Comparison of two formulations of intravenous lipid emulsions in pediatric intestinal failure.

PURPOSE: The effect of different types of lipid emulsion may guide therapy of patients with intestinal failure (IF) to limit morbidity such as intestinal failure-associated liver disease (IFALD). METHODS: A retrospective chart review of pediatric patients with IF who received soybean oil lipid emulsion (SL) or mixed oil lipid emulsion (ML) was performed. Data over 1 year were collected. RESULTS: Forty-five patients received SL and 34 received ML. There were no differences in the incidence (82 versus 74%, P = 0.35) or resolution (86 versus 92%, P = 0.5) of IFALD between the cohorts. The median dose of ML was higher compared to SL (2 versus 1 g/kg/day, P < 0.001). If resolved, IFALD resolved rapidly in the ML cohort compared to the SL cohort (67 versus 37 days, P = 0.01). Weight gain was higher in the ML compared to the SL cohort at resolution of IFALD or 1 year from diagnosis of IF (P = 0.009). CONCLUSION: The administration of ML did not alter the incidence or resolution of IFALD compared to SL in pediatric IF. There was rapid resolution of IFALD and enhanced weight gain in the ML cohort compared to SL in pediatric IF.

Rare Case of Pediatric Post-transplant Lymphoproliferative Disorder Presenting With Pleural Masses Complicated by Pleural Effusions.

Post-transplant lymphoproliferative disorder is a complication in organ transplant recipients characterized by uncontrolled proliferation of B-lymphocytes, occurring in 6% of pediatric patients, with risk factors including primary Epstein-Barr virus infection, intensity of immunosuppression, and cytomegalovirus infection. The clinical symptoms are often nonspecific, and it is associated with a high mortality rate if left untreated. We describe a rare case of post-transplant lymphoproliferative disorder who presented with pleural-based masses resulting in pleural effusions.

Comparison of Two Lipid Emulsions on the Incidence of Parenteral Nutrition Associated Cholestasis in Neonates.

OBJECTIVE: Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE. METHODS: This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were the incidences of PNAC among all patients and patients without intestinal failure. The secondary outcomes were clinical outcomes and incidence of PNAC stratified by GA. Clinical outcomes included liver function tests, growth parameters, and development of retinopathy of prematurity and intraventricular hemorrhage. RESULTS: Forty-three neonates who received SMOF-ILE were matched to 43 neonates who received SOILE. There were no significant differences in baseline characteristics. The incidence of PNAC in the total population was 12% in the SMOF-ILE cohort and 23% in the SO-ILE cohort (p = 0.26). The lipid dosage of SMOF-ILE was significantly higher at time of peak direct serum bilirubin concentration compared with SO-ILE cohort (p = 0.05). Clinically significant differences were noted in laboratory endpoints in several subgroups. CONCLUSIONS: There was no significant difference in the incidence of PNAC among neonates in a SMOFILE cohort compared with a historical SO-ILE cohort.

Renal-hepatic-pancreatic dysplasia type 2: Perinatal lethal condition or a multisystemic disorder with variable expressivity.

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data. METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the oldest known living patient, and report the cumulative phenotypes from the existing published patients. RESULTS: With now examining the 17 known patients in the literature, 13 died within the perinatal period-pregnancy to one year of life. Of the four cases living past the first year of life, one case died at 5 years secondary to renal failure, the other at 30 months secondary to liver and kidney failure. Two are currently alive and well at one year and 13 years. Two cases have had transplantation with one resulting in long-term survival. CONCLUSIONS: These patients serve to expand the existing phenotype of RHPD2 as a perinatal lethal condition into a pediatric disorder with variable expressivity. Additionally, we introduce the consideration of transplantation and outcomes within this cohort and future patients.

Sodium Bicarbonate Locks May Be a Safe and Effective Alternative in Pediatric Intestinal Failure: A Pilot Study.

This was a retrospective study that compared outcomes in pediatric intestinal failure (IF) patients that were switched from ethanol lock therapy (ELT) to sodium bicarbonate lock therapy (SBLT). The primary outcome was rate of catheter-related blood stream infections (CRBSI). The secondary outcomes were number of hospitalizations, emergency room (ER) visits, central venous catheter (CVC)-related complications. In 4 patients, median rates of CRBSI were 2.77 (interquartile range [IQR] 0.6-5.6) on ELT versus 0 on SBLT per 1000 catheter days ( P = 0.17). The median rates of hospitalizations and ER visits for CVC-related complications were 6.1 (IQR 3.2-10.2) on ELT versus 0 on SBLT (IQR 0-0; P = 0.11) and 2.8 (IQR 2-3.6) on ELT versus 1.8 (IQR 0-3.7) on SBLT per 1000 catheter days ( P = 0.50), respectively. Rates of CVC-related complications were similar. No adverse events were reported. SBLT may be safe and effective for pediatric IF.

Pediatric intestinal failure and the microbiome.

Neonatal intestinal failure is a complex medical condition that is associated with the need for long term parenteral nutrition and its associated complications. The microbiome in this diseased state is different from what is now understood to be a healthy microbiome. The effect of this dysbiotic microbiome on the complications of intestinal failure are only starting to be understood. The ability to modulate the microbiome with enteral/parenteral nutrients, as well probiotics to a healthier state, is an exciting opportunity that holds promise.

Tunneled central venous catheters in pediatric intestinal failure: a single-center experience.

BACKGROUND: Parenteral nutrition for intestinal failure (IF) often requires a tunneled central venous catheter (CVC). The purpose of this study was to characterize complications after CVC placement and contributors to line loss in pediatric IF patients. METHODS: An institutional review board-approved retrospective review of pediatric (<18 y) IF patients who had a silicone tunneled CVC newly inserted or exchanged from 2012 to 2016 in an IF center was conducted. Patient demographics, procedure service (surgery versus interventional radiology), procedure type (new versus exchange), vessel, and complications related to CVCs were evaluated. Complications included dislodgement, infection, break, occlusion/malfunction, and others. An ethanol-lock protocol for silicone CVCs in IF patients was instituted in January 2012. RESULTS: Twenty-nine IF patients with tunneled CVCs were identified with 182 lines and 18,534 line d. Median age at line insertion was 17.1 mo (interquartile range [IQR] 7.6-31.5) with a median of five catheters (IQR 2-8) per patient. There were 19.2 complications per 1000 line d. Occlusions/malfunctions were the most common complication (6.0/1000 line d) followed by breaks (5.6/1000 line d). Median life of catheters was 51.5 d (IQR 21-129). On regression, adjusting for age, insertion service, and procedure type, shorter line life was associated with younger age (P = 0.04) and placement by interventional radiology (P < 0.01). Dislodgement was associated with newly placed lines relative risk 6.5 (95% CI 2.2-28.8). CONCLUSIONS: CVCs in pediatric IF patients have frequent complications and short line lifetimes. Dislodgement of CVC was an unexpectedly common complication with loss of access in newly placed lines. There may be modifiable processes to mitigate CVC complications.

Insufflation With Carbon Dioxide During Pediatric Colonoscopy for Control of Postprocedure Pain.

GOALS: To determine if carbon dioxide (CO2) insufflation in children would improve postprocedure pain following colonoscopy in children. BACKGROUND: CO2 insufflation during colonoscopy has been found to reduce postcolonoscopy pain in the adult population, but limited data exist in pediatrics. MATERIALS AND METHODS: We conducted a prospective study with 40 pediatric patients scheduled for outpatient colonoscopy. Patients were enrolled continuously and were randomized to receive CO2 or air insufflation. Patients and colonoscopists were blinded to insufflation method. End tidal CO2 (EtCO2) was documented throughout the procedure. Abdominal pain was established preprocedure then at 1-, 6-, and 24-hour postprocedure. Subject demographics, indications, colonoscopists' year of training, time to cecum, adverse events, and final diagnoses were recorded. RESULTS: Twenty patients were randomized to each group. Patients receiving air had a statistically significant increase in pain from baseline at 1- and 6-hours after colonoscopy (P=0.007 and 0.008). This was not seen in the CO2 group (P=0.740 and 0.289). There was an increase in postprocedure pain in the air group compared with CO2 group at the 1-hour mark (P=0.032). EtCO2 increased during the procedure, regardless of insufflation method, but no difference was seen between groups (P=0.822). CONCLUSIONS: Our results demonstrate that higher levels of pain were reported by patients following air compared with those receiving CO2 insufflation. This is the first study to show CO2 is as safe as air, with no increase in EtCO2 between groups in the pediatric population. CO2 is an effective and safe modality and should be considered for pediatric colonoscopies.

Case of hepatocellular carcinoma in a patient with hereditary tyrosinemia in the post-newborn screening era.

Hereditary tyrosinemia type 1 (HT-1) is a metabolic disorder caused by a defect in tyrosine degradation. Without treatment, symptoms of hepatomegaly, renal tubular dysfunction, growth failure, neurologic crises resembling porphyrias, rickets and possible hepatocellular carcinoma can develop. The use of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione and early diagnosis through newborn screening initiatives have resulted in a sharp decline in morbidity and mortality associated with this disease. We present a case report of a 7-year-old patient with HT-1 who was born prior to the addition of tyrosinemia to the newborn screening in her birth area. At her time of diagnosis, the patient had developed many of the symptoms associated with her disease, including chronic kidney disease, rickets, and myopathy that left her non-ambulatory. During her initial evaluation, she was also noted to have hepatocellular carcinoma. With cadaveric liver transplantation and nutritional support, her symptoms all either resolved or stabilized. Her case illustrates the severity of the disease if left untreated, the need for vigilance in populations who do not routinely receive newborn screens, and the markedly improved outcomes in patients following transplant.

Review on hepatic explant pathology of pediatric intestinal transplant recipients: Is it time for an oil change?

A recent study attempts to add to the body of evidence that is emerging regarding the fish oil parenteral lipid product Omegaven™. The authors have shown from explant livers of children on chronic parenteral nutrition with Omegaven™ that biochemical improvement in cholestasis does not always reflect improvement in liver histology. These findings support 2 small case series that were previously published. Despite improvement and resolution of hyperbilirubinemia in all six infants, five of six infants had persistent or progressive hepatic fibrosis, while only one infant had regression of fibrosis. The study raises questions of whether there is a window of opportunity for efficacy of this preparation; also, an important question is if this omega-3 fatty acid-rich preparation is superior to newer "blended lipids" containing olive, coconut, soy, and fish oil.

The economic burden of gastroschisis: costs of a birth defect.

BACKGROUND: Intestinal dysfunction and feeding intolerance are comorbidities associated with the abdominal wall birth defect of gastroschisis (GS). These factors contribute to prolonged hospitalization in this population of patients. The purpose of this study was to evaluate the economic burden on a state and national level. METHODS: From 2007-2011, the Healthcare Cost and Utilization Project database was queried for the following national and state of Texas data: number of discharges, length of stay (LOS), costs, and charges for all pediatric hospital stays ± CPT code 54.71 denoting GS repair for infants aged <1 y. The effect of GS on LOS, cost, and charges was calculated by the weighted average of the differences and is represented by the combined estimated difference (CED). RESULTS: Infants <1 y represent 74% of all pediatric discharges nationally and only 0.04% of these discharges are accounted for by GS patients. Nationally, GS patients had significantly longer LOS (CED 38.5 ± 0.9 d, P < 0.0001); increased costs (CED $79,733 ± $2119, P < 0.0001); and charges (CED $249,999 ± $9562, P < 0.0001). The Texas state data mirrored our findings for the national data. There was no significant difference in the LOS, costs, and charges between the national and state level. CONCLUSIONS: Our study shows that GS patients represent an extremely small minority of national and Texas pediatric discharges; however, these patients LOS and costs greatly exceed non-GS patients. Further investigation into factors influencing the development of intestinal dysfunction in these patients is needed to significantly impact the economic burden of the abdominal wall birth defect of GS.

Natural history of conjugated bilirubin trajectory in neonates following parenteral nutrition cessation.

BACKGROUND: There is little published data regarding the rate of bilirubin clearance in newborns following total parenteral nutrition (TPN) cessation, particularly in the neonatal intensive care unit (NICU) population without intestinal failure. METHODS: The primary aim of this retrospective chart review was to determine the duration and severity of bilirubin elevation in neonates without intestinal failure. Secondary aims were to determine factors that would influence the duration and severity of this biochemical elevation. The authors conducted a retrospective chart review of all infants receiving TPN for ≥ 21 days and with elevated conjugated bilirubin (CB) ≥3 mg/dL upon TPN cessation in a tertiary care NICU from January 1, 2008 to December 1, 2010. Patients with known causes of liver disease or without laboratory values at least four weeks after PN cessation were excluded. Time to maximum conjugated bilirubin (maxCB) post TPN cessation and normalization were the primary outcomes. Secondary factors including number/timing of sepsis events, ethnicity, and ursodiol use were also evaluated. RESULTS: Forty three infants met inclusion criteria. The majority of patients had increased CB post TPN cessation ("up" group; 27/43, 63%) with maxCB reached 13 days (SD ± 10.3) after TPN cessation. The majority of the cohort achieved normalization of the bilirubin prior to discharge (28/43, 65%). There was no difference in rate of normalization (p = 0.342) between the "up" group (59%) and the group of patients whose bilirubin trended downward following PN cessation ("down" group, 75%). There were no differences between the two groups with respect to gestational age at birth, birth weight, number of sepsis events, gram negative sepsis events, or intestinal resection. Only 30% of Hispanic patients had increased CB post TPN cessation compared to the majority (71%) of non-Hispanic patients. The maxCB of those that had complete normalization was significantly lower value than the maxCB of those that did not normalize (p = 0.016). CONCLUSIONS: Nearly two-thirds of infants experience a rise in serum bilirubin following PN cessation that can last for weeks, but cholestasis generally improves with time in the majority of infants.

Post-transplant diabetes mellitus in pediatric liver transplantation.

To determine the characteristics of pediatric liver transplant recipients who develop GI and/or PTDM, data on children undergoing their first liver transplant from the SPLIT database were analyzed (n = 1611). Recipient and donor characteristics that were evaluated included age at transplant, gender, race, primary disease, hospitalization status at transplant, BMI, recipient and donor CMV status, donor type, donor age, and primary immunosuppression. GI/PTDM was found in 214 individuals (13%) of whom 166 (78%) were diagnosed within 30 days of transplantation (early GI/PTDM). Multivariate analyses suggests that age >5 yr at transplant, hospitalization at transplant, a primary diagnosis other than BA, early steroid use, and tacrolimus use are associated with increased incidence of early GI. Routine monitoring for the development of GI and post-transplant diabetes is indicated in the short- and long-term care of children after liver transplantation.