NUDCD3 deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome.

Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 11 affected patients across four consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain-containing 3 (NUDCD3). Two infants had severe combined immunodeficiency with the complete absence of T and B cells (T -B- SCID), whereas nine showed classical features of Omenn syndrome (OS). Restricted antigen receptor gene usage by residual T lymphocytes suggested impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, which was associated with pathologic sequestration of RAG1 in the nucleoli. Although impaired V(D)J recombination in a mouse model bearing the homologous variant led to milder immunologic abnormalities, NUDCD3 is absolutely required for healthy T and B cell development in humans.

A systematic review of tourniquet use in paediatric orthopaedic surgery: can we extrapolate from adult guidelines?

Purpose: Tourniquets are commonly used intraoperatively in orthopaedic surgery to control bleeding and improve visibility in the surgical field. Recent evidence has thrown into question the routine use of tourniquets in the adult population resulting in a British Orthopaedic Association standard for intraoperative use. This systematic review evaluates the evidence on the practice, benefits, and risks of the intraoperative use of tourniquets for trauma and elective orthopaedic surgery in the paediatric population. Methods: A prospectively registered systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO: CRD42022359048). A search of MEDLINE, Embase, the Cochrane Library and a Grey literature search was performed from their earliest record to 23 March 2023. Studies reporting tourniquet data in paediatric patients undergoing orthopaedic surgery were included. Data extracted included demographics, involved limb, trauma versus elective use, tourniquet use as primary or secondary measure, and tourniquet parameters and complications. Results: Thirty-nine studies were included. Tourniquet practices and information reporting varied considerably. Tourniquets were used uneventfully in the majority of patients with no specific benefits reported. Several physiological and biochemical changes as well as complications including nerve injury, compartment syndrome, skin burns, thrombosis, post-operative limb swelling, and pain were reported. Conclusions: Tourniquets are routinely used in both trauma and elective paediatric orthopaedic surgery with no high-quality research affirming benefits. Severe complications associated with their use are rare but do occur. High-quality studies addressing their benefits, the exact indication in children, and the safest way to use them in this population are necessary.

Use of a non-anatomic mini-fragment fixation system for foot fractures.

BACKGROUND: Plating techniques for the fixation of foot fractures can utilize pre-contoured region-specific plates or non-anatomic non-specific mini-fragment plating systems, however there is limited published data describing complication rates. METHODS: This study reviewed the complication rates and performed a cost analysis of 45 foot fractures that had fixation with the use of mini-fragment non-anatomic implants, comparing them to a series from the same centre fixed using anatomic implants and the published literature. RESULTS: Complication rates seemed equivalent. Cost analysis demonstrated that non-anatomic implants were more expensive on average. CONCLUSIONS: Non-anatomic mini-fragment fixation is an appropriate method for use in a variety of foot trauma situations, with comparable complication rates to pre-contoured implants, although the potential for cost savings has not been realized in this patient cohort.