Malnutrition-Related Health Outcomes in Older Adults with Hip Fractures: A Systematic Review and Meta-Analysis.

Hip fracture is a common condition in older adults, leading to disability and mortality. Several studies have demonstrated the association between nutritional status and the risk of a negative health outcome after fractures. In this systematic review, we evaluated the association between malnutrition and mortality, changes in mobility/living arrangements, and postoperative complications, such as delirium, in older patients with hip fractures. A literature search on the PubMed, Web of Science, and Scopus databases, up to September 2023, was conducted to identify all studies involving older subjects that reported an association between MNA/GNRI/PNI/CONUT and health outcome after hip fracture. Meta-analysis was performed by a random-effects model using risk values (RR, OR, and HR) extracted from the 14 eligible selected studies. Malnutrition significantly increased the risk of any analyzed adverse outcome by 70% at 1 month, and up to 250% at 1 year. Malnutrition significantly increased delirium risk by 275% (OR = 2.75; 95% CI 1.80-4.18; p ≤ 0.05), mortality risk by 342% (OR = 3.42; 95% CI 2.14-5.48; p ≤ 0.05), mortality hazard risk by 351% (HR = 3.51; 95% CI 1.63-7.55; p ≤ 0.05) at 1 month, and transfer-to-more-supported-living-arrangements risk by 218% (OR = 2.18; 95% CI 1.58-3.01; p ≤ 0.05), and declined mobility risk by 41% (OR = 1.41; 95% CI 1.14-1.75; p ≤ 0.05), mortality risk by 368% (OR = 3.68; 95% CI 3.00-4.52; p ≤ 0.05), and mortality hazard risk by 234% (HR = 2.34; 95% CI 1.91-2.87; p ≤ 0.05) at 1 year. Malnutrition of older patients increases the risk of death and worsens mobility and independence after hip fractures. The results of the present study highlight the importance of nutritional status evaluation of older subjects with hip fractures in order to prevent potential adverse outcomes (Registration No: CRD42023468751).

Hepatic expression of lipopolysaccharide-binding protein (Lbp) is induced by the gut microbiota through Myd88 and impairs glucose tolerance in mice independent of obesity.

OBJECTIVE: Gut-derived inflammatory factors can impair glucose homeostasis, but the underlying mechanisms are not fully understood. In this study, we investigated how hepatic gene expression is regulated by gut colonization status through myeloid differentiation primary response 88 (MYD88) and how one of the regulated genes, lipopolysaccharide-binding protein (Lbp), affects insulin signaling and systemic glucose homeostasis. METHODS: Liver transcriptomics analysis was conducted on four groups of mice fed a chow diet: conventionally raised (CONV-R) wild-type, germ-free (GF) wild-type, CONV-R Myd88 KO, and GF Myd88 KO. Primary hepatocytes were exposed to combinations of lipopolysaccharide (LPS), LBP, and the LBP-blocking peptide LBPK95A, and the effect on insulin signaling was determined. To assess how LBP affects glucose metabolism in vivo, two mouse models were applied: treatment with LBPK95A and hepatic knockdown of Lbp using CRISPR-CAS9. RESULTS: We showed that the colonization status regulates gene expression in the liver and that a subset of these genes, including Lbp, is regulated through MYD88. Furthermore, we demonstrated that LBP impairs insulin signaling in hepatocytes in the presence of low levels of LPS and that the effect of LBP is abolished by LBPK95A. We showed that both systemic pharmacological blocking of LBP by LBPK95A and CRISPR-CAS9-mediated downregulation of hepatic Lbp improve glucose homeostasis. CONCLUSIONS: Our results demonstrate that the gut microbiota regulates hepatic expression of Lbp through MYD88-dependent signaling. LBP potentiates LPS inhibition of insulin signaling in vitro and impairs systemic glucose homeostasis in vivo.