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Objectives: Fatigue is common in people with inflammatory bowel disease (IBD) and is associated with IBD activity, sleep disturbance, anxiety and depression. The relative contribution of these factors to fatigue is unclear. This study aimed to investigate the relationship between fatigue and these factors through a novel approach using structural equation modelling., Design: Online questionnaire circulated via three tertiary IBD centres and Crohn's Colitis Australia., Methods: Fatigue was assessed using the Functional assessment of chronic illness measurement system fatigue subscale. Validated measures of sleep, anxiety, depression and IBD activity were included. Following correlation analyses, a structural equation model was developed for the outcome of the fatigue score. Direct and indirect effects were calculated., Results: There were 630 complete responses to the online questionnaire. The median age of respondents was 41 with the majority female and over half (52%) on biologic medication. Structural equation models for Crohn's disease and ulcerative colitis demonstrated a good fit. In Crohn's disease, the relationship between IBD activity and fatigue was mostly mediated indirectly through the influence of IBD activity on sleep, anxiety and primarily depression. Sleep quality mediated the influence of IBD activity and the indirect effects of depression on fatigue, but not anxiety. Unlike in Crohn's disease, the direct influence of IBD activity on fatigue in ulcerative colitis was non-negligible, although remained of lesser magnitude than the indirect effect of IBD activity on fatigue. Depression was the primary indirect mediator of the influence of IBD activity on fatigue in ulcerative colitis., Conclusion: In Crohn's disease, IBD activity leads to fatigue through its influence on sleep quality and mental health. The data suggest treatment of clinically significant depression, in both ulcerative colitis and Crohn's disease, may result in the largest decline in fatigue score compared to other variables. Treatment algorithms for fatigue should consider depression a priority., Competing Interests: Conflicts of interest include speakers fees, and Ad Boards from Abbott, AbbVie, Allergan, Anatara, AstraZeneca, Bayer, BMS 2020, Celegene, Celltrion, Falk, Ferring, Gilead, Hospira, Immuninc, ImmunsanT, Janssen, MSD, Nestle, Novartis, Progenity, Pfizer, Sandoz, Shire, Takeda, Vifor, RAH research Fund, The Hospital Research Fund 2020–2022, The Helmsley Trust 2020–2023., (© The Author(s), 2024.)

Background and Aim: Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally, but little is known about contemporary resistance patterns, virulence factors, and phylogenetic patterns of isolates within Australia. We aimed to characterize antimicrobial resistance and genetic mutations associated with adverse clinical outcomes., Methods: Whole genome sequencing, culturing, and antibiotic sensitivity data for refractory H. pylori isolates at Australian centers were collected between 2013 and 2022. Phylogenetic origins, antibiotic resistance mutations, and virulence factors were examined with phenotypic resistance profiles., Results: One hundred thirty-five isolates underwent culture, with 109 of these undergoing whole genome sequencing. Forty-three isolates were isolated from patients in South Australia and 66 from Western Australia. Isolates originated primarily from hpEurope (59.6%), hpEastAsia (25.7%), and hpNEAfrica (6.4%). Antimicrobial resistance to clarithromycin was seen in 85% of isolates, metronidazole in 52%, levofloxacin in 18%, rifampicin in 14%, and amoxicillin in 9%. Most isolates (59%) were multi-drug resistant. Resistance concordance between genetically determined resistance and phenotypic resistance was 92% for clarithromycin and 94% for levofloxacin. Analysis of virulence factors demonstrated cag pathogenicity island (cagPAI) in 67% of isolates and cagA in 61%, correlating with isolate genetic origin. The most virulent s1m1 vacuolating cytotoxin A genotype was present in 26% of isolates., Conclusion: Refractory H. pylori isolates in Australia emanate from multiple global origins. Strong concordance between genetic and phenotypic antibiotic resistance profiles raises the possibility of utilizing genetic profiling in clinical practice. The dynamic landscape of H. pylori in Australia warrants the establishment of a national database to monitor H. pylori resistance and evolving virulence., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Diagnostic imaging using CT enterography, magnetic resonance enterography, and intestinal ultrasound are important tools in evaluating stricturing Crohn's disease. Definitions of strictures have been developed for CT enterography and magnetic resonance enterography. However, expert recommendations for definitions and treatment response of strictures on intestinal ultrasound are not available. The aim of this study was to standardise definitions, diagnosis, and treatment response criteria in small bowel stricturing Crohn's disease on intestinal ultrasound., Methods: Using modified RAND-University of California Los Angeles Appropriateness Method, a diverse expert panel of 13 gastroenterologists, seven radiologists, and two patient representatives was assembled. A total of 466 statements on definitions and response to therapy of stricturing Crohn's disease on intestinal ultrasound were generated from a systematic review and from expert opinion, with subsequent rating for appropriateness. Two rounds of voting with an interposed survey result discussion were performed. Statements were classified as inappropriate, uncertain, or appropriate based on the median panel rating and degree of disagreement. Appropriateness was rated using a nine-point Likert scale (1 being inappropriate, 9 being highly appropriate)., Findings: A naive or anastomotic small bowel Crohn's disease stricture on intestinal ultrasound is defined by the combination of bowel wall thickening, luminal narrowing, and pre-stenotic dilation. Bowel wall thickness is defined as being more than 3 mm. Luminal narrowing is defined as either a luminal diameter reduction of more than 50% in the narrowest area and relative to a normal adjacent bowel loop, or a luminal diameter of less than 1 cm. Pre-stenotic dilation is defined as more than 2·5 cm or an increase in bowel diameter relative to a normal adjacent bowel loop. Definitions for grading hyperaemia, inflammatory fat, wall stratification, intestinal ultrasound machine technical parameters, and image acquisition were also devised. Treatment response of strictures was defined as reduction in stricture length, bowel wall thickening, luminal narrowing, pre-stenotic dilation, and motility abnormalities., Interpretation: To our knowledge, this is the first intestinal ultrasound appropriateness rating exercise conducted for defining, diagnosing, and measuring response to therapy in small bowel stricturing Crohn's disease and informs future clinical use and intestinal ultrasound index development for clinical trials., Funding: Leona M and Harry B Helmsley Charitable Trust., Competing Interests: Declaration of interests CL has received speaker fees from AbbVie, Celltrion, Janssen, and Fresenius Kabi, and advisory board fees from AbbVie, Janssen, Lilly, Pfizer, Takeda, Fresenius Kabi, Pendopharm, and Ferring. CEP is an employee of Alimentiv. JR is an employee of Alimentiv. SRW has received partial research support from Samsung for an unrelated project, and equipment support from Samsung, Siemens, and Philips. MEB receives grant support to his institution from Siemens Healthineers, the Leona M and Harry B Helmsley Charitable Trust, and Pfizer, and provides informal consulting to Agomab. JB has received speaker and advisory board fees from Abbvie. DHB has received advisory board fees from Janssen. RVB has received speaker and advisory board fees from AbbVie, BiomeBank, Ferring, Janssen, Shire, and Takeda, and is a shareholder in BiomeBank. BC has received research support and speaker fees from AbbVie, Janssen, Takeda, Celltrion, Sandoz, and Falk. BGF has received speaker and advisory board fees from AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport, Arena Pharma, Avoro Capital Advisors, Atomwise, BioJamp, Biora Therapeutics, Boehringer-Ingelheim, Boxer, Celsius Therapeutics, Celgene or Bristol Myers Squibb, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech or Roche, Gilead, Gossamer Pharma, GSK, Hinge Bio, Hot Spot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAK Academy, Janssen, Japan Tobacco, Kaleido Biosciences, Landos Biopharma, Leadiant, LEK Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen, Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared, Viatris, Ysios, Ysopia, and Zealand Pharma, and is a shareholder in Gossamer Bio. JGF has received grant support from Siemens Healthineers. VJ has received speaker and advisory board fees from AbbVie, Alimentiv, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead Sciences, Innomar, JAMP Pharma, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Sandoz, SCOPE, Second Genome, Sorriso pharmaceuticals, Takeda, Teva, Tigenix, Topivert, Ventyx, and Vividion, and research support from Abbvie, Boehringer Ingelheim, Celgene/BMS, Eli Lilly, Gilead Sciences, Janssen, Pfizer, and Tigenix. TK has received advisory board and speaker fees from AbbVie, Amgen, Boehringer Ingelheim, Biogen, Celltrion, Celgene, Bristol-Myers Squibb, Hospira, Mundipharma, Dr Falk Pharma GmbH, Ferring Arzneimittel GmbH, Galapagos, Gilead, Janssen, Merck Sharp & Dohme GmbH, Novartis, Pfizer, Roche, Takeda Pharma GmbH, and UCB Pharma. CM has received speaker or honoraria fees AbbVie, Astra Zeneca, Biogen, Bristol-Myers Squibb, Dr Falk Pharma GmbH, Ferring Arzneimittel, Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, Roche, Samsung, Takeda Pharma, and Vifor Pharma. GM has received speaker and advisory board fees from Alfa Sigma, Fresenius Kabi, and Gilead. KN has received speaker and advisory board fees from AbbVie, Amgen, Bristol Myers Squibb, Janssen, Lily, Organon, Pendopharm, Pfizer, Ferring, Takeda, and Fresenius Kabi, research support from Pfizer and Janssen, and equipment support from Samsung. JR has received speaker and advisory board fees from Alimentiv, Boehringer Ingelheim, Gilead, Janssen Pharmaceuticals, Takeda, TiGenix, Ferring, and Origo, and research support from AbbVie and Genentech. SAT has received speaker and advisory board fees from Alimentiv and AstraZeneca, and is a shareholder in Motilent. RW has received speaker and advisory board fees from AbbVie, Alimentiv, Janssen, Pfizer, and Takeda. FR is consultant to Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, Celltrion, Clinical Data Interchange Standards Consortium, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis, Index Pharma, Landos, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Palisade, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, and 89Bio. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background & Aims: Intestinal ultrasound (IUS) is increasingly used to assess Crohn's disease (CD) activity in clinical practice. However, application in clinical trials has been limited by heterogeneous scoring methods and concerns about reliability. We aimed to determine the inter- and intra-rater reliability of locally and centrally read IUS parameters for evaluating CD using prospectively performed scans., Methods: Twenty-four participants with CD and 6 gastroenterologists participated in a 2-day workshop where each participant underwent 6 IUS scans in total. Eight IUS parameters (bowel wall thickness [BWT], bowel wall stratification [BWS], color Doppler signal [CDS], inflammatory mesenteric fat [i-fat], submucosal prominence, submucosal layer thickness, haustra coli/peristalsis, and affected segment length) and an overall measure of sonographic disease activity were blindly assessed by the 6 local readers and 4 central gastroenterologist-sonographers. Reliability was quantified using intraclass correlation coefficients (ICCs). Institutional review board approval was granted for this study (12938)., Results: Five IUS parameters demonstrated at least moderate (ICC ≥0.41) inter- and intra-rater reliability when local and central reading was performed (BWT, CDS, i-fat, submucosal prominence, and affected segment length). Reliability was generally better with central, in distinction to local, reading. ICCs for BWS and i-fat were highest when evaluated as binary outcomes. Sensitivity analyses demonstrated that IUS parameters are most reliable when evaluated in the worst affected segment. Fair reliability was observed when local readers identified the worst affected segment., Conclusions: Local and central reading of IUS demonstrated at least moderate inter- and intra-rater reliability for several parameters. This study supports refining existing activity indices and incorporating IUS central reading into clinical trials., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Quality of life is reduced in people with inflammatory bowel disease (IBD) and poor sleep is prevalent in people with IBD. This study aimed to investigate the influence of sleep on quality of life (QoL) in people with inflammatory bowel disease., Methods: An online questionnaire was administered through three tertiary IBD centers, social media, and through Crohn's Colitis Australia. The questionnaire included the EQ-5D-5L measures of health-related QoL, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index (PSQI), and validated IBD activity and mental health scores., Results: There were 553 responses included with a diagnosis of Crohn's disease (62.2%), with over half on biologic therapy (53.1%). Poor sleep and clinically significant insomnia were associated with lower QoL (EQ-5D-5L scores: EQVAS, utility score, P  < 0.001 for all). Sleep quality scores correlated with the EQ-5D-5L domains of "pain" ( ρ 0.35, P  < 0.001), "usual activities" ( ρ 0.32, P  < 0.001), and "depression-anxiety" ( ρ 0.37, P  < 0.001). After adjusting for demographic variables, IBD activity, and depression and anxiety via multivariate regression, the "pain" domain continued to be associated with PSQI components "sleep quality" ( P  < 0.001), "sleep disturbance" ( P  < 0.001), and "sleep duration" ( P  < 0.001). Clinically significant insomnia was associated with a reduction in QoL (EQVAS, utility score) independent of IBD activity ( P  < 0.001) and of a similar magnitude to that seen with IBD activity., Conclusion: Health-related QoL in IBD is influenced by aspects of sleep quality irrespective of IBD activity and mental health conditions. The presence of insomnia is associated with a reduction in health-related QoL. Consideration should be given to sleep targeting interventional studies in an IBD population., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Diet therapy for inflammatory bowel disease (IBD) is an international research priority but guidance for IBD-specific diet trial design is lacking. This review critically evaluates key elements of prospective IBD food-based intervention trials and identifies gaps. Electronic databases were searched for interventional IBD diet studies. Prospective primary studies/trials were included if used food-based dietary strategies. Forty studies/trials evaluating 29 food-based strategies as therapy for IBD were identified. Considerable heterogeneity in diets, trial design, and methodology exists. Thirty-one trials (78%) intended the diet to modulate inflammation but 14/31 (46%) did not have a primary endpoint measuring an objective change in inflammatory activity and 20/31 (65%) controlled for medication stability prior to application of diet at baseline. Higher-quality IBD diet trials used symptom-based assessment tools coupled with an objective evaluation of inflammatory activity. Dietary advice trials are the most common. One-third of trials developed and administered diet education without a dietitian. Evaluation and reporting on adherence to diet therapy occurred in <60% of trials. Failure to include or report on key elements of trial design reduced the interpretability and validity of the results. This is a considerable limitation to advancing scientific knowledge in this area. Diet therapy trials should adhere to similar rigorous quality standards used to develop other IBD therapies. Therefore, a set of practical recommendations was generated to provide the authors' perspective to help inform the future design of high-quality IBD diet trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring., Methods and Analysis: The DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants., Ethics and Dissemination: Multisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment., Trial Registration Number: ACTRN12622001458729., Competing Interests: Competing interests: RDL has received conference fees from Janssen and Celltrion Healthcare. AS has received speaker fees from Sandoz and received research support and advisory fees from AbbVie, Pfizer, and Arrow Pharmaceuticals. GJW has served as a speaker, a consultant or an advisory board member for Janssen, Galapagos, AbbVie, Ferring, Dr Falk Pharma, Nova Labs and Sandoz. GTM has received educational grants or research support from GESA, The Gutsy Group, NHMRC, MRFF, AbbVie, Janssen, Pfizer, Shire and Takeda; speaker fees from AbbVie, Ferring, Janssen, Orphan, Pfizer, Roche, Sandoz, Shire and Takeda and has serve on advisory boards for AbbVie, Emerge, Eli-Lilly, Gilead, Hospira, Janssen, Orphan, MSD, Pfizer, Shire and Takeda. KL declares speaker fees, advisory Board fees and/or conference travel/registration support from AbbVie, Bristol Myers Squibb, Chiesi, Dr Falk, Ferring, Gilead, Guidepoint, Intercept Pharmaceuticals, Janssen-Cilag, MSD, Norgine, Pfizer, Sandoz, Takeda and the RAH Research Fund. JA has served as a speaker, a consultant and an advisory board member for, and has received research funding from, Abbott, AbbVie, Allergan, Anatara, AstraZeneca, Bayer, Celgene, Falk, Ferring, Gilead, Hospira, Immunic, ImmunsanT, Janssen, MSD, Nestle, Progenity, Pfizer, Sandoz, Shire, Takeda, Vifor, RAH Research Fund, The Hospital Research Fund with all monies received by her department for research support. YKA reports grants from Janssen, during the conduct of the study; has received speaking and consulting fees from AbbVie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire and Takeda; served on advisory boards for AbbVie, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise, Microba and received research and educational funding from Abbvie, Celltrion, Dr Falk, Janssen, Pfizer, Sandoz and Takeda. RVB has received grant/research support/speaker fees from AbbVie, Ferring, Janssen, Shire, Takeda, Bristol Myer Squibb and Emerge Health; and is a shareholder in Biomebank. SC declares advisory board participation, speaker fees, educational support and/or research support for Liverpool Hospital, South Western Sydney Local Health District (SWSLHD) Academic Unit or Crohn’s Colitis Cure from: AbbVie, Amgen, BMS, Celltrion, Chiesi, Eli-Lilly, Dr Falk, Ferring, Fresenius Kabi, Gilead, GSK, Janssen, MSD, Novartis, Organon, Pfizer, Sandoz, Takeda and non-pharmacological research support from Agency for Clinical Innovation, Gastroenterological Society of Australia, The Leona M and Harry B Helmsley Charitable Trust, Medical Research Future Fund, SWSLHD, Sydney Partnership for Health, Research and Enterprise (SPHERE). MG has served on the advisory board of Pfizer and has received speaker fees, research or travel grants from AbbVie, Celltrion, Dr Falk, Janssen, Pfizer, Pharmacosmos, Takeda. EKW declares speaker and consulting fees from AbbVie, BMS, Celltrion, Falk, Ferring, Janssen, Pfizer and research funding/support from AbbVie, Ferring, Janssen. JPS has received conference fees from Janssen, BMS, Takeda, educational grants from Pfizer, speaker fees from AbbVie, Takeda and Pfizer and an unrestricted grant from Tillots. PDC has served as a consultant, an advisory board member or a speaker for AbbVie, Baxter, Ferring, Janssen, Celltrion, Emerge Health, Shire and Takeda and received research support from Ferring, Shire, Janssen, AbbVie, and Takeda. MGW has received educational grants and speakers fees from AbbVie, Takeda and Ferring; travel grants from Pfizer; and has served on advisory boards for AbbVie. MPS has received educational grants or research support from Ferring, Orphan and Gilead; speakers fees from Janssen, AbbVie, Ferring, Takeda, Pfizer and Shire; and has served on advisory boards for Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead and BMS. JM, PH, RBG, DC, MS, EC, LT, GH and AB declare no relevant competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Until recently, diet as a therapeutic tool to treat inflammatory bowel disease (IBD) has not been proven effective. Nearly a century in the making we are in the grips of a revolution in diet therapies for IBD, driven by emerging data revealing diet as a key environmental factor associated with IBD susceptibility, and observational studies suggesting that dietary intake may play a role in the disease course of established IBD. This review summarizes the current evidence for diets trialed as induction and maintenance therapy for IBD. For Crohn's disease, exclusive enteral nutrition and the Crohn's disease exclusion diet with partial enteral nutrition are supported by emerging high-quality evidence as induction therapy, but are short-term approaches that are not feasible for prolonged use. Data on diet as maintenance therapy for Crohn's disease are conflicting, with some studies supporting fortification, and others suppression, of certain food components. For ulcerative colitis, data are not as robust for diet as induction and maintenance therapy; however, consistent themes are emerging, suggesting benefits for diets that are plant-based, high in fiber and low in animal protein. Further studies for both Crohn's disease and ulcerative colitis are eagerly awaited, which will allow specific recommendations to be made. Until this time, recommendations default to population based healthy eating guidelines., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Constipation can be diagnosed clinically using the Rome criteria. Ultrasound (US), which lacks the radiation exposure of conventional X-ray, holds promise as a non-invasive tool to evaluate colonic contents and constipation., Aim: To examine the role of US in the assessment of constipation., Methods: We performed a systematic search of Embase (OVID, 1984), Medline (Ovid, 1946), Cochrane Central, ClinicalTrials.gov and Australia New Zealand Clinical Trials Registry from database inception to 26 January 2024 according to PRISMA guidelines and prospectively registered with PROSPERO. All studies using US to assess constipation or colonic contents in either adults or children were included. Rectal diameter measurements were pooled in meta-analysis. Risk of bias was assessed using the Newcastle Ottawa Scales and Joanna Briggs Institute checklists., Results: Of 12,232 studies screened, 51 articles (6084 patients; 3422 children) describing US to assess symptoms in patients with constipation were included. Most studies used Rome criteria to diagnose constipation. Rectal diameter was associated with clinical constipation in 29 paediatric studies (3331 patients). Meta-analysis showed the mean rectal diameter of constipated patients was significantly higher than controls (mean difference 12 mm, 95% confidence intervals (CI): 6.48, 17.93, p < 0.0001, n = 16 studies). Other features of constipation on US included posterior acoustic shadowing and echogenicity of luminal contents., Conclusion: US is an appealing imaging modality to assess luminal contents and constipation. Further well-designed studies are required to validate US metrics that accurately identify constipation., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Introduction: Fatigue is prevalent in people with inflammatory bowel disease (IBD) and has been associated with IBD activity, sleep quality, depression, and anxiety. This study aimed to identify fatigue profiles or clusters through latent profile analysis., Methods: An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn's Colitis Australia. Fatigue was assessed via the Functional assessment of chronic illness measurement system fatigue subscale (FACIT-F), a validated assessment of fatigue and its severity. Validated measures of anxiety, depression, IBD activity and sleep quality were also included. Latent profile analysis was performed including fatigue, sleep quality, active IBD, and depression and anxiety. The relationships between profiles and IBD and demographic data were investigated., Results: In a cohort of 535 respondents, 77% were female, the median age was 41 years (range 32-52 years), and the majority had Crohn's disease (62%). Severe fatigue was seen in 62%. Latent profile analysis identified four distinct profiles differing by fatigue score - low fatigue, at-risk profile, active IBD, and a poor mental health profile. Female gender, obesity and opioid usage were associated with higher risk of being in the active IBD and poor mental health profile. Age over 40 was associated with lower risk of being in the poor mental health profile., Conclusion: Latent profile analysis identifies four classes of fatigue in an IBD cohort with associations with specific risk factors for fatigue along with specific IBD and demographic attributes. This has implications for the classification of fatigue in IBD and treatment algorithms., (© 2024. The Author(s).)

There is demand from patients and clinicians to use the Crohn's disease exclusion diet (CDED) with or without partial enteral nutrition (PEN). However, the therapeutic efficacy and nutritional adequacy of this therapy are rudimentary in an adult population. This review examines the evidence for the CDED in adults with active luminal Crohn's disease and aims to provide practical guidance on the use of the CDED in Australian adults. A working group of nine inflammatory bowel disease (IBD) dietitians of DECCAN (Dietitians Crohn's and Colitis Australian Network) and an IBD gastroenterologist was established. A literature review was undertaken to examine (1) clinical indications, (2) monitoring, (3) dietary adequacy, (4) guidance for remission phase, and (5) diet reintroduction after therapy. Each diet phase was compared with Australian reference ranges for food groups and micronutrients. CDED with PEN is nutritionally adequate for adults containing sufficient energy and protein and meeting > 80% of the recommended daily intake of key micronutrients. An optimal care pathway for the clinical use of the CDED in an adult population was developed with accompanying consensus statements, clinician toolkit, and patient education brochure. Recommendations for weaning from the CDED to the Australian dietary guidelines were developed. The CDED + PEN provides an alternate partial food-based therapy for remission induction of active luminal Crohn's disease in an adult population. The CDED + PEN should be prioritized over CDED alone and prescribed by a specialist IBD dietitian. DECCAN cautions against using the maintenance diet beyond 12 weeks until further evidence becomes available., (© 2023 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Beyond endoscopic remission, histological remission in ulcerative colitis (UC) is predictive of clinical outcomes. Intestinal ultrasound (IUS) may offer a noninvasive surrogate marker for histological activity; however, there are limited data correlating validated ultrasound and histological indices., Aim: Our aim was to determine the correlation of IUS activity in UC with a validated histological activity index., Methods: Twenty-nine prospective, paired, same-day IUS/endoscopy/histology/fecal calprotectin (FC) cases were included. Intestinal ultrasound activity was determined using the Milan Ultrasound Criteria, histological activity using the Nancy Histological Index, endoscopic activity using Mayo endoscopic subscore and Ulcerative Colitis Endoscopic Index of Severity, and clinical activity using the Simple Clinical Colitis Activity Score., Results: Histological activity demonstrated a significant linear association with overall IUS activity (coefficient 0.14; 95% CI, 0.03-0.25; P = .011). Intestinal ultrasound activity was also significantly associated with endoscopic activity (0.32; 95% CI, 0.14-0.49; P < 0.001), total Mayo score (0.31; 95% CI, 0.02-0.60; P = .036) but not FC (0.10; 95% CI, -0.01 to 0.21; P = .064) or clinical disease activity (0.04; 95% CI, -0.21 to 0.28; P = .768). A composite of IUS and FC showed the greatest association (1.31; 95% CI, 0.43-2.18; P = .003) and accurately predicted histological activity in 88% of cases (P = .007), with sensitivity of 88%, specificity 80%, positive predictive value 95%, and negative predictive value 57%., Conclusions: Intestinal ultrasound is an accurate noninvasive marker of histological disease activity in UC, the accuracy of which is further enhanced when used in composite with FC. This can reduce the need for colonoscopy in routine care by supporting accurate point-of-care decision-making in patients with UC., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background/aims: Insomnia is common in people with chronic medical conditions, such as inflammatory bowel disease (IBD), and is readily treatable through cognitive behavioral therapy for insomnia. This study aimed to describe the associations with insomnia in people with IBD and its relationship to IBD-related disability., Methods: An online questionnaire was administered through 3 tertiary IBD centers, social media, and Crohn's Colitis Australia. The questionnaire included the Insomnia Severity Index (ISI), a validated assessment of insomnia. Measures of anxiety, depression, physical activity, and disability were also included. IBD activity was assessed using validated patient reported scores. A multivariate model was constructed for clinically significant insomnia and ISI scores. Subpopulations of Crohn's disease and ulcerative colitis were considered., Results: In a cohort of 670 respondents the median age was 41 years (range, 32-70 years), with the majority female (78.4%), the majority had Crohn's disease (57.3%). Increasingly severe disability was associated with worse insomnia score. Clinically significant insomnia was associated with clinically active IBD, abdominal pain, anxiety, and depression, in a multivariate model. In an ulcerative colitis population, Simple Clinical Colitis Activity Index components of general well-being and urgency were associated with worse ISI score in a model including depression and anxiety. In those with Crohn's disease, the multivariate model included Harvey Bradshaw Index score in addition to depression and anxiety., Conclusions: Insomnia is common in people with IBD and is associated with increased disability. Abdominal pain and mental health conditions should prompt consideration for screening for insomnia and referral for cognitive behavioral therapy for insomnia.

Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we aimed to evaluate the feasibility of faecal microbiota transplantation (FMT) delivered during the acute phase after HSCT. Of note, this trial opted for FMT prepared using the individual's own stool (autologous FMT) to mitigate the risks of disease transmission from a donor stool. Adults (>18 years) with multiple myeloma were recruited from a single centre. The stool was collected prior to starting first line therapy. Patients who progressed to HSCT were offered FMT via 3 × retention enemas before day +5 (HSCT = day 0). The feasibility was determined by the recruitment rate, number and volume of enemas administered, and the retention time. Longitudinally collected stool samples were also collected to explore the influence of auto-FMT using 16S rRNA gene sequencing. n = 4 (2F:2M) participants received auto-FMT in 12 months. Participants received an average of 2.25 (1-3) enemas 43.67 (25-50) mL total, retained for an average of 60.78 (10-145) min. No adverse events (AEs) attributed to the FMT were identified. Although the minimum requirements were met for the volume and retention of auto-FMT, the recruitment was significantly impacted by the logistical challenges of the pretherapy stool collection. This ultimately undermined the feasibility of this trial and suggests that third party (donor) FMT should be prioritised.

Background and Aim: Helicobacter pylori infection is responsible for considerable morbidity and mortality worldwide and eradication rates are falling globally because of increasing antimicrobial resistance. However, there is a paucity of local data to guide the choice of eradication therapy in Australia. This study aimed to evaluate current Australian rates of H. pylori antibiotic resistance in patients who had failed prior eradication therapy., Methods: A retrospective analysis of routine culture and antibiotic susceptibility data from two pathology laboratories servicing multiple tertiary referral hospitals in Western Australia (WA) and South Australia (SA), between 2018 and 2022, was performed. Rates of antimicrobial resistance and prevalence of multiresistant isolates in both SA and WA were calculated and comparison of temporal trends and differences between the two states was conducted., Results: A total of 796 H. pylori isolates revealed a clarithromycin resistance rate of 82%, metronidazole 68%, amoxicillin 4.4% and tetracycline 0.5%. Resistance to levofloxacin was observed in 22% and rifampicin 14%. Rates of resistance to clarithromycin were lower in SA compared with WA (incidence rate ratio [IRR]: 0.69, P = 0.0001). Multiresistant isolates were discovered in 63% of patients, with lower rates in SA compared with WA (IRR: 0.74, P = 0.002)., Conclusion: This first multicentre, multistate study of H. pylori resistance in Australian patients exposed to prior therapy demonstrated high rates of antimicrobial resistance, including levofloxacin (>20%). This raises concern about recommending levofloxacin in empirical second-line therapies. Increased monitoring and awareness of current H. pylori resistance rates in Australia are needed to guide local eradication practices., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: Patients with inflammatory bowel disease (IBD) require accessible, timely, and noninvasive strategies to monitor disease. The aim was to assess the integration of intestinal ultrasound (IUS) on decision-making and endoscopy utilization in a standardized care pathway., Methods: This prospective, multicenter, international, observational cohort study included patients seen within a centralized model for IBD care was conducted during the COVID pandemic. Patients were evaluated with IUS alone or in combination with an in-clinic, unsedated sigmoidoscopy. Demographic, clinical, laboratory, and imaging data, clinical decisions, and need for urgent endoscopy, hospitalization, and surgeries were recorded., Results: Of the 158 patients included, the majority had an established diagnosis of Crohn's disease ( n  = 123, 78%), and 47% ( n  = 75) of patients were on biologic therapy. IUS identified active inflammation in 65% ( n  = 102) of patients, and strictures in 14% ( n  = 22). Fecal calprotectin levels correlated with inflammation detected on IUS (median of 50 μg/g [Q1-Q3: 26-107 μg/g] without inflammation and 270 μg/g [Q1-Q3: 61-556 μg/g] with inflammation; p  = 0.0271). In the majority of patients, clinical assessment with IUS led to an acute change in IBD-specific medications (57%, n  = 90) and avoided or delayed the need for urgent endoscopy (85%, n  = 134). Four patients were referred for urgent surgical consultation., Conclusions: Point-of-care IUS used in a flare clinic pathway is a useful strategy to improve effective IBD care delivery and to assist in therapeutic management decisions, in many cases avoiding the acute need for endoscopy., Competing Interests: K.L.N. reports advisory board fees from AbbVie, Janssen, Pfizer, Ferring; speaker’s fees from AbbVie, Janssen; and research support from AbbVie, Janssen. J.S., H.K., and J.H. report no conflicts. M.D. reports fees for participation on advisory committees from Amgen, Fresenius Kabi, Pendopharm, and Takeda; fees for participation on advisory committees from Bristol Myers Squibb, McKesson, Pendopharm, and Takeda; educational, clinical, or research grants from Abbvie, Amgen, Organon, Pfizer, Sandoz, and Takeda. T.M.G. reports support through provision of an Australian Government research training program scholarship and grant support from Janssen. R.J.M.I. reports travel support from AbbVie and speaker’s fees from Takeda. R.V.B. reports Grant/Research support/Speaker fees (all paid to employer for research support): AbbVie, Ferring, Janssen, Shire, Takeda, Emerge Health; shareholder in Biomebank. B.C. has served as a consultant and advisory board member, and received grants from AbbVie, Ferring, Janssen, Pfizer, Fresenius Kabi, Falk Pharama, Gilead, Celgene, and Takeda. R.V. has served as a consultant for Janssen. A.A.-A. was funded by scholarships from Crohn’s and Colitis Australia, Avant, the Australian Commonwealth Government, and University of Melbourne and received grants from the Gastroenterological Society of Australia/Celltrion Healthcare and Janssen. D.C. reports speaker’s fees and/or research support from Takeda, Janssen, Abbvie, and Tarp and consultancy fees from Takeda, Abbvie, and Taro. C.L. reports consulting or advisory board fees from AbbVie, Ferring, Janssen, and Takeda. C.M. reports consulting or advisory board fees from AbbVie, AVIR Pharma Inc, Janssen, Takeda, Pfizer, Roche, and Robarts Clinical Trials Inc.; speaker’s fees from AbbVie, Janssen, Takeda, and Pfizer., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Patients with ulcerative proctitis have favorable long-term outcomes but are typically excluded from ulcerative colitis clinical trials. Refractory proctitis presents a management conundrum for gastroenterologists, and there remains a lack of clarity as to the best therapeutic strategy. This study aimed to undertake a systematic review of studies assessing the clinical efficacy and safety of therapies for refractory proctitis. PubMed, Embase, Cochrane Library, and MEDLINE databases were searched without restriction from inception to October 27, 2022. Both interventional and noninterventional studies examining efficacy of therapeutic modalities for the induction and/or maintenance of remission in refractory proctitis were included. Included studies were grouped by therapeutic modalities as follows: (i) immunomodulators, (ii) monoclonal antibodies, (iii) topical calcineurin inhibitors, (iv) other topical therapies, and (v) appendicectomy. The search strategy identified 3301 studies, of which 13 met eligibility criteria for inclusion. Clinical remission rates for systemic therapies ranged from 20-26% for azathioprine to 50-69% for tumor necrosis factor-α inhibitor therapies. The use of systemic therapies for proctitis raised safety concerns, with 22-37% of patients discontinuing therapies due to adverse effects across four retrospective cohort studies. Prospective clinical trials of topically applied tacrolimus demonstrated clinical remission rates of 42-46%, with a favorable safety profile. Substantial heterogeneity in study design precluded meta-analysis. Refractory ulcerative proctitis remains a neglected entity, with a dearth of prospective clinical trials to guide therapeutic decision-making. Current evidence supports a role for topically administered tacrolimus., (© 2023 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Inflammatory bowel disease (IBD) has been associated with an increased risk of obstructive sleep apnea (OSA). We aimed to examine the associations of obstructive sleep apnea, sleepiness, and IBD-related data and comorbidities, with the aim of developing a screening tool for sleep apnea in this population., Methods: An online survey of adults with IBD was administered which included measures of assessment of the risk of OSA, and measures of IBD activity, IBD-related disability, anxiety, and depression. Logistic regression was performed to investigate the associations between the risk of OSA and IBD data, medications, demographics, and mental health conditions. Further models were built for an outcome of severe daytime sleepiness and a combined outcome of risk of OSA and at least mild daytime sleepiness. A simple score was constructed for the purpose of screening for OSA., Results: There were 670 responses to the online questionnaire. The median age was 41 years, the majority had Crohn's disease (57%), the median disease duration was 11.9 years, and approximately half were on biologics (50.5%). Moderate-high risk of OSA was demonstrated in 22.6% of the cohort. A multivariate regression model for moderate-high risk of OSA included increasing age, obesity, smoking, and abdominal pain subscore. For a combined outcome of moderate-high risk of OSA and at least mild daytime sleepiness, a multivariate model included abdominal pain, age, smoking, obesity, and clinically significant depression. A simple score was constructed for screening for OSA utilizing age, obesity, IBD activity, and smoking status with an area under the receiver-operating curve of 0.77. A score >2 had a sensitivity of 89% and a specificity of 56% for moderate-high risk of OSA and could be utilized for screening for OSA in the IBD clinic., Conclusions: Over one-fifth of an IBD cohort met significantly high-risk criteria for OSA to warrant referral for a diagnostic sleep study. The risk of OSA was associated with abdominal pain, along with more traditional risk factors such as smoking, increasing age, and obesity. Consideration should be given for screening for OSA in IBD patients utilizing a novel screening tool that utilizes parameters typically available in IBD clinic., Competing Interests: It include speakers fees and Ad Boards from Abbott, AbbVie, Allergan, Anatara, AstraZeneca, Bayer, BMS 2020, Celegene, Celltrion, Falk, Ferring, Gilead, Hospira, Immuninc, ImmunsanT, Janssen, MSD, Nestle, Novartis, Progenity, Pfizer, Sandoz, Shire, Takeda, Vifor, RAH research Fund, The Hospital Research Fund 2020-2022, The Helmsley Trust 2020-2023., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background and Aim: This study evaluates whether a stool donor program to supply fecal microbiota transplantation (FMT) product is feasible in the Australian regulatory environment. The primary outcome was capacity to supply FMT product. The secondary outcomes were donor eligibility, retention, and output., Methods: Prospective observational cohort study using data collected from the stool donor and FMT production records from BiomeBank, South Australia. Participants were people who engaged with BiomeBank's donor screening and FMT manufacturing process between 01 January 2021 and 31 December 2021., Results: In total 176 people registered interest in the program, 74 of 176 (42.0%) proceeded to written questionnaire, 14 of 176 (8.0%) underwent clinical assessment, and 8 of 176 (4.5%) enrolled in the program. Two people were ineligible based on laboratory tests: both had an extended spectrum beta-lactamase producing organism in stool and one also tested positive for hepatitis B core antibody. Two donors remained eligible from 2020, resulting in 10 enrolled donors in 2021; 5 of 10 (50%) male with a median age of 36.9 years (interquartile range, 30.3-42.7 years). All donors were ineligible to donate at some time point. There were 144 stool donations processed into 1480 50 mL FMT; 413 FMT were shipped to 33 Australian hospitals for treatment, 470 for clinical trials, and 89 were destroyed prior to release from quarantine., Conclusion: Recruitment into the program, retention, and maximizing the yield from a donation period was challenging. Despite this, BiomeBank was able to produce and supply FMT to Australian hospitals under the TGA-regulated Class 2 Biologicals framework., (© 2023 Biome Bank. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis (UC). However, the knowledge of histology guidelines and the attitudes towards their use in clinical practice by gastroenterologists and pathologists is unknown., Aim: To evaluate the knowledge of histology guidelines and attitudes towards the use of histology in UC by gastroenterologists and pathologists., Methods: A prospective, cross-sectional nationwide survey of gastroenterologists and pathologists who analyse UC specimens was conducted. The survey consisted of 34 questions to assess gastroenterologists' and pathologists' knowledge (score out of 19) and attitudes towards histological assessment in UC. Survey questions were formulated using the European Crohn's and Colitis position paper on histopathology and the British Society of Gastroenterology biopsy reporting guidelines. It included knowledge of histological assessment of disease activity and dysplasia, knowledge of histological scoring systems for ulcerative colitis, uptake of histology scoring systems in routine practice, attitudes towards the role of histological activity, and the use of histological activity in clinical scenarios., Results: Of 89 responders (77 gastroenterologists, 12 pathologists), there was almost universal acceptance that histological assessment should form part of UC evaluation [95% gastroenterologists, 92% pathologists]. However, gastroenterologists reported that 92% of their pathologists do not use a histological scoring system. Utilisation of a formal histological scoring system was preferred by 77% of gastroenterologists and 58% of pathologists. Both groups lacked awareness of the Geboes Score, Nancy Index and Robarts Histopathological Index scoring systems with 91%, 87%, and 92% of gastroenterologists respectively; and 83%, 83%, and 92% pathologists respectively, being uncertain of scoring systems' remission definitions. Histology knowledge score was not significantly different between gastroenterologists and pathologists [9/19 (IQR: 8-11) vs 8/19 (IQR: 7-10), P = 0.54]. Higher knowledge scores were predicted by hospital attending gastroenterologists ( P = 0.004), participation in inflammatory bowel disease (IBD) multidisciplinary teams ( P = 0.009), and self-declared IBD sub-specialist ( P = 0.03)., Conclusion: Histological remission is a recognised target for both gastroenterologists and pathologists. Despite this, knowledge of histological scoring systems and their utilisation is poor., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested., Aim: To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis., Methods: We conducted a comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC., Results: A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking., Conclusions: The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

There is mounting evidence that microbiome composition is intimately and dynamically connected with host energy balance and metabolism. The gut microbiome is emerging as a novel target for counteracting the chronically positive energy balance in obesity, a disease of pandemic scale which contributes to >70 % of premature deaths. This scoping review explores the potential for therapeutic modulation of gut microbiota as a means of prevention and/or treatment of obesity and obesity-associated metabolic disorders. The evidence base for interventional approaches which have been shown to affect the composition and function of the intestinal microbiome is summarised, including dietary strategies, oral probiotic treatment, faecal microbiota transplantation and bariatric surgery. Evidence in this field is still largely derived from preclinical rodent models, but interventional studies in obese populations have demonstrated metabolic improvements effected by microbiome-modulating treatments such as faecal microbiota transplantation, as well as drawing attention to the unappreciated role of microbiome modulation in well-established anti-obesity interventions, such as dietary change or bariatric surgery. The complex relationship between microbiome composition and host metabolism will take time to unravel, but microbiome modulation is likely to provide a novel strategy in the limited armamentarium of effective treatments for obesity.

Background & Aims: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease., Methods: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists., Results: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities., Conclusions: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Helicobacter pylori infection is responsible for considerable morbidity and mortality worldwide, and eradication rates are falling in many countries, primarily due to clarithromycin and metronidazole resistance., Aims: There is a paucity of contemporary Australian data, which we sought to address by evaluating local rates of resistance of H. pylori to amoxicillin, clarithromycin, metronidazole and tetracycline over the past 20 years., Methods: All gastric biopsy specimens collected at endoscopy to detect H. pylori infection at a single centre underwent routine culture and antibiotic susceptibility testing between 1998 and 2017. Specimens from 12 842 patients were cultured for H. pylori, of which 1473 positive cultures were tested for antibiotic susceptibility., Results: Antibiotic resistance to clarithromycin increased by 3.7% per year (incidence rate ratio [IRR] 1.037; P = 0.014) over 20 years, with a corresponding 5.0% annual increase in minimum inhibitory concentration (MIC) (odds ratio 1.050; P < 0.001). Since 2010, average clarithromycin resistance has exceeded 20%, with >25% of isolates resistant in the past 2 years of data capture. In contrast, rates of resistance to metronidazole (35.3%), amoxicillin (0.14%) and tetracycline (0.34%) and their MIC have remained stable. Review of a representative sample (n = 120; 8%) of these patients revealed that only 5% had documented prior H. pylori eradication therapy., Conclusions: Over the past 20 years there has been a substantial rise in clarithromycin resistance, with stable metronidazole resistance and low rates of resistance to amoxicillin and tetracycline. Current first-line H. pylori eradication therapy may fail to achieve adequate eradication rates, and optimal first-line therapy in Australia should be revisited., (© 2021 Royal Australasian College of Physicians.)

Intestinal ultrasound (IUS) is emerging as a key tool to achieving the therapeutic target of transmural healing in inflammatory bowel disease (IBD). IUS is a non-invasive, radiation-free, imaging modality comparable to MRI, CT and ileocolonoscopy (IC). With the appropriate training and equipment, IUS can be an easily repeatable bedside test for IBD diagnosis and disease monitoring, including treatment response. Core to successful high quality IUS employment are appropriate training and expert techniques; however, the training pathway will not be explored in this review. Given the increasing shift towards objective assessment for tight disease control, gastroenterologist-led IUS should be incorporated into the armamentarium of imaging modalities alongside radiologists, to enhance our diagnostic and monitoring toolbox. This comprehensive review aims to outline the current literature around IUS and propose the placement of IUS in a treat-to-target algorithm in IBD. Ultimately, IUS facilitates timely management decisions to optimise patient care with potential to revolutionise patient outcomes, moving towards transmural healing as the holy grail of therapy in IBD.

Background: Diet therapy may bridge the therapeutic gap in ulcerative colitis (UC)., Objectives: The novel 4-SURE diet (4-strategies-to-SUlfide-REduction), designed to modulate colonic fermentation and influence production of excess hydrogen sulfide, was examined in a feasibility study for tolerability, clinical efficacy, and effects on microbial endpoints., Methods: Adults aged ≥18 y old with mild to moderately active UC were advised to increase intake of fermentable fibers, restrict total and sulfur-containing proteins, and avoid specific food additives for 8 wk. The primary outcome was tolerability of diet [100-mm visual analogue scale (VAS) with 100-mm being intolerable]. Secondary exploratory outcomes were self-reported adherence (always adherent ≥76-100%), clinical and endoscopic response (reduction in partial Mayo ≥2 and Mayo endoscopic subscore ≥1), modulation of fecal characteristics including markers of protein and carbohydrate fermentation, and food-related quality of life (IBD-FRQoL-29). Primary analysis was by intention to treat, performed using paired t and Wilcoxon signed-rank statistical tests., Results: Twenty-eight adults with UC [mean (range) age: 42 (22-72) y, 15 females, 3 proctitis, 14 left-sided, and 11 extensive] were studied. Prescribed dietary targets were achieved overall. The diet was well tolerated (VAS: 19 mm; 95% CI: 7, 31 mm) with 95% frequently or always adherent. Clinical response occurred in 13 of 28 (46%) and endoscopic improvement in 10 of 28 participants (36%). Two participants (7%) worsened. Fecal excretion of SCFAs increased by 69% (P < 0.0001), whereas the proportion of branched-chain fatty acids to SCFAs was suppressed by 27% (-1.34%; 95% CI: -2.28%, -0.40%; P = 0.007). The FRQoL improved by 10 points (95% CI: 4, 16; P < 0.001)., Conclusions: The 4-SURE dietary strategy is considered tolerable and an acceptable diet by adults with mild to moderately active UC. The dietary teachings achieved the prescribed dietary and fecal targets. Given signals of therapeutic efficacy, further evaluation of this diet is warranted in a placebo-controlled trial. This trial was registered at https://www.anzctr.org.au (Australian New Zealand Clinical Trials Registry) as ACTRN12619000063112., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic., Aim: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development., Methods: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'., Results: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics., Conclusions: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background and Aim: Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally; however, geospatial location and its interaction with risk factors for infection have not been closely examined., Methods: Gastric biopsy specimens were collected to detect H. pylori infection at multiple centers in Adelaide, South Australia, between 1998 and 2017. The geospatial distribution of antibiotic-resistant H. pylori in the Greater Adelaide region was plotted using choropleth maps. Moran's I was used to assess geospatial correlation, and multivariate linear regression (MLR) was used to examine associations between migration status, socioeconomic status, age, gender, and rates of H. pylori positivity and antibiotic resistance. Geographically weighted regression (GWR) was used to determine the extent to which the associations varied according to geospatial location., Results: Of 20 108 biopsies across 136 postcodes within the Greater Adelaide region, 1901 (9.45%) were H. pylori positive. Of these, 797 (41.9%) displayed clarithromycin, tetracycline, metronidazole, or amoxicillin resistance. In MLR, migration status was associated with the rate of H. pylori positivity (β = 3.85% per 10% increase in a postcode's migrant population; P < 0.001). H. pylori positivity and resistance to any antibiotic were geospatially clustered (Moran's I = 0.571 and 0.280, respectively; P < 0.001 for both). In GWR, there was significant geospatial variation in the strength of the migrant association for both H. pylori positivity and antibiotic resistance., Conclusion: Our study demonstrates the heterogeneous geospatial distribution of H. pylori positivity and antibiotic resistance, as well as its interaction with migrant status. Geographic location and migrant status are important factors to consider for H. pylori eradication therapy., (© 2022 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The majority of the Australian public are willing to have a Coronavirus disease 2019 (COVID-19) vaccination. It is unclear whether people with inflammatory bowel disease (IBD) have the same attitude towards COVID-19 vaccination. A survey was performed to assess the attitude of patients with IBD towards COVID-19 vaccination in South Australia. Two-thirds of surveyed patients with IBD were willing to accept COVID-19 vaccine. Females and younger patients were less likely to accept the COVID-19 vaccine, as were those who had never had a discussion around vaccines., (© 2022 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background and Aims: No consensus exists on defining intestinal ultrasound response, transmural healing, or transmural remission in inflammatory bowel disease, nor clear guidance for optimal timing of assessment during treatment. This systematic review and expert consensus study aimed to define such recommendations, along with key parameters included in response reporting., Methods: Electronic databases were searched from inception to July 26, 2021, using pre-defined terms. Studies were eligible if at least two intestinal ultrasound [IUS] assessments at different time points during treatment were reported, along with an appropriate reference standard. The QUADAS-2 tool was used to examine study-level risk of bias. An international panel of experts [n = 18] rated an initial 196 statements [RAND/UCLA process, scale 1-9]. Two videoconferences were conducted, resulting in additional ratings of 149 and 13 statements, respectively., Results: Out of 5826 records, 31 full-text articles, 16 abstracts, and one research letter were included; 83% [40/48] of included studies showed a low concern of applicability, and 96% [46/48] had a high risk of bias. A consensus was reached on 41 statements, with clear definitions of IUS treatment response, transmural healing, transmural remission, timing of assessment, and general considerations when using intestinal ultrasound in inflammatory bowel disease., Conclusions: Response criteria and time points of response assessment varied between studies, complicating direct comparison of parameter changes and their relation to treatment outcomes. To ensure a unified approach in routine care and clinical trials, we provide recommendations and definitions for key parameters for intestinal ultrasound response, to incorporate into future prospective studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: The diagnosis and follow up of patients with inflammatory bowel disease [IBD] requires cross-sectional imaging modalities, such as intestinal ultrasound [IUS], magnetic resonance imaging [MRI] and computed tomography [CT]. The quality and homogeneity of medical reporting are crucial to ensure effective communication between specialists and to improve patient care. The current topical review addresses optimized reporting requirements for cross-sectional imaging in IBD., Methods: An expert consensus panel consisting of gastroenterologists, radiologists and surgeons convened by the ECCO in collaboration with ESGAR performed a systematic literature review covering the reporting aspects of MRI, CT, IUS, endoanal ultrasonography and transperineal ultrasonography in IBD. Practice position statements were developed utilizing a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when ≥80% of the participants agreed on a recommendation., Results: Twenty-five practice positions were developed, establishing standard terminology for optimal reporting in cross-sectional imaging. Assessment of inflammation, complications and imaging of perianal CD are outlined. The minimum requirements of a standardized report, including a list of essential reporting items, have been defined., Conclusions: This topical review offers practice recommendations to optimize and homogenize reporting in cross-sectional imaging in IBD., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)