Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial.

Importance: 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. Objective: To assess the virologic efficacy of casirivimab and imdevimab across different IV and SC doses compared with placebo. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT04666441.

Intraoperative fistulograms in the management of branchial apparatus abnormalities in children.

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.

Body position and obstructive sleep apnea in 8-12-month-old infants.

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+/-1.9S.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<0.001). Mean time in REM sleep was 26% (range 5-42%). 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.

Contemporary Approach to the Diagnosis and Management of Cerebrospinal Fluid Rhinorrhea.

BACKGROUND: Cerebrospinal fluid (CSF) rhinorrhea, when left untreated, can lead to meningitis and other serious complications. Treatment traditionally has entailed an open craniotomy, although the paradigm has now evolved to encompass endoscopic procedures. Trauma, both accidental and iatrogenic, causes the majority of leaks, and trauma involving skull base and facial fractures is most likely to cause CSF rhinorrhea. Diagnosis is aided by biochemical assay and imaging studies. METHODS: We reviewed the literature and summarized current practice regarding the diagnosis and management of CSF rhinorrhea. RESULTS: Management of CSF leaks is dictated by the nature of the fistula, its location, and flow volume. Control of elevated intracranial pressure may require medical therapy or shunt procedures. Surgical reconstruction utilizes a graduated approach involving vascularized, nonvascularized, and adjunctive techniques to achieve closure of the CSF leak. Endoscopic techniques have an important role in select cases. CONCLUSION: An active surgical approach to closing CSF leaks may provide better long-term outcomes in some patients compared to more conservative management.

Intraoperative recurrent laryngeal nerve monitoring in thyroid surgery: is it worth the cost?

BACKGROUND: Intraoperative nerve monitoring (IONM) has been used in head and neck surgery since the 1970s. Its utilization for monitoring and protecting the recurrent laryngeal nerve, however, is a controversial subject. This paper details the use, value, and cost of this technology within a single institution. METHODS: We conducted a retrospective chart review, analysis of surgery time with and without IONM, analysis of postoperative vocal cord function, and review of the literature. RESULTS: IONM did not reduce the operative time during either thyroid lobectomies or total thyroidectomies in 119 surgeries. Use of IONM increased the cost of each surgery by $387. IONM did not decrease the number of injured nerves (postoperative paresis). CONCLUSIONS: IONM has proven to be highly useful in certain circumstances but has not been definitively proven to protect the nerve any more effectively than the gold standard of nerve visualization. In our study, the use of IONM did not reduce the time of thyroid surgery and did increase the cost. While IONM may, in special clinical circumstances such as revision and malignant thyroid surgery, increase the value of the operation, its use for every thyroid surgery does not appear to be cost effective or valuable to the patient.