiary care pediatric medical center. METHODS: Medical records review of patients under 18 years of age who presented to pediatric otolaryngology with symptoms related to a salivary gland disorder from 2002 to 2014. RESULTS: Fifty patients were identified with an average age of 7.5 years at presentation. Eighty percent (40/50) of cases were diagnosed with juvenile recurrent parotitis (JRP), and 15 underwent sialendoscopy. The other 10 (20%) patients presented with sialolithiasis. These patients had a higher average age at presentation (12.4 vs. 6.3 years), and the majority were successfully removed with sialendoscopic techniques. Juvenile recurrent parotitis patients who underwent sialendoscopy had significantly higher costs of care during the period of observation compared to those who did not have a procedure, without a statistically significant difference in outcomes. CONCLUSIONS: Sialendoscopy is an effective tool for stone retrieval in pediatric sialolithiasis. Juvenile recurrent parotitis patients who underwent sialendoscopy had outcomes similar to those selected for conservative therapy, calling into question whether the substantially higher care costs can be justified. Further prospective studies addressing cost-effectiveness will help define the role of sialendoscopy in JRP. LEVEL OF EVIDENCE: 4.

Infantile hemangiomas of the head and neck.

Infantile hemangiomas (IHs) are benign vascular tumors. Clinical history and physical examination are the most important factors for diagnosis, with most IHs having a typical presentation. Treatment is required for some IHs that cause significant cosmetic deformity or functional compromise. Propranolol is the first-line treatment of most IHs. Ongoing research is increasing our understanding of the pathophysiology of these tumors and should help to identify future potential therapeutic targets.

Clinical consensus statement: appropriate use of computed tomography for paranasal sinus disease.

OBJECTIVE: To develop a consensus statement on the appropriate use of computed tomography (CT) for paranasal sinus disease. SUBJECTS AND METHODS: A modified Delphi method was used to refine expert opinion and reach consensus by the panel. RESULTS: After 3 full Delphi rounds, 33 items reached consensus and 16 statements were dropped because of not reaching consensus or redundancy. The statements that reached consensus were grouped into 4 categories: pediatric sinusitis, medical management, surgical planning, and complication of sinusitis or sinonasal tumor. The panel unanimously agreed with 13 of the 33 statements. In addition, at least 75% of the panel strongly agreed with 14 of 33 statements across all of the categories. CONCLUSIONS: For children, careful consideration should be taken when performing CT imaging but is needed in the setting of treatment failures and complications, either of the pathological process itself or as a result of iatrogenic (surgical) complications. For adults, imaging is necessary in surgical planning, for treatment of medical and surgical complications, and in all aspects of the complete management of patients with sinonasal and skull base pathology.

Airway hemangiomas in PHACE syndrome.

OBJECTIVES/HYPOTHESIS: To describe the clinical presentation and airway characteristics of infants with airway hemangiomas and concomitant PHACE syndrome and to determine the prevalence of airway hemangiomas in PHACE subjects at our institution. STUDY DESIGN: Case series. METHODS: Retrospective review including clinical presentation, airway findings, treatment measures, and outcomes. RESULTS: A total of 23 subjects were diagnosed with definite PHACE at our institution between September 1, 2005 and September 1, 2011. Twelve (52%) of these subjects had documented airway hemangiomas, six of whom were diagnosed and treated at our institution. All six subjects underwent direct laryngoscopy and bronchoscopy by a pediatric otolaryngologist. Five (83%) subjects had subglottic hemangioma. Three subjects (50%) had additional hemangioma within the airway located on the epiglottis, vocal folds, posterior pharyngeal wall, and tracheal wall. Five subjects (83%) were treated with propranolol, five (83%) were treated with systemic steroids, and one subject received vincristine. One subject required laser ablation of subglottic hemangioma and tracheotomy. All subjects were airway symptom free at last follow-up (average, 35 months; range, 13-76 months). CONCLUSIONS: Airway hemangiomas can be a life-threatening complication of PHACE syndrome. At our institution, 52% of all PHACE subjects were diagnosed with airway hemangiomas. Early detection of airway involvement is paramount. Given the high rates of airway hemangiomas, we recommend performing direct laryngoscopy and bronchoscopy in all PHACE patients with respiratory symptoms. We recommend having a low threshold for airway evaluation in asymptomatic PHACE patients, especially those who will not be otherwise started on propranolol.

Drug-induced sleep endoscopy in persistent pediatric sleep-disordered breathing after adenotonsillectomy.

OBJECTIVES: To demonstrate the feasibility of drug-induced sleep endoscopy (DISE) in the pediatric population and to examine DISE results in children with persistent sleep-disordered breathing (SDB) after tonsillectomy and adenoidectomy (T&A). DESIGN: Retrospective case series with medical chart review. SETTING: Tertiary pediatric medical center. PATIENTS: Thirteen pediatric subjects with persistent SDB after T&A are included in the study. INTERVENTION: Drug-induced sleep endoscopy was per-formed on all patients with documentation of all sites of persistent airway obstruction. RESULTS: Multilevel upper-airway obstruction was identified in the majority of patients, most commonly related to tongue base obstruction, adenoid regrowth, and/or inferior turbinate hypertrophy. There were no differences among the 4 subgroups. CONCLUSIONS: Findings from DISE suggest that multiple factors contribute to airway obstruction in persistent SDB after T&A. Further research can address the extent to which directed surgical treatment can improve outcomes in these patients.

Comparison of imaging modalities in pediatric thyroglossal duct cysts.

OBJECTIVES/HYPOTHESIS: To determine and compare the accuracy of different imaging modalities including ultrasound (US), magnetic resonance imaging (MRI), and computed tomography (CT) in the diagnosis of thyroglossal duct cysts (TGDC) in children. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review was performed on patients under the age of 18 years who had undergone surgical excision of midline neck masses between January 2002 and June 2011. All patients had preoperative imaging. Data including age at surgery, preoperative imaging results, and postoperative pathology results were recorded. Preoperative imaging diagnoses were then compared to postoperative pathologic diagnoses. Diagnostic test statistics were performed. RESULTS: A total of 44 patients met the study criteria. There were 15 patients who underwent more than one modality of imaging study. US had a sensitivity of 75% in diagnosis of TGDC. MRI sensitivity was 60% and CT was 82%. None of the tests had high specificity for TGDC; US was the highest at 80%. All three modalities had positive predictive values higher than 90%. US had the highest positive likelihood ratio (3.8), although the 95% confidence interval was not statistically significant. CONCLUSIONS: In a comparison of the three most commonly used imaging modalities for pediatric TGDC, US was the preferred exam given its comparable accuracy, ease of administration, and lower cost. In addition, the added risks of general anesthesia with MRI and ionizing radiation with CT are not justified in this setting given their equivalent or inferior performance when compared to US in this cohort.