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Background: Exclusive enteral nutrition (EEN) supplementation of the standard of care (SOC) augments steroid responsiveness in patients with acute severe ulcerative colitis (ASUC). EEN is known to alter gut microbial composition. The present study investigates EEN-driven gut microbial alterations in patients with ASUC and examines their correlations with clinical parameters., Methods: Stool samples from patients with ASUC (n = 44) who received either EEN-supplemented SOC (EEN group; n = 20) or SOC alone (SOC group; n = 24) for 7 days were collected at baseline (day 0) and postintervention (day 7). Microbiome analysis was carried out using 16S ribosomal RNA gene sequencing followed by data processing using QIIME2 and R packages., Results: Seven-day EEN-conjugated corticosteroid therapy in patients with ASUC enhanced the abundances of beneficial bacterial genera Faecalibacterium and Veillonella and reduced the abundance of Sphingomonas (generalized linear model fitted with Lasso regularization with robustness of 100%), while no such improvements in gut microbiota were observed in the SOC group. The EEN-associated taxa correlated with the patient's clinical parameters (serum albumin and C-reactive protein levels). Unlike the SOC group, which retained its preintervention core microbiota, EEN contributed Faecalibacterium prausnitzii, a beneficial gut bacterial taxon, to the gut microbial core. EEN responders showed enhancement of Ligilactobacillus and Veillonella and reduction in Prevotella and Granulicatella. Analysis of baseline gut microbiota showed relative enhancement of certain microbial genera being associated with corticosteroid response and baseline clinical parameters and that this signature could conceivably be used as a predictive tool., Conclusions: Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by beneficial gut microbial changes in patients with ASUC., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Digital collection of patient-reported outcome measures [PROMs] is largely unexplored as a basis for follow-up for patients with ulcerative colitis [UC]. Our aim was to develop a model to predict the likelihood of escalation of therapy or intervention at an outpatient appointment that may be used to rationalize follow-up., Methods: TrueColours-IBD is a web-based, real-time, remote monitoring software that allows longitudinal collection of ePROMs. Data for prediction modelling were derived from a Development Cohort, guided by the TRIPOD statement. Logistic regression modelling used ten candidate items to predict escalation of therapy or intervention. An Escalation of Therapy or Intervention [ETI] calculator was developed, and applied in a Validation Cohort at the same centre., Results: The Development Cohort [n = 66] was recruited in 2016 and followed for 6 months [208 appointments]. From ten items, four significant predictors of ETI were identified: SCCAI, IBD Control-8, faecal calprotectin, and platelets. For practicality, a model with only SCCAI and IBD Control-8, both entered remotely by the patient, without the need for faecal calprotectin or blood tests was selected. Between 2018 and 2020, a Validation Cohort of 538 patients [1188 appointments] was examined. A 5% threshold on the ETI calculator correctly identified 343/388 [88%] escalations and 274/484 [57%] non-escalations., Conclusions: A calculator based on digital, patient-entered data on symptoms and quality of life can predict whether a patient with UC requires escalation of therapy or intervention at an outpatient appointment. This may be used to streamline outpatient appointments for patients with UC., (© The Author(s) 2023. 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.)

Background: Bowel urgency reduces ulcerative colitis patients' quality of life. Mirikizumab, a p19-directed anti-IL-23 antibody, demonstrates ulcerative colitis efficacy. Mirikizumab efficacy to reduce bowel urgency and bowel urgency association with other endpoints were analyzed in 2 Phase 3 trials., Methods: LUCENT-1 (Induction): 1162 patients randomized 3:1 to intravenous 300 mg mirikizumab or placebo every 4 weeks for 12 weeks. LUCENT-2 (Maintenance): 544 mirikizumab responders during induction were re-randomized 2:1 to subcutaneous mirikizumab 200 mg or placebo every 4 weeks for 40 weeks (52 weeks of continuous treatment). Bowel urgency was measured using the Urgency Numeric Rating Scale (0-10); for patients with LUCENT-1 baseline score ≥3, bowel urgency clinically meaningful improvement (≥3-point decrease) and remission (score ≤1) rates in mirikizumab versus placebo groups were compared at Weeks 12 and 52. Associations between bowel urgency and other efficacy endpoints were assessed at Weeks 12 and 52., Results: A significantly higher proportion of mirikizumab patients versus placebo achieved clinically meaningful improvement in bowel urgency and remission at Weeks 12 and 52. Significantly higher percentages of patients achieving bowel urgency clinically meaningful improvement or remission, compared with those who did not, also achieved endpoints for clinical, corticosteroid-free, endoscopic, and symptomatic remission; clinical response; normalized fecal calprotectin and C-reactive protein; and improved quality of life., Conclusions: In patients with ulcerative colitis, bowel urgency improvement was associated with better clinical outcomes than in patients without improvement during induction and maintenance. A greater proportion of mirikizumab patients achieved sustainable bowel urgency improvement and remission compared to placebo patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Patient-reported outcome measures [PROMs] are key to documenting outcomes that matter most to patients and are increasingly important to commissioners of health care seeking value. We report the first series of the ICHOM Standard Set for Inflammatory Bowel Disease [IBD]., Methods: Patients treated for ulcerative colitis [UC] or Crohn's disease [CD] in our centre were offered enrolment into the web-based TrueColours-IBD programme. Through this programme, e-mail prompts linking to validated questionnaires were sent for symptoms, quality of life, and ICHOM IBD outcomes., Results: The first 1299 consecutive patients enrolled [779 UC, 520 CD] were studied with median 270 days of follow-up (interquartile range [IQR] 116, 504). 671 [52%] were female, mean age 42 years (standard deviation [sd] 16), mean body mass index [BMI] 26 [sd 5.3]. At registration, 483 [37%] were using advanced therapies. Median adherence to fortnightly quality of life reporting and quarterly outcomes was 100% [IQR 48, 100%] and 100% [IQR 75, 100%], respectively. In the previous 12 months, prednisolone use was reported by 229 [29%] patients with UC vs 81 [16%] with CD, p <0.001; 202 [16%] for <3 months; and 108 [8%] for >3 months. An IBD-related intervention was reported by 174 [13%] patients, and 80 [6%] reported an unplanned hospital admission. There were high rates of fatigue [50%] and mood disturbance [23%]., Conclusions: Outcomes reported by patients illustrate the scale of the therapeutic deficit in current care. Proof of principle is demonstrated that PROM data can be collected continuously with little burden on health care professionals. This may become a metric for quality improvement programmes or to compare outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Visceral adipose tissue (VAT) has been proposed to play a pathogenic role in Crohn's disease (CD); however, prospective clinical data are lacking. The aim was to evaluate whether VAT, beyond body mass index (BMI), is associated with CD behavior, disease activity, quality of life (QoL), or outcomes., Methods: Body composition data and clinical, anthropometric, disease activity (fecal calprotectin [FC]), and QoL scores were gathered prospectively on adults with CD at 0, 12, and 24 months. BMI and, VAT metrics (visceral adipose tissue volume [cm3]/height [m2] index and VAT:subcutaneous adipose tissue [SAT] ratio) were calculated. Inflammatory bowel disease-related surgery and hospitalization were recorded over extended follow-up (median, 51 months). Multivariable linear mixed effects and logistic regression analyses were performed., Results: Ninety-seven participants were assessed at baseline (55% male; median age, 31 years), 84 at 12 months, and 72 at 24 months. VAT:SAT was positively associated with stricturing disease behavior (log odds ratio [OR], 1.7; 95% confidence interval [CI], 0.32 to 3; P = 0.01) and elevated FC in patients with ileocolonic disease (β, 1.3; 95% CI, 0.32 to 2.3; P = 0.01). VAT:SAT was associated with lower QoL, particularly in those with ileal disease (β, -12; 95% CI, -19 to -4.5; P = 0.05). However, no prospective associations were observed between serial VAT measurements and time to surgery or hospitalization. No correlations were found between BMI and disease behavior, activity, or QoL., Conclusions: VAT:SAT, rather than BMI, is associated with stricturing CD behavior, elevated FC, and reduced QoL in a disease distribution-dependent manner. Further studies are required to substantiate the role of VAT as a useful biomarker in CD., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: During surveillance colonoscopy of patients with long-standing ulcerative colitis [UC], a variety of dysplastic and non-dysplastic lesions are detected. The aim of this study was to address the diagnostic accuracy of endoscopic characterization of endoscopic trimodal imaging [ETMI] and chromoendoscopy [CE]. ETMI includes the combination of autofluorescence imaging [AFI], narrow band imaging [NBI] and white light endoscopy [WLE]., Methods: This is a pre-specified additional analysis of a multi-centre, randomized controlled trial that compared AFI with CE for dysplasia detection in 210 patients with long-standing UC [FIND-UC trial]. In the AFI arm, endoscopists used the ETMI system to record AFI colour, Kudo pit pattern using NBI and WLE for lesion characterization. For AFI, purple colour and ambiguous colour combined with pit pattern type III-V on NBI was considered dysplastic. Kudo pit pattern was described in the CE arm. For pit pattern description using NBI and CE, type III-V was considered dysplastic. Histology was the reference standard., Results: In total, 52 dysplastic and 255 non-dysplastic lesions were detected. Overall sensitivity for real-time prediction of dysplasia was 76.9% (95% confidence interval [CI] 46.2-95.0) for ETMI, and 81.6% [95% CI 65.7-92.3] for CE. Overall negative predictive value [NPV] for ETMI was 96.9% [95% CI 92.0-98.8] and 94.7% [90.2-97.2] for CE., Conclusions: Sensitivity for endoscopic differentiation of dysplastic lesions detected during surveillance of patients with long-standing UC seems limited using ETMI and CE. Future research is warranted as the high NPV indicates that these techniques are valuable for the exclusion of dysplastic lesions [NTR4062].

Background and Aims: Endoscopy and histopathology are pivotal for evaluating disease activity in ulcerative colitis [UC]; correlation between validated endoscopic and histological indices has not been examined. We aim to correlate the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] with two new validated histological indices in patients with established UC., Methods: This was a single-centre cohort of patients with established UC, who underwent flexible sigmoidoscopy or colonoscopy by a single endoscopist. The UCEIS was scored at the worst affected area in the distal colon, which was biopsied; histological disease activity using Nancy [NI] and Robarts' Histological [RHI] indices was scored by a pathologist blinded to the endoscopy. Spearman correlation between the UCEIS, NI, and RHI, and between NI and RHI, was performed., Results: A total of 125 patients, median age 37 years [range 16-81 years], with UCEIS scores [scale 0-8]: 0, n = 21; 1-3, n = 48; 4-6, n = 51; and 7-8, n = 5, were included. Correlation coefficients between UCEIS and NI [scale 0-4] were r = 0.84 (95% confidence interval [CI] 0.76-0.89, p < 0.001) and between UCEIS and RHI [scale 0-33] r = 0.86 [95% CI 0.80-0.90, p < 0.001]. The difference in correlation was not significant [p = 0.57]. There was excellent correlation between the two histological indices [r = 0.92, 95% CI 0.87-0.95, p < 0.001]. Quiescent disease activity defined as the absence of neutrophils [Nancy 0-1, Robarts 0-3] was most closely correlated with UCEIS = 0., Conclusions: The UCEIS strongly correlates with both NI and RHI. Complete mucosal healing is best defined as a UCEIS = 0/8, since this correlates with the absence of microscopic disease activity.

Background and Aims: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for patients with severe, treatment-refractory Crohn's disease [CD]. The evidence base for AHSCT for CD is limited, with one randomised trial [ASTIC] suggesting benefit. The aim of this study was to evaluate safety and efficacy for patients undergoing AHSCT for CD in Europe, outside the ASTIC trial., Methods: We identified 99 patients in the European Society for Blood and Marrow Transplantation [EBMT] registry, who were eligible for inclusion. Transplant and clinical outcomes were obtained for 82 patients from 19 centres in seven countries., Results: Median patient age was 30 years [range 20-65]. Patients had failed or been intolerant to a median of six lines of drug therapy; 61/82 [74%] had had surgery. Following AHSCT, 53/78 [68%] experienced complete remission or significant improvement in symptoms at a median follow-up of 41 months [range 6-174]; 22/82 [27%] required no medical therapy at any point post-AHSCT. In patients who had re-started medical therapy at latest follow-up, 57% [24/42] achieved remission or significant symptomatic improvement with therapies to which they had previously lost response or been non-responsive. Treatment-free survival at 1 year was 54%. On multivariate analysis, perianal disease was associated with adverse treatment-free survival (hazard ratio 2.34, 95% confidence interval [CI] 1.14-4.83, p = 0.02). One patient died due to infectious complications [cytomegalovirus disease] at Day +56., Conclusions: In this multicentre retrospective analysis of European centres, AHSCT was relatively safe and appeared to be effective in controlling otherwise treatment-resistant Crohn's disease. Further prospective randomised controlled trials against standard of care are warranted., (© The Author(s) 2018. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Vedolizumab, a humanised monoclonal antibody for the treatment of inflammatory bowel disease, selectively blocks gut lymphocyte trafficking. This may reduce the risk of respiratory tract infections [RTIs] compared with systemic immunosuppressive therapies. To assess this possibility, we evaluated the rates of RTIs in clinical trials of vedolizumab., Methods: Patient-level data from Phase 3 randomised controlled trials [RCTs] of vedolizumab in ulcerative colitis [UC; GEMINI 1] and Crohn's disease [CD; GEMINI 2], and a long-term safety study [UC and CD] were pooled. Cox proportional hazards models were used to estimate the incidence of upper RTIs [URTIs] and lower RTIs [LRTIs] with adjustment for significant covariates., Results: In the RCTs [n = 1731 patients], the incidence of URTIs was numerically higher in patients receiving vedolizumab compared with those receiving placebo, although this difference was not statistically significant (38.7 vs 33.0 patients per 100 patient-years; hazard ratio [HR] 1.12; 95% confidence interval [CI]: 0.83-1.51; p = 0.463). The rate of LRTIs, including pneumonia, was numerically lower in the vedolizumab versus the placebo group: this difference was not statistically significant (7.7 vs 8.5 per 100 patient-years [HR 0.85; 95% CI: 0.48-1.52; p = 0.585]). Both URTIs and LRTIs were more frequent in patients with CD compared with UC. Most RTIs in patients receiving vedolizumab were not serious and did not require treatment discontinuation., Conclusions: Vedolizumab therapy was not associated with an increased incidence of respiratory tract infection compared with placebo.

Introduction: Patients with inflammatory bowel disease (IBD) undergoing polypectomy are recommended by current guidelines to have biopsies taken from adjacent mucosa to determine whether there is dysplasia present. With improvements in endoscopic imaging, it is now possible to characterize colonic lesions with higher levels of confidence than previously. We have reviewed the diagnostic yield of polyp-adjacent biopsies in IBD., Materials and Methods: A systematic search of our histopathology database revealed cases in which polyps had been endoscopically resected or biopsied in patients with IBD. Endoscopy reports and medical records were reviewed, and patient demographic and disease-specific details were recorded, along with details of polyp characteristics and histopathology outcomes., Results: Three hundred and two polyps were biopsied or resected in 131 patients undergoing 178 colonoscopies. The median polyp size was 4 mm (range 1-45), and the predominant morphology was Paris 0-Is (n = 98, 32%). The histology was tubular adenoma in 76 (25%), tubulovillous adenoma in 14 (5%), hyperplastic in 112 (37%), post-inflammatory in 32 (11%), sessile serrated polyp in 31 (10%), traditional serrated adenoma in 2 (0.7%), flat high-grade dysplasia or cancer in 2 (0.7%) and other in 33 (11%). Dysplasia in adjacent biopsies was detected in 2 patients (0.7%), and was endoscopically visible in both cases. The proportion of endoscopically unsuspected dysplasia was 0/300 (0%, 95% CI 0-1.6%)., Conclusion: The diagnostic yield for polyp-adjacent biopsies in patients with IBD is negligible. With high-definition technology and chromoendoscopy, it may no longer be necessary to biopsy endoscopically normal adjacent tissue to detect invisible dysplasia.

Background and Aims: Early objective markers for failure of intravenous[iv] corticosteroid for acute severe colitis [ASC] can avoid delay in rescue therapy or colectomy. We investigated faecal calprotectin [FC], C-reactive protein [CRP], and endoscopy using the ulcerative colitis endoscopic index of severity [UCEIS] as predictors of steroid failure following intensive therapy of ASC., Methods: Consecutive patients with ASC satisfying Truelove and Witts' criteria, hospitalised at a single centre from May 2015 to November 2016, were included; all received iv corticosteroids. The primary outcome measure was steroid failure defined as colectomy and/or rescue therapy with ciclosporin or infliximab during admission. FC levels were measured at admission and on Day 3 of intensive therapy. UCEIS was scored at admission, and CRP on Day 3 of intensive therapy., Results: Of 49 patients, 21 [43%] failed iv corticosteroids and 15 [31%] underwent surgery. FC levels were significantly higher in steroid failures (2522 [590-9654] µg/g) compared with steroid responders (1530 [352-10278] µg/g) at admission [p = 0.04], as well as on Day 3 of iv corticosteroid therapy (2718 [222-9175] µg/g vs 727 [218-4062] µg/g, p = 0.001). Steroid failures had a higher median [range] UCEIS score than responders (6 [4-8] vs 5 [4-7] [p = 0.001]). CRP level did not differ significantly between steroid failures and responders. A UCEIS > 6 at admission and FC > 1000 µg/g on Day 3 were independent predictors of steroid failure and need for rescue therapy/colectomy., Conclusions: All patients with UCEIS > 6 and Day 3 FC > 1000 µg/g failed iv corticosteroids. The UCEIS score on admission and Day 3 FC are early predictors of failure of ivcorticosteroid therapy., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background and Aims: Histological remission and low faecal calprotectin are positive prognostic factors in ulcerative colitis [UC]. Intramucosal calprotectin [iMC], which can be readily determined by immunohistochemistry, has not so far been evaluated as a predictor of outcome in UC. We aimed to investigate the relationship between iMC and clinical, endoscopic, and histological measures of remission in UC, and the independent prognostic value of iMC., Methods: Ambulant patients with UC were recruited for a study comparing clinical activity indices. Sigmoidoscopy and biopsy were performed at the index visit. Clinical, endoscopic, and histological activity were scored and iMC semi-quantitatively measured using immunohistochemistry for the S100A8/9 heterodimer on colonic biopsies, scored as the mean number of positive cells in five high-power fields [HPF]. At the end of follow-up [6 years], data on steroid use, hospitalisation, and colectomy ['adverse outcomes'] were collected., Results: iMC was determined in 83 patients and 20 controls, and correlated with clinical, endoscopic, and histological activity [r = 0.51, 0.65, 0.53, p > 0.001, respectively]. iMC was lowest (median 2.4, interquartile range [IQR]: 5.2-5, p < 0.001) in patients with concordance between clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcome (hazard ratio [HR] 3.36, confidence interval [CI] 1.58, 7.15, p < 0.001). Only 53%, 33%, and 25% of patients in histological remission with iMC > 5 cells/HPF avoided an adverse outcome after 1, 3, and 6 years, respectively., Conclusions: iMC was lowest in patients with concordant clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcomes despite histological remission. Therefore iMC is a potentially useful independent marker of activity., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background and Aims: Acute severe colitis [ASC] is associated with major morbidity. We aimed to develop and externally validate an index that predicted ASC within 3 years of diagnosis., Methods: The development cohort included patients aged 16-89 years, diagnosed with ulcerative colitis [UC] in Oxford and followed for 3 years. Primary outcome was hospitalization for ASC, excluding patients admitted within 1 month of diagnosis. Multivariable logistic regression examined the adjusted association of seven risk factors with ASC. Backwards elimination produced a parsimonious model that was simplified to create an easy-to-use index. External validation occurred in separate cohorts from Cambridge, UK, and Uppsala, Sweden., Results: The development cohort [Oxford] included 34/111 patients who developed ASC within a median 14 months [range 1-29]. The final model applied the sum of 1 point each for extensive disease, C-reactive protein [CRP] > 10mg/l, or haemoglobin < 12g/dl F or < 14g/dl M at diagnosis, to give a score from 0/3 to 3/3. This predicted a 70% risk of developing ASC within 3 years [score 3/3]. Validation cohorts included different proportions with ASC [Cambridge = 25/96; Uppsala = 18/298]. Of those scoring 3/3 at diagnosis, 18/18 [Cambridge] and 12/13 [Uppsala] subsequently developed ASC. Discriminant ability [c-index, where 1.0 = perfect discrimination] was 0.81 [Oxford], 0.95 [Cambridge], 0.97 [Uppsala]. Internal validation using bootstrapping showed good calibration, with similar predicted risk across all cohorts. A nomogram predicted individual risk., Conclusions: An index applied at diagnosis reliably predicts the risk of ASC within 3 years in different populations. Patients with a score 3/3 at diagnosis may merit early immunomodulator therapy., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background and Aims: To determine whether clinical information influences endoscopic scoring by central readers using the Ulcerative Colitis Endoscopic Index of Severity [UCEIS; comprising 'vascular pattern', 'bleeding', 'erosions and ulcers']., Methods: Forty central readers performed 28 evaluations, including 2 repeats, from a library of 44 video sigmoidoscopies stratified by Mayo Clinic Score. Following training, readers were randomised to scoring with ['unblinded', n = 20, including 4 control videos with misleading information] or without ['blinded', n 20] clinical information. A total of 21 virtual Central Reader Groups [CRGs], of three blinded readers, were created. Agreement criteria were pre-specified. Kappa [κ] statistics quantified intra- and inter-reader variability., Results: Mean UCEIS scores did not differ between blinded and unblinded readers for any of the 40 main videos. UCEIS standard deviations [SD] were similar [median blinded 0.94, unblinded 0.93; p = 0.97]. Correlation between UCEIS and visual analogue scale [VAS] assessment of overall severity was high [r blinded = 0.90, unblinded = 0.93; p = 0.02]. Scores for control videos were similar [UCEIS: p ≥ 0.55; VAS: p ≥ 0.07]. Intra- [κ 0.47-0.74] and inter-reader [κ 0.40-0.53] variability for items and full UCEIS was 'moderate'-to-'substantial', with no significant differences except for intra-reader variability for erosions and ulcers [κ blinded: 0.47 vs unblinded: 0.74; p 0.047]. The SD of CRGs was lower than for individual central readers [0.54 vs 0.95; p < 0.001]. Correlation between blinded UCEIS and patient-reported symptoms was high [stool frequency: 0.76; rectal bleeding: 0.82; both: 0.81]., Conclusions: The UCEIS is minimally affected by knowledge of clinical details, strongly correlates with patient-reported symptoms, and is a suitable instrument for trials. CRGs performed better than individuals., (© European Crohn’s and Colitis Organisation 2015.)

Inflammatory bowel disease (IBD) is a disease-specific risk factor for incident and recurrent venous thromboembolism (VTE). The reasons are acquired, multifactorial, and related to prothrombotic aberrations during active disease, although the mechanisms remain incompletely elucidated. VTE represents a potentially life-threatening extraintestinal manifestation of IBD, but the associated morbidity and mortality can be reduced by appropriate use of thromboprophylaxis. Nevertheless, despite international guidelines advocating thromboprophylaxis in hospitalised patients with IBD, practice is highly variable, since 65% of gastroenterologists may not use pharmacological VTE prophylaxis in hospitalised patients with acute severe colitis. Furthermore, there is no guidance on appropriate prophylaxis for ambulatory outpatients with active disease who are at an appreciable risk of VTE. Thus the question: are we tailoring thromboprophylaxis to those patients with IBD who are most at risk?, (© 2013.)

Background: The prognosis of acute severe ulcerative colitis (ASC) influences therapeutic decisions, but data on prevalence or long-term outcome are few., Methods: A systematic review of all patients with UC diagnosed in Oxford was performed to assess the prevalence of ASC defined by Truelove and Witts' (TW) criteria and determine whether outcome is related to disease activity on admission, likelihood of recurrence and long-term prognosis., Results: 750 patients (median follow up 12.7 yr, range 0-648 mo) met inclusion criteria out of a total cohort of 1853 patients. 24.8% (186/750) had at least one admission for ASC (294 admissions in 186 patients). Overall, 12% (93/750) had a colectomy, compared to 39.8% (74/186) of patients with one or more episodes of ASC (p<0.0001) and 3.4% (19/564) in those with no admission. The colectomy rate on first admission (37/186, 19.9%) was lower than on the second or subsequent admissions (OR 2.35, 95% CI 1.33-4.14, p=0.003), being 29.0%, 36.6%, 38.2% after two, three, or subsequent episodes respectively. It was 8.5% (11/129) if patients had one TW criterion in addition to ≥6 bloody bowel motions/day, compared to 31% (29/94) if two additional criteria were present and 48% (34/71) if three or more additional criteria were present (p=1.4 × 10⁻⁵; OR 4.35, 95% CI 2.20-8.56 one criterion vs two or more)., Conclusions: A quarter of all patients with ulcerative colitis experience at least one episode of ASC; 20% come to colectomy on first admission, but 40% after two admissions. The likelihood of colectomy is related to biological severity on admission., (Copyright © 2010. Published by Elsevier B.V.)

Background and Aims: Steroid-resistance presents a management challenge in ulcerative colitis. How steroid-resistance occurs is unknown, but cytomegalovirus infection, often unrecognised, may be the cause in some patients. Current evidence and therapeutic recommendations are examined., Methods: A systematic review of PubMed and EMBASE databases was performed. Search and exclusion criteria are defined in the text., Results: Heterogeneity of experimental design and definitions of key terms were notable. Criteria for cytomegalovirus disease, infection or detection varied, as did definitions of steroid-resistance. CMV infection defined by antigenaemia or serology was common in patients on steroids and associated with a higher rate of steroid-resistance (41.66-61% versus 0-68% in steroid-responsive patients). Colonic mucosal cytomegalovirus disease detected by histopathology was associated with intravenous steroid-resistance in 5-36%, compared to 0-10% of steroid-responsive patients. CMV colitis has rarely been reported in association with ulcerative colitis without steroids or other immunomodulators. CMV colitis in healthy individuals is so exceptional as to be the topic of case reports., Conclusion: Ulcerative colitis and its treatment put patients at risk of CMV infection or reactivation. A distinction is necessary between CMV disease (colitis) and CMV infection. Only colonic mucosal CMV infection detected by histopathology appears clinically relevant and appropriate for antiviral therapy. CMV antigenaemia may be associated with steroid-resistance, but may also be a self-limiting marker of viral reactivation. The impact of CMV on steroid-resistance is complicated by inconsistencies in the literature. Coherent definitions of clinically relevant CMV infection and steroid-resistance are needed.

Introduction: A previous randomised controlled trial has demonstrated that oral plus topical mesalazine enema is more effective than oral mesalazine alone for achieving clinical remission in mild-to-moderately active extensive ulcerative colitis (UC). To evaluate whether this strategy is cost-effective we conducted an economic evaluation comparing 1 g topical mesalazine in combination with 4 g oral mesalazine compared to 4 g mesalazine monotherapy in mild-to-moderately active UC., Methods: The economic evaluation was based on the ability to achieve remission using changes from baseline in the ulcerative colitis disease activity instrument (UCDAI). A cost-utility analysis was used where the main outcome was quality-adjusted life years to reflect improved quality of life associated with achieving remission compared with active disease. A simulated Markov model with five health states was constructed to model cost and outcome changes over time: (1) active UC; (2) mesalazine-refractory active UC; (3) steroid-refractory active UC; (4) infliximab-responsive active UC; and (5) remission. To reflect parameter uncertainty in the cost-effectiveness analysis probabilistic sensitivity analysis (PSA) was conducted by varying relevant clinical parameters., Results: Average treatment costs required to transition a patient from active UC to remission using oral and topical mesalazine compared with oral alone were £1812 and £2390, respectively. Improved remission rates attributed to oral and topical mesalazine resulted in moderate improvements in quality-adjusted life years (QALYs) compared to oral mesalazine alone. Disaggregation of medical costs indicated that medical consultations and diagnostic costs were similar for both treatment arms. An abbreviated analysis which considered costs up to steroid-refractory patients in subacute UC indicated that combination therapy offered a cost-savings of £285 over 16 weeks of therapy compared with monotherapy., Conclusions: The results indicate that the addition of 1 g topical mesalazine results in significant cost-savings and moderate quality of life improvements. We have also shown that irrespective of which treatment modality is used in steroid-refractory patients (eg, infliximab, azathioprine, ciclosporine) that topical mesalazine is cost-saving.

Background and Aims: Standard practice to maintain remission in ulcerative colitis (UC) consists of daily mesalazine therapy. However, frequent dosing is associated with poor adherence and increased failure rates. The PODIUM (Pentasa™ Once Daily In UC Maintenance) randomised control trial showed 2 g once daily (OD) to be superior to twice daily (BD) dosing for maintaining remission. We sought to determine whether this alternative dosing regimen is cost-effective., Methods: An economic evaluation was conducted to compare costs and outcomes of OD with twice daily (BD) dosing. The main outcome considered was quality-adjusted life years (QALYs) based on health state utilities derived from the primary outcome measure, remission without relapse at 12 months defined by a UCDAI score ≤1. The economic evaluation consisted of two health states: (1) remission and (2) active UC., Results: Annual average treatment costs for OD and BD dosing were £654 (95% CI: £536-£759) and £747 (£620-£860), respectively with an average per person savings of £93 per year. Average annual costs of ancillary care for relapse for OD and BD dosing were £307 (£241-£383) and £396 (£320-£483), respectively. Treatment with OD 2 g mesalazine resulted in an incremental QALY improvement of 0.004 units, indicating that it was the dominant treatment option (i.e. improved outcomes and cost-saving). Variations in parameter estimates in the sensitivity analysis indicated that mesalazine had >0.95 probability of being cost-effective compared to BD based on accepted willingness to pay thresholds applied by the UK National Health Service., Conclusions: Once daily 2 g mesalazine for maintaining remission in UC is cost-saving compared with 1 g twice daily. Cost-savings with 2 g once daily were achieved by differences in ancillary care attributed to higher failure rates observed with 1 g twice daily.

Background: Ocular episcleritis and uveitis are well-recognised extra-intestinal manifestations of Crohn's disease. Orbital myositis is rare: to our knowledge it has been associated with Crohn's disease in thirteen cases. Posterior scleritis, orbital myositis and Crohn's disease have been reported as coexisting in only two cases., Methods and Results: We describe a third case, that of a 31-year old female with Crohn's colitis for 8 years, complicated by enteropathic arthritis and pyoderma gangrenosum. She presented with intense and intractable periorbital pain, particularly at night and worse on eye movements. B-scan ultrasonography confirmed posterior scleritis and treatment with high dose oral steroids (up to 60 mg prednisolone) was initially effective, but subsequently failed to control the inflammation. There was only a partial response to infliximab. Five months after presentation, diplopia developed, with failure of abduction of the left eye. MRI scan of the orbits confirmed orbital myositis involving the left lateral and medial rectus muscles. Pulsed intravenous methylprednisolone and six cycles of intravenous cyclophosphamide over a three month period resulted in complete resolution of inflammatory symptoms., Conclusions: This case highlights a rare combination of ocular abnormality secondary to Crohn's disease and reports successful resolution with aggressive immunosuppressive therapy.

Background: Post-inflammatory polyps >15 mm in diameter or length are termed "giant". This benign and rare sequel of ulcerative colitis or colonic Crohn's disease can mimic colorectal carcinoma., Objective: To illustrate this rare complication of inflammatory bowel disease and outline the characteristic radiological, endoscopic and histopathological features, by reviewing all previously published cases of giant post-inflammatory polyps in the English literature., Results: Reports of 81 giant post-inflammatory polyps in 78 patients were identified by systematic review of the literature. The incidence of giant post-inflammatory polyps is related to the extent of ulcerative colitis (incidence: 0%, 30%, and 70%, in proctitis, left-sided, and extensive disease, respectively). These lesions are typically located in the transverse or descending colon. Giant post-inflammatory polyps are as common in Crohn's disease (n=36) as in ulcerative colitis (n=42, 54%). Clinical presentations varies, including pain (n=29), rectal bleeding (n=20), diarrhoea (n=19), luminal obstruction (n=15), or a palpable mass (n=11). Symptomatic presentation results in surgical resection. Clinical details and outcomes are comprehensively tabulated., Conclusion: Recognition of this rare entity will prevent unnecessary radical surgical resection for presumed carcinoma. It highlights the need for clinical, radiological, endoscopic and histopathological correlation.