Influence of the bile acid/microbiota axis in ileal surgery: a systematic review.

AIM: The gastrointestinal bile acid (BA)/microbiota axis has emerged as a potential mediator of health and disease, particularly in relation to pathologies such as inflammatory bowel disease (IBD) and colorectal cancer. Whilst it presents an exciting new avenue for therapies, it has not yet been characterized in surgical resection of the ileum, where BA reabsorption occurs. The identification of BA/microbiota signatures may provide future therapies with perioperative personalized medicine. In this work we conduct a systematic review with the aim of investigating the microbiome and BA changes that are associated with resection of the ileum. METHOD: The databases included were MEDLINE, EMBASE, Web of Science and Cochrane libraries. The outcomes of interest were faecal microbiome and BA signatures after ileal resection. RESULTS: Of the initial 3106 articles, three studies met the inclusion/exclusion criteria for data extraction. A total of 257 patients (46% surgery, 54% nonsurgery controls) were included in the three studies. Two studies included patients with short bowel syndrome and the other included patients with IBD. Large-scale microbiota changes were reported. In general, alpha diversity had decreased amongst patients with ileal surgery. Phylum-level changes included decreased Bacteroidetes and increased Proteobacteria and Fusobacteria in patients with an intestinal resection. Surgery was associated with increased total faecal BAs, cholic acid and chenodeoxycholic acid. There were decreases in deoxycholic acid and glycine and taurine conjugated bile salts. Integrated BA and microbiota data identified correlations with several bacterial families and BA. CONCLUSION: The BA/microbiota axis is still a novel area with minimal observational data in surgery. Further mechanistic research is necessary to further explore this and identify its role in improving perioperative outcomes.

Venous thromboembolic prophylaxis: current practice of surgeons in Australia and New Zealand for major abdominal surgery.

BACKGROUND: Surgical prophylaxis for venous thrombo-embolic disease (VTE) includes risk assessment, chemical prophylaxis and mechanical prophylaxis (graduated compression stockings [GCS] and/or intermittent pneumatic compression devices [IPCD]). Although there is overwhelming evidence for the need and efficacy of VTE prophylaxis in patients at risk, only about a third of those who are at risk of VTE receive appropriate prophylaxis. OBJECTIVE: There is debate as to the best combination of VTE prophylaxis following abdominal surgery due to lack of evidence. The aim of this survey was to understand this gap between knowledge and practice. METHODS: In 2019 and 2020, a survey was conducted to investigate the current practice of venous thromboembolism (VTE) prophylaxis for major abdominal surgery, with a focus on colorectal resections. The study received ethics approval and involved distributing an 11-item questionnaire to members of two professional surgical societies: the Colorectal Surgical Society of Australia and New Zealand (CSSANZ) and the General Surgeons Australia (GSA). RESULTS: From 214 surgeons: 100% use chemical prophylaxis, 68% do not use a risk assessment tool, 27% do not vary practice according to patient risk factors while > 90% use all three forms of VTE prophylaxis at some stage of treatment. Most surgeons do not vary practice between laparoscopic and open colectomy/major abdominal surgery and only 33% prescribe post-discharge chemical prophylaxis. 42% of surgeons surveyed had equipoise for a clinical trial on the use of IPCDs and the vast majority (> 95%) feel that IPCDs should provide at least a 2% improvement in VTE event rate in order to justify their routine use. CONCLUSION: Most surgeons in Australia and New Zealand do not use risk assessment tools and use all three forms of prophylaxis regardless. Therfore there is a gap between practice and VTE prophylaxis for the use of mechanical prophylaxis options. Further research is required to determine whether dual modality mechanical prophylaxis is incrementally efficacious. Trial Registration- Not Applicable.

C1q and mobility score in predicting sarcopenia in an Australian cohort of cancer surgery patients.

BACKGROUND: Sarcopenia has been shown to have significant adverse health outcomes in a range of patient populations. Particularly, sarcopenic patients having cancer surgery are a unique group who demonstrate poorer post-operative outcomes. Currently, the gold standard in diagnosing sarcopenia is through the use of computed tomography. However, the widespread use of imaging to diagnose patients with sarcopenia is neither cost-effective nor practical. Identifying a serum biomarker or a simple mobility scoring system as an alternative diagnostic tool may aid in identifying more patients at risk of sarcopenia. C1q, a novel biomarker, has previously been shown to correlate with sarcopenia. Similarly, we sought to explore whether mobility scores may provide a useful surrogate marker for sarcopenia. METHODS: This was a prospective cohort study of patients who presented for colorectal cancer surgery between the dates of 6/10/2016 and 4/10/2017 at John Hunter Hospital. Computed tomography was utilized to calculate the psoas area at the L3 spinal level. Pre-operative blood samples were obtained for C1q analysis and de Morton Mobility Index (DEMMI) was also performed. RESULTS: A total of 51 patients were included in the study. The median age of the patients were 69 years old. We did not demonstrate a correlation between serum C1q and DEMMI scores with psoas area. CONCLUSION: Our findings suggest that neither C1q nor DEMMI scores are correlated with psoas area in a colorectal cancer population.

Novel role of extracellular matrix protein 1 (ECM1) in cardiac aging and myocardial infarction.

INTRODUCTION: The prevalence of heart failure increases in the aging population and following myocardial infarction (MI), yet the extracellular matrix (ECM) remodeling underpinning the development of aging- and MI-associated cardiac fibrosis remains poorly understood. A link between inflammation and fibrosis in the heart has long been appreciated, but has mechanistically remained undefined. We investigated the expression of a novel protein, extracellular matrix protein 1 (ECM1) in the aging and infarcted heart. METHODS: Young adult (3-month old) and aging (18-month old) C57BL/6 mice were assessed. Young mice were subjected to left anterior descending artery-ligation to induce MI, or transverse aortic constriction (TAC) surgery to induce pressure-overload cardiomyopathy. Left ventricle (LV) tissue was collected early and late post-MI/TAC. Bone marrow cells (BMCs) were isolated from young healthy mice, and subject to flow cytometry. Human cardiac fibroblast (CFb), myocyte, and coronary artery endothelial & smooth muscle cell lines were cultured; human CFbs were treated with recombinant ECM1. Primary mouse CFbs were cultured and treated with recombinant angiotensin-II or TGF-ß1. Immunoblotting, qPCR and mRNA fluorescent in-situ hybridization (mRNA-FISH) were conducted on LV tissue and cells. RESULTS: ECM1 expression was upregulated in the aging LV, and in the infarct zone of the LV early post-MI. No significant differences in ECM1 expression were found late post-MI or at any time-point post-TAC. ECM1 was not expressed in any resident cardiac cells, but ECM1 was highly expressed in BMCs, with high ECM1 expression in granulocytes. Flow cytometry of bone marrow revealed ECM1 expression in large granular leucocytes. mRNA-FISH revealed that ECM1 was indeed expressed by inflammatory cells in the infarct zone at day-3 post-MI. ECM1 stimulation of CFbs induced ERK1/2 and AKT activation and collagen-I expression, suggesting a pro-fibrotic role. CONCLUSIONS: ECM1 expression is increased in ageing and infarcted hearts but is not expressed by resident cardiac cells. Instead it is expressed by bone marrow-derived granulocytes. ECM1 is sufficient to induce cardiac fibroblast stimulation in vitro. Our findings suggest ECM1 is released from infiltrating inflammatory cells, which leads to cardiac fibroblast stimulation and fibrosis in aging and MI. ECM1 may be a novel intermediary between inflammation and fibrosis.