Although parenteral nutrition (PN) is life-sustaining, it is associated with many complications including parenteral nutrition-associated liver disease (PNALD) and central line-associated bloodstream infections (CLASBIs), which carry a high morbidity and mortality and impose a burden on the health care system. Evidence has emerged that the dose and composition of intravenous lipid products may alter the incidence of PNALD. However, other patient and PN-related factors, such as prematurity, birth weight, and gastrointestinal anatomy and function, are important. To improve neonatal care, future research on optimizing the content of PN and decreasing the incidence IFALD and CLASBIs is required.

The current United Network for Organ Sharing (UNOS) policy is to allocate liver grafts to pediatric patients with chronic liver disease based on the pediatric end-stage liver disease (PELD) scoring system, while children with fulminant hepatic failure may be urgently listed as Status 1a. The objective of this study was to identify pre-transplant variables that influence patient and graft survival in those children undergoing LTx (liver transplantion) for FHF (fulminant hepatic failure) compared to those patients transplanted for extrahepatic biliary atresia (EHBA), a chronic form of liver disease. The UNOS Liver Transplant Registry was examined for pediatric liver transplants performed for FHF and EHBA from 1987 to 2002. Variables that influenced patient and graft survival were assessed using univariate and multivariate analysis. Kaplan-Meier analysis of FHF and EHBA groups revealed that 5 year patient and graft survival were both significantly worse (P < 0.0001) in those patients who underwent transplantation for FHF. Multivariate analysis of 29 variables subsequently revealed distinct sets of factors that influenced patient and graft survival for both FHF and EHBA. These results confirm that separate prioritizing systems for LTx are needed for children with chronic liver disease and FHF; additionally, our findings illustrate that there are unique sets of variables which predict survival following LTx for these two groups.

We report a 9-year-old patient with abnormal liver tests found incidentally during routine bloodwork as part of a preoperative evaluation for excision of a benign cyst. A liver biopsy demonstrated hepatocytes to have pale and expanded cytoplasm that contained multiple vague globular eosinophilic inclusions. Electron microscopy showed fingerprint-like structures in the dilated cisternae of the rough endoplasmic reticulum, characteristic of fibrinogen. Whole exome sequencing identified a heterozygous missense mutation at codon 35 of the fibrinogen α (FGA) gene. No mutation was identified in the β or γ chains. His plasma fibrinogen levels were found to be decreased to 85 mg/dL (normal range 215-464). His family history was pertinent for his mother and maternal grandfather with hypofibrinogenemia. He had not had any significant bleeding episodes except for minor bruising over the shins. This case illustrates a rare etiology of storage disease that causes abnormal liver function tests.

BACKGROUND: We propose a novel clinically significant finding, de novo lupus-like glomerulonephritis (DNLLGN), in patients with autoantibodies and kidney abnormalities in pediatric liver transplant (LT) and intestinal inclusive transplants (ITx). METHODS: We describe the clinical, serologic, and histopathologic presentation and kidney outcomes in eight patients from our center found to have DNLLGN on kidney biopsy. RESULTS: Pediatric recipients of non-kidney solid organ transplants developed an unusual de novo immune complex glomerulonephritis with morphologic similarity to lupus nephritis. Six had isolated LT (0.9% of all pediatric LT at our center) and two had ITx (2.1% of all ITx). Five (63%) presented with nephrotic syndrome. Five patients had autoantibodies. Patients underwent kidney biopsy at a mean of 11.5 years in LT and 2.8 years in ITx after the index transplant. Biopsies demonstrated changes similar to focal or diffuse active lupus. Follow-up eGFR at a mean of 6 years after biopsy showed a mean decrease of 30 ml/min/1.73 m2 in all patients (p = 0.11). CONCLUSIONS: DNLLGN has not been previously recognized in this clinical setting, yet 8 kidney biopsies from pediatric recipients of LT and ITx at our center in 25 years demonstrated this finding. DNLLGN appears to be an under-reported phenomenon of clinical significance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Outcomes for pediatric SBT patients requiring perioperative RRT in the PICU remain unknown. The objectives were to document our center's experience with PICU SBT patients receiving perioperative RRT and to identify variables predictive of survival to discharge. A retrospective chart review of patients (ages, 0-18 yr) between January 1, 2000 and December 31, 2011 that received RRT within a SBT perioperative period and were transplanted at our university-affiliated, tertiary care children's hospital was performed. Six SBT patients received perioperative RRT (ages, 5-12 yr). Three patients (50%) survived to hospital discharge. Among survivors, RRT was required for a total of 1-112 days (mean, 49.7 days). All three survivors survived to hospital discharge without renal transplantation and free of RRT. There was a trend toward increased survival among older patients receiving RRT (p = 0.05). Survivors had a higher I-125 GFR prior to PICU admission (p = 0.045). A higher I-125 GFR prior to PICU admission among survivors may support this test's utility during SBT evaluation. In our experience, a high survival rate and freedom from RRT at the time of discharge support RRT use in the SBT population.

Outcomes for pediatric SBT patients requiring perioperative RRT in the PICU remain unknown. The objectives were to document our center's experience with PICU SBT patients receiving perioperative RRT and to identify variables predictive of survival to discharge. A retrospective chart review of patients (ages, 0-18 yr) between January 1, 2000 and December 31, 2011 that received RRT within a SBT perioperative period and were transplanted at our university-affiliated, tertiary care children's hospital was performed. Six SBT patients received perioperative RRT (ages, 5-12 yr). Three patients (50%) survived to hospital discharge. Among survivors, RRT was required for a total of 1-112 days (mean, 49.7 days). All three survivors survived to hospital discharge without renal transplantation and free of RRT. There was a trend toward increased survival among older patients receiving RRT (p = 0.05). Survivors had a higher I-125 GFR prior to PICU admission (p = 0.045). A higher I-125 GFR prior to PICU admission among survivors may support this test's utility during SBT evaluation. In our experience, a high survival rate and freedom from RRT at the time of discharge support RRT use in the SBT population.

Ileoscopy with mucosal biopsy is fundamental in the management and surveillance of inflammatory bowel disease patients and intestinal transplant recipients. There is a paucity of data describing the risks of ileoscopy in the presence of a prolapsed stoma. Parastomal hernias are frequently associated with prolapsed stomas. We report the first case of perforation during ileoscopy in the setting of a prolapsed stoma and unrecognized parastomal hernia. Recognition of parastomal hernia associated with stoma prolapse is of paramount importance in patients undergoing ileoscopy as it may increase the risk of perforation.

Objective

To further refine a measure of self-management, the Responsibility and Familiarity with Illness Survey (REFILS), and to determine if this score predicts medication adherence and, thus, fewer instances of allograft rejection among pediatric liver transplant recipients.

Study design

Participants were 400 liver transplant recipients and their parents recruited for the Medication Adherence in Children Who Had a Liver Transplant study, from 5 US pediatric transplant centers. The REFILS was administered to participants (ages 9-17 years) and their parents at enrollment (n = 213 completed dyads). The REFILS scores, and a discrepancy score calculated between patient and parent report of the patient's self-management, were used to predict Medication Level Variability Index (MLVI), a measure of medication adherence (higher MLVI = more variability in medication levels) and central pathologist-diagnosed rejection over a 2-year follow-up.

Results

When patients reported greater self-management, their adherence was lower (higher MLVI, r = 0.26, P < .01). Discrepancies between patient and parent report (patients endorsing higher levels than parents) were associated with lower adherence (r = 0.20, P < .01). Greater patient-reported self-management and higher discrepancy scores also predicted rejection.

Conclusions

We found that when patients endorse more responsibility for their care, clinical outcomes are worse, indicating that indiscriminate promotion of self-management by adolescents may not be advisable. A discrepancy between patient and parent perception of self-management emerged as a novel strategy to gauge the degree of risk involved in transitioning care responsibilities to the child.

Objectives

Congenital diarrhea disorders are a group of genetically diverse and typically autosomal recessive disorders that have yet to be well characterized phenotypically or molecularly. Diagnostic assessments are generally limited to nutritional challenges and histologic evaluation, and many subjects eventually require a prolonged course of intravenous nutrition. Here we describe next-generation sequencing techniques to investigate a child with perplexing congenital malabsorptive diarrhea and other presumably unrelated clinical problems; this method provides an alternative approach to molecular diagnosis.

Methods

We screened the diploid genome of an affected individual, using exome sequencing, for uncommon variants that have observed protein-coding consequences. We assessed the functional activity of the mutant protein, as well as its lack of expression using immunohistochemistry.

Results

Among several rare variants detected was a homozygous nonsense mutation in the catalytic domain of the proprotein convertase subtilisin/kexin type 1 gene. The mutation abolishes prohormone convertase 1/3 endoprotease activity as well as expression in the intestine. These primary genetic findings prompted a careful endocrine reevaluation of the child at 4.5 years of age, and multiple significant problems were subsequently identified consistent with the known phenotypic consequences of proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations. Based on the molecular diagnosis, alternate medical and dietary management was implemented for diabetes insipidus, polyphagia, and micropenis.

Conclusions

Whole-exome sequencing provides a powerful diagnostic tool to clinicians managing rare genetic disorders with multiple perplexing clinical manifestations.