Fat malabsorption in short bowel syndrome: A review of pathophysiology and management.

Fat malabsorption is central to the pathophysiology of short bowel syndrome (SBS). It occurs in patients with insufficient intestinal surface area and/or function to maintain metabolic and growth demands. Rapid intestinal transit and impaired bile acid recycling further contribute to fat malabsorption. A significant portion of patients require parenteral nutrition (PN) for their survival but may develop sepsis and liver dysfunction as a result. Despite advancements in the treatment of SBS, fat malabsorption remains a chronic issue for this vulnerable patient population. Peer-reviewed literature was assessed on the topic of fat malabsorption in SBS. Current management of patients with SBS involves dietary considerations, PN management, antidiarrheals, glucagon-like peptide 2 agonists, and multidisciplinary teams. Clinical trials have focused on improving intestinal fat absorption by facilitating fat digestion with pancreatic enzymes. Targeting fat malabsorption in SBS is a potential pathway to improving lifestyle and reducing morbidity and mortality in this rare disease.

Inflammation drives pathogenesis of early intestinal failure-associated liver disease.

Patients with intestinal failure who receive long-term parenteral nutrition (PN) often develop intestinal failure-associated liver disease (IFALD). Although there are identified risk factors, the early pathogenesis is poorly understood and treatment options are limited. Here, we perform a transcriptomic analysis of liver tissue in a large animal IFALD model to generate mechanistic insights and identify therapeutic targets. Preterm Yorkshire piglets were provided PN or bottle-fed with sow-milk replacer for 14 days. Compared to bottle-fed controls, piglets receiving PN developed biochemical cholestasis by day of life 15 (total bilirubin 0.2 vs. 2.9 mg/dL, P = 0.01). RNA-Seq of liver tissue was performed. Ingenuity Pathway Analysis identified 747 differentially expressed genes (343 upregulated and 404 downregulated) with an adjusted P < 0.05 and a fold-change of > |1|. Enriched canonical pathways were identified, demonstrating broad activation of inflammatory pathways and inhibition of cell cycle progression. Potential therapeutics including infliximab, glucocorticoids, statins, and obeticholic acid were identified as predicted upstream master regulators that may reverse the PN-induced gene dysregulation. The early driver of IFALD in neonates may be inflammation with an immature liver; identified therapeutics that target the inflammatory response in the liver should be investigated as potential treatments.

Concomitant use of monoamine oxidase inhibitor and tyrosine in parenteral nutrition.

Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of tyramine in the body, and can cause a sudden increase in blood pressure with significant tyramine build up. This phenomenon, when it occurs, is known as tyramine pressor response. It is unknown if tyrosine administered in parenteral nutrition (PN) leads to tyramine build-up with concomitant use of MAOIs. It is also unknown if PN patients who are taking MAOI are at risk for the tyramine pressor response. This is a theoretical possibility as tyrosine endogenously undergoes decarboxylation to produce tyramine. We describe our experience with a 67-year-old woman with severe depression who was on the MAOI, transdermal selegiline. Her clinical course was complicated by an inability to take adequate per oral (PO) intake and she met criteria for unspecified severe protein-calorie-malnutrition in the context of social or environmental circumstances. Therefore, she required PN initiation. PlenamineTM (B. Braun, Bethlehem, PA, USA) was used as the amino acid source in the PN, which contains 39 mg of tyrosine per 100 ml of solution. The patient was monitored closely for any signs of hypertensive crisis while on PN and selegiline. She safely tolerated the combined therapy without any side effects. This is the first documented report of co-administration of PN containing tyrosine along with a MAOI. Our findings suggest that the dose of selegiline used in this patient can be co-administered safely in the setting of PN. However, further study is needed to verify our findings beyond this one patient. In conclusion, we recommend initiating PN and increasing it to goal in patients taking MAOIs, gradually, while monitoring for hypertensive crisis given the theoretical possibility of the tyramine pressor response.

A medium-chain fatty acid analogue prevents hepatosteatosis and decreases inflammatory lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis.

BACKGROUND: Parenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis. METHODS: Two in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro. RESULTS: In the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both ß- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake. CONCLUSIONS: SEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both ß- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis.

Absorption of an engineered medium-chain fatty acid analogue in two short bowel syndrome minipig models.

BACKGROUND: Enteral drug therapy is challenging in short bowel syndrome with intestinal failure (SBS-IF) because of unpredictable absorption. SEFA-6179 is an enterally administered medium-chain fatty acid analogue under development for intestinal failure-associated liver disease. We investigate the pharmacokinetics of two SEFA-6179 formulations in two large-animal models of SBS-IF, including a new pseudojejunostomy model. METHODS: Twenty Yucatan minipigs were obtained. Half underwent pre-resection pharmacokinetic study with single-dose SEFA-6179 administration. All minipigs then underwent 90% jejunoileal resection, with either a jejunoileal anastomosis or bypass of the intraperitoneal colon with anastomosis just proximal to the rectum (pseudojejunostomy). On postoperative day 3, a single-dose pharmacokinetic study was performed. RESULTS: Both SBS-IF models were well tolerated. Compared with the jejunoileal anastomosis minipigs, pseudojejunostomy minipigs had a more severe malabsorptive phenotype with weight loss by postoperative day 4 (+0.1 vs -0.9 kg, P = 0.03) and liquid diarrhea (Bristol 5 vs Bristol 7, P = 0.0007). Compared with pre-resection minipigs, both jejunoileal and pseudojejunostomy minipigs had lower total plasma exposure of SEFA-6179 measured by area under the curve (jejunoileal: 37% less, P = 0.049; pseudojejunostomy: 74% less, P = 0.0001). Peak plasma concentration was also lower in the pseudojejunostomy group compared with pre-resection (65% less, P = 0.04), but not lower in the jejunoileal group (P = 0.47). CONCLUSION: In two SBS-IF minipig models, SEFA-6179 had substantially decreased absorption compared with pre-resection minipigs. Dose optimization for different intestinal anatomy and function may be required. We describe a new SBS-IF pseudojejunostomy model that may improve the translation of preclinical research to patients with SBS-IF who have enterostomies.

A Medium-Chain Fatty Acid Analogue Prevents Intestinal Failure-Associated Liver Disease in Preterm Yorkshire Piglets.

BACKGROUND & AIMS: At least 20%-30% of patients with intestinal failure receiving long-term parenteral nutrition will develop intestinal failure-associated liver disease (IFALD), for which there are few therapeutic options. SEFA-6179 is a first-in-class structurally engineered medium-chain fatty acid analogue that acts through GPR84, PPARα, and PPARγ agonism. We hypothesized that SEFA-6179 would prevent biochemical and histologic liver injury in a preterm piglet model of IFALD. METHODS: Preterm Yorkshire piglets were delivered by cesarean section, and parenteral nutrition was provided for 14 days via implanted central venous catheters. Animals were treated with either medium-chain triglyceride vehicle control or SEFA-6179. RESULTS: Compared to medium-chain triglyceride vehicle at day of life 15, SEFA-6179 prevented biochemical cholestasis (direct bilirubin: 1.9 vs <0.2 mg/dL, P = .01; total bilirubin: 2.7 vs 0.4 mg/dL, P = .02; gamma glutamyl transferase: 172 vs 30 U/L, P = .01). SEFA-6179 also prevented steatosis (45.6 vs 13.9 mg triglycerides/g liver tissue, P = .009), reduced bile duct proliferation (1.6% vs 0.5% area cytokeratin 7 positive, P = .009), and reduced fibrosis assessed by a masked pathologist (median Ishak score: 3 vs 1, P = 0.007). RNA sequencing of liver tissue demonstrated that SEFA-6179 broadly impacted inflammatory, metabolic, and fibrotic pathways, consistent with its in vitro receptor activity (GPR84/PPARα/PPARγ agonist). CONCLUSIONS: In a preterm piglet model of IFALD, SEFA-6179 treatment prevented biochemical cholestasis and steatosis and reduced bile duct proliferation and fibrosis. SEFA-6179 is a promising first-in-class therapy for the prevention and treatment of IFALD that will be investigated in an upcoming phase II clinical trial.

IMPOWER: a national patient-generated registry for intestinal malrotation exploring diagnosis, treatment, and surgical outcomes.

BACKGROUND: Intestinal malrotation is a rare congenital condition with potentially devastating consequences due to potential volvulus and massive intestinal necrosis. Diagnosis is often delayed and long-term symptoms following surgical correction are poorly characterized. We developed the Intestinal Malrotation Patient Outcomes and WEllness Registry (IMPOWER), a national patient-generated registry (PGR), to capture data related to presenting symptoms, testing, diagnosis, treatment, and follow-up of individuals diagnosed with malrotation. IMPOWER captures patient-reported information from adult patients and parents/caregivers of children diagnosed with malrotation at the time of enrollment and at ongoing 6-month intervals. We present baseline characteristics of patients enrolled during the first two months of the registry. RESULTS: Within the first two months, 354 patients with malrotation enrolled in IMPOWER, and 191 (53.9%) completed all baseline assessments. Nearly 90% of the 119 pediatric participants and 37.7% of the 72 adult participants experienced symptoms prior to diagnosis. Vomiting was the predominant symptom for pediatric participants compared to abdominal pain in adults. Yellow bilious emesis was more commonly reported than green, and volvulus at diagnosis occurred in 70% of pediatric and 27% of adult participants. One-third of pediatric participants had a bowel resection as part of their initial surgical procedure, resulting in 23.4% with diagnosed short bowel syndrome. More than 60% of pediatric and 80% of adult registrants reported gastrointestinal symptoms that persisted throughout the first year following their initial operation. Approximately 25% of registrants reported visiting four or more gastroenterologists for management of ongoing symptoms. CONCLUSIONS: Fewer than half of pediatric patients presented with the "classic" presentation of green bilious colored emesis. Yellow bilious emesis was more commonly reported, and chronic gastrointestinal symptoms (i.e., abdominal pain, reflux, constipation, diarrhea) and feeding intolerance were common following surgical procedures for malrotation. This novel PGR highlights the need for a multicenter prospective registry to characterize the natural history and develop consistent standards of care related to the diagnosis, treatment, and long-term care for patients with malrotation.

Ethanol lock therapy increases mechanical catheter complications in a pediatric intestinal failure population: A retrospective cohort study.

BACKGROUND: Ethanol lock therapy (ELT) decreases central line-associated bloodstream infections; however, the effect on mechanical catheter complications is unclear. In recent years, ELT has become unavailable for many patients, often resulting in high-risk patients switching back to heparin locks. We investigated the impact of ELT on mechanical catheter complications during this period. METHODS: We performed a retrospective cohort study of the Boston Children's Hospital intestinal rehabilitation program from January 1, 2018, to December 31, 2020. Pediatric patients with a central venous catheter requiring parenteral support for 3 months were included. The primary outcome was the composite rate of mechanical catheter complications (repairs and replacements). RESULTS: The pediatric intestinal failure cohort consisted of 122 patients. Forty-four percent received ELT for the entirety of the study period, 29% used only heparin locks, and 27% used ELT and heparin locks at different periods. During ELT use, there was 1.65 times the risk of mechanical catheter complications (composite outcome of repairs and replacements) compared with heparin locks (adjusted incidence rate ratio [aIRR] = 1.65, 95% CI = 1.18-2.31). Current ELT use was associated with 2.3 times the risk of catheter repairs (aIRR = 2.30, 95% CI = 1.36-3.89) but no significant increase in catheter replacement risk (aIRR = 1.41, 95% CI = 0.91-2.20). CONCLUSION: In the largest pediatric intestinal failure cohort evaluated to date, the use of ELT, compared with heparin locks, increased the risk of mechanical catheter complications. Mechanical complications carry morbidity requiring urgent clinic or emergency department visits and additional procedures. The investigation of alternative lock solutions is warranted.

Fat digestion using RELiZORB in children with short bowel syndrome who are dependent on parenteral nutrition: Protocol for a 90-day, phase 3, open labeled study.

BACKGROUND: Short bowel syndrome (SBS) is a leading cause of intestinal failure resulting in parenteral nutrition (PN) dependence and nutritional deficiencies. Long-term PN use is associated with the development of sepsis and intestinal failure-associated liver disease. Achieving enteral autonomy is the optimal way to prevent these complications. In SBS, the decreased intestinal length, bile acid deficiency, and rapid transit time contribute to fat malabsorption and continued PN dependence. We propose the use of an immobilized lipase cartridge (ILC; RELiZORB) that connects in-line with enteral feed tubing sets and is designed to breakdown the majority of fats provided in enteral nutrition (EN). Preclinical studies have demonstrated both improved fat and fat-soluble vitamin absorption with ILC use in a porcine model of SBS. To evaluate the clinical applicability of these findings, we designed a phase 3, open labeled, single center, clinical trial to determine the safety, tolerability, and efficacy of the RELiZORB enzyme cartridge when used daily with EN for 90 days. METHODS: The patient population will include PN dependent children with SBS, aged 2-18 years. The primary outcome is the change in PN calories from baseline, assessed weekly throughout the study. Changes in growth Z-scores, 72-hour fecal fat and coefficient of fat absorption, plasma fatty acids and fat-soluble vitamins will also be evaluated. Assessment of change in continuous outcomes will be made using the area under the curve, expressed as a percent change relative to baseline, calculated over study day 7 to 90 (AUC7-90). The incidence of adverse events will be monitored and summarized by system organ class. DISCUSSION: If successful, RELiZORB may offer a safe alternative to reducing PN dependence and achieving enteral autonomy in pediatric intestinal failure. These results would be clinically significant given the clear association between long-term PN use and complications in SBS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03530852; registered on May 21st, 2018, last update posted on September 14th, 2022.

A Digestive Cartridge Reduces Parenteral Nutrition Dependence and Increases Bowel Growth in a Piglet Short Bowel Model.

OBJECTIVE: To determine whether the use of an immobilized lipase cartridge (ILC) to hydrolyze fats in enteral nutrition (EN) reduces parenteral nutrition (PN) dependence in a porcine model of short bowel syndrome with intestinal failure (SBS-IF). BACKGROUND: SBS-IF occurs after intestinal loss resulting in malabsorption and PN dependence. Limited therapeutic options are available for achieving enteral autonomy. METHODS: Eleven Yorkshire piglets underwent 75% jejunoileal resection and were randomized into control (n=6) and treatment (n = 5) groups. PN was initiated postoperatively and reduced as EN advanced if predefined clinical criteria were fulfilled. Animals were studied for 14 days and changes in PN/EN calories were assessed. Intestinal adaptation, absorption, and nutrition were evaluated at the end of the study (day 15). Comparisons between groups were performed using analysis of covariance adjusted for baseline. RESULTS: ILC animals demonstrated a 19% greater reduction in PN calories ( P < 0.0001) and higher mean EN advancement (66% vs 47% of total calories, P < 0.0001) during the 14-day experiment. Treatment animals had increased intestinal length (19.5 vs 0.7%, P =0.03) and 1.9-fold higher crypt cell proliferation ( P =0.02) compared with controls. By day 15, ILC treatment resulted in higher plasma concentrations of glucagon-like peptide-2 ( P = 0.02), eicosapentaenoic acid ( P < 0.0001), docosahexaenoic acid ( P = 0.004), vitamin A ( P = 0.02), low-density lipoprotein ( P = 0.02), and high-density lipoprotein ( P = 0.04). There were no differences in liver enzymes or total bilirubin between the two groups. CONCLUSIONS: ILC use in conjunction with enteral feeding reduced PN dependence, improved nutrient absorption, and increased bowel growth in a porcine SBS-IF model. These results support a potential role for the ILC in clinical SBS-IF.

Incidence and development of cholestasis in surgical neonates receiving an intravenous mixed-oil lipid emulsion.

BACKGROUND: Intestinal failure-associated liver disease (IFALD), initially manifesting as cholestasis, is a complication in neonates receiving parenteral nutrition (PN). Soybean oil lipid emulsion (SOLE), though implicated in IFALD, was the only US Food and Drug Administration (FDA)-approved initial intravenous lipid emulsion (ILE) for infants and children in the United States. A mixed-oil lipid emulsion (MOLE) gained popularity in patients at risk for IFALD and was recently FDA approved as an initial ILE in children. Given the presence of soybean oil in MOLE, we hypothesized that MOLE would not be effective at preventing cholestasis in surgical neonates. METHODS: Neonates with gastrointestinal surgical conditions necessitating PN for ≥14 days and receiving MOLE (SMOFlipid) from July 2016 to July 2019 were analyzed retrospectively. Unpaired and pair-matched historical surgical neonates treated with SOLE (Intralipid) served as controls. The primary outcome measure was development of cholestasis (direct bilirubin ≥2 mg/dl). RESULTS: Overall, 63% (10 of 16) of MOLE patients and 22% (30 of 136) of SOLE patients developed cholestasis after ≥14 days of therapy (P = 0.005). The latency to developing cholestasis was significantly shorter in MOLE patients compared with SOLE patients. CONCLUSION: In surgical neonates, MOLE may not prevent cholestasis and should not be considered hepatoprotective. Regardless of ILE source, all surgical neonates should be closely monitored for development of IFALD. To date, there is still no ILE able to prevent IFALD.

Direct thrombin inhibitors as alternatives to heparin to preserve lung growth and function in a murine model of compensatory lung growth.

Infants with congenital diaphragmatic hernia (CDH) may require cardiopulmonary bypass and systemic anticoagulation. Expeditious lung growth while on bypass is essential for survival. Previously, we demonstrated that heparin impairs lung growth and function in a murine model of compensatory lung growth (CLG). We investigated the effects of the direct thrombin inhibitors (DTIs) bivalirudin and argatroban. In vitro assays of lung endothelial cell proliferation and apoptosis were performed. C57BL/6 J mice underwent left pneumonectomy and subcutaneous implantation of osmotic pumps. Pumps were pre-loaded with normal saline (control), bivalirudin, argatroban, or heparin and outcomes were assessed on postoperative day 8. Heparin administration inhibited endothelial cell proliferation in vitro and significantly decreased lung volume in vivo, while bivalirudin and argatroban preserved lung growth. These findings correlated with changes in alveolarization on morphometric analysis. Treadmill exercise tolerance testing demonstrated impaired exercise performance in heparinized mice; bivalirudin/argatroban did not affect exercise tolerance. On lung protein analysis, heparin decreased angiogenic signaling which was not impacted by bivalirudin or argatroban. Together, this data supports the use of DTIs as alternatives to heparin for systemic anticoagulation in CDH patients on bypass. Based on this work, clinical studies on the impact of heparin and DTIs on CDH outcomes are warranted.

Structurally-engineered fatty acid 1024 (SEFA-1024) improves diet-induced obesity, insulin resistance, and fatty liver disease.

Obesity is a global epidemic that drives morbidity and mortality through cardiovascular disease, diabetes, and non-alcoholic fatty liver disease (NAFLD). No definitive therapy has been approved to improve glycemic control and treat NAFLD in obese patients. Here, we investigated a semi-synthetic, long chain, structurally-engineered fatty acid-1024 (SEFA-1024), as a treatment for obesity-induced hyperglycemia, insulin-resistance, and fatty liver disease in rodent models. A single dose of SEFA-1024 was administered to evaluate glucose tolerance and active glucagon-like peptide 1 (GLP-1) in lean rats in the presence and absence of a DPP-4 inhibitor. The effects of SEFA-1024 on weight loss and glycemic control were assessed in genetic (ob/ob) and environmental (high-fat diet) murine models of obesity. Liver histology, serum liver enzymes, liver lipidomics, and hepatic gene expression were also assessed in the high-fat diet murine model. SEFA-1024 reversed obesity-associated insulin resistance and improved glycemic control. SEFA-1024 increased active GLP-1. In a long-term model of diet-induced obesity, SEFA-1024 reversed excessive weight gain, hepatic steatosis, elevated liver enzymes, hepatic lipotoxicity, and promoted fatty acid metabolism. SEFA-1024 is an enterohepatic-targeted, eicosapentaenoic acid derivative that reverses obesity-induced dysregulated glucose metabolism and hepatic lipotoxicity in genetic and dietary rodent models of obesity. The mechanism by which SEFA-1024 works may include increasing aGLP-1, promoting fatty acid oxidation, and inhibiting hepatic triglyceride formation. SEFA-1024 may serve as a potential treatment for obesity-related diabetes and NAFLD.

Safe care transitions for patients receiving parenteral nutrition.

Transitions of care require coordination between inpatient healthcare providers, care managers, outpatient/ambulatory providers, and the patient/caregiver and family members. Poor communication during transitions of care can affect health outcomes and economic costs for patients/caregivers, healthcare providers, and healthcare systems. The goal of this paper is to identify risk-prone processes in the transition of care for patients requiring parenteral nutrition (PN) between healthcare environments, including the hospital, home, skilled nursing facility, and long-term acute care hospital settings. To facilitate the evaluation of the transition, a sequential series of steps in the transition process were identified: initial notification, assessment in preparation for transfer, identifying the receiving organization, identifying accountable providers at each sending/receiving organization, communicating the nutrition care plan, implementing the plan and additional considerations regarding PN preparation and readmissions. Safety concerns with risk-prone processes are identified and recommended best practices are proposed for improving processes at each step of the transition. Pediatric considerations are included in the evaluation of the various steps in the transition of care. This paper was approved by the American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors.

Outcomes and Perioperative Nutritional Management in a Porcine Model of Short Bowel Syndrome.

INTRODUCTION: Short bowel syndrome (SBS) results from significant intestinal loss and is characterized by insufficient absorption of nutrients and fluids. Preclinical large animal SBS models typically require parenteral nutrition (PN) support and may not be appropriate for studying interventions to improve intestinal absorption or adaptation. Here, we describe the development of a porcine SBS model that does not require PN support. METHODS: Eight male Yorkshire piglets underwent either a 75% or 90% jejunoileal resection (n = 5) or no resection (n = 3). Continuous enteral nutrition (EN) was provided via a gastrostomy tube. The final SBS model consisted of a 75% resection and nutrition provided via combination EN (60%) and per oral pig chow (40%). Body weight and concentration of fat-soluble vitamins were assessed on postoperative days (POD) 7, 14, and 21. For assessing fat malabsorption, the coefficient of fat absorption (CFA) was calculated following a 72-h stool collection. RESULTS: Resected animals had decreased weight gain compared to unresected controls (POD21 + 8.3% versus +28.8%, P = 0.048). Vitamin D concentration was significantly lower in resected animals compared to controls on POD 7, POD 14, and POD 21. Serum vitamin E concentration was also lower on POD 21. Resected animals developed fat malabsorption with lower CFA (76.5% versus 95.3%, P = 0.014). CONCLUSIONS: We describe the development of a porcine SBS model that does not require PN support. Piglets in this model gain less weight, demonstrate fat malabsorption, and develop fat-soluble vitamin deficiencies. This model will benefit investigations of intestinal absorption or adaptation while potentially decreasing costs and confounding complications related to PN administration.

Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events.

OBJECTIVE: To compare extrahepatic adverse events during fish oil lipid emulsion (FOLE) or soybean oil lipid emulsion (SOLE) treatment in children with intestinal failure-associated liver disease (IFALD). STUDY DESIGN: In this multicenter integrated analysis, bleeding, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), infections, and signs of lipid emulsion intolerance were compared between FOLE recipients (1 g/kg/d) (n = 189) and historical controls who received SOLE (≤3 g/kg/d) (n = 73). RESULTS: When compared with SOLE recipients, FOLE recipients had a lower gestational age (30.5 vs 33.0 weeks; P = .0350) and higher baseline direct bilirubin (DB) (5.8 vs 3.0 mg/dL; P < .0001). FOLE recipients had a decreased incidence of bleeding (P < .0001), BPD (P < .001), ROP (P < .0156), bacterial and fungal infections (P < .0001), and lipid intolerance signs (P < .02 for all). Patients with bleeding vs patients without bleeding had higher baseline DB; the ORs for baseline DB (by mg/dL) and treatment (FOLE vs SOLE) were 1.20 (95% CI: 1.10, 1.31; P ≤ .0001) and 0.22 (95% CI: 0.11, 0.46; P ≤ .0001), respectively. In preterm infants, a higher BPD (P < .0001) and ROP incidence (P = .0071) was observed in SOLE recipients vs FOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had fewer extrahepatic adverse events, including a decreased incidence of bleeding, preterm comorbidities, and lipid intolerance signs compared with children with IFALD who received SOLE. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT00910104 and NCT00738101.

ASPEN lipid injectable emulsion safety recommendations part 2: Neonate and pediatric considerations.

Lipid injectable emulsions (ILEs) are complex pharmaceutical formulations intended as a source of energy and fatty acids for parenteral nutrition (PN) therapy. Part 1 of this series addressed issues associated with and safety recommendations pertaining to adult ILE use. Part 2 addresses ILE safety in neonatal and pediatric patients. Considerations for ILE use in the neonatal and pediatric populations differ from those of adults. For example, these patients often require higher doses compared with adult counterparts to support growth, development, and daily metabolic needs. ILE is also frequently administered as a separate infusion as opposed to in a total nutrient admixture owing to compatibility and stability issues and limitations to intravenous access in the neonatal and pediatric populations. ILE is the most frequent PN ingredient associated with PN errors occurring in the administration, prescribing, and transcribing processes. Concerns exist with use of in-line filters and repackaging of commercial products for infusion. ILE use in neonatal and pediatric patients has been associated with both minor and major adverse effects, which most often occur with doses exceeding manufacturer recommendations. Gaps in ILE best practices for neonatal and pediatric patients predispose to errors in the PN use system. This paper describes safe-use considerations for ILE products available in the United States in neonatal and pediatric patients, including indications, prescribing, order review, preparation, administration, and monitoring. This paper has been approved by the American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors.

Recommendations for photoprotection of parenteral nutrition for premature infants: An ASPEN position paper.

Although crucial in improving health outcomes in the preterm infants, parenteral nutrition (PN) is not without risk, especially if handled improperly. A growing body of evidence suggests that components of PN admixtures, including lipid injectable emulsions (ILEs), are susceptible to degradation, including oxidation when exposed to light (ie, photo-oxidation), resulting in the production of reactive oxygen species. Infants, especially those born preterm, are considered more susceptible to consequences of oxidative stress than children and adults. Oxidative stress is associated with bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intestinal failure-associated liver disease. The American Society for Parenteral and Enteral Nutrition (ASPEN) assembled a working group to provide recommendations on clinical practice surrounding photoprotection of PN.This Position Paper reviews the scientific literature on the formation of quantifiable peroxides and other degradation products when PN admixtures and ILEs are exposed to light and reports adverse clinical outcomes in premature infants exposed to PN. Recommendations for photoprotection of PN admixtures and ILEs are provided, as well as the challenges in achieving complete photoprotection with the equipment, supplies, and materials currently available in the US. ASPEN and the authors understand that the full implementation of complete photoprotection may not currently be feasible given current product availability; recommendations provided in this paper serve to represent the goal to which to strive as well as to highlight the importance of product availability to achieve these practices. This paper has been approved by the ASPEN Board of Directors.