Prognostic Factors for Survival Using a Clinical Severity Staging System Among Patients With Acute Invasive Fungal Sinusitis.

Importance: Despite the aggressive progression of fulminant acute invasive fungal sinusitis (AIFS), data on prognostic factors have been disparate, hindering the development of a staging system. A composite staging system may improve prognostication for patient counseling and conduct of clinical research. Objective: To identify prognostically important factors in AIFS and to incorporate the factors into a comprehensive Functional Severity Staging System and Clinical Severity Staging System. Design, Setting, and Participants: This retrospective cohort study included adult patients diagnosed with pathology-proven AIFS from June 1, 1992, to December 31, 2022, at Washington University Medical Center and Barnes-Jewish Hospital, a tertiary care center in St Louis, Missouri. Data were analyzed from April to July 2023. Main Outcome and Measures: Sequential sequestration and conjunctive consolidation was used to develop a composite staging system to predict 6-month overall survival. Results: Of 71 patients with pathology-proven AIFS over the 30-year period, the median (range) age of the cohort was 56 (19-63) years, and there were 47 (66%) male patients. The median (range) follow-up time was 2 (0-251) months. There were 28 patients alive within 6 months, for a 39% survival rate. Symptoms, comorbidity burden, and presence and duration of severe neutropenia were associated with 6-month survival and were consolidated into a 3-category Clinical Severity Staging System with 6-month survival of 75% for stage A (n = 16), 41% for stage B (n = 27), and 18% for stage C (n = 28). The discriminative power of the composite staging system was moderate (C statistic, 0.63). Conclusion and Relevance: This cohort study supports the clinical importance of symptomatology, comorbidity burden, and prolonged severe neutropenia at the time of AIFS presentation. The composite clinical staging system may be useful for clinicians when counseling patients with AIFS and conducting clinical research.

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.

Stellate Ganglion Block for the Treatment of COVID-19-Induced Olfactory Dysfunction: A Prospective Pilot Study.

OBJECTIVE: The objective of this study was to explore the safety and feasibility of stellate ganglion blocks (SGBs) to treat persistent COVID-19-induced olfactory dysfunction (OD). Secondarily, the goal was to determine effect sizes to plan a future randomized clinical trial. STUDY DESIGN: Prospective case series. SETTING: Quaternary Care Academic Medical Center. METHODS: In this single-arm pilot trial, adult participants with a COVID-19 diagnosis ≥ 12 months prior to enrollment with OD underwent bilateral SGBs. Subjects were followed for 1 month after completion of SGB. The primary outcome measure was the change in the Clinical Global Impression-Improvement Scale for smell loss. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Olfactory Dysfunction Outcomes Rating (ODOR). RESULTS: Twenty participants were enrolled with a mean (SD) age of 46 (11) years and a mean (SD) duration of OD of 21 (5) months. At 1 month, 10 (50%) participants experienced at least slight subjective improvement in their OD, 11 (55%) attained a clinically meaningful improvement in smell identification using the UPSIT, and 7 (35%) achieved a clinically meaningful improvement in olfactory-specific quality of life (QoL) measured by the ODOR. The median difference between UPSIT scores at baseline and 1 month was 6 (95% confidence interval: 3-11), exceeding the minimal clinically important difference of 4. There were no serious adverse events. CONCLUSION: Sequential SGBs for COVID-19-associated OD were safe and associated with modest improvements in subjective olfaction, odor identification, and olfactory-specific QoL. A placebo-controlled trial is warranted to determine the efficacy of SGBs for COVID-19-associated OD.

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.

Invasive fungal sinusitis risk factors among immunosuppressed hematopoietic stem cell transplant recipients.

KEY POINTS: Invasive fungal sinusitis (IFS) rate and risk factors in transplant recipients were explored IFS rate is higher in allogeneic recipients with prior transplants and worse comorbidity scores The at-risk timeframes for IFS development were identified.

Layperson Perception of Symptoms Caused by the Sinuses.

OBJECTIVE: To assess the perceived symptoms caused by the sinuses as defined by otolaryngology patients and clinicians. STUDY DESIGN: Multi-institutional cross-sectional study. SETTING: Six academic outpatient otolaryngology practices. METHODS: We performed a multi-institutional, cross-sectional study using a semantics-based questionnaire. Consecutive patients were enrolled at 6 academic otolaryngology centers from June 2020 to May 2021. The primary outcome examined patient and provider definitions for the symptoms caused by the sinuses from a list of 28 proposed terms covering 6 general categories. These data were also collected from otolaryngology faculty at the same institutions. RESULTS: Responses were obtained from 451 patients (54% female, mean age 48.3 years) and 29 otolaryngologists (38% female, mean age 37.4 years). Patients selected a median of 12 terms, compared to 8.5 for otolaryngologists. Among patients, the most frequently selected symptom domains were mucus (419, 92.9%), airflow (412, 91.4%), and pain (389, 86.3%). Compared to clinicians, patients more frequently selected symptoms related to the ear (difference, 48.3%; 95% confidence interval [CI], 34.8%-59.3%), throat (difference, 35.7%, 95% CI, 22.0%-47.5%), systemic (difference, 34.4%, 95% CI, 21.2%-46.0%), mucus (difference, 20.5%, 95% CI, 10.2%-30.6%), and airflow domains (difference, 19.0%, 95% CI, 8.4%-29.3%). Multiple domains were selected by 98% of patients and 79% of providers. CONCLUSION: Semantic differences exist between patients and clinicians regarding the symptoms caused by the sinus with patients having a broader range of perceived symptoms. These differences may provide clues to improve communication between otolaryngologists and their patients.

Development and Psychometric Validation of the Olfactory Dysfunction Outcomes Rating.

Importance: Olfactory dysfunction (OD) is an increasingly common and morbid condition, especially given the ongoing COVID-19 pandemic. Thus, the ability to reproducibly measure smell loss-associated quality of life (QOL) and its response to treatment is paramount. Objective: To develop and validate a concise and visually appealing smell loss-associated QOL patient-reported outcome measure for OD. Design, Setting, and Participants: A secondary analysis of comments to an online survey by 1000 patients with olfactory dysfunction published in 2013 was used as the primary source to generate items of the Olfactory Dysfunction Outcomes Rating (ODOR). In addition, 30 patients with OD enrolled in 2 clinical studies at a tertiary care medical center (Washington University) were asked to identify their main concerns associated with smell loss. And finally, 4 otolaryngologists reviewed the items generated from the online survey and the patients' interviews to identify any additional items. Prospective study design was used for data collection from the 30 patients and 4 otolaryngologists. Prospective study design was used for survey validation. Validation of the ODOR was performed with 283 patients enrolled in several prospective studies at a single institution that completed the ODOR as an outcome measure. Main Outcomes and Measures: Item generation and selection were the outcomes of ODOR development. The psychometric and clinimetric measures evaluated for validation were internal consistency, test-retest reliability, face and content validity, concurrent validity, and discriminant validity. Minimal clinically important difference was also determined. Results: The ODOR is a 28-item instrument with each item scored as either no difficulty or very rarely bothered (0) to complete difficulty or very frequently bothered (4) with a total instrument score range of 0 to 112 points. Higher scores indicate higher degree of dysfunction and limitation. Validation in the cohort of 283 patients (mean [SD] age, 47.0 [14.4] years; 198 female participants [73%]; 179 White participants [80%]) revealed that the instrument has high internal consistency (Cronbach α = 0.968), test-retest reliability (r = 0.90 [95% CI, 0.81-0.95]), face validity, content validity, concurrent validity (r = 0.87 [95% CI, 0.80-0.91] compared with the Questionnaire of Olfactory Disorders-Negative Statements; ρ = -0.76 [95% CI, -0.81 to -0.71] compared with a patient-reported symptom severity scale), and divergent validity (mean score difference, -33.9 [95% CI, -38.3 to -29.6] between normosmic patients and hyposmic/anosmic patients). The minimal clinically important difference was 15 points. The estimated time for survey completion was approximately 5 minutes. Conclusions and Relevance: In this survey creation and validation study, the ODOR was shown to be a novel, concise, reliable, and valid patient-reported outcome measure of OD-associated QOL. It can be used to measure physical problems, functional limitations, and emotional consequences associated with OD and how they change after a given intervention, which is clinically applicable and particularly pertinent given the growing burden of OD associated with COVID-19.

Surgery for Pituitary Tumor Apoplexy Is Associated with Rapid Headache and Cranial Nerve Improvement.

Pituitary tumor apoplexy (PTA) classically comprises sudden-onset headache, loss of vision, ophthalmoparesis, and decreased consciousness. It typically results from hemorrhage and/or infarction within a pituitary adenoma. Presentation is heterologous, and optimal management is debated. The time course of recovery of cranial nerve deficits (CNDs) and headaches is not well established. In this study, a retrospective series of consecutive patients with PTA managed at a single academic institution over a 22-year period is presented. Headaches at the time of surgery were more severe in the early and subacute surgical cohort and improved significantly within 72 h postoperatively (p < 0.01). At one year, 90% of CNDs affecting cranial nerves (CNs) 3, 4, and 6 had recovered, with no differences between early (<4 d), subacute (4−14 d), and delayed (>14 d) time-to-surgery cohorts. Remarkably, half recovered within three days. In total, 56% of CN2 deficits recovered, with the early surgery cohort including more severe deficits and recovering at a lower rate (p = 0.01). No correlation of time-to-surgery and rapidity of recovery of CNDs was observed (p = 0.65, 0.72). Surgery for PTA is associated with rapid recovery of CNDs in the early, subacute, and delayed time frames, and with rapid headache improvement in the early and subacute time frames in 50% or more of patients.

Chronic rhinosinusitis as a risk factor for intracranial and extracranial complications after endoscopic transsphenoidal surgery.

PURPOSE: To elucidate whether chronic rhinosinusitis (CRS), usually an inflammatory-mediated rather than infectious process, is a risk factor for extracranial and intracranial complications after elective endoscopic transsphenoidal surgery (ETSS). MATERIALS AND METHODS: A single-center retrospective cohort study of consecutive patients who underwent ETSS between January 2015 and July 2019 was performed, which included chart review and computed tomography assessment. CRS was defined by symptomatology and concurrent endoscopic or radiographic findings. RESULTS: Of 292 subjects, 11% (n = 33) met criteria for CRS. Median difference in Lund-Mackay scores between the CRS and non-CRS groups was 3.0 (95% CI 2.0-4.0). Complications included acute rhinosinusitis requiring antibiotics (23%, 68/292), epistaxis (10%, 28/292), meningitis (1%, 3/292), cerebrospinal fluid (CSF) leak (7%, 20/292), revision sinonasal procedures (10%, 28/292), and frequent in-office debridement (13%, 39/292). CRS was strongly associated with postoperative acute rhinosinusitis (aRR 1.85, 95% CI 1.18-2.90) and frequent debridement (aRR 1.96, 95% CI 1.00-3.83). Conversely, CRS was not associated with epistaxis (aRR 1.52, 95% CI 0.62-3.72), postoperative CSF leak (aRR 0.91, 95% CI 0.24-3.44), or additional sinonasal procedures (aRR 0.70, 95% CI 0.21-2.29). The rate of meningitis was not significantly higher in the CRS cohort (difference 2.2%, 95% CI -1.0% to 14.5%). CONCLUSIONS: CRS was a strong risk factor for acute rhinosinusitis and need for frequent in-office debridement after ETSS. It was not associated with other postoperative complications including epistaxis, CSF leak, or revision sinonasal procedures. CRS patients had a slightly higher rate of meningitis, which is likely not clinically meaningful.

Computed Tomography as a Predictor of Sinonasal Inverted Papilloma Origin, Skull Base Involvement, and Stage.

Objective To investigate the diagnostic performance of computed tomography (CT) to determine the origin, skull base involvement, and stage of sinonasal inverted papilloma (IP). Design This is a retrospective cohort study. Setting This is set at a tertiary care medical center. Participants Patients with preoperative CT imaging who underwent extirpative surgery for histologically confirmed sinonasal IP between January 2005 and October 2019. Main Outcome Measures The likely sites of tumor origin, skull base involvement, and radiographic tumor stage were determined by two board-certified neuroradiologists after re-reviewing preoperative CT imaging. These radiologic findings were then compared with intraoperative and pathologic findings. Results Of 86 patients, 74% (64/86) had IP lesions with correctly classified sites of origin on CT. CT was not sensitive for diagnosing ethmoid sinus origin (48%, 52%), frontal sinus origin (80%, 40%), and skull base origin (17%, 17%). CT was not sensitive (62%, 57%) but specific (86%, 98%) for identifying any skull base involvement. There was substantial-to-near perfect agreement between radiographic and pathologic Cannady stages (weighted κ = 0.61 for rater 1; weighted κ = 0.81 for rater 2). Interrater agreement was substantial for identifying tumor origin (κ = 0.75) and stage (weighted κ = 0.62) and moderate for identifying skull base involvement (κ = 0.43). Conclusion Interrater agreement on CT findings was substantial except on skull base involvement. CT correctly predicted site of tumor origin in up to 74% of subjects. CT was not sensitive for diagnosing skull base involvement but had substantial-to-near perfect agreement with pathologic tumor staging. CT is a useful but albeit limited adjunct for tumor localization and surgical planning for sinonasal IP.

Association of Olfactory Training With Neural Connectivity in Adults With Postviral Olfactory Dysfunction.

Importance: Viral upper respiratory tract infections are a major cause of olfactory loss. Olfactory training (OT) is a promising intervention for smell restoration; however, a mechanistic understanding of the changes in neural plasticity induced by OT is absent. Objective: To evaluate functional brain connectivity in adults with postviral olfactory dysfunction (PVOD) before and after OT using resting-state functional magnetic resonance imaging. Design, Setting, and Participants: This prospective cohort study, conducted from September 1, 2017, to November 30, 2019, recruited adults with clinically diagnosed or self-reported PVOD of 3 months or longer. Baseline olfaction was measured using the University of Pennsylvania Smell Identification Test (UPSIT) and the Sniffin' Sticks test. Analysis was performed between December 1, 2020, and July 1, 2020. Interventions: Participants completed 12 weeks of OT using 4 essential oils: rose, eucalyptus, lemon, and clove. The resting-state functional magnetic resonance imaging measurements were obtained before and after intervention. Main Outcome and Measures: The primary outcome measure was the change in functional brain connectivity before and after OT. Secondary outcome measures included changes in UPSIT and Sniffin' Sticks test scores, as well as patient-reported changes in treatment response as measured by subjective changes in smell and quality-of-life measures. Results: A total of 16 participants with PVOD (11 female [69%] and 14 White [88%]; mean [SD] age, 60.0 [10.5] years; median duration of smell loss, 12 months [range, 3-240 months]) and 20 control participants (15 [75%] female; 17 [85%] White; mean [SD] age, 55.0 [9.2] years; median UPSIT score, 37 [range, 34-39]) completed the study. At baseline, participants had increased connectivity within the visual cortex when compared with normosmic control participants, a connection that subsequently decreased after OT. Furthermore, 4 other network connectivity values were observed to change after OT, including an increase in connectivity between the left parietal occipital junction, a region of interest associated with olfactory processing, and the cerebellum. Conclusions and Relevance: The use of OT is associated with connectivity changes within the visual cortex. This case-control cohort study suggests that there is a visual connection to smell that has not been previously explored with OT and that further studies examining the efficacy of a bimodal visual and OT program are needed.

Survival Outcomes of De Novo vs Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

Importance: Overall, the prognosis of sinonasal squamous cell carcinoma (SCC) is poor. This malignancy can arise de novo or from inverted papillomas, but it is unclear whether survival differences between the 2 pathologies exist. Objective: To assess for survival differences between patients with sinonasal de novo SCC (dnSCC) and those with inverted papilloma-associated SCC (IPSCC). Data Sources: A search of Ovid MEDLINE, Embase, Scopus, and the Cochrane Library from inception to January 23, 2020, with cross-referencing of retrieved studies, was performed. Additional data were requested from authors. Study Selection: Inclusion and exclusion criteria were designed to capture studies with survival outcomes of adults with sinonasal SCC who underwent regular treatment. Clinical trials, cohort studies, case-control studies, and case series with more than 10 adults aged 18 years or older with sinonasal SCC were included. Exclusion criteria were studies on non-SCC sinonasal neoplasms, studies without histopathologic diagnoses, non-English language articles, nonhuman animal studies, and abstract-only articles. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) screened each abstract and full text, and a third investigator (J.J.L. or P.P.) adjudicated discrepancies. Of 729 unique citations, 26 studies of 1194 total patients were included. Data Extraction and Synthesis: Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The Methodological Index for Nonrandomized Studies (MINORS) criteria were used to assess study quality. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) independently extracted data from each study. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was overall survival, and secondary outcomes were disease-free and disease-specific survival. Before data collection, it was hypothesized that the dnSCC cohort would have worse survival outcomes than the IPSCC cohort. Results: One study of patients with dnSCC, 12 studies of patients with IPSCC, and 5 studies with both cohorts were included in the meta-analysis of overall survival. The pooled 5-year overall survival rate for 255 patients with dnSCC was 56% (95% CI, 41%-71%; I2 = 83.8%) and for 475 patients with IPSCC was 65% (95% CI, 56%-73%; I2 = 75.7%). Five comparative studies of both cohorts totaling 240 patients with dnSCC and 155 patients with IPSCC were included in another meta-analysis. The pooled overall survival hazard ratio was 1.87 (95% CI, 1.24-2.84; I2 = 0%). Conclusions and Relevance: This systematic review and meta-analysis found that patients with dnSCC had almost a 2-fold increased risk of mortality compared with those with IPSCC. Large, multicenter studies are necessary to validate these findings before considering treatment alterations such as de-escalation based on histopathology.

Development and Validation of the Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia (NOSE HHT).

Importance: Epistaxis is the greatest cause of morbidity in patients with hereditary hemorrhagic telangiectasia (HHT); because of this, a validated epistaxis-specific quality-of-life instrument for HHT should be made available. Objective: To develop and validate an epistaxis-specific quality-of-life patient-reported outcome measure for HHT. Design, Setting, and Participants: This survey study focused on the development and validation of the Nasal Outcome Score for Epistaxis (NOSE) in HTT (NOSE HHT) outcome measure with data prospectively collected from December 10, 2019, to March 15, 2020. A total of 401 patients were recruited from within the Cure Hemorrhagic Telangiectasia online patient advocacy social media network, the Washington University HHT Center of Excellence, and a randomized clinical trial investigating an intranasal timolol gel for HHT-associated epistaxis. Main Outcomes and Measures: Face and content validity, factor analysis, internal consistency as measured through Cronbach α, construct validity, responsiveness to change, and minimal clinically important difference. Results: The NOSE HHT was developed and validated with a possible score ranging discretely from 0 to 4 for each of the 29 items and a total score ranging continuously from 0 to 4 after dividing by the total number of items answered. A total of 401 participants completed the NOSE HHT. Factor analysis identified 3 factors that matched the a priori specified subgroups of particular aspects of life affected by HHT-associated epistaxis: physical problems (mean [SD] magnitude, 1.59 [0.83]), functional limitations (mean [SD] magnitude, 1.28 [0.84]), and emotional consequences (mean [SD] magnitude, 1.95 [1.02]). The instrument had high internal consistency with an overall Cronbach α of 0.960. Convergent validity determined the total NOSE HHT score to be a strong predictor of disease severity; total NOSE HHT score can be split up into the following epistaxis severity categories: mild (0-1), moderate (1.01-2), and severe (>2). The instrument was found to be sensitive to change, and the minimal clinically important difference for the total NOSE HHT score was 0.46. Conclusions and Relevance: Evaluation of the consistency, reliability, and responsiveness of the NOSE HHT survey found it to be a valid instrument to assess severity and change in epistaxis. Study results suggest that the NOSE HHT survey is clinically applicable and useful as an outcome measure of future HHT-associated epistaxis trials.

Efficacy of Timolol in a Novel Intranasal Thermosensitive Gel for Hereditary Hemorrhagic Telangiectasia-Associated Epistaxis: A Randomized Clinical Trial.

Importance: Other than nasal moisturizers, no standard-of-care medical therapy exists for epistaxis in hereditary hemorrhagic telangiectasia (HHT). With epistaxis as the greatest cause of morbidity in patients with HHT, there is a need to identify effective topical therapies. Objective: To determine the efficacy and safety of an intranasal timolol thermosensitive gel vs placebo thermosensitive gel in treating HHT-associated epistaxis. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial was conducted from October 29, 2019, to May 20, 2020, at a tertiary care center. A total of 27 patients with HHT and moderate-to-severe epistaxis were recruited and included in this prespecified analysis: 14 in the timolol group and 13 in the placebo group. Inclusion criteria included (1) age 18 years or older, (2) clinical or genetic diagnosis of HHT, (3) screening Epistaxis Severity Score (ESS) of 4 or greater and 2 or more nosebleeds cumulatively lasting at least 5 minutes per week, (4) stable epistaxis pattern over the preceding 3 months, and (5) no change in epistaxis treatment or nasal hygiene regimen in the preceding month. Exclusion criteria included (1) contraindications to systemic ß-blocker administration, (2) use of medications interacting with timolol, (3) use of antiangiogenic medications in the last month before recruitment, and (4) use of anticoagulants, antiplatelets, or fibrinolytic therapies within the last month. Interventions: Novel thermosensitive intranasal timolol (0.1%) gel vs placebo thermosensitive gel applied twice daily to each nostril for 8 weeks. Main Outcomes and Measures: The primary outcome was the median change in ESS and percentage of participants reaching the minimal clinically important difference in ESS. Secondary outcomes were changes in Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores, Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia, and hemoglobin level. Results: Of 27 participants randomized (median [range] age, 55 [20-76] years; 14 women [52%]; 25 White [93%]), a total of 23 patients with HHT completed the primary outcome measure. Within the timolol gel and placebo gel groups, respectively, the median change (range) in ESS was 2.32 (0.22 to 5.97) vs 1.96 (-0.91 to 5.98), and 9 of 11 (82%) vs 9 of 12 (75%) participants experienced a clinically meaningful improvement in ESS. Twenty-two of the 23 participants (96%) reported improvement via the Clinical Global Impression-Improvement score, with 81% vs 58% of participants reporting reduced severity of epistaxis in the timolol vs placebo group, respectively. Of participants completing the Nasal Outcome Score for Epistaxis in HHT at follow-up visit, 7 of 10 (70%) in the timolol group achieved a clinically important difference vs 5 of 10 (50%) in the placebo group. There was no change in hemoglobin level between or within groups. Zero participants in the placebo group and 2 of 13 (15%) in the timolol group withdrew because of adverse events. Conclusions and Relevance: Thermosensitive gel, alone or in combination with timolol, was highly effective in reducing HHT-associated epistaxis. The timolol group had greater improvement in epistaxis and quality of life than the placebo group, but effect estimates were imprecise, and no definitive conclusions on the superiority of timolol can be drawn. Physicians treating patients with HHT-associated epistaxis should consider a thermosensitive gel (with or without timolol) for their patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04139018.

Axis-specific analysis and predictors of endocrine recovery and deficits for non-functioning pituitary adenomas undergoing endoscopic transsphenoidal surgery.

PURPOSE: Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS: A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. RESULTS: Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. CONCLUSIONS: Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.

Risk Factors for Patient-Reported Olfactory Dysfunction After Endoscopic Transsphenoidal Hypophysectomy.

Importance: Iatrogenic olfactory dysfunction after endoscopic transsphenoidal hypophysectomy (ETSH) is an overlooked complication without elucidated risk factors. Objective: To assess the independent prognostic role of demographic, comorbidity, cephalometric, intraoperative, histological, and postoperative parameters in patient-reported postoperative olfactory dysfunction, and to explore the association between anatomical measurements of the skull base and sinonasal cavity and postoperative olfactory dysfunction. Design, Setting, and Participants: This retrospective cohort study in a tertiary care medical center enrolled consecutive patients with primary sellar lesions who underwent ETSH between January 1, 2015, and January 31, 2019. Patients were excluded if they underwent multiple sinonasal surgical procedures, presented with a sellar malignant neoplasm, required an expanded transsphenoidal approach, had nasal polyposis or a neurodegenerative disease, or sustained traumatic brain injury. After undergoing medical record review and telephone screening, patients were asked to participate in a 3-item telephone survey. Main Outcomes and Measures: The primary outcome was the Clinical Global Impressions change in smell rating, a validated transitional patient-reported outcome measure. Patients rated their change in smell before and after ETSH on a 7-point Likert scale, with the following response options: (1) much better, (2) somewhat better, (3) slightly better, (4) neither better nor worse, (5) slightly worse, (6) somewhat worse, or (7) much worse. Responses of slightly worse, somewhat worse, and much worse were surrogates for postoperative olfactory dysfunction status. Patient medical records, preoperative imaging scans, operative notes, and pathology reports were reviewed. Results: Of the 147 patients (mean [SD] age, 54 [15] years; 79 women [54%]) who responded to the telephone survey, 42 (29%) reported olfactory dysfunction after ETSH. Median (interquartile range [IQR]) time between the ETSH completion and survey response was 31.1 (21-43) months. On multivariable analysis, abdominal fat grafting (adjusted relative risk [aRR], 2.95; 95% CI, 1.89-4.60) was associated with postoperative olfactory dysfunction, whereas smoking history (aRR, 1.54; 95% CI, 0.95-2.51) demonstrated a clinically meaningful but imprecise effect size. A more obtuse angle between the planum sphenoidale and face of the sella turcica on sagittal imaging was protective (aRR, 0.98; 95% CI, 0.96-0.99). Increased number of months after the ETSH was associated with patient-reported normosmia (aRR, 0.93; 95% CI, 0.91-0.95). In contrast, other comorbidities; intraoperative variables such as turbinate resection, nasoseptal flap, and mucosal or bone grafting; histological variables such as pathology and proliferative index; and postoperative variables such as adjuvant radiotherapy were not associated with postoperative olfactory dysfunction. Conclusions and Relevance: This study found that abdominal fat grafting, acute skull base angle, and smoking history appeared to be clinically significant risk factors for patient-reported postoperative olfactory dysfunction. Increased time after ETSH may be associated with better olfactory outcomes.

Randomized clinical trial to evaluate mometasone lavage vs spray for patients with chronic rhinosinusitis without nasal polyps who have not undergone sinus surgery.

BACKGROUND: There is no consensus regarding the best route of intranasal delivery of corticosteroids in the treatment of chronic rhinosinusitis (CRS). The study objective of this work was to compare the impact of mometasone furoate nasal spray (MFNS) vs mometasone nasal irrigation in the management of CRS patients who have not undergone sinus surgery. METHODS: A double-blind, placebo-controlled, randomized clinical trial was conducted in adults with CRS. Individuals with nasal polyps and/or history of sinus surgery were excluded. Patients were randomized to receive 8 weeks of either MFNS or mometasone nasal irrigation. The primary outcome measure was change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score between the 2 groups. Secondary outcome measures included patient global response to treatment and Lund-Kennedy endoscopy scores. RESULTS: A total of 43 participants completed the study (n = 22, MFNS; n = 21,mometasone nasal irrigation). Fourteen (64%) participants in the MFNS group and 17 (81%) in the mometasone lavage group had a clinically meaningful improvement in SNOT-22 scores with a proportion difference of 17% (95% confidence interval [CI], -9% to 44%). The least-squares (LS) mean difference between the 2 groups for SNOT-22 was -8.6 (95% CI, -17.7 to 0.58; p = 0.07), whereas the LS mean difference between the 2 groups for Lund-Kennedy endoscopy scores was 0.16 (95% CI, -0.84 to 1.15; p = 0.75). No adverse events were associated with the study. CONCLUSION: Both MFNS and mometasone nasal irrigations are beneficial in symptom management of CRS. Our study suggests that patients who perform mometasone lavage do better in a clinically meaningful way, but our results are not definitive and further studies are warranted.