Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity.

The microvasculature plays a key role in tissue perfusion and exchange of gases and metabolites. In this study we use human blood vessel organoids (BVOs) as a model of the microvasculature. BVOs fully recapitulate key features of the human microvasculature, including the reliance of mature endothelial cells on glycolytic metabolism, as concluded from metabolic flux assays and mass spectrometry-based metabolomics using stable tracing of 13C-glucose. Pharmacological targeting of PFKFB3, an activator of glycolysis, using two chemical inhibitors results in rapid BVO restructuring, vessel regression with reduced pericyte coverage. PFKFB3 mutant BVOs also display similar structural remodelling. Proteomic analysis of the BVO secretome reveal remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovers microvessel structure. In this work we demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.

Home to Stay: A Randomized Controlled Trial Evaluating the Effect of a Postdischarge Mobile App to Reduce 30-Day Readmission Following Elective Colorectal Surgery.

OBJECTIVE: A randomized controlled trial was conducted to evaluate the effect of a postdischarge app on 30-day readmissions and patient-reported outcomes following colorectal surgery. BACKGROUND: Patients undergoing colorectal surgery are particularly vulnerable during their transition from hospital-to-home. There has been increasing interest in e-health to provide cost-effective transitional care. An integrated discharge monitoring program using a mobile app platform was developed to support patients after surgery. METHODS: A 2 arm, superiority randomized control trial was conducted at an academic tertiary care center with patients undergoing elective colorectal surgery. The intervention group received usual postoperative care and postdischarge monitoring with the app. The primary outcome was 30-day readmissions following hospital discharge. RESULTS: Two hundred eighty-two participants were randomized. The majority were young, had inflammatory bowel disease and underwent laparoscopic surgery. Intention to treat analysis showed no difference between groups for 30-day readmission (14.8% vs 17.6%, P =0.55), ER visits (25.0% vs 28.8%, P =0.49), primary care visits (12.5% vs 8.8%, P =0.34) or unplanned healthcare visits (34.4% vs 35.2%, P =0.89). All patient reported outcomes were significantly improved with median scores higher with the app for satisfaction [9, interquartile range (IQR): 8-10 vs 8, IQR: 7-9, P =0.001], well-being (7, IQR: 6-8 vs 6, IQR: 5-7, P =0.001) and significantly lower for anxiety (3, IQR: 2-5 vs 5, IQR: 3-6, P =0.001). CONCLUSIONS: Although the app did not show a significant reduction in 30-day readmission or ER visits, it did lead to significant improvements in patient-reported outcomes. The app may be an important tool to support patients following colorectal surgery.

Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis.

Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis.