bluuebunny/crossref_metadata_2025 huggingface dataset:
P123 Characteristics of small bowel involvement and association with clinical outcome in patients with Crohn’s disease
Authors: Yoon H , Park J , Kim H Y , Lee Y J , Shin C M , Park Y S , Kim N , Lee D H
Published: January 2022

Background

The location and number of involved sub-segments in small bowel Crohn’s disease (CD) vary on each patient. This study aimed to evaluate the distribution and characteristics of involved small intestine lesions through a detailed image review at the time of diagnosis and to evaluate the relationship between them and clinical outcomes.

Methods

CD patients who underwent computed tomography (CT) at the initial diagnosis were retrospectively enrolled. Two abdominal radiologists reviewed the CT images of all patients. They independently rated the presence of “bowel wall thickening”, “stricture”, and “fistula or abscess” in the jejunum, distal jejunum/proximal ileum, ileum, and terminal ileum, respectively. Score 1 was assigned if both radiologists concurred regarding the presence of a lesion. Based on the total score summed across different locations in the small bowel (e.g., imaging score), we divided the patients into three groups as 0, 1–2, and 3–4. Major clinical outcomes were compared among these groups.

Results

A total of 152 patients were enrolled. The proportion of the patients involved in the jejunum, distal jejunum/proximal ileum, ileum, and terminal ileum was 2.0%, 30.3%, 82.2%, and 71.7%, respectively; 32.3% of the patients had Montreal classification L4 (involvement of jejunum or distal jejunum/proximal ileum). Agreement on fistula or abscess was almost perfect (kappa value = 1.0 for most segments); the degree of agreement on bowel wall thickness and stricture varied according to involved segments (kappa value = 0.690–0.936). There were 15 (9.9%), 100 (65.8%), and 37 (24.3%) patients in groups 0, 1–2, and 3–4, respectively. In Kaplan-Meier survival analysis, there was no difference in the major clinical outcomes among three groups based on the imaging score (emergency room visit p = 0.093; operation p = 0.080; new use of corticosteroid p = 0.139; and new use of biologics p = 0.126). In the multivariable analysis, disease behavior was the only risk factor associated with all clinical outcomes after adjusting other factor (emergency room visit, HR 2.127 [1.356–3.337], p = 0.001; operation, HR 8.216 [2.629–25.683], p < 0.001; new use of corticosteroid, HR 1.816 [1.249–2.642], p =0.002; and new use of biologics, HR 2.352 [1.492–3.708], p < 0.001).

Conclusion

As a result of a detailed CT review, about one-third and one-fourth of patients newly diagnosed as small bowel CD had L4 lesions and multiple lesions (> 2 segments), respectively. However, the location and number of involved sub-segments in small bowel CD did not affect the clinical outcomes. Initial disease behavior is a more critical factor associated with clinical outcomes than characteristics of disease location.
P142 Inflammatory bowel diseases associated with primary immunodeficiency: a multicenter study
Authors: Malamut G , Simon M , Nachury M , Uzzan M , Serrero M , Fumery M , Trang-Poisson C , Zallot C , Abitbol V , Charbit-Henrion F , Gornet J M , Picard C , Cerf-Bensussan N , Chaussade S , Sokol H
Published: January 2022

Background

Inflammatory bowel diseases (IBD) associated with primary immunodeficiency (PID) remain poorly known. We aimed to isolate characteristics of IBD associated with PID.

Methods

Using a GETAID register, we reviewed medical files of recorded patients with PID and IBD (Crohn’s disease, ulcerative colitis (UC) or microscopic colitis) followed in 9 adult university hospitals. Results of genetic investigations were available for 46 patients (62%).

Results

74 patients (30 F, 44M) were included with a mean age of 26 years (median: 24 years) at diagnosis of IBD. Forty-four (59%) patients had Crohn’s disease with anoperineal lesions in 12, 26(35%) patients had microscopic (mainly lymphocytic) colitis and 4 patients had UC. PID was predominantly antibody deficiency in 40(54%) patients [34 common variable immunodeficiency, 4 X-linked agammaglobulinemia, 2 selective IgA deficiencies], disease of immune dysregulation in 18(24%) patients [CTLA4, LRBA, NFKB1, TNFAi3, XIAP deficiencies, STAT3 and STAT1 hyperactivation], phagocytosis deficiency in 15(20%) patients (12 chronic granulomatous diseases (CGD), 3 congenital neutropenia] and C1s deficiency (n=1). In order of frequency, Crohn’s disease was associated with antibody deficiencies (52%), phagocytosis deficiencies (29%) and immune dysregulation (18%), microscopic colitis with antibody deficiencies (65%), immune dysregulation (27%) and more rarely with phagocytosis deficiencies (8%) and UC with antibody deficiencies (75%) and immune dysregulation (25%). 46% of patients received immunoglobulin supplementation, 70% steroids, equally corticosteroids and budesonide, 49% biotherapy mainly anti-TNF-alpha antibody (38%) and ustekinumab (16%), 23% immunosuppressive drugs, mainly azathioprine and sirolimus and 18% aminosalicylates. Three patients (2 CGD, 1 XIAP) had been treated with allogeneic stem cell transplantation (SCT) and one patient (TNFRS13B deficiency) with autologous SCT. Eleven (15%) patients had intestinal surgery, mainly ileocecal resection. During follow-up [mean: 16 years], 51% of patients had transient or sustained clinical remission mainly with an anti-TNF-alpha antibody, ustekinumab, steroids (budesonide) and specific therapy (targeted therapy such as abatacept and ASCT), 41% of patients had severe infections, 22% developed neoplasia mainly gastrointestinal dysplasia and/or cancers (n=8), B cell lymphoma (n=3) and 4 patients died.

Conclusion

At adulthood in our series, IBD associated with PID are mainly Crohn’s disease and lymphocytic colitis. The first most frequent associated PID is antibody deficiency. Biotherapies (anti-TNF-alpha antibody, ustekinumab), steroids and specific therapies are commonly used to induce clinical remission.
P144 Changes of fecal metabolic and lipidomic features by anti-tumor necrosis factor treatment and prediction of clinical remission in patients with ulcerative colitis
Authors: Shin Shin S , Kim S Y , Park S J , Im J P , Kim H J , Lee K M , Kim J W , Jung S A , Lee J , Kang S B , Shin S J , Kim E S , Kim Y S , Kim T O , Kim H S , Park D I , Kim H K , Kim E S , Kim Y H , Teng D , Kim J H , Kim W , Saeed M , Moon J M , Kim K , Choi C H , Choi H K
Published: January 2022

Background

Tumor necrosis factor (TNF) antagonists are recommended for patients with ulcerative colitis (UC) for the effectiveness in inducing and maintaining clinical remission. We investigated the altered fecal metabolites and lipids by anti-TNF treatment and prediction model of remission in patients with UC.

Methods

A prospective, observational multicenter study was conducted at 17 academic hospitals in Korea. Fecal samples were collected from adult patients with moderately to severely active UC (n=116) before and after 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n=37). Clinical remission was assessed using Mayo score. Metabolome and lipidome analyses were performed using gas chromatography-, and nano electro spray ionization-mass spectrometry, respectively. Prediction models of remission were developed using baseline fecal samples by Fourier transform-infrared (FT-IR) spectroscopy combined with machine learning algorithms.

Results

Fecal metabolites and lipids in UC were different from HC at baseline and were changed similarly to HC during treatment. Fecal metabolites and lipids in remitters (RM) after treatment were more grouped and clustered with those of HC compared with non-remitters (NRM). In RM, 2-aminobutyric acid, galactose and dodecanoate levels which were previously decreased at baseline compared to HC increased to the levels of HC, whereas benzoate, stigmasterol, 3-hydroxybutyrate, diacylglycerol and triacylglycerol levels which were previously increased at baseline compared to HC decreased to the levels of HC after 56 weeks of treatment. The best model predicting short-term remission was developed by applying logistic regression (LR) and radial basis functions (rbf) support vector machine (SVM) with an accuracy of 0.99 (95% confidence interval [CI], 0.98–1.01). For long-term remission, the best prediction model was developed by rbf-SVM revealing 0.99 [CI 0.98–1.01]. LR and K-nearest neighbors also showed excellent performance for prediction of long-term remission (accuracy of 0.96 [CI 0.90–1.02] and 0.96 [CI 0.92–1.00], respectively.

Conclusion

Fecal characteristics in UC were changed after anti-TNF treatment and became similar to those of HC. Potential therapeutic target compounds were suggested to develop novel therapeutic strategies for UC. Novel remission prediction models by FT-IR spectroscopy were also established.
P147 Do IBD Patient Treatment Outcomes Expectations Differ by Ethnicity and Gender?
Authors: Broide E , Richter V , Mari A , Khoury T , Shirin H , Naftali T
Published: January 2022

Background

Understanding IBD Patient’s expectations of treatments outcomes may improve understanding of patient’s needs. These expectations may differ in different ethnic groups. Awareness of the patient’s expectations and preferences will decrease the gap between patients and physicians.

We aimed to investigate patient’s preferences and priorities for treatment outcomes among Jewish and Muslim IBD patients in Israel.

Methods

A prospective survey of Muslim IBD patients was compared to historical data of Jewish IBD patients. Data included demographics, socioeconomics, and disease parameters. Patients were asked to rank ten items regarding their preferences for treatment outcome, based on the ten IBD disk items.

Results

121 Muslim patients were compared to 240 Jewish patients. Both groups were equal regarding age and IBD type (Crohn’s or ulcerative colitis). The Jewish IBD patients were characterized by including more female (p<0.001), higher education level (p=0.02), more urban residence (p<0.001), less unemployment (p=0.012), higher income level (p<0.001), and less relationship with a partner (p<0.001).

Patient’s priorities stratified according to the 10 IBD disk items revealed that disease symptoms including abdominal pain, energy, and regular defecation ranked highest in both Muslims and Jews. The scores given by the Muslim patients were significantly lower (range 6.69 - 4.29) than the scores given by the Jewish patients (range: 9.03 – 6.25) regarding all items, except for body image. Jewish women attached higher priority to abdominal pain, energy, education and work, sleep, and joint pain compared to Muslim women.

Cluster analysis and multivariable regression analysis revealed that factors associated with higher patients’ preferences (cluster 2) were Jewish religion [OR, 4.77; 95% CI, 2.36–9.61, p<0.001], and disease activity [1–2 attacks: OR, 2.13; 95% CI, 1.02–4.45, p=0.043; primarily active disease: OR, 5.29; 95% CI, 2.30–12.18, p<0.001].

Factors unlikely to be associated with higher patient’s preference (cluster 2) were male gender [OR, 0.5; 95% CI, 0.271–0.935, p=0.030], and income level above average [OR, 0.267; 95% CI, 0.124–0.577, p=0.001].

Conclusion

Ethnic, gender, and socioeconomic disparity have a high impact on patient’s ranking of priorities for treatment outcome. Despite the ethnic and cultural differences, symptoms relief is in the highest priority in both patient groups. Understanding patient’s priorities will improve communication and enable a better personalized approach.
P149 Prioritising colonoscopy by faecal immunochemical test result does not delay the diagnosis of inflammatory bowel disease
Authors: White K , Makin A
Published: January 2022

Background

Due to the Covid-19 pandemic there has been unprecedented pressure on endoscopy services. Faecal immunochemical tests (FIT) are designed to detect small amounts of blood in stool samples using antibodies specific to human haemoglobin. This test is highly specific and sensitive for colorectal cancer (CRC) and has been shown to detect mucosal healing in ulcerative colitis(1). FIT was utilised at our hospital to prioritise urgency of colonoscopy referrals. We aimed to determine whether this caused a delay in the diagnosis of inflammatory bowel disease (IBD) in this cohort.

Methods

Consecutive colonoscopy referrals (urgent, semi-urgent and routine) from September 2020 to April 2021 were prioritised by FIT result. Any patient with a FIT>/=10mcg were deemed category 1 (colonoscopy within 30 days) and FIT<10mcg were deemed category 2 (colonoscopy within 90 days). Demographic data were collected along with procedure result and histology.

Results

One hundred and twelve patients (52% female) had a FIT test and a subsequent diagnostic test (96 had a colonoscopy, 12 had a flexible sigmoidoscopy, 3 had a CT colonography and 1 patient declined a colonoscopy but later had a CT abdomen and pelvis. Patients who did not go on to have a diagnostic test were excluded. Sixty four patients had a FIT<10 (mean age 61), 35 had a FIT 10–400 (mean age 64) and 13 patients had a FIT>400 (mean age 52).

Median number of days from FIT result to diagnostic test was 56 (range -9–163) in the group with FIT<10, 44 (-28–93) in the group with FIT 10–400 and 44 (10–89) in the group with FIT>400.

There were no cancer diagnoses in the FIT<10 group. No patients in this group had colonic inflammation. Of the patients with FIT 10–400; 4 had colonic or ileocaecal valve inflammation, 12 had polyps and 2 had a CRC. Of the patients with inflammation one had mild right sided inflammation (FIT 228), one had colitis (FIT 367), one had proctitis (FIT 87) and one had ileitis of the ileocaecal valve (FIT 119).

Of the patients with FIT>400; 4/13 had a colorectal malignancy (one of which was a polyp cancer), 4/13 had colonic polyps and 3/13 had active colonic inflammation. Of the patients with inflammation one had right sided inflammation, likely crohns disease, one had severely active ulcerative colitis (UC) and one had mild proctitis, likely UC.

Conclusion

In this cohort there were no CRC or IBD diagnoses in the patients with FIT<10. Therefore there was no delay in investigation of any patient subsequently diagnosed with IBD. This suggests that FIT may be safely used to stratify the priority of referrals for colonoscopy in symptomatic patients. Further work is required to confirm this.
P161 Implementation of Outcome Measurement – Case Finnish IBD register
Authors: Mustonen A , Asikainen S , Hermansson L L , Jussila A
Published: January 2022

Background

Inflammatory bowel diseases (IBD) are becoming increasingly common. In Finland, during 2020, in total of 54 000 patients were diagnosed with IBD, and over 2000 new diagnoses are made every year. The Finnish university hospitals in collaboration with BCB Medical Ltd have built disease-specific registers to support and monitor the quality and effectiveness of health care. The IBD register (IBDR) collects data on the effectiveness of IBD treatments and their follow-up, where e.g. disease severity, treatment and outcomes are profoundly monitored. As combination, IBDR, MyHealth service, and IBD Symptom Diary enables patients’ health, functional status, experience and QoL monitoring to reach the health care goals. The service supports patient treatment pathway and makes designing more personalized treatments for IBD possible.

Methods

The IBDR is a web-based system integrated with electronic health record (EHR) systems, through which patient data is captured. Nationally convergent register allows for peer review of treatment outcomes. To complement registers’ clinical data, PROMs are collected with online MyHealth service to enable automatic, recurring data collection directly from the patient. The first questionnaire is activated 14 days before the visit, whereas new questionnaire is sent to the patient two months after visit, and then at time points according to the disease activity index calculated from the questionnaire. The disease activity is reflecting the severity of the IBD symptoms[1]. Captured measures are immediately available for clinician review.

Results

MyHealth for IBD is actively used in four Finnish university hospitals and two central hospitals with some inter-regional variation. By November 2021, the questionnaires were answered 31 506 times since the beginning of the implementation in 2019. The response rate is yearly increasing (Figure 1). Distribution of disease activity index among IBD patients in Tampere University Hospital is shown in Figure 2.

Conclusion

IBDR enables the evaluation and comparison of patient care quality, which is not accessible through EHR systems alone. Our electronic data collection model brings out the patients’ voice and saves resources since cyclic questionnaires are automatically send to patients, and answers are immediately reached by clinician. In future, international comparison and monitoring of treatment outcomes will be emphasized. As MyHealth deployment proceeds across hospitals, the availability of the patient reported outcomes data will increase. International research and peer development will continue to be an essential part of our activities.

Reference

1. Puolanne A-M et al. Dig Dis Sci (2017) 62:3123–3130.
P166 Predictive markers of Crohn’s disease in small bowel capsule endoscopy
Authors: Mattila J , Stenholm T , Löyttyniemi E , Koffert J
Published: January 2022

Background

To distinguish between functional gastrointestinal disorders like irritable bowel syndrome (IBS) and Crohn’s disease (CD) can be a burden. The diagnosis is based on symptoms and findings in laboratory tests, endoscopy and imaging. As CD can be limited to small bowel, the diagnosis often requires small bowel capsule endoscopy (SBCE), which is time consuming for both the patient and clinician.

Methods

To answer this problem, we conducted a retrospective study of 374 patients who underwent SBCE for suspected small bowel CD in Turku University Hospital between 2012 and 2020 and gathered data on the patient’s laboratory, imaging and endoscopic findings at the time of SBCE. The patient’s history, medications and procedures related to CD were also documented after SBCE. SBCE findings were graded along CECDAI (Capsule Endoscopy Crohn’s Disease Activity Index) -scoring system. The main goal was to find predictive markers to rule out clinically significant small bowel CD without proceeding to SBCE.

Results

Small bowel CD was diagnosed in 110 (29.4%) patients (CD-group). The mean follow-up time for the whole population was 4.4 years. Fecal calprotectin (FC), serum albumin (Alb) and erythrocyte sedimentation rate (ESR) were significantly different between CD and non-CD-groups (p=<0.001, 0.025 and 0.022). Hemoglobin (Hb) and C-reactive protein (CRP) had no significant differences between the two groups (p=0.59, 0.24). FC <50ug/g had sensitivity 96.4%, specificity 19.6%, positive predictive value (PPV) 34.6% and negative predictive value (NPV) 92.5% for small bowel CD. 13 (11.8%) patients in CD-group had FC <100ug/g. CECDAI-score has no previously established clear cut-off-value for the diagnosis of CD. In this study 98.2% of patients in CD-group had CECDAI of 3 or more whereas 90.5% of patients in non-CD-group had CECDAI less than 3 (PPV=81.1%, NPV=99.1%). Sensitivity and specificity were the highest between CECDAI 2.5 and 3.5. Small bowel imaging also had relatively low sensitivity (65.1%) and specificity (72.7%) considering small bowel CD (PPV=52.2%, NPV=81.8%).

Conclusion

These findings underline our experience, that diagnosis of small bowel CD can be difficult. In this study, we found out that clinically relevant small bowel CD is possible even with FC<100ug/g. Based on our results, we suggest for a follow-up with FC before SBCE for patients with no endoscopic ileitis, negative imaging results and FC <50 ug/g. CECDAI-score of 3 would be a reasonable cut-off value for small bowel CD.
P170 Point-of-care ultrasound accurately quantifies skeletal muscle index in patients with Inflammatory Bowel Disease
Authors: Nguyen A , Burns M , Lambell K , Holt D , Herath M , Gibson P R , Ebeling P , Milat F , Moore G
Published: January 2022

Background

Body composition is frequently altered in patients with Inflammatory Bowel Disease (IBD) and difficult to quantify without expensive and radiation-prone techniques. Low skeletal muscle index (SMI) has been associated with increased surgical complications and poor quality of life. Aim: To develop a portable ultrasound (US) protocol to estimate SMI, to compare this with SMI from paired whole-body dual-energy X-ray absorptiometry (DXA) in patients with IBD and controls, and to assess its responsive to change over time.

Methods

Adult patients with IBD and gender-matched controls underwent prospective assessment of body composition by US (Philips Lumify) and DXA (GE Lunar Prodigy) for which low SMI was defined as men ≤7.26 kg/m2 and women ≤5.45 kg/m2. Sonographic muscle thickness of the dominant arm and bilateral thighs (Figure 1) were multiplied by respective bone lengths (humerus or femur) and described in cm2. Results were analysed by Spearman correlation and receiver operating characteristic (ROC) curves using just arm measurements (USarm) or combined arm and thigh measurements (UScombined). A subgroup of patients with active IBD (faecal calprotectin of ≥150 µg/g) were assessed again ≥14 weeks after initiating biologic induction therapy. Response was defined with faecal calprotectin reduction of ≥50%.

Results

48 patients with IBD had similar SMI compared with 30 controls (7.1 vs 7.7 kg/m2), but a higher proportion had low SMI (19% vs. 3%, p=0.048). In both IBD and control participants, DXA-derived SMI was strongly associated with USarm measurements (r=0.89 and r=0.88, p<0.0001) and UScombined measurements (r=0.90 and r=0.87, p<0.0001).

On ROC analysis in patients with IBD, low SMI was identified best with USarm <73 cm2 in women (AUC 0.93, sensitivity 100%, specificity 89%) and <117 cm2 in men (AUC 0.88, sensitivity 100%, specificity 81%). In 7 of 14 patients who responded to biologic induction, only DXA-SMI increased significantly (7.9 to 9 kg/m2) compared to USarm (109 to 124 cm2, p=0.249) and UScombined (270 to 323 cm2, p=0.080). Including both responders and non-responders, change in UScombined correlated well with change in DXA-SMI (r=0.77, p=0.007).

Conclusion

Sonographic measurement of the dominant arm ± bilateral thigh muscle thickness accurately assesses DXA-derived SMI at the point-of-care. In preliminary evaluation, it was responsive to change after biologic induction therapy, but larger sample sizes and longer follow up are needed to evaluate its monitoring role.
P178 Fecal incontinence and rectal anal function in Crohn’s Diseases patients
Authors: Góes de Codes L M , Costa de Jeus A C , Góes de Codes J J , da Silva Beda Sacramento C , Dias Marques da Cruz I , Freitas Ferreira R , Baqueiro Sena N , Moreira Gusmão V , Araujo Mota J , Pamponet Motta M , Martins Netto E , Oliveira santana G
Published: January 2022

Background

Anoperineal damage in Crohn’s Disease (CD) is caused by inflammation, its sequelae, and the surgery’s sequelae. Fecal incontinence (FI) is an important complaint reported by patients with CD. Literature data regarding to FI, anatomical and functional abnormalities and its associated clinical factors are controversial, with few surveys with a limited number of participants.1 The aim of this study is to analyze FI and the associated manometric and clinical findings in patients with CD.

Methods

Observational, cross-sectional study in patients older than 18 years old with CD under outpatient follow-up at a tertiary center, who, after sign informed consent, were submitted to specific questionnaire, anorectal manometry and medical record review.

The Jorge and Wexner Fecal Incontinence Scale was applied to grade incontinence.2

SPSS 21.0 (SPSS, Chicago, IL, USA) was used for statistical analysis, with description of categorical variables with absolute and relative frequency, and continuous variables with median and interquartile range (IIQ). To study the association, we used Pearson’s Chi-Square and Mann Whitney test. The null hypothesis was rejected with p<0.05.

Results

Of 104 patients with CD, 51% were male, median age of 41 years old (IIQ 29.2–50.0) and median disease duration of 6.1 years (IIQ 2.5 to 11 .5). Most of the sample was diagnosed between 17 and 40 years old, (68.3%), with non-penetrating, non-stricturing disease (63.4%), with colonic location (77.9%), isolated (30.8%) or with ileal involvement (47.1%); 78.8% had disease in remission and 11.5% had mild disease, representing 90,4% of our casuistic, according to the Harvey Bradshaw Index. Among patients; 41.3% had perianal disease, and 49% were incontinent, of these 66.7% had mild incontinence and 33.3% had moderate and severe incontinence. It was found association between FI and lower mean resting pressures (p=0.04) and lower mean squeeze pressures (p=0.04) along the anal canal. There was also association between FI and perianal disease (p=0.02), and FI and disease activity (p<0.01).

Conclusion

The study, unprecedented in America Latin, showed a high frequency of FI and found its association with disease activity, structural abnormalities (perianal disease) and anorectal disfunction (lower resting and squeeze pressures), reenforcing the importance of controlling CD activity. Furthermore, the data showed to be crucial during follow-up of CD patients the adequate manometric assessment and specialized evaluation for the management of FI.

References

1. Litta, F, Ratto C, et al. Anorectal function and quality of life in IBD patients with a perianal complaint, J Invest Surg. 2019 Oct 18;1–6

2. Jorge JMN, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum 1993;36:77–97
P208 Enthesopathies in patients with inflammatory bowel diseases
Authors: Gainullina G , Abdulganieva D , Kirillova E , Odintsova A
Published: January 2022

Background

Background. The aim of study was to evaluate the enthesis in patients with inflammatory bowel diseases (IBD) and to assess the involvement of enthesis in different IBD behavior.

Methods

Methods. 95 IBD pts were prospectively enrolled into the study: 55 pts with ulcerative colitis (UC) and 40 - with Crohn’s disease (CD). The average duration of the disease was 48 (12; 102) months in UC, and 42 (18; 87) months in CD. The severity of UC exacerbation was assessed by the Mayo index, in CD – by Harvey-Bradshaw index. In UC, moderate and severe exacerbation was revealed in 40 pts (73%), in CD - in 17 (43%). Among 95 pts with IBD, extraintestinal manifestations occurred in 67 pts (71%), of which 34 (62%) pts with UC and 33 (82%) pts with CD. 70 enthesis were evaluated clinically and by US in each pt. The clinical examination included tenderness of enthesis, US examination with power Doppler detected inflammatory (hypoechogenicity of enthesis, thickening of enthesis, presence of vascularization) and structural (erosion, enthesophyte) changes in enthesis. Fisher’s exact test, Spearman’s coefficient and binary logistic regression to determine the odds ratio (OR) were used to calculate differences.

Results

Results. The duration of IBD course directly correlated with the number of tender entheses (SR = 0.24; p = 0.017), as well as the number of enthesophytes (SR = 0.20; p = 0.044). The severity of IBD exacerbation and enthesis involvement didn’t have statistically significant correlation. However, the inflammatory lesions of entheses (the number of erosions with vascularization) correlated with CRP level (SR = 0.25; p = 0.01). We also identified a relationship between the presence of extraintestinal manifestations and the enthesis involvement: for example, the presence of at least one extraintestinal manifestation increased the likelihood of detecting erosions by 4.77 times (95% CI 1.6–13.9, p = 0.003). The presence of joint pain increased the likelihood of detecting erosions of entheses by 3.37 times (95% CI 1.18–9.65, p = 0.02). Clinical signs of musculoskeletal system involvement (tenderness of enthesises on palpation) significantly increased the frequency of enthesitis, including vascularized enthesitis (p = 0.01).

Conclusion

Conclusion. In IBD pts with long disease duration and the presence of extraintestinal manifestations, structural (erosion, enthesophytes) changes in enthesis were observed significantly more often. The frequency of entheses erosions was higher in the presence of pain in the joints, and the number of erosions with vascularization with an increase in laboratory markers of inflammation (CRP).
P212 The DUBLIN Score is a Useful Tool for Predicting Disease Course in Patients with Ulcerative Colitis
Authors: Doherty J , Stack R , O Morain N , Mc Namara D , Coe C , Kevans D , Doherty G
Published: January 2022

Background

The DUBLIN (Degree of Ulcerative colitis Burden of Luminal Inflammation) is a novel simple clinical score of inflammation in patients with Ulcerative Colitis (UC) which can be used easily in outpatients and at the bedside.

Methods

We sought to validate the clinical utility of scoring UC inflammatory burden at diagnosis in predicting disease outcomes using the DUBLIN score (DS). We performed a multicentre retrospective study of patients recruited to the Genuity medicine IBD research project at three centres. DS at diagnosis was calculated based on disease extent and endoscopic severity. Study outcomes were need for immunomodulators and/or biologic therapy and need for surgery. We also examined the association between DS and FCP, albumin and C-reactive protein.

Results

679 patients with confirmed UC were identified. 291 had data allowing calculation of DS at diagnosis (median age 38.9 years, 53% male). Median DS was 4 [1–9]. 122 patients were treated with biologic therapy during follow-up. Median DS at diagnosis was significantly higher in patients requiring biologic therapy compared to those not requiring biologic therapy [4 versus 3, p = < 0.001]. Of patients requiring biologic therapy patients with a DS > 3 had a significantly shorter time on 1st biologic therapy [2.1 versus 3.9 years, p = 0.005]. There was no difference in median DS dependent on immunomodulator use. Similarly median DS at diagnosis was significantly higher in patients requiring colectomy compared to those not requiring colectomy [6 versus 4, p = 0.001].

There was a weak positive correlation between both DS and faecal calprotectin [correlation coefficient 0.27, p = 0.001] and C-reactive protein [correlation coefficient 0.7, p = 0.01] and a weak negative correlation between DS and albumin level [correlation coefficient -0.22, p = 0.04].

Conclusion

Our study validates the clinical utility DS is an accurate clinical tool at diagnosis and during a patients’ disease course for identifying disease burden. A higher DS correlates with an increased need for biologic therapy, need for colectomy and increased biomarkers of disease activity. This is a useful tool for day to day use in clinical practise providing personalised management of patients with UC.
P220 CROHN’S DISEASE (CD): The predictive value of Montreal clinical patterns, and biological treatment in a Latin American IBD reference center
Authors: Sambuelli MD A , Gil A , Tirado P , Huernos S , Negreira S , Goncalves S , Rothwain M J , Candel I
Published: January 2022

Background

CD is a potencially disabling condition, with high rate of complications and surgical requirement. Biological treatments have revolutionized the CD treatment management, but their efficacy and predictive factors could be influenced for epidemiological and environmental conditions which should be locally analyzed wordly.

AIMS

to describe by a retrospective study in a Latin American IBD reference center, clinical features of the CD casuistic, predictive Montreal patterns for surgical risk and efficay of biologs and immunosuppressant drugs.

Methods

Data of CD patients (pts) assisted from 1990-June 2020 (CD duration ≥1 yr), categorized by Montreal classification, and by biological and IMM treatment in the prevention as first mayor surgery. Clinical patterns were evaluated as predictive factors at the basal time (up to 90 days from debut) in: Age at diagnosis (A)A1:≦16yrs, A2:17–40, A3:>40, Behavior (B): nonstricturing nonpenetrating (B1), stricturing (B2), penetrating (B3), perianal disease modifier (p), Location (L): L1: ileal, L2: colonic, L3: ileocolonic, L4: upper G.I. Incidence rates of surgery and preventive treatment efficacy were estimated by a Cox regression model.

Results

598 CD pts (M 313, F 285) with mentioned available data, CD median duration 13.9 yr (IQR 7.1–21.2) were analyzed. Montreal patterns A1: n 93 (15.6%), A2: n 335 (56.0%), A3: n 170 (28.4%), B1: n 523 (87.5%), B2: n 52 (8.7%), B3: n 23 (3.8%) L1: 52 (8.7%), L2: n 368 (61.5%), L3: n 176 (29.4%), L4: iUGI: n 2 (0.33%) and L4 combined with L1, L2, L3: n 47 (7.9%) Perianal disease (p) n 286 (47.8%). Biologics (before first surgery) in 202 pts, primary non response in 45 pts. Major surgery was performed in 304/598 pts (50.8%) Kaplan Meier estimates: Major surgery incidence rate was 5.1 per 100 person/yrs. Median survival without surgery: 14.2 yrs. Signifficant variables of Cox model for surgery risk were: B1 HR 1 (reference), B2 HR 3.03 (95%CI 2.14–4.29, p=0.000), B3 HR 3.27 (95%CI 2.03–5.29, p=0.000), L2 HR 1 (reference), L1 HR 2.025 (95%CI 1.37–2.99, p=0.000), L3 HR 2.51 (95%CI 1.95–3.23, p=0.000), A1 HR 1 (reference), A2 HR 1.48 (95%CI 1.05–2.10, p=0.027), A3 HR 1.89 (95%CI 1.27–2.83, p=0.002), Biologics (mainly Anti-TNFs) only induction 1.49 (95%CI 1.005–2.195, p=0.047). Induction plus maintenance HR 0.388 (95% CI 0.27–0.55), p=0.000. Non signifficant variables involved in the risk for surgery were: gender, perianal complication, and IMM treatment.

Conclusion

In our CD population we found: 1) Montreal patterns associated with surgical risk (fistulizing and stricturing behaviors), ileal and ileocolonic locations, A2, but also A3 (debut beyond 40 yrs). 2) Biologics showed a reduction in surgical risk (induction plus maintenance versus only induction).
P229 Capsule endoscopy is useful in the diagnosis and monitoring of postoperative recurrence in Crohn’s disease. Analysis from an 11-year cohort
Authors: Elosua Gonzalez A , Rullan M , Rubio S , Elizalde I , Rodríguez C , Aznárez M R , Vicuña M , Juanmartiñena J F , Fernández-Urién I , Nantes Ó
Published: January 2022

Background

Small bowel capsule endoscopy (SBCE) has been proposed as a non-invasive method to detect endoscopic postoperative recurrence (POR). To date, few studies with small-sized cohorts have evaluated the role of SBCE in monitoring patients with CD in the postoperative setting, targeting the early POR (≤ 12 months). Our aim was to conduct a retrospective analysis of the performance of SBCE in assessing POR comparing three different situations encountered in clinical practice: detecting early POR, monitoring for late POR (≥ 12 months) and assessing response to treatment in patients with previous endoscopic-POR.

Methods

We included all patients with known CD with previous ileocolonic resection followed in the Inflammatory Bowel Disease Unit of Hospital Universitario de Navarra from 01/01/2008 to 31/12/2019 in which a SBCE was performed. Patients were divided in three groups (early POR, late POR and monitoring POR)

Results

A total of 113 SBCE procedures were included after excluding 18 cases (13.7%) due to a negative SB patency test. Patients were divided in early-POR group (n= 34), late-POR group (n=44) and monitoring-POR group (n=35). A total of 105 procedures (92.9%) were complete and 97 SBCE (85.5%) were considered conclusive since they allowed a correct assessment of the neoterminal ileum.

Disease activity in the neoterminal ileum according to the Rutgeert’s score is shown in figure 1. SBCE assessment was feasible for early (85%) and late (89%) detection of POR but with significant differences in the results. While in the Early-POR most patients (85%) had disease activity in the neoterminal ileum, only 64% of patients assessing late-POR had mucosal lesions (p= 0.03). There was relevant POR (Rutgeert’s ≥i2) in 58.8% of the early-POR group compared to 27.3% in the late POR (p=0.02).

For patients with previous POR, assessment with SBCE is also feasible with conclusive results in 83% of the patients. The predominant score was i2 with 26% of the group with similar proportions in the remaining scores (figure 1). Within the Monitoring-POR group, for those with previously assessed POR by endoscopy (either ileocolonoscopy or SBCE), the Rutgeerts Score improved in 43.5% of patients, worsened in 26% and remained unchanged in 30.5%. Overall, 45.7% of patients had relevant POR with 60% classified as i2.

No adverse events occurred in our cohort.

Conclusion

SBCE is a safe and effective method to assess the postoperative recurrence after an ileocecal resection in the early (≤ 12 months) and late setting in clinical practice. SBCE is a safe and effective method to assess the response to treatment in patients with previous endoscopic POR
P237 Proteomic analyses do not reveal subclinical inflammation in fatigued patients with quiescent Inflammatory Bowel Disease
Authors: Bourgonje A R , Wichers S J , Hu S , van Dullemen H M , Visschedijk M C , Faber K N , Festen E A M , Dijkstra G , Samsom J N , Weersma R K , Spekhorst L M
Published: January 2022

Background

Fatigue is a common and clinically challenging symptom in patients with inflammatory bowel diseases (IBD). While fatigue occurs most often in patients with active disease, up to 50% of patients with quiescent disease still report significant fatigue of unknown aetiology. Here, we aimed to investigate whether fatigue in patients with quiescent IBD is reflected by circulating inflammatory proteins, that in turn might reflect ongoing subclinical inflammation.

Methods

Ninety-two (92) different inflammation-related proteins were measured in plasma of 350 patients with quiescent IBD (188 Crohn’s disease [CD]; 162 ulcerative colitis [UC]). Quiescent IBD was defined as clinical (Harvey-Bradshaw Index [HBI] <5 or Simple Clinical Colitis Activity Index [SCCAI] <2.5) and biochemical remission (C-reactive protein [CRP] <5 mg/L) at time of sampling. Fatigue severity was assessed on a visual analogue scale (VAS).

Results

None of the analysed plasma proteins were differentially abundant between mildly (1st quartile, Q1) or severely (4th quartile, Q4) fatigued patients under a false discovery rate of 10%. Considering nominal significance (P<0.05), however, leukemia inhibitory factor receptor (LIF-R) concentrations were inversely associated with severe fatigue, also after adjustment for confounding factors (P <0.05) (Figure 1). Although solely LIF-R showed weak ability to discriminate between mild (Q1) and severe (Q4) fatigue (area under the curve [AUC]=0.61, 95% CI: 0.53–0.69, P<0.05), a combined set of the top seven (7) fatigue-associated proteins (LIF-R, vascular endothelial growth factor-A [VEGF-A], glial-derived neurotrophic factor [GDNF], interleukin-20 receptor subunit alpha [IL-20RA], Delta and Notch-like epidermal growth factor-related receptor [DNER], T-cell surface glycoprotein CD5 [CD5], and extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE], also known as protein S100-A12, all P<0.10) was observed to have reasonable discriminative performance (AUC=0.82 [95% CI: 0.74–0.91], P<0.01).

Conclusion

Fatigue in patients with IBD is not clearly reflected by distinct circulating inflammatory protein signatures, which suggests that subclinical immune activation as defined by the studied panel of inflammatory proteins could not be detected. Reduced shedding of the LIF-R protein could be related to fatigue in IBD through modification of the oncostatin-M (OSM) signaling pathway, or through induction of pro-inflammatory phenotypes of T-cells, macrophages, or neural cells. Future studies are warranted to investigate other proteomic or metabolic markers that may accurately reflect fatigue in quiescent IBD, which might represent alternative pathophysiological pathways.
P250 Clinical validation of a point of care test for fecal calprotectin in distinguishing irritable bowel syndrome from Inflammatory Bowel Disease
Authors: Bray K , Bahur B , Yadav M , Skinner M , Wong M , Chon K , Huang R , Day V , Mimms L , Hale M
Published: January 2022

Background

Calprotectin is a small calcium-binding protein that when measured in human stool has shown utility in assessing the degree of bowel inflammation in inflammatory bowel disease (IBD) and in distinguishing IBD from irritable bowel syndrome (IBS). However, most fecal calprotectin (FCP) assays are slow and inconvenient. This study examined the analytical agreement and clinical utility of a point of care (POC) assay for FCP.

Methods

A fast (~5 min.), time-resolved fluorescence resonance energy transfer based immunoassay (Procise FCP™) was developed for the POC measurement of FCP using 15 mg of fecal specimen eluted in collection fluid from the Procise Stool Collection Device™. The analytical agreement between the Procise FCP assay and a commercial ELISA assay: Inova Quanta Lite Calprotectin Extended Range was assessed using 46 leftover deidentified fecal specimens.

Clinical performance of the assay was assessed using stored frozen stool specimens from a nested cohort derived from a prospective study of chronic diarrhea patients. Chronic diarrhea was defined as unexplained diarrhea of at least 4 weeks duration. Study subjects were males and females of ages 2 – 70 with no chronic liver disease and were consecutively enrolled. Diagnoses were made by attending physicians, and IBD patients did not necessarily have active disease beyond diarrhea at the time of specimen collection. Primary endpoint: Proportion of patients diagnosed with either IBS or IBD testing positive for FCP.

Statistical analysis

Method comparison analysis was performed by Deming linear regression. A post hoc analysis of patients from the diarrhea study diagnosed with either IBS or IBD was performed. The significance of the proportion of patients diagnosed with either IBS or IBD testing positive for FCP was calculated using Fisher’s Exact Probability Test. The assay was assessed at cut-offs of 50 µg/g and 120 µg/g.

Results

Figure 1.

Table 1.

Table 2.

Conclusion

The Procise FCP assay shows excellent analytical agreement to another commercial FCP assay and can clinically significantly distinguish between IBD and IBS in chronic diarrhea patients. Thus, the assay can aid in the differentiation of IBD from IBS. Distinguishing IBS from IBD with a convenient POC format test enhances the clinical utility of FCP by enabling faster treatment response
P255 Mirikizumab modulates genes associated with the symptom of bowel urgency
Authors: Krishnan G , Steere B , Higgs R , Wang Y C , Harris C J , Milch C , Escobar R , Reinisch W , Dubinsky M
Published: January 2022

Background

Bowel urgency (BU) is one of the most common and distressing symptoms experienced by patients (pts) with ulcerative colitis (UC). Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and an acceptable safety profile in a phase 2 randomized clinical trial in pts with moderately to severely active UC. We have previously shown that miri significantly downregulates transcripts associated with disease activity defined by modified Mayo score and Robart‘s Histopathology Index, and upregulates genes expressing transporter proteins associated with healthy mucosa in pts with UC. Here we investigate associations between colon tissue transcripts and patient-reported BU at Baseline (BL) and Week (W)12. We assess the effect of miri induction treatment on genes associated with BU.

Methods

Pts were randomized 1:1:1:1 to receive intravenous placebo (N=63), miri 50mg (N=63) or 200mg (N=62) with possibility of exposure-based dose increases, or fixed miri 600mg (N=61) every 4 weeks for 12 weeks. Patient colonic biopsies were collected at BL and W12 (placebo N=58, miri 50mg N=52, 200mg N=51, 600mg N=54). Gene expression was measured using an Affymetrix HTA2.0 microarray workflow. Differential gene expression was determined by paired T-test comparing expression values at W12 and BL. BU was reported daily by pts as yes/no. Proportion of days of BU at BL and at W12 was calculated for the 3 days prior to visit on a 4-point ordinal scale (0: absence of urgency on all 3 days; 3: presence of urgency all 3 days). BL and W12 gene expression and BU values were pooled and associations identified based on non-parametric Kendall’s tau. Pathway analysis of correlated genes were performed using over-representation analysis on Hallmark and Reactome gene sets from MSigDB. p values of enrichment were determined by hypergeometric distribution test and adjusted for multi-testing with Benjamini-Hochberg (BH) procedure.

Results

A total of 249 pts reported BU scores at BL and W12. The presence of BU was associated with 320 genes (|tau|> 0.225 and qval <0.001). Pathway analysis identified pathways significantly associated with BU (Table). Among the 320 correlated transcripts, 296 were positively correlated (higher gene expression) and 24 were negatively correlated (lower gene expression) with the frequency of BU. Treatment with miri (200mg) resulted in a statistically significant decrease in the 296 transcripts positively correlated with BU, and an increase in the 24 transcripts negatively correlated with BU.

Conclusion

This is the first study to identify colon-based transcripts pertinent to mucosal inflammation and healing that correlate with bowel urgency and that are consistently modulated by miri.
P262 Decreased infliximab trough levels (TLI) is a moderate predictor of loss of response to IFX in IBD patients
Authors: Roblin X , Berger A E , Bastide L , Tournier Q , Veyrard P , Paul S
Published: January 2022

Background

If the use of anti-TNF trough levels (TDM) are proposed in case of loss of response (reactive attitude), a proactive strategy has not shown in most randomized trials its interest. The aim of this study was to analyze the predictive value of a decrease of TLI in IBD patients in terms of loss of response over time.

Methods

This was a retrospective study that included all IBD patient followed in our university hospital. Eligible patients had to have IBD treated with IFX as maintenance therapy (5mg/kg/8weeks). Patients had to be in clinical remission of the disease at inclusion with calprotectin levels < 100 µg/g stool and therapeutic levels of IFX concentration (TLI > 5 µg/ml) on IFX mono- or combination therapy. IFX levels were analyzed by ELISA (Theradiag, France). Every two months, patients were reviewed in the day hospital with fecal calprotectin, TLI and a measure of the clinical activity score (CDAI for CD and Mayo clinical score for UC). Loss of response was defined for CD as a CDAI > 220 with fecal calprotectin > 250µg/g stool and for UC as a full Mayo score > 5 with an endoscopic Mayo score > 1. Low TLI during follow-up was defined as a level below 3 µg/mL. Patients who had dose optimization based on calprotectin or TLI alone were excluded from the study.

Results

145 patients (65% CD, mean age 34 years, disease duration 4.5 years) were included. The mean follow-up was 66 months. 79 patients (55%) showed a loss of response. A decrease of TLI was found in 65% of patients who relapsed within 6 months versus 33% in patients in long-term clinical remission (p=0.14). The predictive value of loss of response within 6 months was moderate in the presence of low IFX levels (sensitivity: 71%, specificity: 73%; PPV: 73%, NPV: 68%). Conversely, fecal calprotectin (> 250 µg/g stools) increase was strongly predictive of loss of response within 6 months (sensitivity: 85%, specificity: 85%). The association of the two markers (decrease of TLI and/or increase of fecal calprotectin) improved the predictivity of relapse in the follow-up (sensitivity: 90%, Specificity: 89%). For the 79 patients who relapsed, for 35% (28 patients) of the cases, the rise of fecal calprotectin preceded the fall of TLI but for 25% of the cases (25 patients), apparition of low TLI preceded the rise of fecal calprotectin.

Conclusion

The decrease of TLI is n moderately predictive of a loss of clinical response in the short or medium term under IFX for IBD. These results may explain the negative results of a proactive attitude based on TDM alone. A proactive strategy based on TDM and fecal calprotectin could be very interesting but needs to be confirmed.