Importance of Ileum and Colon in Children with Short Bowel Syndrome.

BACKGROUND: It is well known that small bowel length is a dominant prognostic indicator in patients with short bowel syndrome (SBS). The relative importance of jejunum, ileum, and colon is less well defined in children with SBS. Here we review the outcome of children with SBS with respect to the type of remnant intestine. METHODS: A retrospective review of 51 children with SBS was conducted at a single institution. The duration of parenteral nutrition use was the main outcome variable. The length of the remaining intestine as well as the type of intestine were recorded for each patient. Kaplan-Meier analyses were conducted to compare the subgroups. RESULTS: Children with greater than 10% expected small bowel length or more than 30 cm of small bowel achieved enteral autonomy faster than those with less. The presence of ileocecal valve enhanced the ability to wean from parenteral nutrition. The presence of ileum significantly enhanced the ability to wean from parenteral nutrition. Patients with the entire colon also achieved enteral autonomy sooner than those with partial colon. CONCLUSIONS: The preservation of ileum and colon is important in patients with SBS. Approaches to preserve or lengthen ileum and colon may be beneficial for these patients. LEVEL OF EVIDENCE: IV.

Risk Factors of Ambulatory Central Line-Associated Bloodstream Infection in Pediatric Short Bowel Syndrome.

BACKGROUND: Children with short bowel syndrome (SBS) receiving home parenteral nutrition (HPN) are predisposed to ambulatory central line-associated bloodstream infection (A-CLABSI). Data describing risk factors of this infection in children are limited. METHODS: Retrospective cohort, single-center, case-crossover study of children ≤18 years old with SBS receiving HPN from January 2012 to December 2016. Univariate and multivariate mixed effect Poisson regression identified the relative risk (RR) of A-CLABSI with proposed risk factors. RESULTS: Thirty-five children were identified; median follow-up was 30 months. A-CLABSI rate was 4.2 per 1000 central line (CL) days. Univariate analysis identified younger age (RR: 0.92 per 12-month increase [95% confidence interval {CI}: 0.85-0.99; P = 0.036]), shorter small intestine length (RR: 0.96 per 10-cm increase [95% CI: 0.92-0.99; P = 0.008]), lower citrulline level (RR: 0.86 per 5-nmol/mL increase [95% CI: 0.75-0.99; P = 0.036]), and recent CL break (RR: 1.55 [95% CI: 1.06-2.28; P = 0.024]) as risk factors for A-CLABSI. Multivariate analysis showed increased A-CLABSI with clinical diagnosis of small intestine bacterial overgrowth (SIBO) (RR: 1.87 [95% CI: 1.1-3.17; P = 0.021]) and CL breaks (RR: 1.49 [95% CI: 1-2.22; P = 0.024]). CONCLUSIONS: Factors influencing gut integrity increase A-CLABSI rate, supporting translocation as an important mechanism and target for prevention. Clinical diagnosis of SIBO increases A-CLABSI rate, but whether dysbiosis or diarrhea is responsible is an area for future research. CL maintenance is crucial, and prevention of breaks would likely decrease A-CLABSI rate.

Procalcitonin as a Predictive Marker for Bacteremia in Children With a Central Line and Fever.

OBJECTIVES: Unnecessary use of antibiotics is an increasing problem. In this study, we sought to determine the diagnostic accuracy of procalcitonin in predicting bacteremia in children with a central line and fever, and we sought to determine optimal cutoff values to maximize sensitivity and specificity. This is the largest study to date in which procalcitonin is examined as a predictive marker of bacteremia in pediatric patients with a central line and fever. METHODS: We conducted a retrospective cohort study of children aged 0 to 23 years with a central line and fever of 38°C who had procalcitonin and blood cultures drawn before initiation of antibiotics and had no other identified bacterial infection. Patients were also prospectively monitored via a custom-built electronic medical record dashboard for eligibility. RESULTS: There were 523 patients and >2500 procalcitonin values reviewed for eligibility. Of these, 169 (47%) patients and 335 blood cultures with procalcitonin were included. There were 94 (28%) positive bacterial blood cultures and 241 (72%) negative bacterial blood cultures. In bacteremic cultures, the mean procalcitonin level was 9.96 ± 15.96 ng/mL, and the median procalcitonin level was 4.85 ng/mL (interquartile range 18.5). In nonbacteremic cultures, the mean procalcitonin level was 1.23 ± 10.37 ng/mL, and the median procalcitonin level was 0.3 ng/mL (interquartile range 0.7). A receiver operating characteristic analysis indicated a procalcitonin level of ≥0.6 ng/mL as the best cutoff point that produced a sensitivity of 85.6% and a specificity of 65.7% (area under the curve 0.85). CONCLUSIONS: Procalcitonin is a sensitive biomarker in predicting bacteremia in children with a central line and fever.

Correction to: Delayed appearance of mature ganglia in an infant with an atypical presentation of total colonic and small bowel aganglionosis: a case report.

Following publication of the original article [1], the authors reported error on the images/figures used which also resulted in un-sequential order. The updated figures and captions are provided below.

Delayed appearance of mature ganglia in an infant with an atypical presentation of total colonic and small bowel aganglionosis: a case report.

BACKGROUND: Total colonic and small bowel aganglionosis (TCSA) occurs in less than 1% of all Hirschsprung's disease patients. Currently, the mainstay of treatment is surgery. However, in patients with TCSA, functional outcomes are often poor. A characteristic transition zone in TCSA can be difficult to identify which may complicate surgery and may often require multiple operations. CASE PRESENTATION: We present the case of a male infant who was diagnosed with biopsy-proven total colonic aganglionosis with extensive small bowel involvement as a neonate. The patient was diverted at one month of age based on leveling biopsies at 10 cm from the Ligament of Treitz. At 7 months of age, during stoma revision for a prolapsed stoma, intra-operative peristalsis was observed in nearly the entire length of the previously aganglionic bowel, and subsequent biopsies demonstrated the appearance of mature ganglion cells in a previously aganglionic segment. CONCLUSIONS: TCSA remains a major challenge for pediatric surgeons. Our case introduces new controversy to our understanding of aganglionosis. Our observations warrant further research into the possibility of post-natal ganglion maturation and encourage surgeons to consider a more conservative surgical approach.

Nutritional Needs and Support for Children with Chronic Liver Disease.

Malnutrition has become a dangerously common problem in children with chronic liver disease, negatively impacting neurocognitive development and growth. Furthermore, many children with chronic liver disease will eventually require liver transplantation. Thus, this association between malnourishment and chronic liver disease in children becomes increasingly alarming as malnutrition is a predictor of poorer outcomes in liver transplantation and is often associated with increased morbidity and mortality. Malnutrition requires aggressive and appropriate management to correct nutritional deficiencies. A comprehensive review of the literature has found that infants with chronic liver disease (CLD) are particularly susceptible to malnutrition given their low reserves. Children with CLD would benefit from early intervention by a multi-disciplinary team, to try to achieve nutritional rehabilitation as well as to optimize outcomes for liver transplant. This review explains the multifactorial nature of malnutrition in children with chronic liver disease, defines the nutritional needs of these children, and discusses ways to optimize their nutritional.

Management of short bowel syndrome in postoperative very low birth weight infants.

Short bowel syndrome is a potentially devastating morbidity for the very low birth weight infant and family with a high risk for mortality. Prevention of injury to the intestine is the ideal, but, if and when the problem arises, it is important to have a systematic approach to manage nutrition, use pharmaceutical strategies and tools to maximize the outcome potential. Safely maximizing parenteral nutrition support by providing adequate macronutrients and micronutrients while minimizing its hepatotoxic effects is the initial postoperative strategy. As the infant stabilizes and starts to recover from that initial injury and/or surgery, a slow and closely monitored enteral nutrition approach should be initiated. Enteral feeds can be complemented with medications and supplements emerging as valuable clinical tools. Engaging a multidisciplinary team of neonatologists, gastroenterologists, pharmacists, skilled clinical nutrition support staff including registered dietitians and nutrition support nurses will facilitate optimizing each and every infant's long term result. Promoting intestinal rehabilitation and adaptation through evidence-based practice where it is found, and ongoing pursuit of research in this rare and devastating disease, is paramount in achieving optimal outcomes.

Iodine Supplementation for Pediatric Patients Receiving Long-Term Parenteral Nutrition.

BACKGROUND: Patients dependent on parenteral nutrition (PN) are among a group at risk of developing iodine deficiency. Supplementation with iodine in this population has been debated in a number of studies, resulting in variable clinical practices. The Committee on Clinical Practice Issues of the American Society for Clinical Nutrition recommends a dose of 1 mcg/kg/d of parenteral iodine for patients receiving PN. At our institution, PN trace elements do not include iodine, although this is not the case internationally. Our study sought to assess iodine levels and thyroid function in a cohort of PN-dependent pediatric patients. METHODS: A retrospective analysis studied 32 pediatric patients with a variety of medical diagnoses who received PN as a primary means of nutrition for 6 months or longer. Patients received variable proportions of their total caloric intake as PN, which ranged from 14%-100%. Iodine and thyroid function levels were obtained by serum sampling. RESULTS: No patient in our cohort of 32 demonstrated thyroid dysfunction or developed iodine deficiency. The length of time on PN and the percentage of total nutrition intake as PN were not associated with iodine levels (P < .89 and P < .73, respectively). There were no significant associations between age (P < .342), clinical diagnosis (P < .46), or sex (P < .43) on iodine status. There were no incidences of abnormal iodine levels in our cohort. Our study suggests that pediatric patients older than 6 months receiving PN may not benefit from iodine supplementation, but further investigation is needed.

ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.

Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS) is a rare congenital disorder, in which heterozygous missense variants in the Enteric Smooth Muscle actin γ-2 (ACTG2) gene have been recently identified. To investigate the mechanism by which ACTG2 variants lead to MMIHS, we screened a cohort of eleven MMIHS patients, eight sporadic and three familial cases, and performed immunohistochemistry, molecular modeling and molecular dynamics (MD) simulations, and in vitro assays. In all sporadic cases, a heterozygous missense variant in ACTG2 was identified. ACTG2 expression was detected in all intestinal layers where smooth muscle cells are present in different stages of human development. No histopathological abnormalities were found in the patients. Using molecular modeling and MD simulations, we predicted that ACTG2 variants lead to significant changes to the protein function. This was confirmed by in vitro studies, which showed that the identified variants not only impair ACTG2 polymerization, but also contribute to reduced cell contractility. Taken together, our results confirm the involvement of ACTG2 in sporadic MMIHS, and bring new insights to MMIHS pathogenesis.

Evaluation of intestinal biopsies for pediatric enteropathy: a proposed immunohistochemical panel approach.

Congenital enteropathies are rare disorders with significant clinical consequences; however, definitive diagnosis based on morphologic assessment of duodenal biopsies with routine stains alone is often impossible. To determine the role of immunohistochemistry (IHC) in the evaluation for microvillous inclusion disease, congenital tufting enteropathy (intestinal epithelial dysplasia), and enteroendocrine cell dysgenesis, a series of duodenal biopsies from 26 pediatric patients with chronic/intractable diarrhea was retrospectively reviewed. IHC stains for CD10, EpCAM, chromogranin, and villin were performed on all biopsies, and the results were correlated with hematoxylin and eosin and ultrastructural findings using electron microscopy, when available. Biopsies from 2 patients diagnosed with microvillous inclusion disease at the time of original biopsy demonstrated diffuse CD10-positive cytoplasmic inclusions within enterocytes and normal expression of EpCAM and chromogranin. Biopsies from 3 patients, including 2 siblings with confirmed EPCAM mutations, demonstrated complete loss of EpCAM expression and normal expression of CD10 and chromogranin; electron microscopic evaluation revealed characteristic ultrastructural findings of tufting enteropathy. Biopsies from 1 patient with a confirmed NEUROG3 mutation demonstrated an absence of intestinal enteroendocrine cells by chromogranin staining, consistent with enteroendocrine cell dysgenesis. Four patients' biopsies displayed nonspecific staining patterns for CD10 and/or EpCAM with normal expression of chromogranin, and 16 patients' biopsies exhibited normal expression for all 3 markers. Villin stains demonstrated heterogenous brush border labeling with nonspecific cytoplasmic reactivity, a pattern variably present throughout the biopsy series. In conclusion, the routine use of an IHC panel of CD10, EpCAM, and chromogranin is warranted in patients meeting specific age and/or clinical criteria, as the morphologic findings of congenital enteropathies may be subtle, focal, or inapparent on routine stains.