Incidence, prevention, and treatment of parenteral nutrition-associated cholestasis and intestinal failure-associated liver disease in infants and children: a systematic review.

BACKGROUND: Cholestasis is a significant life-threatening complication in children on parenteral nutrition (PN). Strategies to prevent/treat PN-associated cholestasis (PNAC) and intestinal failure-associated liver disease (IFALD) have reached moderate success with little supporting evidence. Aims of this systematic review were (1) to determine the incidence of PNAC/IFALD in children receiving PN for ≥ 14 days and (2) to review the efficacy of measures to prevent/treat PNAC/IFALD. METHODS: Of 4696 abstracts screened, 406 relevant articles were reviewed, and studies on children with PN ≥ 14 days and cholestasis (conjugated bilirubin ≥ 2 mg/dL) were included. Analyzed parameters were (1) PNAC/IFALD incidence by decade and by PN length and (2) PNAC/IFALD prevention and treatment (prospective studies). RESULTS: Twenty-three articles (3280 patients) showed an incidence of 28.2% and 49.8% of PNAC and IFALD, respectively, with no evident alteration over the last decades. The incidence of PNAC was directly proportional to the length of PN (from 15.7% for PN ≤ 1 month up to 60.9% for PN ≥ 2 months; P < .0001). Ten studies on PNAC met inclusion criteria. High or intermediate-dose of oral erythromycin and aminoacid-free PN with enteral whey protein gained significant benefits in preterm neonates (P < .05, P = .003, and P < .001, respectively). None of the studies reviewed met inclusion criteria for treatment. CONCLUSIONS: The incidence of PNAC/IFALD in children has no obvious decrease over time. PNAC is directly correlated to the length of PN. Erythromycin and aminoacid-free PN with enteral whey protein have shown to prevent PNAC in preterm neonates. There is a lack of high-quality prospective studies, especially on IFALD.

Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach.

Induced pluripotent stem cells (iPSCs) with potential for therapeutic applications can be derived from somatic cells via ectopic expression of a set of limited and defined transcription factors. However, due to risks of random integration of the reprogramming transgenes into the host genome, the low efficiency of the process, and the potential risk of virally induced tumorigenicity, alternative methods have been developed to generate pluripotent cells using nonintegrating systems, albeit with limited success. Here, we show that c-KIT+ human first-trimester amniotic fluid stem cells (AFSCs) can be fully reprogrammed to pluripotency without ectopic factors, by culture on Matrigel in human embryonic stem cell (hESC) medium supplemented with the histone deacetylase inhibitor (HDACi) valproic acid (VPA). The cells share 82% transcriptome identity with hESCs and are capable of forming embryoid bodies (EBs) in vitro and teratomas in vivo. After long-term expansion, they maintain genetic stability, protein level expression of key pluripotency factors, high cell-division kinetics, telomerase activity, repression of X-inactivation, and capacity to differentiate into lineages of the three germ layers, such as definitive endoderm, hepatocytes, bone, fat, cartilage, neurons, and oligodendrocytes. We conclude that AFSC can be utilized for cell banking of patient-specific pluripotent cells for potential applications in allogeneic cellular replacement therapies, pharmaceutical screening, and disease modeling.

Infliximab and pediatric stricturing Crohn's disease: a possible alternative to surgery? Experience of seven cases.

INTRODUCTION: Infliximab (IFX) is one of the treatments of choice for the different phenotypes of pediatric Crohn's disease (CD). Although it was initially feared that anti-TNFα treatment might cause bowel stenosis, recent studies have validated the efficacy of IFX as an anti-stricturing agent. AIM: To assess the efficacy of IFX treatment for pediatric stricturing CD. PATIENTS AND METHODS: Data were obtained on pediatric patients treated at our tertiary level Pediatrics Department (years 2000-2010). Indications for IFX therapy included persistent disease activity (PCDAI > 20) unresponsive to corticosteroids and thiopurines. All patients treated with IFX underwent upper and lower intestinal endoscopy, abdominal ultrasound and magnetic resonance enterography. CASE SERIES: Among 44 pediatric CD patients, 21 were treated with IFX. Seven of these cases had luminal strictures and in 6 patients the inflammatory strictures disappeared after treatment with IFX. One child with ileal fibrotic stenosis (MR) required a surgical resection. CONCLUSION: Our data support the efficacy of IFX in pediatric CD, including the stricturing phenotype.