The viral and atypical bacterial causes of acute respiratory infection in children in Recife, Brazil

Introduction: Acute respiratory infections (ARI) are the commonest cause of mortality in childre

Unbiased molecular definition of epithelial barrier formation and defects driving inflammatory bowel disease

The intestinal epithelial barrier is one of the body’s largest mucosal surfaces. The cells involved reflect the numerous functions the epithelium must perform. The barrier requires time critical co-ordination with other intestinal cell compartments in utero for normal development. In maturity, dysregulation of the barrier or cross-talk can lead to disease such as inflammatory bowel disease (IBD). Despite the importance of the intestinal epithelium in development and health, characterisation of the origins of dysregulation are lacking. Questions also remain about the full spectrum of epithelial cell diversity and its mutualistic relationship with other intestinal compartments. This project characterises the development of the epithelial and mesenchymal cross talk in utero, in health and in IBD at high resolution using single cell RNA-sequencing (scRNAseq). Studying intestinal epithelial diversity in health and disease, isolating epithelial cells from IBD and controls and mapping over 11,000 cells from health and UC inflammation, mapped cell diversity through the maturation of epithelium. This identified a hitherto unappreciated BEST4/OTOP2 cell that sensed pH and was dysregulated in inflammation and cancer. Furthermore, a second project mapped human intestinal development from 8-22 post conceptual weeks. This charted 101 cell types across developmental time and through spatial transcriptomics (ST) could map these to tissue revealing origins of diverse cellular compartments along with fibroblast and intestinal stem cells across space and time. These results provide a platform that maps the human intestinal epithelium and previously unappreciated resolution and from which the normal developmental cues can be established and allow identification of the drivers of dysregulation in IBD

Wilms' tumor - Lessons and outcomes - A 25-year single center UK experience

Wilms' tumor (WT) is a common childhood renal cancer. A 25-year single center UK experience is reported. During 1985-2010, 97 children underwent immediate nephrectomy or delayed resection of tumor after chemotherapy. Survival, morbidity, and late effects following treatment are described. Tumor distribution was: Stage I, 25.7% (n = 25); Stage II, 24.7% (n = 24); Stage III, 26.8% (n = 26); Stage IV, 17.5% (n = 17); and Stage V, 5.2% (n = 5). Immediate nephrectomy was performed in 39% (n = 38) patients with elective delayed resection in 61% (n = 59) cases. Ten patients had cavotomy to excise tumor involving vena cava territory. Two cases required cardiopulmonary bypass. Tumor rupture was recorded in eight (8.5%) total operated cases-after immediate (n = 5/37), 13.5% vs delayed nephrectomy-(n = 3/57), 5.2%; X P = .154. From 2001 onwards, one case of tumor rupture was recorded at this center after the universal adoption of UKW3 and SIOP guidelines advocating preoperative chemotherapy and delayed nephrectomy for all WT. Three treatment-related deaths occurred-hepatic veno-occlusive disease (n = 2) with actinomycin D and a single WT fatality due to vascular injury. Overall survival was 84.5% (82/97 cases). Two patients developed "late malignancies" -thyroid cancer and a basal cell carcinoma. This study demonstrates excellent survival for WT comparable with national outcomes and international cooperative studies. Adverse events with chemotherapy and surgery, including "late onset," second malignancies deserve special consideration. © 2014 Informa Healthcare USA, Inc

Diagnostic accuracy of blood tests of inflammation in paediatric appendicitis: a systematic review and meta-analysis

OBJECTIVE: Possible childhood appendicitis is a common emergency presentation. The exact value of blood tests is debated. This study sought to determine the diagnostic accuracy of four blood tests (white cell count (WCC), neutrophil(count or percentage), C reactive protein (CRP) and/or procalcitonin) for childhood appendicitis. DESIGN: A systematic review and diagnostic meta-analysis. Data sources included MEDLINE, EMBASE, Central, Web of Science searched from inception-March 2022 with reference searching and authors contacted for missing/unclear data. Eligibility criteria was studies reporting the diagnostic accuracy of the four blood tests compared to the reference standard (histology or follow-up). Risk of bias was assessed (QUADAS-2), pooled sensitivity and specificity were generated for each test and commonly presented cut-offs. To provide insight into clinical impact, we present strategies using a hypothetical cohort. RESULTS: 67 studies were included (34 839 children, 13 342 with appendicitis), all in the hospital setting. The most sensitive tests were WCC (≥10 000 cells/µL, 53 studies sensitivity 0.85 (95% CI 0.80 to 0.89)) and absolute neutrophil count (ANC) (≥7500 cells/µL, five studies sensitivity 0.90 (95% CI 0.85 to 0.94)). Combination of WCC or CRP increased sensitivity further(≥10 000 cells/µL or ≥10 mg/L, individual patient data (IPD) of 6 studies, 0.97 (95% CI 0.93 to 0.99)).Applying results to a hypothetical cohort(1000 children with appendicitis symptoms, of whom 400 have appendicitis) 60 and 40 children would be wrongly discharged based solely on WCC and ANC, respectively, 12 with combination of WCC or CRP.The most specific tests were CRP alone (≥50 mg/L, 38 studies, specificity 0.87 (95% CI 0.80 to 0.91)) or combined with WCC (≥10 000 cells/µL and ≥50 mg/L, IPD of six studies, 0.93 (95% CI 0.91 to 0.95)). CONCLUSIONS: The best performing single blood tests for ruling-out paediatric appendicitis are WCC or ANC; with accuracy improved combining WCC and CRP. These tests could be used at the point of care in combination with clinical prediction rules. We provide insight into the best cut-offs for clinical application. PROSPERO REGISTRATION NUMBER: CRD42017080036

The Impact of the H1n1 Influenza Pandemic on Clinical Presentations and Viral Epidemiology of Acute Respiratory Infection in Preschool Children in Brazil

We assessed the impact of the H1N1 influenza pandemic on acute respiratory infection in young children from low-income families in Brazil. Influenza (specifically H1N1) detection in acute respiratory infection quintupled during the pandemic and, during its peak, it was associated with 30% of all acute respiratory infection visits to the emergency department. H1N1 was also associated with increased risk of hospitalization and coinfection

Appendicitis risk prediction models in children presenting with right iliac fossa pain (RIFT study): a prospective, multicentre validation study.

Background Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. Methods We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5\u201315 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. Findings 15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34\ub75%) underwent appendicectomy. The normal appendicectomy rate was 15\ub79% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0\ub784 (95% CI 0\ub782\u20130\ub786). Applying score cutoffs of 3 points or lower for children aged 5\u201310 years and girls aged 11\u201315 years, and 2 points or lower for boys aged 11\u201315 years, the failure rate was 3\ub73% (95% CI 2\ub70\u20135\ub72; 18 of 539 patients), specificity was 44\ub73% (95% CI 41\ub74\u201347\ub72; 521 of 1176), and positive predictive value was 41\ub74% (38\ub75\u201344\ub74; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72\ub76%, 67\ub74\u201377\ub74) was similar to that of ultrasound scan (75\ub70%, 65\ub73\u201383\ub71). Interpretation The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. Funding None