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.

PR1P, a VEGF-stabilizing peptide, reduces injury and inflammation in acute lung injury and ulcerative colitis animal models.

Acute Respiratory Distress Syndrome (ARDS) and Ulcerative Colitis (UC) are each characterized by tissue damage and uncontrolled inflammation. Neutrophils and other inflammatory cells play a primary role in disease progression by acutely responding to direct and indirect insults to tissue injury and by promoting inflammation through secretion of inflammatory cytokines and proteases. Vascular Endothelial Growth Factor (VEGF) is a ubiquitous signaling molecule that plays a key role in maintaining and promoting cell and tissue health, and is dysregulated in both ARDS and UC.

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).

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.

Racial and Socioeconomic Disparities in Necrotizing Soft-Tissue Infection.

Necrotizing soft-tissue infection (NSTI) is a medical emergency. We investigated the impact of racial, socioeconomic disparities, and comorbidities on mortality, complications, length of stay, and charges in patients with NSTI. Data were acquired from the National Inpatient Sample from Q4 2015 to 2017.

Deficiency in pigment epithelium-derived factor accelerates pulmonary growth and development in a compensatory lung growth model.

Children with hypoplastic lung disease associated with congenital diaphragmatic hernia (CDH) continue to suffer significant morbidity and mortality secondary to progressive pulmonary disease. Recently published work from our lab demonstrated the potential of Roxadustat (FG-4592), a prolyl hydroxylase inhibitor, as a treatment for CDH-associated pulmonary hypoplasia. Treatment with Roxadustat led to significantly accelerated compensatory lung growth (CLG) through downregulation of pigment epithelium-derived factor (PEDF), an anti-angiogenic factor, rather than upregulation of vascular endothelial growth factor (VEGF).

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.

PR1P Stabilizes VEGF and Upregulates Its Signaling to Reduce Elastase-induced Murine Emphysema.

Emphysema is a progressive and fatal lung disease with no cure that is characterized by thinning, enlargement, and destruction of alveoli, leading to impaired gas exchange. Disease progression is due in part to dysregulation of VEGF (vascular endothelial growth factor) signaling in the lungs and increased lung-cell apoptosis. Here we asked whether PR1P (Prominin-1-derived peptide), a novel short peptide we designed that increases VEGF binding to endothelial cells, could be used to improve outcome in and models of emphysema.

Laparoscopic Transabdominal Colopexy for Prolapse of a Newborn End Colostomy: A Novel Technique.

Prolapse can occur in up to 20% of newborn end colostomies and may be associated with significant morbidities that require operative intervention. Prolapse repair is traditionally performed through an open parastomal or laparotomy incision. We report on 2 cases that utilized a novel laparoscopic transabdominal colopexy technique, which offered a minimally invasive solution uniquely suited to neonates and infants while obviating the morbidity of open reoperative surgery.

Is there a role for rehabilitation streaming following total knee arthroplasty? Preliminary insights from a randomized controlled trial.

Objective: To determine whether total knee arthroplasty recipients demonstrating comparatively poor mobility at entry to rehabilitation and who received supervised therapy, had better rehabilitation outcomes than those who received less supervision.

Design: Retrospective analysis of randomized trial data.

Patients: Total knee arthroplasty participants randomized to supervised (n = 159) or home-based therapy (n = 74).

One-to-one therapy is not superior to group or home-based therapy after total knee arthroplasty: a randomized, superiority trial.

Background: The aim of this study was to determine whether center-based, one-to-one physical therapy provides superior outcomes compared with group-based therapy or a simple monitored home-based program in terms of functional and physical recovery and health-related quality of life after total knee arthroplasty.

Methods: Patients awaiting primary total knee arthroplasty at two Sydney metropolitan hospitals were enrolled into this prospective, randomized, superiority trial preoperatively. At two weeks postoperatively, participants were randomly allocated to one of three six-week treatment programs (twelve one-to-one therapy sessions, twelve group-based therapy sessions, or a monitored home program) with use of a computer-generated sequence.

The six-minute walk test is an excellent predictor of functional ambulation after total knee arthroplasty.

Background: The Six-minute walk (6 MW) and Timed-Up-and-Go (TUG) are short walk tests commonly used to evaluate functional recovery after total knee arthroplasty (TKA). However, little is known about walking capacity of TKA recipients over extended periods typical of everyday living and whether these short walk tests actually predict longer, more functional distances. Further, short walk tests only correlate moderately with patient-reported outcomes.

Tourniquet application only during cement fixation in total knee arthroplasty: a double-blind, randomized controlled trial.

Background:   The functional benefits of tourniquet application for short periods compared with standard duration applications during total knee arthroplasty surgery have not been well explored. We aimed to compare functional outcomes between tourniquet application of short duration (during cement fixation only) and tourniquet application of longer duration (from skin incision to just after cement fixation).

Methods:   We planned to randomize 230 patients to short and long duration groups.

Improvements in knee range and symptomatic and functional behavior after knee arthroplasty based on preoperative restriction in range.

Recovery of knee range and Oxford Knee Score post knee arthroplasty based on preoperative knee range is described. A total of 191 patients recruited across 5 hospitals were assessed preoperatively, at 8 weeks postoperatively and 1 year. Preoperative knee range was categorized into "low" (≤ 109), "moderate" (> 109 to ≤ 120), and "high" (> 120°) flexion and "normal" (± -5) and "restricted" (> +5°) terminal extension.

Validity and reliability of using photography for measuring knee range of motion: a methodological study.

Background: The clinimetric properties of knee goniometry are essential to appreciate in light of its extensive use in the orthopaedic and rehabilitative communities. Intra-observer reliability is thought to be satisfactory, but the validity and inter-rater reliability of knee goniometry often demonstrate unacceptable levels of variation. This study tests the validity and reliability of measuring knee range of motion using goniometry and photographic records.

Is discharge knee range of motion a useful and relevant clinical indicator after total knee replacement? Part 2.

Objective: Knee range of motion (ROM) at discharge from acute care is used as a clinical indicator following total knee replacement (TKR) surgery. This study aimed to assess the clinical relevance of this indicator by determining whether discharge knee ROM predicts longer-term knee ROM and patient-reported knee pain and function.

Methods: A total of 176 TKR recipients were prospectively followed after discharge from acute care.

Is discharge knee range of motion a useful and relevant clinical indicator after total knee replacement? Part 1.

Objectives: Knee range of motion (ROM) at the point of discharge from acute care is used as a clinical indicator to benchmark performance between hospital services after total knee replacement (TKR). The utility of the current benchmark, including whether discharge ROM varies between hospitals, is unknown. This study aimed to determine whether the benchmark [≥80 degrees flexion and ≤5 degrees fixed flexion (extension)] is realistic and whether the service provider is a predictor of knee ROM.

Heart rate response and factors affecting exercise performance during home- or class-based rehabilitation for knee replacement recipients: lessons for clinical practice.

Objectives: Patients undergoing total knee replacement (TKR) are typically de-conditioned and manifest medical co-morbidities associated with a lack of fitness. Consequently, an argument exists for rehabilitation programmes to target cardiovascular fitness. Doubt exists, however, as to the capacity of TKR recipients to exercise intensely and effectively.

Changes in the temporal and distance parameters of gait evoked by negotiation of curbs.

We report a study in which we examined the gait modulations performed by a group of healthy adults, naïve to the purpose of the study, while walking across a curb under natural environmental conditions out of doors. Data were collected for step time and step length using a videocamera and a 20m walkway. Location of foot position was achieved using a novel method to account for parallax and out of plane motion.