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.

Racial and Ethnic Bias in Letters of Recommendation and Personal Statements for Application to Otolaryngology Residency.

INTRODUCTION: The persistent lack of racial and ethnic diversity within the field of otolaryngology calls for an analysis of potential bias within the residency application system. Letters of recommendation (LORs) and personal statements (PSs) are the most important subjective application constituents. This subjectivity predisposes these components to implicit bias. In applications to various surgical subspecialties, prior linguistic studies assessing bias in reviews of LOR show race-based differences. Thus far, racial and ethnic linguistic differences in LORs for otolaryngology applicants have not been analyzed in the literature. METHODS: LORs and PSs were abstracted from otolaryngology - head and neck surgery applications in the Electronic Residency Application Service for the 2019-20 and 2020-21 application cycles. Linguistic Inquiry and Word Count 2015 was used for quantitative analysis of emotional, cognitive, and structural components of written text. RESULTS: Race-pair analysis of the 2019-2021 application cycles revealed higher mean "teaching" scores for LORs for Asian, black, Hispanic, and white applicants when compared to applicants who self-identified as Other. White applicants had lower scores for the terms "research" and "analytic" when compared to Asian and black applicants, respectively. Analysis of PSs revealed greater scores for an "authentic" writing style for white versus Asian applicants. White applicants were found to have higher scores for "tone" compared to black applicants. CONCLUSION: Minor racial and ethnic language differences exist in both LORs and PSs. A statistically significant difference was observed among LORs, with the "teaching" term used more frequently for Asian, black, Hispanic, and white applicants compared to self-identified Other individuals. For PSs, statistically significant differences were observed among white applicants, who wrote about themselves using more "authentic" language when compared with Asian applicants and who also had higher scores for "tone" compared to black applicants. Although these differences were statistically significant, the practical impact of the variances is likely small.

Impact of Masks on Speech Recognition in Adult Patients with and without Hearing Loss.

INTRODUCTION: The coronavirus 2019 pandemic has altered how modern healthcare is delivered to patients. Concerns have been raised that masks may hinder effective communication, particularly in patients with hearing loss. The purpose of this study is to determine the effect of masks on speech recognition in adult patients with and without self-reported hearing loss in a clinical setting. METHODS: Adult patients presenting to an otolaryngology clinic were recruited. A digital recording of 36 spondaic words was presented to each participant in a standard clinical exam room. Each word was recorded in 1 of 3 conditions: no mask, surgical mask, or N95 mask. Participants were instructed to repeat back the word. The word recognition score was determined by the percent correctly repeated. RESULTS: A total of 45 participants were included in this study. Overall, the mean word recognition score was 87% without a mask, 78% with a surgical mask, and 61% with an N95 mask. Among the 23 subjects (51.1%) with self-reported hearing loss, the average word recognition score was 46% with an N95 mask compared to 79% in patients who reported normal hearing (p < 0.001). CONCLUSION: Our results suggest that masks significantly decrease word recognition, and this effect is exacerbated with N95 masks, particularly in patients with hearing loss. As masks are essential to allow for safe patient-physician interactions, it is imperative that clinicians are aware they may create a barrier to effective communication.

Post-operative budesonide irrigations for patients with polyposis: a blinded, randomized controlled trial.

OBJECTIVE: To compare normal saline (NS) vs. NS+budesonide irrigations in post- functional endoscopic sinus surgery (FESS) patients with chronic rhinosinusitis with polyposis (CRSwNP). Currently, no evidence exists for NS+budesonide irrigation over NS irrigation alone. STUDY DESIGN: Prospective, single-blind, randomized controlled trial. METHODS: Subjects were prospectively enrolled to NS or NS+budesonide arms. Patients were evaluated at pre-operative and three post-operative visits (POV): POV1 (1-2 weeks post-op), POV2 (3-8 weeks post-op), and POV3 (3-6 months post-op). Patients were evaluated by three quality of life (QOL) questionnaires (SNOT-22, RSOM-31, and RSDI) and two olfaction scores (UPSIT and the PEA test). RESULTS: Fifty patients were randomized, with 25 patients in the NS arm and 25 patients in the NS+budesonide arm. Two patients had unexpected pathology and were excluded from the study. By POV2 and POV3, patients experienced a significant improvement in all three QOL surveys, although the degree of improvement between arms was not significant up through POV3. Neither arm experienced significant olfactory improvement up through POV3. CONCLUSIONS: While both NS and NS+budesonide treatments improve QOL for post-FESS patients, neither intervention significantly increases QOL as compared to the other. Olfaction was not significantly improved in either treatment group.

Endoscopic skull base reconstruction: a review and clinical case series of 152 vascularized flaps used for surgical skull base defects in the setting of intraoperative cerebrospinal fluid leak.

Endoscopic skull base surgery continues to rapidly evolve, requiring comparable advances in reconstructive techniques. While smaller skull base defects with low intraoperative CSF flow have been successfully managed with a variety of avascular and/or noncellular techniques, larger defects with high CSF flow require more robust repairs often in the form of vascularized flaps, which confer excellent success rates in this setting. Despite these successful outcomes, a paucity of data describing specific patient and operative characteristics and their effects on repair exist. Therefore, a retrospective, consecutive chart review was performed on patients who underwent endoscopic skull base reconstruction with a vascularized flap in the setting of intraoperative CSF leaks. In this series, 151 patients with a mean age of 51 years underwent 152 vascularized flap skull base reconstructions for an array of benign and malignant pathologies. These vascularized flaps included 144 nasoseptal flaps, 6 endoscopic-assisted pericranial flaps, 1 facial artery buccinator flap, and 1 inferior turbinate flap that were used throughout all regions of the skull base. Perioperative (< 3 months) and postoperative (> 3 months) flap complications were assessed and revealed 3 perioperative flap defects (2.0%) defined as a visualized defect within the substrate of the flap and a total of 5 perioperative CSF leaks (3.3%). No patient experienced flap death/complete flap loss in the cohort. Assessed postoperative flap complications included 1 case (0.7%) of mucocele formation, 8 cases (5.3%) of prolonged skull base crusting, and 2 cases (1.3%) of donor-site complication, specifically septal perforation secondary to nasoseptal flap harvest. Among the 152 cases identified, 37 patients received radiation therapy while 114 patients did not undergo radiation therapy as part of the treatment profile. No significant association was found between perioperative complication rates and radiation therapy (p = 0.634). However, a significant association was found between postoperative complication rates and radiation therapy, primarily accounted for by an increased risk for prolonged (> 6 months) skull base crusting (p = 0.025). It is clear that larger skull base defects with high intraoperative CSF flow require thoughtful approach and strong consideration for vascularized repair.

Comprehensive quality of life outcomes for pediatric patients undergoing endoscopic sinus surgery.

BACKGROUND: Limited quality of life data exist for pediatric chronic rhinosinusitis (CRS) patients undergoing endoscopic sinus surgery (ESS). Further exploration of the following areas will enhance understanding and support clinical decision-making: baseline and post-ESS general and disease-specific quality of life, parent vs. child report, and correlation of nasal endoscopy to sinus CT scores. METHODOLOGY: A prospective cohort study evaluated CRS patients age 5-18 undergoing ESS. Surveys were completed at two timepoints: (1) pre-ESS and (2) 30-90 days post-ESS, with parents completing general (PedsQLTM) and CRS-specific (SNOT-16 and SN-5) quality of life surveys and children completing PedsQLTM and SNOT-16 surveys. Preoperative Lund-Kennedy nasal endoscopy and Lund-Mackay sinus CT scores were calculated. Where appropriate, outcomes were stratified by cystic fibrosis status. RESULTS: Impaired preoperative general quality of life was evidenced by parent proxy-report of PedsQLTM scores in 10 cystic fibrosis and 11 non-CF patients. ESS was associated with decreased sinus symptoms at 1-3 months postoperatively with SN-5 change scores of -1.85 and -2.2, in CF and non-CF patients, respectively. Parents reported worse CRS symptoms via higher preoperative SNOT-16 scores than their children did. Nasal endoscopy and sinus CT scores correlated with a Spearman correlation coefficient of 0.51. Scores not reaching statistical significance included CF-related CRS SNOT-16 change scores and PedsQLTM general quality of life change scores. CONCLUSION: In pediatric patients with CRS electing ESS, general quality of life is impaired preoperatively and sinus symptoms improve significantly 1-3 months after sinus surgery. Parents report statistically worse CRS symptom scores than their children do. Nasal endoscopy scores in this cohort correlated with sinus CT scores.

In Vivo Fluticasone Absorption in Surgical Patients.

BACKGROUND: Intranasal corticosteroids (INCS) are a treatment mainstay of chronic rhinosinusitis and allergic rhinitis. Current computational models demonstrate that >90% of INCS drug deposition occurs on the head of the inferior turbinate and nasal valve, rather than the actual sinuses. These models do not consider mucociliary clearance which propels mucus posteriorly, nor do they consider the absorption of the drug. The purpose of this study is to better understand the exact anatomical location where INCS are absorbed. METHODS: Patients with chronic rhinosinusitis and allergic rhinitis taking fluticasone pre-operatively who were scheduled for functional endoscopic sinus surgery and inferior turbinate reduction, respectively, were recruited. Intra-operative tissue samples were obtained from predetermined locations within the sinonasal cavity. Mass spectrometry was then used to quantify the amount of absorption in each specific anatomic location to determine the largest amount of absorption. RESULTS: Eighteen patients were included in our study. The greatest fluticasone absorption levels across the sinonasal anatomy were at the anterior inferior turbinate (5.7 ngl/mL), ethmoid sinus, (4.4 ng/mL), posterior inferior turbinate (3.7 ng/mL), maxillary sinus (1.3 ng/mL), and the sphenoethmoidal recess (0.72 ng/mL) respectively. Absorption was significantly higher in revision surgery compared to surgically naïve patients. CONCLUSIONS: Computation fluid dynamic models of the nasal passage are useful models to help predict intranasal particle flow. However, these models do not incorporate or consider the important mucociliary clearance system, leading to absorption of fluticasone throughout the sinonasal cavity far beyond that predicted by these models. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1551-1555, 2024.

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.

Inhalational exposure history is associated with differential sinonasal gene expression profiles and clinical outcomes in chronic rhinosinusitis patients: A pilot study.

KEY POINTS: Inhalational exposure (IE) history assessment is important and may guide chronic rhinosinusitis disease management. Combined exposure status was the most significant factor across differential gene expression analyse IE history was associated with pro-inflammatory transcriptome changes and worse clinical outcomes.

The Surprising Effect of Priming on SNOT-22 Results.

BACKGROUND: Priming is a psychological phenomenon where subconscious cues in the environment impact our behavioral responses in certain situations. Well studied in the worlds of business, marketing, and even politics, it is unclear how the priming phenomenon impacts patient perception of their own disease state nor how they report that perception using tools like the Sinonasal Outcomes Test (SNOT-22), used to measure that perception in chronic rhinosinusitis. OBJECTIVE: To determine the impact of positive or negative priming on self-reported patient perception of their chronic rhinosinusitis disease using the SNOT-22 disease-specific quality of life instrument. METHODS: Single-blind, randomized, prospective cohort pilot study of 206 consecutive adult patients with a clinical diagnosis of chronic rhinosinusitis presenting to a university rhinology clinic. Patients were randomized to receive "positive priming" (103) or "negative priming" (103) by reading a passage about the positive or negative aspects of chronic sinusitis and its treatment respectively. Patients were then asked to fill out the SNOT-22 and results between the two groups were compared. RESULTS: The negative priming group had a higher median SNOT-22 score of 49 [IQR = 39] compared to the positive priming groups' score of 22 [IQR = 27], p < 0.0001), a difference of nearly three times the minimal clinical impactful difference (MCID). This effect was consistent regardless of age or sex of the patient. Subgroup analysis revealed a greater impact when priming was performed by the senior male attending regardless of patient age or sex (p < 0.001), while priming performed by the younger female research fellow had greater impact on older patients (>59 years, p = 0.001) and female patients (p = 0.003). CONCLUSIONS: Priming impacts how patient's perceive their chronic rhinosinusitis as determined by the SNOT-22. It is imperative that the rhinologist understand this when using this instrument in research applications and in clinical decision-making for patients.

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.

Detection of plagiarism among rhinology scientific journals.

KEY POINTS: Automated plagiarism-checking software can be a valuable tool for detecting plagiarism in manuscripts. Twenty-five of 60 articles (42%) had at least one incidence of plagiarism, predominately text recycling. A "similarity score" ranging from 22% to 35% could be a potential cut-off value when screening submitted manuscripts.

The Impact of Occupational Exposures on Chronic Rhinosinusitis: A Scoping Review.

Chronic rhinosinusitis (CRS) is a prevalent and burdensome condition worldwide, characterized by inflammation of the paranasal sinuses. Ideally, instead of treating CRS, we would identify ways to prevent the development of this chronic condition. Occupational exposures may be an excellent target for prevention. Occupational exposures have been shown to play a critical role in the pathogenesis of multiple lower airway diseases, such as asthma, silicosis, asbestosis, and hypersensitivity pneumonitis. However, evidence for the association between occupational exposures and the development of upper airway disease, like CRS, is less well-defined. This manuscript examines the association between occupational exposures and CRS. A scoping review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 19 relevant studies. The populations examined and the methods and criteria used for defining CRS diagnosis and occupational variables significantly varied between the studies. Diagnosis of CRS was most often determined by self-reported symptoms or medical record review. Occupational variables ranged from employment status to occupation type to specific exogenous compounds encountered. Overall, substantial evidence demonstrates a general association between occupational exposures and CRS diagnosis; however, limitations in study methodologies, including variations in CRS diagnostic criteria, occupational exposures, assessment methods, and populations, hinder drawing more specific conclusions. Moving forward, rigorous research methodologies and standardized criteria are essential to draw conclusions supported by multiple studies. Critical components of future studies should include large, diverse populations, use of consensus CRS diagnostic criteria, and inclusion of many specific and quantitatively defined exposures. Ultimately, such efforts can help inform preventative measures and interventions for CRS, thus mitigating the burden of CRS on individuals and populations worldwide.

Limitations in Faculty Advancement for Underrepresented Groups in Academic Otolaryngology.

OBJECTIVE: Despite the increasing racial diversity of the United States, representation in academic medicine faculty does not reach concordance with the general population and worsens with higher rank. Few studies have examined this within academic Otolaryngology and surgical subspecialties. This project aims to compare rank equity in academic Otolaryngology on self-reported gender and race/ethnicity between the years 2000 and 2020. METHODS: Publicly available data were obtained from the Association of American Medical Colleges under the "Data & Reports" section for the years 2000 and 2020. The report comprised of full-time faculty from all U.S. medical schools. To determine parity between faculty ranks across gender and race/ethnicity, rank equity index (REI) was calculated for associate/assistant, professor/associate, and professor/assistant professor comparisons. RESULTS: The percentage of women faculty in Otolaryngology has increased from 21% in 2000 to 37% in 2020; however, they did not achieve parity at all rank comparisons for both years. On the contrary, men were above parity at all rank comparisons. Improvements in rank equity occurred for Black/African American (Black) and Hispanic Latino/Spanish Origin (Latine) faculty between the years 2000 and 2020; however, when accounting for gender, benefits were concentrated among men. CONCLUSION: Advancement along the academic ladder is limited for women of all racial groups in academic Otolaryngology. While improved rank equity was seen for Black and Latine faculty, these improvements were largely among men. Future directions should aim to identify barriers to recruitment, retention, and promotion for women and underrepresented in medicine (URiM) academic otolaryngologists and create interventions that diversify Otolaryngology faculty at all ranks. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1625-1632, 2024.

"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.

Minimally Invasive Transnasal Approach to the Anteromedial Temporal Fossa and Lateral Sphenoid Using a Novel Landmark between Periorbita and Periosteum of the Pterygopalatine Fossa: A Cadaveric Study.

The anteromedial temporal region and the lateral wall of the sphenoid can be the site of an array of pathology including trigeminal schwannoma, encephalocele, cholesterol granuloma of the petrous apex, malignancy, infection, and sellar pathology extending to the lateral cavernous sinus. Approaches to this region are technically challenging and the existing approach requires sacrifice of all of the turbinates including the nasolacrimal duct, which can cause postoperative complications. We describe a novel anatomical landmark between the periorbita and the periosteum of the pterygopalatine fossa (which is located at the inferolateral periorbital periosteal line [ILPPL]). The posterior one-third of the incision line lies between the foramen rotundum and the superior orbital fissure, which is proximal to the maxillary strut. A 1.5-cm incision can divide the orbital and pterygoid contents and lead us to the posterior inferolateral orbital region, anteromedial temporal region, lateral wall of the sphenoid sinus, and lateral wall of the cavernous sinus. A combined multiangled approach to the ILPPL will enable us to preserve all of the turbinates and the septum, and the nasolacrimal duct, allowing for the preservation of the physiological function and pedicled flaps, such as the middle turbinate, inferior turbinate, and septal membrane flap. The ILPPL is a simple, effective, and novel landmark for the minimally invasive approach to the anteromedial temporal fossa.

Unilateral Periorbital Swelling in a Pediatric Patient.

Infratemporal fossa (ITF) tumors are rare in children and may present with a variety of symptoms. Teratomas are neoplasms derived from the 3 germ layers and approximately 6% to 10% are within the head and neck. Our study discusses one of the first reported cases of teratoma in the ITF in a pediatric patient. A 3-year-old girl presents with 2 years of recurrent monthly left periorbital swelling accompanied by fevers, skin discoloration, and pain. Prior episodes were treated with antibiotics with incomplete resolution. Imaging revealed a cystic lesion centered in the ITF. She was taken for endoscopic endonasal biopsy of the lesion and had no complications. Pathology revealed a mature teratoma composed primarily of pancreatic tissue. Providers should consider masses such as teratoma in the differential for ITF tumors and periorbital edema unresponsive to typical treatment.

Improved quality of life in patients with chronic rhinosinusitis with nasal polyps associated with expanded types of endoscopic sinus surgery: A 2-year retrospective study.

KEY POINTS: Expanded types of functional endoscopic sinus surgery (FESS) significantly improve quality of life and reduce revision surgeries rates, supporting their early application for moderate-to-severe cases. Minimal clinically important difference may play as a crucial role in defining surgical treatment response (i.e., responder and super-responder conditions). Expanded FESS benefits patients with chronic rhinosinusitis with nasal polyps but more data are required to have a clearer understanding of its uses due to varied approaches and reported outcomes in the literature.

The relationship between survey-based subjective olfactory awareness and objective olfactory function.

KEY POINTS: Correlation between symptom-based surveys and objective olfactory testing is variable. For diagnosis and symptom monitoring, surveys should correlate with objective testing. The Odor Awareness Scale (OAS) and Affective Importance of Odor Scale (AIO) showed significant but moderate positive correlations with University of Pennsylvania Scent Identification Test (UPSIT) score.

Long-Term Clinical Outcomes in Patients with Chronic Rhinosinusitis with Nasal Polyps Associated with Expanded Types of Endoscopic Sinus Surgery.

(1) Background: Surgical criteria for chronic rhinosinusitis with nasal polyps (CRSwNP) remain unresolved. This study addresses these discrepancies by comparing the clinical outcomes of expanded-functional endoscopic sinus surgeries (E-FESS) with more-limited FESS (L-FESS). (2) Methods: A database was analyzed retrospectively to compare surgical outcomes in CRSwNP patients who underwent E-FESS versus those subjected to L-FESS. Quality of life, endoscopic and radiological outcomes were compared at the baseline and two years after surgery. The clinical status of the responder was defined when a minimal clinically important difference of 12 points in SNOT-22 change was achieved. (3) Results: A total of 274 patients met the inclusion criteria and were analyzed; 111 underwent E-FESS and 163 were subjected to L-FESS. Both groups exhibited significant clinical improvements, although a greater magnitude of change in SNOT-22 (14.8 ± 4.8, p = 0.002) was shown after E-FESS. Higher significant improvements for endoscopic and radiological scores and lower surgical revision rates were also noted in the E-FESS group. (4) Conclusions: E-FESS provides better clinical outcomes and reduced revision surgery rates when compared to L-FESS in CRSwNP patients two years after surgery, irrespective of any comorbidity. Further randomized prospective studies are needed to comprehensively contrast these results.