Background & Aims Genome-wide association studies (GWAS) and transcriptome analyses have been performed to better understand the pathogenesis of ulcerative colitis (UC). However, current studies mainly focus on European ancestry, highlighting a great need to identify the key genes, pathways and cell types in colonic mucosal cells of adult UC patients from other ancestries. Here we aimed to identify key genes and cell types in colonic mucosal of UC. Methods We performed Single-cell RNA sequencing (scRNA-seq) analysis of 12 colon biopsies of UC patients and healthy controls from Chinese Han ancestry. Results Two novel plasma subsets were identified. Five epithelial/stromal and three immune cell subsets show significant difference in abundance between inflamed and non-inflamed samples. In general, UC risk genes show consistent expression alteration in both Immune cells of inflamed and non-inflamed tissues. As one of the exceptions, IgA defection, marking the signal of immune dysfunction, is specific to the inflamed area. Moreover, Th17 derived activation was observed in both epithelial cell lineage and immune cell lineage of UC patients as compared to controls , suggesting a systemic change of immune activities driven by Th17. The UC risk genes show enrichment in progenitors, glial cells and immune cells, and drug-target genes are differentially expressed in antigen presenting cells. Conclusions Our work identifies novel population-specific plasma cell molecular signatures of UC. The transcriptional signature of UC is shared in immune cells from both inflamed and non-inflamed tissues, whereas the transcriptional response to disease is a local effect only in inflamed epithelial/stromal cells.

OBJECTIVES:Patient-reported outcomes such as quality of life are gaining importance in the assessment of patients suffering from inflammatory bowel disease (IBD). The association of objectively measured physical activity and quality of life in patients with IBD has not been studied in depth. To investigate the association of disease-specific quality of life and physical activity as well as clinical and biochemical disease activity in patients with IBD.METHODS:A total of 91 patients with IBD were stratified into 4 groups (Crohn's disease and ulcerative colitis, in remission and with moderate-severe activity, respectively) and evaluated in terms of disease-specific quality of life (Inflammatory Bowel Disease Questionnaire [IBDQ]), physical activity (accelerometry), body composition (bioelectrical impedance analysis), as well as clinical (Harvey-Bradshaw Index and Simple Clinical Colitis Activity Index) and biochemical (C-reactive protein and fecal calprotectin) parameters of disease activity.RESULTS:In patients with moderate-severe disease activity, the IBDQ was significantly lower as compared to patients in remission (Mann-Whitney U test and Kruskal-Wallis test, P < 0.001). The physical activity level was higher in remission than in active disease (Mann-Whitney U test, P < 0.05). The IBDQ was significantly correlated with the duration of strenuous physical activity per day (P = 0.029178, r = 0.235), skeletal muscle mass (P = 0.033829, r = 0.229), and biomarkers of inflammation (C-reactive protein: P < 0.005, r = −0.335 and fecal calprotectin: P < 0.005, r = −0.385).DISCUSSION:In this prospective, cross-sectional study, disease-specific quality of life was significantly associated with accelerometrically determined physical activity and disease activity in patients with IBD. This may be related to a reciprocal impact of these factors (DRKS00011370).

Background & Aims: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited.We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival. Methods:We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.Results: A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI).Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.

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