Objective To characterize the natural history of intestinal failure (IF) among 14 pediatric centers during the intestinal transplantation (ITx) era. Study design The Pediatric Intestinal Failure Consortium performed a retrospective analysis of clinical and outcome data for a multi-center cohort of infants with IF. Entry criteria included infants <12 mo receiving parenteral nutrition (PN) for >60 continuous days. Enteral autonomy was defined as discontinuation of PN for >3 consecutive months. Values are presented as median (25th, 75th percentiles) or as (n, %). Results 272 infants with a gestational age of 34 wks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 mo (11.2, 40.9). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). Prescribed medications included oral antibiotics (207, 76%), H2 blockers (187, 69%), and PPIs (156, 57%). Enteral feeding approaches varied among centers; 19% of the cohort received human milk. The cohort experienced 8.9 new catheter-related blood stream infections per 1,000 catheter days. The cumulative incidences for enteral autonomy, death, and ITx were 47%, 27%, and 26%, respectively. Enteral autonomy continued into the 5th year after study entry. Conclusions Children with IF endure significant mortality and morbidity. Enteral autonomy may require years to achieve. Improved medical, nutritional, and surgical management may reduce time on PN, mortality and need for transplantation.

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Awareness of the spectrum of eosinophilic esophagitis should promote optimal diagnosis and treatment of this elusive entity, both in children and in adults.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder of the esophagus that is compounded by genetic predisposition and hypersensitivity to environmental antigens. Using high-density oligonucleotide expression chips, a disease-specific esophageal transcript signature was identified and shown to be largely reversible with therapy. In an effort to expand the molecular signature of EoE, we performed RNA sequencing on esophageal biopsies from healthy controls and patients with active EoE and identified a total of 1 607 significantly dysregulated transcripts (1 096 upregulated, 511 downregulated). When clustered by raw expression levels, an abundance of immune-cell specific transcripts that are highly induced in EoE are expressed at low (or undetectable) levels in healthy controls. Moreover, 66% of the gene signature identified by RNA sequencing was previously unrecognized in the EoE transcript signature by microarray-based expression profiling and included several long non-coding RNAs (lncRNA), an emerging class of transcriptional regulators. The lncRNA BANCR was upregulated in EoE and induced in IL-13–treated primary esophageal epithelial cells. Repression of BANCR significantly altered the expression of IL-13–induced pro-inflammatory genes. Together, these data comprise new potential biomarkers of EoE and demonstrate a novel role for lncRNAs in EoE and IL-13–associated responses.

ABSTRACT. Objective. To determine whether medically unexplained recurrent abdominal pain (RAP) in childhood predicts abdominal pain, irritable bowel syndrome (IBS), other somatic complaints, and psychiatric symptoms and disorders in young adulthood.Methods. A sample of 28 young adults evaluated for RAP between the ages of 6 and 17 years were compared with 28 individually matched former childhood participants in a study of tonsillectomy and adenoidectomy. RAP caseness was established by structured retrospective chart review requiring agreement by 2 independent reviewers. Standardized assessments of abdominal pain, IBS, other somatic symptoms, psychopathology, perceived health, and history of maltreatment were performed an average of 11.1 years after the index visit.Results. Former RAP patients were significantly more likely than controls to endorse anxiety symptoms and disorders, hypochondriacal beliefs, greater perceived susceptibility to physical impairment, poorer social functioning, current treatment with psychoactive medication, and generalized anxiety in first degree relatives. There were trends suggesting associations between childhood RAP and lifetime psychiatric disorder, depression, migraine, and family history of depression, but group differences on abdominal pain, IBS, other somatic symptoms, and history of maltreatment were not statistically significant.Conclusions. There is a strong and relatively specific association between childhood RAP and anxiety in young adulthood. Affected children may be at special risk to perceive physical symptoms as threatening, and should be evaluated for psychiatric disorder on initial presentation. Pediatrics 2001;108(1). URL: http://www. pediatrics.org/cgi/content/full/108/1/e1; abdominal pain, pain, anxiety, depression, colonic diseases, functional.ABBREVIATIONS. RAP, recurrent abdominal pain; FGD, functional gastrointestinal disorder; IBS, irritable bowel syndrome; DSM, Diagnostic and Statistical Manual of Mental Disorders; SCID-NP, Structured Clinical Interview for DSM-IV, Non-patient Version; BSI, brief symptom inventory; NS, not significant. R ecurrent abdominal pain (RAP) has been most consistently defined in the pediatric literature as at least 3 episodes of abdominal pain occurring during a period of at least 3 months that are severe enough to affect the activities of the child. 1,2 RAP is common, affecting between 7% to 25% of school-aged children and adolescents, 1,3-11 and may be responsible for 2% to 4% of pediatric office visits. 12 RAP becomes more prevalent with increasing age into adolescence 1,5,7,10 and is more common in girls, 4,13 with an equal gender ratio in early childhood, 11,14 but greater female symptom reporting in late childhood and adolescence. 1,9,10 Specific structural, infectious, inflammatory, or laboratory abnormalities are unusual in RAP, particularly in the absence of "red flags" such as weight loss, gastrointestinal bleeding, pain awakening the child at night, systemic symptoms such as fever, or laboratory evidence of anemia or inf...

Purpose-A clinical trial of intestinal transplantation (Itx) under tacrolimus and prednisone immunosuppression was initiated in June 1990 in children with irreversible intestinal failure and who were dependent on total parenteral nutrition (TPN).Methods-Fifty-five patients (28 girls, 27 boys) with a median age of 3.2 years (range, 0.5 to 18 years) received 58 intestinal transplants that included isolated small bowel (SB) (n = 17), liver SB (LSB) (n = 33), and multivisceral (MV) (n = 8) allografts. Nine patients also received bone marrow infusion, and there were 20 colonic allografts. Azathioprine, cyclophosphamide, or mycophenolate mofetil were used in different phases of the series. Indications for Itx included: gastroschisis(n = 14), volvulus (n = 13), necrotizing enterocolitis (n = 6), intestinal atresia (n = 8), chronic intestinal pseudoobstruction (n = 5), Hirschsprung's disease (n = 4), microvillus inclusion disease (n = 3), multiple polyposis (n = 1), and trauma (n = 1).Results-Currently, 30 patients are alive (patient survival, 55%; graft survival, 52%). Twenty-nine children with functioning grafts are living at home and off TPN, with a mean follow-up of 962 (range, 75 to 2,424) days. Immunologic complications have included liver allograft rejection (n = 18), intestinal allograft rejection (n = 52), posttransplant lymphoproliferative disease (n = 16), cytomegalovirus (n = 16) and graft-versus-host disease (n = 4). A combination of associated complications included intestinal perforation (n = 4), biliary leak (n = 3), bile duct stenosis (n = 1), intestinal leak (n = 6), dehiscence with evisceration (n = 4), hepatic artery thrombosis (n = 3), bleeding (n = 9), portal vein stenosis (n = 1), intraabdominal abscess (n = 11), and chylous ascites (n = 4). Graft loss occurred as a result of rejection (n = 8), infection (n = 12), technical complications (n = 8), and complications of TPN after graft removal (n = 3). There were four retransplants (SB, n = 1; LSB n = 3).Conclusions-Intestinal transplantation is a valid therapeutic option for patients with intestinal failure suffering complications of TPN. The complex clinical and immunologic course of these patients is reflected in a higher complication rate as well as patient and graft loss than seen after heart, liver, and kidney transplantation, although better than after lung transplantation.

Objectives In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. Study design A multicenter retrospective cohort analysis from the Pediatric Intestinal Failure Consortium (PIFCon) was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with PN dependence >60 days. Enteral autonomy was defined as PN discontinuation >3 months. Results 272 infants were followed for a median (IQR) of 33.5(16.2, 51.5) months. Enteral autonomy was achieved in 118(43%); 36(13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified NEC [OR 95% CI: 2.42 (1.33, 4.47)], care at an IF site without an associated intestinal transplant (ITx) program [OR 2.73 (1.56, 4.78)] and an intact ileocecal valve (ICV) [OR 2.80 (1.63, 4.83)] as independent risk factors for enteral autonomy. A second model (n=144) including only patients with intra-operatively measured residual small bowel length (RSB) found NEC [OR 3.44 (1.36, 8.71)], care at a non-ITx center [OR 6.56 (2.53, 16.98)] and RSB (cm) [OR 1.04 (1.02, 1.06)] to be independently associated with enteral autonomy. Conclusions A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ICV and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.

ClinicalTrials.gov:NCT01952080; EudraCT: 2013-004588-30.