Fernanda Salgado

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV. Adults aged ≥ 60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022-2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥ 3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post- vaccination respectively, and SAEs for the entire study period. In total, 18348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9% (95% CI: -16.1; 71.9) against RSV-associated LRTD with ≥ 3 symptoms, 59.0% (95% CI: 34.7; 74.3) against LRTD with ≥ 2 symptoms, and 48.8% (95% CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥ 3 symptoms since the lower bound of the 95% CI was below 20%, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified. MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases.

Extubation failure (EF) after cardiac surgery is associated with poorer outcomes. Approximately 50% of children with Down syndrome (DS) have congenital heart disease. Our primary aim was to describe the frequency of EF and identify risk factors for its occurrence in a population of patients with DS after cardiac surgery. Secondary aims were to describe complications, length of hospital stay, and mortality rates. This report was a retrospective case–control study and was carried out in a national reference congenital heart disease repair center of Chile. This study includes all infants 0–12 months old with DS who were admitted to pediatric intensive care unit after cardiac surgery between January 2010 and November 2020. Patients with EF (cases) were matched 1:1 with children who did not fail their extubation (controls) using the following criteria: age at surgery, sex, and type of congenital heart disease. Overall, 27/226 (11.3%) failed their first extubation. In the first analysis, before matching of cases and controls was made, we found association between EF and younger age (3.8 months vs 5 months; p = 0.003) and presence of coarctation of the aorta (p = 0.005). In the case–control univariate analysis, we found association between an increased cardiothoracic ratio (CTR) (p = 0.03; OR 5 (95% CI 1.6–16.7) for a CTR > 0.59) and marked hypotonia (27% vs 0%; p = 0.01) with the risk of EF. No differences were found in ventilatory management. Conclusions: In pediatric patients with DS, EF after cardiac surgery is associated with younger age, presence of aortic coarctation, higher CTR reflecting the degree of cardiomegaly and hypotonia. Recognition of these factors may be helpful when planning extubation for these patients. What is Known: • Extubation failure after cardiac surgery is associated with higher morbidity and mortality rates. Some studies report higher rates of extubation failure in patients with Down syndrome. What is New: • In children with Down syndrome, extubation failure after cardiac surgery is associated with younger age, presence of aortic coarctation, higher CTR reflecting cardiomegaly and severe hypotonia.