The role of ANCA in the management of cocaine-induced midline destructive lesions or ENT pseudo-granulomatosis with polyangiitis: a London multicentre case series.

OBJECTIVE: In this multicentric study involving three London hospitals, we compared ANCA-positive and ANCA-negative cocaine-induced midline destructive lesions (CIMDL) patients to assess how presence of antineutrophil cytoplasmic antibodies (ANCA) may correlate with disease severity. Our secondary aims are to better classify etiology centered around ANCA positivity and, consequently, better disease management. METHODS: A retrospective review was performed to identify patients with CIMDL seen between January 2019 and December 2022. Population data including age, sex, presentation, endoscopic findings, duration of cocaine use and active use of cocaine, type of treatment, laboratory (including ANCA serology), radiological, and histological findings were collected. RESULTS: Forty CIMDL patients (25 male, median age of 42 years) were identified. The majority of them (72.5%) presented with either a septal perforation, a saddle nose deformity (22.5%), and/or a palatal fistula (20.0%). ANCA was positive in 71.1% of cases (66.7% p-ANCA). No statistically significant differences in the general characteristics, type of treatment, laboratory results, radiological or histological findings were observed when comparing ANCA-positive and ANCA-negative CIMDL patients or when comparing p-ANCA and c-ANCA patients. Similarly, no statistically significant difference was obtained when comparing the pattern of distribution of lesions between the two groups. CONCLUSIONS: A large percentage of CIMDL patients showed positive ANCA test (71.1%) and in the majority of the cases a p-ANCA pattern specifically targeting PR3 (p-ANCA, PR3 + MPO-). However, ANCA positivity or presence of a specific ANCA pattern was not associated with more severe presentation or more aggressive disease. Given its similarities to granulomatosis with polyangiitis (GPA), we recommend the use of the term "cocaine-induced ENT pseudo-GPA" instead of CIMDL. LEVEL OF EVIDENCE: IV Laryngoscope, 2023.

Clinical factors influencing olfactory performance in patients with persistent COVID-19 smell loss longer than 1 year.

Objectives: Factors affecting persistence of COVID-19-related olfactory dysfunction (OD) remain partially unknown. We aim to evaluate the clinical factors which could influence olfactory performance in patients with persistent COVID-19-related smell loss. Methods: A retrospective analysis of 100 patients with persistent COVID-19-related OD was performed between October 2020 and December 2022 at a single-center long-COVID smell clinic. All subjects underwent smell assessment using Sniffin' Sticks (S'S) extended test, nasal endoscopy, nasal airflow evaluation (peak nasal inspiratory flow [PNIF]), allergy test (skin prick test [SPT]) for common aeroallergens, MRI of the head and patient-reported outcome measures (PROMs-VAS, SF-36, Short QOD-NS, SNOT-22). Based on S'S score, subjects were divided into normosmics (TDI ≥ 30.75) and dysosmics (TDI < 30.75). Results: The median age was 42 years and the median length of patient-reported OD was 1.4 years. 20 patients (20.0%) were normosmic at the time of S'S assessment. Dysosmic patients were found to have significantly lower scores at the SF-36 health domains for energy/fatigue (p = .0004) and emotional wellbeing (p = .04) when compared to normosmics. A moderate correlation (r = .45-.59) between S'S scores and some PROMs was also demonstrated. At the multivariate analysis higher PNIF scores positively influenced odor threshold (p = .001) while positivity to SPT negatively influenced odor identification (p = .04). Conclusions: Impairment of nasal airflow and sensitivity to aeroallergens can negatively affect olfactory performance in COVID-19-related OD. Long-COVID smell loss deeply affects QoL although recovery of olfaction can bring it back to a normal range. Level of Evidence: IV.

International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Functional septorhinoplasty alters brain structure and function: Neuroanatomical correlates of olfactory dysfunction.

Introduction: We previously demonstrated functionally significant structural plasticity within the central olfactory networks, in association with improved olfaction after surgical treatment of chronic rhinosinusitis (CRS). In order to confirm and expand on these findings, the primary aim of this study was to determine whether these same regions undergo functionally significant structural plasticity following functional septorhinoplasty (fSRP), in patients with non-CRS olfactory dysfunction (OD) of mixed cause. fSRP has previously been shown to improve olfactory function, and the secondary aim of this study was to provide initial insights into the mechanism by which fSRP affects olfaction. Methods: We performed a pilot prospective, multimodal neuroimaging study in 20 participants undergoing fSRP, including patients with non-CRS OD of mixed cause, as well as normosmic surgical controls. Participants underwent psychophysical olfactory testing, assessment of nasal airway, structural and functional neuroimaging. This was performed pre- and postoperatively in patients, and preoperatively in controls. Results: There was a statistically and clinically significant improvement in mean psychophysical olfactory scores after surgery. This was associated with structural and functional plasticity within areas of the central olfactory network (anterior cingulate, orbitofrontal cortex, insula, temporal pole). Improved psychophysical scores were significantly correlated with change in bilateral measures of nasal airflow, not measures of airflow symmetry, suggesting that improved overall airflow was more important than correction of septal deviation. Conclusion: This work highlights the importance of these neuroanatomical regions as potential structural correlates of olfactory function and dysfunction. Our results also provide initial insight into the mechanistic effects of fSRP on olfaction. Further work could investigate the utility of these regions as personalised biomarkers of OD, as well as the role of fSRP in treating OD.

Safety of day-case endoscopic sinus surgery in England: An observational study using an administrative dataset.

INTRODUCTION: As elective surgical services recover from the COVID-19 pandemic a movement towards day-case surgery may reduce waiting lists. However, evidence is needed to show that day-case surgery is safe for endoscopic sinus surgery (ESS). The aim of this study was to investigate the safety of day-case ESS in England. DESIGN: Secondary analysis of administrative data. METHODS: We extracted data from the Hospital Episodes Statistics database for the 5 years from 1 April 2014 to 31 March 2019. Patients undergoing elective ESS procedures aged ≥17 years were included. Exclusion criteria included malignant neoplasm, complex systemic disease and trans-sphenoidal pituitary surgery. The primary outcome was readmission within 30 days post-discharge. Multilevel, multivariable logistic regression modelling was used to compare outcomes for those operated on as day-cases and those with an overnight stay after adjusting for demographic, frailty, comorbidity and procedural covariates. RESULTS: Data were available for 49 223 patients operated on across 129 NHS hospital trusts. In trusts operating on more than 50 patients in the study period, rates of day-case surgery varied from 20.6% to 100%. Nationally, rates of day-case surgery increased from 64.0% in the financial year 2014/2015 to 78.7% in 2018/2019. Day-case patients had lower rates of 30-day emergency readmission (odds ratio 0.71, 95% confidence interval 0.62 to 0.81). Outcomes for patients operated on in trusts with ≥80% day-case rates compared with patients operated on in trusts with <50% rates of day-case surgery were similar. CONCLUSIONS: Our data support the view that ESS can safely be performed as day-case surgery in most cases, although it will not be suitable for all patients. There appears to be scope to increase rates of day-case ESS in some hospital trusts in England.

The Role of Social Media in Improving Patient Recruitment for Research Studies on Persistent Post-Infectious Olfactory Dysfunction.

Background and Objectives: Since the COVID-19 pandemic, the number of cases of post-infectious olfactory dysfunction (PIOD) has substantially increased. Despite a good recovery rate, olfactory dysfunction (OD) becomes persistent in up to 15% of cases and further research is needed to find new treatment modalities for those patients who have not improved on currently available treatments. Social media has emerged as a potential avenue for patient recruitment, but its role in recruiting patients with smell dysfunction remains unexplored. We conducted a survey using the AbScent Facebook page to evaluate the feasibility of using this platform for future studies on smell dysfunction. Materials and Methods: Between 26 October and 4 November 2021, we conducted an online survey to evaluate propensity of patients with PIOD who would be willing to participate in research studies on smell dysfunction. Results: Sixty-five subjects were surveyed with a response rate of 90.7%. The median visual analogue scale (VAS) for sense of smell was 0 at infection and 2 at survey completion. The median length of OD was 1.6 years, and the main cause of OD was SARS-CoV-2 (57.6%). Parosmia was reported in 41 subjects (69.5%) whilst phantosmia in 22 (37.3%). The median length of olfactory training (OT) was 6 months but subjectively effective in 15 subjects (25.4%). Twenty-seven subjects (45.8%) tried other medications to improve olfaction, but only 6 participants (22.2%) reported an improvement. All subjects expressed their propensity to participate in future studies with most of them (38; 64.4%) willing to be enrolled either in medical and surgical studies or to be part of a randomised study design (11; 18.6%). Conclusions: Using the AbScent Facebook platform we successfully selected a population of subjects with persistent and severe OD that have failed to improve on available treatments and are willing to participate in further clinical trials.

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.

INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

Prevalence of olfactory dysfunction and quality of life in hospitalised patients 1 year after SARS-CoV-2 infection: a cohort study.

OBJECTIVES: To determine the long-term prevalence of olfactory and/or gustatory dysfunction (OD±GD), associated risk factors and impact on quality of life (QoL) in previously hospitalised patients with COVID-19 1 year after infection. DESIGN: A single-centre cohort study. SETTING: Patients admitted at a large central London hospital with COVID-19 infection between 10 February 2020 and 22 May 2020. PARTICIPANTS: 150 adult subjects with previously confirmed SARS-CoV-2 infection were recruited between 10 December 2020 and 29 January 2021. Participants were predominantly male (102/150, 68.0%); mean age 58.0±15.9 years and 41.2% (56/136) were of black, Asian and minority ethnic backgrounds. MAIN OUTCOME MEASURES: EQ-5D-5L values and Sino-Nasal Outcome Test-22 (SNOT-22) scores. RESULTS: Long-term prevalence of OD±GD was 12.8% (19/149) at median time of 264.5 days following SARS-CoV-2 infection onset. Patients with OD±GD had a significantly higher median total SNOT-22 score (46.1; Q1-Q3: 23.0-60.0; 95% CI 23.0 to 60.0) compared with those without (16.0; Q1-Q3: 5.0-30.5; 95% CI 12.0 to 18.0) (p=0.0002), reflecting poorer QoL, particularly psychological well-being (p=0.0004), which was not alleviated with time (p=0.4977). Median EQ-5D-5L value was not significantly different between patients with OD±GD (0.70; Q1-Q3: 0.38-0.83; 95% CI 0.38 to 0.83) and those without (0.83; Q1-Q3: 0.61-0.94; 95% CI 0.75 to 0.89) (p=0.0627). Age, sex, ethnicity, smoking status, highest C reactive protein value, intubation and ventilation, and oxygen supplementation were not found to influence OD±GD (p>0.05). CONCLUSIONS: 12.8% of previously hospitalised patients with COVID-19 in London still report persistent problems with smell or taste up to a year after infection, impacting their QoL. Increased holistic support including psychological therapy and olfactory rehabilitation for affected patients may help to reduce long-term morbidity.

A retrospective study on long-term efficacy of intranasal lysine-aspirin in controlling NSAID-exacerbated respiratory disease.

PURPOSE: Aspirin treatment after desensitization (ATAD) represents an effective therapeutic option suitable for NSAID-exacerbated respiratory disease (N-ERD) patients with recalcitrant disease. Intranasal administration of lysine-aspirin (LAS) has been suggested as a safer and faster route than oral ATAD but evidence for its use is less strong. We investigated nasal LAS therapy long-term efficacy based on objective outcomes, smell function, polyp recurrence and need for surgery or rescue therapy. Clinical biomarkers predicting response to intranasal LAS, long-term side effects and consequences of discontinuing treatment have been evaluated. METHODS: A retrospective analysis of a database of 60 N-ERD patients seen between 2012 and 2020 was performed in March 2021. They were followed up at 3-months, 1-, 2- and 3-years with upper and lower airway functions assessed at each follow-up. RESULTS: Higher nasal airflow and smell scores were found at each follow-up in patients taking LAS (p < 0.001 and p = 0.048 respectively). No influence of LAS on pulmonary function measurements was observed. Patient on intranasal LAS showed a lower rate of revision sinus surgery when compared to those who discontinued the treatment (p < 0.001). None of the variables studied was found to influence LAS treatment response. CONCLUSION: Our study demonstrates the clinical effectiveness of long-term intranasal LAS in the management of N-ERD in terms of improved nasal airflow and olfaction and a reduced need for revision sinus surgery. Intranasal LAS is safe, being associated with a lower rate of side effects when compared to oral ATAD. However, discontinuation of the treatment at any stage is associated with a loss of clinical benefit.

A multicenter real-life study to determine the efficacy of corticosteroids and olfactory training in improving persistent COVID-19-related olfactory dysfunction.

Background: No definitive treatment exists to effectively restore function in patients with persistent post-infectious olfactory dysfunction (OD). Corticosteroids have been considered as a therapeutic option in post-infectious OD but their benefit in COVID-19-related OD remains unexplored. We aim to determine the role of the combination of corticosteroids plus olfactory training (OT) in improving persistent COVID-19-related OD. Methods: A multicenter real-life cohort study was conducted between December 2020 and April 2022 on patients with reported COVID-19-related OD. Only patients with confirmed OD at Sniffin' Sticks (S'S) and those who attended their 6-month follow-up were included. Patients were started on a combined treatment of corticosteroids and OT. Patients refusing corticosteroids or not doing any treatment formed the control groups. Visual analogue scale (VAS) for sense of smell and SNOT-22 were used to assess patients reported symptoms. Results: Sixty-seven subjects with reported COVID-19-related OD were initially seen. Normosmic patients at S'S (n = 14) and those not attending their follow-up (n = 9) were excluded. Of the 44 patients included in the analysis, 19 patients had the combined treatment (group A), 16 patients refused to take corticosteroids and did the OT alone (group B) whereas 9 patients did not do any treatment (group C). An improvement of threshold + discrimination + identification (TDI) score (p = .01) and VAS for smell (p = .01) was found in group A whereas only the TDI score improved in group B (p = .04). Presence of comorbidities, age, sex (male), and length of OD negatively influenced olfactory recovery. Conclusions: Our study confirms the importance of OT in long-term OD suggesting that the addition of corticosteroids may give a benefit in terms of patient's perceived olfaction. Level of Evidence: 2b.

Olfactory and Gustatory Function before and after Laparoscopic Sleeve Gastrectomy.

Background and Objectives: Bariatric surgery is the gold standard for the treatment of morbid obesity, and current evidence suggests that patients undergoing surgery can show changes in their sense of taste and smell. However, no definitive conclusions can be drawn given the heterogeneity of the studies and the contrasting results reported in the literature. Materials and Methods: We enrolled 18 obese patients undergoing laparoscopic sleeve gastrectomy (LSG) and 15 obese controls. At baseline (T0) and 6 months after enrollment/surgery (T1), both groups underwent Sniffin' Sticks and whole mouth test. Post-operative qualitative taste variations were also analyzed and SNOT-22, VAS for taste and smell, and MMSE were administered. Results: An improvement in the olfactory threshold was observed in the treatment group (p = 0.03) at 6 months. At multivariate analysis, the olfactory threshold differences observed correlated with MMSE (p = 0.03) and T0 gustatory identification (p = 0.01). No changes in sense of taste were observed between the two groups at 6 months, even though nine subjects in the treatment group reported a worsening of taste. This negatively correlated with age (p < 0.001), but a positive marginal correlation was observed with the olfactory threshold difference between T0 and T1 (p = 0.06). Conclusions: Olfaction can improve after LSG, and this seems to be the consequence of an improved olfactory threshold. Although we did not observe any change in gustatory identification, food's pleasantness worsened after bariatric surgery.

The Nasal Obstruction Balance Index: A Novel Approach to Improving Correlation Between Unilateral Nasal Airway Measurements and Evaluating Nasal Airway Asymmetry.

OBJECTIVES/HYPOTHESIS: Demonstrate that the Nasal Obstruction Balance Index (NOBI) model fulfils the unmet need of improving unilateral correlation between subjective and objective nasal obstruction outcome measures and identifying the more obstructed side. Improve correlation between unilateral objective nasal airway measurements (nasal inspiratory peak flow [NIPF] and acoustic rhinometry [AR]) and subjective Visual Analogue Scale for nasal obstruction (VAS-NO) scores. Improve assessment of nasal airway asymmetry by evaluating unilateral measurements both before and after the application of nasal decongestant; which the patient could better understand. NOBI represents a ratio calculated by taking the difference between left and right nasal airway measurements and divided by the maximum unilateral measurement. It is based on Poiseuille's law and aims to reduce the confounding variables which challenge nasal airway measurement. STUDY DESIGN: Prospective cohort study. METHODS: Forty-three controls and 34 patients with nasal obstruction underwent both unilateral and bilateral NIPF, AR and VAS-NO measurements; these were repeated after the application of nasal decongestant. The NOBI values for unilateral NIPF, AR, and VAS-NO were calculated both before and after decongestant. RESULTS: The correlation between unilateral NIPF and AR measurements was enhanced considerably (r = 0.57, P < .01) when NOBI was applied. The NOBI metric significantly increased the correlation between unilateral NIPF, AR, and VAS-NO scores. Postdecongestant NOBI for NIPF and AR measurements correctly identified the more obstructed side in 82.4% and 94.1% of the deviated nasal septum (DNS) cases, respectively. CONCLUSION: The NOBI model provides a better correlation between unilateral subjective and objective measurements and identifies the more obstructed side. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2833-E2840, 2021.

Olfactory dysfunction in antineutrophil cytoplasmic antibody-associated vasculitides: A review of the literature.

Olfactory dysfunction (OD) has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides (AAV), but the underlying mechanisms are not completely understood. The causes of altered smell function can generally be divided into conductive, sensorineural or others. To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored. The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV. Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.

The Evidence Base for the Benefits of Functional Septorhinoplasty and its Future Post COVID-19.

Ever since the introduction of the concept of Procedures of Limited Clinical Value (PoLCV), procedures such as functional septorhinoplasty have been subject to additional funding restrictions within the British National Health Service. Recent publications have suggested that 10% of Clinical Commissioning Groups in the United Kingdom no longer fund septorhinoplasty surgery irrespective of the indications, including congenital malformations or post-trauma, and despite the strong evidence available in the literature in treating a range of health conditions. Thus, inequity exists across the country. At present functional septorhinoplasty surgery is frequently but incorrectly grouped together with aesthetic rhinoplasty, both of which are deemed to be cosmetic interventions. Moreover, as we exit the peak of the current coronavirus disease 2019 (COVID-19) pandemic, procedures deemed to be of lower clinical priority will potentially be at risk throughout Europe. The purpose of this review is twofold; the first is to put forward the evidence to commissioners in favor of functional septorhinoplasty surgery on patient well-being and mental health; the second is to demonstrate why functional septorhinoplasty surgery is a distinct procedure from aesthetic rhinoplasty and why it ought not to be classified as a procedure of limited clinical value.