Neonates living with enterostomy following necrotising enterocolitis are at high risk of becoming severely underweight

Necrotising enterocolitis (NEC) is often managed with a temporary enterostomy. Neonates with enterostomy are at risk of growth retardation during critical neurodevelopment. We examined their growth using z-score. We identified all patients with enterostomy from NEC in two neonatal surgical units (NSU) during January 2012–December 2016. Weight-for-age z-score was calculated at birth, stoma formation and closure, noting severely underweight as z < − 3. We compared those kept in NSU until stoma closure with those discharged to local units or home (LU/H) with a stoma. A total of 74 patients were included. By stoma closure, 66 (89%) had deteriorated in z-score with 31 (42%) being severely underweight. There was no difference in z-score at stoma closure between NSU and LU/H despite babies sent to LU/H having a more distal stoma, higher birth weight and gestational age. Babies in LU/H spent a much shorter period on parenteral nutrition while living with their stoma for longer, many needing readmission. Conclusion: Growth failure is a common and severe problem in babies living with enterostomy following NEC. z-score allowed growth trajectory to be accounted for in nutrition prescription and timing of stoma closure. Care during this period should be focused on minimising harm.What is Known:• Necrotising enterocolitis (NEC) is a life-threatening condition affecting predominately premature and very low birth weight neonates. Emergency treatment with temporary enterostomy often leads to growth failure.• There is no consensus on the optimal timing for stoma reversal, hence prolonging impact on growth during crucial developmental periods. Both malnutrition and surgical NEC are independently associated with poor neurodevelopment outcome.What is New:• Our study found growth in 89% of babies deteriorated while living with a stoma, with 42% having a weight-for-age z-score < − 3, meeting the WHO criteria of being severely underweight, despite judicial use of parenteral nutrition. Applying z-score to weight measurements will allow growth trajectory to be accounted for in clinical decisions, including nutrition prescription (both enteral and parenteral), and guide timing of stoma closure.• Surgeons who target stoma closure at a certain weight risk waiting for an indefinite period of time, during which babies’ growth may falter

Age-associated modifications of intestinal permeability and innate immunity in human small intestine

The physical and immunological properties of the human intestinal epithelial barrier in aging are largely unknown. Ileal biopsies from young (7–12 years), adult (20–40 years) and aging (67–77 years) individuals not showing symptoms of gastrointestinal (GI) pathologies were used to assess levels of inflammatory cytokines, barrier integrity and cytokine production in response to microbial challenges. Increased expression of interleukin (IL)-6, but not interferon (IFN)γ, tumour necrosis factor (TNF)-α and IL-1β was observed during aging; further analysis showed that cluster of differentiation (CD)11c+ dendritic cells (DCs) are one of the major sources of IL-6 in the aging gut and expressed higher levels of CD40. Up-regulated production of IL-6 was accompanied by increased expression of claudin-2 leading to reduced transepithelial electric resistance (TEER); TEER could be restored in in vitro and ex vivo cultures by neutralizing anti-IL-6 antibody. In contrast, expression of zonula occludens-1 (ZO-1), occludin and junctional-adhesion molecule-A1 did not vary with age and overall permeability to macromolecules was not affected. Finally, cytokine production in response to different microbial stimuli was assessed in a polarized in vitro organ culture (IVOC). IL-8 production in response to flagellin declined progressively with age although the expression and distribution of toll-like receptor (TLR)-5 on intestinal epithelial cells (IECs) remained unchanged. Also, flagellin-induced production of IL-6 was less pronounced in aging individuals. In contrast, TNF-α production in response to probiotics (VSL#3) did not decline with age; however, in our experimental model probiotics did not down-regulate the production of IL-6 and expression of claudin-2. These data suggested that aging affects properties of the intestinal barrier likely to impact on age-associated disturbances, both locally and systemically

Faecal interleukin-8 and Tumour necrosis factor a concentrations and disease activity in Cystic Fibrosis

By speculatively using an ELISA technique optimised for measuring cytokine concentrations in cell culture supernatants, I have demonstrated massively elevated faecal IL-8 and TNFα concentrations in 9 UK patients with cystic fibrosis, and have shown a correlation between lung disease severity and faecal IL-8 concentration. Such an assay had the potential to be a repeatable non invasive gauge of the severity of pulmonary inflammation in these patients. However subsequent assays in 14 Australian CF patients detected no faecal cytokines. The assays used proved to be inaccurate and non linear, and I developed and validated an accurate and linear assay protocol by using newborn calf serum as a sample diluent. With this assay patients with crohn's colitis were shown to have high faecal IL-8 and TNFα concentrations, but 19 patients with CF and patients with pneumonia, asthma, bronchiectasis and healthy control children had no detectable faecal cytokine.Subsequent experiments showed that pancreatic enzyme supplements efficiently digest both cytokines at both pH8 and pH4.5, that CF patients' faecal flora do not have a major digestive effect on these cytokines, and that when gavaged into rat stomach these cytokines do not pass through the intestine in detectable quantities.The hypothesis that faecal cytokines are produced in response to high lipase pancreatic enzyme therapy in CF was tested by serially measuring cytokine concentrations in cases and controls as this therapy was commenced. TNFα was detected in no patient or control, but low concentrations of IL-8 were found in one pre exposure sample and in two isolated post exposure samples in three separate patients.The enzyme dosage in this study was one third of that in the initial UK study and it is possible that a higher enzyme dosage might have replicated those initial results, it is however equally possible that the non linear assay used in the initial study greatly over-estimated the cytokine concentration in that study.It now seems unlikely that cytokine detected in faeces has it's origins in swallowed pulmonary secretions. It is certain that measurement of faecal IL-8 and TNFα does not give a reliable measure of the severity of pulmonary inflammation in cystic fibrosis.</p

Diagnosis and management of children with Blue Rubber Bleb Nevus Syndrome: A multi-center case series

Background: Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare, severe, sporadically occurring disorder characterized by multiple venous malformations. Aims: To present and analyze a case series of pediatric patients with BRBNS and to describe diagnostic approaches and management options applied. Patients and methods: Multicenter, retrospective study, evaluating the diagnosis and management of children with BRBNS. Results: Eighteen patients diagnosed with BRBNS were included. Cutaneous venous malformations were observed in 78% and gastrointestinal venous malformations in 89%. Lesions were also found in other organs including muscles, joints, central nervous system, eyes, parotid gland, spine, kidneys and lungs. Gastrointestinal lesions were more common in the small intestine than in stomach or colon. The management varied significantly among centers. Endoscopic therapy and surgical therapy alone failed to prevent recurrence of lesions. In younger children and in patients with musculoskeletal or other organ involvement, sirolimus was used with 100% success rate in our series (5 patients treated) although poor compliance with subtherapeutic sirolimus trough levels led to recurrence in a minority. Conclusions: Considering the multi-organ involvement in BRBNS, diagnosis and management requires a multidisciplinary approach. The treatment includes conservative, medical, endoscopic and surgical options. Prospective multicenter studies are needed to identify the optimal management of this rare condition

Computing solutions to algebraic problems using a symbolic versus a schematic strategy

10.1007/s11858-010-0265-6ZDM1-1