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Objective Previously, we used a proteomics approach for the discovery of new diagnostic markers of acute appendicitis (AA) and identified LRG that was elevated in the urine of children with AA and enriched in diseased appendices. Here, we sought to evaluate the diagnostic utility of enzyme-linked immunoassay (ELISA) of urine LRG in a blinded, prospective, cohort study of children being evaluated for acute abdominal pain. Methods Urine LRG concentration was measured using a commercially available LRG ELISA, and selected ion monitoring (SIM) mass spectrometry (MS). Urine LRG test performance was evaluated blindly against the pathologic diagnosis and histologic grade of appendicitis. Results Urine LRG was measured in 49 patients. Mean urine LRG concentration measured using commercial LRG ELISA was significantly elevated in patients with AA, but exhibited an interference effect. Direct measurements using SIM MS demonstrated that LRG was elevated more than 100-fold in patients with AA as compared to those without, with the receiver operating characteristic area under the curve of 0.98 (95% CI = 0.96-1.0). Among patients with AA, elevations of urine LRG measured using ELISA and SIM MS correlated with the histologic severity of appendicitis. Conclusion Urine LRG ELISA allows for discrimination between patients with and without AA, but exhibits limited accuracy due to immunoassay interference. Direct measurements of urine LRG using SIM MS demonstrate superior diagnostic performance. Development of a clinical-grade urine LRG assay is needed to advance the diagnostic accuracy of clinical evaluations of appendicitis.

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence of definitive diagnostic markers limits the accuracy of clinical evaluations of suspected KD with significant increases in morbidity. In turn, incomplete understanding of its molecular pathogenesis hinders the identification of rational targets needed to improve therapy. We used high-accuracy mass spectrometry proteomics to analyse over 2000 unique proteins in clinical urine specimens of patients with KD. We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A. Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients. Meprin A and filamin C exhibited superior diagnostic performance as compared to currently used markers of disease in a blinded case-control study of 107 patients with suspected KD, with receiver operating characteristic areas under the curve of 0.98 (95% confidence intervals [CI] of 0.97–1 and 0.95–1, respectively). Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD. In all, urine proteome profiles revealed novel candidate molecular markers of KD, including filamin C and meprin A that exhibit excellent diagnostic performance. These disease markers may improve the diagnostic accuracy of clinical evaluations of children with suspected KD, lead to the identification of novel therapeutic targets, and allow the development of a biological classification of Kawasaki disease.

BackgroundMobile apps for mobile phones and tablet devices are widely used by children and young people aged 0-18 years with long-term health conditions, such as chronic kidney disease (CKD), and their healthy peers for social networking or gaming. They are also poised to become a major source of health guidance. However, app development processes that are coproduced, rigorously developed, and evaluated to provide tailored, condition-specific, practical advice on day-to-day care management are seldom systematic or sufficiently described to enable replication. Furthermore, attempts to extrapolate to the real world are hampered by a poor understanding of the effects of key elements of app components. Therefore, effective and cost-effective novel, digital apps that will effectively and safely support care management are critical and timely. To inform development of such an app for children with CKD, a user requirements-gathering exercise was first needed.ObjectiveTo explore the views of children with CKD, their parents, and health care professionals to inform future development of a child-focused, care-management app.MethodsUsing age- and developmentally appropriate methods, we interviewed 36 participants: 5-10-year-olds (n=6), 11-14-year-olds (n=6), 15-18-year-olds (n=5), mothers (n=10), fathers (n=2), and health care professionals (n=7). Data were analyzed using Framework Analysis and behavior change theories.ResultsOf the 27 interviews, 19 (70%) interviews were individual and 8 (30%) were joint—5 out of 8 (63%) joint interviews were with a child or young person and their parent, 1 out of 8 (13%) were with a child and both parents, and 2 out of 8 (25%) were with 2 professionals. Three key themes emerged to inform development of a software requirement specification for a future home-based, digital care-management app intervention: (1) Gaps in current online information and support, (2) Difficulties experienced by children with a long-term condition, and (3) Suggestions for a digital care-management app. Reported gaps included the fact that current online information is not usually appropriate for children as it is “dry” and “boring,” could be “scary,” and was either hard to understand or not relevant to individuals’ circumstances. For children, searching online was much less accessible than using a professional-endorsed mobile app. Children also reported difficulty explaining their condition to others, maintaining treatment adherence, coping with feeling isolated, and with trying to live a “normal” life. There was recognition that a developmentally appropriate, CKD-specific app could support the process of explaining the condition to healthy peers, reducing isolation, adhering to care-management plans, and living a “normal” life. Participants recommended a range of media and content to include in a tailored, interactive, age- and developmentally appropriate app. For example, the user would be able to enter their age and diagnosis so that only age-appropriate and condition-specific content is displayed.ConclusionsFu...

The sensitivity of MRA and CTA is still too low to reliably rule out renovascular disease in children with a strong suspicion of this diagnosis. DSA remains the gold standard to diagnose renovascular hypertension and is recommended when clinical and laboratory criteria are highly suggestive of renovascular disease even with normal radiological investigations from non-invasive methods.

BackgroundLong-term childhood conditions are often managed by hospital-based multidisciplinary teams (MDTs) of professionals with discipline specific expertise of a condition, in partnership with parents. However, little evidence exists on professional–parent interactions in this context. An exploration of professionals' accounts of the way they individually and collectively teach parents to manage their child's clinical care at home is, therefore, important for meeting parents' needs, informing policy and educating novice professionals. Using chronic kidney disease as an exemplar this paper reports on one aspect of a study of interactions between professionals and parents in a network of 12 children's kidney units in Britain.MethodsWe conducted semi-structured, qualitative interviews with a convenience sample of 112 professionals (clinical-psychologists, dietitians, doctors, nurses, pharmacists, play-workers, therapists and social workers), exploring accounts of their parent-educative activity. We analysed data using framework and the concept of distributed expertise.ResultsFour themes emerged that related to the way expertise was distributed within and across teams: (i) recognizing each other's' expertise, (ii) sharing expertise within the MDT, (iii) language interpretation, and (iv) acting as brokers. Two different professional identifications were also seen to co-exist within MDTs, with participants using the term ‘we’ both as the intra-professional ‘we’ (relating to the professional identity) when describing expertise within a disciplinary group (for example: ‘As dietitians we aim to give tailored advice to optimize children's growth’), and the inter-professional ‘we’ (a ‘team-identification’), when discussing expertise within the team (for example: ‘We work as a team and make sure we're all happy with every aspect of their training before they go home’).ConclusionsThis study highlights the dual identifications implicit in ‘being professional’ in this context (to the team and to one's profession) as well as the unique role that each member of a team contributes to children's care. Our methodology and results have the potential to be transferred to teams managing other conditions.

BackgroundNephrotic syndrome (NS) presenting early in life is caused by heterogeneous glomerular diseases. We retrospectively evaluated whether histological diagnosis in children presenting with NS in the first year of life predicts remission or progression to end-stage kidney disease (ESKD).MethodsThis is a single centre retrospective review of all children diagnosed with NS before one year of age between 1990 and 2009. All subjects had a renal biopsy, which was independently blindly reviewed by a single renal pathologist for the purpose of this study.ResultsForty-nine children (25 female) who presented at 0.1–11.6 (median 1.6) months were included with 31 presenting within the first three months of life. Histopathological review diagnostic categories were; 13 Mesangial proliferative glomerulopathy (MesGN), 12 Focal and segmental glomerulosclerosis (FSGS), 11 Finnish type changes, eight Diffuse Mesangial Sclerosis (DMS), three Minimal change disease (MCD) and one each of Dense Deposit Disease (DDD) and Membranous nephropathy. Two children died from haemorrhagic complications of the biopsy. Eight children achieved remission (four MesGN, one Finnish type changes, one FSGS, one MCD and one membranous) with patient and renal survival of 73 % and 43 %, respectively, at follow-up duration of 5–222 (median 73) months (with five lost to follow-up). All children with Finnish-type histopathological changes presented within five months of age. Due to the historical nature of the cohort, genetic testing was only available for 14 children, nine of whom had an identifiable genetic basis (seven NPHS1, one PLCE1 and one ITGA3) with none of these nine children achieving remission. All of them had presented within four months of age and required renal replacement therapy, and two died.ConclusionsHistopathological findings are varied in children presenting with NS early in life. Whilst groups of histological patterns of disease are associated with differing outcomes, accurate prediction of disease course in a specific case is difficult and more widespread genetic testing may improve the understanding of this group of diseases and their optimal management

We studied the ability of pre- and postcaptopril renal scintigraphy to predict renovascular disease (RVD) in children. Retrospective review of medical notes and radiology reports of all hypertensive children who had had both pre- and postcaptopril renal scintigraphy with [(99m)Tc] dimercaptosuccinic acid (DMSA) and/or [(99m)Tc] mercaptoacetyltriglycine (MAG3) and digital subtraction angiography (DSA). 81 children aged 1-18 (median 10) years were studied with 62% (51) having a diagnosis of RVD. Main renal artery disease, intrarenal disease, and both main and intrarenal artery disease were present in 25, 14, and 12 patients respectively. The isotope study accurately diagnosed RVD, confirmed by DSA, in 47% (24 of 51) children, with eight false positive studies. The sensitivity, specificity, and positive and negative predictive values of the isotope study to predict RVD were 48%, 73%, 76%, and 51%, respectively. Pre- and postcaptopril renal scintigraphy was unable to predict RVD in children.