Symptoms suggestive of ET dysfunction are frequent in CRS, and for most patients the symptoms will decrease post-ESS to a level comparable with a non-CRS population. Patients whose ET symptoms do not respond to ESS may represent a target population for emerging therapeutic options for ET dysfunction.

Background The sinonasal microbiome is believed to play an important role in the pathophysiology of refractory chronic rhinosinusitis CRS We evaluated changes in the microbiome following a-month course of low-dose azithromycin Assessing microbiome alterations following such a treatment may help identify underlying mechanisms of this drug Methods A total of adults with refractory CRS were enrolled in a double-blind randomized placebo-controlled trial Patients were randomized to mg of azithromycin or placebo times weekly for months During this time daily budesonide saline irrigations were continued Sinonasal swabs were collected by endoscopically-assisted method prior to treatment initiation and at the end of it and sent for S ribosomal RNA gene sequencing Highresolution ANCHOR pipeline was used to infer and annotate putative species The patient groups were compared using DESeq differential abundance analysis Results From initiation to the end of azithromycin treatment patients showed a significant difference in beta diversity analysis p = along with a significant decrease in different operational taxonomic units OTUs of Staphylococcus aureus false discovery rate FDR < obtained from the differential abundance analysis This was not observed in placebo-treated patients By the end of treatments azithromycin-treated patients had a significant decrease in different OTUs of S aureus FDR < when compared to placebo Conclusion A-month course of mg of azithromycin times weekly in patients with refractory CRS significantly decreases S aureus abundance in the sinonasal microbiome Considering the pathogenic role of S aureus in the refractory CRS population azithromycin may constitute an additional therapeutic option to help control this disease

Objectives: Identify whether identification of S. aureus on conventional culture is a predictor of success or failure after ESS followed by budesonide nasal irrigations (BUD) in chronic rhinosinusitis (CRS) patients at high risk of recurrence.Methodology: Prospective clinical trial including 116 patients from a tertiary care center at high-risk of disease recurrence following ESS+BUD. Blood samples, microbial swabs, and SNSS/SNOT-22 were taken on the day of surgery (Visit-1) and 4 months postoperatively (Visit-2). Outcomes were evaluated using symptoms and mucosal status as assessed by the Lund-Kennedy endoscopic score.Results: Seventy-five patients (69.4%) attained SNOT-22 MCID or higher. (Mean = 33.4, range 9–75). Objective documentation of recurrence of disease, as defined by combined endoscopic/symptomatic criteria, was noted in 58/116 patients (50%). Revision surgery was associated with a significantly higher rate of disease recurrence (60.0 vs. 28.0%; p < 0.001). Culture for Staphylococcus aureus was associated with disease recurrence, preoperatively and at 4 months post-surgery (p = 0.020; p < 0.001). This was restricted to post-operative cultures in the revision group (10.0 vs. 48.8%; p < 0.001). Other factors associated with poor outcome included intolerance to non-steroidal anti-inflammatory drugs (NSAID) (p = 0.036). Significantly higher Lund-Kennedy scores in the recurrence groups despite similar symptom intensity, emphasizing the importance of considering objective outcome in addition to patient-reported ones.Conclusion: Patients undergoing revision ESS are at high risk of disease recurrence, even when budesonide irrigations are used post operatively. Presence of S. aureus on culture pre-operatively or at 4 months post-ESS is associated with a negative outcome. This suggests that S. aureus negatively influences outcome, possibly via a number of mechanisms, including interactions with the (i) immune system, (ii) regeneration and repair of the sinus epithelium, or (iii) via interference with the sinus microbiome. This suggests that S. aureus may be a simple and inexpensive biomarker for disease severity and indicates a clear need to better appreciate S. aureus on how it contributes mechanistically to disease development and persistence in order to develop targeted therapeutic strategies.

Objectives Endolymphatic sac (ELS) pathophysiology in Ménière's disease (MD) remains poorly understood. We identified from the literature a group of proteins expressed on the ELS and involved in endolymph volume regulation: aquaporin-2 (AQP2), vasopressin receptor V2R, sodium potassium chloride cotransporter 2 (NKCC2), and transient receptor potential cation channel V4 (TRPV4). Our objective was to determine whether their ELS expression was altered in MD, to better understand the pathophysiology of endolymphatic hydrops. Study Design Prospective case-control study. Setting Tertiary care center. Subjects Twenty-four patients with definite MD undergoing endolymphatic duct blockage surgery were recruited, as well as 23 controls with no history of MD undergoing surgery for vestibular schwannoma (VS). Methods ELS biopsies and blood samples for plasma arginine vasopressin (AVP) were obtained. Immunohistochemistry for AQP2, V2R, NKCC2, and TRPV4 was performed. Slides were scanned digitally for highly sensitive pixel density analysis by specialized software (VIS; Visiopharm). Results Global scores generated by the software represent total and relative protein expression density of 3 staining intensity levels, exclusively on ELS epithelium. AQP2 expression density was significantly elevated in MD compared to VS ( P = .003). There was no significant difference in plasma AVP, V2R, NKCC2, and TRPV4 expression. Conclusion This original study evaluates simultaneous in situ expression of AQP2, V2R, NKCC2, and TRPV4 on the human ELS in MD, with a control group. Our results show only AQP2 upregulation on the ELS of patients with MD. We suggest a constitutively increased expression of AQP2 in MD, independent of its regulatory axis (AVP-V2R). Acquired regulator sequence mutations could support this model.

Background Refractory chronic rhinosinusitis CRS remains a significant burden for patients o en leaving them with few therapeutic options that provide low-morbidity long-term and meaningful symptomatologic and endoscopic disease improvement Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect Our objective was to evaluate the efficacy of low-dose long-term azithromycin in a carefully selected high-risk population failing appropriate medical therapy of budesonide nasal irrigations BNIs and endoscopic sinus surgery ESS Methods A double-blind randomized placebo-controlled trial was completed in a single tertiary-care center assessing the addition of mg azithromycin times per week for weeks in adults failing ESS and high-volume BNIs Associated comorbidities as well as symptomatologic microbiologic and serologic values were systematically collected Results A total of patients were enrolled and underwent ESS followed by BNI At the-month post-ESS visit patients showed disease persistence and were randomized to azithromycin or placebo Overall azithromycin when compared with placebo did not show a statistically significant difference in disease clearance vs respectively p = although patients with disease clearance who were on azithromycin showed significantly betteritem Sino-Nasal Outcome Test score improvements than patients on placebo vs − respectively p = In a subgroup analysis excluding aspirin-exacerbated respiratory disease AERD patients azithromycin significantly improved disease clearance when compared with placebo vs respectively p = with a number needed to treat of Conclusion Low-dose azithromycin is a therapeutic option with few side effects Its use can show favorable clinical outcomes in this difficult-to-treat population especially if patients are AERD-negative © 2020 ARS-AAOA, LLC.