Role of intraoperative processes of care during major upper gastrointestinal oncological resection in postoperative outcomes: a scoping review protocol.

INTRODUCTION: Optimal delivery and organisation of care is critical for surgical outcomes and healthcare systems efficiency. Anaesthesia volumes have been recently associated with improved postoperative recovery outcomes; however, the mechanism is unclear. Understanding the individual processes of care (interventions received by the patient) is important to design effective systems that leverage the volume-outcome association to improve patient care. The primary objective of this scoping review is to systematically map the evidence regarding intraoperative processes of care for upper gastrointestinal cancer surgery. We aim to synthesise the quantity, type, and scope of studies on intraoperative processes of care in adults who undergo major upper gastrointestinal cancer surgeries (oesophagectomy, hepatectomy, pancreaticoduodenectomy, and gastrectomy) to better understand the volume-outcome relationship for anaesthesiology care. METHODS AND ANALYSIS: This scoping review will follow the Arksey and O'Malley framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension framework for scoping reviews. We will systematically search MEDLINE, Embase and Cochrane databases for original research articles published after 2010 examining postoperative outcomes in adult patients undergoing either: oesophagectomy, hepatectomy, pancreaticoduodenectomy, or gastrectomy, which report at least one intraoperative processes of care (intervention or framework) applied by anaesthesia or surgery. The data from included studies will be extracted, charted, and summarised both quantitatively and qualitatively through descriptive statistics and narrative synthesis. ETHICS AND DISSEMINATION: No ethics approval is required for this scoping review. Results will be disseminated through publication targeted at relevant stakeholders in anaesthesiology and cancer surgery. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/392UG; https://archive.org/details/osf-registrations-392ug-v1.

Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases.

BACKGROUND: Ectopic expression of a defined set of transcription factors allows the reprogramming of mammalian somatic cells to pluripotency. Despite continuous progress in primate and rodent reprogramming, limited attention has been paid to cell reprogramming in domestic and companion species. Previous studies attempting to reprogram canine cells have mostly assessed a small number of presumptive canine induced pluripotent stem cell (iPSC) lines for generic pluripotency attributes. However, why canine cell reprogramming remains extremely inefficient is poorly understood. METHODS: To better characterize the initial steps of pluripotency induction in canine somatic cells, we optimized an experimental system where canine fetal fibroblasts (cFFs) are transduced with the Yamanaka reprogramming factors by Sendai virus vectors. We use quantitative PCR arrays to measure the expression of 80 target genes at various stages of canine cell reprogramming. We ask how cFF reprogramming is influenced by small molecules affecting the epigenomic modification 5-hydroxymethylcytosine, specifically L-ascorbic acid and retinoic acid (AA/RA). RESULTS: We found that the expression and catalytic output of a class of 2-oxoglutarate-dependent (2-OG) hydroxylases, known as ten-eleven translocation (TET) enzymes, can be modulated in canine cells treated with AA/RA. We further show that AA/RA treatment induces TET1 expression and facilitates early canine reprogramming, evidenced by upregulation of epithelial and pluripotency markers. Using a chemical inhibitor of 2-OG hydroxylases, we demonstrate that 2-OG hydroxylase activity regulates the expression of a subset of genes involved in mesenchymal-to-epithelial transition (MET) and pluripotency in early canine reprogramming. We identify a set of transcription factors depleted in maturing reprogramming intermediates compared to pluripotent canine embryonic stem cells. CONCLUSIONS: Our findings highlight 2-OG hydroxylases have evolutionarily conserved and divergent functions regulating the early reprogramming of canine somatic cells and show reprogramming conditions can be rationally optimized for the generation of maturing canine iPSC.