Risk Factors for Infection in Neonates With Intestinal Failure.

PURPOSE: Neonates with intestinal failure (IF) are at risk for infection due to central venous access, and intestinal surgery. Infection can cause systemic inflammation and sepsis, potentially affecting growth. The purpose of this study was to identify risk factors for, and the potential impact of infection to help with preventative strategies. METHODS: A retrospective review of infants with IF, at a single centre from 2018 to 2022 was conducted. Clinical characteristics, intestinal pathology, nutritional intake, and growth were compared among infants with bloodstream infection (BSI), other infection (OI) (urinary, respiratory, or wound), or no infection (NI) within 2 months of diagnosis. Mann-Whitney and Kruskal-Wallis tests were used for comparisons with p-values <0.05 considered significant. RESULTS: Eighty-six infants were included, with gastroschisis (41%) and necrotizing enterocolitis (26%) the most common diagnoses. Fifty-nine % of infants developed infection (22% BSI and 37% OI). Those with BSI or OI had a lower gestational age and birthweight, and were more likely to have a stoma. All infants with complex gastroschisis developed infection compared to 38% of infants with simple gastroschisis. Median daily weight gain was suboptimal across all groups and did not differ over 6 weeks following infection. CONCLUSION: Most infants with IF develop infection shortly after diagnosis. Risk factors include prematurity, complex gastroschisis, and the presence of a stoma. Growth was suboptimal but did not differ among infants with or without infection. TYPE OF STUDY: Retrospective Review. LEVEL OF EVIDENCE: Level III Retrospective Comparative Study.

A Mechanically Resilient Soft Hydrogel Improves Drug Delivery for Treating Post-Traumatic Osteoarthritis in Physically Active Joints.

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel's potential for PTOA treatment in active patients.

Intestinal phenotype in mice overexpressing a heparin-binding EGF-like growth factor transgene in enterocytes.

PRIMARY OBJECTIVE: Heparin-binding EGF-like growth factor (HB-EGF) protects the intestine from damage in animals. Future clinical trials of HB-EGF may involve administration of repeated doses of HB-EGF. Since HB-EGF activates EGF receptors which have been implicated in tumor development, we examined the effects of HB-EGF overexpression in the intestine. RESEARCH DESIGN: We generated transgenic (TG) mice in which the human HB-EGF gene is driven by the villin promoter to overexpress HB-EGF along the crypt-villous axis from the duodenum to the colon. RESULTS: HB-EGF TG mice have increased enterocyte proliferation balanced by increased enterocyte apoptosis. Despite prolonged overexpression of HB-EGF, no evidence of intestinal hyperplasia or tumor formation occurs. Although HB-EGF TG mice have no significant phenotypic alterations under basal conditions, they have increased resistance to intestinal injury. CONCLUSIONS: Prolonged intestinal HB-EGF overexpression results in no significant phenotypic alterations under basal conditions, but confers protection against intestinal injury.