Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology and in situ localization across three cohorts of patients with IBD (total n = 376), we identify coexpressed gene modules within the heterogeneous tissular inflammatory response in IBD that map to distinct histopathological and cellular features (pathotypes). One of these pathotypes is defined by high neutrophil infiltration, activation of fibroblasts and vascular remodeling at sites of deep ulceration. Activated fibroblasts in the ulcer bed display neutrophil-chemoattractant properties that are IL-1R, but not TNF, dependent. Pathotype-associated neutrophil and fibroblast signatures are increased in nonresponders to several therapies across four independent cohorts (total n = 343). The identification of distinct, localized, tissular pathotypes will aid precision targeting of current therapeutics and provides a biological rationale for IL-1 signaling blockade in ulcerating disease.

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Most patients with UC do not achieve composite clinical and endoscopic remission in "real-world" practice. Clinician uptake of proposed treat-to-target guidelines is a challenge to their implementation.

Background and Aim Objective monitoring of disease activity is integral to therapeutic decision‐making in inflammatory bowel disease (IBD). Data are sparse on patients' perspectives of tools used to monitor disease activity in IBD. To evaluate patients' perspectives of gastrointestinal ultrasound (GIUS) performed during routine IBD clinical care, along with its impact on IBD‐specific knowledge. Methods Patients with a formal diagnosis of IBD who underwent GIUS at two tertiary IBD services between March 2017 and January 2019 participated in this prospective study. Participants completed a questionnaire measuring the acceptability, tolerability, and usefulness of GIUS using a visual analogue scale (VAS) from 0 (disagree) to 10 (strongly agree). Comparative acceptability of IBD monitoring tools and the impact of GIUS on IBD‐specific knowledge was measured. Results A total of 121 participants completed the questionnaire, with a mean age of 42 years (range 17–78), 54 (45%) males, and 79 (65%) Crohn's disease patients. In the overall population, GIUS was scored as highly acceptable for monitoring IBD (mean 9.20 ± 1.37) compared to colonoscopy (7.94 ± 2.30), stool sampling (8.17 ± 1.96), blood sampling (8.87 ± 1.62), and imaging (8.67 ± 1.60); P < 0.01 for each comparison. GIUS caused little patient discomfort (1.88 ± 1.83), and 98 (81%) participants ranked GIUS as their preferred IBD monitoring tool. GIUS also improved patients' overall IBD‐specific knowledge (VAS IBD‐specific knowledge 7.96 ± 1.92), including their understanding of the need for medical therapy and disease extent. Conclusion GIUS is a highly acceptable and well‐tolerated tool for monitoring disease activity in IBD patients. GIUS is preferred by patients and enhances IBD‐specific knowledge.

Local recurrence after PTA for early-stage HCC is high in routine clinical practice. Poorly differentiated HCC and pretreatment α-fetoprotein are important, independent predictors of LTP. Further well-designed randomized controlled trials with larger sample sizes using adjuvant therapies in combination with PTA to decrease LTP rates are warranted.

Background and study aims Physician-directed nurse-administered balanced propofol sedation (PhD NAPS) in patients undergoing endoscopy and/or colonoscopy is being increasingly utilized worldwide. However, this method of sedation is not universally employed in Australian hospitals due to concerns surrounding its safety. The aim of this study was to assess the safety of PhD NAPS in low-risk patients undergoing endoscopy and/or colonoscopy. Patients and methods This study was conducted at a single tertiary teaching hospital in Adelaide, Australia. It was a prospective study involving 1000 patients with an ASA score of 1 – 3 presenting with any indication for endoscopy, colonoscopy or both. A total of 981 patients (451 male) with a mean age of 53 years (range: 16 – 87) were recruited from January 2010 to October 2012. 440 endoscopies, 420 colonoscopies, and 121 combined procedures were performed. The intra-procedural adverse events (AEs) were recorded. Results There were no major intra-procedural adverse events. Minor AEs occurred in 6.42 % of patients, and resolved spontaneously or with intravenous fluid boluses in all cases. Conclusion PhD NAPS is safe when the proceduralist and nursing staff are adequately trained and strict patient selection criteria are used.

Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology, and in situ localisation, we describe heterogeneity of the tissular inflammatory response in IBD treatment failure. Among inflammatory pathotypes, we found high neutrophil infiltration, activation of fibroblasts, and vascular remodelling at sites of deep ulceration was a feature of non-response to several anti-inflammatory therapies. Activated fibroblasts in the ulcer bed display neutrophil chemoattractant properties that are IL-1R- but not TNF-dependent. The identification of distinct, localised, tissular pathotypes associated with treatment non- response will aid precision targeting of current therapeutics and provide a biological rationale for IL-1 signalling blockade in ulcerating disease.

Background and Aim Point‐of‐care ultrasound (POCUS) is a noninvasive alternative to ileocolonoscopy for monitoring disease activity in inflammatory bowel disease (IBD) but is underutilized in practice. Accuracy data are needed to engender clinician confidence in POCUS and increase uptake. The aim of this study was to evaluate the accuracy of POCUS compared to ileocolonoscopy in detecting active disease and extent in patients with IBD. Methods A prospective, blinded study was performed at a single tertiary center in South Australia between May 2017 and May 2018. Consecutive patients with a formal diagnosis of IBD who underwent both POCUS and ileocolonoscopy within 30 days of one another, performed to evaluate IBD disease activity, were eligible for participation. The accuracy of POCUS compared to ileocolonoscopy was assessed using sensitivity, specificity, and Cohen's kappa coefficient analyses. Results A total of 74 patients were included in the final analysis, 35 (47%) of whom had Crohn's disease and 39 (53%) ulcerative colitis; 37 subjects (50%) underwent a POCUS and ileocolonoscopy on the same day. POCUS demonstrated 91% sensitivity and 83% specificity for detecting endoscopically active IBD, correlating with a positive predictive value (PPV) of 89%, a negative predictive value (NPV) of 86%, and a kappa coefficient of 0.74 (88%). POCUS defined disease extent with 87% sensitivity and 81% specificity, correlating with a PPV of 85% and NPV of 83% and a kappa coefficient of 0.70 (85%). Conclusion POCUS is accurate in defining disease activity and extent in IBD compared to ileocolonoscopy. POCUS represents an appealing, noninvasive alternative to ileocolonoscopy for monitoring disease activity in IBD.