Preoperative Malnutrition Increases Risk of In-Hospital Mortality, Major Infection, and Longer Intensive Care Unit Stay After Ventricular Septal Defect Closure.

BACKGROUND: High energy requirements and poor feeding can lead to growth failure in patients with ventricular septal defect (VSD), but effects of preoperative malnutrition on surgical outcomes are poorly understood, especially in low-resource settings. METHODS AND RESULTS: We analyzed a cohort of children <5 years of age undergoing VSD closure at 60 global centers participating in the International Quality Improvement Collaborative for Congenital Heart Disease, 2015 to 2020. We calculated adjusted odds ratios (ORs) for in-hospital death and major infection and adjusted coefficients for duration of intensive care unit stay for 4 measures of malnutrition: severe wasting (weight-for-height Z score, <-3), moderate wasting (-3

Surgical capacity is disaster preparedness: A scoping review of how surgery and anesthesiology departments responded to COVID-19.

OBJECTIVE: This study evaluated how surgical and anesthesiology departments adapted their resources in response to the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: This scoping review used the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews protocol, with Covidence as a screening tool. An initial search of PubMed, Embase, Web of Science, Global Index Medicus, and Cochrane Systematic Reviews returned 6,131 results in October 2021. After exclusion of duplicates and abstract screening, 415 articles were included. After full-text screening, 108 articles remained. RESULTS: Most commonly, studies were retrospective in nature (47.22 percent), with data from a single institution (60.19 percent). Nearly all studies occurred in high-income countries (HICs), 78.70 percent, with no articles from low-income countries. The reported responses to the COVID-19 pandemic involving surgical departments were grouped into seven categories, with multiple responses reported in some articles for a total of 192 responses. The most frequently reported responses were changes to surgical department staffing (29.17 percent) and task-shifting or task-sharing of personnel (25.52 percent). CONCLUSION: Our review reflects the mechanisms by which hospital surgical systems responded to the initial stress of the COVID-19 pandemic and reinforced the many changes to hospital policy that occurred in the pandemic. Healthcare systems with robust surgical systems were better able to cope with the initial stress of the COVID-19 pandemic. The well-resourced health systems of HICs reported rapid and dynamic changes by providers to assist in and ultimately improve the care of patients during the pandemic. Surgical system strengthening will allow health systems to be more resilient and prepared for the next disaster.

Prospective randomized controlled trial of the safety and feasibility of a novel mesenchymal precursor cell therapy in hypoplastic left heart syndrome.

Objective: To assess the safety and feasibility of low-dose, novel, allogenic mesenchymal precursor cell (MPC) therapy as an adjunct to left ventricular (LV) recruitment for patients with hypoplastic left heart syndrome (HLHS) and borderline left ventricles. MPC injections into the hypoplastic left ventricle may stimulate neovascularization and beneficial LV remodeling and may improve the likelihood of achieving biventricular (BiV) or 1.5 ventricle (1.5V) circulation. Methods: Children <5 years with prior single ventricle palliation undergoing LV recruitment surgery at a single center were randomized to MPC injections into the LV endocardium/papillary muscles (MPCs) or standard-of-care (controls) and followed for 24 months. The primary endpoint was safety, including (serious) adverse events (S/AEs), and panel reactive antibodies (PRAs). Secondary endpoints included BiV/1.5V conversion and LV size and function. Results: Nineteen subjects were enrolled, including 9 MPC recipients and 10 controls. Fourteen patients (74%) had >1 AE, and 2 patients had SAEs, both deemed unrelated to the trial product. AE severity and frequency were similar in the 2 groups. Baseline PRA levels were high, with no difference between the groups at 12 months. The overall probability of BiV/1.5V conversion was 0.16 (95% confidence interval [CI], 0.05 to 0.41) at 12 months and 0.52 (95% CI, 0.31 to 0.77) at 24 months. For patients with imaging data at both time points, increases in LV volumes from baseline to 12 months were larger in the MPC group by 3-dimensional echocardiography and cardiac magnetic resonance imaging. For children who successfully underwent BiV conversion (n = 12), full BiV conversion was achieved at 24 months in 5 of 5 (100%) MPC-treated children compared with 4 of 7 (57%) controls. Conclusions: MPC injections were considered safe and feasible in HLHS patients. More than 50% of subjects underwent BiV/1.5V conversion within 2 years. Larger trials are needed to investigate the therapeutic potential of MPCs in this population.

Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants.

Tuberculosis vaccine development is hindered by the lack of validated immune correlates of protection. Exploring immune correlates of risk of disease and/or infection in prospective samples can inform this field. We investigate whether previously identified immune correlates of risk of TB disease also associate with increased risk of M.tb infection in BCG-vaccinated South African infants, who became infected with M.tb during 2-3 years of follow-up. M.tb infection is defined by conversion to positive reactivity in the QuantiFERON test. We demonstrate that inflammation and immune activation are associated with risk of M.tb infection. Ag85A-specific IgG is elevated in infants that were subsequently infected with M.tb, and this is coupled with upregulated gene expression of immunoglobulin-associated genes and type-I interferon. Plasma levels of IFN-[Formula: see text]2, TNF-[Formula: see text], CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with M.tb.

Phase I Trial Evaluating the Safety and Immunogenicity of Candidate TB Vaccine MVA85A, Delivered by Aerosol to Healthy M.tb-Infected Adults.

The immunogenicity of the candidate tuberculosis (TB) vaccine MVA85A may be enhanced by aerosol delivery. Intradermal administration was shown to be safe in adults with latent TB infection (LTBI), but data are lacking for aerosol-delivered candidate TB vaccines in this population. We carried out a Phase I trial to evaluate the safety and immunogenicity of MVA85A delivered by aerosol in UK adults with LTBI (NCT02532036). Two volunteers were recruited, and the vaccine was well-tolerated with no safety concerns. Aerosolised vaccination with MVA85A induced mycobacterium- and vector-specific IFN-γ in blood and mycobacterium-specific Th1 cytokines in bronchoalveolar lavage. We identified several important barriers that could hamper recruitment into clinical trials in this patient population. The trial did not show any safety concerns in the aerosol delivery of a candidate viral-vectored TB vaccine to two UK adults with Mycobacterium tuberculosis (M.tb) infection. It also systemically and mucosally demonstrated inducible immune responses following aerosol vaccination. A further trial in a country with higher incidence of LTBI would confirm these findings.