The tryptophan metabolite kynurenine has critical immunomodulatory properties and can function as an aryl hydrocarbon receptor (AHR) ligand. Here we show that the ability of T cells to transport kynurenine is restricted to cells activated by the T-cell antigen receptor or proinflammatory cytokines. Kynurenine is transported across the T-cell membrane by the System L transporter SLC7A5. Accordingly, the ability of kynurenine to activate the AHR is restricted to T cells that express SLC7A5. We use the fluorescence spectral properties of kynurenine to develop a flow cytometry-based assay for rapid, sensitive and quantitative measurement of the kynurenine transport capacity in a single cell. Our findings provide a method to assess the susceptibility of T cells to kynurenine, and a sensitive single cell assay to monitor System L amino acid transport.

Summary Background 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov , NCT03471494 . Findings Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding National Institute for Health Research Global Health Research Unit.

Most patients with stage 4 CKD, in particular the elderly, die without commencing RRT. Patients at low risk of progression can be identified and discharged safely to primary care with an active management plan.

Background The WHO Surgical Safety Checklist has been implemented widely since its launch in 2008. It was introduced in Scotland as part of the Scottish Patient Safety Programme (SPSP) between 2008 and 2010, and is now integral to surgical practice. Its influence on outcomes, when analysed at a population level, remains unclear. Methods This was a population cohort study. All admissions to any acute hospital in Scotland between 2000 and 2014 were included. Standardized differences were used to estimate the balance of demographics over time, after which interrupted time‐series (segmented regression) analyses were performed. Data were obtained from the Information Services Division, Scotland. Results There were 12 667 926 hospital admissions, of which 6 839 736 had a surgical procedure. Amongst the surgical cohort, the inpatient mortality rate in 2000 was 0·76 (95 per cent c.i. 0·68 to 0·84) per cent, and in 2014 it was 0·46 (0·42 to 0·50) per cent. The checklist was associated with a 36·6 (95 per cent c.i. –55·2 to –17·9) per cent relative reduction in mortality (P < 0·001). Mortality rates before implementation were decreasing by 0·003 (95 per cent c.i. –0·017 to +0·012) per cent per year; annual decreases of 0·069 (–0·092 to –0·046) per cent were seen during, and 0·019 (–0·038 to +0·001) per cent after, implementation. No such improvement trends were seen in the non‐surgical cohort over this time frame. Conclusion Since the implementation of the checklist, as part of an overall national safety strategy, there has been a reduction in perioperative mortality.