Impact of modern recreational conveyances on rates of pediatric craniofacial fractures.

Objective: Trauma remains the leading cause of death for children over a year old. Motorized recreational conveyances (RCs) adds another potential cause of pediatric trauma. This study aims to determine the impact of adding electric motors to RCs on the severity and frequency of pediatric injuries and craniofacial fractures. Methods: Pediatric trauma information was obtained from the National Electronic Injury Surveillance System (NEISS) database between 2012 and 2021. Demographics, injury cause, diagnoses, and incident narrative were collected. Bivariate and multivariate regression analyses were used to determine injury factors associated with serious injuries. Results: One million five hundred ninety-six thousand five hundred fifty-nine encounters were examined; 113,905 (7.1%) were related to pediatric RCs and 5354 (5.4%) of those involved RCs with electric motors. 14.3% of injuries were related to scooters, 18.6% to skateboards, 54.2% to bicycles, and 12.9% to other RCs. There were significant differences in age, sex, race, helmet use, serious injuries, and craniofacial fractures between RC modalities. RC users were more likely to develop facial fractures (OR 2.12; 95%CI 2.01, 2.23; p < .001) and be involved in serious injuries (OR 1.42; 95%CI 1.38, 1.46; p < .001). Compared to their self-propelled counterparts, motorized scooters (OR 2.24; 95%CI 1.86, 2.69; p < .001) but not motorized skateboards (OR 1.01; 95%CI 0.88, 1.17; p = 0.88) were more likely to cause serious injuries. Helmet use was associated with fewer serious injuries (OR 0.5; 95%CI 0.46, 0.54; p < .001), facial fractures (OR 0.48; 95%CI 0.41, 0.55; p < .001), and skull fractures (OR 0.13; 95%CI 0.09, 0.17; p < .001). Conclusions: The addition of electric motors to RCs significantly increases the risk of pediatric craniofacial fractures and serious injuries. Level of Evidence: 3.

The A2ml1-Knockout mouse as an animal model for non-syndromic otitis media.

BACKGROUND: Inflammation and infection of the middle ear, known as otitis media (OM), is a leading cause of hearing loss and the most frequently diagnosed disease in children worldwide. Traditionally, mouse models for OM rely on inducing acute infection through inoculation of the middle ear, e.g. with the human otopathogen non-typeable Haemophilus influenzae (NTHi), and with very few genetic models with spontaneous or chronic OM. A2ML1 variants, including loss-of-function variants, were associated with susceptibility to OM in humans, but no animal model has been reported for A2ml1-related OM. Here, we report our middle ear findings in a mouse line with a CRISPR-induced knockout (KO) of A2ml1. METHODS: Mice were X-rayed prior to harvest to determine if there are craniofacial or skeletal abnormalities. Tissue from mouse middle ears, as well as other upper respiratory mucosal tissues, were harvested. The harvested middle ear bullae were examined under microscope and submitted for histologic preparation to study phenotypic indications of OM. RNA samples isolated from middle ear tissue were assayed for expression of genes correlated with A2ML1 expression in humans. RESULTS: Data from a total of 119 mice (35 wildtype, 40 heterozygous, 44 homozygous) are presented here, with each analyses being performed on subsets of these mice. There were no significant craniofacial differences by genotype (n = 22). Findings in mice with the A2ml1-KO indicated an increased incidence of OM (n=29; odds ratio = 11; CI: 1.1, 573.6; Fisher exact two-sided p = 0.02) with tympanic membrane perforations or thickening, as well as cases of middle ear effusion, inflammatory cells, or fluid from histologic sections. Dsp was upregulated in the middle ear tissues of homozygous mice (Wilcoxon test p = 0.001). CONCLUSION: Thus far, our results in this A2ml1-KO mouse line indicate spontaneous occurrence of OM and dysregulation of Dsp in the middle ear as a potential disease mechanism for A2ml1-related OM.

Decrease in Rates of Hearing Loss From Pediatric Bacterial Meningitis Over Time: A Database Review.

OBJECTIVES: Bacterial meningitis is a leading cause of acquired sensorineural hearing loss (SNHL). Treatment and prevention of bacterial meningitis have improved over time, but rates of neurologic complications have not been recently studied. The objective here is to present an updated population-based review of hearing loss as a sequela of bacterial meningitis. METHODS: A retrospective cohort study was conducted between 2010 and 2022 of children discharged with bacterial meningitis, using the Pediatric Health Information System's (PHIS) database. Rates of hearing loss and mortality were evaluated over time. RESULTS: A total of 6138 children with a primary diagnosis of bacterial meningitis were identified (3520 male [57.3%], mean age 5.8 months [2.0, 61.2]). Of these, 277 (4.51%) were diagnosed with hearing loss. Children with hearing loss were significantly older (23.6 vs. 5.3 months, p < 0.01), but differences in gender, race, or ethnicity had no association with hearing loss. Streptococcus pneumoniae, Hemophilus influenzae, and Neisseria meningiditis were associated with significantly higher rates of hearing loss than other etiologies (p < 0.01). Children with hearing loss had a higher rate of receiving dexamethasone than children without hearing loss. Overall mortality rate was 2.1%. Hearing loss and mortality demonstrated significant decreases over the study period. CONCLUSION: Hearing loss remains a common sequela of bacterial meningitis despite widespread uptake of vaccines for preventing S. pneumoniae, H. influenzae, and N. meningitidis. Dexamethasone was not associated with decreased rates of hearing loss in this cohort. From 2010 to 2022, there was a significant decrease in overall rates of mortality and hearing loss for children with bacterial meningitis. LEVEL OF EVIDENCE: 3: retrospective case-control series Laryngoscope, 134:3820-3825, 2024.

Otitis Media in Children with Down Syndrome Is Associated with Shifts in the Nasopharyngeal and Middle Ear Microbiotas.

Background: Otitis media (OM) is defined as middle ear (ME) inflammation that is usually due to infection. Globally, OM is a leading cause of hearing loss and is the most frequently diagnosed disease in young children. For OM, pediatric patients with Down syndrome (DS) demonstrate higher incidence rates, greater severity, and poorer outcomes. However, to date, no studies have investigated the bacterial profiles of children with DS and OM. Method: We aimed to determine if there are differences in composition of bacterial profiles or the relative abundance of individual taxa within the ME and nasopharyngeal (NP) microbiotas of pediatric OM patients with DS (n = 11) compared with those without DS (n = 84). We sequenced the 16S rRNA genes and analyzed the sequence data for diversity indices and relative abundance of individual taxa. Results: Individuals with DS demonstrated increased biodiversity in their ME and NP microbiotas. In children with OM, DS was associated with increased biodiversity and higher relative abundance of specific taxa in the ME. Conclusion: Our findings suggest that dysbioses in the NP of DS children contributes to their increased susceptibility to OM compared with controls. These findings suggest that DS influences regulation of the mucosal microbiota and contributes to OM pathology.

Patient Chief Complaint and Otolaryngology Referral Rationale: Discordance and Opportunities for Quality Improvement.

OBJECTIVE: As medical systems focus on patient satisfaction as an important care outcome, specialty clinics are tasked with continued improvement of patients' experience. When patient expectations for a consultation differ from that of the specialty provider, dissatisfaction with the experience can occur. One source of differing expectations is discordance between the patient's chief complaint and the clinical rationale for the consultation as requested by the referring provider. We sought to better understand when this discordance occurs, as well as factors contributing to this disorientation of patient and provider expectations in a safety net otolaryngology practice. METHODS: A retrospective observational study was performed and records were examined from new patient consultations. Patient questionnaires, including self-reported chief concerns, were compared with the electronic referral documentation. A difference between the patient's Chief Complaint (CC) and Referral Reason (RR) was defined as CC-RR Discordance. Medical records, pre-consultation patient communication, and scheduling data were also reviewed to evaluate contributing factors. RESULTS: Of the 1155 consultations examined, 952 were included in the analysis. A CC-RR Discordance was found in 175 (18.4%) of new-patient encounters, including 117 (12.3%) that were unable to articulate a CC (unsure of the reason for the appointment), and 58 (6.1%) that stated a CC that was different than the RR. The rate of CC-RR Discordance was higher in patients with female sex (P < .05), older age (P < .001), and longer time intervals between referral and appointment (P < .05). Lack of communication with the patient (instructions or referral notification) by the referring provider was not associated with CC-RR Discordance. CONCLUSIONS: Discordance between patient CC and the rationale for a consultation is common in this safety-net otolaryngology practice and may be an important source of patient dissatisfaction. Future opportunities for quality improvement include pre-consultation communication between the specialist and the patient and reducing time intervals between referral and appointment.

The role of CDHR3 in susceptibility to otitis media.

Otitis media (OM) is common in young children and can cause hearing loss and speech, language, and developmental delays. OM has high heritability; however, little is known about OM-related molecular and genetic processes. CDHR3 was previously identified as a locus for OM susceptibility, but to date, studies have focused on how the CDHR3 p.Cys529Tyr variant increases epithelial binding of rhinovirus-C and risk for lung or sinus pathology. In order to further delineate a role for CDHR3 in OM, we performed the following: exome sequencing using DNA samples from OM-affected individuals from 257 multi-ethnic families; Sanger sequencing, logistic regression and transmission disequilibrium tests for 407 US trios or probands with OM; 16S rRNA sequencing and analysis for middle ear and nasopharyngeal samples; and single-cell RNA sequencing and differential expression analyses for mouse middle ear. From exome sequence data, we identified a novel pathogenic CDHR3 splice variant that co-segregates with OM in US and Finnish families. Additionally, a frameshift and six missense rare or low-frequency variants were identified in Finnish probands. In US probands, the CDHR3 p.Cys529Tyr variant was associated with the absence of middle ear fluid at surgery and also with increased relative abundance of Lysobacter in the nasopharynx and Streptomyces in the middle ear. Consistent with published data on airway epithelial cells and our RNA-sequence data from human middle ear tissues, Cdhr3 expression is restricted to ciliated epithelial cells of the middle ear and is downregulated after acute OM. Overall, these findings suggest a critical role for CDHR3 in OM susceptibility. KEY MESSAGES: • Novel rare or low-frequency CDHR3 variants putatively confer risk for otitis media. • Pathogenic variant CDHR3 c.1653 + 3G > A was found in nine families with otitis media. • CDHR3 p.Cys529Tyr was associated with lack of effusion and bacterial otopathogens. • Cdhr3 expression was limited to ciliated epithelial cells in mouse middle ear. • Cdhr3 was downregulated 3 h after infection of mouse middle ear.

Elimination of pain improves specificity of clinical diagnostic criteria for adult chronic rhinosinusitis.

OBJECTIVE: Determine whether the elimination of pain improves accuracy of clinical diagnostic criteria for adult chronic rhinosinusitis. STUDY DESIGN: Retrospective cohort study. METHODS: History, symptoms, nasal endoscopy, and computed tomography (CT) results were analyzed for 1,186 adults referred to an academic otolaryngology clinic with presumptive diagnosis of chronic rhinosinusitis. Clinical diagnosis was rendered using the 1997 Rhinosinusitis Taskforce (RSTF) Guidelines and a modified version eliminating facial pain, ear pain, dental pain, and headache. RESULTS: Four hundred seventy-nine subjects (40%) met inclusion criteria. Among subjects positive by RSTF guidelines, 45% lacked objective evidence of sinonasal inflammation by CT, 48% by endoscopy, and 34% by either modality. Applying modified RSTF diagnostic criteria, 39% lacked sinonasal inflammation by CT, 38% by endoscopy, and 24% by either modality. Using either abnormal CT or endoscopy as the reference standard, modified diagnostic criteria yielded a statistically significant increase in specificity from 37.1% to 65.1%, with a nonsignificant decrease in sensitivity from 79.2% to 70.3%. Analysis of comorbidities revealed temporomandibular joint disorder, chronic cervical pain, depression/anxiety, and psychiatric medication use to be negatively associated with objective inflammation on CT or endoscopy. CONCLUSION: Clinical diagnostic criteria overestimate the prevalence of chronic rhinosinusitis. Removing facial pain, ear pain, dental pain, and headache increased specificity without a concordant loss in sensitivity. Given the high prevalence of sinusitis, improved clinical diagnostic criteria may assist primary care providers in more accurately predicting the presence of inflammation, thereby reducing inappropriate antibiotic use or delayed referral for evaluation of primary headache syndromes. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1011-1016, 2017.

Neonatal Soft Tissue Reconstruction Using a Bioengineered Skin Substitute.

Total parenteral nutrition (TPN) can be a lifesaving intervention for premature neonates and it is often delivered through peripheral access in this unique population. However, extravasation and tissue damage can result. Current literature lacks strong evidence regarding the treatment and reconstruction of such injuries in this age group. The authors present a patient with a 30-week gestational age premature newborn whom suffered an extravasation injury with peripherally administered TPN leading to full thickness skin and soft tissue necrosis of the dorsum of the right hand. This was serially debrided and ultimately repaired using Apligraf (Graftskin, Living Skin Equivalent, LSE; Organogenesis Inc, Canton, MA), which rapidly facilitated secondary healing.

Subcutaneous emphysema after vigorous sneezing in the setting of acute frontal sinusitis.

INTRODUCTION: Subcutaneous emphysema [SCE] can develop due to traumatic, infectious, and spontaneous causes and usually localizes to the periorbital space. CASE: We present a case of an 18-year-old male with an 8-day history of migraine-like headaches followed by the acute onset of frontofacial swelling after vigorous sneezing. Radiologic and physical exam findings supported a diagnosis of frontofacial SCE in the setting of frontal sinusitis. DISCUSSION: A sneeze, although usually benign, causes a significant increase in intranasal pressure. When coupled with a history significant for facial trauma or rhinosinusitis, this rise in pressure can be sufficient to cause fracturing of the bone overlying a paranasal sinus, leading to the formation of SCE.

Psychogenic nonepileptic seizures and chronic pain: a retrospective case-controlled study.

PURPOSE: Psychogenic nonepileptic seizures (PNES) can be challenging to diagnose, but certain clinical features can help to distinguish PNES from epileptic seizures. The purpose of this study is to assess chronic pain and prescribed pain medication use in PNES patients. METHODS: A case-controlled, retrospective analysis was performed examining pain medication use in 85 PNES patients versus an active control group of 85 patients with idiopathic generalized epilepsy (IGE). RESULTS: Chronic pain was more frequent among PNES patients (N=40) than active controls (N=10) (p<0.0001). Reported use of prescription pain medication was higher among PNES patients (N=20) versus active controls (N=6) (p=0.0048). The Positive Predictive Value of prescription pain medications for PNES patients was 76.9%. Opioid use in the PNES population was higher compared with active controls (p=0.0096). When excluding patients with a dual diagnosis of PNES and epilepsy from the latter two analyses and comparing these results to those that included this patient population, no statistically significant difference in results was found. CONCLUSIONS: Patients with PNES are more likely than those with IGE to report chronic pain disorders. A history of chronic pain and opioid use among patients with seizures raises the possibility of PNES. Among patients with PNES and chronic pain, a psychogenic etiology for pain and non-opiate pain management strategies should be considered.

Aripiprazole in children and adolescents with Tourette's disorder: an open-label safety and tolerability study.

OBJECTIVE: The aim of this study was to conduct a prospective safety and tolerability study of aripiprazole for the treatment of tics in children and adolescents with Tourette's disorder (TD). METHOD: Eleven subjects (10 males) with TD (age 9-19 years, mean 13.36, standard deviation [SD] 3.33) who did not respond or were unable to tolerate previous tic medication were treated with aripiprazole in an open-label, flexible-dosing study over 10 weeks. Tic severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impressions Scale for tics (CGI-Tics) at baseline and at follow-up. RESULTS: The mean (+/-SD) daily dose for aripiprazole was 4.5 +/- 3.0 mg. Mean (+/-SD) YGTSS Global Severity scores reduced from 61.82 +/- 13.49 at baseline to 33.73 +/- 15.18 at end point; mean YGTSS total tic scores reduced from 28.18 +/- 7.74 at baseline to 16.73 +/- 7.54 at end point. Mean (+/-SD) CGI-Tic severity scores reduced from 4.45 +/- 0.52 (moderate-marked) at baseline to 3.18 +/- 0.60 (mild) at end point. On the CGI-Tic improvement scale, 10 (91%) subjects achieved 1 ("very much improved") or 2 ("much improved") at end point. Most common adverse effects included appetite increase and weight gain in 5 subjects, mild extrapyramidal effects in 7 subjects, and headaches and tiredness/fatigue in 7 subjects; 1 subject experienced akathisia and muscle cramps. CONCLUSION: Aripiprazole appears to be a safe and tolerable treatment in children and adolescents with TD that appears to reduce tics; it should be further investigated as a treatment option in controlled trials.

Motor worsening and tardive dyskinesia with aripiprazole in Lewy body dementia.

Aripiprazole (APZ) is a novel antipsychotic agent which does not block dopamine (DA) receptors but is rather a partial DA agonist. Thus, it has been proposed that APZ may not induce tardive dyskinesia (TD), a disfiguring and sometimes disabling and irreversible side effect of neuroleptics. Our patient had Lewy body dementia (LBD) and developed severe worsening of parkinsonism over 1 month of APZ treatment. Within days of discontinuation of APZ dramatic orobuccal dyskinesias emerged. Treatment emergent worsening of parkinsonism improved but orobuccal dyskinesias persisted unchanged until his death 8 months later. Others have reported severe extrapyramidal reactions including neuroleptic malignant syndrome and TD with APZ. APZ has been suggested as a treatment for TD but treatment benefit may reflect "masked" dyskinesia. We conclude that, despite an attractive in vitro profile and promising animal data, APZ can induce serious extrapyramidal side effects, including TD.

Use of a chemically modified antisense oligonucleotide library to identify and validate Eg5 (kinesin-like 1) as a target for antineoplastic drug development.

A library of 2'-methoxyethyl-modified antisense oligonucleotides (2'MOE ASO) targeting 1,510 different genes has been developed, validated, and used to identify cell cycle regulatory genes. The most effective molecular target identified was Eg5 (kinesin-like-1), which when inhibited gave the largest increase in 4N DNA in various tumor cells. The Eg5 ASO reduced Eg5 levels, inhibited proliferation, increased apoptosis, and altered the expression of other cell cycle proteins, including survivin and Aurora-A. To examine the therapeutic utility of the Eg5 ASO, the compound was also evaluated in xenograft models. Treatment with Eg5 ASO produced a statistically significant reduction of tumor growth, reduction in Eg5 expression in the tumors, and changes in histone phosphorylation, consistent with a loss of Eg5 protein expression. These data show, for the first time, the utility of a 2'MOE ASO library for high-throughput cell culture-based functional assays and suggest that an Eg5 ASO also has potential in a therapeutic strategy.