The autosomal recessive form of human complete Stat-1 deficiency is a rare disorder, thus far reported in two unrelated patients, both of whom developed disseminated bacillus Calmette-Guérin (BCG) and subsequently died of viral illnesses before detailed studies of the condition could be performed. It is associated with impaired cellular responses to both IFN-γ and IFN-αβ via Stat-1-containing complexes. We describe a third patient with complete Stat-1 deficiency and disseminated BCG infection, who died 3 mo after bone marrow transplantation. The patient’s EBV-transformed B cells did not express Stat-1 protein and did not activate Stat-1-containing transcription factors. We also report the ex vivo responses of a Stat-1-deficient patient’s fresh blood cells to IFN-γ and the in vitro responses of a SV40-transformed fibroblastic cell line to IFN-γ and IFN-αβ. There was no response to IFN-γ in terms of IL-12 production and HLA class II induction, accounting for vulnerability to BCG. Moreover, IFN-αβ did not suppress HSV and vesicular stomatitis virus replication in fibroblasts, although in vivo the patient was able to successfully clear at least some viruses. This study broadens our understanding of complete Stat-1 deficiency, a severe form of innate immunodeficiency. Stat-1 deficiency should be suspected in children with severe infections, notably but not exclusively patients with mycobacterial or viral diseases.
Lung transplant survivors are at increased risk of developing an acute abdomen because of the use of high-dose immunosuppressive agents. Physicians who evaluate lung transplant patients for an acute abdomen should have a low threshold for surgical intervention.
Microcirculatory dysfunction is present in children with severe MCD with improvement alongside clinical recovery. Microcirculatory dysfunction correlated with markers of endothelial activation. Sublingual SDF imaging is feasible in children ventilated on PICU for severe sepsis and may prove useful in studies assessing illness severity and therapy.
Background
There are no currently agreed upon international standards for reporting of pediatric deceased organ donation activity. This leads to difficulty in comparisons between jurisdictions for both researchers and policy stakeholders. The goal of this project was to develop and test a standardized registry for pediatric deceased donation activity.
Methods
Four countries (Canada, Spain, USA, and the UK) with geographical and practice diversity were approached to participate. Iterative exchanges were used to create data fields and definitions that were acceptable to all participants. Data from 2011 to 2015 (inclusive) were requested from national health databases and analyzed on a secure, web‐based survey platform.
Results
Data were obtained from three of the four countries (Canada unable to provide). Total pediatric donation rates were stable over the 5‐year period, but with variation between countries. pDCD rates were the most variable, representing 32.2% of total pediatric donation in the UK, 14.4% in the United States, and 2.6% in Spain during the studied period. Most organs from pediatric donors were allocated to adult recipients, though the rates of allocation of pediatric kidneys to pediatric recipients ranged from 7% in the United States to 40% in Spain.
Discussion
In this limited cohort of three countries, we demonstrated substantial variation in pediatric donation rates and practice. These data highlight opportunities for practice improvement such as the development of rigorous clinical practice guidelines. Future development of this registry will seek to engage more countries, and address barriers that prevented full participation of approached jurisdictions.
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