Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis.

OBJECTIVES: The 22-question SinoNasal Outcome Test (SNOT-22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT-22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT-22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF). METHODS: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT-22 scores were obtained at baseline and after 3-6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution-based methods were used to assess internal consistency and calculate the MCID of the SNOT-22. RESULTS: A total of 184 PwCF participated with mean baseline SNOT-22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre- and post-HEMT data reported improvement in SNOT-22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT-22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02-1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14-18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39-20.11) were associated with greater SNOT-22 improvement. The mean MCID calculated via distribution-based methods was 8.5. CONCLUSION: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT-22 in PwCF is 8.5 points, similar to non-CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT-22 has strong internal consistency in PwCF. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Comparison of patient-reported outcomes and clinical characteristics among patients with pituitary macroadenomas and giant adenomas.

KEY POINTS: Patients with giant adenomas are more likely to have tumor extension into the paranasal sinuses. Compared to macroadenomas, giant adenomas are not associated with worse preoperative SNOT-22 scores.

Current and Novel Biologic Therapies for Patients with Asthma and Nasal Polyps.

A substantial portion of asthma and nasal polyps (NPs) share a common pathogenesis, which includes type 2-mediated inflammation. Distinct endotypes and phenotypes characterizing asthma and chronic rhinosinusitis have been identified. With emerging evidence describing pathophysiology, novel targets for biologic monoclonal antibody treatments have been developed. There are currently six biologic therapies approved by the US Food and Drug Administration to treat asthma, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, three of these-omalizumab, mepolizumab, and dupilumab-are also approved for NPs.

Determining the minimal clinically important difference for the questionnaire of olfactory disorders in people with cystic fibrosis and factors associated with improvement after highly effective modulator therapy.

INTRODUCTION: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory-specific quality-of-life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. METHODS: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution-based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. RESULTS: Of 129 PwCF included, 65 had QOD scores before and 3-6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was -1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04). CONCLUSION: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner.

Chronic rhinosinusitis and olfaction after highly effective modulator therapy: The role of individual sinus inflammation.

KEY POINTS: Individual sinus opacification (ISO) is measurable via a convolutional neural network approach. ISO decreased through 2 years after highly effective modulator therapy was initiated. In adults with cystic fibrosis, ISO did not correlate with quality of life or olfaction.

Olfactory loss in people with cystic fibrosis: Community perceptions and impact.

BACKGROUND: Olfactory dysfunction (OD) is prevalent in people with cystic fibrosis (PwCF) and can negatively impact quality-of-life (QOL). This study evaluated perceptions of OD, investigated how OD impacts QOL, and assessed willingness to participate in OD research among the CF community. METHODS: A 21-question survey was distributed through the CF Foundation's Community Voice program in 2023. The survey included questions on olfaction and interest in research. The Brief Questionnaire of Olfactory Disorders (BQOD), a validated person-reported outcome measure to assess QOL, was included. RESULTS: Seventy-six responses were received. Overall, 91% (69/76) reported olfactory problems. Mean BQOD score was 5.0 (standard deviation=4.8), indicating olfactory QOL impairment was present. Ninety-five percent (72/76) reported research on OD is worthwhile and were willing to participate in research. CONCLUSION: Among PwCF, OD and olfactory-specific QOL impairments are prevalent. There is strong interest and willingness to participate in OD research among the CF community.

Safety of Antibiotic Irrigations for Acute Exacerbations of Chronic Rhinosinusitis in Patients with Identical Drug Allergies or Adverse Reactions: A Pilot Study.

Objectives: The use of topical antibiotics in the treatment of acute exacerbation of chronic rhinosinusitis (AECRS) represents a viable option prior to initiation of parenteral antibiotics when no oral antibiotic alternatives are available due to patient allergy or adverse reactions. The main objectives of this pilot study were to determine the safety and efficacy of antibiotic irrigations in the treatment of AECRS in patients with documented adverse reactions to the oral form of the drug. Methods: A retrospective review was performed of patients diagnosed with AECRS treated with antibiotic irrigations. Inclusion criteria included a documented allergy or adverse event to the systemic form of the same antibiotic. Patient demographics, medical history, prior sinus surgery, nasal endoscopy findings, and microbiology results were obtained. Side effects to the antibiotic irrigations were recorded. Results: Six patients met the inclusion criteria resulting in 7 treated cases of AECRS. Four patients with adverse effects to oral trimethoprim/sulfamethoxazole (TMP/SMZ) received TMP/SMZ irrigations, and 1 patient with an adverse reaction to oral ciprofloxacin was treated with ciprofloxacin irrigations. One patient with adverse effects to both oral TMP/SMZ and levofloxacin was treated with TMP/SMZ and levofloxacin irrigations, respectively during 2 separate AECRS episodes. Following treatment, 1 case (14.3%) resulted in complete resolution of infection, 1 (14.3%) had partial improvement, and 5 (71.4%) had minimal to no endoscopic improvement at the subsequent clinic visit. There were no adverse reactions to antibiotic irrigations among the entire cohort. Conclusions: Currently, no prior study has examined whether adverse reactions to a systemic antibiotic also occur when the medication is delivered topically via sinonasal irrigations. Our findings suggest that topical administration of antibiotics may be a safe alternative for patients with adverse effects to the systemic form.

Transoral Robotic Surgery for a Parapharyngeal Space Tumor.

A 71-year-old woman had a parapharyngeal space mass that was found on magnetic resonance imaging of the face. She experienced left jaw tightness, aural fullness, and facial discomfort. What is your diagnosis?

Ghost Cell Odontogenic Carcinoma: A Case Report and Literature Review.

Ghost cell odontogenic carcinoma (GCOC) is an exceptionally rare malignant odontogenic neoplasm with a significant potential for aggressive growth. Although the literature on this tumor is limited, its high recurrence rates suggest that early and multimodal intervention may be beneficial. This study reports a case of GCOC of the mandible that was successfully treated with surgical resection, reconstruction, and radiation. A comprehensive literature review was performed, and the relevant genomic and histopathological characteristics of this malignancy were determined. Laryngoscope, 133:830-833, 2023.

Endoscopic Management of a Post-Traumatic Internal Maxillary Artery Pseudoaneurysm: Case Report and Review of the Literature.

Internal maxillary artery (IMA) pseudoaneurysms are rare, and typically occur following trauma or orthognathic surgery. Pseudoaneurysms are life-threatening conditions, and expeditious workup and treatment is critical. Endoscopic treatment of an IMA pseudoaneurysm is a feasible option and should be considered when IR embolization is not available. The objective of this study is to review the literature on IMA pseudoaneurysms and present the first reported case of an IMA pseudoaneurysm successfully treated endoscopically.

Gender Microaggressions During Virtual Residency Interviews and Impact on Ranking of Programs During the Residency Match.

Background: Microaggressions are one form of gender bias contributing to gender disparities and mistreatment, but their prevalence during virtual residency interviews has not been explored. Objective: To explore applicants' recall of experiencing gender microaggressions during virtual residency interviews and whether these experiences affected programs' rank position on applicants' rank lists. Methods: Fourth-year medical students at a single institution who participated in the 2021 Match were surveyed after submitting their rank lists. Students were surveyed categorically on (1) their recall of the frequency they experienced 17 gender microaggressions during interviews, and (2) how these affected reported ranking of programs on their rank lists. Results: Sixty-one percent (103 of 170) of eligible students responded to the survey. Seventy-two percent (36 of 50) of women experienced at least one microaggression compared to 30% (9 of 30) of men. The largest difference was in the experience of environmental microaggressions, which are demeaning cues communicated individually or institutionally, delivered visually, or that refer to climate (P<.001). Women experienced more microaggressions than men in nonsurgical (P=.003) and surgical specialties excluding obstetrics and gynecology (P=.009). When microaggressions were experienced at 1 to 2 programs, 36% of applicants (26 of 73) reported significantly lowering program ranking, compared to 5% (1 of 19) when microaggressions occurred at more than 5 programs (P=.038). Conclusions: Women applicants experience more microaggressions than men do during nonsurgical and male-dominated surgical specialty residency interviews. Respondents who recalled experiencing microaggressions at fewer programs were more likely to report significantly lowering the rank of those programs compared to those who experienced them at more programs.

Association of Operating Room Costs With Head and Neck Surgical Instrumentation Optimization: A Surgeon-Led Quality Improvement Initiative.

Importance: In an era of increasing health care expenditure, reduction of redundant head and neck surgical instrumentation may minimize waste. Objective: To (1) optimize head and neck surgical instrument trays at a single large academic tertiary care center and (2) identify associated direct cost savings. Design, Setting, and Participants: This prospective quality improvement initiative was conducted at an academic tertiary care medical center from July 2017 through July 2021. Participants were a multidisciplinary surgical quality team consisting of head and neck surgeons, operating room nurses, surgical technicians, and supply chain analysts. Main Outcomes and Measures: The 4 primary surgical instrument trays (major otolaryngology [Oto], Oto plastics, direct laryngoscopy, and microdirect laryngoscopy) used in all head and neck procedures were reviewed by 10 head and neck surgical faculty with detailed case observation of instrument utilization performed by trained operating room nurses and surgical technologists. Instruments used in less than 40% of cases were excluded from surgical trays, and novel instrument trays were established based on faculty feedback and utilization. Data on instrument processing, utilization, and associated institutional direct costs were prospectively collected over a 3-year period. The primary outcome measure was change in operating room direct costs. Surgeon satisfaction with the quality improvement intervention was the secondary outcome. Direct cost savings were identified as a function of surgical volume, labor and supply costs, and instrument depreciation. Results: More than 1500 eligible surgical cases were reviewed during the preintervention period. Of the 149 instruments in the major Oto tray, only 118 (79%) instruments were used in more than 40% of cases. There were 58 (49%) and 32 (21%) instruments in this tray that were used in more than 40% of neck dissections and sentinel lymph node biopsies, respectively. Resulting intervention included development of a streamlined major Oto tray with 118 instruments and novel neck dissection and sentinel lymph node biopsy trays. Similar processes were applied to the remaining head and neck trays, with a total of 257 instruments removed. Over a 3-year postintervention period, streamlined surgical trays were used 9284 times with direct cost savings of $228 338 (95% CI, $227 817-$228 854). Overall surgeon satisfaction with the optimized head and neck surgical trays was 100%. Conclusions and Relevance: In this quality improvement study, surgeon-led elimination of redundant or rarely used instruments from surgical instrument trays was associated with reduced operating room direct costs while maintaining stakeholder satisfaction.

Osteochondroma Arising from the Thyroid Cartilage: A Case Report and Literature Review.

INTRODUCTION: Osteochondromas are relatively common benign bone tumors often located at the metaphyseal ends of long bones; however, they are rare in the head and neck region. The objective of this study is to present a case of an osteochondroma arising from the thyroid cartilage causing insidious dysphonia and to present a literature review. METHODS: The medical record of a patient treated for osteochondroma of the thyroid cartilage was reviewed. A literature search on osteochondromas was conducted using PubMed and Google Scholar. The epidemiology, presentation, diagnosis, treatment, and outcomes of osteochondromas were reviewed. RESULTS: A 50-year-old female presented with nine months of dysphonia and aphonic voice breaks. Laryngovideostroboscopy revealed a left false vocal fold fullness, glottal gap, and vibratory phase asymmetry. A CT neck demonstrated a well-circumscribed 5 × 8 × 9 mm mass arising from the left thyroid cartilage lamina with a thin calcified rim and a heterogeneous decreased attenuation center. The tumor was excised surgically. Histopathologic analysis demonstrated hyaline cartilage overlying lamellar bone with fatty bone marrow, consistent with osteochondroma. English language literature review revealed no cases of osteochondroma of the thyroid cartilage. The presenting features of osteochondroma may depend on the size and location of the lesion. It is critical to differentiate between benign and malignant bone tumors, and physicians must rely on their clinical examination, radiographic findings, and histopathologic analysis to make the correct diagnosis. CONCLUSIONS: Osteochondromas of the laryngeal framework are extremely rare, and to our knowledge, there have been no reports in the literature of this tumor arising from the thyroid cartilage. Dysphonia may be the presenting symptom in a patient with a thyroid cartilage mass causing restricted mobility of the true vocal folds.

CT and FDG-PET radiologic biomarkers in p16+ oropharyngeal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

PURPOSE: To assess associations between imaging biomarkers from standard of care pre-treatment CT and FDG-PET scans and locoregional (LR) and distant metastatic (DM) recurrences in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). METHODS: An institutional database from a single NCI-designated cancer center identified 266 patients with p16+ OPSCC treated with definitive CRT in our department from 2005 to 2016 with evaluable pre-treatment FDG-PET scans. Quantitative SUV metrics and qualitative imaging metrics were determined from FDG-PET and CT scans, while clinical characteristics were abstracted from the medical record. Associations between clinical/imaging features and time to LR (TTLRF) or DM (TTDMF) failure and overall survival (OS) were assessed using univariable Cox regression and penalized stepwise regression for multivariable analyses (MVA). RESULTS: There were 27 LR and 32 DM recurrences as incident failures. Imaging biomarkers were significantly associated with TTLRF, TTDMF and OS. FDG-PET metrics outperformed CT and clinical metrics for TTLRF, with metabolic tumor volume being the only significant feature selected on MVA: C-index = 0.68 (p = 0.01). Radiographic extranodal extension (rENE), positive retropharyngeal nodes (RPN+), and clinical stage were significant on MVA for TTDMF: C-index = 0.84 (p < 0.001). rENE, group stage, and RPN+ were significant on MVA for OS: C-index = 0.77 (p < 0.001). CONCLUSIONS: In the largest study to date of uniformly treated patients with CRT to evaluate both pretreatment CT and FDG-PET, radiographic biomarkers were significantly associated with TTLRF, TTDMF and OS among patients with p16+ OPSCC treated with CRT. CT metrics performed best to predict TTDMF, while FDG-PET metrics showed improved prediction for LRRFS. These metrics may help identify candidates for treatment intensification or de-escalation of therapy. STATEMENT OF TRANSLATIONAL RELEVANCE: Pre-treatment imaging features from standard-of-care PET/CT imaging show promise for predicting long-term outcomes following HPV-associated oropharynx cancer (HPV-OPC) therapy. This study comprehensively characterizes qualitative and quantitative pre-treatment imaging metrics associated with time to pattern-specific failure in a cohort of 266 patients treated uniformly with definitive chemoradiation. Multivariate analysis (MVA) for time to locoregional failure (TTLRF), time to distant metastatic failure (TTDMF), and overall survival (OS) was performed. FDG-PET metrics outperformed CT and clinical metrics for TTLRF. CT radiographic extranodal extension, positive retropharyngeal nodes, and stage strongly predicted TTDMF (combined C-index = 0.84, log rank p < 0.001). Number of smoking pack-years complemented clinical and imaging features only in patients without radiographic extranodal extension or positive retropharyngeal nodes. Time to pattern-specific failure is important for guiding treatment de-escalation strategies, which intend to reduce treatment-related toxicity in patients with relatively long expected survival times. This study suggests that PET/CT features should play a crucial role in future de-escalation trials and management of HPV-OPC patients.