Non-invasive biomarkers of disease activity and organ damage in ANCA-associated vasculitis: a systematic review.

BACKGROUND: In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and assessment of disease extent. There is a requirement for validated non-invasive biomarkers to avoid the need for serial tissue biopsies. METHODS: A systematic review of scientific databases from 2012 until present was performed to identify studies fulfilling the inclusion criteria. Studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cohort, case-control and cross-sectional studies and the Risk of Bias Assessment tool for Non-randomised Studies, or the Cochrane Risk of Bias tool 2.0 for randomised controlled trials. A descriptive synthesis of the data for non-invasive (blood-based or urinary) biomarkers of AAV-related disease activity and organ damage was performed. RESULTS: Twenty-two high quality studies were included. These articles reported the value of blood-based and urinary biomarkers including anti-neutrophil cytoplasmic antibodies, immune cells, complement factors, gene expression profiles, cytokines, chemokines and other proteins in the assessment of disease activity and/or organ damage in patients with AAV. Many of these biomarkers involve the alternative complement pathway, neutrophil activation and macrophage activation. CONCLUSION: This is the first contemporary systematic review synthesising the value of non-invasive biomarkers of AAV-related disease activity and organ damage. The incorporation of individual markers in combined biomarker profiles might enhance clinical decision-making. Many unmet needs were identified; few studies involve oeosinophilic granulomatosis with polyangiitis and patients with childhood-onset AAV. Further validation of the candidate biomarkers is warranted in large prospective studies to bridge the existing knowledge gaps and apply precision health to systemic vasculitis.

Reducing physician voiding cystourethrogram ordering in children with first febrile urinary tract infection: evaluation of a purposefully sequenced educational intervention.

BACKGROUND: Physicians often fail to implement clinical practice guidelines. Our aim was to evaluate whether a purposefully sequenced, multifaceted educational intervention would increase physician adherence to a guideline for voiding cystourethrogram (VCUG) use following first urinary tract infection (UTI) in young children. METHODS: Using a single centre, pretest-posttest design, we compared the proportion of guideline adherent VCUG orders and the VCUG ordering rate before and after three educational interventions (interactive lecture, clinical pathway, faxed reminder) selected and sequenced according to the PRECEDE (Predisposing, Reinforcing and Enabling Constructs in Educational Diagnosis and Evaluation) health promotion model. RESULTS: One hundred and nine physicians ordered 219 VCUGs for 219 children. Following the interventions, there was an increase in the monthly proportion of adherent VCUGs ordered by pediatricians (analysis of variance (ANOVA) F(2,29) = 3.38, p = .048) and non-pediatricians (ANOVA F(2,28) = 14.71, p < .001). Also, pediatricians decreased their monthly VCUG ordering rate (linear trend incidence rate ratio 0.74, 95% confidence interval (CI) [0.54, 0.99]). Pediatricians were more likely to adhere with the guideline than were non-pediatricians (odds ratio 2.91, 95% CI [1.5, 5.5]). CONCLUSION: Exposure to purposefully sequenced educational interventions based on the PRECEDE model was associated with increased adherence to guideline recommendations.

A Pediatric Case of Diffuse Alveolar Hemorrhage Secondary to Poststreptococcal Glomerulonephritis.

This report summarizes a case of a 4-year-old girl with poststreptococcal glomerulonephritis and diffuse alveolar hemorrhage, an atypical presentation in this age group and type of vasculitic disease. We propose that her rapid improvement in clinical status was due to her treatment, continuous renal replacement therapy (CRRT). This mechanism would have impacted recovery by removing factors such as endothelial microparticles, superantigens, and immune complexes that have been postulated as the pulmonary-renal link. This may be an interesting avenue of exploration going forward given the lack of evidence in treating such conditions and emergence of CRRT.

Interleukin-6 is an essential determinant of on-time parturition in the mouse.

IL-6 abundance in amniotic fluid and uterine tissues increases in late gestation or with infection-associated preterm labor. A role in regulation of labor onset is suggested by observations that IL-6 increases expression of genes controlling prostaglandin synthesis and signaling in isolated uterine cells, but whether IL-6 is essential for normal parturition is unknown. To evaluate the physiological role of IL-6 in parturition in mice, we investigated the effect of Il6 null mutation on the timing of parturition and expression of genes associated with uterine activation. Il6 null mutant mice delivered 24 h later than wild-type mice, although circulating progesterone fell similarly in both genotypes during the prepartal period. Il6 null mutant mice were also refractory to low doses of lipopolysaccharide sufficient to induce preterm delivery in wild-type mice. The characteristic late-gestation elevation in uterine expression of Oxtr mRNA encoding oxytocin receptor, and peripartal increases in Ptgfr and Ptgs2 mRNAs regulating prostaglandin synthesis and signaling were delayed by 24 h in Il6 null mutant mice. Conversely, Ptger4 mRNA encoding the prostaglandin E receptor-4 was abnormally elevated in late-gestation in Il6 null mutant mice. Administration of recombinant IL-6 from d 11.5 postcoitum until term restored the normal timing of delivery and normalized Ptger4 mRNA expression in late gestation. We conclude that IL-6 has a key role in controlling the progression of events culminating in parturition and that it acts downstream of luteolysis in the uterus to regulate genes involved in the prostaglandin-mediated uterine activation cascade.