bluuebunny/crossref_metadata_2025 huggingface dataset:
P276 Development and validation of a computed tomography-based radiomic nomogram to predict early-onset surgery risk in patients with Crohn’s disease
Authors: Yao J , Zhong Y , Zhou J , Zhi M
Published: January 2023

Background

Identifying patients with aggressive Crohn’s disease (CD) threatened by a high risk of early onset surgery is challenging. We aimed to establish and validate a radiomic nomogram to predict one-year surgery risk after the diagnosis of CD, thereby facilitating therapeutic strategies making.

Methods

Patients with CD who had undergone computed tomography enterography (CTE) examination at diagnosis were recruited and randomly divided into training and test cohorts at a ratio of 7:3. Arterial phase CTE images were obtained. Inflamed segments and mesenteric fat were semiautomatically segmented, followed by feature selection and signature building. A radiomic nomogram was constructed and validated using a multivariate logistic regression algorithm. (Figure 1)

Results

A total of 268 eligible patients were retrospectively included, 69 of whom underwent surgery one-year after diagnosis. A total of 1208 features from inflamed segments and 1100 features from peripheral mesenteric fat were extracted, and reduced to 11 and 16 potential predictors, respectively, to construct two radiomic signatures. By incorporating the radiomics signatures and clinical factors, the radiomic-clinical nomogram showed favorable calibration and discrimination in the training cohort, with an area under the curve (AUC) of 0.957, which was confirmed in the test set (AUC, 0.917). Decision curve analysis and net reclassification improvement index demonstrated the clinical usefulness of the nomogram. (Figure 2)

Conclusion

We successfully established and validated a CTE-based radiomic nomogram with both inflamed segment and mesenteric fat simultaneously evaluated to predict one-year surgery risk in CD patients, which assisted in clinical decision-making and individualized management.
P279 Ileo-caecal stenosis in Crohn's disease: correlation between imaging, biology and endoscopy : preliminary results of a prospective study
Authors: Azzouzi D , Azzouzi D , Berhili C , Lagdali N , Benelbarhdadi I , Borahma M , Ajana F
Published: January 2023

Background

Stenosis is the most common complication of Crohn's disease (CD). Imaging of the ileo-caecal junction is mainly based on endoscopy, ultrasound, CT-enteroclysis or entero-MRI. The aim was to evaluate the performance of digestive ultrasound in the monitoring of Crohn's disease.The purpose of this work is to show the performance of digestive ultrasound and fecal calprotectin in the monitoring of CD. We compared the results of digestive ultrasound, enteroscan or enteroIRM with endoscopy and biology

Methods

This is a prospective study including 42 patients, spanning between July 2021 and July 2022. Clinical, biological, radiological and endoscopic data were studied. Khi-2 test was used with a value of p<0.05 which was considered statistically significant.

Results

We included 42 patients in our study, divided into 18 men 24 women (sex ratio M/F is 0.75), mean age was 43.2 years, with a CD of L1 or L3 location, according to the Montreal classification were prospectively included. The main risk factor found was smoking in 61.9% of patients.

The majority of patients (80.95%, n = 34) had koenig syndrome. All patients underwent digestive ultrasound, CT-enteroclysis and colonoscopy with an average delay of 15 days between the examinations.

Digestive ultrasound showed intestinal thickening in 85.71% (n=36), of the small intestines in 57.14% of patients and localized at the terminal ileum (21.42%). Loss of stratification was found in 40.47% of patients, ileo-caecal stenosis in 57.14%, a directed fistula in 23.80% of patients, a deep collection in 28.57% (n=10). The CT-enteroclysis showed stenosing thickening of the ileo-caecal junction in 66.67% (n=28), a deep collection in 38.09%, a combed aspect of the mesentery in 33.33% and intestinal thickening associated with a fistulous path in 35.71%.

Colonoscopy was performed with catheterisation of the last ileal loop in the majority of patients (73.80%, n=31). It showed ulcerations in 88.09% (70.5% deep and 17.6% superficial) and a stenosis that could not be crossed by the colonoscope in 40.47% (n=17). The mean level of faecal calprotectin was 532.5 with a standard deviation of 265.1 reflecting moderate to severe disease activity.

There was a correlation between ultrasound and endoscopy in 71.4% of cases (n=30). There was significant correlation between endoscopic and ultrasound inflammatory activity (p=0.01) and between the location of intestinal thickening and ulcerations on endoscopy (p=0.01).

Conclusion

Ultrasound is non-radiating, reproducible and available, coupled with fecal calprotectin constitutes an accessible and easy monitoring tool. Our preliminary results are satisfactory and the study is still in progress to confirm the interest of ultrasound in the follow-up of patients with CD.
P283 Awareness and perceptions of colorectal cancer risk and screening in Inflammatory Bowel Disease
Authors: Liu E , Erande A , McLaughlin J , Limdi J K
Published: January 2023

Background

Patients with inflammatory bowel disease (IBD) are at higher risk of developing colorectal cancer (CRC). Guidelines recommend periodic endoscopic surveillance to detect and manage dysplasia. We aimed to explore patient knowledge and perceptions of CRC risk and colonoscopic surveillance and identify potential barriers to surveillance practice.

Methods

A 44-item questionnaire was administered to IBD patients with colonic involvement attending gastroenterology clinics between July 2021 and April 2022.

Results

Of 418 respondents (demographics see table 1), 266 (64%) had ulcerative colitis and 145 (34%) had Crohn’s disease, with 177 (42%) diagnosed for ≥10 years. Two hundred and sixty-five (66%) patients rated their IBD control moderate/good (score ≥7/10), and 314 (75%) self-rated their understanding of IBD as good/excellent. Two hundred and ninety-eight patients (71%) recognised that CRC risk is higher in IBD but 83 (20%) felt the risk of CRC was lower in IBD or were unsure. Age (p=0.02), being a Crohn’s and Colitis UK (CCUK) member (p<0.001), patient rated IBD control (p=0.04) and self-rated understanding of IBD (p=0.01) were associated with better CRC risk awareness. One hundred and forty-nine (36%) respondents stated that their IBD healthcare professional (HCP) had previously discussed CRC risk with them; this was associated with better CRC knowledge (p=0.001). On multivariate analysis CCUK membership (OR 2.75; 95% CI 1.57- 4.83; p<0.001), prior HCP discussion (OR 1.57; 95% CI 0.85-2.87; p=0.01) and age ≥65 years (OR 0.3; 95% CI 0.09- 0.99; p=0.05) were predictive of greater CRC risk awareness. Concerning the most appropriate screening test for dysplasia, 369 patients (88%) stated colonoscopy, but only 29 (7%) were aware that colonic surveillance should commence 8-10 years after diagnosis; 153 (37%) recognised that optimal timing is when IBD is in remission. Patient reported information sources included gastroenterology HCPs (43%), patient support groups (28%), and patient leaflets (17%). The majority (78%) stated they would agree to have surveillance colonoscopy if advised by their HCP. Bowel preparation (50%) and discomfort (45%) were factors most likely to dissuade patients from agreeing to surveillance.

Conclusion

Patient knowledge of CRC risk and surveillance practice in IBD is variable. Modifiable factors associated with improved knowledge are discussion with HCPs and CCUK membership. Our findings underscore the need for better patient education to aid informed decision-making between patients and HCPs and improve adherence to colonoscopic surveillance.
P292 Complications in elderly-onset Inflammatory Bowel Diseases – A population-based study from the epidemiological database of the Israeli IBD Research Nucleus (Epi-IIRN)
Authors: Ben Hur D , Lebedenko B , Issaschar G , Moshe R , Lujan R , Focht G , Loewenberg Weisband Y , Kariv R , Ledderman N , Matz E , Dotan I , Turner D , Pinto G , Waterman M
Published: January 2023

Background

The population of elderly-onset (diagnosis >=65 years old) inflammatory bowel disease (IBD) is growing worldwide. Management of this population poses challenges, given the overall increased morbidity at the elderly age. Data related to complications in this population are limited. We performed a population-based study of elderly IBD patients to characterize complications compared with non -IBD matched individuals.

Methods

As part of the validated epidemiological cohort of the Israeli IBD Research Nucleus (epi-IIRN), we included all elderly-onset IBD patients (age at diagnosis >65 years) from the four Israeli health funds diagnosed from 1.1.2005 until 30.06.2020, covering 98% of the Israeli population. Each IBD case was matched at diagnosis to 3 non-IBD individuals by year of birth, sex, geographic district, and health fund. Comparison of incidence of pneumonia, osteoporotic fractures, bacteremia/septicemia and venous thromboembolism events were made. Time to complication was compared using the Kaplan-Meier survival analysis, stratified by IBD subtype, sex and any exposure of >3 months to immunosuppressive IBD medications. Cox proportional hazard models were sought to explore complications risk adjusted by comorbidities (chronic obstructive pulmonary disease, ischemic heart disease and other diseases).

Results

A total of 2,163 elderly-onset IBD patients were identified (46% males; 48% with Crohn’s disease, median (IQR) age at inclusion 71 [68, 76] years, exposure to >3 months of systemic CS 25%, thiopurines 10%, methotrexate 3.3%, anti-TNF 10.2%, Vedolizumab 5.7%, Ustekinumab 1.7%) and compared to 6,489 matched non-IBD controls. Median (IQR) follow-up time was 74 (40, 118) months. Incidence rates of pneumonia, fractures, bacteremia and venous thromboembolism are shown in table 1. On univariate analysis event-free survival analyses were similar in IBD and controls in pneumonia (p=0.72), osteoporotic fractures (p=0.79), bacteremia (p=0.085) and venous thromboembolism (p=0.14) Figure 1. Survival analysis remained similar when stratified by sex, IBD subtype and drug exposure. Using the comorbidity adjusted Cox model, the overall HR of pneumonia was 1.04 (95% CI 0.835-1.294), for osteoporotic fractures was 1.026 (95% CI 0.815-1.293); of bacteremia 2.161 (95% CI 0.865-5.397) and of venous thromboembolism 0.579 (95% CI 0.272-1.23).

Conclusion

In this population-based nation-wide study elderly onset IBD was not associated with increased risk of pneumonia, bacteremia, venous thromboembolism, and osteoporotic fractures compared with matched non-IBD elderly individuals. Studies in other populations are still needed to assess complications risk in diverse populations.
P296 MAGNIFI-CD index is appropriate for treatment monitoring in perianal Crohn’s Disease
Authors: Beek K , Mulders L , Tielbeek J , Horsthuis K , Buskens C , D'Haens G , Gecse K , Stoker J
Published: January 2023

Background

Perianal Crohn’s Disease (pCD) is a frequent and debilitating complication of Crohn’s Disease (CD). Magnetic Resonance Imaging (MRI) is the imaging modality for diagnosis, classification, and treatment monitoring in pCD. To evaluate treatment response, a validated radiological index is mandatory. Recently, the MAGNIFI-CD index has been developed. The aim of our study was to validate the MAGNIFI-CD index; evaluating reliability, responsiveness and accuracy.

Methods

At two tertiary IBD referral centers, patients (≥16yrs) with complex pCD that had pelvic MRI before and 3-24 months after medical and/or surgical treatment were included. Two independent, blinded abdominal radiologists randomly scored total MAGNIFI-CD and its separate items. Two clinicians scored clinical outcomes (remission, response, non-response) using the “fistula drainage assessment” (FDA). Interobserver agreement (ICCs or weighted K), responsiveness (according to FDA; Wilcoxon signed rank test), and test accuracy (ROC analyses for the follow-up (FU) MAGNIFI-CD) were determined. Youden indices (YI) were used to choose optimal cut-off values for the FDA categories.

Results

Sixty-seven patients (median age 30 [IQR 23-47], 51% female) were eligible with mean CD and pCD duration of 7.0 yrs (SD 8.7) and 3.7 yrs (SD 4.3), respectively. 44% was biological naïve, 9% had defunctioning ostomy and 20% had proctitis. Baseline MAGNIFI-CD was 18 [IQR 9–20]. MAGNIFI-CD had an almost perfect ICC of 0.88 (95%CI 0.78-0.92); reliability of the separate items was moderate to substantial. Between baseline and FU MAGNIFI-CD a significant decrease was observed in responders and remitters (p<0.05), while a non-significant decrease (p=0.14) was seen in clinical non-responders. AUROCFU MAGNIFI-CD was 0.80 (SD 0.05) discriminating remission and non-response/response, YImax of 0.61 resulted in a cut-off value ≤10 with a sensitivity and specificity of 70% and 80%. The AUROCFU MAGNIFI-CD was 0.75 (SD 0.07) discriminating response/remission and non-response, YImax of 0.50 resulted in a cut-off value ≤14 with a sensitivity and specificity of 73% and 75%.

Conclusion

The MAGNIFI-CD index is a reliable radiological index supported by an almost perfect agreement. Given the moderate agreement, the item “dominant feature” would need additional training or better definitions. The index shows a robust responsiveness to clinical change and does not improve significantly in non-responders. The MAGNIFI-CD seems to be an acceptable to excellent test to accurately determine response or remission. We suggest a cut-off value of ≤14 for response and ≤10 for remission at follow-up MAGNIFI-CD. These results support that the MAGNIFI-CD is suitable for treatment monitoring in clinical trials.
P298 Risk factors for the progression of non-alcoholic fatty liver disease in people with inflammatory bowel disease
Authors: Walker C , Dempsey M , Connaughton R , Carroll A , Breslin N , McNamara D , O'Donnell S , Ryan B , O'Connor A
Published: January 2023

Background

Non-alcohol fatty liver disease (NAFLD) is one of the most common liver disorders, and occurs more frequently in people with inflammatory bowel disease (IBD). Previous research suggests that increased age, BMI, and IBD duration, previous bowel resection, and co-morbid diabetes are risk factors for the development of NAFLD with IBD. Our aim was to investigate possible risk factors for the progression of NAFLD in people with IBD.

Methods

A prospective single centre cohort study. In total, we recruited 203 patients from the IBD service of our tertiary, academic centre. 7 participants were excluded due to later diagnosed non-NAFLD liver disease. Following informed consent, participants underwent a fibroscan and blood tests for liver function tests and a FIB-4 and score were taken.

Basic demographics, information about IBD, exercise measured on the Godin-Shepard Leisure Time Physical Activity Questionnaire, LFTs, FIB4 score, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were recorded. T-test, Fishers exact, and Pearson’s correlation coefficient were used to test for statistical significance as appropriate.

Results

Of the 196 IBD patients included, 16.3% (n=32) had a CAP score >294dB/m consistent with NAFLD, and 2.6% (n=5) had a LSM >8.1kPa consistent with fibrosis. Only 40.6% of those with NAFLD (n=13/32), had abnormal liver enzymes. In regards to FIB 4 score, 8.1% (n=8/91) of those without NAFLD had a FIB4 score >1.3, none with NAFLD alone, and 50% (n=2/4) of those with fibrosis.

We found a positive correlation between BMI and waist circumference with CAP score, Pearson’s r= 0.514 and 0.536 respectively. In those with NAFLD, the fibrosis group had higher BMIs and waist circumferences, 37.44 vs 31.44 (p=0.0265) and 108.6cm vs 107.6cm (p=0.0781) respectively, than the NAFLD without fibrosis cohort. They also had a higher alcohol intake in units/week (21 vs 4.1 p=0.0204), smoking pack year history (31.66 vs 23.63 p=0.482), and HbA1c (6.36% vs 5.76% p=0.108) and had lower exercise scores (0.6 vs 20.1 p=0.0186). Longer IBD disease duration, biologic therapy, anti-TNF therapy, azathioprine, previous surgery, or extra-intestinal IBD did not seem to affect those who developed fibrosis.

Conclusion

The development of fibrosis secondary to NAFLD in people with IBD seems to be driven by metabolic risk factors rather than related to IBD. A high index of suspicion for IBD patients with a high BMI even without deranged LFTs, should lead to consideration for fibroscan. Further research is needed on whether FIB-4 scoring has utility in the IBD population.
P302 Precision medicine for a case with monogenic inflammatory bowel disease
Authors: Schwärzler J P , Zollner A , Dolejsi T , Enrich B , Mayr L , Sturm W , Tancevski I , Zschocke J , Adolph T E , Tilg H
Published: January 2023

Background

Here we report the case of a 33-year-old patient suffering from recurring infections since childhood, and Crohn’s disease (CD)-like inflammation in the ileum and colon for 5 years. The patient was transferred to our hospital due to severe pneumonia with Pseudomonas aeruginosa and Mycobacterium chimaera infection, recurrent fever, bronchiectasis, cachexia (BMI 12.9) and severe gastrointestinal symptoms (diarrhoea with blood 15 times per day). Colonoscopy revealed a peculiar inflammatory pattern in the ileum and the colon without healthy sections and deep punched lesions which did not fit to a diagnosis of CD.

Methods

Exome sequencing was performed and pathogenic variants identified by in silico prediction. Peripheral blood mononuclear cells (PBMCs) were isolated and Signal Transducer And Activator Of Transcription 1 (STAT1) activation was assessed by immunoblot after treatment with JAK-inhibitors. STAT1 activation was quantified in leukocytes of whole blood samples by flow cytometry. Mucosal sections were used to quantify STAT1 activation within mucosal cells by multicolour immunofluorescence. Two healthy individuals served as controls.

Results

Exome sequencing revealed a pathogenic mutation (c.1256C>G) in the STAT1 gene, which was predicted to cause a gain-of-function. STAT1 is part of the JAK/STAT1 pathway which is induced by different stimuli and orchestrates proliferation and responses of immune cells as a transcription factor. Isolated PBMCs from the patient exhibited increased STAT1 activation, and in whole blood samples increased levels were particularly observed in Monocytes and T-helper cells. In mucosal sections activated STAT1 was especially expressed in immune cells but also epithelial cells. Stimulation of PBMCs with Upadacitinib or Tofacitinib and partially with Filgotinib decreased STAT1 levels. We initiated treatment with Tofacitinib due to the in vitro results and its approval to treat ulcerative colitis. After two weeks, clinical symptoms improved drastically and endoscopy performed after 3 month indicated full remission, which was paralleled by a normalisation of STAT1 in PBMCs.

Conclusion

We present a case with a rare form of Inflammatory bowel disease (IBD) caused by a gain-of-function mutation affecting the STAT1 gene. IBD-like symptoms are unusual for STAT1 mutations, which usually present as immunodeficiency, and this specific mutation was only identified twice before and listed in data bases without describing the clinical phenotype. Our results and approach demonstrate how delineating the specific pathomechanism of a case with IBD enables targeted and precision treatment, a currently intensively investigated concept which might be implemented into clinical routine to treat IBD in the future.
P305 Normal reference ranges and cut-off values for considering and performing endoscopy using the Sentinel CaliaGold® Calprotectin assay
Authors: Schoorl M , Beugelink T , Grasman M E , Jongbloed W
Published: January 2023

Background

Fecal calprotectin, a calcium-binding protein, is used as a sensitive marker for gastrointestinal mucosal inflammation. It is a simple, non-invasive test that can be used to differentiate irritable bowel syndrome (IBS) from inflammatory bowel disease (IBD), where there can be significant overlap in clinical symptoms. Recently, Sentinel Diagnostics launched a new CALiaGold® pierce Tube in combination with a new latex immunoassay for calprotectin measurement on the SENTiFIT® 270 analyzer.

The aim of the study is to evaluate the current used normal reference range for calprotectin <60 µg/g*) and the current used cut-off values for considering and performing an endoscopy in case of IBD (considering endoscopy: calprotectin 60-250 µg/g*, performing endoscopy: calprotectin >250 µg/g*).

Methods

Patients received the CALiaGold® pierce Tube (Sentinel, ref. 1151300) along with the instruction protocol for stool collection at home. Within two days after fecal sampling, calprotectin was measured with the corresponding Quantitative Calprotectin latex immunoassay (Sentinel, REF 115100) on the SENTiFIT® 270 analyzer.

Endoscopies were performed within one month around the fecal collection. Results of the endoscopies were registered and interpreted by the gastroenterologist. Calprotectin results were classified according to the clinical diagnosis.

Results

In total 438 symptomatic patients participated in the study (163 men, age 18-83 and 275 female, age 18-90): 239 with active inflammatory bowel disease, 43 with IBD in clinical remission, 43 with IBS, 17 with other intestinal diseases and 96 controls without identified intestinal disease.

The normal reference range for calprotectin was established as <70 µg/g (= p5 positive samples) and the cut-off for performing endoscopy as >355 µg/g (= p95 negative samples). The range 70-355 µg/g calprotectin can be used for considering an endoscopy. Using the new reference range, sensitivity and specificity was calculated as 92% and 93%, respectively. The negative predictive value (NPV) and positive predictive value (PPV) were calculated as 88% and 95%.

Using the routinely used reference range (<60 µg/g calprotectin) a 95% sensitivity, 86% specificity, 90% NPV and 92% PPV was established.

Conclusion

In case of stool collection at home with the CALiaGold® pierce Tube, the Sentinel CaliaGold® Calprotectin assay is highly sensitive in detecting mucosal inflammation.

To differentiate between IBS and IBD, it is recommended to adjust the cut-off for differential diagnosis to 70 µg/g calprotectin. In case of IBD monitoring, it is recommended to adjust the cut-off for endoscopy to >355 µg/g calprotectin to reduce the risk of relapse.

* Ref.: Nederlandse Vereniging van Maag-. Darm- en Leverartsen, oktober 2015
P312 Retrospective study using ultrasonography in predicting clinical relapse of Crohn's disease
Authors: Fukushima S , Katsurada T , Keiya A , Sakurai K , Yamanashi K , Omotehara S , Onishi R , Nishida M , Sakamoto N
Published: January 2023

Background

Endoscopy is the standard modality for inflammatory bowel disease, but it is invasive and poorly tolerated. On the other hand, trans-abdominal ultrasonography (US) is minimally invasive, inexpensive, and has excellent characteristics not found in other examinations, such as the ability to detect minute changes in the intestinal wall. It would be clinically useful if US could predict clinical relapse.

Methods

Of 185 patients with CD who underwent US between April 2011 and April 2021, we retrospectively evaluated 75 patients who were in clinical remission (CDAI < 150) at the time of their first US at our hospital for clinical relapse and maintenance of remission at 1 year after the procedure. The severity of US was evaluated by US-CD (0-52 points in total), which divided the intestine into four segments(ileum, right-sided colon, transverse colon, and left-sided colon) and was calculated the following US parameters: bowel wall thickness (BWT) (0–3), loss of stratification (0–2), degree of blood flow signaling by a color Doppler study (0–3), presence of increasing echogenicity mesentery (0–2), and intestinal stenosis (0–3). US images were analyzed and interpreted in a consensus manner by two technologists with more than 10 years of experience, blinded to the patient's clinical information.

Results

Of the 75 cases, 58 were males and 17 were females with a median age of 30 years (range 18-58), median BMI of 20.6 kg/square meter (range 16.2-32.5), 23 cases were ileal type, 47 cases were ileocolonic type, and 5 cases were colonic type. Sixty-eight patients remained in clinical remission during the observation period, and 7 patients had clinical relapse (CDAI > 150). The median CDAI at US was 71 (range 14-143), median CDAI at relapse was 189 (range 151-288), and median observation period was 365 days (range 6-365). The median time to relapse was 193 days (range 166-288). ROC analysis was performed on the US-CD, and the highest AUC of 0.820 was obtained when the cutoff value was 11. Six patients in the relapse group and 20 patients in the remission maintenance group had US-CD of 11 or higher, and 1 patient in the relapse group and 48 patients in the remission maintenance group had a score of less than 11. The sensitivity was 85.7%, specificity was 70.6%, positive predictive value was 23.1%, and negative predictive value was 98%. Logistic regression analysis identified "US-CD 11 or higher" as a factor contributing to clinical relapse (p=0.018).

Conclusion

US-CD ≥11 is a prognostic predictor of clinical relapse in CD.
P318 Protein FingerPrint assays reflecting neutrophil activity, mucosal damage, and tissue fibrosis are surrogate biomarkers for mucosal healing in pediatric Crohn’s disease
Authors: Mortensen J , Focht G , Pehrsson M , Griffiths A M , Alexdóttir M S , Quteineh A , Church P C , Baldassano R N , Silverstein J , Karsdal M A , Turner D
Published: January 2023

Background

Mucosal healing (MH) has become a treatment goal for inflammatory bowel disease (IBD), especially for ulcerative colitis. However, MH is less feasible to assess frequently in patients with Crohn’s disease (CD). In this study, we investigated Protein Fingerprint Assays (PFA) of collagen degradation and formation, and neutrophil and macrophage activity markers in the ImageKids study as non-invasive markers of MH.

Methods

This is a proteomics planned sub-study of the multi-center prospective ImageKids study which included serum samples from children with CD (n=178) undergoing MRE and ileocolonoscopy concurrently (ImageKids study: NCT01881490). Serum from healthy age and gender-matched controls were obtained from BioIVT (n=83). PFA panel for mucosal damage (C1M, C3M, C4M, C6M, ELP-3), Immune cell activity panel (CPa9-HNE, VICM, C4G), and tissue fibrosis panel (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6, PRO-C11, PRO-C22) were determined. MH was classified as having an SES-CD score of 0 and global radiologist assessment of inflammation in the MRE of 0, using a visual analogue scale (VAS) 0-100mm, and mucosal damage (MD) was defined as having SES-CD or MRE VAS>0. Spearman rho correlations, one-way ANOVA with Tukey correction, and receiver operator characteristics (ROC) curves were applied for statistical analysis.

Results

Some of the previous biomarkers demonstrated to correlate with the SES-CD score and ulcer size (C1M, C3M, C6M, PRO-C4, VICM, PRO-C1, PRO-C3). CPa9-HNE, ELP-3, and PRO-C22 also correlate with the SES-CD score (table 1). The combined SES-CD and MRE VAS score of MH correlated positively with CPa9-HNE (r=0.30, p<0.0001), VICM (r=0.39, p<0.0001), C1M (r=0.29, p=0.0001), C3M (r=0.22, p=0.0022), C6M (r=0.35 p<0.0001), PRO-C4 (r=0.2, p<0.0001), PRO-C22 (r=0.32, p<0.0001), (figure 1 and 2) and showed significantly lower serum levels in pCD patients with MH compared to patients with mild, moderate, or severe mucosal damage (p<0.001) (figure 2). PRO-C3 correlated negatively with the combined SES-CD and MRE VAS score (r=-0.17, p=0.0211). These PFA biomarkers were combined in a multivariate regression model, demonstrating increased accuracy to identify patients in MH healing compared to the individual biomarkers (p<0.001, MH vs. MD: AUC=0.82 [CI:0.69-0.95), MH+Mild MD vs. moderate+severe MD: AUC=0.77 [0.70-0.84], (figure 3).

Conclusion

PFA biomarkers of Neutrophil activity (CPa9-HNE), Macrophage activity (VICM), mucosal damage (C1M, C3M, C4M, C6M, ELP-3), and tissue fibrosis (PRO-C3, PRO-C22) are potential surrogate biomarkers for identifying pCD patients with mucosal healing and for monitoring of mucosal damage and stenosis.
P328 Holistic well-being as Patient-reported outcomes (PROs) in translational IBD research: Prospective capture of CUCQ32 as study endpoints for mechanistic biomarker MUSIC/GIDAMPs study.
Authors: Hall R , Chuah C S , Brownson E , Poulose B , Athena O , Mowat C , Macdonald J , Seenan J P , Ho G T
Published: January 2023

Background

There is increasing recognition of ‘holistic’ wellbeing as a key target in the management of IBD. Patient-reported outcomes (PROs) capture the impact of IBD on social, emotional and general wellbeing. Recently, regulatory bodies such as FDA/EMA mandates the study of PROs in interventional clinical trials. However, the role of PROs has never been investigated as a potential end-point in translational scientific research in IBD

Methods

CUCQ32 is a 32-question form that captures well-being of IBD patients including aspects of fatigue/anxiety/sexual/emotional health – score range from 0-272 (↑score correlating with worse quality QoL). We prospectively captured CUCQ32-PROs in our on-going MUSIC (Cohort 1) and GI-DAMPs (Cohort 2) IBD biomarker studies (www.musicstudy.uk) based in Edinburgh, Glasgow and Dundee (2018-present, ~total n=700 patients recruited). MUSIC is a prospective 12-month longitudinal study (over 5 time points) following active IBD patients in response to current drug treatment whilst GI-DAMPs is a cross-sectional study across IBD disease activity at one-time point. CUCQ32-PROs has been recorded since 2021 with 163 data-points captured. CUCQ32 were filled independently by patients.

Results

In IBD, CUCQ32-PROs scores were high with medians of 113 (IQR of 67.5-152.2) and 132 (IQR of 91-179) in Cohorts 1 and 2 respectively. In MUSIC Cohort 1, CUCQ32 decreased in response to treatment 113→62→58→45→30 over 3-monthly intervals. CUCQ32 scores are significantly correlated to clinical indices of disease activity, SCCAI for UC (Cohort 1, p=0.003/Cohort 2, p<0.001) and HBI for CD (Cohort 1, p<0.001/Cohort 2, p<0.001). Of interest, no correlation was observed with CRP and faecal calprotectin. Notably, although overall CUCQ32 scores associated with active disease, those deemed in ‘clinical remission’ continue to have high score (median 154 vs. 87 respectively, p=0.06). High CUCQ32 scores were observed even in those achieving complete mucosal healing (defined as either endoscopic SESCD or UCEIS score of 0) from longitudinal prospective endoscopic follow-up; median decrease from 116 (baseline) to 55 (6-months SESCD/UCEIS =0), paired data available in n=14 patients. There is no statistical correlation with endoscopic mucosal healing (p=0.6; in 34 patients).

Conclusion

Although patient wellbeing improved with medical treatment in IBD and PROs are correlated with clinical indices of IBD activity, high CUCQ32 (thereby poor quality of life) scores were observed in traditional categorisation of ‘clinical remission’. This suggests a far-reaching impact of IBD beyond gut-related signs/symptoms. Our current work incorporates PROs into our scientific biomarker studies and molecular analyses) and will be the first in IBD, to our knowledge.
P334 Respiratory Manifestations and Association Between Disease Activity in Patients with Inflammatory Bowel Disease in a Reference Center in Salvador, Bahia, Brazil.
Authors: Fortes F , Gonçalves J , Nery E , Arenas L , Mota J , Pimentel A , Almeida N , Santos A M , Surlo V , Santana G
Published: January 2023

Background

Inflammatory bowel diseases (IBD) are chronic diseases that may have a variety of extraintestinal manifestations(EIM), including pulmonary1. Although less frequent than other types of EIM, these alterations have been increasingly. Manifestations present with a wide variety of phenotypes, which can affect different parts of the respiratory system2. As most of these patients are asymptomatic, this type of manifestation is less diagnosed than the other extraintestinal manifestations3,4.

Methods

Cross-sectional, analytical, single-center study, carried out from April/2021 to October/2022, with the application of a questionnaire and review of medical records of patients from an outpatient clinic specialized in IBD in Salvador/BA, at Hospital Geral Roberto Santos(HGRS). Approved by the HGRS Research Ethics Committee. Inclusion criteria: patients ≥18 years old, diagnosed with IBD and signed the informed consent form. Dyspnea symptoms were evaluated using the Modified Medical Research Council Dyspnea Scale(mMRC), dry or productive cough, chest pain and hemoptysis. The clinical activity of the IBD was evaluated using the Harvey-Bradshaw Index in CD and the Lichtiger Index in UC. To test the association between the presence of respiratory manifestations and the clinical activity of the IBD, the chi-square test was used. Significant associations were considered at p < 0.05.

Results

Total of 255 patients were included, 47.1% with CD and 52.9% with UC, 44 had respiratory symptoms. Table 1 shows the general and clinical characteristics. Current treatments: mesalazine suppository and oral(63,2%), azathioprine(29.8%), infliximab(17.3%), sulfasalazine(15.7%), adalimumab(8.6%), prednisone(7.5%), ustekinumab(1.6%), methotrexate(1.6%), vedolizumab(0.8%), tacrolimus or cyclosporine(0.4%), tofacitinib(0.4%). Most of these patients(70.6%) were in clinical remission of IBD at the time the questionnaire was collected, while a minority (29.5%) were in clinical activity. In the 44 patients with respiratory symptoms, the majority are female(77.3%). Patients in clinical remission had respiratory symptoms in 12.9%(22/171), while patients in active remission had respiratory symptoms in 26.2%(22/74). Dyspnea was the most frequent symptom. Statistically significant association was found between the presence of respiratory manifestations and clinical activity(p=0.008). No difference in relation to the type of IBD, nor for medication. Table 2 shows association between disease activity and the presence of respiratory symptoms.

Conclusion

The frequency of respiratory symptoms was high in patients with IBD, with a higher prevalence in patients with active disease. This finding draws attention to a possible mechanism associated with the IBD activity.
P355 Motility in small bowel strictures in Crohn’s Disease measured with cine-MRI
Authors: Beek K , de Jonge C S , van Rijn K , de Voogd F A E , Buskens C J , D'Haens G , Gecse K B , Stoker J
Published: January 2023

Background

Strictures develop in over half of Crohn’s Disease (CD) patients and can lead to complaints of bowel obstruction, requiring treatment. A study showed that strictures and pre-stricture small bowel (SB) have lower motility measured with cine-MRI, compared to normal bowel in CD. However, stricture motility has not been correlated with disease duration or Harvey Bradshaw Index (HBI). Investigating this correlation can provide insight in the physiologic behavior of a stricture in relation to the extent of bowel damage (disease duration) and clinical complaints (HBI). This could possibly support the clinician in treatment decisions. Our aim is to investigate correlations between stricture motility measured with cine-MRI and disease duration and HBI, respectively.

Methods

At a tertiary center CD patients (≥18yrs) with SB strictures were included. Patients fasted 4 hours, after which they drank 1600 mL (2.5%-mannitol-solution) in 60 minutes prior to 3T MRI. All underwent coronal dynamic 2D bFFE scans of the most stenotic SB and the pre-stenotic dilation if present, during a 20-second expiration breath-hold. Bowel motility was assessed with a validated displacement mapping technique (GIQuant, Entrolytics, Motilent, UK). Strictures (wall thickening >3mm and ≥50% luminal reduction) and pre-stenotic dilations (luminal diameter >3cm) were delineated on a reference image and motility was quantified on a motility map within these regions of interest (ROI), producing a single, numerical motility score (Arbitrary Units=AU). Stricture and pre-stenotic dilation motility scores are presented in medians [IQR]. Correlation was tested between stricture motility, disease duration and HBI by means of spearman’s rank correlation test.

Results

Twenty-two patients (55% male, age 37yrs [IQR 25-55], disease duration 7yrs[IQR 4-12]) were included. SB stricture motility was 57AU[IQR 48-71]. Pre-stenotic dilation motility (n=6) was 131AU[IQR 88-340]. Disease duration and stricture motility showed no correlation(r=0.2, p=0.4). HBI and stricture motility were inversely correlated(r=-0.6, p<0.01).

Conclusion

We found an inverse correlation between SB stricture motility and HBI. No correlation was found between SB stricture motility and disease duration. The inverse correlation between HBI and stricture motility suggests that lower motility is associated with poorer clinical condition. This finding can possibly lead to earlier endoscopic or surgical intervention, since it indicates lower motility is associated with poorer clinical condition. Interestingly, we also measured higher pre-stenotic dilation motility compared to stricture motility, presumably a physiological response of the pre-stenotic dilation to the distal stricture and ongoing proximal peristalsis.
P360 Role of intestinal ultrasound scores in the diagnosis of post-operative recurrence in Crohn's disease
Authors: Amor Costa C , Suárez Ferrer C , Poza Cordón J , Yebra Carmona J , Rueda García J L , Sánchez Azofra M , Martín Arranz E , González Díaz I , Amiama Roig C , Martín Arranz M D
Published: January 2023

Background

Ileocolonoscopy is the gold standard to evaluate post-operative recurrence (POR) in Crohn's disease (CD) patients. Rutgeerts endoscopic score remains the gold standard in the evaluation of post-operative recurrence in CD.

Intestinal ultrasound (IUS) is proposed as a non-invasive alternative to ileocolonoscopy for the diagnosis of POR, with a sensitivity of 94% and specificity of 84%. There are several IUS scores that evaluate CD disease activity such as SUS-CD (validated), IBUS-SAS and Simple US Score, which have not yet been studied in the diagnosis of POR. The aim of this study is to assess whether these ultrasound scores correlate with endoscopy in the diagnosis of PR.

Methods

A retrospective study was performed. Patients with CD who had undergone ileocecal resection, with both an ileocolonoscopy and intestinal ultrasound performed for the detection of POR were included. The time between tests was less than 6 months and there was no therapeutic change between tests.

Endoscopic POR was evaluated with Rutgeers score (RS), considering POR RS ≥i2b. In IUS, were used: Simple US Score, SUS-CD and IBUS-SAS.

Results

Forty-five patients were included (female 48,89%, male 51,11%). The Montreal classification was: L1 n=22 (48,89%), L2=1 (2,22%), L3 n=22 (48,89%), B1 n=3 (6,67%), B2 24 (54,4%) and B3 n=18 (40%).

24 patients (53%) had no endoscopic POR, 6 (6%) had RS i2b and 15 (33.33%) had severe POR. The mean wall thickness measured by IUS was 4.39 mm (SD +/- 1.92) and 26 patients (57.77%) had hyperemia (Limberg score >1). The mean values for IUS scores were: Simple US Score 5.79 (SD +/- 2.81), SUS-CD 2.35 (SD +/- 1.62) and IBUS-SAS 34.04 (SD +/- 24.21). For the Simple US Score an area under the ROC curve (AUC) of 80.65% (95% CI 67.7 - 93.6) was obtained, with a score ≥5.4. The sensitivity (S) was 95.24% and specificity (E) 66.67%. IBUS-SAS presented an AUC of 87% (95% CI 76.98 - 97.02), a result ≥28 granted a S 90.48% and E 70.83%. The SUS-CD index had an AUC of 79% (95% CI 76.98 - 97.92), a result ≥3 presented S 90.48% and E 62.5%.

Conclusion

In our experience, IUS scores (IBUS-SAS, SUS-CD and Simple US Score) show a high sensitivity in the diagnosis of POR.
P363 Depression and anxiety in Clostridioides difficile infection compared with inflammatory bowel disease during the Covid-19 pandemic
Authors: Țurcan S , Platon V , Negru I
Published: January 2023

Background

Numerous studies and their meta-analysis have shown a high prevalence of anxiety and depression in patients with inflammatory bowel disease (IBD): up to a third of patients with anxiety symptoms and a quarter with depression symptoms. These rates increase even more with high disease activity: up to half of patients with anxiety criteria and up to a third with depression symptoms.

Data on the frequency and severity of depression and anxiety in patients with Clostridioides difficile infection (CDI) are not so numerous and unambiguous. During the Covid-19 pandemic, the frequency of depression and anxiety increased among healthy individuals and, even more so, among patients with intestinal diseases.

The aim of the study was to evaluate the degree of anxiety and depression in patients with IBD and those with CDI during the Covid-19 pandemic.

Methods

Thirty patients with IBD and 30 patients with CDI were included in the study. IBD was confirmed by endoscopy and histology. CDI was confirmed by enzyme analysis for glutamate dehydrogenase and toxins A and B in the feces of patients with nosocomial infection.

Hamilton scale (17 items) was used in order to assess the depression grade. This scale divides patients into four groups: no depression, mild, moderate and severe depression. Anxiety was diagnosed by the Spielberger scale (40 items) which includes analysis of State anxiety (SA) and Trait anxiety (TA).

Results

Depression was determined in 56.7% of patients in the IBD group: 46.7% had mild depression, and 10% moderate depression. In the CDI group depression was diagnosed significantly more frequently – 86.7% of cases: mild grade in 76.6% and moderate in 10%, predominantly among women.

SA was identified in 46.7% of patients in IBD group, and severe SA in 10.0%. In CDI group the frequency and grade of SA were similar: 40.0% and 13.3% respectively.

The of TA was extremely high in both groups: 93.3% in the IBD group, of which 50.0% with severe TA, and 96.7% in the CDI group, of which 40.0% with severe TA.

Conclusion

The results of the study confirm the presence of anxiety and depression in an extremely large number of patients with IBD and CDI during the Covid-19 pandemic. The frequency of anxiety and depression in this study is significantly higher than previously reported. Patients with IBD and CDI should be monitored for early diagnosis and adequate treatment of depression and anxiety.
P375 Izencitinib induction treatment in patients with moderately-to-severely-active Crohn’s Disease: A phase 2 double-blind, randomized, placebo-controlled study
Authors: Schreiber S , Reinisch W , Nguyen D , Guerin T , Kierkus J , Rozpondek P , Bourdet D , Abhyankar B , Peyrin-Biroulet L
Published: January 2023

Background

The unmet need in Crohn’s disease (CD) exists for new medications with an optimized risk-benefit ratio with avoidance of systemic side effects. This Phase 2 study evaluated the efficacy and safety of the oral, once-daily, gut-selective pan-Janus kinase inhibitor izencitinib as an induction therapy for CD.

Methods

This trial was a multicentre, randomized, double-blind, Phase 2 study of adults with moderately-to-severely active CD (≥220 and ≤ 450 CDAI with SES-CD score of ≥6 [or ≥4 if isolated ileal disease]) who were corticosteroid-dependent or had demonstrated failure to aminosalicylates, corticosteroids, immunosuppressive agents, and/or biologic therapies. Patients were randomised 2:3:3 to receive placebo or izencitinib, 80, or 200 mg once daily for 12 weeks.

The primary endpoint was change in CDAI score from baseline to week 12 and was analysed using a mixed-model repeated measures analysis. Change from baseline in SES-CD was analysed with an analysis of covariance model and binary endpoints were analyzed using a stratified Cochran-Mantel-Haenszel chi-square test.

Results

159 and 145 patients were included in the safety and modified ITT populations, respectively.

At week 12, the LS mean change in CDAI was -105.6 (SE: 12.7) and -117.9 (12.4) points for patients randomized to izencitinib 80 and 200 mg, respectively, vs -104.86 (SE: 15.496) for those randomized to placebo. There were no improvements observed in change from baseline in SES-CD. There were non-significant numerical improvements in clinical and endoscopic response between placebo and the highest dose 200mg. No improvements were observed in CDAI-based clinical remission or PRO2 (SF/AP)-based remission at any dose of izencitinib relative to placebo.

As expected, plasma izencitinib exposure was low. Serious adverse events (AEs; n = 13) were well balanced among the treatment groups and not considered related to study treatment; no deaths were observed.

Exacerbation of Crohn’s Disease, headache, rash, abdominal pain and nausea were the most common treatment-emergent AEs observed with izencitinib treatment. No clinically important changes in laboratory values, electrocardiography parameters, or vital signs were noted in patients treated with izencitinib compared with placebo, and no drug-related AEs of special interest were observed.

Conclusion

In patients with moderately-to-severely active Crohn’s Disease, izencitinib treatment for 12 weeks did not demonstrate a statistically significant reduction in CDAI or endoscopic severity. Izencitinib at both doses was well tolerated without a new safety signal.
P382 Serum Ustekinumab Concentrations are Associated with Improved Outcomes with the Magnetic Resonance Index of Activity for Crohn’s Disease
Authors: Chen K , Chen J , Smith E , Mathani P , Longman R , Lukin D , Scherl E , Battat R
Published: January 2023

Background

Controversy exists for ustekinumab concentrations needed in Crohn’s disease (CD). No data exist comparing ustekinumab concentrations and validated radiologic outcomes. We characterized these relationships and clarified concentrations needed.

Methods

CD patients on maintenance (> 16 weeks) ustekinumab with both ustekinumab concentrations and simplified magnetic resonance index of activity (sMaRIA) scoring were included. Ustekinumab concentrations were compared between those with and without (1) radiologic remission (sMaRIA < 2), (2) severe radiologic inflammation (sMaRIA < 3) and (3) fecal calprotectin (FCP) biomarker remission (FCP < 50μg/g). Area under the receiver-operating characteristic (AUROC) curve determined optimal ustekinumab concentrations. Outcomes were compared between patients above and below identified ustekinumab thresholds.

Results

Thirty-eight paired ustekinumab concentrations and magnetic resonance enterography imaging results were included. Ustekinumab concentrations were higher with radiologic remission (11.4μg/mL vs. 6.4μg/mL, P=.005) and had good diagnostic accuracy for radiologic remission (AUROC 0.76, 95% CI 0.60 – 0.91) and for absence of severe inflammation (AUROC 0.71, 95% CI 0.55 – 0.88, optimal concentration 8.4μg/mL). With ustekinumab ≥8.4μg/mL, higher proportions had radiologic remission (63.2% vs. 21.1%, P=.01) and absence of severe inflammation (78.9% vs. 36.8%, P=.01) compared to patients with lower concentrations. Ustekinumab concentrations had good diagnostic accuracy (AUROC 0.73, 95% CI 0.52 – 0.94) for FCP biomarker remission (optimal concentration: 6.1μg/mL). Patients with ustekinumab concentrations ≥6.1μg/mL had higher proportions with biomarker remission (72.2% vs. 12.5% P<.01) compared to those with lower concentrations.

Conclusion

Ustekinumab concentrations are associated with radiologic and biomarker outcomes in CD. These data validate the need for higher ustekinumab concentrations.