Prophylaxis against venous thromboembolism in pediatric trauma: A practice management guideline from the Eastern Association for the Surgery of Trauma and the Pediatric Trauma Society

BACKGROUND: Despite the increasing incidence of venous thromboembolism (VTE) in hospitalized children, the risks and benefits of VTE prophylaxis, particularly for those hospitalized after trauma, are unclear. The Pediatric Trauma Society and the Eastern Association for the Surgery of Trauma convened a writing group to develop a practice management guideline on VTE prophylaxis for this cohort of children using the Grading of Recommendations Assessment, Development, and Evaluation framework. METHODS: A systematic review of MEDLINE using PubMed from January 1946 to July 2015 was performed. The search retrieved English-language articles on VTE prophylaxis in children 0 to 21 years old with trauma. Topics of investigation included pharmacologic and mechanical VTE prophylaxis, active radiologic surveillance for VTE, and risk factors for VTE. RESULTS: Forty-eight articles were identified and 14 were included in the development of the guideline. The quality of evidence was low to very low because of the observational study design and risks of bias. CONCLUSIONS: In children hospitalized after trauma who are at low risk of bleeding, we conditionally recommend pharmacologic prophylaxis be considered for children older than 15 years old and in younger postpubertal children with Injury Severity Score (ISS) greater than 25. For prepubertal children, even with ISS greater than 25, we conditionally recommend against routine pharmacologic prophylaxis. Second, in children hospitalized after trauma, we conditionally recommend mechanical prophylaxis be considered for children older than 15 years and in younger postpubertal children with ISS greater than 25 versus no prophylaxis or in addition to pharmacologic prophylaxis. Lastly, in children hospitalized after trauma, we conditionally recommend against active surveillance for VTE with ultrasound compared with routine daily physical examination alone for earlier detection of VTE. The limited pediatric data and paucity of high-quality evidence preclude providing more definitive recommendations and highlight the need for clinical trials of prophylaxis

Neutralizing anti-interferon beta antibodies are associated with reduced side effects and delayed impact on efficacy of Interferon-beta.

UNLABELLED: Interferon-beta (IFNbeta) is a biological therapy which is immunogenic, inducing anti-IFN-beta neutralizing antibodies (Nabs) in some subjects. The frequency of Nabs varies depending on IFN-beta product and the Nab assay used. OBJECTIVE: Assess frequency of Nabs using novel Luciferase assay, evaluate association with relapses, frequency of side effects and to compare results with published data. METHODS: Serum samples at 12 and 24 months and a follow up sample were tested for binding and Nabs. Titre >20 NU was considered positive. Charts were reviewed retrospectively for clinical data. RESULTS: Out of 327 subjects included, 130 subjects (40%) were binding antibody positive, 89 (27%) were Nab +ve at anytime. Risk at 12 months for being Nab +ve: Avonex 8%, Betaferon 39%, Rebif 33%, P < 10(-5); at 24 months 8, 31 and 27% respectively, P = 0.002. Nab titres were highest in Rebif Nab +ve subjects - 50% >320 NU. Annualized relapse rate was 1.53 pre-treatment, after treatment relapse rate was higher in Nab +ve group 0.67 (95% CI 0.38-0.97) versus 0.5 (0.38-0.61) Nab -ve P = 0.04. Nab status at 12 and 24 months was significantly associated with risk of subsequent relapse, risk being greatest in those with highest titres. Side effects were also significantly associated with Nab -ve status.

Molecular and genetic characterization of a novel pleiotropic tomato-ripening mutant

In this paper we describe a novel, dominant pleiotropic tomato (Lycopersicon esculentum)-ripening mutation, Cnr (colorless nonripening). This mutant occurred spontaneously in a commercial population. Cnr has a phenotype that is quite distinct from that of the other pleiotropic tomato-ripening mutants and is characterized by fruit that show greatly reduced ethylene production, an inhibition of softening, a yellow skin, and a nonpigmented pericarp. The ripening-related biosynthesis of carotenoid pigments was abolished in the pericarp tissue. The pericarp also showed a significant reduction in cell-to-cell adhesion, with cell separation occurring when blocks of tissue were incubated in water alone. The mutant phenotype was not reversed by exposure to exogenous ethylene. Crosses with other mutant lines and the use of a restriction fragment length polymorphism marker demonstrated that Cnr was not allelic with the pleiotropic ripening mutants nor, alc, rin, Nr, Gr, and Nr-2. The gene has been mapped to the top of chromosome 2, also indicating that it is distinct from the other pleiotropic ripening mutants. We undertook the molecular characterization of Cnr by examining the expression of a panel of ripening-related genes in the presence and absence of exogenous ethylene. The pattern of gene expression in Cnr was related to, but differed from, that of several of the other well-characterized mutants. We discuss here the possible relationships among nor, Cnr, and rin in a putative ripening signal cascade.