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Background & AimsMucosal-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.MethodsThe 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.ResultsIntrahepatic 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 αEβ7. 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 α4β7 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.ConclusionsOur 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.

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ObjectiveTo identify research priorities for Anaesthesia and Perioperative Medicine.DesignProspective surveys and consensus meetings guided by an independent adviser.SettingUK.Participants45 stakeholder organisations (25 professional, 20 patient/carer) affiliated as James Lind Alliance partners.OutcomesFirst ‘ideas-gathering’ survey: Free text research ideas and suggestions. Second ‘prioritisation’ survey: Shortlist of ‘summary’ research questions (derived from the first survey) ranked by respondents in order of priority. Final ‘top ten’: Agreed by consensus at a final prioritisation workshop.ResultsFirst survey: 1420 suggestions received from 623 respondents (49% patients/public) were refined into a shortlist of 92 ‘summary’ questions. Second survey: 1718 respondents each nominated up to 10 questions as research priorities. Top ten: The 25 highest-ranked questions advanced to the final workshop, where 23 stakeholders (13 professional, 10 patient/carer) agreed the 10 most important questions:▸ What can we do to stop patients developing chronic pain after surgery?▸ How can patient care around the time of emergency surgery be improved?▸ What long-term harm may result from anaesthesia, particularly following repeated anaesthetics?▸ What outcomes should we use to measure the ‘success’ of anaesthesia and perioperative care?▸ How can we improve recovery from surgery for elderly patients?▸ For which patients does regional anaesthesia give better outcomes than general anaesthesia?▸ What are the effects of anaesthesia on the developing brain?▸ Do enhanced recovery programmes improve short and long-term outcomes?▸ How can preoperative exercise or fitness training, including physiotherapy, improve outcomes after surgery?▸ How can we improve communication between the teams looking after patients throughout their surgical journey?ConclusionsAlmost 2000 stakeholders contributed their views regarding anaesthetic and perioperative research priorities. This is the largest example of patient and public involvement in shaping anaesthetic and perioperative research to date.

Preoperative TAP blocks in patients undergoing laparoscopic colorectal resection reduced opioid use in the first postoperative day in this study.