Immunity to commensal skin fungi promotes psoriasiform skin inflammation.

Under steady-state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiota-specific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi preexposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.

Utility of arterial stiffness assessment in children.

Atherosclerotic cardiovascular disease is a leading cause of death and disability worldwide, and the atherosclerotic process begins in childhood. Prevention or containment of risk factors that accelerate atherosclerosis can delay the development of atherosclerotic cardiovascular disease. Although current recommendations are to periodically screen for commonly prevailing risk factors for atherosclerosis in children, a single test that could quantify the cumulative effect of all risk factors on the vasculature, thus assessing arterial health, would be helpful in further stratifying risk. Measurement of pulse wave velocity and assessment of augmentation index - measures of arterial stiffness - are easy-to-use, non-invasive methods of examining arterial health. Various studies have assessed pulse wave velocity and augmentation index in children with commonly occurring conditions including obesity, hypertension, insulin resistance, diabetes mellitus, dyslipidaemia, physical inactivity, chronic kidney disease, CHD and acquired heart diseases, and in children who were born premature or small for gestational age. This article summarises pulse wave velocity and augmentation index assessments and the effects of commonly prevailing chronic conditions on arterial health in children. In addition, currently available reference values for pulse wave velocity and augmentation index in healthy children are included. Further research to establish widely applicable normative values and the effect of lifestyle and pharmacological interventions on arterial health in children is needed.

Vitamin D, Low-Grade Inflammation and Cardiovascular Risk in Young Children: A Pilot Study.

Vitamin D has anti-inflammatory properties, and deficiency is prevalent in children. There is a paucity of data regarding vitamin D status and its correlation with low-grade inflammation and vasculature. We prospectively enrolled 25 children, 9-11 years old (13 male); 21 obese. Eight atherosclerosis-promoting risk factors were scored as categorical variables with the following thresholds defining abnormality: body mass index Z score ≥ 1.5; systolic blood pressure ≥ 95th percentile (for age, sex, and height); triglyceride ≥ 100 mg/dL; low-density lipoprotein cholesterol (LDL-C) ≥ 110 mg/dL; high-density lipoprotein cholesterol ≤ 45 mg/dL; hemoglobin A1C (HBA1C) ≥ 5.5; 25-hydroxyvitamin D [25(OH) D] ≤ 30 ng/mL, and tobacco smoke exposure. High-sensitivity C-reactive protein (hsCRP) was measured to assess low-grade inflammation and classified as low- (<1 mg/L), average- (1-3 mg/L), and high-risk (>3 to <10 mg/L) groups. The proportion of children within each hsCRP group who had above threshold risk factors was calculated. Carotid artery ultrasound was performed to measure carotid artery intima-media thickness (CIMT). Median (range) for 25(OH) D was 24 (17-45) ng/mL. Eighteen were either 25 (OH) D deficient (<20 ng/mL) or insufficient (20-30 ng/mL), and seven were sufficient (>30 ng/mL). hsCRP was 1.7 (0.2-9.1) mg/L, with 11 being <1.0 mg/L, 8 between 1.0-3.0 and 6 > 3.0 to < 10.0 mg/L. Risk factor score was 3.9 ± 1.7 out of eight. 25(OH) D levels did not correlate with hsCRP or CIMT. While vitamin D deficiency, inflammation, and risk factors coexist at a very young age, causative mechanisms remain unclear.

Outcomes after prolonged extracorporeal membrane oxygenation support in children with cardiac disease--Extracorporeal Life Support Organization registry study.

OBJECTIVE: Extracorporeal membrane oxygenation remains the mainstay of mechanical circulatory support initiation and maintenance in children with cardiac insufficiency. However, the outcomes after prolonged extracorporeal membrane oxygenation for cardiac insufficiency in children remain ill defined. METHODS: We reviewed the International Extracorporeal Life Support Organization data from January 1, 2000, through December 31, 2011. We defined prolonged extracorporeal membrane oxygenation as uninterrupted support for ≥14 days. RESULTS: A total of 777 children aged <18 years required extracorporeal membrane oxygenation support for ≥14 days. Of these, 176 (23%) survived to hospital discharge. Compared with the nonsurvivors, the survivors were older (median age, 0.64 vs 0.10 years; P < .01), weighed more (median weight, 7.0 kg; range, 2-90; vs median, 4.0; range, 1.4-100 kg; P < .01), had a shorter duration of support (mean, 20 ± 6 vs 22 ± 9 days; P < .01), and a fewer number of organ system complications (mean, 2.8 ± 1.7 vs 3.6 ± 1.6, P < .01). Children with congenital heart disease had worse survival than those with cardiomyopathy and myocarditis (15% vs 42% and 52%, respectively; P < .01), and those with 1-ventricle physiology had worse survival than those with 2-ventricle physiology (10% vs 18%, P = .01). Seven percent (n = 56) reached cardiac transplantation, with 66% surviving to hospital discharge versus 19% of those not transplanted (P < .01). CONCLUSIONS: The attrition is high after prolonged extracorporeal membrane oxygenation support for cardiac insufficiency in children. Cardiac transplantation in this cohort was rarely achieved and was associated with high mortality compared with benchmarks for cardiac transplantation survival. Earlier redirection of care or conversion to other modes of mechanical support as a bridge to transplantation should be considered.