Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients

IMPORTANCE: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. OBJECTIVE: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. EXPOSURES: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. MAIN OUTCOME AND MEASURE: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. RESULTS: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. CONCLUSIONS AND RELEVANCE: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella

Genetic Dissection of Grain Zinc and Iron Concentration, Protein Content, Test Weight and Thousand Kernel Weight in Wheat (Triticum Aestivum L.) through Genome Wide Association Study

Abstract Malnutrition due to micronutrients and protein deficiency is recognized among the major global health issues. Genetic biofortification of wheat varieties is both cost-effective and sustainable strategy to contain global micronutrient and protein malnutrition. Genomic regions governing grain zinc concentration (GZnC), grain iron concentration (GFeC), grain protein content (GPC), test weight (TW), and thousand kernel weight (TKW) were investigated in a set of 183 diverse bread wheat genotypes through genome wide association study (GWAS). The RIL population was genotyped using Breeders' 35K Axiom Array and phenotyped in three environments during 2019-2020. A total of 55 marker-trait associations (MTAs) were identified, of which four significant MTAs for GFeC on chromosome 2B, 3A, 3B, 6A and two for GZnC on chromosomes 1A and 7B. Further, a stable SNP was detected for TKW and also identified pleiotropic regions controlling GPC and TKW. In silico analysis revealed a few important putative candidate genes viz., F-box-like domain superfamily, Zinc finger CCCH-type proteins, Serine-threonine/tyrosine-protein kinase, Histone deacetylase domain superfamily and SANT/Myb domain superfamily proteins, etc. The identified novel MTAs will be validated to estimate their effects on different genetic backgrounds for subsequent use in marker-assisted selection (MAS).</jats:p

Klinische Evaluation eines Überdruckventils für Kindertuben mit Cuff

OBJECTIVE: The safe use of cuffed tracheal tubes for children necessitates a cuff pressure limitation at 20-25 cmH2O. The aim of the study was to evaluate the reliability and benefit of a new cuff pressure release valve (opening pressure 20 cmH2O) for children intubated with a cuffed tracheal tube. METHODS: In a prospective, observational trial cuff pressure was recorded in paediatric and adolescent patients intubated with a cuffed tracheal tube during sevoflurane/nitrous oxide anaesthesia. The cuff pressure release valve was interposed between the cuff manometer and the pilot balloon. In 25 patients measurements were started at the initial opening pressure (group A) and in a further 25 patients measurements were started at the minimal sealing cuff pressure (group B). RESULTS: A total of 50 patients, aged from 0.4 to 17.8 years (median 7.4 years) were enrolled in the study. The opening pressure measured (group A) was 19.7+/-0.8 cmH(2)O and the cuff sealing pressure (group B) was 11.7+/-2.9 cmH2O (range 6-16 cmH2O). Mean cuff pressure values in group A were 20.4+/-1.6 cmH2O and 16.5+/-3.3 cmH2O in group B. In one patient (group A) the cuff pressure exceeded 25 cmH2O and was manually decreased to 20 cmH2O. In total, 24 filling procedures (group A 14; group B 10) were required during 103.1 h of investigation because of cuff pressure drop and audible air leakage, mainly caused by cuff pressure increases and consequent releases during patient positioning. CONCLUSION: Our data demonstrate that the tested cuff pressure release valve was useful and reliable to limit cuff pressure in tracheal intubated children and adolescents within an acceptable pressure range