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.

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.

Effects of systemic anticoagulation in a murine model of compensatory lung growth.

Background: Neonates with congenital diaphragmatic hernia (CDH) suffer from pulmonary hypoplasia (PH) and may require extracorporeal membrane oxygenation (ECMO) and anticoagulation, often with unfractionated heparin (UFH). UFH interacts with vascular endothelial growth factor (VEGF), a factor important in lung development. We investigated the effects of UFH, low molecular weight heparin (LMWH), and bivalirudin (BV) on a murine model of compensatory lung growth (CLG).

Multi-institutional outcomes after femoropopliteal bypass in octogenarians.

Objectives: Open lower extremity revascularization is controversial among octogenarians; however, the indications for surgical bypass are higher in the elderly population. The aim of the study was to compare postoperative outcomes between octogenarians and non-octogenarians following femoropopliteal bypass surgery.

Methods: Our regional, multi-institutional database was queried for femoropopliteal bypass procedures performed between 1995 and 2020.

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.

Investigation of the mechanisms of VEGF-mediated compensatory lung growth: the role of the VEGF heparin-binding domain.

Morbidity and mortality for neonates with congenital diaphragmatic hernia-associated pulmonary hypoplasia remains high. These patients may be deficient in vascular endothelial growth factor (VEGF). Our lab previously established that exogenous VEGF164 accelerates compensatory lung growth (CLG) after left pneumonectomy in a murine model.

Optimizing Duration of Empiric Management of Suspected Central Line-Associated Bloodstream Infections in Pediatric Patients with Intestinal Failure.

Objectives: To assess whether a 24-hour length of hospitalization and empiric antibiotic therapy to exclude central line-associated bloodstream infection (CLABSI) in children with intestinal failure is potentially as safe as 48 hours, which is the duration most commonly used but not evidence based.

Study Design: A prospective single-institution observational cohort study was conducted among pediatric patients with intestinal failure from July 1, 2015, through June 30, 2018, to identify episodes of suspected CLABSI. The primary end point was time from blood sampling to positive blood culture.

Metabolic and Inflammatory Effects of an ω-3 Fatty Acid-Based Eucaloric Ketogenic Diet in Mice With Endotoxemia.

Background: Dietary strategies can aid in the management of critically ill patients. Very-low-carbohydrate diets have been shown to improve glucose control and the inflammatory response. We aimed to determine the effects of a eucaloric ketogenic diet (EKD) enriched with ω-3 fatty acids (O3KD) on glucose levels and inflammation in mice with endotoxemia.

Alpha-tocopherol in intravenous lipid emulsions imparts hepatic protection in a murine model of hepatosteatosis induced by the enteral administration of a parenteral nutrition solution.

Intestinal failure-associated liver disease (IFALD) is a risk of parenteral nutrition (PN)-dependence. Intravenous soybean oil-based parenteral fat can exacerbate the risk of IFALD while intravenous fish oil can minimize its progression, yet the mechanisms by which soybean oil harms and fish oil protects the liver are uncertain. Properties that differentiate soybean and fish oils include α-tocopherol and phytosterol content.

Omega-3 fatty acids are protective in hepatic ischemia reperfusion injury in the absence of GPR120 signaling.

Background: A single dose of IV fish oil (FO) before hepatic ischemia reperfusion injury (HIRI) increases hepatocyte proliferation and reduces necrosis in wild type (WT) mice. It has been suggested that the GPR120 receptor on Kupffer cells mediates FO's ability to reduce HIRI. The purpose of this study was to determine whether GPR120 is required for FO to reduce HIRI.

Fish oil protects the liver from parenteral nutrition-induced injury via GPR120-mediated PPARγ signaling.

Intravenous fish oil lipid emulsions (FOLE) can prevent parenteral nutrition (PN)-induced liver injury in murine models and reverse PN-induced cholestasis in pediatric patients. However, the mechanisms by which fish oil protects the liver are incompletely characterized. Fish oil is rich in omega-3 fatty acids, which are ligands for the G-protein coupled receptor 120 (GPR120), expressed on hepatic Kupffer cells.

Fish oil-based injectable lipid emulsions containing medium-chain triglycerides or added α-tocopherol offer anti-inflammatory benefits in a murine model of parenteral nutrition-induced liver injury.

Background: Fish oil (FO) intravenous lipid emulsions (ILEs) are used as a monotherapy to treat parenteral nutrition (PN)-associated liver disease and provide essential fatty acids (EFAs) needed to sustain growth and prevent EFA deficiency (EFAD). Studies have suggested that medium-chain triglycerides (MCTs) and α-tocopherol have anti-inflammatory properties.

Objective: The purpose of this study was to test whether FO-ILEs containing MCTs and/or additional α-tocopherol decrease the inflammatory response to an endotoxin challenge compared with FO-ILE alone and preserve the ability to prevent PN-induced liver injury in mice.

Vascular Endothelial Growth Factor Enhances Compensatory Lung Growth in Piglets.

Background: Vascular endothelial growth factor has been found to accelerate compensatory lung growth after left pneumonectomy in mice. The aim of this study was to determine the natural history and the effects of vascular endothelial growth factor on compensatory lung growth in a large animal model.

Methods: To determine the natural history of compensatory lung growth, female Yorkshire piglets underwent a left pneumonectomy on days of life 10-11.

Assessment of Micronutrient Status in Critically Ill Children: Challenges and Opportunities.

Micronutrients refer to a group of organic vitamins and inorganic trace elements that serve many functions in metabolism. Assessment of micronutrient status in critically ill children is challenging due to many complicating factors, such as evolving metabolic demands, immature organ function, and varying methods of feeding that affect nutritional dietary intake. Determination of micronutrient status, especially in children, usually relies on a combination of biomarkers, with only a few having been established as a gold standard.

Technique and perioperative management of left pneumonectomy in neonatal piglets.

Background: Although commonly performed in adult swine, unilateral pneumonectomy in piglets requires significant modifications in the surgical approach and perioperative care because of their smaller size and limited physiological reserve.

Methods: Nineteen neonatal piglets underwent a left pneumonectomy. They were allowed 5-7 d of preoperative acclimation and nutritional optimization.

A Comparison of Fish Oil Sources for Parenteral Lipid Emulsions in a Murine Model.

Background: Fat emulsions are important components of parenteral nutrition (PN). Fish oil (FO) emulsions reverse cholestasis in PN-associated liver disease. There are 2 FO monographs.

In vitro modeling of endothelial interaction with macrophages and pericytes demonstrates Notch signaling function in the vascular microenvironment.

Angiogenesis is regulated by complex interactions between endothelial cells and support cells of the vascular microenvironment, such as tissue myeloid cells and vascular mural cells. Multicellular interactions during angiogenesis are difficult to study in animals and challenging in a reductive setting. We incorporated stromal cells into an established bead-based capillary sprouting assay to develop assays that faithfully reproduce major steps of vessel sprouting and maturation.