Retrospective Cohort Study: Scope for Improvement-Barriers to Post-Polypectomy Surveillance in the Integrated Technologies for Improved Polyp Surveillance Cohort.

Background: Adherence to post-polypectomy surveillance is poor despite evidence that it is associated with lower risk of future colorectal cancer.

Methods: We evaluated 6,210 bowel screening participants between 2009-2016 in NHS Greater Glasgow and Clyde to assess potential barriers to post-polypectomy surveillance.

Results: Increasing deprivation (Scottish Index of Multiple Deprivation quintile 1 vs 5; OR 1.

Fighting the enemy within: Systemic immune defense against mucosal Salmonella infection.

Salmonella infection remains a persistent global health threat, as different serovars induce a range of clinical disease, depending upon bacterial virulence and host susceptibility. While some Salmonella serovars induce gastroenteritis in healthy individuals, others can cause more serious systemic enteric fever or invasive nontyphoidal Salmonellosis. The rise of antibiotic resistance, coupled with the absence of effective vaccines for most serovars, perpetuates the spread of Salmonella in endemic regions.

Cachexia index for prognostication in surgical patients with locally advanced oesophageal or gastric cancer: multicentre cohort study.

Background: Features of cancer cachexia adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of the cachexia index (CXI), a novel prognostic marker, in patients for whom neoadjuvant chemotherapy and surgery for oesophagogastric cancer is planned.

Methods: Consecutive patients newly diagnosed with locally advanced (T3-4 or at least N1) oesophagogastric cancer between 1 January 2010 and 31 December 2015 were identified through the West of Scotland and South-East Scotland Cancer Networks.

Robotic-assisted surgery for left-sided colon and rectal resections is associated with reduction in the postoperative surgical stress response and improved short-term outcomes: a cohort study.

Introduction: There is growing evidence that the use of robotic-assisted surgery (RAS) in colorectal cancer resections is associated with improved short-term outcomes when compared to laparoscopic surgery (LS) or open surgery (OS), possibly through a reduced systemic inflammatory response (SIR). Serum C-reactive protein (CRP) is a sensitive SIR biomarker and its utility in the early identification of post-operative complications has been validated in a variety of surgical procedures. There remains a paucity of studies characterising post-operative SIR in RAS.

Vitamin A deficiency impairs neutrophil-mediated control of Salmonella via SLC11A1 in mice.

In sub-Saharan Africa, multidrug-resistant non-typhoidal Salmonella serovars are a common cause of fatal bloodstream infection. Malnutrition is a predisposing factor, but the underlying mechanisms are unknown. Here we show that vitamin A deficiency, one of the most prevalent micronutrient deficits afflicting African children, increases susceptibility to disseminated non-typhoidal Salmonella disease in mice and impairs terminal neutrophil maturation.

Elimination of Chlamydia muridarum from the female reproductive tract is IL-12p40 dependent, but independent of Th1 and Th2 cells.

Chlamydia vaccine approaches aspire to induce Th1 cells for optimal protection, despite the fact that there is no direct evidence demonstrating Th1-mediated Chlamydia clearance from the female reproductive tract (FRT). We recently reported that T-bet-deficient mice can resolve primary Chlamydia infection normally, undermining the potentially protective role of Th1 cells in Chlamydia immunity. Here, we show that T-bet-deficient mice develop robust Th17 responses and that mice deficient in Th17 cells exhibit delayed bacterial clearance, demonstrating that Chlamydia-specific Th17 cells represent an underappreciated protective population.

The role of tissue resident memory CD4 T cells in Salmonella infection: Implications for future vaccines.

Salmonella infections cause a wide range of intestinal and systemic disease that affects global human health. While some vaccines are available, they do not mitigate the impact of Salmonella on endemic areas. Research using Salmonella mouse models has revealed the important role of CD4 T cells and antibody in the development of protective immunity against Salmonella infection.

Management of malignant T1 colorectal cancer polyps: results from a 10-year prospective observational study.

Aim: The recurrence risk associated with residual malignant cells (bowel wall/regional nodes) following T1 colorectal cancer (CRC) polypectomy must be weighed against operative morbidity. Our aim was to describe the management and outcomes of a large prospective cohort of T1 CRCs.

Method: All T1 CRCs diagnosed between March 2007 and March 2017 at the Glasgow Royal Infirmary were included.

Cutting Edge: Optimal Formation of Hepatic Tissue-Resident Memory CD4 T Cells Requires T-bet Regulation of CD18.

CD4 tissue-resident memory T cells (TRMs) allow robust protection of barrier surfaces against pathogens. We investigated the role of T-bet in the formation of liver CD4 TRMs using mouse models. T-bet-deficient CD4 T cells did not efficiently form liver TRMs when compared with wild-type (WT).

Risk stratification for the detection of metachronous polyps after bowel screening polypectomy: clinical outcomes from the Integrated Technologies for Improved Polyp Surveillance (INCISE) study cohort.

Background: After colorectal polypectomy, 20-50 per cent of patients develop metachronous polyps and some have increased colorectal cancer risk. British Society of Gastroenterology (BSG) 2020 guidelines recommend surveillance colonoscopy for high-risk patients based on index pathology. The aim of this study was to evaluate metachronous lesion outcome using BSG 2020 criteria.

Optimal generation of hepatic tissue-resident memory CD4 T cells requires IL-1 and IL-2.

Hepatic CD4 tissue-resident memory T cells (TRM) are required for robust protection against infection; however, the generation of this T cell population is poorly understood. To interrogate the contribution of inflammation, we developed a simple -specific T cell transfer system that allowed direct visualization of hepatic TRM formation. -specific (SM1) T cell receptor (TCR) transgenic CD4 T cells were activated in vitro and adoptively transferred into C57BL/6 mice while hepatic inflammation was induced by acetaminophen overdose or infection.

Prevalence of repeat faecal immunochemical testing in symptomatic patients attending primary care.

Aim: The faecal immunochemical test (FIT) for faecal haemoglobin (f-Hb) helps determine the risk of colorectal cancer (CRC) and has been integrated into symptomatic referral pathways. 'Safety netting' advice includes considering referral for persistent symptoms, but no published data exists on repeated FITs. We aimed to examine the prevalence of serial FITs in primary care and CRC risk in these patients.

Host cells subdivide nutrient niches into discrete biogeographical microhabitats for gut microbes.

Changes in the microbiota composition are associated with many human diseases, but factors that govern strain abundance remain poorly defined. We show that a commensal Escherichia coli strain and a pathogenic Salmonella enterica serovar Typhimurium isolate both utilize nitrate for intestinal growth, but each accesses this resource in a distinct biogeographical niche. Commensal E.

Cohousing with Dirty Mice Increases the Frequency of Memory T Cells and Has Variable Effects on Intracellular Bacterial Infection.

The presence of memory lymphocytes in nonlymphoid tissues reflects prior immunological experience and can provide nonspecific defense against infection. In this study, we used a mouse cohousing approach to examine the effect of prior immunological experience on and infection. As expected, cohousing of "dirty mice" with specific pathogen-free laboratory mice increased the frequency of effector memory T cells in laboratory mice and enhanced protection against systemic infection.

Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice.

Protective immune responses to Chlamydia infection within the female reproductive tract (FRT) are incompletely understood. MHC class II-restricted CD4 Th1 responses are believed to be vital for bacterial clearance due to their capacity to secrete IFN-γ, but an essential requirement for T-bet-expressing Th1 cells has yet to be demonstrated in the mouse model of Chlamydia infection. Here, we investigated the role of T-bet and IFN-γ in primary clearance of Chlamydia after FRT infection.

Alternative diagnoses and demographics associated with a raised quantitative faecal immunochemical test in symptomatic patients.

Background: The faecal immunochemical test (FIT) has proven utility for colorectal cancer detection in symptomatic patients. However, most patients with a raised faecal haemoglobin (f-Hb) do not have colorectal cancer. We investigated alternative diagnoses and demographics associated with a raised f-Hb in symptomatic patients.

Combining the quantitative faecal immunochemical test and full blood count reliably rules out colorectal cancer in a symptomatic patient referral pathway.

Purpose: Faecal Immunochemical Test (FIT) has proven utility for Colorectal Cancer (CRC) detection in symptomatic patients. Most studies have examined FIT in symptomatic patients subsequently referred from primary care. We investigated associations between CRC and FIT in both referred and non-referred symptomatic patients.

CD4+ T cell immunity to Salmonella is transient in the circulation.

While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells, identifying circulating protective cells has proved very difficult, inhibiting steps to identify key antigen specificities. Exploiting a mouse model of vaccination, we show that the spleens of C57BL/6 mice vaccinated with live-attenuated Salmonella serovar Typhimurium (S. Typhimurium) strains carried a pool of IFN-γ+ CD4+ T cells that could adoptively transfer protection, but only transiently.

Longitudinal Changes in CT Body Composition in Patients Undergoing Surgery for Colorectal Cancer and Associations With Peri-Operative Clinicopathological Characteristics.

There is evidence for the direct association between body composition, the magnitude of the systemic inflammatory response, and outcomes in patients with colorectal cancer. Patients with a primary operable disease with and without follow-up CT scans were examined in this study. CT scans were used to define the presence and changes in subcutaneous fat, visceral fat, skeletal muscle mass, and skeletal muscle density (SMD).

Postoperative C-reactive protein concentrations to predict infective complications following gastrectomy for cancer.

Background And Objectives: Gastrectomy for gastric cancer is associated with significant infective postoperative complications. C-reactive protein (CRP) is a useful biomarker in the early detection of infective complications following major abdominal surgery. This single-centre retrospective study aimed to determine the relationship between postoperative CRP levels and development of postoperative infective complications after gastrectomy.

Novel Methods of Risk Stratifying Patients for Metachronous, Pre-Malignant Colorectal Polyps: A Systematic Review.

Introduction: Despite conventional measures of future polyp risk (histology, dysplasia, size, number), surveillance places a burden on patients and colonoscopy services. We aimed to review novel risk stratification techniques.

Methods: A systematic literature review was performed for studies using genomics, transcriptomics, IHC or microbiome as markers of metachronous polyp risk.

The inflammatory microenvironment in screen-detected premaligant adenomatous polyps: early results from the integrated technologies for improved polyp surveillance (INCISE) project.

Introduction: Around 40% of patients who attend colonoscopy following a positive stool screening test have adenomatous polyps. Identifying which patients have a higher propensity for malignant transformation is currently poorly understood. The aim of the present study was to assess whether the type and intensity of inflammatory infiltrate differ between screen-detected adenomas with high-grade dysplasia (HGD) and low-grade dysplasia (LGD).

Circulating immunity protects the female reproductive tract from infection.

Anatomical positioning of memory lymphocytes within barrier tissues accelerates secondary immune responses and is thought to be essential for protection at mucosal surfaces. However, it remains unclear whether resident memory in the female reproductive tract (FRT) is required for Chlamydial immunity. Here, we describe efficient generation of tissue-resident memory CD4 T cells and memory lymphocyte clusters within the FRT after vaginal infection with Despite robust establishment of localized memory lymphocytes within the FRT, naïve mice surgically joined to immune mice, or mice with only circulating immunity following intranasal immunization, were fully capable of resisting infection via the vaginal route.

Impact of anaemia in oesophago-gastric cancer patients undergoing curative treatment by means of neoadjuvant chemotherapy and surgery.

Background: The present study investigated factors associated with pre-neoadjuvant chemotherapy (NAC), and pre-operative anaemia, and examined their impact on outcomes in patients with oesophago-gastric cancer treated with curative intent.

Methods: Patients diagnosed with oesophago-gastric cancer (January 2010 to December 2015) and treated with curative intent by NAC then surgery at a tertiary centre were included. Patients were grouped by the presence of anaemia (haemoglobin <130 mg/L in males and <120 mg/L in females) and into microcytic (MCV <80 fL), normocytic (80-100 fL) and macrocytic (>100 fL) subgroups.

SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques.

CD4 T follicular helper (T) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates T cells and stimulates the germinal center (GC) response is an important question as we investigate vaccine induced immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating T cells with a T1 profile in peripheral blood.