MRI-predicted extramural vascular invasion and tumour deposit are main predictors of disease-free survival in patients undergoing surgical resection for rectal cancer.

BACKGROUND: MRI is crucial in staging patients with rectal cancer and planning treatment. The aim was to analyse the prognostic role of MRI-predicted tumour deposits and/or extramural vascular invasion (mrTD/EMVI) in a cohort of patients with rectal cancer undergoing surgical resection, with selective neoadjuvant chemoradiotherapy (nCRT). METHOD: Retrospective analysis of a single-centre cohort of consecutive patients with rectal cancer undergoing low anterior resection or abdominoperineal excision between 2008 and 2020. Unit policy was selective nCRT for MRI-predicted threatened or involved circumferential resection margin (mrCRM), or radiologically involved pelvic sidewall nodes. The primary outcome was disease-free survival. Secondary outcomes were rates of local recurrence, distant recurrence and overall survival. RESULTS: A total of 314 patients were analysed. Median age was 65 years (female/male: 114/200). A total of 54/314 (17%) had nCRT and 35 patients (11%) underwent abdominoperineal excision. Median follow-up was 64 months. Overall, local recurrence was detected in 18/314 (5.7%) and distant recurrence in 45/314 (14.3%). In patients not receiving nCRT (n = 260), local recurrence was detected in 11/260 (4.2%) and distant recurrence in 35/260 (13.5%). Disease-free survival was 80.5% at 5 years. Specifically, disease-free survival was 89% in mrTD/EMVI-negative and mrCRM-negative, 67% in mrTD/EMVI-positive and mrCRM-negative, and 64% in the mrCRM-positive rectal cancer (log-rank, P < 0.001). On multivariable Cox-regression analysis mrTD/EMVI was the only MRI variable associated with disease-free survival (hazard ratio 2.95; P < 0.001). CONCLUSION: mrTD/EMVI is a major prognostic indicator. Rectal cancer patients with mrCRM-negative and mrTD/EMVI-negative have excellent long-term outcomes with surgery alone. Patients with mrTD/EMVI-positive should be selectively stratified for neoadjuvant treatments in future clinical trials.

Two-year real-world outcome data from a single tertiary centre shows reduced ustekinumab persistence in a non-bio-naïve Crohn's disease cohort with penetrating disease, -ostomies and sarcopenia.

Background: Ustekinumab was approved in 2016 for the treatment of moderate-severe Crohn's disease (CD). Clinical trials and real-world studies have suggested ustekinumab to be a safe and effective treatment; however, studies to date infrequently use imaging techniques to predict response to biologics in CD. Objectives: We assessed the 2-year real-world effectiveness and safety of ustekinumab in a tertiary CD cohort with the use of novel imaging techniques. Design: Retrospective cohort study. Methods: Retrospective data were collected between 2016 and 2021. Study end points included ustekinumab persistence, biological and/or clinical response and remission at 12, 18 and 24 months. Statistical analysis included demographic and inferential analyses. Results: In all, 131 CD patients [57.3% female, median age of 26.0 (21.0-37.0)] were included. Patients were non-bio naïve, and the majority received ustekinumab as third- or fourth-line treatment. At 24 months, 61.0% (80/131) persisted with ustekinumab [52.7% (69/131) steroid free]. Clinical response was reported in 55.2% (37/67), clinical remission in 85.7% (57/67), biological response in 46.8% (22/47) and biological remission in 31.9% (15/47) of patients at 24 months. The low outcome numbers were attributable to missing data. Improvements in routine disease markers, including C-reactive protein and Harvey-Bradshaw Index, were also reflected in magnetic resonance imaging-derived disease scores. The presence of penetrating CD, an -ostomy and sarcopenia were all predictors of poorer ustekinumab outcomes (p < 0.05). Conclusion: Ustekinumab is effective in non-bio-naïve CD patients with non-stricturing, non-penetrating disease with an unremarkable safety profile but may be less effective in those with penetrating disease, -ostomies and sarcopenia.

Imaging features for the prediction of clinical endpoints in chronic liver disease: a scoping review protocol.

INTRODUCTION: Chronic liver disease is a growing cause of morbidity and mortality in the UK. Acute presentation with advanced disease is common and prioritisation of resources to those at highest risk at earlier disease stages is essential to improving patient outcomes. Existing prognostic tools are of limited accuracy and to date no imaging-based tools are used in clinical practice, despite multiple anatomical imaging features that worsen with disease severity.In this paper, we outline our scoping review protocol that aims to provide an overview of existing prognostic factors and models that link anatomical imaging features with clinical endpoints in chronic liver disease. This will provide a summary of the number, type and methods used by existing imaging feature-based prognostic studies and indicate if there are sufficient studies to justify future systematic reviews. METHODS AND ANALYSIS: The protocol was developed in accordance with existing scoping review guidelines. Searches of MEDLINE and Embase will be conducted using titles, abstracts and Medical Subject Headings restricted to publications after 1980 to ensure imaging method relevance on OvidSP. Initial screening will be undertaken by two independent reviewers. Full-text data extraction will be undertaken by three pretrained reviewers who have participated in a group data extraction session to ensure reviewer consensus and reduce inter-rater variability. Where needed, data extraction queries will be resolved by reviewer team discussion. Reporting of results will be based on grouping of related factors and their cumulative frequencies. Prognostic anatomical imaging features and clinical endpoints will be reported using descriptive statistics to summarise the number of studies, study characteristics and the statistical methods used. ETHICS AND DISSEMINATION: Ethical approval is not required as this study is based on previously published work. Findings will be disseminated by peer-reviewed publication and/or conference presentations.

Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome.

BACKGROUND: FODMAPs produce similar small bowel water and colonic gas in patients with irritable bowel syndrome (IBS) and healthy controls (HCs), despite IBS patients reporting increased gastrointestinal (GI) symptoms. AIM: To unravel the mechanisms underlying FODMAP-induced symptom reporting, we investigated gut and brain responses to fructan administration in IBS patients and HC. METHODS: This randomised, double-blind, cross-over study consisted of three visits where fructans (40 g/500 mL saline), glucose (40 g/500 mL saline) or saline (500 mL) were infused intragastrically during 1 h MR brain scanning; abdominal MRI was performed before, 1 h, and 2 h post-infusion. Symptoms were rated using validated scales. RESULTS: In IBS (n = 13), fructans induced more cramps, pain, flatulence and nausea compared to glucose (P = 0.03, 0.001, 0.009 and <0.001 respectively), contrary to HC (n = 13) (all P > 0.14), with between-group differences for cramps and nausea (P = 0.004 and 0.023). Fructans increased small bowel motility and ascending colonic gas and volume equally in IBS and HC (between-group P > 0.25). The difference in colonic gas between fructans and saline covaried with differences in bloating and cramps in IBS (P = 0.008 and 0.035 respectively). Pain-related brain regions responded differentially to fructans in IBS compared to HC, including the cerebellum, supramarginal gyrus, anterior and midcingulate cortex, insula and thalamus (pFWE-corrected  < 0.05); these brain responses covaried with symptom responses in IBS. CONCLUSIONS: Fructans increase small bowel motility and colon gas and volume similarly in IBS patients and HC. Increased symptom responses to fructans in IBS covary with altered brain responses in pain-related regions, indicating that gut-brain axis dysregulation may drive FODMAP-induced symptom generation in IBS.

Assessment of body composition and association with clinical outcomes in patients with lung and colorectal cancer.

Objectives: To assess body composition in patients with non-small cell lung cancer (NSCLC) and colorectal cancer using whole-body MRI and relate this to clinical outcomes. Methods: 53 patients with NSCLC (28 males, 25 females; mean age 66.9) and 74 patients with colorectal cancer (42 males, 32 females; mean age 62.9) underwent staging whole-body MRI scans, which were post-processed to derive fat mass (FM), fat free mass (FFM) and skeletal muscle (SM) indices and SM fat fraction (FF). These were compared between the two cancer cohorts using two-sided t-tests and the chi-squared test. Measurements of body composition were correlated with outcomes including length of hospital stay, metastatic status and mortality. Results: Patients with NSCLC had significantly lower FFM (p = 0.0071) and SM (p = 0.0084) indices. Mean SM FF was greater in patients with NSCLC (p = 0.0124) and was associated with longer hospital stay (p = 0.035). There was no significant relationship between FM, FFM and SM indices and length of hospital stay, metastatic status or mortality. Conclusions: Patients with NSCLC had lower FFM and SM indices than patients with colorectal cancer and greater SMFF, indicating lower SM mass with fatty infiltration. These findings reflect differences in the phenotype of the two groups and suggest patients with lung cancer are more likely to require additional nutritional support. Advances in knowledge: Body composition differs between NSCLC and colorectal cancer. Patients with NSCLC have both a reduced SM mass and greater SM FF suggesting that they are more nutritionally deplete than patients with colorectal cancer.

Improving the management of Acute Kidney Injury in a District General Hospital: Introduction of the DONUT bundle.

The NCEPOD report (2009) on Acute Kidney Injury (AKI) found 20% of post-admission AKIs were avoidable and only 50% of AKI care was considered 'good'. The DONUT bundle comprises of six interventions aimed at improving the management of AKI. Baseline data was collected prospectively using the biochemistry eAlert system, identifying 50 patients with Stage 1 AKI over a two week period. Management was assessed 24 hours after the eAlert using a standardised proforma. After data analysis, a DONUT sticker was introduced within the Emergency Admissions Unit, providing an efficient method of recording interventions in the notes. Education sessions outlining the DONUT bundle and stickers were delivered via Foundation Program teaching, along with summary flash cards. A re-audit assessed these interventions. Of the initial cohort (n=50), only 8% of cases had all components of the care bundle completed. Following introduction of the education programme and AKI sticker, re-audit showed a rise in full compliance to 17% (n=42). Only 7% of cases used the AKI sticker but where it was used, there was 100% compliance with the bundle. In conclusion, AKI management is sub-standard. An education program and the use of a simple sticker can improve management. Further education regarding AKI is needed and work is ongoing to improve compliance with sticker use.

CD161(+)CD4(+) T cells are enriched in the liver during chronic hepatitis and associated with co-secretion of IL-22 and IFN-γ.

Hepatitis C virus infection is a major cause of chronic liver disease. CD4(+) T cells play a key role in disease outcome. However, the critical functions and associated phenotypes of intrahepatic CD4(+) T cells are not well defined. We have previously shown that CD8(+) T cells expressing the C type lectin CD161 are highly enriched in the human liver, especially during chronic hepatitis. These cells are associated with a type 17 differentiation pattern and express cytokines including IL-17A, IL-22, and IFN-γ. We therefore analyzed expression of CD161 on CD4(+) T cells in blood and liver and addressed the relevant phenotype and functional capacity of these populations. We observed marked enrichment of CD161(+)CD4(+) T cells in the liver during chronic hepatitis such that they are the dominant subtype (mean 55% of CD4(+) T cells). IL-22 and IL-17 secreting CD4(+) T cells were readily found in the livers of HCV(+) and NASH donors, although not enriched compared to blood. There was, however, specific enrichment of a novel subset of IL-22/IFN-γ dual secretors (p = 0.02) compared to blood, a result reconfirmed with direct ex vivo analyses. These data indicate the dominance of CD161(+) expressing lymphocyte populations within the hepatic infiltrate, associated with a distinct cytokine profile. Given their documented roles as antiviral and hepatoprotective cytokines respectively, the impact of co-secretion of IFN-γ and IL-22 in the liver may be particularly significant.

Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties.

CD8(+) T lymphocytes play a key role in host defense, in particular against important persistent viruses, although the critical functional properties of such cells in tissue are not fully defined. We have previously observed that CD8(+) T cells specific for tissue-localized viruses such as hepatitis C virus express high levels of the C-type lectin CD161. To explore the significance of this, we examined CD8(+)CD161(+) T cells in healthy donors and those with hepatitis C virus and defined a population of CD8(+) T cells with distinct homing and functional properties. These cells express high levels of CD161 and a pattern of molecules consistent with type 17 differentiation, including cytokines (e.g., IL-17, IL-22), transcription factors (e.g., retinoic acid-related orphan receptor gamma-t, P = 6 x 10(-9); RUNX2, P = 0.004), cytokine receptors (e.g., IL-23R, P = 2 x 10(-7); IL-18 receptor, P = 4 x 10(-6)), and chemokine receptors (e.g., CCR6, P = 3 x 10(-8); CXCR6, P = 3 x 10(-7); CCR2, P = 4 x 10(-7)). CD161(+)CD8(+) T cells were markedly enriched in tissue samples and coexpressed IL-17 with high levels of IFN-gamma and/or IL-22. The levels of polyfunctional cells in tissue was most marked in those with mild disease (P = 0.0006). These data define a T cell lineage that is present already in cord blood and represents as many as one in six circulating CD8(+) T cells in normal humans and a substantial fraction of tissue-infiltrating CD8(+) T cells in chronic inflammation. Such cells play a role in the pathogenesis of chronic hepatitis and arthritis and potentially in other infectious and inflammatory diseases of man.