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The perceived risk of necrotising enterocolitis (NEC) can result in overtreatment of the otherwise adapting preterm neonate. We aim to develop an assessment tool to aid the decision making in the management of preterm neonates at risk of NEC.An evidence-based assessment tool was designed bringing together clinical, laboratory and radiological signs commonly associated with NEC. A numerical score was awarded for each sign, with those more specific to NEC being graded higher. A multi-centre validation was conducted of the proposed assessment tool over three tertiary neonatal units.A total of 125 patients were included, 53 (42.4 %) with a final diagnosis of NEC and 72 (57.6 %) with an alternative diagnosis. The NEC group had a significantly higher total score compared to the non-NEC group; 15(2-28) vs. 4(1-9) (p ≤ 0.0001). In ROC analysis, using a cut-off of eight, the assessment tool gave a sensitivity of 92.3 % and a specificity of 90.4 % for identifying NEC compared to an alternative diagnosis.This comprehensive scoring system encourages a full assessment of the infant before deciding on withholding feeds, starting antibiotics, and transferring to a surgical centre. It is a safe objective measure to support a diagnosis of NEC in the presence of certain clinical signs.

ObjectivesTo describe the range of concurrent cardiac malformations in biliary atresia (BA) while providing a functional framework of risk.MethodsDemographic and variables were collected from a prospectively maintained single-centre database. Infants were grouped according to a cardiac functional framework (A=acyanotic, B=cyanotic and C=insignificant shunt). Primary outcome was set as clearance of jaundice (bilirubin ≤20 μmol/L) following Kasai portoenterostomy (KPE). Native liver survival and overall actuarial survival were compared with a date-matched control infant with BA (n=77). P value Results524 infants with histologically confirmed BA were treated between January 1999 and December 2018, 37 (7%) had a concurrent cardiac anomaly (A: n=23 (62%), B: n=10 (27%), C: n=4 (11%)). Infants with biliary atresia splenic malformation (BASM) or cat-eye syndrome (CES) contributed over half of the cases (21/37; 57%).Overall, 20 (54%) infants cleared jaundice (vs 50/77 (65%) controls; p=0.2), but with higher mortality compared with the non-cardiac controls (15/37 (40%) vs 3/77 (4%); HR 15.5 (95% CI 5.5 to 43.4); pConclusionWe propose the term cardiac-associated biliary atresia (CABA) as a high-risk group. We believe that restorative cardiac surgery should precede KPE wherever possible to improve outcome.

Fibrosis is associated with almost all forms of chronic cardiac and skeletal muscle diseases. The accumulation of extracellular matrix impairs the contractility of muscle cells contributing to organ failure. Transforming growth factor beta (TGF-β) plays a pivotal role in fibrosis, activating pro-fibrotic gene programs via phosphorylation of SMAD2/3 transcription factors. However, the mechanisms that control de-phosphorylation of SMAD2/3 have remained poorly characterized. Here we show that tissue non-specific alkaline phosphatase (TNAP) is highly upregulated in hypertrophic hearts and in dystrophic skeletal muscles, and the abrogation of TGF-β signalling in TNAP positive cells reduces vascular and interstitial fibrosis. We show that TNAP co-localizes and interacts with SMAD2. TNAP inhibitor MLS-0038949 increases SMAD2/3 phosphorylation, while TNAP overexpression reduces SMAD2/3 phosphorylation and the expression of downstream fibrotic genes. Overall our data demonstrate that TNAP negatively regulates TGF-β signalling and likely represents a mechanism to limit fibrosis.Summary statementThis paper shows that tissue non-specific alkaline phosphatase negatively regulates TGF-β signalling and may represent a mechanism to limit fibrosis through SMAD dephosphorylation.

Aim: The diagnosis of anorectal malformations (ARM) is made at birth by perineal examination of the newborn, yet small series reported late diagnosis in almost 13%1. No large series to date have looked into the magnitude of missed ARM cases in the neonatal period across Europe. This study aimed to define the rate of missed ARM at birth across four UK and EU centers. Methods: All ARM cases treated at two UK tertiary centers in the past 15 years were compared to two tertiary European centers. Demographic and relevant clinical data were collected. Late diagnosis was defined as any diagnosis made after discharge from the birth unit. Factors associated with late diagnosis were explored with descriptive statistics. Results: Across the four centers (117/1350, 8.7%) were sent home from the birth unit without recognizing the anorectal anomaly. Missed cases showed a slight female predominance (1.3:1), and the majority (113/117, 96.5%) were of the low anomaly with a fistula to the perineum. The rate of missed ARM cases was significantly higher in the UK centers combined (74/415, 17.8%) compared to those in the EU (43/935, 4.6%), (p Conclusion: Significant variation exist between the UK and other European countries in the detection of ARM at birth. We recommend raising the awareness of accurate perineal examination at time of newborn physical examination. We feel this highlights an urgent need for a national initiative to assess and address the timely diagnosis of ARM in the UK. Key words: anorectal malformations, pediatric surgery, postnatal checks, congenital anomaly.

Aim The aim of this study was to report our initial experience using spiral intestinal lengthening and tailoring (SILT) technique in selected cases of short bowel syndrome (SBS). Materials and Methods We analyzed all cases of SBS underwent SILT in our unit since the introduction of the procedure in 2012. We retrospectively analyzed patients' demographics, pre- and postprocedure bowel length, surgical complications, and postoperative parenteral nutrition (PN) requirements. Data were compared using independent samples, Mann–Whitney's U-test. Results Five children with SBS underwent SILT between 2012 and 2017. Median age at procedure was 8.3 months (4.5–16). Preoperative small bowel length measured a median of 22 cm (17.5–50) with a median diameter of 4 cm (3.5–4.6). SILT allowed a median increase in length of 56% (10–15 cm; p = 0.03) and tailoring of the dilated segment providing a reduction in diameter of 50% (4.3–2.1 cm; p = 0.01). No major complications related to SILT were encountered and none of the children required further surgical intervention following a median follow-up of 26 months (14.5–41). Interestingly, we observed a significant reduction of PN requirement at 6 months (p = 0.008) associated with liver function preservation during the follow-up period. Conclusion In our experience, SILT is a promising adjunct in the surgical management of SBS. It can be used to tailor and lengthen mildly dilated segments of the bowel where other procedures are technically challenging, with a view to reduce the risk of intestinal failure associated liver disease and thereby improving chances for quality survival. Further studies are needed to investigate long-term outcomes of SILT in pediatric SBS.

Ventral body wall (VBW) defects are among the most common congenital malformations, yet their embryonic origin and underlying molecular mechanisms remain poorly characterised. Transforming growth factor beta (TGFβ) signalling is essential for VBW closure, but the responding cells are not known. Here, we identify in mouse a population of migratory myofibroblasts at the leading edge of the closing VBW that express the actin-binding protein transgelin (TAGLN) and TGFβ receptor (TGFβR). These cells respond to a temporally regulated TGFβ2 gradient originating from the epithelium of the primary body wall. Targeted elimination of TGFβR2 in TAGLN+ cells impairs midline closure and prevents the correct subsequent patterning of the musculature and skeletal components. Remarkably, deletion of Tgfbr2 in myogenic or chondrogenic progenitor cells does not manifest in midline defects. Our results indicate a pivotal significance of VBW myofibroblasts in orchestrating ventral midline closure by mediating the response to the TGFβ gradient. Altogether, our data enable us to distinguish highly regulated epithelial-mesenchymal signalling and successive cellular migration events in VBW closure that explain early morphological changes underlying the development of congenital VBW defects., Summary: A population of migratory myofibroblasts at the leading edge of the closing ventral body wall expresses cytoskeletal components and TGFβR2 and responds to an epithelial TGFβ2 morphogen gradient to drive midline closure.