Substantial cost savings of ultrasound-based management over magnetic resonance imaging-based management in an inflammatory bowel disease service.

BACKGROUND: Imaging is used to monitor disease activity in small bowel Crohn's disease (CD). Magnetic Resonance Enterography is often employed as a first modality in the United Kingdom for assessment and monitoring; however, waiting times, cost, patient burden and limited access are significant. It is as yet uncertain if small bowel intestinal ultrasound (IUS) may be a quicker, more acceptable, and cheaper alternative for monitoring patients with CD. METHODS: A clinical service evaluation of imaging pathways was undertaken at a single NHS site in England, United Kingdom. Data were collected about patients who were referred and underwent an imaging analysis for their IBD. Only patients who underwent a therapy change were included in the analysis. Data were collected from care episodes between 01 January 2021-30 March 2022. RESULTS: A combined total of 193 patient care episodes were reviewed, 107 from the IUS pathway and 86 from the MRE pathway. Estimated costs per patient in the IUS pathway was £78.86, and £375.35 per patient in the MRE pathway. The MRE pathway had an average time from referral to treatment initiation of 91 days (SD= ±61) with patients in the IUS pathway waiting an average of 46 days (SD= ±17). CONCLUSIONS: Findings from this work indicate that IUS is a potential cost-saving option when compared to MRE when used in the management of CD. This is in addition to the cost difference of the radiological modalities. A large, multicentre, prospective study is needed to validate these initial findings.

What is already known on this topic ­ Ultrasound is a quick and accurate imaging investigation for patients living with Crohn's disease. Its effect on the cost utility of an Inflammatory Bowel Disease service is unknown.What this study adds ­ This work provides initial data suggesting that an ultrasound-based service may provide significant cost savings when compared to a magnetic resonance imaging-based service.How this study might affect research, practice, or policy ­ This work is part of a larger programme of work to investigate the barriers to wider ultrasound implementation in UK IBD services. This work will contribute to the design of an implementation and training package for intestinal ultrasound in the UK.

Association between body mass index and age of disease onset with clinical outcomes in paediatric-onset Crohn's Disease (CD): a UK nation-wide analyses using the NIHR-IBD BioResource.

BACKGROUND: The evidence on the relationship between adiposity and disease outcomes in paediatric Crohn's disease (CD) is limited and lacks consensus. AIM: To investigate the relationship between (a) body mass index (BMI) and clinical CD outcomes (hospitalisation, surgery, disease behaviour, biologic use, extra-intestinal manifestations (EIMs)) and (b) the age of CD onset with clinical outcomes. DESIGN: Clinical outcomes were examined in CD patients diagnosed at age <17 years and enroled in the National Institute for Health Research IBD-UK BioResource at a median age of 24 years. All outcomes and BMI were recorded at the time of enrolment. Participants were categorised into normal (<25 kg/m2) and high (≥25 kg/m2) BMI. Age at disease diagnosis was categorised into pre-puberty/early puberty (<11 years), puberty (11-14 years) and post-puberty (15-17 years). Spearman rank correlation was used to test the associations between continuous variables and chi-square test to compare categorical variables. RESULTS: 848 participants with CD were included (51.8% males) and median age at diagnosis was 14 years. Participants with high BMI experienced a greater frequency of EIMs (P = 0.05) than those with low BMI (1 type of EIM: 18.5% vs. 13.2%, respectively; ≥2 types of EIMs: 7.8% vs. 5.6%, respectively). Age at diagnosis and BMI showed weak correlations with corticosteroid use (ρ = 0.08, P = 0.03 and ρ = -0.09, P = 0.01; respectively). An early diagnosis (<11 years) was associated with higher occurrence of stenosing and penetrating disease behaviour (P = 0.01) and hospitalisations (P < 0.001). CONCLUSIONS: A higher BMI and an earlier age of disease onset are associated with worse CD clinical presentation.

Safety and efficacy of autologous haematopoietic stem-cell transplantation with low-dose cyclophosphamide mobilisation and reduced intensity conditioning versus standard of care in refractory Crohn's disease (ASTIClite): an open-label, multicentre, randomised controlled trial.

BACKGROUND: A previous controlled trial of autologous haematopoietic stem-cell transplantation (HSCT) in patients with refractory Crohn's disease did not meet its primary endpoint and reported high toxicity. We aimed to assess the safety and efficacy of HSCT with an immune-ablative regimen of reduced intensity versus standard of care in this patient population. METHODS: This open-label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18-60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease [SES-CD] ulcer sub-score of ≥2) refractory to two or more classes of biological therapy, with no perianal or intra-abdominal sepsis or clinically significant comorbidity, were recruited. Participants were centrally randomly assigned (2:1) to either HSCT with a reduced dose of cyclophosphamide (intervention group) or standard care (control group). Randomisation was stratified by trial site by use of random permuted blocks of size 3 and 6. Patients in the intervention group underwent stem-cell mobilisation (cyclophosphamide 1 g/m2 with granulocyte colony-stimulating factor (G-CSF) 5 µg/kg) and stem-cell harvest (minimum 2·0 × 106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin [thymoglobulin] 7·5 mg/kg in total) and subsequent stem-cell reinfusion supported by G-CSF. Patients in the control group continued any available conventional, biological, or nutritional therapy. The primary outcome was absence of endoscopic ulceration (SES-CD ulcer sub-score of 0) without surgery or death at week 48, analysed in the intention-to-treat population by central reading. This trial is registered with the ISRCTN registry, 17160440. FINDINGS: Between Oct 18, 2018, and Nov 8, 2019, 49 patients were screened for eligibility, of whom 23 (47%) were randomly assigned: 13 (57%) to the intervention group and ten (43%) to the control group. In the intervention group, ten (77%) participants underwent HSCT and nine (69%) reached 48-week follow-up; in the control group, nine (90%) reached 48-week follow-up. The trial was halted in response to nine reported suspected unexpected serious adverse reactions in six (46%) patients in the intervention group, including renal failure due to proven thrombotic microangiopathy in three participants and one death due to pulmonary veno-occlusive disease. At week 48, absence of endoscopic ulceration without surgery or death was reported in three (43%) of seven participants in the intervention group and in none of six participants in the control group with available data. Serious adverse events were more frequent in the intervention group (38 in 13 [100%] patients) than in the control group (16 in four [40%] patients). A second patient in the intervention group died after week 48 of respiratory and renal failure. INTERPRETATION: Although HSCT with an immune-ablative regimen of reduced intensity decreased endoscopic disease activity, significant adverse events deem this regimen unsuitable for future clinical use in patients with refractory Crohn's disease. FUNDING: Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial.

BACKGROUND: Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies. METHODS: PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP >upper limit of normal or faecal calprotectin ≥200 µg/g, or both), while remission was the converse-ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 µg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228). FINDINGS: Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0-191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker-treatment interaction effect (absolute difference 1 percentage points, 95% CI -15 to 15; p=0·944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p<0·0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infections (three vs eight). INTERPRETATION: Top-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease. FUNDING: Wellcome and PredictImmune Ltd.

Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial.

INTRODUCTION: Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC. METHODS AND ANALYSIS: In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score <2B.0), endoscopic remission and symptomatic remission (group 3). Treatment is escalated using vedolizumab according to a treatment algorithm that is dependent on the patient's baseline UC therapy until the target is achieved at weeks 16, 32 or 48. The primary outcome, the time from target achievement to a UC-related complication, will be compared between groups 1 and 3 using a Cox proportional hazards model. ETHICS AND DISSEMINATION: The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. A full list of ethics committees is available on request. Study results will be disseminated in peer-reviewed journals and at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT: 2019-002485-12; NCT04259138.

Digital pathology for reporting histopathology samples, including cancer screening samples - definitive evidence from a multisite study.

AIMS: To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples. METHODS: A total of 2024 cases (608 breast, 607 GI, 609 skin, 200 renal) were studied, including 207 breast and 250 bowel cancer screening samples. Cases were examined by four pathologists (16 study pathologists across the four speciality groups), using both LM and DP, with the order randomly assigned and 6 weeks between viewings. Reports were compared for clinical management concordance (CMC), meaning identical diagnoses plus differences which do not affect patient management. Percentage CMCs were computed using logistic regression models with crossed random-effects terms for case and pathologist. The obtained percentage CMCs were referenced to 98.3% calculated from previous studies. RESULTS: For all cases LM versus DP comparisons showed the CMC rates were 99.95% [95% confidence interval (CI) = 99.90-99.97] and 98.96 (95% CI = 98.42-99.32) for cancer screening samples. In speciality groups CMC for LM versus DP showed: breast 99.40% (99.06-99.62) overall and 96.27% (94.63-97.43) for cancer screening samples; [gastrointestinal (GI) = 99.96% (99.89-99.99)] overall and 99.93% (99.68-99.98) for bowel cancer screening samples; skin 99.99% (99.92-100.0); renal 99.99% (99.57-100.0). Analysis of clinically significant differences revealed discrepancies in areas where interobserver variability is known to be high, in reads performed with both modalities and without apparent trends to either. CONCLUSIONS: Comparing LM and DP CMC, overall rates exceed the reference 98.3%, providing compelling evidence that pathologists provide equivalent results for both routine and cancer screening samples irrespective of the modality used.

Biologic therapy for inflammatory bowel disease: Real-world comparative effectiveness and impact of drug sequencing in 13,222 patients within the UK IBD BioResource.

BACKGROUND AND AIMS: To compare effectiveness of different biologic therapies and sequences in patients with Inflammatory Bowel Disease (IBD) using real-world data from a large cohort with long exposure. METHODS: Demographic, disease, treatment and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan-Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups. RESULTS: 13,222 evaluable patients received at least one biologic. In ulcerative colitis (UC) first line vedolizumab (VDZ) demonstrated superior effectiveness over five years compared to anti-TNF agents (p=0.006). VDZ was superior to both infliximab (IFX) and adalimumab (ADA) after ADA and IFX failure respectively (p<0.001 and p<0.001). Anti-TNF therapy showed similar effectiveness when used first-line, or after failure of VDZ. In Crohn's disease (CD) we found significant differences between first line treatments over ten years (p=0.045), with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first line anti-TNF failure in CD (p=0.035). Patients with UC or CD experiencing TNF-failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF. CONCLUSIONS: We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF.

Systematic review: Sarcopenia in paediatric inflammatory bowel disease.

BACKGROUND: Low skeletal muscle mass (MM) and deteriorated function (sarcopenia) can be a frequent complication in paediatric inflammatory bowel disease (IBD). AIM: To conduct a systematic review of the paediatric IBD literature on skeletal muscle function and mass and identify interventions that could affect them. METHODS: Systematic searches (EMBASE, Medline, Cochrane library central for registered control trials and Web of Science) were conducted using the terms 'lean body mass' (LM), 'fat free mass' (FFM) or 'MM' and 'IBD'. RESULTS: Fourteenth studies were included, presenting data from 439 Crohn's disease (CD), 139 ulcerative colitis (UC) and 2 IBD-unclassified participants compared with healthy matched or unmatched groups or reference populations. Six out of 14 studies reported lower LM, whilst 7 studies observed lower MM and FFM in CD patients compared to healthy controls. Research in UC patients reported lower LM in 3 studies, lower MM in 3 studies and lower FFM in 4 studies. Three prospective studies measured the impact of enteral feeding and showed improvement on disease activity and LM or FFM, while one retrospective study did not show any impact on LM. CONCLUSION: Despite the variety of experimental approaches and methods used to assess sarcopenia, most studies showed reduction in MM, LM and FFM in IBD. Nutritional intervention may have a positive effect on LM and FFM. Future research should focus on standardizing the terminology and methodologies used in assessing body composition and investigating sarcopenia in diseased and matched healthy control cohorts in adequately powered studies with a longitudinal design.

Systematic review with meta-analysis: Medical therapies for treatment of ulcerative proctitis.

BACKGROUND: Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat. AIM: To assess the efficacy of medical treatments for UP. METHODS: We searched MEDLINE, EMBASE, and CENTRAL on 23 November 2022 for randomised controlled trials (RCTs) of medical therapy for adults with UP. Primary outcomes included induction and maintenance of clinical remission. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome. RESULTS: We included 53 RCTs (n = 4096) including 46 induction studies (n = 3731) and seven maintenance studies (n = 365). First-line therapies included topical 5-aminosalicylic acid (5-ASA), conventional corticosteroids, budesonide, and oral 5-ASA. Therapy for refractory UP included topical tacrolimus and small molecules. Topical 5-ASA was superior to placebo for induction (RR 2.72, 95% CI 1.94-3.82) and maintenance of remission (RR 2.09, 95% CI 1.26-3.46). Topical corticosteroids were superior to placebo for induction of remission (RR 2.83, 95% CI 1.62-4.92). Topical budesonide was superior to placebo for induction of remission (RR 2.34, 95% CI 1.44-3.81). Combination therapy with topical 5-ASA and topical corticosteroids was superior to topical monotherapy with either agent. Topical tacrolimus was superior to placebo. Etrasimod was superior to placebo for induction (RR 4.71, 95% CI 1.2-18.49) and maintenance of remission (RR 2.08, 95% CI 1.31-3.32). CONCLUSIONS: Topical 5-ASA and corticosteroids are effective for active UP. Topical 5-ASA may be effective for maintenance of remission. Tacrolimus may be effective for induction of remission. Etrasimod may be effective for induction and for maintenance of remission. Trials should include UP to expand the evidence base for this under-represented population.

In Vitro and in Vivo Assays for Testing Retinoids Effect on Intestinal Progenitors' Lineage Commitments.

The intestine consists of epithelial cells surrounded by a complex environment as mesenchymal cells and the gut microbiota. With its impressive stem cell regeneration capability, the intestine is able to constantly replenish cells lost through apoptosis or abrasion by food passing through. Over the past decade, researchers have identified signaling pathways involved in stem cell homeostasis such as retinoids pathway. Retinoids are also involved in cell differentiation of healthy and cancer cells. In this study, we describe several approaches in vitro and in vivo to further investigate the effect of retinoids on stem cells, progenitors, and differentiated intestinal cells.

MRI tagging of colonic chyme mixing in healthy subjects: Inter-observer variability and reliability of the measurement with time.

BACKGROUND: Magnetic resonance imaging (MRI) tagging techniques have been applied to the GI tract to assess bowel contractions and content mixing. We aimed to evaluate the dependence of a tagging measurement (for assessing chyme mixing) on inter-observer variability in both the ascending colon (AC) and descending colon (DC) and to investigate the temporal variation and hence reliability of the colonic tagging technique by acquiring multiple measurements over time on healthy participants. METHODS: Two independent datasets of healthy adults were used for the retrospective inter-observer variability (Study 1: 13 datasets and Study 2: 31 datasets), and ten participants were scanned for the prospective temporal variation study following a 1 L mannitol oral preparation. All colonic tagging data were acquired on 3 T MRI scanners. The mean and the standard deviation (SD) maps were generated pixel-by-pixel using custom-written software in MATLAB. The colonic regions of interest were defined using MIPAV software. Bland-Altman plots and scatter plots were used for the inter-observer variability. The mean and SD of all repeated measures for each subject were calculated along with a one-way ANOVA to test for variations with time. RESULTS: Scatter plots and Bland-Altman plots showed a large range of data with low variation and small limits of agreements (<5% CoV). The intraclass correlation coefficient of inter-rater reliability was excellent and 0.97 or above for the AC and DC measurements for both datasets. The temporal variation study shows that there was no significant difference found between the multiple measures with time (p = 0.53, one-way repeated measures ANOVA test). CONCLUSIONS: MRI tagging technique can provide an assessment of colonic chyme mixing. The inter-observer study data showed high inter-rater agreement. The temporal variation study showed some individual variations with time suggesting multiple measurements may be needed to increase accuracy.

Delphi consensus survey: the opinions of patients living with refractory ulcerative proctitis and the health care professionals who care for them.

BACKGROUND: Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive condition but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance, resulting in many patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions related to refractory proctitis disease burden and best practice for management. METHODS: A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease from the UK. A brainstorming stage involving a focus group where the participants came up with an initial list of statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the importance of the statements and provide any additional comments or clarifications. Calculation of mean scores, analysis of comments and revisions were performed to produce a final list of statements. RESULTS: In total, 14 statements were suggested by the focus group at the initial brainstorming stage. Following completion of three Delphi survey rounds, all 14 statements reached consensus following appropriate revision. CONCLUSIONS: We established consensus on the thoughts and opinions related to refractory proctitis from both the experts who manage this disease and the patients living with it. This represents the first step towards developing clinical research data and ultimately the evidence needed for best practice management guidance of this condition.

BSG 2024 IBD guidelines protocol (standard operating procedures).

INTRODUCTION: In the past 5 years, there have been several advances in the management of inflammatory bowel disease (IBD). We aim for a new guideline to update the most recent guideline published in 2019. We present the prospective operating procedure and technical summary protocol in the manuscript. METHODS: 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) will be followed in the development of the guideline, approach as laid out in the GRADE handbook, supported by the WHO. The guideline development group is formed by a variety of disciplines, across both primary and secondary care that took part in an online Delphi process and split into key areas. A final consensus list of thematic questions within a 'patient, intervention, comparison, outcome' format has been produced and agreed in the final phase of the Delphi process.There will be a detailed technical evidence review with source data including systematic reviews appraised with AMSATAR 2 tool (Assessment of multiple systematic reviews), randomised controlled trial data that will be judged for risk of bias with the Cochrane tool and observational studies for safety concerns assessed through the Robins-I tool. Based on the available evidence, some of the recommendations will be based on GRADE while others will be best practice statements.A full Delphi process will be used to make recommendations using online response systems.This set of procedures has been approved by the Clinical Services and Standards Committee, the British Society of Gastroenterology executive board and aligned with IBD UK standards.

The impact of Inflammatory Bowel Disease related fatigue on Health-Related Quality of Life: a qualitative semi-structured interview study.

Background: Fatigue is a frequently reported symptom of Inflammatory Bowel Disease (IBD), having a negative impact on Health-Related Quality of Life (HRQoL). Patients' experiences of this have not been researched in IBD. Methods: Semi-structured interviews were conducted with adults with Crohn's Disease from out-patient clinics in the United Kingdom. Interviews were audio-recorded and transcribed verbatim, then analysed using thematic analysis. Results: Fourteen participant interviews were conducted. Three key themes were identified: 1) 'The new normal' established through adaptation and acceptance; 2) 'Energy as a resource' describing attempts to better manage fatigue through planning and prioritising tasks; 3) 'Keeping healthy' encompasses participants' beliefs that 'good health' allows better management of fatigue. Conclusion: Participants establish a 'new' normality, through maintaining the same or similar level of employment/education activities. However, this is often at the expense of social activities. Further research is required to explore patient led self-management interventions in IBD fatigue.

Acute effects of prior dietary fat ingestion on postprandial metabolic responses to protein and carbohydrate co-ingestion in overweight and obese men: A randomised crossover trial.

BACKGROUND: Obesity and insulin resistance are associated with an impaired sensitivity to anabolic stimuli such as dietary protein (anabolic resistance). Omega-3 polyunsaturated fatty acids (n-3 PUFA) may be protective against the deleterious effects of saturated fatty acids (SFA) on insulin resistance. However, the contribution of excess fat consumption to anabolic and insulin resistance and the interaction between SFA and n-3 PUFA is not well studied. AIM: The primary aim of this study was to investigate the effects of an oral fat pre-load, with or without the partial substitution of SFA with fish oil (FO)-derived n-3 PUFA, on indices of insulin and anabolic sensitivity in response to subsequent dietary protein and carbohydrate (dextrose) co-ingestion. METHODS: Eight middle-aged males with overweight or obesity (52.8 ± 2.0 yr, BMI 31.8 ± 1.4 kg·m-2) ingested either an SFA, or isoenergetic SFA and FO emulsion (FO), or water/control (Con), 4 h prior to a bolus of milk protein and dextrose. RESULTS: Lipid ingestion (in particular FO) impaired the early postprandial uptake of branched chain amino acids (BCAA) into the skeletal muscle in response to protein and dextrose, and attenuated the peak glycaemic response, but was not accompanied by differences in whole body (Matsuda Index: Con: 4.66 ± 0.89, SFA: 5.10 ± 0.94 and FO: 4.07 ± 0.59) or peripheral (forearm glucose netAUC: Con: 521.7 ± 101.7; SFA: 470.2 ± 125.5 and FO: 495.3 ± 101.6 µmol·min-1·100 g lean mass·min [t = 240-420 min]) insulin sensitivity between visits. Postprandial whole body fat oxidation was affected by visit (P = 0.024) with elevated rates in SFA and FO, relative to Con (1.85 ± 0.55; 2.19 ± 0.21 and 0.65 ± 0.35 kJ·h-1·kg-1 lean body mass, respectively), however muscle uptake of free fatty acids (FFA) was unaffected. CONCLUSION: Oral lipid preloads, consisting of SFA and FO, impair the early postprandial BCAA uptake into skeletal muscle, which occurs independent of changes in insulin sensitivity. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov Identifier NCT03146286.

Quantitative Magnetic Resonance Imaging in Perianal Crohn's Disease at 1.5 and 3.0 T: A Feasibility Study.

Perianal Crohn's Disease (pCD) is a common manifestation of Crohn's Disease. Absence of reliable disease measures makes disease monitoring unreliable. Qualitative MRI has been increasingly used for diagnosing and monitoring pCD and has shown potential for assessing response to treatment. Quantitative MRI sequences, such as diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and magnetisation transfer (MT), along with T2 relaxometry, offer opportunities to improve diagnostic capability. Quantitative MRI sequences (DWI, DCE, MT and T2) were used in a cohort of 25 pCD patients before and 12 weeks after biological therapy at two different field strengths (1.5 and 3 T). Disease activity was measured with the Perianal Crohn's Disease Activity index (PDAI) and serum C-reactive protein (CRP). Diseased tissue areas on MRI were defined by a radiologist. A baseline model to predict outcome at 12 weeks was developed. No differences were seen in the quantitative MR measured in the diseased tissue regions from baseline to 12 weeks; however, PDAI and CRP decreased. Baseline PDAI, CRP, T2 relaxometry and surgical history were found to have a moderate ability to predict response after 12 weeks of biological treatment. Validation in larger cohorts with MRI and clinical measures are needed in order to further develop the model.

Diagnostic Accuracy of Non-Invasive Imaging for Detection of Colonic Inflammation in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Endoscopy is the gold standard for objective assessment of colonic disease activity in inflammatory bowel disease (IBD). Non-invasive colonic imaging using bowel ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) may have a role in quantifying colonic disease activity. We reviewed the diagnostic accuracy of these modalities for assessment of endoscopically or histopathologically defined colonic disease activity in IBD. We searched Embase, MEDLINE, and the Web of Science from inception to 20 September 2021. QUADAS-2 was used to evaluate the studies' quality. A meta-analysis was performed using a bivariate model approach separately for MRI and US studies only, and summary receiver operating characteristic (ROC) curves were obtained. CT studies were excluded due to the absence of diagnostic test data. Thirty-seven studies were included. The mean sensitivity and specificity for MRI studies was 0.75 and 0.91, respectively, while for US studies it was 0.82 and 0.90, respectively. The area under the ROC curves (AUC) was 0.88 (95% CI, 0.82 to 0.93) for MRI, and 0.90 (95% CI, 0.75 to 1.00) for US. Both MRI and US show high diagnostic accuracy in the assessment of colonic disease activity in IBD patients.

Review article: The aetiology of fatigue in inflammatory bowel disease and potential therapeutic management strategies.

BACKGROUND: Fatigue is the inability to achieve or maintain an expected work output resulting from central or peripheral mechanisms. The prevalence of inflammatory bowel disease (IBD) fatigue can reach 86% in active disease, persisting in 50%-52% of patients with mild to inactive disease. Fatigue is the commonest reason for work absence in IBD, and patients often report fatigue burden to be greater than that of primary disease symptoms. Relatively few evidence-based treatment options exist, and the aetiology is poorly understood. AIM: To review the available data and suggest a possible aetiology of IBD fatigue and to consider the efficacy of existing management strategies and highlight potential future interventions. METHODS: We reviewed fatigue-related literature in IBD using PubMed database. RESULTS: Disease related factors such as inflammation and pharmacological treatments negatively impact skeletal muscle and brain physiology, likely contributing to fatigue symptoms. Secondary factors such as malnutrition, anaemia, sleep disturbance and psychological comorbidity are potential determinants. Immune profile, faecal microbiota composition and physical fitness differ significantly between fatigued and non-fatigued patients, suggesting these may be aetiological factors. Solution-focused therapy, high-dosage thiamine supplementation and biological therapy may reduce fatigue perception in IBD. The effect of physical activity interventions is inconclusive. CONCLUSIONS: A multimodal approach is likely required to treat IBD fatigue. Established reversible factors like anaemia, micronutrient deficiencies and active disease should initially be resolved. Psychosocial intervention shows potential efficacy in reducing fatigue perception in quiescent disease. Restoring physical deconditioning by exercise training intervention may further improve fatigue burden.

Test-retest assessment of non-contrast MRI sequences to characterise and quantify the small bowel wall in healthy participants.

OBJECTIVE: Quantitative Magnetic Resonance Imaging sequences have been investigated as objective imaging biomarkers of fibrosis and inflammation in Crohn's disease. AIM: To determine the repeatability and inter- and intra-observer agreement of these measures in the prepared small bowel wall. METHODS: Ten healthy participants were scanned at 3 T on 2 separate occasions using T1 and T2 relaxometry, IVIM-DWI and MT sequences. Test-retest repeatability was assessed using the coefficient of variation (CoV) and intra-class correlation coefficients (ICCs) were used to evaluate the intra- and inter-observer agreement RESULTS: Test-retest repeatability in the bowel wall was excellent for apparent diffusion coefficient (ADC), magnetisation transfer ratio (MTR), T1, and diffusion coefficient D (CoV 5%, 7%, 8%, and 10%, respectively), good for perfusion fraction (PF) (CoV 20%) and acceptable for T2 (CoV 21%). Inter-observer agreement was good for the T2, D and ADC (ICC = 0.89, 0.86, 0.76, respectively) and moderate for T1 (ICC = 0.55). Intra-observer agreement was similar to inter-observer agreement. DISCUSSION: This study showed variable results between the different parameters measured. Test-retest repeatability was at least acceptable for all parameters except pseudo-diffusion coefficient D*. Good inter- and intra-observer agreement was obtained for T2, ADC and D, with these parameters performing best in this technical validation study.