This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e16 (https://www. gastrojournal.org/cme/home). Learning Objective: Upon completion of this CME activity, successful learners will be able to (1) evaluate the potential impact of psychological interventions on psychological disability in patient with inflammatory bowel disease and (2) identify current limitations associated with treatments. Gastroenterology 2019;156:935-945 CLINICAL AT period (all P values >.05). Hair cortisol concentrations correlated with stress (r s ¼ 0.205, P ¼ .050) and anxiety (r s ¼ 0.208, P ¼ .046) at baseline but did not change significantly in the ACT group over the study period compared with the control group (P ¼ .831). CONCLUSION: In a randomized controlled trial of patients with IBD, an 8-week ACT therapy course improved stress and other indices of psychological health.ClinicalTrials.gov Identifier: NCT02350920.

A 35-year old woman with ileocolonic, perianal, and vulval Crohn's disease was treated with subcutaneous ustekinuamb [USK] throughout pregnancy. Dose intervals were shortened from 6-weekly to 4-weekly to maintain clinical remission. The last dose of USK was administered at 33 weeks of gestation, and a healthy baby boy was delivered by caesarean section at 37 weeks. Maternal trough USK levels remained stable during pregnancy. Cord blood USK levels were nearly 2-fold higher than contemporaneous maternal serum levels. To our knowledge, this is the first report of maternal and cord USK levels in a patient with Crohn's disease.

Background and Aims Endoscopic scores of local severity do not reflect disease extent, or disease burden. The DUBLIN score is a simple bedside clinical score that estimates inflammatory burden using both disease severity and extent. As the need to personalize therapy for ulcerative colitis [UC] patients increases, a score accurately assessing disease burden will be of great relevance. The aim of this study was to assess the clinical utility of the DUBLIN score by comparing its performance with objective biomarkers. Methods The DUBLIN score was calculated as a product of the Mayo Endoscopic Score [0–3] and disease extent [E1–E3]. Correlation with objective biomarkers was performed in a retrospective ‘discovery cohort’. A ‘validation cohort was recruited from a single centre, where clinical outcomes, colectomy rate, and biochemical data were collected prospectively. Results The discovery cohort included 70 patients with UC. The DUBLIN score correlated significantly with faecal calprotectin [FCP] levels [r = 0.394; p < 0.01]. Receiver operating characteristic [ROC] analysis using FCP>50μg/g showed a higher area under the ROC curve [AUC] with the DUBLIN score [AUC = 0.76] than with the Mayo Score [AUC = 0.73]. The validation cohort included 41 patients. Patients with a high inflammatory burden [DUBLIN >3] had higher C-reactive protein and FCP, and lower albumin than patients with a low inflammatory burden. A high DUBLIN score was associated with an increased risk of treatment failure. [hazard ratio 2.98 95%, confidence interval 1.002–8.87; p = 0.049] Conclusion The DUBLIN score is a simple measure of inflammatory burden, which correlates with objective inflammatory markers and is associated with clinical outcomes, such as treatment failure. The DUBLIN score has the potential to assist in personalizing therapy for patients with UC.

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Ustekinumab trough concentrations are comparable whether ustekinumab induction treatment was administered subcutaneously or intravenously. A significant improvement in symptoms and faecal calprotectin was noted. These results support the use of subcutaneous induction as an alternative if there are barriers to intravenous induction.

The HIF hydroxylase enzymes (PHD1‐3 and FIH) are cellular oxygen‐sensors which confer hypoxic‐sensitivity upon the hypoxia‐inducible factors HIF‐1α and HIF‐2α. Microenvironmental hypoxia has a strong influence on the epithelial and immune cell function through HIF‐dependent gene expression and consequently impacts upon the course of disease progression in ulcerative colitis (UC), with HIF‐1α being protective while HIF‐2α promotes disease. However, little is known about how inflammation regulates hypoxia‐responsive pathways in UC patients. Here we demonstrate that hypoxia is a prominent microenvironmental feature of the mucosa in UC patients with active inflammatory disease. Furthermore, we found that inflammation drives transcriptional programming of the HIF pathway including downregulation of PHD1 thereby increasing the tissue responsiveness to hypoxia and skewing this response toward protective HIF‐1 over detrimental HIF‐2 activation. We identified CEBPα as a transcriptional regulator of PHD1 mRNA expression which is downregulated in both inflamed tissue derived from patients and in cultured intestinal epithelial cells treated with inflammatory cytokines. In summary, we propose that PHD1 downregulation skews the hypoxic response toward enhanced protective HIF‐1α stabilization in the inflamed mucosa of UC patients.

These real-world clinical data suggest that GLB is an effective and safe therapy for a UC cohort with significant previous anti-TNF exposure. An elevated baseline C-reactive protein, likely reflective of increased inflammatory burden, is associated with a reduced likelihood of a successful outcome of GLB therapy.