EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

In-Vitro Effects of Secreted Frizzled-Related Protein 1 (SFRP1) On Human Corneal Epithelial Cells

© 2018 Taylor & Francis Group, LLC. Purpose: Limbal corneal epithelial cells (LCECs) are responsible for corneal epithelial cell regeneration. However, corneal central epithelial cells (CCECs) are also suggested to display potential for self-renewal. Additionally, a better understanding of molecules that regulate corneal epithelial cell regeneration is important for studying conditions affecting the cornea, for example, keratoconus. Given our previous findings of reduced levels of secreted frizzled-related protein 1 (SFRP1) in tears from keratoconus patients compared to controls, we investigated the effects of SFRP1 on the proliferation and survival of cultured central and limbal human corneal epithelial cells. Material and methods: Limbal and central corneal explants were established from postmortem human corneas, and cultured in CnT-PR, an epithelial-specific tissue culture media. Subcultured cells from explants were immunostained for the cytokeratins CK3, 12, 19, and the proliferative/oligopotent markers Ki67 and p63. BrdU flow cytometry, Alamar Blue and LDH assays were used to assess effects of SFRP1 treatment on central and LCECs. Results: Primary limbal and central corneal epithelial cells were successfully cultured in vitro to confluence (P6 and P4, respectively). They all expressed varying levels of cytokeratins CK3, CK12 and CK19, and Ki67 and p63. Additionally, they showed significantly increased metabolic activity after SFRP1 treatment (p < 0.05), with a maximum response at 1 μg/mL of SPRF1. No difference in proliferation was detected in SFRP1 treated LCECs; however, a reduction in cell death was noted (p < 0.05). Conclusion: Similar to the LCECs, primary human CCECs can be cultured in vitro, and expressed epithelial markers. SFRP1 demonstrated an improvement on the metabolic activity of both CCECs and LCECs, which in LCECs could be resulted from reduced cell death. This may have implications in degenerative corneal disorders, such as keratoconus

Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization.

The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s-a DC2 population unique to the dermis-required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization

Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization

The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s-a DC2 population unique to the dermis-required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.</p