Evidence before this study: Acute appendicitis is the most common general surgical emergency in children. Its diagnosis remains challenging and children presenting with acute right iliac fossa (RIF) pain may be admitted for clinical observation or undergo normal appendicectomy (removal of a histologically normal appendix). A search for external validation studies of risk prediction models for acute appendicitis in children was performed on MEDLINE and Web of Science on 12 January 2017 using the search terms ["appendicitis" OR "appendectomy" OR "appendicectomy"] AND ["score" OR "model" OR "nomogram" OR "scoring"]. Studies validating prediction models aimed at differentiating acute appendicitis from all other causes of RIF pain were included. No date restrictions were applied. Validation studies were most commonly performed for the Alvarado, Appendicitis Inflammatory Response Score (AIRS), and Paediatric Appendicitis Score (PAS) models. Most validation studies were based on retrospective, single centre, or small cohorts, and findings regarding model performance were inconsistent. There was no high quality evidence to guide selection of the optimum model and threshold cutoff for identification of low-risk children in the UK and Ireland. Added value of this study: Most children admitted to hospital with RIF pain do not undergo surgery. When children do undergo appendicectomy, removal of a normal appendix (normal appendicectomy) is common, occurring in around 1 in 6 children. The Shera score is able to identify a large low-risk group of children who present with acute RIF pain but do not have acute appendicitis (specificity 44%). This low-risk group has an overall 1 in 30 risk of acute appendicitis and a 1 in 270 risk of perforated appendicitis. The Shera score is unable to achieve a sufficiently high positive predictive value to select a high-risk group who should proceed directly to surgery. Current diagnostic performance of ultrasound is also too poor to select children for surgery. Implications of all the available evidence: Routine pre-operative risk scoring could inform shared decision making by doctors, children, and parents by supporting safe selection of lowrisk patients for ambulatory management, reducing unnecessary admissions and normal appendicectomy. Hospitals should ensure seven-day-a-week availability of ultrasound for medium and high-risk patients. Ultrasound should be performed by operators trained to assess for acute appendicitis in children. For children in whom diagnostic uncertainty remains following ultrasound, magnetic resonance imaging (MRI) or low-dose computed tomography (CT) are second-line investigations.

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urothelial cells. McLatchie and Fry [5] stimulated urothelial cells in suspension by imposing upon them a mild drag force stress and found that urothelial ATP release was reduced with 1.8 mM external calcium, and was increased approximately two-fold by increasing intracellular calcium. ATP release was reduced by agents blocking pannexin and connexin hemichannels. The calcium-dependence of ATP release and its influence by connexin/pannexin blockers suggested to the investigators that a major fraction (up to 50%) of release is through such channels. However, the conspicuous effect of Nethylmaleimide, which has been proposed to reduce vesicular docking to the surface membrane of secretory cells, is consistent with a substantial fraction of release by vesicular exocytosis.It is obvious that more than 15 years after the observation of urothelial ATP release, this remains a fruitful research field. As suggested by McLatchie and Fry [5], characterisation of the pathways involved may help to develop new therapeutics for disorders assumed to be characterised by increased ATP release, such as bladder pain and overactive bladder syndromes. Conflicts of Interest

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