Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1.

BACKGROUND & AIMS: Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells characterised by the invariant TCR-chain, Vα7.2-Jα33, and are restricted by MR1, which presents bacterial vitamin B metabolites. They are important for antibacterial immunity at mucosal sites; however, detailed characteristics of liver-infiltrating MAIT (LI-MAIT) and their role in biliary immune surveillance remain unexplored. METHODS: The phenotype and intrahepatic localisation of human LI-MAIT cells was examined in diseased and normal livers. MAIT cell activation in response to E. coli-exposed macrophages, biliary epithelial cells (BEC) and liver B cells was assessed with/without anti-MR1. RESULTS: Intrahepatic MAIT cells predominantly localised to bile ducts in the portal tracts. Consistent with this distribution, they expressed biliary tropic chemokine receptors CCR6, CXCR6, and integrin αEß7. LI-MAIT cells were also present in the hepatic sinusoids and possessed tissue-homing chemokine receptor CXCR3 and integrins LFA-1 and VLA-4, suggesting their recruitment via hepatic sinusoids. LI-MAIT cells were enriched in the parenchyma of acute liver failure livers compared to chronic diseased livers. LI-MAIT cells had an activated, effector memory phenotype, expressed α4ß7 and receptors for IL-12, IL-18, and IL-23. Importantly, in response to E. coli-exposed macrophages, liver B cells and BEC, MAIT cells upregulated IFN-γ and CD40 Ligand and degranulated in an MR1-dependent, cytokine-independent manner. In addition, diseased liver MAIT cells expressed T-bet and RORγt and the cytokines IFN-γ, TNF-α, and IL-17. CONCLUSIONS: Our findings provide the first evidence of an immune surveillance effector response for MAIT cells towards BEC in human liver; thus they could be manipulated for treatment of biliary disease in the future.

Risk of post-transplantation diabetes mellitus is greater in South Asian versus Caucasian kidney allograft recipients.

South Asians have increased risk for type 2 diabetes mellitus compared with Caucasians in the general population, but data for the development of post-transplantation diabetes mellitus (PTDM) is scarce. In this retrospective analysis, data was extracted from electronic patient records at a single centre (2004-2014). Caucasians were more likely to be male, with higher age and BMI than South Asians. Case-control matching was therefore undertaken to remove this bias, resulting in 102 recipient pairs. Median follow-up was 50 months (range 4-127 months). Matched groups had similar baseline characteristics, although South Asians compared with Caucasians received more deceased-donor kidneys (74% vs. 43%, respectively, P < 0.001) and were more likely to be CMV positive (77% vs. 43%, respectively, P < 0.001). PTDM incidence was significantly higher in South Asians versus Caucasians (35% vs. 10%, respectively, subhazard ratio 4.2 [95% CI: 2.1-8.5, P < 0.001]). Donor type had significant interaction with ethnicity, with the observed difference in PTDM rates between ethnicities most visible with receipt of deceased-donor kidneys. No significant difference was detected in allograft function, rejection episodes, adverse cardiovascular events or patient/graft survival. South Asians have increased risk of PTDM, especially recipients of deceased kidneys, and recognition of this allows appropriate patient counselling and development of targeted strategies.

Improving resuscitation decisions: a trust-wide initiative.

INTRODUCTION: Treatment escalation plans (TEPs) are important to ensure that every patient has their ceiling of care discussed and documented formally. At Medway Foundation Trust, we introduced TEP forms in September 2016 which are to be completed by the relevant consultant within 24 hours of admission. AIMS AND METHODS: To evaluate whether TEP forms had been effective at improving escalation planning and whether they had a subsequent impact in do not attempt cardiopulmonary resuscitation (DNACPR) decision-making. We carried out three plan-do-study-act cycles over a 2-year period across 100 patients in medicine and surgery. RESULTS: TEP forms were initially found in 66% (66/100) of the patient notes and 34% (34/100) were completed appropriately. There was a 13% relative improvement in resuscitation decision-making, since the introduction of the TEP forms from November 2015 to January 2017. There was also a 12% reduction in inappropriate referrals to critical care during the same period. We decided to revise the TEP form through extensive collaboration and educate all staff members about the importance of escalation planning. This has led to an improvement in TEP discussion and documentation across the entire trust. CONCLUSION: TEPs can be an effective way of considering and communicating ceilings of care. They should encourage doctors to consider DNACPR decisions for patients who otherwise would not have been considered, and therefore may help reduce inappropriate referrals to critical care. The higher completion rates of the new form and increased clarity among staff regarding escalation planning should lead to an improvement in patient safety outcomes and communication between all patients and staff members. We believe it would be feasible to implement our user-friendly TEP form across other National Health Service organisations in order to develop a universal TEP form.