Background:Tofacitinib, filgotinib, and upadacitinib are Janus kinase inhibitors (JAKi) that have demonstrated efficacy in ulcerative colitis (UC) against placebo. This study aims to compare the clinical efficacy between these drugs. Methods:This is a multicentered, retrospective cohort study. Patients with UC starting a JAKi were recruited between 2018 and 2024 when starting their first JAKi. Clinical remission and response, based on clinical scores, calprotectin, and endoscopic measurement, were assessed at 3 and 6 months. Both independent and combined variable outcomes were analyzed. Results:Two hundred and seventy patients were included in the analysis, of which 70 (26%) were on upadacitinib, 51 (19%) on filgotinib, and 149 (55%) on tofacitinib. Clinical, biochemical, and endoscopic remission at 6 months was 91%, 71%, and 80% for upadacitinib; 78%, 67%, and 50% for filgotinib; 73%, 51%, and 44% for tofacitinib. Upadacitinib demonstrated significantly greater clinical response (P = .027) and remission (P = .037) rates at 6 months than tofacitinib. Drug persistence at 12 months was 86% for upadacitinib, 72% for filgotinib, and 69% for tofacitinib. Upadacitinib demonstrated significantly greater 6-month remission rates compared to tofacitinib in the bio-exposed cohort (71% vs 52%, P = .022) and in the bio-naïve cohort (93% vs 50%, P = .009). The incidence rates for hospital admissions were 10.2, 21.9, and 14.1 and for colectomies were 6.7, 10.0, and 5.0 per 1000 patient-months at risk for upadacitinib, filgotinib and tofacitinib, respectively. Conclusion:This study demonstrates that upadacitinib is more likely to achieve 6-month response and remission compared to tofacitinib. In both bio-naïve and bio-exposed patients, upadacitinib was more likely to achieve remission at 6 months. The efficacy of JAKi does not appear diminished by prior biologic use.

Objective The incidence rate of inflammatory bowel disease (IBD) in England is 37/100 000 patient years. There is limited literature on IBD outcomes in prison populations. We aimed to determine differences in outcomes for patients with IBD who have spent time in prison. Method Prisoners seen in the IBD clinic at our trust were identified electronically. A control cohort (1:2) was selected using the patients from the same clinic in the two neighbouring slots and matched by gender. Demographic, disease-specific and process-based variables, including time from diagnosis to clinic and final clinical contact, were identified. Results A total of 151 male patients with IBD was identified (53 prisoners and 98 controls). Of the imprisoned patients, 24/53 (45%) were newly diagnosed patients, of which two were diagnosed at emergency admission. This demonstrates a prisoner IBD incidence rate to be 88.5/100 000 patient years. 29/53 (55%) were known patients with IBD transferred in services during imprisonment. The median follow-up was 16.9 (IQR 7.4-40.9) months and 48.6 (19.1-112.0) months in the prisoners and controls, respectively. The 'Did not attend or DNA' rate was 78.6 per 1000 patient months versus 22.2 (p<0.001), respectively. The incidence rate among prisoners compared with controls for patients transferred in for steroid use was 20.8 per 1000 patient months versus 4.08 (p<0.001), the incidence rate for initiation or switch in advanced therapy was 11.7 vs 2.91 (p=0.004) and the incidence rate for hospital admission was 13.1 vs 3.2 (p=0.002). Conclusion There was a higher frequency of steroid use, initiation or switch in advanced therapy and hospital admission in prisoners, suggesting greater treatment needs. These findings warrant further investigation.

Objective Participation in clinical research confers tangible benefits for patients and healthcare organisations. Achieving adequate and representative recruitment into studies remains challenging, and variable recruitment rates between different hospitals and studies are well-known challenges. This study aims to characterise recruitment patterns across England’s secondary and tertiary care National Health Service (NHS) Trusts registered on the National Institute for Health and Care Research (NIHR) Clinical Research Network (CRN) portfolio. Design/method Recruitment data submitted to the NIHR portfolio was extracted for all Gastroenterology and Hepatology studies that were actively recruiting between the period 1 April 2014 to 31 March 2024. All NHS Trusts within the UK were categorised into either secondary or tertiary care hospitals. We evaluated recruitment patterns, study distribution and temporal trends, comparing performance between secondary and tertiary sites, subspecialties and study designs. Results Of 346 hospital sites involved in study recruitment, 262 (76%) were secondary care hospitals and 84 (24%) were tertiary centres. A total of 853 studies were identified, with 485 (57%) being Gastroenterology-specific studies, recruiting 1 92 800 patients (79%), while Hepatology had 368 (43%) studies, recruiting 48 800 (21%) patients. Recruitment into Gastroenterology-specific studies was equally distributed between secondary and tertiary sites (51:49, p=0.69). 71% (p<0.01) of recruitment into Hepatology studies came from tertiary sites. Conclusion While Gastroenterology-specific studies showed similar recruitment volumes between secondary and tertiary care, recruitment into Hepatology studies remained predominantly from tertiary centres. Future work should focus on building Gastroenterology and Hepatology research delivery capability and capacity, while aligning with the recommendations from the Lord O’Shaughnessy report.

Objective Telemonitoring has the potential to improve healthcare delivery. While the field continues to develop, ensuring interventions are accessible across disease populations is essential for successful clinical translation. This systematic review of telemonitoring aims to understand the generalisability of study findings in the distinctly different patient cohorts of inflammatory bowel disease (IBD) and decompensated cirrhosis, focusing on differences in sociodemographic characteristics.Design/method Relevant studies were identified by searching Ovid MEDLINE, EMBASE and Cochrane databases from 2013 to January 2024. A narrative review was conducted.Results 27 studies with 3806 patients were included. IBD-based studies predominated (n=23, 85%) with four (15%) studies in patients with decompensated cirrhosis. All studies were undertaken in high-income economies. While age and gender were documented in most studies, only 11% documented ethnicity, 33% documented socioeconomic status and 33% documented education status. Substance misuse with alcohol, smoking or other illicit drugs was documented in 7%. Multiple languages were available in 15% of studies. There was significant heterogeneity in endpoints used across studies investigating interventions in both patient cohorts.Conclusions This systematic review demonstrates the lack of reporting in critical demographic domains with significant heterogeneity in study design and endpoints across both disease processes. This potentially limits the use of telemonitoring outside of a trial setting. To improve real-world implementation and reduce the impact of health inequalities, it is critical that a consensus is reached for minimum reporting standards for telemedicine interventions.PROSPERO registration number CRD42024497369.

Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). Similar to other chronic diseases, IBD is associated with negative mental health outcomes. The prevalence of anxiety and depression with IBD is increasing in western societies and there is a growing body of evidence suggesting a bidirectional relationship which remains poorly understood. This review seeks to distil current evidence on the epidemiology, biological mechanisms and microbial changes through which anxiety and depression may lead to worse IBD outcomes. The literature demonstrates that a prior diagnosis of depression is associated with an increased risk of developing IBD. Co-morbid anxiety or depression doubles the odds of adverse outcomes in IBD. Antidepressants appear to have class dependent effects on modulating disease activity in IBD with co-morbid depression. Chronic stress may drive IBD through a number of mechanisms, including inducing the hypothalamic pituitary axis, glucocorticoid resistance, increasing intestinal permeability, and releasing inflammatory cytokines. Alterations in the microbiome on either a genus or species' level has been shown to be affected by and have an impact on both mental health illness and IBD activity. Further research with high quality longitudinal follow-up data is required to clarify causal associations of anxiety/depression and IBD onset as well as measure the impact of different antidepressant classes and microbiome targeted strategies on disease progression and outcomes.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract with increasing rates of incidence and prevalence across the world. Complex inflammatory and prothrombotic pathophysiology in IBD makes venous thromboembolism (VTE) a common complication with significant morbidity and mortality. This risk is increased in pregnancy. As we continue to understand the pathogenesis of IBD, this article highlights the continued risk of VTE following discharge, for which there is currently no clear guidance, yet the risk of VTE remains high. Furthermore, we discuss this increased VTE risk in the context of pregnant IBD patients and the relevant current guidelines. Alongside this, medications that are used to manage IBD carry their own thrombotic risk, which clinicians should be aware of. Assessing VTE risks in IBD populations using newer medications should be a focus of future research.

Trainee research networks are a collaborative effort to enable high-quality multicentre audits or research that is more widely accessible to trainees. Such networks lead, design and deliver research at a far higher scale than could be achieved locally and are carried out solely by trainees. There is an increasing focus on delivering research that is not only environmentally sustainable but also focuses on areas that can reduce the carbon footprint of service provision in gastroenterology and hepatology. In this manuscript, we performed a scoping review to understand the current evidence base of the impact of gastroenterology and hepatology services on the environment as well as exploring any association between pollution and climate change with gastrointestinal and liver disease. We further discuss the barriers that researchers face in delivering environmentally sustainable research, the limitation in clinical guidelines related to practicing environmentally sustainable gastroenterology and hepatology and how the trainee research networks are ideally placed to initiate change by developing, disseminating and implementing best practice in 'green Gastroenterology'.

Background: While surgery plays a pivotal role in the management of ileal Crohn's disease, the risk of endoscopic recurrence following an ileocaecal resection can be greater than 65% within 12 months of surgery. More than 90% of patients with Crohn's disease have a concomitant diagnosis of bile acid diarrhea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in patients with Crohn's disease who have undergone a primary terminal ileal resection with concomitant bile acid diarrhea can alter the microbiome and prevent disease recurrence. Methods: Patients with Crohn's disease who underwent a primary terminal ileal resection and had symptoms of diarrhea within 1-3 months of surgery underwent (75)SeHCAT testing for bile acid diarrhea. If positive ((75)SeHCAT <= 15%), patients were treated with colesevelam and stool samples were collected at 4 weeks, 8 weeks, and 6-12 months posttreatment. If negative ((75)SeHCAT > 15%), treatment was not given and were reviewed in the clinic as per local guidelines. All patients underwent a 6-12 month postoperative colonoscopy where further stool samples and mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert's score, with disease remission defined as Rutgeert's score = i2. 16S ribosomal RNA gene analysis was undertaken for the collected fecal and mucosal samples to assess alpha/beta-diversity and microbial composition. Results: A total of 14 patients who completed the study, 10 of whom had a (75)SeHCAT positive diagnosis of bile acid diarrhea and were started on treatment with colesevelam. Four patients did not require treatment as 3 were asymptomatic and 1 had a negative( 75)SeHCAT scan. Three of the fourteen patients had disease recurrence at their 6-12 month postoperative colonoscopy assessment, of which 1 patient was taking colesevelam and 2 patients were not taking colesevelam. A total of 44 fecal samples and 44 mucosal biopsies underwent 16S ribosomal RNA gene analysis to assess alpha/beta-diversity and microbial composition. In the colesevelam treated patients there was no significant difference in alpha/beta-diversity pre- and posttreatment. Pretreatment, the 3 most abundant bacterial classes in all patients were Bacteroidia, Clostridia, and Gammaproteobacteria. Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the 2 patients not given colesevelam, one showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria. Conclusions: This small pilot study demonstrated that patients who were given colesevelam, were more likely to be in disease remission at their 6-12 months colonoscopy review compared with those not treated. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in postoperative Crohn's disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance as well as investigate whether this benefit may be present even in those patients with (75)SeHCAT negative disease.

Inflammatory bowel disease (IBD) is a complex, multisystemic disease and is associated with ocular pathology in 4–12% of patients. In general, ocular disease affects Crohn’s patients more frequently than those with ulcerative colitis. Episcleritis and uveitis are the most common presentations, with episcleritis often correlating with IBD flares, whereas uveitis presents independently of IBD activity and, in some cases, may even alert clinicians to a new diagnosis of IBD. Corneal EIMs encompass a range of pathologies, such as the common and benign keratoconjunctivitis sicca (dry eye disease), which nevertheless causes significant patient discomfort, and the rarer condition of peripheral ulcerative keratitis, which warrants urgent review due to the risk of corneal perforation. Alongside EIMs, clinicians should also be aware of the iatrogenic consequences to the eye following treatment of IBD. Corticosteroids may cause cataracts, glaucoma, and—indirectly via hyperglycaemia—diabetic retinopathy. Methotrexate is irritating to ocular tissues and may cause conjunctivitis and blepharitis. Biologic medications, such as anti-TNFα agents, overlap in their use as treatment of both IBD and uveitis, and yet in some patients may also increase the risk of acute uveitis flares, as well as opportunistic, sight-threatening infections. With integrated care between gastroenterology and ophthalmology, patient outcomes can be improved by facilitating earlier detection and management of ocular disease. This narrative review summarises the ocular extraintestinal manifestations of IBD, including pathophysiology, epidemiology, and current treatment strategies.

Inflammatory bowel disease is a complex and debilitating disease which is known to cause mental burden for patients. Even though few studies look at mental health disease in this cohort of patients, there is growing evidence of a correlation between disease activity and prevalence of mental health conditions such as anxiety, depression and post-traumatic stress disorder. In this literature review, the relationship between inflammatory bowel disease and mental health disorders is explored, with an emphasis on recognition, screening and therapeutic options and special considerations for these complex comorbidities. The relationship between medical and psychological disease is not often considered and less well understood and there is a need for further research in these fields. Patients would have much to gain both medically and psychologically from a multidisciplinary approach to this chronic disease association.

IntroductionBile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity.Materials and methodsPatients with symptoms of diarrhoea underwent 75-selenium homocholic acid (75SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn’s disease BAD and 75SeHCAT negative control group. Patients with a positive 75SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6–12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken.ResultsA total of 257 samples were analysed from 134 patients. α-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%); p < 0.05. Colesevelam did not alter bacterial α/β-diversity but patients who clinically responded to treatment had a significantly greater abundance of Fusobacteria and Ruminococcus, both of which aid in the conversion of primary to secondary bile acids.ConclusionThis is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.

Abstract Background Bile Acid Diarrhoea (BAD) is a common gastrointestinal condition estimated to affect 1% of the population. It is, however, significantly under-diagnosed. This is partly due to lack of diagnostic methods. In the United Kingdom (UK) the 75-SeHCAT retention scan is considered the gold-standard diagnostic method and is the only routinely available diagnostic test for BAD. SeHCAT retention of <15% is considered consistent with BAD. The SeHCAT test is, however, expensive, time consuming, and exposes the patient to a dose of radiation. 7-alpha-hydroxy-4-cholesten-3-one (7αC4) is a precursor in the bile acid synthesis pathway and has demonstrated utility as a marker of BAD. There is limited data comparing 7αC4, which is measured in the United States, to the SeHCAT test, as SeHCAT is not licensed in the United States. 7αC4 can be measured by LC-MS/MS, thus can provide a more convenient, low cost and high throughput option for diagnosis of BAD. Aims 1) To develop and validate an LC-MS/MS method for analysis of 7αC4. 2) To analyse serum samples taken from patients referred for SeHCAT scans. 3) To determine the utility of 7αC4 compared to SeHCAT for diagnosis of BAD. Methods The method was adapted from Donato et al. 750 µL of ice-cold acetonitrile containing 50 nmol/L D7-7αC4 as internal standard was added to 250 µL serum. Samples were vortexed for 30 s, centrifuged at 3000g for 10 min, and supernatant transferred into a vial for LC-MS/MS analysis. The LC-MS/MS system utilised a Gemini 5um NX-C18 column coupled to a Sciex 6500 TripleQuad mass spectrometer. Ethical approval was obtained to collect serum on patients undergoing SeHCAT retention scans for investigation of BAD. 40 patients who attended for SeHCAT scans had serum collected and stored at −80 degrees Celsius until analysis for 7αC4. Sensitivity and specificity of 7αC4 was calculated and ROC curve analysis performed. Results The 7αC4 method demonstrated an LoQ of 1.5 nmol/L, linearity up to 1095 nmol/L, and intra-assay %CV of 3.0%–7.7%. Using SeHCAT retention of <15% as positive for BAD, ROC curve analysis demonstrated an AUC of 0.765. 7aC4 at a concentration of 175 nmol/L provided a sensitivity of 30% and a specificity of 92%. 7αC4 at a concentration of 50 nmol/L provided a sensitivity of 93% and a specificity of 46%. Conclusion The 7αC4 method demonstrated good analytical performance and was suitable for use in a routine laboratory. 7αC4 results of <50 nmol/L suggest BAD is unlikely, and results of >175 nmol/L make a diagnosis of BAD likely. Results in between these two values may be considered indeterminate and referral for SeHCAT scanning may be considered appropriate. The 7αC4 assay provides an opportunity to stratify patients for SeHCAT testing in the UK, improving diagnosis and management of BAD in patients with chronic diarrhoea and streamlining the patient pathway.