Comprehensive Summary of Safety Data on Nirsevimab in Infants and Children from All Pivotal Randomized Clinical Trials.

BACKGROUND: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks' gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and/or chronic lung disease of prematurity [CLD] or born ≤35 wGA). METHODS: Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab. RESULTS: The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment. CONCLUSIONS: A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.

Infants Receiving a Single Dose of Nirsevimab to Prevent RSV Do Not Have Evidence of Enhanced Disease in Their Second RSV Season.

To characterize nirsevimab in the prevention of RSV, children from the Phase 3 MELODY trial were followed through their second RSV season. No increase in medically attended RSV lower respiratory tract infections or evidence of antibody-dependent enhancement of infection or disease severity was found for nirsevimab vs placebo recipients. Clinical Trial Registration: Clinicaltrials.gov, NCT03979313, https://clinicaltrials.gov/ct2/show/NCT03979313.

Safety of Re-dosing Nirsevimab Prior to RSV Season 2 in Children With Heart or Lung Disease.

In children with congenital heart disease and/or chronic lung disease entering their second respiratory syncytial virus (RSV) season, 200 mg nirsevimab had a similar safety profile to that of palivizumab and resulted in nirsevimab serum exposures associated with efficacy in healthy infants, supporting efficacy in this population at risk of severe RSV disease.

Use of bilateral internal thoracic arteries in CABG through lateral thoracotomy with robotic assistance in 150 patients.

BACKGROUND: Internal thoracic arteries (ITA) have been shown to offer longer graft patency. Off-pump coronary artery bypass graft surgery (CABG) through small lateral thoracotomy has been reported. The present study deals with feasibility of using bilateral ITAs (BITA) in CABG through small lateral thoracotomy facilitated by the da Vinci robotic system. METHODS: Since July 2002, 150 patients underwent CABG through small lateral thoracotomy using robotic assistance for harvesting of BITA. After single lung ventilation, three 1- to 2-cm incisions were made in the third, fifth, and seventh intercostal spaces 2 to 3 cm medial to the anterior axillary line. After insertion of camera and instrument arms, both ITAs were harvested in a completely skeletonized fashion. A small anterolateral thoracotomy was done, enlarging the camera port incision. Distal anastomoses were performed on a beating heart using nitinol surgical clips. Intercostal cryoanalgesia and local anesthetic infusion were used for pain management. RESULTS: Planned arterial revascularization was completed in 148 patients. Mean number of arterial grafts per patient was 2.6 +/- 0.8. All coronary arteries could be reached with BITA as in situ or composite grafts. There was no mortality, stroke, myocardial infarction, or wound infection. Seven patients had new onset atrial fibrillation. Four patients required exploration of postoperative bleeding. Mean postoperative length of stay was 3.6 +/- 2.9 days. CONCLUSIONS: The da Vinci robotic system was found to be safe and feasible for BITA harvesting in multivessel CABG through small lateral thoracotomy. Further follow-up for graft patency is necessary. Postoperative pain may be reduced with aggressive management strategies. The approach offers fast recovery. This sternum-sparing approach may be an evolutionary step toward closed-chest coronary artery bypass graft surgery.