Systemic inflammation, resulting from massive release of pro-inflammatory molecules into the circulatory system, is a major risk factor for severe illness, but the precise mechanisms underlying its control are incompletely understood. We observed that prostaglandin E2 (PGE2) through its receptor EP4 is down-regulated in human systemic inflammatory disease. Mice with reduced PGE2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented by treating with EP4 agonists. Mechanistically, we demonstrate that PGE2–EP4 signaling directly acts on type 3 innate lymphoid cells (ILCs), promoting their homeostasis and driving them to produce interleukin-22 (IL-22). Disruption of the ILC/IL-22 axis impairs PGE2–mediated inhibition of systemic inflammation. Hence, PGE2–EP4 signaling inhibits systemic inflammation through ILC/IL-22 axis–dependent protection of gut barrier dysfunction.
Preoperative fasting aims to increase patient safety by reducing the risk of adverse events during general anaesthesia. However, prolonged fasting may be associated with dehydration, hypoglycaemia and electrolyte imbalance as well as patient discomfort. We aimed to examine compliance with the current best practice guidelines in a large surgical unit and to identify areas for improvement. Adult patients undergoing elective and emergency general, orthopaedic, gynaecology and vascular surgery procedures in the Royal Infirmary of Edinburgh were surveyed over a 3-month period commencing November 2011. A standardised questionnaire was used to collect information on the duration of preoperative fasting and the advice administered by medical and nursing staff. 292 patients were included. Median fast from solids was 13.5 h for elective patients (IQR 11.5-16) and 17.38 h for emergency patients (IQR 13.68-28.5 h). Similarly, the median fast from fluids was 9.36 h for elective patients (IQR 5.38-12.75 h) and 12.97 h for emergency patients (IQR 8.5-16.22 h). The instructions that elective patients received contributed to prolonged fasting times. The median fast for elective patients fully compliant with fasting advice would be 10 h for solids (IQR 8.75-12 h) and 6.25 h (IQR 3.83-9.25 h) for clear fluids. Elective patients fasted for longer than recommended confirming that clinical practice is slow to change. The use of universal fasting instructions and patient choice are factors that unnecessarily prolong preoperative fasting, which however appears to be multifactorial. Service improvement by abbreviation of the observed fasting periods will rely on targeted staff education and effective clinical communication by provision of written information for both elective and emergency surgical patients. The routine use of preoperative nutritional supplements may need to be re-examined when further evidence is available.
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