Optimising triage of urgent referrals for suspected IBD: results from the Birmingham IBD inception study

Objective: Diagnostic delays in inflammatory bowel disease (IBD) result in adverse outcomes. We report a bespoke diagnostic pathway to assess how best to combine clinical history and faecal calprotectin (FCP) for early diagnosis and efficient resource utilisation. Methods: A rapid-access pathway was implemented for suspected IBD patients referred outside urgent ‘two-week wait’ criteria. Patients were triaged using symptoms and FCP. A 13-point symptom history was taken prediagnosis and clinical indices, including repeat FCP, collected prospectively. Results: Of 767 patients (January 2021–August 2023), 423 were diagnosed with IBD (208 Crohn’s disease (CD), 215 ulcerative colitis (UC)). Most common symptoms in CD were abdominal pain (84%), looser stools (84%) and fatigue (79%) and in UC per-rectal bleeding (94%), urgency (82%) and looser stools (81%). Strongest IBD predictors were blood mixed with stools (CD OR 4.38; 95% CI 2.40–7.98, UC OR 33.68; 15.47–73.33) and weight loss (CD OR 3.39; 2.14–5.38, UC OR 2.33; 1.37–4.00). Repeat FCP testing showed reduction from baseline in non-IBD. Both measurements >100 µg/g (area under the curve (AUC) 0.800) and >200 µg/g (AUC 0.834) collectively predicted IBD. However, a second value ≥220 µg/g considered alone, regardless of the first result, was more accurate (Youden’s index 0.735, AUC 0.923). Modelling symptoms with FCP increased AUC to 0.947. Conclusion: Serial FCP measurement prevents unnecessary colonoscopy. Two FCPs >200 µg/g could stream patients direct to colonoscopy, with two >100 µg/g prompting clinic review. A second result ≥220 µg/g was more accurate than dual-result thresholds. Coupling home FCP testing with key symptoms may form the basis of effective self-referral pathways

Emerging drugs for the treatment of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a rare immune-mediated cholestatic disease for which no medical therapy has been shown to slow disease progression. Consequently, liver transplantation is the only lifesaving intervention for patients, and despite being a rare disease, PSC is the lead indication for transplantation across several European countries. The vast majority of patients (>70%) also develop inflammatory bowel disease (IBD) at some point in their lifetime, which imparts added lifetime risks of hepatobiliary malignancy and colorectal cancer. The rare disease nature, variable and often slow rates of disease progression (years rather than months), and lack of robust surrogate biomarkers for early stage yet high risk disease, represent critical challenges in trial design that have long precluded the development of effective medical treatment. However, the horizon for new treatments is encouraging, given innovative clinical trial programmes led by industry, alongside several investigator-initiated studies. Herein, we outline the current platform of interventional trials in PSC, before discussing emerging areas of therapeutic interest

IS GUT MICROBIOME DIVERSITY IMPORTANT AT IBD ONSET? A SYSTEMATIC REVIEW OF THE LITERATURE AND META-ANALYSIS OF ALPHA DIVERSITY DATA

Introduction Disruption of the gut microbiome has been widely reported in inflammatory bowel disease (IBD), particularly reduced bacterial diversity. Determining the role of this in IBD onset is hampered by a paucity of studies in newly diagnosed disease. We present outputs from a systematic review of the microbiome in pre-treatment IBD. Methods We searched MEDLINE, Embase between inception and December 2022 for any study presenting microbial analysis of patients diagnosed with IBD in the pre-treatment phase. All screening and extractions were done independently in duplicate. Data extracted included all measures of microbial diversity, the source of samples, any reported controls and clinical/patient parameters. Where appropriate, we performed random-effects meta-analysis of standardised mean difference, reporting 95% CI values and sub-grouped by type of IBD. Results 10,805 abstracts were screened and 217 full texts reviewed. Ultimately, 92 studies were included. 22 studies based on high-throughput technologies presented alpha diversity indices from IBD and controls. 86% of these offered a Shannon index. This was therefore used for synthesis and included faecal samples from 405 IBD (116 mixed, 225 Crohn’s disease [CD], 64 Ulcerative colitis [UC]) and 324 healthy controls (HC); alongside mucosal biopsies from 171 CD with 172 symptomatic controls (SC) and 42 UC with 60 SC. 68% of studies were paediatric. 12 studies presented Shannon diversity from faeces vs HC cohorts. The studies were highly heterogenous. Nonetheless, alpha diversity was significantly lower in IBD, across both UC and CD. 7 studies presented Shannon diversity from mucosal biopsies vs SC cohorts. No papers presented mixed IBD, so subtypes were reviewed separately. Heterogeneity was lower across these studies but differences in diversity did not reach significance (see figure 1 ). Conclusions In IBD, faecal bacterial alpha diversity is significantly reduced compared to healthy controls, but mucosal alpha diversity is not in comparison with symptomatic patients without IBD. Factors influencing the faecal stream, such as rapid transit and malabsorption may exaggerate the difference between IBD and healthy. The similarity between mucosal diversity in IBD and symptomatic controls bolsters the view that other factors must be present alongside microbiome disruption to precipitate IBD. These signals will be further explored using secondary analysis of available inception sequencing datasets

Assessment, endoscopy, and treatment in patients with acute severe ulcerative colitis during the COVID-19 pandemic (PROTECT-ASUC): a multicentre, observational, case-control study

BackgroundThere is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. MethodsThe PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov, NCT04411784. FindingsWe included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. InterpretationThe COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders