bluuebunny/crossref_metadata_2025 huggingface dataset:
P107 IL10 secretion endows intestinal human iNKT cells with regulatory functions towards pathogenic T lymphocytes in Crohn’s disease patients
Authors: Burrello C , Strati F , Diaz-Basabe A , Lattanzi G , Lopez G , Trombetta E , Conforti F S , Botti F , Vecchi M , Fantini M C , Caprioli F , Facciotti F
Published: January 2022

Background

Invariant Natural Killer T (iNKT) cells perform pleiotropic functions in different tissues by secreting a vast array of pro-inflammatory and cytotoxic molecules. However, the presence and function of human intestinal iNKT cells capable to secrete immunomodulatory molecules such as IL-10 has never been reported so far. Here we describe for the first time the presence of IL10-producing iNKT cells (NKT10 cells) in the intestinal lamina propria of healthy individuals and of Crohn’s Disease (CD) patients.

Methods

Frequency and phenotype of NKT10 cells were analyzed ex-vivo from intestinal specimens of Crohn’s disease (n=17) and controls (n=7). Stable CD-derived intestinal NKT10 cell lines were used to perform in vitro suppression assays and cocultures with patients’-derived mucosa-associated microbiota. Experimental colitis models were performed by adoptive cell transfer of murine splenic naïve CD4+ T cells in the presence or absence of IL10-sufficient or deficient iNKT cells. In vivo induction of NKT10 cells was performed by administration of SCFA by oral gavage.

Results

Patient’s derived intestinal NKT10 cells demonstrated suppressive capabilities towards pathogenic CD4+ T cells. The presence of increased proportions of mucosal NKT10 cells associated with better clinical outcomes in CD patients. Moreover, an intestinal microbial community enriched in SCFA-producing bacteria sustained the production of IL10 by iNKT cells. Finally, IL10- deficient iNKT cells failed to control the pathogenic activity of adoptively transferred CD4+ T cells in an experimental colitis model.

Conclusion

These results describe an unprecedent IL10-mediated immunoregulatory role of intestinal iNKT cells in controlling the pathogenic functions of mucosal T-helper subsets and in maintaining the intestinal immune homeostasis.
P109 Risk of cervical cancer in incident Ulcerative Colitis during the first 10 years after diagnosis: A nationwide population-based study
Authors: Kim J , Kim H , Park S C , Lee J K , Kang D R , Kim S Y , Kim H S , Kim H M
Published: January 2022

Background

Several studies suggested association between inflammatory bowel disease (IBD) and risk of cervical cancer in women. We investigated the risk of cervical cancer in patients with ulcerative colitis (UC) using the nationwide population-based claims data in South Korea.

Methods

We analysed the claims data of the Korean National Health Insurance (2006–2015). UC and cervical cancer were defined using International Classification of Diseases-10 codes and UC-specific prescription. Age- and sex-matched individuals without UC (control group) were randomly selected from the general population. Hazard ratios (HRs), adjusted for different covariates, were calculated using multivariate Cox proportional hazard regression.

Results

In total, 30,546 and 88,829 individuals with UC and without UC, respectively, were enrolled. Cervical cancer developed in 26 (0.21%) among UC patients, and 51 (0.14%) among control group, respectively. The standardized incidence ratio (SIR) of cervical cancer in the UC and non-UC groups were 2.04(95% confidence interval [CI], 1.33–2.98), and 1.35(95% CI, 1.00–1.77). The HR of cervical cancer in UC group, with reference to the non-UC group, was 1.56 (95% CI, 0.97–2.50). Further, UC groups were stratified according to age (HR=9.89, 1.62, 0.79 and 3.65 for 0–19, 20–39, 40–59, and ≥60 years, respectively). HR was significantly higher for early-onset UC (0–19 years) and late-onset UC (≥60 years). Among UC, age≥40, low socioeconomic status, rural residence, cerebral vascular disease are risk factors for cervical cancer.

Conclusion

UC patients had an increased risk of cervical cancer, especially with early-onset (0–19 years) and late-onset (>59 years). Since cervical cancer incidence is higher in UC patients than in the general population, UC patients should receive the human papillomavirus vaccine prophylactically.
P112 The road to disease control: Combination of histologic and endoscopic remission predicts long-term disease outcome in ulcerative colitis
Authors: Bretschneider F , Kormilez D , Sari S , Pflaum T , Le H D , Nikolaus S , Lassen A , Rosenstiel P , Roecken C , Szymczak S , Schreiber S , Aden K
Published: January 2022

Background

Independent assessments of histologic and endoscopic scores are two commonly used parameters as therapeutic endpoints in ulcerative colitis. However, our individual goal for patients is to achieve (long-term) disease-control. It has been recently shown that the individual combination of histologic and endoscopic remission is related to favorable long-term outcomes1. However, real world evidence for the benefit of using combined endoscopic and histologic remission endpoints is scarce.

Methods

We collected data from a retrospective cohort study of n=398 patients with active UC who underwent clinical assessment and routine colonoscopy. All patients donated data and biomaterials at the University Hospital Schleswig-Holstein (Kiel) using the broad consent2. The patients were observed over a minimum of 6 months and three individual outcomes were pre-defined as outcome-endpoints: i) therapy escalation (systemic steroids/new targeted MoA), ii) long-term hospitalization and iii) IBD-related surgery.

Results

398 UC patients (female: n=166, 41.7%, male: n=232, 58.29% with a median age of 47 years at time of routine colonoscopy) were analyzed. We observed therapy escalation in 134 cases (42.27%), hospitalization in 70 cases (21.21%) and IBD-related surgery in 34 cases (10.66%). Remission at the time of colonoscopy was assessed by endoscopic Mayo (eMayo=0) or Nancy-Index (=0) and used for prediction of long-term outcome.We investigated the benefit of combined endoscopic and histologic remission on long-term outcome by comparing a combination of both eMayo=0 and Nancy=0 against eMayo=0 and Nancy>0. Patients with combined histologic and endoscopic remission show a significantly reduced hazard ratio for all three outcome endpoints, such as therapy escalation (HR 0.20, CI 0.10–0.39, p<0.001), hospitalization (HR 0.24, CI 0.09–0.59, p=0.002) and IBD-related surgery (HR 0.20, CI 0.05–0.84, p=0.028).

Conclusion

We show that the combined assessment of endoscopic and histologic remission substantially increases the identification of patients with favorable long-term outcome in UC. However, even in patients with combined endoscopic and histologic remission approx. 20% underwent therapy escalation within 6-month period. These data highlight the need of combined endpoints using histology, endoscopy and probably other parameters (e.g. inflammatory biomarkers, patient reported outcomes) to define disease control and predict favorable disease trajectories in the future course of patients with UC.
P121 Second-Line Biologic Therapy Persistence in a Multicentre Cohort of Inflammatory Bowel Disease Patients
Authors: Doherty J , Stack R , O Morain N , Corcoran R , Ryan B , Doherty G , Mc Namara D , Kevans D
Published: January 2022

Background

Anti-TNF agents are effective treatments for Inflammatory Bowel Disease (IBD), however, a significant proportion of patients require second-line biologic therapy. Real-world data on the outcome of second line biologic therapy can inform clinical decision-making.

Methods

To evaluate prescribing practice and second-line biologic therapy persistence in IBD patients. IBD patients, who had received one prior anti-TNF agent and commenced a second-line biologic, at participating centres, were identified. Baseline demographic data, concomitant medication and biologic therapy history were characterised by retrospective review of patients records. Adalimumab(ADA) and golimumab(GOL) were considered subcutaneous(SC) anti-TNF agents. Date of commencement and discontinuation of therapies were documented. Kaplan-Meier survival curves were constructed for time based analyses. P values < 0.05 were considered significant in analyses.

Results

N=395 IBD patients were included; 30%, 68% and 2% had UC, CD and IBD-U respectively; age (median[IQR]) 26[18–35] years; 56% female; 35% receiving a concomitant immunomodulator (IMM); follow-up time (median [IQR]) 1.5[0.7–3.3] years. Second-line biologic therapy with SC anti-TNF, infliximab(IFX), vedolizumab(VDZ), and ustekinumab(USTK) was used in 36%(n=143), 38%(n=151), 10%(n=38), and 16%(n=63) of patients respectively. Follow-up time (median[IQR]) was significantly longer for SC anti-TNF and IFX compared with VDZ and USTK groups: 1.7 [0.7–3.6], 1.7 [0.7–3.5], 1.1[0.3–2.5], 1.3[0.5–2.3] years respectively, p=0.03. A greater proportion of patients receiving anti-TNF therapy versus alternate class biologic therapy received a concomitant IMM: 42%, 34%, 18% and 29% of SC anti-TNF, IFX, VDZ and USTK treated patients respectively, p=0.03. In a univariate survival analysis there was no significant difference in survival-free of drug discontinuation comparing second-line biologic agents, p=0.8. In a multivariate analysis, including second-line biologic agent type, concomitant IMM use, gender and IBD phenotype the only factor significantly associated with time to drug discontinuation was UC phenotype, Hazard ratio (95%CI): 1.5 (1.1 – 2.1), p=0.007.

Conclusion

While follow-up time was shorter for VDZ and USTK treated patients, the durability of response to second-line biologic therapy, assessed by drug persistence, appeared similar between agents. UC phenotype was associated with a shorter time to therapy discontinuation.
P131 Impact of Inflammatory Bowel Disease on patients’ caregivers: Results from a French cohort
Authors: El Hajj MD W , Buisson A , Olympie A , Ravel M H , Devos C , Trang C , Nahon S
Published: January 2022

Background

Inflammatory Bowel Disease (IBD) has an important impact on patients’ quality of life (QOL). Data on its impact on patients’ close relatives are limited. This study aims at exploring the effect of IBD on patients’ caregivers (PC).

Methods

We have conducted an online survey about the impact of IBD on PCs via the social network of the French association of IBD patients (Association François Aupetit) between october 16th and november 23rd 2020. The burden the disease had on their psychological, professional and social life was evaluated through a computerized questionnaire.

Results

Eight hundred and fifty-three PCs aged > 16 years were interrogated. 77% were females. Their relatives had Crohn’s disease (CD) in 63% and Ulcerative colitis (UC) in 35% of cases. Patient was the child in 57% or the partner in 31% of cases. Fifty four percent of PCs had never heard about IBD before the diagnosis of their relatives, and upon disease announcement, 86% experienced a feeling of worry, sadness or anxiety. They were regularly searching informations about the disease through internet websites, IBD associations or health care professionals in 72, 68 and 53% of cases, respectively. Main concerns included novel therapies (55%), treatment side effects (45%), long term disease consequences (52%) and dietary limitations (47%). Twenty percent considered that they were still not well informed about the disease. The most significant impact on daily PCs’ life was psychological as they were regularly experiencing anxiety and incapacity in 94% of cases. Concerning professional impact, 36% of PCs needed to reduce or to adjust their work time, to work from home or even to change or leave their work. Among partners, the disease impacted their sexual life as 22% reported a decrease in their desire/libido and 14% reported an absence of sexual relation for weeks or months. Sixty four percent have waived many social activities as going out with friends, holidays or cinema. More than 50% wished they had more psychological support as well as more information about the disease and the way they could help their relatives. The main factors associated with a higher psychological impact were the following: Female sex (OR 2.23; 95%CI 1.51–3.28; p<0.0001), parental status (OR 2.29; 95%CI 1.28–4.11; P<0.0001), IBD duration <5 years (OR 1.72; 95%CI 1.11–2.66; P=0.005) and the lack of information about the disease (OR 0.59; 95%CI 0.39–0.88; P=0.01).

Conclusion

IBD had an important impact on PCs’ QOL at personal and social levels. A psychological support and an appropriate information about the disease and the help they can provide to their relatives are essential to reduce the burden of IBD on their daily life.
P134 Are hepatic steatosis predictive scores still useful to predict metabolic associated fatty liver disease (MAFLD) in Crohn’s disease patients?
Authors: Capela T , Macedo Silva V , Freitas M , Cúrdia Gonçalves T , Magalhães J
Published: January 2022

Background

Crohn’s disease (CD) patients have a higher risk of nonalcoholic fatty liver disease (NAFLD) compared with the general population. There are many NAFLD predictive scores, including Hepatic Steatosis Index (HSI), Fatty Liver Index (FLI) and the Clinical Prediction Tool for NAFLD in Crohn’s Disease (CPN-CD), a recently validated score specifically developed for CD patients. However, it is not known whether these scores are useful in predicting metabolic associated fatty liver disease (MAFLD) in CD patients.

Our aim was analyze and compare the performances of CPN-CD, Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI) in identifying CD patients with MAFLD.

Methods

Retrospective cohort study which consecutively included all adult CD patients submitted to transient elastography (TE) from January to December 2020. Patients’ demographic, clinical and biochemical data were recorded. MAFLD criteria were assessed and hepatic steatosis (HS) was defined by a controlled attenuation parameter (CAP) >248 dB/m using TE. CPN-CD, HSI, and FLI were calculated, their accuracy for the prediction of MAFLD was evaluated through a receiver-operating characteristic (ROC) curve and their areas under the ROC curve (AUROC) were compared.

Results

Of 103 CD patients, 56 (54.4%) were female with a mean age of 38.2±11.5 years. Body mass index >25, type 2 diabetes mellitus, dyslipidemia and arterial hypertension were present in 53 (51.5%), 4 (3.9%), 27 (26.2%) and 9 patients (8.7%), respectively. HS was identified in 50 patients (48.5%), of which 44 (88%) fulfilled MAFLD criteria. Median HSI was 38.9 (IQR 7.2) and mean FLI and CPN-CD were 36.7±27.7 and -0.5±1.5, respectively. FLI (AUROC, 0.919; 95% confidence interval, 95% IC, 0.866–0.972), HSI (AUROC, 0.850; 95% CI, 0.775–0.925) and CPN-CD (AUROC, 0.809; 95% CI, 0.722–0.896) had excellent discrimination in predicting MAFLD. FLI performance was significantly higher than CPN-CD (P=0.01) but not significantly different from HSI (P=0.06). Additionality, HSI performance was not significantly different from CPN-CD (P=0.81).

Conclusion

The FLI, HSI and CPN-CD scores can accurately identify MAFLD in CD patients, allowing the selection of those in whom hepatic steatosis and metabolic risk factors assessment may be particularly beneficial.
P137 Lesions of Cytomegalovirus and Epstein Barr virus of the proximal gastrointestinal tract in patients with Inflammatory Bowel Disease after COVID-19
Authors: Babayeva-Sadigova G , Makhmudov U , Quliyev F , Asadova G , Mirzazade O , Samadova T , Hasanova A
Published: January 2022

Background

The problem of opportunistic infections in IBD remains one of the most pressing issues in the diagnosis and treatment of this pathology. Particular attention among opportunistic infections in IBD is given to cytomegalovirus infection(CMV), the Epstein-Barr virus(EBV). Aim: To assess the frequency of detection of CMV and EBV in biopsies taken from the mucous membranes of the proximal gastrointestinal tract (GIT) in patients with IBD who underwent COVID-19.

Methods

72 patients with CD(40 w/32 m) and 69 patients with UC(39 m/30 w) who underwent COVID-19, in whom CMV and EBV were not previously detected, were examined. The age of the patients was from 18 to 62 years(39.4±2.7). All patients(p.) underwent a standard endoscopic examination(EE), disease activity was assessed in accordance with the ECCO regulations; the determination of CMV and EBV was carried out by PCR in biopsies of mucous membranes from the proximal GIT.

Results

EE in 27 p.with CD revealed deeper and more widespread ulcerative lesions of the gastric mucosa(CMV+11 p.40.7%/15.3%;EBV+12 p.44.4%/16.7 %;CMV and EBV+4 p.14.8%/5.5%), in 16 p.similar changes were detected in the esophagus(CMV+7 p.43.7%/9.7%,EBV+6 p.37.5%/8.3%;CMV and EBV+3 p.18.7%/4.2%),in 49 p.in the duodenal region(CMV+17 p.34.7%/23.6 %,EBV+23 p.46.9%/31.9%;CMV and EBV+9 p.18.4%/12.5%).

EE with UC revealed deeper and more widespread ulcerative lesions of the gastric mucosa in 29 p. (CMV+12 p.41.4%/17.4%;EBV+13 p.44.8%/18.8%; CMV and EBV+4 p.3.8%/5.8%),in 19 p. similar changes were detected in the esophagus(CMV+9 p.47.7%/13.1%,EBV+6 p.31.6%/8.7%;CMV and EBV+4 p.21.1%/5.8%),in 44 p. in the duodenal region(CMV+17 p.38.6%/24.6%,EBV+23 p. 52.3%/33.3%;CMV and EBV+4 p.9.1%/5.8%).

Thus, in patients with CD, when determining CMV in biopsy materials by PCR,an isolated positive result(48.6%) was obtained in 35 cases,for EBV(isolated)-41 cases(56.9%), in 16 pat. a combined lesion of CMV and EBV was revealed(22.2%); the localization of lesions was dominated by the duodenal region(68.1%),the stomach (37.5%)and the esophagus(22.2%). In patients with UC, when determining CMV in biopsy materials by PCR,an isolated positive result(55.1%) was obtained in 38 cases,for EBV(isolated)-42 cases(60.7%),in 12 pat. a combined damage to CMV and EBV(17.4%); the localization of lesions was dominated by the duodenal region(63.8%),the stomach(42%) and the esophagus(27.5%).

The clinical and endoscopic picture indicates a more severe course of IBD in the presence of herpes viruses detected by PCR examination of biopsies taken from the mucous membranes of the proximal GIT.

Conclusion

The findings allow us to recommend the need for more thorough inspection during endoscopy in patients with IBD who have undergone COVID-19.
P145 Ultrasonographic parameters associated with mucosal healing 1 year after infliximab therapy in Crohn’s Disease: a multicentric and prospective study
Authors: Nascimento C , Frias Gomes C , Morão B , Cúrdia Gonçalves T , Dias de Castro F , Moreira M J , Cotter J , Pereira F , Caldeira A , Rosa C , Macedo G , Macedo C , Ferreira M , Cravo M , Glória L , Torres J , Palmela C
Published: January 2022

Background

Bowel wall thickness (BWT) is an accurate ultrasonographic parameter to assess disease activity in Crohn’s disease (CD). The IBUS-SAS score includes BWT, doppler sign, loss of stratification and inflammatory fat (i-fat) and allows a reproducible assessment of inflammation in CD using intestinal ultrasound (IUS). Our aim: to assess clinical, laboratorial and ultrasonographic predictors of mucosal healing (MH) at 1 year of infliximab (IFX) therapy.

Methods

Prospective multicentric cohort study including patients with active CD starting IFX. Harvey-Bradshaw index, C-reactive protein (CRP), fecal calprotectin (FC) and IUS were performed at week 0, 14, 30 and 54. IUS remission was defined as BWT normalization (≤3mm) in the most affected segment. Ileocolonoscopy was performed at W0 and W54. MH was defined as SES-CD <3 with no ulcers.

Results

We included 28 patients with CD (61% male; mean age of 34±12y). Clinical, laboratory and sonographic parameters are shown in Table 1. At week 54, 89% were in clinical remission, 79% had normalization of CRP and FC, 50% had IUS remission and 39% had MH. MH at W54 was associated with lower BWT at W14 (3.7 vs 5.2mm, p=0.049), lower Limberg score at W14 (1 vs 2, p=0.006), lower levels of i-fat at W14 (18 vs 72%, p=0.006) and lower IBUS-SAS score at W0, W14 and W30 (47 vs 71, p=0.002; 26 vs 58, p=0.001; 25 vs 50 p=0.046). We found a fair to good correlation between SES-CD W54 and BWT at W14 (r=0.45, p=0.015), Limberg score at W14 (r=0.4, p=0.037), IBUS-SAS at W0 and W14 (r=0.49, p=0.008; r=0.58, p=0.001). The area under the curve of IBUS-SAS for MH was 0.86 at W0 and W14 and 0.69 at W30. Best IBUS-SAS cut-off value was 27.6 at W14.

Conclusion

Lower values of BWT, Limberg score and i-fat after induction (W14) were associated with MH at 1 year of therapy. IBUS-SAS score at W14 had the highest AUC to predict MH at 1 year. Early IUS monitoring can be a helpful tool to predict response to therapy in CD patients at 1 year.
P148 Subclinical inflammatory bowel disease precedes the diagnosis and leads to an increase on healthcare resources utilization: multicentric case-control study in the Basque Country
Authors: Rodríguez-Lago I , Aguirre U , Ramírez de la Piscina P , Muñagorri A , Zapata E , Higuera R , Montalvo I , Iriarte A , Fernández-Calderón M , Arreba P , Carrascosa J , Cabriada J L , Barreiro-de Acosta M
Published: January 2022

Background

The inflammatory process associated to ulcerative colitis (UC) and Crohn’s disease (CD) starts before the onset of symptoms and the diagnosis, but this period has not yet been well defined. Our aim was to determine if patients with an incidental diagnosis of UC or CD have an increase in healthcare utilization in the years preceding the symptomatic onset of the disease.

Methods

All asymptomatic patients with a diagnosis of UC or CD during the colorectal cancer screening program between October 2010-January 2021 were included in this multicentric retrospective case-control study. Cases were matched 1:3 with controls adjusted by sex, age and date, excluding subjects with any visit to Gastroenterology. The main outcomes were the number of outpatient or Emergency Rooms visits, admissions, radiological examinations (US, CT, MRI), sick-leaves, and drug prescriptions (antibiotics, systemic steroids) up to 5 years before the diagnosis. Descriptive statistics were used, with chi-square tests and a multivariable hurdle or negative binomial regression model, adjusted by smoking habits and Charlson index.

Results

A total of 124 patients were included (87 UC, 30 CD, 7 IBD-U; median 56 years (IQR, 53–62); 56% male), compared with 372 controls. Baseline characteristics including comorbidities were balanced between both cohorts. Patients demonstrated an increase in the number of visits to Primary Care physician during both 3 and 5 years before the diagnosis, but there were no differences in the remaining outcomes including hospital admissions, Emergency Room or outpatients visits, and sick-leaves (Figure 1 and 2). Systemic steroids were more frequently prescribed to patients in the preceding 3 to 5 years before diagnosis. Patients underwent US and/or CT scan less frequently in the preceding 5-year period.

Conclusion

Patients with IBD show an increased need of medical assistance in the years prior to the diagnosis, even during the presymptomatic phase of the disease. Tools focused on early identification of IBD may start on Primary Care facilities, but certain factors as steroids may alter the development of symptoms and the full spectrum of the disease.
P151 Rationalizing colonoscopy utilization for Inflammatory bowel disease diagnosis: time to reset the Calprotectin threshold to >600?
Authors: Desoki R , Abdellah Ahmed M , Taylor K , Woodward J , Corbett G , Parkes M
Published: January 2022

Background

Faecal calprotectin (FC) measurement is used to stratify risk of IBD in primary care. Typically the normal range for FC is 0–50 ug/g, and in established practice FC>200 mandates gastroenterology referral for further investigations, including colonoscopy. The optimal FC threshold for referral is, however, debated: most people with FC>200 do not have IBD and some with IBD have FC<200.

We aimed to assess FC at different thresholds, and whether the threshold might be safely raised (hence reducing the numbers referred for colonoscopy) by combining FC with other easily ascertained parameters without significantly impacting IBD diagnostic yield.

Methods

We included all patients aged 18–45 in whom FC testing was requested in primary care in 2018 and 2019, regardless of FC result, and who subsequently underwent colonoscopy at Cambridge University Hospitals (CUH). We excluded patients with a prior IBD diagnosis. Based on the retrospective review of findings at colonoscopy and case notes, we classified the final diagnosis as one of (1) normal (2) IBD/subtype (3) non-IBD intestinal inflammation (e.g. infection, microscopic colitis, NSAID enteropathy) and (4) cancer.

Results

852 patients were included, 60% female, median age 33. The FC ranged from 10 to >600. 98/189 with FC>600 had IBD, compared to 17/166 with FC 200–600 and 15/497 with FC<200 (Figure 1). Only 52% with small bowel CD had FC>600 (Figure 2).

74% of colonoscopies showed no inflammation. 10.5% of these patients had FC >600 and 18.6% had FC 200–600.

Of the 32/130 (24.6%) patients with newly diagnosed IBD who had FC<600, 24 reported rectal bleeding, 13 had raised CRP >6, and 6 had a family history (FH) of IBD (table 1). Only one patient with FC <600 subsequently diagnosed with IBD had none of these parameters. Sensitivity and specificity data are provided in table 2. For patients with intermediate FC the UK advice is to repeat the test. In our cohort 168 patients had an initial FC of <600 and had a repeat. In this group the subsequent FC was <50 in 88. 6 cases of IBD were identified in those in whom the repeat FC was >50 but <600, but all had one or more of rectal bleeding, raised CRP or FH of IBD.

12/852 were found to have colorectal cancer, however, 8 of them had been referred to CUH on the ‘suspected cancer’ pathway. Of the 4 referred on the ‘suspected IBD’ pathway, only 1 had FC >600 – others were in the 50–600 range.

Conclusion

Based on our observations, using an FC threshold of >600, or 50–600 with one or more of rectal bleeding, raised CRP or FH of IBD, would substantially reduce the number of colonoscopies undertaken and have a minimal impact on diagnosis of IBD. Repeat testing following a modestly elevated FC had no further utility. These data require independent validation.
P156 A multicentric study on the development and application of a deep learning algorithm for automatic detection of ulcers and erosions in the novel PillCam™ Crohn’s capsule
Authors: Ribeiro T , Mascarenhas M , Afonso J , Cardoso H , Andrade A P , Lopes S , Mascarenhas Saraiva M , Ferreira J , Macedo G
Published: January 2022

Background

Crohn’s disease has the potential to involve all segments of the gastrointestinal tract, requiring frequent and judicious clinical and endoscopic surveillance. Capsule endoscopy (CE) has revolutionized the management of these patients, playing a role in diagnosis, classification, and assessment of response to treatment. In 2017, PillCam™ Crohn’s Capsule (PCC) was introduced to provide a panenteric assessment to this panenteric disease. However, reviewing each PCC exam is time-consuming and prone to errors as it implies examining thousands of images while significant lesions may only be represented in a small number of frames. Recently, the development of artificial intelligence (AI) algorithms for automatic interpretation of endoscopic images has generated a large interest. The performance of these tools, particularly convolutional neural networks have shown potential to overcome some of the main drawbacks of CE. This multicentric study aims to assess the performance of a deep learning algorithm for the automatic detection of small intestinal and colonic ulcers and erosions in PCC images.

Methods

We included a total of 59 PCC exams from two centres (ManopH Gastroenterology Clinic and Centro Hospitalar Universitário de São João) performed between 2017 and 2021. A total of 78415 frames were extracted. This pool of images was constituted by 14124 images depicting ulcers and erosions and 64291 with normal enteric and colonic mucosa. For the automatic identification of these findings, this image pool was split into training and validation datasets in a patient-based manner. Therefore, images from the same patient were restricted to a single dataset. A CNN model with transfer learning was developed using tensorflow and keras tools.

Results

The neural architecture of our CNN was optimized for the detection of enteric and colonic ulcers and erosions. An example of the output provided by the CNN is shown in Figure 1.

The deep learning model had a sensitivity of 86.7%, a specificity of 98.6%, a positive predictive value of 92.3% and a negative predictive value of 97.4%. The overall accuracy of our network was 96.6% (Figure 2).

At a threshold value of 50%, our CNN had an area under the curve of 0.98 for the detection of ulcers and erosions (Figure 3).

Conclusion

In this multicentric study, our group has developed a CNN and assessed its performance in a patient-based design, which provides significant robustness to our results. Patient-split analyses are the first step towards real-life application of AI solutions which, allied to the high-performance results of our model, may significantly improve the diagnostic yield of this panendoscopic tool.
P177 Validation of UC Intestinal Ultrasound (UC-IUS) Index for children with Ulcerative Colitis
Authors: Huynh Dr H , Ma H , Isaac D , Novak K , Almeida P , Kim J , Kuc A , Carroll M , Wine E
Published: January 2022

Background

Transabdominal bowel ultrasound (TABUS) is an ideal tool to assess transmural inflammation in children with Ulcerative Colitis (UC). The UC intestinal US (UC-IUS) Index was developed and validated using endoscopy with strong correlation between UC-IUS Index and Mayo subscore (ρ 0.830; p<0.001). Our aim was to determine how bowel wall thickness (BWT) and UC-IUS Index performed in children at diagnosis in comparison to endoscopy using the Mayo score.

Methods

Subjects (0–18 years old) with suspected inflammatory bowel disease (IBD) were prospectively enrolled. Baseline TABUS (excluding rectum due to poorly seen) done prior to endoscopy. Pediatric Ulcerative Colitis disease Activity Index (PUCAI) and Mayo were calculated, albumin, C-reactive protein (CRP) and fecal calprotectin (FCP) collected. The UC-IUS Index was calculated for each segment – sigmoid (SC), descending (DC), transverse (TC) and ascending (AC) [bowel wall thickness (BWT) (mm): > 2 =1, >3 =2 and >4 =3; doppler: spots=1 and stretches =2, abnormal haustrations = 1 and fat wrapping =1]. Spearman’s rank (rho) and Pearson’s correlation (r) assess for a correlation. Receiver operating characteristic [ROC] analysis performed for BWT to determine sensitivity and specificity of BWT cut-offs in the UC-IUS.

Results

Of the 75 subjects recruited for suspected IBD, 26 had UC with mean age 15 years (SD 3.33) and 5 had normal US. Twenty three have extensive pancolitis. Mean PUCAI score: 60 (SD 23.28), CRP 22.62 (SD 39.5) mg/l, albumin 35.6 (SD 6.96) g/l and fecal calprotectin of 2223 (SD 1757) mg/kg. ROC curves generated using a total of 122 colonic segments. BWT of 2 mm discriminates between active and inactive:Mayo 0 and Mayo1-3 [sensitivity 84.9%; specificity 86.2%; an area under the curve [AUC] 0.900]; a cut-off of 3mm discriminates between Mayo 1 from Mayo 2–3 [sensitivity of 61.3%; specificity 90.5%; AUC 0.858]; a cut of 4mm discriminates Mayo 3 (sensitivity 64.7%; specificity 85.7 %; AUC 0.876). BWT and UC-IUS scores of all colonic segments correlated highly positively with the Mayo score of corresponding segments (rho=0.684, r=0.660, p<0.001) and (rho=0.750, r=0.722, P<0.001) respectively. The UC-IUS Index correlates poorly with CRP, ESR, and Fecal Calprotectin - r = 0.262, 0.346 and 0.100 respectively; p>0.05.

Conclusion

BWT and UC-IUS Index correlated highly positively with the Mayo subscore in children with UC. UC-IUS has a better correlation than BWT. BWT cut-off of 2mm discriminate between normal and mild Mayo is optimal. Cut-offs of 3 mm and 4 mm for moderate and severe Mayo may be too high in children with lower sensitivity. A larger cohort of children with UC will need to be studied to determine optimal BWT cut-off for moderate and severe disease.
P181 IBD patients with early clinical and sonographic improvements achieve better long-term outcomes than patients with clinical improvements alone – one-year interim results of the TRUST BEYOND study
Authors: Kucharzik T , Helwig U , Seibold F , Biedermann L , Högenauer C , Fischer I , Kolterer S , Rath S , Hammer L , Maaser C
Published: January 2022

Background

In the treat-to-target era, frequent and objective monitoring of disease activity in IBD patients is emphasized [1]. Over the past years, intestinal ultrasound (IUS) has become a useful modality to monitor and assess disease activity and response to therapy. (Trans)mural response and healing examined by IUS have emerged as outcome measures of growing interest and potential therapeutic goals in the IBD community [2–4]. However, the predictive value of a composite clinical/IUS improvement for the long-term outcome remains elusive.

Methods

TRUST BEYOND is an ongoing, prospective, observational, multi-centre study in patients with active CD or UC initiating a biologic- or Januskinase-inhibitor (JAKi)-therapy at baseline. The aim of this study is to assess the predictive value of IUS parameters evaluated at week 12 for the long-term outcome after 52 weeks (assessed by clinical+ sonographic endpoints). For this interim analysis, 89 IBD patients (39 CD, 50 UC) with a documented visit at week 52 until September were included. The predictive value of (trans)mural response (TR; reduction of ≥ 25% in bowel wall thickness, BWT) and clinical remission at W12 was evaluated for the outcome at W52.

Results

Eighty-nine IBD patients in clinical flare with increased BWT were included into this analysis. Patients were predominantly female (53.9%,n=48) with a median age of 34.3 years (29.0–51.5) and a median disease duration of 7.18 years (2.31–13.47). Following the induction of advanced therapy, the rate of IBD patients with a (trans)mural response increased from 67.4% (n=60) at W12 to 73.0% (n=65) at W52. Likewise, the proportion of IBD patients demonstrating a (trans)mural healing rose from 32.6% (n=29) at W12 to 41.6% (n=37) at W52. Of note, 53.5% (n=38) of IBD patients who achieved the composite endpoint “clinical remission and (trans)mural response” at W12 were in clinical remission at W52 while only 23.9% of patients who were only in clinical remission at W12 sustained clinical remission until W52 (p=0.007). Moreover, patients achieving both early clinical remission and (trans)mural response had better sonographic outcomes at W52.

Fig 1: W52 outcomes of patients with either clinical remission and (trans)mural response or only clinical remission at W12.

Conclusion

IBD patients who reached the composite endpoint clinical remission and (trans)mural response at week 12 had better outcomes after 1 year compared to patients in early clinical remission only. Our results strongly suggest that it is worth treating patients to composite clinical and sonographic endpoints.

Reference

1. Turner D et al. Gastroenterol. 2021; 2 Kucharzik T et al. Clin Gastroenterol Hepatol. 2017; 3 Maaser C et al. Gut 2020; 4 Wilkens R et al. Therap Adv Gastroenterol 2021
P197 Anogenital Crohn’s disease and granulomatosis: A systematic review of epidemiology, clinical manifestations, and treatment
Authors: Honap S , Meade S , Spencer A , Pavlidis P , Luber R , Calonje E , Rashid E , Bunker C , Lewis F , Irving P
Published: January 2022

Background

Metastatic Crohn’s disease (CD) is an extra-intestinal manifestation (EIM) characterised by ulceration, swelling or inflammatory lesions that are non-contiguous with the gut; genital involvement is rare. We conducted a systematic review of ACD and granulomatosis to provide a synthesis of epidemiology, clinical features, and treatment outcomes in adults and children.

Methods

A systematic literature search was conducted via MEDLINE, EMBASE and the Cochrane database from inception to 1st December 2020 to identify studies of ACD presentation and/or treatment outcomes. Investigators extracted, analysed, and reported study data in accordance with PRISMA. Clinical response was defined as a reduction in symptoms, genital swelling or partial healing of ulcers and fissures. Remission was defined as complete resolution of symptoms and examination findings.

Results

Of 9,381 screened studies, 185 articles, (comprising 410 cases; 273 female (F), 137 male (M)), were included (figure 1). The median age at diagnosis was 29 (F) and 16 (M) and up to 50% did not have a prior CD diagnosis. Luminal CD was subsequently diagnosed in 80% of cases including 45–80% patients without gastrointestinal symptoms (time to CD diagnosis from ACD presentation [range] –43 to 11 years). The predominant clinical features across both sexes were, oedema (79%), ulcers/fissures (47%), and hypertrophic, exophytic lesions (nodules and plaques) (23%) (table 1). Adults and children present similarly. Most patients, 81% (331/410), underwent genital biopsy (106 (M), 225 (F)). Granulomas were noted in 71% (234/331) cases and an inflammatory cell infiltrate was documented in 191/331 (58%). Systemic antibiotics, corticosteroids, thiopurines and anti-TNF therapy were the most frequently prescribed agents with the highest response and remission rates (table 2). At final follow-up, where reported, non-response, response, and remission rates were 37/304 (12%), 267/304 (88%) and 114/304 (38%), respectively. Oedema was associated with a poor response to topical corticosteroids vs. those with ulcers or fissures without oedema (p=0.03). Greater response rates to anti-TNF therapy were seen in patients prescribed concomitant immunomodulation (24/25, 96% vs 67/90, 74%, p=0.02).

Conclusion

To our knowledge this is the first systematic review of ACD in adult and paediatric males and females. ACD and granulomatosis are rare EIMs of CD that are under-recognised, leading to treatment delay, and significant morbidity. There is a wide heterogeneity in presentation and some of the treatments used in luminal and perianal CD appear to be effective. Further studies with longer follow up are required to define optimal treatment strategies.
P202 Performance characteristics of serum FGF19 measurement compared with the Se-HCAT retention test in the diagnosis of bile acid diarrhoea in Crohn’s Disease
Authors: Ruiz-Cerulla A , Blat Serra R , Sánchez-Pastor E , Notta P C , Rodríguez-Alonso L , Aràjol Gonzalez C , Serra Nilsson K , Antón Güell S , Serrano Santacruz I , Luque Gómez A , Aran J M , Rodríguez-Moranta F , Guardiola Capon J
Published: January 2022

Background

Bile acid diarrhoea (BAD) is common in patients with Crohn’s disease (CD), but its recognition is challenging since symptoms are similar to those of active inflammatory disease. The current clinical gold standard for diagnosing BAD is the Se-HCAT test, however, it is inconvenient to the patient and has limited availability. FGF19 is a hormone produced in the enterocytes of the ileum in response to absorbed BAs. Serum FGF19 levels are a direct marker of BA absorption, and they are reduced in BAD. The aim of this study was to evaluate the performance of FGF19 as a diagnostic tool for BAD in Crohn’s disease.

Methods

Fasting serum FGF19 levels and Se-HCAT retention were measured before bowel preparation in 63 consecutive Crohn’s disease patients referred for an ileocolonoscopy. Clinical, endoscopic and biologic data were prospectively recorded. BAD was defined as an abdominal retention <10% and severe BAD as <5% at day seven.

Results

BAD was present in 60% of non-resected CD (NR-CD) patients and in 93% of ileal-resected (IR-CD) patients. FGF19 levels were lower in IR-CD patients (median 23 pg/ml; IQR, 3–44) than in the NR-CD patients (61 pg/ml; IQR, 18–121) (p = 0.02). FGF19 levels were inversely related with ileal resection length in IR-CD patients (rs = -0.52, P = 0.01). FGF19 and Se-HCAT values were positively related (rs = 0.57, P < 0.0001), whereas FGF19 was inversely related with the number of bowel movements (rs = -0.31, P=0.01) and Bristol scale (rs = -0.27, P= 0.04). No significant relation was found between FGF19 and clinical (CDAI) nor endoscopic (SES-CD) scores. Area under the ROC curve for FGF19 to detect SeHCAT at <10% and <5% were 0.75 (95% CI 0.62–0.88) and 0.81 (95% CI 0.71–0.92) respectively.

Conclusion

Serum FGF19 can be used as a simple blood test to the diagnostic of BAD in CD. FGF19 measurement could be an adjunct in guiding treatments for diarrhoea in CD.
P205 Eliakim and CECDAIic scores are useful pan-intestinal tools for CD diagnosis and activity monitoring
Authors: Freitas M , Capela T , Macedo Silva V , Arieira C , Xavier S , Cúrdia Gonçalves T , Boal Carvalho P , Dias de Castro F , Rosa B , Moreira M J , Cotter J
Published: January 2022

Background

Capsule endoscopy is a valuable tool in the diagnosis and monitoring of Crohn’s disease (CD). Recently, a new panenteric capsule (pan-CE), PillCam Crohn’s (Medtronic, USA) was approved. A novel quantitative score of inflammation for PillCam Crohn’s, the Eliakim score, has emerged. However, the optimal index for panenteric monitoring disease activity is far from being completely defined. We aimed to evaluate the correlation and accuracy between the pan-CE Eliakim and capsule endoscopy Crohn’s disease activity index (CECDAIic) scores and inflammatory parameters.

Methods

Retrospective study, including a cohort of consecutive patients with suspected or established CD that underwent Pan-CE PillCam Crohn’s over 4 years. The Eliakim and CECDAIic scores were calculated. Spearman correlation (rs) was used to access the correlation between the scores and inflammatory biomarkers.

Results

Thirty-two patients were included, 71.9% females, with mean age of 35±13 years, 59.4% with suspected CD. The median Eliakim and CECDAIic scores were 5.5 (0–13) and 6.5 (0–15.5), respectively. The diagnosis of CD was established in 31.6% of patients with suspected CD. We found a very good correlation between Eliakim and CECDAIic scores (rs=0.87; p<0.001), and a moderate correlation between Eliakim and CECDAIic scores with C-reactive protein (rs=0.53; p=0.003), (rs=0.44; p=0.02), and fecal calprotectin (rs=0.46; p=0.02), (rs=0.54; p=0.01), respectively. In patients with suspected CD, an Eliakim ≥3.5 and CECDAIic score ≥5.5 had a sensitivity of 100%, and specificity of 84.6%, and 75.0%, respectively, for the diagnosis of CD.

Conclusion

The Eliakim and CECDAIic scores have a strong correlation in assessing panenteric CD activity, and a moderate correlation with inflammatory biomarkers. The application of Eliakim ≥3.5 and CECDAIic score ≥5.5 as the cutoff values for the presence of significant inflammatory activity in patients undergoing pan-CE for suspected CD may be useful to establish the diagnosis.
P210 Assessment of disease specific knowledge and quality of life among patients with Inflammatory Bowel Disease
Authors: Sequeira C , Santos I , Coelho M , Teixeira C , Mangualde J , Cremers I , Oliveira A
Published: January 2022

Background

Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract that leads to a marked decrease in quality of life. Patients should develop coping strategies. Higher levels of IBD-related knowledge are associated with lower disease-related helthcare costs and less need for a step-up strategy.

Aims

To determine individual factors influencing the level of patient knowledge and whether this has an impact on therapeutic adherence and quality of life.

Methods

The IBD-KNOW, Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and Morisky Medication Adherence Scale (MMAS-8) questionnaires were applied to IBD patients who were consecutively assessed at outpatient consultation or day-care hospital. Factors associated with higher levels of knowledge about IBD were analysed

Results

We included 74 patients (male: 51%; median age: 46 years [interquartile range (IQR): 25–67]), 54% (n=40) had Crohn’s Disease. The median duration of IBD was 5 years (IQR: 1–16 years). Physicians/nurses (n=67) and the internet (n=26) were considered the main sources of knowledge. Median IBD-KNOW score was 13 (IQR: 7–19), the percentage of correct answers was highest in the areas of vaccination (78%), epidemiology (43%) and anatomy (27%) and lowest in knowledge regarding reproduction (21%), lifestyle (21%), physiology (14%) and surgery (14%). Most patients (68%, n= 53) know that IBD with several years of evolution is a risk factor for colorectal cancer and recognize the importance of screening. The IBD-KNOW median score was statistically significantly higher in patients with previous hospitalisation (p=0.01), bowel surgery (p=0.04) and disease with more than 5 years of evolution (p=0.04). No differences were identified according to educational level. Patients adherent to therapy (MMAS-8=8) did not present higher scores (p=0.09) and no positive correlation was found between IBD-KNOW score and SIBDQ (p=0.415).

Conclusion

A longer duration of disease and previous hospitalisation/surgery related to the disease were associated with a higher level of knowledge. There was no association between quality of life and therapeutic adherence and level of knowledge. The authors intend to use this analysis to target future promotion of health education programmes to address the areas with the greatest knowledge deficits.
P216 Effect of the Crohn’s disease exclusion diet (CDED) on the fecal calprotectin level in children with active Crohn’s disease
Authors: Matuszczyk M , Meglicka M , Wiernicka A , Jarzebicka D , Osiecki M , Kotkowicz-Szczur M , Kierkus J
Published: January 2022

Background

The CDED + PEN (partial enteral nutrition) is a promising method of nutritional treatment in active Crohn’s disease (CD). An increase of fecal calprotectin (FCP) level - a marker of mucosal inflammation – happens to be the first evidence of the Crohn’s disease exacerbation, ahead of clinical symptoms, and usually accompanies clinical symptoms. In this study we present our own experience with using the CDED + PEN in treatment of children with CD and higher FCP level.

Methods

Forty eight children (male/female: 27/21) in age 4–18 years (median value = 13.6; IQR=3.7) were treated with CDED + PEN. The main inclusion criteria to the study was active CD defined as FCP level ≥ 250 µg/g. Patients with severe clinical manifestation of CD (PCDAI >40) or who started any new concomitant CD’s treatment together with the dietary intervention were excluded from the analysis. The PCDAI and fecal calprotectin level were assessed at week 0 and 12. The primary endpoint was ITT normalization of FCP level that is result< 250 µg/g at week 12. Wilcoxon Matched Pairs Test was used for statistical analysis.

Results

The normalization of FCP level was obtained in 35 % (17) of children and the minimum 50% decrease of FCP level in 56% (27). The reduction of fecal calprotectin level between week 0 and week 12 was statistically significant with median value = 1045 µg/g; IQR=1188 and 363 µg/g; IQR=665, respectively (p<0.05). In the group of 29 patients who were not in clinical remission (PCDAI≥10) at baseline 16 (55%) obtained clinical remission (PCDAI<10) at week 12 and 20 (69%) clinical response defined as a drop in PCDAI of at least 12.5 points or PCDAI<10 points. The reduction of PCDAI between baseline and week 12 was statistically significant (median value = 20 points; IQR=7.5 and 5 points; IQR=6.2, respectively (p<0.05)). All patients with normal FCP level at week 12 were in clinical remission. In 10 children (21%) the full course of 12 weeks with CDED+PEN was not completed or the concomitant therapy had been started before week 12 due to the lack of efficacy/ intolerance of nutritional treatment.

Conclusion

The 12-weeks course of treatment with the CDED + PEN has a beneficial effect on the fecal calprotectin level in children with active CD. Dietary intervention leaded to significant decrease in the FCP level in studied group and to the normalization of this parameter in every third patient.