When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 2: Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (eGPA) are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of GPA and eGPA were collected and reported in this review. RESULTS: 467 references were discovered during literature review process. In total, 42 references for GPA and 35 references for eGPA were included in this review. CONCLUSION: GPA and eGPA are vasculitis syndromes which commonly present in the context of multisystem disease. For GPA, pulmonary and renal disease are common; for eGPA a history of asthma is nearly ubiquitous. Sinonasal disease is a very common feature for both disease processes and may precede the development of systemic symptoms in many patients. Clinical work up and diagnosis is complex and generally requires multidisciplinary care. Treatment primarily consists of immunosuppressive agents, and a number of steroids, steroid sparing agents, and biologics have been shown to be effective. The role of sinus surgery includes tissue biopsy for diagnosis, functional surgery for symptom management in select cases, and reconstruction of cosmetic and functional defects.

When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 1: IgG4-related disease and sarcoidosis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. IgG4-related disease (IgG4-RD) and sarcoidosis are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of sinonasal IgG4-RD and sarcoidosis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of IgG4-RD and sarcoidosis were collected and reported in this review. RESULTS: 404 references were discovered during literature review process. In total, 42 references for IgG4-RD and 34 references for sarcoidosis were included in this review. CONCLUSION: IgG4-RD and sarcoidosis are autoimmune inflammatory conditions that can affect many systems of the body. For both disease entities, sinonasal disease is a less common presentation which can lead to delayed diagnosis. Sinonasal IgG4-RD commonly presents in the setting of multisystem disease. All with other clinical features, biopsy plays a key role in the diagnosis for both diseases. Treatment for IgG4-RD consists primarily of steroids and rituximab which can lead to excellent and durable remission. A variety of immunosuppressive agents are used in the management of sarcoidosis. Surgery for IgG4-RD is primarily utilized for tissue biopsy, although resection or debulking may be considered. For sarcoidosis, surgery can be used for tissue biopsy and functional sinus surgery can offer symptomatic relief in many patients.

Development and Validation of the Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR).

OBJECTIVE: Develop and validate a quality-of-life (QoL) outcome measure for patients with dysosmia. STUDY DESIGN: Cross-sectional survey study. SETTING: Otolaryngology clinics, research registries, and Facebook support groups. METHODS: A 59-item pilot survey with questions addressing parosmia concerns was developed using input from subjects with parosmia and clinical expertise from Otolaryngologists. After item reduction, the Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR) was reduced to its final 29 items. DisODOR maximum score is 116 (each item score 0-4) with higher scores indicating a higher degree of dysfunction from smell distortion. DisODOR was validated using participants with parosmia persisting >3 months after severe acute respiratory syndrome coronavirus 2 (cases) and healthy controls. Reliability, face and content validity, internal consistency, convergent validity, discriminative validity, sensitivity to change, and the minimal clinically important difference (MCID) were assessed. RESULTS: A total of 134 cases and 20 controls completed DisODOR. The mean (SD) age was 45.9 (12.2) for cases and 29.6 (8.9) for controls. The mean score difference between cases and controls was 45.0 (95% confidence interval, 40.5-49.5) displaying good discriminative validity. DisODOR showed strong test-retest reliability (r = .942) with high internal consistency (Cronbach's α = .971). DisODOR had a moderate correlation with SNOT-22 scores (r = .619) indicating good convergent validity. There is an excellent association with the global impression of severity categories (η2 = 0.447). Based on the distribution method, the MCID is 15. CONCLUSION: DisODOR is a valid, reliable QoL instrument for parosmia that can be used to measure the functional impact and QoL impairment for parosmia patients. DisODOR is sensitive to change and thus can be used in studies investigating treatments for parosmia.

Esthesioneuroblastoma: Management of the N0 neck.

Esthesioneuroblastoma is a rare sinonasal malignancy that arises from the olfactory epithelium. The overall incidence of lymph node metastases is 25%. However, neck disease can present in a delayed fashion. As such, management of the clinically negative neck is controversial, with some advocating for elective neck treatment and others recommending observation with salvage treatment if necessary. At this time, no prospective head-to-head comparisons of elective versus salvage treatment have been performed.

Biphenotypic Sinonasal Sarcoma with a Novel PAX7::PPARGC1 Fusion: Expanding the Spectrum of Gene Fusions Beyond the PAX3 Gene.

Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade malignancy occurring in the sinonasal tract that is characterized by dual neural and myogenic differentiation. Rearrangements involving the PAX3 gene, usually with MAML3, are a hallmark of this tumor type and their identification are useful for diagnosis. Rarely, a MAML3 rearrangement without associated PAX3 rearrangement has been described. Other gene fusions have not been previously reported. Herein, we report a 22 year-old woman with a BSNS harboring a novel gene fusion involving the PAX7 gene (specifically PAX7::PPARGC1A), which is a paralogue of PAX3. The histologic features of the tumor were typical with two exceptions: a lack of entrapment of surface respiratory mucosa and no hemangiopericytoma-like vasculature. Immunophenotypically, the tumor was notably negative for smooth muscle actin, which is usually positive in BSNS. However, the classic S100 protein-positive, SOX10-negative staining pattern was present. In addition, the tumor was positive for desmin and MyoD1 but negative for myogenin, a pattern that is common among BSNS with variant fusions. Awareness of the possibility of PAX7 gene fusions in BSNS is important as it may aid in the diagnosis of PAX3 fusion negative tumors.

Depression, anxiety, and suicidal ideation in adults with COVID-induced parosmia.

KEY POINTS COVID-induced parosmia is associated with anxiety, depression, and suicidal ideation. Parosmic patients have low rates of treatment benefit and little hope for improvement. Hyposmia may mitigate the quality-of-life burden in patients with parosmia.

Postmarketing Reporting of Paxlovid-Related Dysgeusia: A Real-World Pharmacovigilance Study.

OBJECTIVE: A novel COVID-19 therapeutic, nirmatrelvir/ritonavir (Paxlovid), is commonly associated with reports of dysgeusia. The Food and Drug Administration Adverse Event Reporting System (FAERS) database was used to determine the real-world reporting of Paxlovid-associated dysgeusia (PAD), identify associated factors, and describe the relative reporting rates of dysgeusia for Paxlovid compared to other COVID-19 therapeutics (OCT), ritonavir alone, and other protease inhibitors (OPI). STUDY DESIGN: Observational retrospective. SETTING: Tertiary academic medical center. METHODS: We collected patient and adverse event characteristics reported in the FAERS database between January 1968 and September 2022. Disproportionality analyses were used to compare the reporting of PAD to dysgeusia reported for OCT, ritonavir, and OPI. RESULTS: 345,229 adverse events were included in the present study. Dysgeusia was a frequently reported Paxlovid-associated adverse event (17.5%) and was associated with nonserious COVID-19 infection (reporting odds ratio [ROR] 1.4; 95% confidence interval [CI] 1.2, 1.7) and female sex (ROR = 1.7; 95% CI 1.6, 1.9). Paxlovid was more likely to be associated with the reporting of dysgeusia compared to OCT (ROR 305.4; 95% CI 164.1, 568.5), ritonavir (ROR 28.0; 95% CI 24.1, 32.7), and OPI (ROR 49.0; 95% CI 42.8, 56.1). CONCLUSION: Dysgeusia is much more likely to be reported by patients receiving Paxlovid than those receiving OCT, ritonavir alone, or OPI. These findings suggest a potential mechanism of dysgeusia that causes distorted taste out of proportion to the background effects of COVID-19 infection and specific to nirmatrelvir. Future studies are needed to determine the underlying pathophysiology and long-term clinical implications for patients who report dysgeusia with Paxlovid.

Opioid use after endoscopic skull base surgery: A descriptive, prospective, longitudinal cohort study.

BACKGROUND: Opioid abuse is a public health crisis and the perioperative period can be a time of first opioid exposure. Little is known about postoperative pain management after endoscopic skull base surgery (ESBS). METHODS: This investigation was a single-institution, longitudinal, prospective cohort study of adult patients undergoing ESBS between November 2019 and March 2020. Participants completed preoperative questionnaires and were contacted every 48 hours postoperatively to quantify pain and opioid consumption. RESULTS: A total of 33 patients were enrolled and 28 of 33 patients (85%) underwent ESBS for sellar pathology. Mean total morphine milligram equivalents (MME) consumed was 381.9 ± 476.0. History of a headache disorder (p = 0.025) and previous opioid use within 60 days preoperatively (p < 0.001) were significantly associated with greater opioid use. Mean duration of opioid use was 6.7 ± 5.1 (range, 0-20) days. Headache disorder (p = 0.01), depression (p = 0.03), anxiety (p = 0.03), age ≤46 years (p = 0.029), and previous opioid use (p = 0.008) were all associated with longer mean opioid use. Patients with headache disorder also reported higher mean postoperative pain scores. Fewer than half of the participants required opioids by postoperative day 8. Prescription of nonsteroidal anti-inflammatory drugs at discharge was significantly associated with less outpatient opioid use (p = 0.032). At 2-month follow-up, 37% of patients reported keeping excess opioids. CONCLUSION: After ESBS, greater total opioid use was significantly associated with history of headaches and previous opioid use within 60 days. Overall, opioid use declined among all patients in the postoperative period, but several factors may contribute to longer duration of use.

Perceived Financial Insecurity Impacts Healthcare Decision-Making Among Patients With Sinusitis.

OBJECTIVES/HYPOTHESIS: The economic burden of sinusitis is significant, and socioeconomic factors can impact patient decision-making. The purpose of this study was to examine the impact of perceived financial insecurity on healthcare decision-making and treatment compliance among sinusitis patients. STUDY DESIGN: Cross-sectional study using the 2018 National Health Interview Survey. METHODS: Survey responses to nine questions regarding financial stressors and nine questions regarding cost-saving healthcare actions were recorded, which included seeking lower cost medication, medication noncompliance, and avoiding care visits due to costs. RESULTS: There was a total weighted sample size of 28.9 million patients who self-reported a diagnosis of sinusitis (12% of the U.S. population). Sinusitis patients who reported cost-saving actions had an increased severity of perceived financial insecurity than those without cost-saving actions (P < .001). Sinusitis patients with perceived financial insecurity had the highest odds of at least one cost-saving action (odds ratio [OR] = 5.94, 95% CI = 5.911-5.970, P < .001), followed by lack of health insurance (OR = 5.13, 95% CI = 5.107-5.159, P < .001), and poor self-reported health status (OR = 2.81, 95% CI = 2.792-2.822, P < .001). Increasing the number of financial stressors increased the odds of at least one cost-saving action (P < .001). Across all financial stressors, the most commonly performed cost-saving action was asking for lower cost medication. CONCLUSIONS: Perceived financial insecurity is associated with cost-saving healthcare actions among sinusitis patients, including treatment noncompliance. Interventions to assess financial insecurity among sinusitis patients may facilitate shared decision-making for optimal, individualized treatment plans that may lead to improved outcomes and quality of life. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2403-2412, 2021.

Patient-reported sleep outcomes lack association with mucosal eosinophilia or neutrophilia in patients with chronic rhinosinusitis undergoing functional endoscopic sinus surgery.

BACKGROUND: Chronic rhinosinusitis (CRS) is associated with sleep dysfunction, but the underlying pathophysiology is poorly understood. The purpose of this study was to determine if mucosal eosinophilia or neutrophilia were associated with sleep dysfunction severity or altered the improvement in sleep dysfunction following functional endoscopic sinus surgery (FESS). METHODS: A total of 104 patients with medically refractory CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP), completed the Pittsburgh Sleep Quality Index (PSQI) before and after FESS. Anterior ethmoid mucosa was collected during FESS and densest infiltrates of eosinophilia and neutrophilia per high-power field (HPF) were determined by microscopy. Eosinophilic (>10 eosinophils/HPF) and neutrophilic (>4 neutrophils/HPF) CRS were then compared to preoperative and postoperative PSQI measures. RESULTS: Of 104 study participants, 88 (85%) reported preoperative PSQI scores consistent with "poor sleep," (PSQI total > 5). The cohort overall demonstrated significant improvement in poor sleep (65%; χ2 = 12.03; p < 0.001) 16.8 ± 5.0 months after FESS. Regardless of nasal polyposis, neither eosinophilic nor neutrophilic CRS was associated with differences in mean postoperative PSQI improvement. However, in patients with neutrophilic CRSsNP, there was a significant relationship between severity of neutrophilia and improvement in sleep latency (R = -0.798, p = 0.003) and sleep efficacy (R = -0.777, p = 0.005). CONCLUSION: Chronic inflammation has been hypothesized to play a pathophysiologic role in sleep dysfunction associated with CRS. This study suggests that in patients with medically refractory CRS, evidence of mucosal eosinophilia and neutrophilia lack strong associations with patient-reported sleep dysfunction or improvements in sleep quality after FESS, overall. However, neutrophilia may impact sleep latency and efficacy in patients with CRSsNP.

Predictors of survival outcomes in sinonasal squamous cell carcinoma: an analysis of the National Cancer Database.

BACKGROUND: Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy that poses management challenges. Although surgery and chemoradiation therapy (CRT) remain therapeutic mainstays, induction chemotherapy (IC) has emerged as a useful adjunct with locally advanced disease. This study used the National Cancer Data Base (NCDB) to examine treatment outcomes for patients diagnosed with SNSCC. METHODS: The NCDB (2004-2015) was queried for cases with SNSCC. Multivariate hazard regression modeling was used to identify significant predictors of 24-month and 60-month overall survival (OS) including treatment modality. RESULTS: A total of 3516 patients with SNSCC met inclusion criteria, including 1750 patients (49.8%) treated with surgery ± adjuvant therapy, 1352 (38.5%) treated with definitive radiotherapy (RT) or CRT, 300 (8.5%) who underwent IC followed by definitive CRT, and 114 (3.2%) who received IC followed by surgery and adjuvant therapy. Hazard modeling for confirmed treatment modality significantly associated (p < 0.001) with OS after adjustment. Patients who received surgical intervention ± adjuvant therapy had lower 24-month and 60-month mortality risk compared to definitive RT or CRT (hazard ratio [HR] ≥ 1.97; p < 0.001) or IC followed by definitive CRT (HR ≥ 1.73; p < 0.001). Compared to primary surgery ± adjuvant therapy, patients undergoing IC then surgery had similar 24-month and 60-month OS (p ≥ 0.672) after adjustment. CONCLUSION: Multimodality therapy, including surgical intervention, associates with improved OS after multifactorial adjustments. IC followed by surgery associated with improved OS compared to IC, followed by CRT and CRT alone. Study results highlight the utility of surgery toward optimizing OS in patients with SNSCC and demonstrates the potential utility of IC when primary surgical management is not preferred.

Development of Chronic Sphenoid Sinusitis After Sellar Reconstruction with Medpor Porous Polyethylene Implant.

OBJECTIVE: The Medpor porous polyethylene implant is reported to be safe and effective for sellar reconstruction after transsphenoidal surgery (TSS). However, we have observed several cases of delayed chronic sphenoid sinusitis related to the implant. The purpose of this study is to describe the presentation and management of implant-related sphenoid sinusitis after sellar reconstruction. METHODS: This is a retrospective study of patients who underwent endonasal TSS with Medpor sellar reconstruction between December 2008 and January 2013 at a tertiary care institution. Patient demographics, initial surgical management, sinonasal symptoms, postoperative imaging, sinusitis management, and resulting outcomes were analyzed. RESULTS: From 2008-2013, 139 patients underwent sellar reconstruction using Medpor. Five patients (3.6%) presented between 8 and 60 months after surgery with chronic sphenoid sinusitis that required surgical management. All 5 patients presented as outpatients for management of headaches and nasal drainage, 4 patients experienced chronic nasal congestion, and 3 patients noted recurrent sinusitis. At the time of revision surgery, all 5 patients were found to have mucosal inflammation and edema surrounding the implant, and 4 of the 5 had an exposed or partially extruded implant that was removed. CONCLUSIONS: Reconstruction of the sellar floor may be performed after TSS to prevent postoperative complications. Although porous polyethylene implants have previously been described as safe and effective for this purpose, surgeons should be aware of the risk of subsequent implant extrusion and chronic sphenoid sinusitis that can occur in a delayed manner.