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Background: Chronic rhinosinusitis with nasal polyps affects approximately 2–4% of the general population, and long-term use of systemic corticosteroids is associated with adverse effects. The aim of this study was to assess the efficacy and safety of mepolizumab in adults with recurrent, refractory severe bilateral chronic rhinosinusitis with nasal polyps. Methods: SYNAPSE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done at 93 centres, mainly hospitals, in 11 countries. Eligible patients were aged 18 years or older with recurrent, refractory, severe, bilateral nasal polyp symptoms (nasal obstruction symptom visual analogue scale [VAS] score of >5), were eligible for repeat nasal surgery (overall symptoms VAS score >7 and endoscopic nasal polyps score of ≥5, with a minimum score of 2 in each nasal cavity) despite standard of care treatment, and had to have at least one nasal surgery in the past 10 years. Patients were randomly assigned (1:1), using permuted block design, to receive either 100 mg mepolizumab subcutaneously or placebo once every 4 weeks, in addition to standard of care (mometasone furoate intranasal spray for at least 8 weeks before screening and during the study, saline nasal irrigations, systemic corticosteroids or antibiotics, or both), as required, for 52 weeks. Site staff, the central study team, and patients were masked to study treatment and absolute blood eosinophil counts. The coprimary endpoints were change from baseline in total endoscopic nasal polyp score at week 52 and in mean nasal obstruction VAS score during weeks 49–52, assessed in the intention-to-treat population (ITT). This study is registered with ClinicalTrials.gov, NCT03085797. Findings: From May 25, 2017, to Dec 12, 2018, 854 patients were screened for eligibility. 414 patients were randomly assigned with 407 included in the ITT population; 206 received mepolizumab and 201 received placebo. Total endoscopic nasal polyp score significantly improved at week 52 from baseline with mepolizumab versus placebo (adjusted difference in medians −0·73, 95% CI −1·11 to −0·34; p

SummaryBackgroundThe monoclonal antibody combination casirivimab and imdevimab (REGEN-COV®) reduced viral load, hospitalisation, or death when administered 1:1 as an intravenous (IV) dose ≥1200 mg in a phase 3 COVID-19 outpatient study. Availability of subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients.MethodsThis is a double-blind, placebo-controlled study of SARS-CoV-2-infected outpatients who were asymptomatic, or symptomatic but without risk factors for severe COVID-19. Patients were randomised to single IV dose (517 patients) of REGEN-COV 300, 600, 1200 or 2400 mg or placebo; or a single SC dose (286 patients) of REGEN-COV 600 or 1200 mg or placebo. The primary endpoint was time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative to SARS-CoV-2 at baseline.FindingsAll REGEN-COV treatments showed significant (p10 copies/mL. Each REGEN-COV treatment showed significant (pInterpretationIn asymptomatic and low-risk symptomatic SARS-CoV-2-infected outpatients seronegative for antibodies against SARS-CoV-2 at baseline, REGEN-COV significantly and comparably reduced viral load at all IV and SC doses.FundingRegeneron Pharmaceuticals, Inc. and Hoffman-La RocheRESEARCH IN CONTEXTEvidence before this studyEarly phase 1/2 data in coronavirus disease 2019 (COVID-19) outpatients (NCT04425629) found that the REGEN-COV® antibody combination, casirivimab and imdevimab, administered 1:1 as a single intravenous (IV) dose of 2400 mg or 8000 mg significantly reduced viral load over the first week compared to placebo. Enhanced viral clearance was more pronounced in patients who were seronegative for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or who had high viral load at baseline. The phase 3 portion of this outpatient treatment study subsequently evaluated 1200 mg IV and 2400 mg IV doses, demonstrating consistent virologic efficacy, further demonstrating that REGEN-COV treatment reduced risk of COVID-19-related hospitalisation or all-cause death, and shortened time to symptom resolution. Virologic clearance was similar among those treated with any of the three doses (8000 mg, 2400 mg, or 1200 mg); therefore, maximal virologic efficacy may have been achieved at the 1200 mg dose in this treatment setting. These results warranted investigation of lower dose regimens.Added value of this studyThe present dose-ranging study evaluated whether a lower dose regimen could demonstrate virologic efficacy similar to that observed with 1200 mg IV and 2400 mg IV doses in outpatient treatment study. Exploration of a wider dose range will provide further characterisation of the clinical effects of REGEN-COV. Moreover, identifying a lower efficacious dose could bolster the ability to provide an adequate therapeutic supply of REGEN-COV in the setting of a global pandemic. A 1200 mg subcutaneous (SC) dose of REGEN-COV also prevented COVID-19 in household contacts of SARS-CoV-2-infected individuals (NCT04452318). The availability of a SC regimen could improve access for patients who have confirmed SARS-CoV-2 infection but for who IV infusion is not feasible.Implications of all the available evidenceDespite the growing number of therapeutics with authorisation or approval for the treatment and/or prevention of COVID-19, there remains a significant global need for effective COVID-19 therapies. Additional therapeutics and dosing regimens will be required to meet demand and to meet the needs of specific patient populations. Lower IV doses of REGEN-COV, and the option of SC administration, should increase accessibility for patients. This increased availability needs to be weighed against several unanswered questions, including 1) whether the correlation between decreased viral load in the nasopharynx and improvement in clinical outcome holds at lower doses of REGEN-COV, and 2) whether the reduced drug exposure margins are sufficient to prevent viral escape and emergence of variants of concern.

The monoclonal antibody combination of casirivimab and imdevimab reduced viral load, hospitalization, or death when administered as a 1200-mg or greater intravenous (IV) dose in a phase 3 COVID-19 outpatient study. Subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients.To assess the virologic efficacy of casirivimab and imdevimab across different IV and SC doses compared with placebo.This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study included outpatients with SARS-CoV-2 infection at 47 sites across the United States. Participants could be symptomatic or asymptomatic; symptomatic patients with risk factors for severe COVID-19 were excluded. Data were collected from December 15, 2020, to March 4, 2021.Patients were randomized to a single IV dose (523 patients) of casirivimab and imdevimab at 300, 600, 1200, or 2400 mg or placebo; or a single SC dose (292 patients) of casirivimab and imdevimab at 600 or 1200 mg or placebo.The primary end point was the time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative for SARS-CoV-2 at baseline.Among 815 randomized participants, 507 (282 randomized to IV treatment, 148 randomized to SC treatment, and 77 randomized to placebo) were seronegative at baseline and included in the primary efficacy analysis. Participants randomized to IV had a mean (SD) age of 34.6 (9.6) years (160 [44.6%] men; 14 [3.9%] Black; 121 [33.7%] Hispanic or Latino; 309 [86.1%] White); those randomized to SC had a mean age of 34.1 (10.0) years (102 [45.3%] men; 75 [34.7%] Hispanic or Latino; 6 [2.7%] Black; 190 [84.4%] White). All casirivimab and imdevimab treatments showed significant virologic reduction through day 7. Least-squares mean differences in TWACB viral load for casirivimab and imdevimab vs placebo ranged from -0.56 (95% CI; -0.89 to -0.24) log10 copies/mL for the 1200-mg IV dose to -0.71 (95% CI, -1.05 to -0.38) log10 copies/mL for the 2400-mg IV dose. There were no adverse safety signals or dose-related safety findings, grade 2 or greater infusion-related or hypersensitivity reactions, grade 3 or greater injection-site reactions, or fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported.In this randomized clinical trial including outpatients with asymptomatic and low-risk symptomatic SARS-CoV-2, all IV and SC doses of casirivimab and imdevimab comparably reduced viral load.ClinicalTrials.gov Identifier: NCT04666441.

Summary Objective We sought to evaluate the role and efficacy of intraoperative fistulograms in visualizing branchial apparatus (fistula/sinus) abnormalities in the pediatric age group (3 months–12 years). Methods This was a retrospective analysis of 20 pediatric patients who underwent fistula and/or sinus excision during a period of 18 years (1988–2006). Results The male:female ratio was 11:9. Eighteen of the 20 patients presented with unilateral abnormalities, 2 with bilateral abnormalities. An intraoperative fistulogram was utilized in every instance. The fistulogram clearly differentiated the sinus tracts from complete fistulas in all cases. It was also highly useful in delineating the exact length and course of the sinus/fistula tracts. Conclusions Intraoperative fistulograms are easy to do in the operating room on the day of the scheduled surgery. They are a very useful tool in the management of branchial apparatus abnormalities.

Summary Aim To determine the association between body position and obstructive events during sleep as determined by polysomnography (PSG) in infants of ages 8–12 months with obstructive sleep apnea (OSA). Methods Consecutive nocturnal polysomnograms (NPSGs) of 50 children ages 8–12 months old referred to the sleep disorders center between 1 January 2003 and 1 June 2006 for possible sleep-disordered breathing were retrospectively reviewed. Data on total obstructive apnea index (AI), total obstructive apnea–hypopnea index (AHI), AI by body position, AHI by body position, rapid eye movement (REM) and non-REM sleep AHI and REM and non-REM AI were recorded. Results The mean age was 9.5 ± 1.9 S.D. months and 46% of the patients were females. There were no significant differences between the mean non-supine AHI (2.0 ± 5.1) and supine AHI (2.5 ± 5.4), p = 0.63. When comparing specific body positions, there were also no significant differences between the mean supine AHI (2.5 ± 5.4), prone AHI (2.9 ± 7.3), left-lateral decubitus AHI (1.1 ± 6.1), or the right-lateral decubitus AHI (2.5 ± 7.6), p = 0.71. Additionally, there were also no significant differences between the mean non-supine AI (0.7 ± 2.9) and supine AI (1.4 ± 3.0), p = 0.23, and no differences between the supine AI (0.7 ± 2.9), prone AI (1.0 ± 2.9), left-lateral decubitus AI (0.3 ± 2.9) or the right-lateral decubitus AI (1.1 ± 3.0), p = 0.44. Children spent an average of 50% of their total sleep time supine. OSA was significantly worse in REM sleep as compared to non-REM sleep (REM AHI 4.3 ± 7.3 versus non-REM AHI 1.4 ± 3.9, p = 0.015; REM AI 5.1 ± 4.9 versus non-REM AI 1.5 ± 4.9, p Conclusions There was no significant effect of body position on sleep-disordered breathing in 8–12 months old infants, although REM sleep represented a significant risk factor for OSA.

Subperiosteal orbital abscess (SPOA) is an uncommon but serious consequence of sinusitis, especially in the pediatric population. Historically, medical and surgical arms have been utilized in the treatment of SPOA. Below is a case report of a 14 year-old-boy with recalcitrant, superiorly based SPOA followed by a literature search and discussion.