Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests

The Bowel Cancer Screening Programme in England began operating in 2006 with the aim of full roll out across England by December 2009. Subjects aged 60-69 are being invited to complete three guaiac faecal occult blood tests (6 windows) every 2 years. The programme aims to reduce mortality from colorectal cancer by 16% in those invited for screening

Patients with Endoscopically Visible Polypoid Adenomatous Lesions Within the Extent of Ulcerative Colitis Have an Increased Risk of Colorectal Cancer Despite Endoscopic Resection.

OBJECTIVES: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Few studies have looked at long-term outcomes of endoscopically visible adenomatous lesions removed by endoscopic resection in these patients. We aimed to assess the risk of developing CRC in UC patients with adenomatous lesions that develop within the segment of colitis compared to the remainder of an ulcerative colitis cohort. METHODS: We identified patients with a confirmed histological diagnosis of UC from 1991 to 2004 and noted outcomes till June 2011. The Kaplan-Meier method was used to estimate cumulative probability of subsequent CRC. Factors associated with risk of CRC were assessed in a Cox proportional hazards model. RESULTS: Twenty-nine of 301 patients with UC had adenomatous lesions noted within the segment of colitis. The crude incidence rate of developing colon cancer in patients with UC was 2.45 (95 % CI 1.06-4.83) per 1000 PYD and in those with UC and polypoid adenomas within the extent of inflammation was 11.07 (95 % CI 3.59-25.83) per 1000 PYD. Adjusted hazards ratio of developing CRC on follow-up in UC patients with polypoid dysplastic adenomatous lesions within the extent of inflammation was 4.0 (95 % CI 1.3-12.4). CONCLUSIONS: The risk of developing CRC is significantly higher in UC patients with polypoid adenomatous lesions, within the extent of inflammation, despite endoscopic resection. Patients and physicians should take the increased risk into consideration during follow-up of these patients

Initiatives to increase colonoscopy capacity - is there an impact on polyp detection? A UK National Endoscopy Database analysis

\ua9 2023 Georg Thieme Verlag. All rights reserved.Background Mismatch between routine endoscopy capacity and demand means centres often implement initiatives to increase capacity, such as weekend working or using locums/agency staff (insourcing). There are concerns about whether increasing workload to meet demand could negatively impact quality. We investigated polyp detection, a key quality metric, in weekend vs weekday and insourced vs standard procedures using data from the UK National Endoscopy Database (NED). Methods We conducted a national retrospective cross-sectional study of diagnostic colonoscopies undertaken 01/01-04/04/2019. The primary outcome was mean number of polyps (MNP) and the secondary, polyp detection rate (PDR). Multi-level mixed-effect regression, fitting endoscopist as a random effect, was used to examine associations between procedure day (weekend/weekday) and type (insourced/standard) and these outcomes, adjusting for patient age, sex and indication. Results 92,879 colonoscopies (weekends: 19,977 (21.5%); insourced: 9,909 (10.7%)) were performed by 2,496 endoscopists. For weekend colonoscopies, patients were more often female and less often having screening-related procedures; for insourced colonoscopies, patients were younger and less often attending for screening-related procedures (all p<0.05). Case-mix adjusted MNP was significantly lower for weekend vs weekday (IRR=0.86, (95%CI 0.83-0.89)) and for insourced vs standard procedures (IRR=0.91, (95%CI 0.87-0.95)). MNP was highest for weekday standard procedures and lowest for weekend insourced procedures, but there was no interaction between procedure day and type. Similar associations were found for PDR. Conclusions Strategies to increase colonoscopy capacity may have adverse effects on polyp detection. Routine quality monitoring should be undertaken following such initiatives. Meantime, reasons for this unwarranted variation require investigation

Meloidogyne floridensis has a unique virulence profile against root-knot nematode resistant and susceptible pepper (Capsicum annuum) lines.

Meloidogyne floridensis is a recently described species of root-knot nematode (RKN) that is very closely related to many other tropical RKN species, including M. incognita. Despite its close phylogenetic relationship, M. floridensis is distinctive from its close relatives in both its meiotic mechanism of reproduction and its documented virulence on many of the most common RKN resistance genes in cultivated peach, tomato, and pepper. To further characterize the virulence profile of M. floridensis, we conducted replicate screens using this nematode to infect a panel of pepper lines that carry different sets of known RKN resistance genes. We found that M. floridensis was virulent against all the most common RKN resistance genes, including N, Me1, and Me3. We also found that two of these lines, PA 136 and PM 217, were highly resistant to M. floridensis. PA136 was previously considered to be universally susceptible to all other RKN species. Further testing of an F1 hybrid of this line confirmed this result and indicated that PA 136 contains a yet uncharacterized and potentially dominant source of species-specific resistance against M. floridensis. These surprising results provide additional data on the differences between M. floridensis and its close relatives, and identify new sources of resistance that could be used by pepper breeding programs to develop new cultivars with resistance against this nematode

Risk stratification of Barrett's oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study

Background Barrett's oesophagus predisposes to adenocarcinoma. However, most patients with Barrett's oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up. Methods In this multicentre cohort study (BEST2), patients with Barrett's oesophagus underwent the Cytosponge test before their surveillance endoscopy. We collected clinical and demographic data and tested Cytosponge samples for a molecular biomarker panel including three protein biomarkers (P53, c-Myc, and Aurora kinase A), two methylation markers (MYOD1 and RUNX3), glandular atypia, and TP53 mutation status. We used a multivariable logistic regression model to compute the conditional probability of dysplasia status. We selected a simple model with high classification accuracy and applied it to an independent validation cohort. The BEST2 study is registered with ISRCTN, number 12730505. Findings The discovery cohort consisted of 468 patients with Barrett's oesophagus and intestinal metaplasia. Of these, 376 had no dysplasia and 22 had high-grade dysplasia or intramucosal adenocarcinoma. In the discovery cohort, a model with high classification accuracy consisted of glandular atypia, P53 abnormality, and Aurora kinase A positivity, and the interaction of age, waist-to-hip ratio, and length of the Barrett's oesophagus segment. 162 (35%) of 468 of patients fell into the low-risk category and the probability of being a true non-dysplastic patient was 100% (99% CI 96–100) and the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 0% (0–4). 238 (51%) of participants were classified as of moderate risk; the probability of having high-grade dysplasia was 14% (9–21). 58 (12%) of participants were classified as high-risk; the probability of having non-dysplastic endoscopic biopsies was 13% (5–27), whereas the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 87% (73–95). In the validation cohort (65 patients), 51 were non-dysplastic and 14 had high-grade dysplasia. In this cohort, 25 (38%) of 65 patients were classified as being low-risk, and the probability of being non-dysplastic was 96·0% (99% CI 73·80–99·99). The moderate-risk group comprised 27 non-dysplastic and eight high-grade dysplasia cases, whereas the high-risk group (8% of the cohort) had no non-dysplastic cases and five patients with high-grade dysplasia. Interpretation A combination of biomarker assays from a single Cytosponge sample can be used to determine a group of patients at low risk of progression, for whom endoscopy could be avoided. This strategy could help to avoid overdiagnosis and overtreatment in patients with Barrett's oesophagus. Funding Cancer Research UK

Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae

F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA+ B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA+ B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity

Performance measures for upper gastrointestinal endoscopy:A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative

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Adolescent Self-Organization and Adult Smoking and Drinking over Fifty Years of Follow-Up:The British 1946 Birth Cohort

Variations in markers of adolescent self-organization predict a range of economic and health-related outcomes in general population studies. Using a population-based birth cohort study we investigated associations between adolescent self-organization and two common factors over adulthood influencing health, smoking and alcohol consumption. The MRC National Survey of Health and Development (the British 1946 birth cohort) was used to test associations between a dimensional measure of adolescent self-organization derived from teacher ratings, and summary longitudinal measures of smoking and alcohol consumption over the ensuing five decades. Multinomial regression models were adjusted for sex, adolescent emotional and conduct problems, occupational social class of origin, childhood cognition, educational attainment and adult occupational social class. With all covariates adjusted, higher adolescent self-organization was associated with fewer smoking pack years, although not with quitting; there was no association with alcohol consumption across adulthood (none or heavy compared with light to moderate). Adolescent self-organization appears to be protective against smoking, but not against heavy alcohol consumption. Interpretation of this differential effect should be embedded in an understanding of the social and sociodemographic context in which these health behaviours occur over time

Atypicalities in Perceptual Adaptation in Autism Do Not Extend to Perceptual Causality

A recent study showed that adaptation to causal events (collisions) in adults caused subsequent events to be less likely perceived as causal. In this study, we examined if a similar negative adaptation effect for perceptual causality occurs in children, both typically developing and with autism. Previous studies have reported diminished adaptation for face identity, facial configuration and gaze direction in children with autism. To test whether diminished adaptive coding extends beyond high-level social stimuli (such as faces) and could be a general property of autistic perception, we developed a child-friendly paradigm for adaptation of perceptual causality. We compared the performance of 22 children with autism with 22 typically developing children, individually matched on age and ability (IQ scores). We found significant and equally robust adaptation aftereffects for perceptual causality in both groups. There were also no differences between the two groups in their attention, as revealed by reaction times and accuracy in a change-detection task. These findings suggest that adaptation to perceptual causality in autism is largely similar to typical development and, further, that diminished adaptive coding might not be a general characteristic of autism at low levels of the perceptual hierarchy, constraining existing theories of adaptation in autism.16 page(s