Characterizing Adverse Events of Biologic Treatment of T2 Disease: A Disproportionality Analysis of the FDA Adverse Event Reporting System.

INTRODUCTION: Over the last 3 years, the FDA has approved dupilumab, omalizumab, and mepolizumab for the treatment of CRSwNP; however, adverse events of these biologics have not been described in post-marketing surveillance trials. By utilizing the FDA Adverse Event Reporting System (FAERS), this study describes and compares biologic-associated adverse events in T2 disease. METHODS: This case-non-case study assessed disproportionate reporting rates using reporting odds ratios (RORs). RORs and p values for biologic-associated AEs were categorized and compared among dupilumab, omalizumab, and mepolizumab. This analysis included AEs associated with all treatment indications. Relative AE rates and outcomes were calculated. RESULTS: There were a total of 112,560, 24,428, and 18,741 unique AE reports associated with dupilumab, omalizumab, and mepolizumab, respectively. Omalizumab had the strongest association with anaphylaxis (ROR = 20.80, 95% confidence interval [CI]: 18.58, 23.29). Dupilumab had large relative proportions and positive signals in the ophthalmologic category (7.76%, ROR = 6.20, 95% CI: 6.06, 6.35), such as with blurry vision (ROR = 3.80, CI: 3.52, 4.12) and visual impairment (ROR = 1.98, CI: 1.80, 2.19). Dupilumab was the only biologic associated with injection-site reactions (7.98%, ROR = 8.17, 95% CI: 7.98, 8.37). DISCUSSION/CONCLUSION: This is the first large-scale comparative analysis of the AE profiles of dupilumab, omalizumab, and mepolizumab. Our data suggest possible relations between dupilumab and ophthalmologic and injection-site AEs. Omalizumab was the only biologic with a positive anaphylaxis signal. This FAERS investigation suggests important AE differences among these biologics.

Hearing Loss Is Associated with Increased Variability in Double Support Period in the Elderly.

Hearing loss is a disabling condition that increases with age and has been linked to difficulties in walking and increased risk of falls. The purpose of this study is to investigate changes in gait parameters associated with hearing loss in a group of older adults aged 60 or greater. Custom-engineered footwear was used to collect spatiotemporal gait data in an outpatient clinical setting. Multivariable linear regression was used to determine the relationship between spatiotemporal gait parameters and high and low frequency hearing thresholds of the poorer hearing ear, the left ear, and the right ear, respectively, adjusting for age, sex, race/ethnicity, and the Dizziness Handicap Inventory-Screening version score. Worsening high and low frequency hearing thresholds were associated with increased variability in double support period. Effects persisted after adjusting for the effects of age and perceived vestibular disability and were greater for increases in hearing thresholds for the right ear compared to the left ear. These findings illustrate the importance of auditory feedback for balance and coordination and may suggest a right ear advantage for the influence of auditory feedback on gait.

The ERM family member Merlin is required for endometrial gland morphogenesis.

Disruption of endometrial gland formation or function can cause female infertility. Formation of endometrial glands via tubulogenesis of luminal epithelial cells requires the establishment and maintenance of cell polarity and cell adhesion. The FERM domain-containing protein Merlin coordinates epithelial cell polarity and cell adhesion and is critical for epithelial tissue function in the skin and kidney. We now demonstrate a requirement for Merlin in endometrial gland development. Conditional deletion of Merlin in the endometrium results in female infertility caused by the absence of gland formation. Interestingly, we observed glandular epithelial markers within discrete groups of cells in the Merlin-deficient luminal epithelium. Wnt signaling, a pathway necessary for endometrial gland development is maintained in Merlin-deficient endometrium, suggesting the glandular fate program is active. Instead, we observe increased levels of apical actin and markers indicative of high membrane tension on the basal surface of the Merlin-deficient luminal epithelium. These findings suggest that the structural integrity of the luminal epithelium during gland formation is required for appropriate endometrial tubulogenesis and tissue function. Moreover, our work implicates Merlin-dependent regulation of mechanical tension in the proper formation of endometrial gland architecture and function.

Primary ciliary dyskinesia: An update on contemporary diagnosis.

KEY POINTS: Primary ciliary dyskinesia (PCD) is a complex diagnosis without a universal diagnostic test Clinicians must have some skepticism of historic diagnoses of PCD Clinicians should consider a diagnosis of PCD in patients with recalcitrant disease.

Which intranasal corticosteroids can be used in patients on highly active antiretroviral therapy or pre-exposure prophylactic?

KEY POINTS: All intranasal corticosteroid spray formulations are safe to use in patients on pre-exposure prophylaxis. Beclomethasone nasal spray can be used safely with all HAART and PrEP regimens.

"Left on their own": Left-handedness among rhinologists and otolaryngology trainees.

KEY POINTS: Left-hand-dominant (LHD) respondents reported higher rates of training difficulties because of handedness differences. LHD respondents cited particular difficulty with functional endoscopic sinus surgery. Both LHD and right-hand-dominant respondents perceived a need for laterality-specific training during residency.

Cochlear Implantation for Unilateral and Asymmetric Hearing Loss: Long-Term Subjective Benefit.

OBJECTIVES: Assess the long-term patterns of perceived tinnitus severity and subjective benefit for adult cochlear implant (CI) users with asymmetric or unilateral hearing loss (AHL or UHL). METHODS: Forty adults underwent cochlear implantation as part of a prospective clinical trial assessing the outcomes of CI use in cases of AHL (n = 20) and UHL (n = 20). Subjective measures included the Tinnitus Handicap Inventory (THI), the Speech, Spatial, & Qualities of Hearing Scale (SSQ), and the Abbreviated Profile of Hearing Aid Benefit (APHAB). Responses were obtained preoperatively and at routine intervals out to 5 years post-activation. RESULTS: For subjective benefit, participants with AHL and UHL reported a significant improvement as compared to preoperative abilities, which was maintained with long-term CI use. For perceived tinnitus severity, participants with AHL and UHL reported a significant reduction with CI use as compared to preoperative perceptions. The perceived tinnitus severity significantly differed for the AHL and UHL cohorts over time. This pattern of results is likely influenced by the worse perceived severity levels for the UHL cohort preoperatively and the fluctuating perceived severity levels for some participants in the AHL cohort post-activation. CONCLUSION: Adults with AHL and UHL report an early, significant reduction in perceived tinnitus severity and improvement in quality of life with CI use that is generally maintained with long-term device use. Questionnaires such as the THI, SSQ, and APHAB may contribute to a more holistic assessment of the benefits of cochlear implantation in this population. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:2792-2797, 2023.

Outcomes in Pediatric Endoscopic Skull Base Surgery: A Systematic Review.

Objectives The frequency of endoscopic skull base surgery in pediatric patients is increasing. This study aims to systematically review the literature for endoscopic skull base surgery outcomes in children/adolescents aged 0 to 18 years. Design A systematic review of the literature was performed in PubMed and SCOPUS databases querying studies from 2000 to 2020 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Final inclusion criteria included: case series with more than 10 patients with pediatric patients aged ≤18 years, endoscopic or endoscopic-assisted skull base surgery, and outcomes reported. Setting This study was conducted at a tertiary care medical center. Participants Children/adolescents aged 0 to 18 years who underwent endoscopic skull base surgery were participated in this study. Main Outcome Measures Patient demographics, pathology, reconstructive technique, intraoperative findings, intraoperative, and postoperative surgical complications were measured through this study. Results Systematic literature search yielded 287 publications. Of these, 12 studies discussing a total of 399 patients aged 0 to 18 years met inclusion criteria for final analysis. Seven of the 12 studies discussed a single pathology. The most common pathology was a skull base defect causing cerebrospinal fluid (CSF) leak. The majority of skull base repairs were made with free tissue grafts. The most common postoperative complication was CSF leak ( n = 40). Twelve cases of meningitis occurred postoperatively with two of these episodes resulting in death. Conclusion Endoscopic skull base surgery has been performed recently in the pediatric population in a variety of disease states. Inconsistent individual-level data and reporting standards are present in existing studies posing challenges for comparative analysis. Standardized reporting will aid future reviews and meta-analysis for rare skull base pathology.

Granulomatosis With Polyangiitis Presenting as an Infratemporal Fossa Mass.

Granulomatosis with polyangiitis is a rare autoimmune disease that affects small to medium-sized blood vessels throughout the body. Here, we present a case of an infratemporal mass that was the result of granulomatosis with polyangiitis. A 51-year-old male presented to the emergency department due to right cheek and facial pain that he had been experiencing for 2 to 3 months. An MRI revealed a mass within the right infratemporal and pterygopalatine fossae extending into the inferior right orbital fissure along the maxillary division of the trigeminal nerve (V2) and the vidian nerve causing concern for malignancy. Histology from an endoscopic biopsy demonstrated multiple arteries with luminal obliteration with non-necrotizing granulomas. The patient was started on steroids and immunosuppressive therapy, which improved his symptoms and decreased the size of the residual mass. This case illustrates the need for laboratory testing, imaging, and biopsy of the involved tissue in cases where GPA is suspected to prevent treatment delays that could lead to the destruction of vital organs.

Recent Trends in Female and Racial/Ethnic Minority Groups in U.S. Otolaryngology Residency Programs.

OBJECTIVES: Our objectives were to analyze the recent trends in applicants of otolaryngology-head and neck surgery (Oto-HNS) residency programs, including evolutions in sex and racial/ethnic distribution within the applicant pool and subsequent residency cohort. METHODS: Retrospective database and literature review. Data regarding applicants to Oto-HNS programs as well as Oto-HNS residents in the United States from 2008 to 2017 were analyzed from the Electronic Residency Application Service, National Resident Matching Program, and Journal of the American Medical Association. RESULTS: Between 2008 and 2018, the number of Oto-HNS residency programs and residency positions offered increased from 105 to 112 and from 273 to 315, respectively. There was no statistically significant difference between applicant sex in 2008 to 2012 compared to 2013 to 2018 (P > .05), but significantly more females made up the residency workforce from 2013 to 2018 compared to 2008 to 2012 (P < .001). However, the percentage increase in female residents from 2008 to 2017 was only 6.1% (29.8% to 35.9%). No statistically significant difference was present between applicant race in 2008 to 2012 compared to 2013 to 2018 (P > .05), but significantly more minority residents made up the residency workforce from 2013 to 2018 compared to 2008 to 2012 (P < .0001). However, the percentage increase in minority residents from 2008 to 2017 was only 4.9% (35.1% to 40%). CONCLUSION: Women and minority racial and ethnic groups continue to be underrepresented among Oto-HNS applicants. However, the presence of these groups among current residents has increased. Understanding and tracking these national trends yearly is critical for training a diverse future otolaryngology workforce. LEVEL OF EVIDENCE: VI Laryngoscope, 131:277-281, 2021.

Influence of Cochlear Implant Use on Perceived Listening Effort in Adult and Pediatric Cases of Unilateral and Asymmetric Hearing Loss.

OBJECTIVE: Assess the influence of cochlear implant (CI) use on the perceived listening effort of adult and pediatric subjects with unilateral hearing loss (UHL) or asymmetric hearing loss (AHL). STUDY DESIGN: Prospective cohort. SETTING: Tertiary referral center. PATIENTS: Adults and children with UHL or AHL. INTERVENTION: Cochlear implantation. Subjects received their CI as part of a clinical trial assessing the effectiveness of cochlear implantation in cases of UHL and AHL. MAIN OUTCOME MEASURES: Responses to the Listening Effort pragmatic subscale on the Speech, Spatial, and Qualities of Hearing Scale (SSQ) or SSQ for Children with Impaired Hearing (SSQ-C) were compared over the study period. Subjects or their parents completed the questionnaires preoperatively and at predetermined postactivation intervals. For the adult subjects, responses were compared to word recognition in quiet and sentence recognition in noise. RESULTS: Forty adult subjects (n = 20 UHL, n = 20 AHL) and 16 pediatric subjects with UHL enrolled and underwent cochlear implantation. Subjects in all three groups reported a significant reduction in perceived listening effort within the initial months of CI use (p < 0.001; η2 ≥ 0.351). The perceived benefit was significantly correlated with speech recognition in noise for the adult subjects with UHL at the 12-month interval (r(20) = .59, p = 0.006). CONCLUSIONS: Adult and pediatric CI recipients with UHL or AHL report a reduction in listening effort with CI use as compared to their preoperative experiences. Use of the SSQ and SSQ-C Listening Effort pragmatic subscale may provide additional information about a CI recipient's experience beyond the abilities measured in the sound booth.

Sinus Development and Pneumatization in a Primary Ciliary Dyskinesia Cohort.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a genetically diverse disease which causes impaired mucociliary clearance, and results in pulmonary, otologic, and rhinologic disease in affected patients. Genetic mutations in multiple genes impair the ability of patients to clear mucous from the lungs, middle ear, and sinonasal cavity and lead to chronic pulmonary and sinonasal symptoms. METHODS: We identified 17 PCD patients who had available CT scans. Volumes for bilateral maxillary, sphenoid, and frontal sinuses were calculated. A control population of patients who had preoperative CT scans for endoscopic endonasal resection of skull base pathology without sinonasal cavity involvement was also identified. RESULTS: The mean age of PCD was 33 and ranged from 13 to 54 years. Patients were age- and gender-matched to a control group that underwent resection of anterior skull-base tumors and had a mean age of 35 that ranged between 17-53 years old. The volumes for all thee sinus cavities were significantly smaller (p < 0.007) compared to the control population. The average Lund-Mackay score was 10.6 in the PCD cohort (range 6-16) in comparison to an average of 0.7 in the control cohort (range 0-2). CONCLUSIONS: Overall sinus volumes were smaller in patients with PCD compared to our control population. Future studies will be aimed at understanding defects in sinus development as a function of specific genetic mutations in PCD patients. Ultimately, a better understanding of the underlying pathophysiology of PCD will allow us to identify the optimal treatment practices for this unique patient group.

Decline in circulating viral and human tumor markers after resection of head and neck carcinoma.

BACKGROUND: DNA sequencing panels can simultaneously quantify human and viral tumor markers in blood. We explored changes in levels of plasma tumor markers following surgical resection of head and neck carcinoma. METHODS: In preresection and postresection plasmas, targeted DNA sequencing quantified variants in 28 human cancer genes and levels of oncogenic pathogens (human papillomavirus [HPV], Epstein-Barr virus [EBV], Helicobacter pylori) from 21 patients with head and neck squamous cell carcinoma. RESULTS: Preresection, 11 of 21 patients (52%) had detectable tumor markers in plasma, most commonly TP53 mutation or HPV genome. Several days postresection, levels fell to undetectable in 8 of 10 evaluable patients, while two high-stage patients retained circulating tumor markers. CONCLUSIONS: Modern sequencing technology can simultaneously quantify human gene variants and oncogenic viral genomes in plasma. Falling levels of cancer-specific markers upon resection can help identify viral and human markers to track at subsequent timepoints as a means to evaluate efficacy of interventions.

Radiologic Analysis of Balloon Sinuplasty in a Human Cadaver Model: Observed Effects on Sinonasal Anatomy.

BACKGROUND: Balloon sinuplasty is increasingly used in the outpatient clinic for treatment of chronic rhinosinusitis, but radiologic analysis of its effects on sinonasal anatomy is largely uncharacterized in the known literature. OBJECTIVE: The purpose of this study is to examine the anatomic effects of balloon sinuplasty in a cadaveric model. METHODS: Five fresh cadaver heads underwent sequential endoscopic balloon dilation of maxillary ostia, frontal recess outflow tracts, and sphenoid ostia bilaterally by fellowship-trained rhinologists. Pre- and post-procedural CT imaging was obtained. CT scans were imported into Mimics™ software and sinonasal anatomy was analyzed systematically. RESULTS: Visual confirmation of balloon dilation was achieved in all 3 sites bilaterally in each cadaver. Radiologic analysis demonstrated that the frontal sinus outflow tract was appropriately dilated 60% (6/10 sites) of the time while the agger was inadvertently dilated 30% of the time (3/10). The sphenoid os was successfully dilated 70% (7/10 sites) of the time. In two cases, a posterior sphenoethmoid (Onodi) cell was dilated instead of the sphenoid. Successful dilation of maxillary os was noted 60% of the time (6/10 sites). No significant change in maxillary os was noted after balloon dilation. Normal middle turbinates were significantly medialized following balloon dilation 75% (6/8 sites) of the time. CONCLUSIONS: While the goal of balloon sinuplasty is to improve natural sinonasal drainage by dilating existing outflow tracts, as evidenced by radiologic evaluation the procedure appears not to achieve this in all cases, while occasionally creating unintended changes in sinonasal anatomy as well. These unrecognized changes in anatomy may be responsible for the post-procedure change in symptomatology that some patients experience.

Comparative study of simulated nebulized and spray particle deposition in chronic rhinosinusitis patients.

BACKGROUND: Topical intranasal drugs are widely prescribed for chronic rhinosinusitis (CRS), although delivery can vary with device type and droplet size. The study objective was to compare nebulized and sprayed droplet deposition in the paranasal sinuses and ostiomeatal complex (OMC) across multiple droplet sizes in CRS patients using computational fluid dynamics (CFD). METHODS: Three-dimensional models of sinonasal cavities were constructed from computed tomography (CT) scans of 3 subjects with CRS refractory to medical therapy using imaging software. Assuming steady-state inspiratory airflow at resting rate, CFD was used to simulate 1-µm to 120-µm sprayed droplet deposition in the left and right sinuses and OMC with spray nozzle positioning as in current nasal spray use instructions. Zero-velocity nebulization simulations were performed for 1-µm to 30-µm droplet sizes, maximal sinus and OMC deposition fractions (MSDF) were obtained, and sizes that achieved at least 50% of MSDF were identified. Nebulized MSDF was compared to sprayed droplet deposition. We also validated CFD framework through in vitro experiments. RESULTS: Among nebulized droplet sizes, 11-µm to 14-µm droplets achieved at least 50% of MSDF in all 6 sinonasal cavities. Four of 6 sinonasal cavities had greater sinus and OMC deposition with nebulized droplets than with sprayed droplets at optimal sizes. CONCLUSION: Nebulized droplets may target the sinuses and OMC more effectively than sprayed particles at sizes achieving best deposition. Further studies are needed to confirm our preliminary findings. Several commercial nasal nebulizers have average particle sizes outside the optimal nebulized droplet size range found here, suggesting potential for product enhancement.