Timing of neonatal stoma closure: a survey of health professional perspectives and current practice.

Optimal timing for neonatal stoma closure remains unclear. In this study, we aimed to establish current practice and illustrate multidisciplinary perspectives on timing of stoma closure using an online survey sent to all 27 UK neonatal surgical units, as part of a research programme to determine the feasibility of a clinical trial comparing 'early' and 'late' stoma closure. 166 responses from all 27 units demonstrated concordance of opinion in target time for closure (6 weeks most commonly stated across scenarios), although there was a high variability in practice. A sizeable proportion (41%) of respondents use weight, rather than time, to determine when to close a neonatal stoma. Thematic analysis of free text responses identified nine key themes influencing decision-making; most related to nutrition, growth and stoma complications. These data provide an overview of current practice that is critical to informing an acceptable trial design.

MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO).

MMPs, which degrade components of the ECM, have roles in embryonic development, tissue repair, cancer, arthritis, and cardiovascular disease. We show that a missense mutation of MMP13 causes the Missouri type of human spondyloepimetaphyseal dysplasia (SEMD(MO)), an autosomal dominant disorder characterized by defective growth and modeling of vertebrae and long bones. Genome-wide linkage analysis mapped SEMD(MO) to a 17-cM region on chromosome 11q14.3-23.2 that contains a cluster of 9 MMP genes. Among these, MMP13 represented the best candidate for SEMD(MO), since it preferentially degrades collagen type II, abnormalities of which cause skeletal dysplasias that include Strudwick type SEMD. DNA sequence analysis revealed a missense mutation, F56S, that substituted an evolutionarily conserved phenylalanine residue for a serine in the proregion domain of MMP13. We predicted, by modeling MMP13 structure, that this F56S mutation would result in a hydrophobic cavity with misfolding, autoactivation, and degradation of mutant protein intracellularly. Expression of wild-type and mutant MMP13s in human embryonic kidney cells confirmed abnormal intracellular autoactivation and autodegradation of F56S MMP13 such that only enzymatically inactive, small fragments were secreted. Thus, the F56S mutation results in deficiency of MMP13, which leads to the human skeletal developmental anomaly of SEMD(MO).