bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt;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

Abstract

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 &gt;294dB/m consistent with NAFLD, and 2.6% (n=5) had a LSM &gt;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 &gt;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

Abstract

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&gt;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

Abstract

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 &lt;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 &gt;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 &lt;70 µg/g (= p5 positive samples) and the cut-off for performing endoscopy as &gt;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 (&lt;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 &gt;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

Abstract

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 &lt; 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 &gt; 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

Abstract

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&gt;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&lt;0.0001), VICM (r=0.39, p&lt;0.0001), C1M (r=0.29, p=0.0001), C3M (r=0.22, p=0.0022), C6M (r=0.35 p&lt;0.0001), PRO-C4 (r=0.2, p&lt;0.0001), PRO-C22 (r=0.32, p&lt;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&lt;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&lt;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

Abstract

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&lt;0.001) and HBI for CD (Cohort 1, p&lt;0.001/Cohort 2, p&lt;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

Abstract

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 &lt; 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.