Background: Early life exposures impact immune system development and therefore the risk of immunemediated diseases, including inflammatory bowel disease (IBD). We systematically reviewed the impact of pre-, peri-, and postnatal exposures up to the age of five years on subsequent IBD diagnosis. Methods: We identified case-control and cohort studies reporting on the association between early life environmental factors and Crohn's disease (CD), ulcerative colitis (UC), or IBD overall. Databases were search from their inception until May 24th, 2019 until July 14th, 2020. We conducted meta-analyses for quantitative review of relevant risk factors that were comparable across studies and qualitative synthesis of the literature for a wide range of early life exposures, including maternal health and exposures during pregnancy, perinatal factors, birth month and related-factors, breastfeeding, hygiene-related factors and social factors, immigration, antibiotics, offspring health, including infections, and passive smoking. PROSPERO registration: CRD42019134980. Findings: Prenatal exposure to antibiotics (OR 1.8; 95% CI 1.2À2.5) and tobacco smoke (OR 1.5; 95% CI 1.2À1.9), and early life otitis media (OR 2.1; 95% CI 1.2À3.6) were associated with IBD. There was a trend towards an association between exposure to antibiotics in infancy and IBD (OR: 1.7, 95% CI 0.97, 2.9), supported by positive data on population-based data. Breastfeeding was protective against IBD. Other early life risk factors had no association with IBD, but data were limited and heterogenous. Interpretation: Early life is an important period of susceptibility for IBD development later in life. Tobacco smoke, infections and antibiotics were associated positively, and breastfeeding was associated negatively with IBD. Our findings offer an opportunity to develop primary prevention strategies. Funding: This study did not receive any funding.

<b><i>Background:</i></b> Intestinal ultrasound is emerging as a non-invasive tool for monitoring disease activity in inflammatory bowel disease patients due to its low cost, excellent safety profile, and availability. Herein, we comprehensively review the role of intestinal ultrasound in the management of these patients. <b><i>Summary:</i></b> Intestinal ultrasound has a good accuracy in the diagnosis of Crohn’s disease, as well as in the assessment of disease activity, extent, and evaluating disease-related complications, namely strictures, fistulae, and abscesses. Even though not fully validated, several scores have been developed to assess disease activity using ultrasound. Importantly, intestinal ultrasound can also be used to assess response to treatment. Changes in ultrasonographic parameters are observed as early as 4 weeks after treatment initiation and persist during short- and long-term follow-up. Additionally, Crohn’s disease patients with no ultrasound improvement seem to be at a higher risk of therapy intensification, need for steroids, hospitalisation, or even surgery. Similarly to Crohn’s disease, intestinal ultrasound has a good performance in the diagnosis, activity, and disease extent assessment in ulcerative colitis patients. In fact, in patients with severe acute colitis, higher bowel wall thickness at admission is associated with the need for salvage therapy and the absence of a significant decrease in this parameter may predict the need for colectomy. Short-term data also evidence the role of intestinal ultrasound in evaluating therapy response, with ultrasound changes observed after 2 weeks of treatment and significant improvement after 12 weeks of follow-up in ulcerative colitis. <b><i>Key Messages:</i></b> Intestinal ultrasound is a valuable tool to assess disease activity and complications, and to monitor response to therapy. Even though longer prospective data are warranted, intestinal ultrasound may lead to a change in the paradigm of inflammatory bowel disease management as it can be used in a point-of-care setting, enabling earlier intervention if needed.

<b><i>Background and Aims:</i></b> Colorectal cancer (CRC) is a heterogeneous disease with distinctive genetic pathways, such as chromosomal instability, microsatellite instability and methylator pathway. Our aim was to correlate clinical and genetic characteristics of CRC patients in order to understand clinical implications of tumour genotype. <b><i>Methods:</i></b> Single-institution retrospective cohort of patients who underwent curative surgery for CRC, from 2012 to 2014. <i>RAS</i> and <i>BRAF</i> mutations were evaluated with the real-time PCR technique Idylla®. Mismatch repair deficiency (dMMR) was characterized by absence of MLH1, MSH6, MSH2 and/or PMS2 expression, evaluated by tissue microarrays. Overall survival (OS) and disease-free survival (DFS) were assessed using survival analysis. <b><i>Results:</i></b> Overall, 242 patients were included (males 57.4%, age 69.3 ± 12.9 years; median follow-up 49 months). <i>RAS</i>-mutated tumours were associated with reduced DFS (<i>p</i> = 0.02) and OS (<i>p</i> = 0.045) in stage I–III CRC. <i>BRAF</i>-mutated tumours were more predominant in females and in the right colon, similarly to dMMR tumours. BRAF status did not influence OS (4 years)/DFS (3.5 years) in stage I–III disease. However, after relapse, length of survival was 3.5 months in <i>BRAF</i>-mutated tumours in contrast to 18.6 months in <i>BRAF</i> wild-type tumours (<i>p</i> = NS). No germline mutations in mismatch repair genes were so far identified in the patients with dMMR tumours. Molecular phenotype (<i>RAS, BRAF</i> and MMR) did not influence OS in metastatic patients. Our small sample size may be a limitation of the study. <b><i>Conclusion:</i></b> In our cohort, <i>RAS</i>-mutated tumours were associated with worse DFS and OS in early-stage CRC, whereas the remaining molecular variables had no prognostic influence.

<b><i>Background:</i></b> Colorectal cancer (CRC) is a leading cause of cancer. The detection of pre-malignant lesions by colonoscopy is associated with reduced CRC incidence and mortality. Narrow band imaging has shown promising but conflicting results for the detection of serrated lesions. <b><i>Methods:</i></b> We performed a randomized clinical trial to compare the mean detection of serrated lesions and hyperplastic polyps ≥10 mm with NBI or high-definition white light (HD-WL) withdrawal. We also compared all sessile serrated lesions (SSLs), adenoma, and polyp prevalence and rates. <b><i>Results:</i></b> Overall, 782 patients were randomized (WL group 392 patients; NBI group 390 patients). The average number of serrated lesions and hyperplastic polyps ≥10 mm detected per colonoscopy (primary endpoint) was similar between the HD-WL and NBI group (0.118 vs. 0.156, <i>p</i> = 0.44). Likewise, the adenoma detection rate (55.2% vs. 53.2%, <i>p</i> = 0.58) and SSL detection rate (6.8% vs. 7.5%, <i>p</i> = 0.502) were not different between the two study groups. Withdrawal time was higher in the NBI group (10.88 vs. 9.47 min, <i>p</i> = 0.004), with a statistically nonsignificant higher total procedure time (20.97 vs. 19.30 min, <i>p</i> = 0.052). <b><i>Conclusions:</i></b> The routine utilization of narrow band imaging does not improve the detection of serrated class lesions or any pre-malignant lesion and increases the withdrawal time.

Background The frequency of inflammatory bowel disease (IBD) is increased after marriage to an individual with the disease. Importantly, the offspring of these couples have a significant risk for developing the disease. Herein, we aimed to better characterize conjugal IBD. Methods A systematic literature search was conducted with predetermined search criteria. Relevant manuscripts reporting on couples with IBD and their offspring were selected. Concomitantly, a cross-sectional survey was conducted of couples where both members were affected with IBD, as well as their offspring, and electronically distributed by patients’ associations. Results We identified 20 reports of IBD in couples, for a total of 68 couples. Of these, 66% were concordant regarding IBD type and 66% were diagnosed after cohabitation. The overall prevalence of IBD in the offspring of these couples was 29%. Our survey identified 58 couples with IBD, with 62% being concordant regarding IBD type; 42.9% were diagnosed prior to cohabitation, in 12.5% one spouse was diagnosed before and the other after cohabitation, and in 44.6% the onset of disease occurred after cohabitation for both. The prevalence of IBD in children born from these couples was 10%. The probability of developing disease in the progeny was 2% at 10 years, 12% at 15 years, and 16% at 20 years of age. Conclusions IBD in couples occurs mostly after marriage to an individual with disease or after many years of cohabitation. In a modern cohort, the risk for the progeny was around 16% by the age of 20, lower than previously reported.