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.

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.

Aim: There is a requirement for an expansive and up to date review of the management of emergency colorectal conditions seen in adults. The primary objective is to provide detailed evidence‐based guidelines for the target audience of general and colorectal surgeons who are responsible for an adult population and who practise in Great Britain and Ireland.Methods: Surgeons who are elected members of the Association of Coloproctology of Great Britain and Ireland Emergency Surgery Subcommittee were invited to contribute various sections to the guidelines. They were directed to produce a pathology‐based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. Each author was asked to provide a set of recommendations which were evidence‐based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after two votes were included in the guidelines.Results: All aspects of care (excluding abdominal trauma) for emergency colorectal conditions have been included along with 122 recommendations for management.Conclusion: These guidelines provide an up to date and evidence‐based summary of the current surgical knowledge in the management of emergency colorectal conditions and should serve as practical text for clinicians managing colorectal conditions in the emergency setting.

Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. National Institute for Health and Care Research.

Background: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. Result: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8⁺ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. Conclusion: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy.

BACKGROUND: The provision of emergency general surgery services is a global issue, with important implications for patients and workforce. The aim of this study was to analyze the characteristics of emergency general surgical patients in the United Kingdom, with reference to diagnostic case mix, operative workload, comorbidity, discharge destination, and outcomes, to facilitate comparisons and future service development. METHODS: This is a cross-sectional population-based study based in the National Health Service in Scotland, one of the home nations of the United Kingdom. All patients aged 16 or older admitted under the care of a general surgeon, as an emergency, to a National Health Service hospital in Scotland, in 2016, were included. RESULTS: There were 81,446 emergency general surgery admissions by 66,498 patients. Median episode age was 53 years. There were more female patients than male (55% vs 45%, p < 0.0001). The most common diagnoses were nonspecific abdominal pain (20.2%), cholecystitis (7.2%), constipation (3.4%), pancreatitis (3.1%), diverticular disease (3.1%), and appendicitis (3.1%). Only 25% of patients had operations (n = 20,292). The most frequent procedures were appendicectomy (13.1%), endoscopy (11.3%), and drainage of skin lesions (9.7%). Diagnoses and operations differed with age. Overall median length of stay was 1 day. With a 6-month follow-up, patients older than 75 years had a 19.8% mortality rate. CONCLUSIONS: Emergency general surgery in the United Kingdom is a high-volume, diagnostically diverse, and low–operative volume specialty with high short-term mortality rate in elderly patients. Consideration should be given to alternative service delivery models, which make better use of surgeons’ skills while also ensuring optimal care for patients who are increasingly elderly and have complex chronic health problems. LEVEL OF EVIDENCE: Epidemiologic study, level III.