bluuebunny/crossref_metadata_2025_split huggingface dataset:
P219 Prognostic potential of mucosal proteins in Ulcerative Colitis
Authors: Salomon B , Carlson M , Bergemalm D , Hedin C R H , Söderholm J D , Keita Å V , Carsten A , Grip O , Marsal J , Eriksson C , Strid H , Lindqvist C M , Öhman L , Magnusson M K , D’Amato M , Repsilber D , Kruse R , Halfvarson J 
Published: January 2024

Abstract

Background
Better prognostic measures for ulcerative colitis (UC) could significantly advance patient care. While the prognostic capacity of circulating proteins in UC has been explored, the role of mucosal proteins remains largely unknown. We examined mucosal protein markers in patients with incident ulcerative colitis and evaluated their prognostic value.

Methods
Biopsies from macroscopically inflamed colonic/rectal mucosa of adult patients in the Swedish inception cohort of IBD (SIC IBD) were obtained at diagnosis of UC. Patients were followed prospectively, and clinical data were recorded after 3 and 12 months. Disease course was categorised as indolent or aggressive at 12 months, based on a composite outcome of colectomy, hospital admission for active disease, treatment refractoriness towards ≥2 biological agents; the use of &gt;2 courses of corticosteroids, or a cumulative dose of &gt;2.5 g. Relative estimates of 162 protein markers were assessed in homogenised tissue supernatants, using proximity extension assay technology (Olink Proteomics, Uppsala, Inflammation and Oncology II panel). Mann-Whitney U test, with Benjamini-Hochberg correction was used to identify differentially regulated mucosal proteins in aggressive vs indolent disease course, with a 5% false discovery rate (FDR). Smoothly clipped absolute deviation regularised logistic regression models were used to identify prognostic signatures distinguishing aggressive from indolent disease course. Performance was estimated in a leave-one-out cross-validation and reported as the area under the receiver operating characteristic (ROC) curve (AUC).

Results
117 patients provided a macroscopically inflamed colonic/rectal biopsy at diagnosis of UC. Basic demographics and clinical characteristics are presented in Table 1. Relative protein levels of WFdc2 and CCL20 were significantly lower in lysates from patients developing an aggressive course vs patients developing an indolent course, while estimates of MMP1, CCL11, WISP-1, OPG, RSPO3 and VEGFR2 were higher (Figure 1A). Regularized logistic regression identified signatures restricted to 28 proteins, distinguishing aggressive from indolent UC courses, yielding an AUC of 0.68 (95% confidence interval (CI): 0.56-0.80) for left-out samples (Figure 1B). Incorporating extent of inflammation at diagnosis in the model improved the AUC to 0.71 (95% CI: 0.60-0.83).

Conclusion
We identified prognostic mucosal protein signatures associated with future course of ulcerative colitis by analysing inflamed mucosal biopsies that were obtained at diagnosis. These protein markers may highlight pathways of relevance for ulcerative colitis outcomes.
P234 Online direct-to-public calprotectin testing in the UK: what is out there in 2023?
Authors: Bishara M , Smith R , Nice R , Roberts C , Kennedy N A , Ahmad T , Goodhand J R 
Published: January 2024

Abstract

Background
The longest component of the time-to-diagnosis is the interval between symptom onset and an individual seeking help. Recent reports in patients with sexually transmitted infections and hepatitis C, who also suffer health related stigma and a delay in diagnosis, suggest that this barrier may be overcome by the anonymity of direct-to-public testing. We sought to characterise the availability of online direct-to-public calprotectin testing in 2023 in the UK.

Methods
We undertook an online search using the Google search engine on May 25th, 2023, with the terms "buy" or "purchase" AND "calprotectin" AND "inflammatory bowel disease". Collection kits were procured, and stool samples tested to receive follow-up advice for known positive and negative stool samples. We recorded data regarding the assay, consumer information and the clinical advice offered on return of a positive and negative test.

Results
Overall, 54.5% (6/11) of available tests were home lateral flow tests, the remainder were home collection laboratory-based tests. Of the laboratory-based tests, three were conventional enzyme-linked immunosorbent assay (ELISA) assays and two were OC sensor tests. The lateral flow tests were considerably cheaper than the laboratory-based tests (median cost £14.20 [£7.85-21.00] vs £75.85 [£59-151], p&lt;0.0001). The median turnaround time for the laboratory tests was 14 (1-23) days. All but one provider used a positivity threshold of 50ug/g. Eight of the eleven platforms (4 lateral flow tests and 4 laboratory-based tests) explicitly stipulated testing in the setting of gastrointestinal symptoms or suggested exclusion criteria. All tests included written and pictorial instructions with the testing kit. The median Flesch Kincaid readability score for the instructions and result reporting were 54.3 (43.9-73.7) and 51.8 (12.9-64.9): equivalent to a school reading grade of 9.2 (6.2-10.8) and 11.3 (7.2-15.8), respectively. Only two of the lateral flow tests provided written recommendations about follow up of positive results, whereas amongst the laboratory-based tests, all but one provider recommended onward discussion with a general practitioner or specialist. Two providers offered private referrals or consultations and six provided safety netting advice with regards to negative results.

Conclusion
In the UK online direct-to-public calprotectin testing is already readily available from multiple providers. Consumers can choose between home-based lateral flow tests or conventional laboratory testing. Further work is needed to redefine the diagnostic accuracy of calprotectin used in this way, however, the rapid turnaround times and anonymity suggest that direct-to-public calprotectin testing could be used to reduce the time to IBD diagnosis.
P240 The impact of environmental factors in the onset, activity and severity of inflammatory bowel diseases in a population-based Danish setting – findings from IBD Prognosis Study
Authors: Attauabi M , Madsen G R , Bendtsen F , Seidelin J , Burisch J 
Published: January 2024

Abstract

Background
The role of environmental exposures in inflammatory bowel diseases (IBD) remains elusive despite their implicated significance. The aim of the current study was to investigate pre-diagnostic environmental factors affecting incident patients with onset of ulcerative colitis (UC) and Crohn’s disease (CD) and their impact on the disease activity at diagnosis.

Methods
Incident adult patients (≥18 years) with newly diagnosed UC or CD according to the Copenhagen IBD Criteria were included in the IBD Prognosis Study, a population-based inception cohort representing approximately 20% of the Danish population (1.1 million). Environmental factors were systematically assessed using the International Organization of Inflammatory Bowel Disease environmental factors scheme.1
A severe disease presentation was defined by the need for glucocorticoids, immunomodulators, biologics, or surgery within three months of disease, while severe disease activity was defined endoscopically (Mayo Endoscopic Score=3; Simple Endoscopic Score-Crohn’s Disease (SES-CD) &gt;16) or as a composite of both high clinical disease activity (Simple Clinical Colitis Activity Index &gt;10 or Harvey-Bradshaw Index&gt;7) and biochemical inflammation (C-reactive protein &gt;10 mg/L or fecal calprotectin &gt;1800 μg/g. Univariate and multivariate logistic regression analyses adjusting for age, gender, and disease phenotype were conducted to examine the association between specific environmental factors and disease activity and severity of UC and CD.

Results
Out of the original cohort, 208 (67.5%) and 128 (63.1%) patients with incident UC and CD, respectively, responded to the questionnaires, with no discernible differences between respondents and non-respondents.
Patients with UC and CD exhibited disparities in the frequency of the following pre-diagnostic environmental factors: first-degree relatives with IBD (UC: 11.5%, CD: 24.2%, p=0.009), previous appendectomy (UC: 2.9%, CD: 10.2%, p=0.005), active smoking (UC: 14.4%, CD: 25.8%, p=0.01), soft drinks daily (UC: 18.3%, CD: 34.4%, p=0.003), and access to mains drainage (UC: 93.3%, CD: 85.2%, p=0.02).
Further, several environmental factors were independently associated with intensive treatment needs, including biologics or surgery, a severe initial presentation of IBD (table 1) as well as heightened disease activity (Figure 1).

Conclusion
This population-based cohort study identified several modifiable and non-modifiable environmental factors associated with the onset, disease activity, and initial presentation of UC and CD. emphasizing the need for heightened awareness and potential intervention strategies.

References
1. Halfvarson J et al., Inflamm Bowel Dis. 2006. doi: 10.1097/01.mib.0000228998.29466.ac.
P243 Multi-modality intestinal ultrasound is accurate and reproducible to distinguish inflammatory from chronic fibrotic strictures in Crohn’s disease – results from the STRICTURE study
Authors: de Voogd F , Pruijt M , Beek K , Van Rijn K , Van der Bilt J , Buskens C , Bemelman W , Neefjes-Borst A , Mookhoek A , Stoker J , D'Haens G , Gecse K 
Published: January 2024

Abstract

Background
In 30%-50% of patients with Crohn’s disease (CD) stenotic complications occur1. There is currently no imaging modality to identify stricture composition, which would allow early targeted (anti-inflammatory vs surgical) treatment. Intestinal ultrasound (IUS) and advanced modalities (contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE)) have the potential for transmural disease evaluation. The STRICTURE study investigated whether (advanced) IUS techniques could distinguish between inflammatory- (IP) and non-inflammatory phenotypes (non-IP) of stricturing CD.

Methods
In this prospective, cross-sectional study consecutive patients with small bowel CD undergoing surgery were included. Patients were eligible if they had a non-passable stricture during endoscopy in the small bowel and/or a stricture at cross-sectional imaging (IUS or MRE)2. Prior to surgery, IUS, CEUS and SWE were performed. Two blinded sonographers scored the cine-loops for IUS and CEUS. After surgery, histological slides were retrieved and location matched with IUS. Two blinded pathologists scored for inflammation, adipocytes and fibrosis. Subsequently the predominant phenotype was determined as: [1] inflammatory (IP; Nancy score 4 with no marked fibrosis/adipocytes), [2] fibrotic (FP; structural changes due to marked fibrosis/adipocytes3) or [3] mixed phenotype (MP; inflammatory and fibrotic aspects but no predominant phenotype). FP and MP were both classified as non-IP.

Results
A total of 36 patients (age: 42±18 years) with a mean BWT of 6.7±1.7 mm were included. Median time between IUS and surgery was 14 [3-50] days. A total of 7 patients had an IP, 18 a FP and 11 a MP. For the conventional IUS parameters, loss of wall layer stratification (WLS) was more frequently found in IP strictures(OR: 7.87 [1.24-50.00], p=0.029). For CEUS, most parameters were significantly higher in IP versus non-IP (Table 1) and at multi-variable logistic regression Wash-in area under the curve remained the only accurate parameter to distinguish IP from non-IP (OR:1.55 [1.03-2.34], p=0.035) [Figure 1]. SWE inversely correlated with CEUS (Table 1, Figure 1) but did not differentiate between IP and non-IP (33.30 kPa vs 43.49 kPa, p=0.48). The agreement for BWT and loss of WLS was good (ICC: 0.77, p&lt;0.001) and moderate (κ: 0.56, p&lt;0.001), respectively. For CEUS, the most accurate parameters had good to excellent agreement [Table 1].

Conclusion
Loss of WLS and CEUS are accurate to distinguish an IP from a non-IP stricture in CD and CEUS inversely correlates with SWE. In addition to accuracy, reproducibility was high and multi-modality IUS could be of additional value in this specific population to select patients most suitable for anti-inflammatory treatment.
Table 1

Figure 1
P251 Proactive Therapeutic drug monitoring of Infliximab, but not HLA-DQA1*05, predicts clinical outcome in inflammatory bowel disease
Authors: Alonso I , Carrillo Palau M , Vera B , Vela M , Morant A , Ramos L , Reygosa C , Medina Chico J S , Barrios Y , Franco A , Gutiérrez-Nicolás F , Jiménez A , Hernández-Guerra M 
Published: January 2024

Abstract

Background
While anti-TNF drugs effectively manage Inflammatory Bowel Disease (IBD), treatment failure rates exceed 40%. Monitoring drug levels, antibodies (Abs), and HLA-DQA1*05 allele typing could optimize patient care. The aim of this study is to evaluate the clinical impact of Infliximab (IFX) and Abs monitoring in IBD patients and to understand the influence of the HLA-DQA1*05 allele on IFX treatment response and maintenance.

Methods
We conducted a multicenter, observational study involving patients initiating IFX treatment between October 2020 and October 2022. Demographic, clinical, analytical, and endoscopic data, along with disease activity indicators, were prospectively collected. IFX and Abs levels were measured at weeks 6, 14, 30, and 12 months. HLA-DQA1*05 genotyping was performed at baseline. Statistical tests assessed correlations between IFX levels and disease activity.

Results
Ninety-three IBD patients (45±17 years, 46% female) initiated IFX treatment, mostly anti-TNF naïve (90%). At baseline, 91% had an active disease (GPA = 1) and 85,7% a FC &gt; 150 mg/kg. PRO at baseline was 59.22±8.72. Median follow up was 15 months. HLA was determined in 91 patients, of whom 35 (38.5%) where HLA-DQA1*05 positive. IFX levels &gt; 7 µg/mL correlated with improved disease outcomes in week 6, 14 and 30. In this way, IFX levels &gt; 7 µg/mL in week 6 were associated with CRP &lt; 5 mg/L (p = 0.008), FC &lt;150 mg/kg (p = 0.011) and GPA = 0 (p = 0.0016) in week 6 and with GPA = 0 (p = 0.042) in week 14. IFX levels &gt; 7 µg/mL in week 14 were associated with GPA = 0 (p = 0,001) and FC &lt;150 mg/kg (p = 0,0015) in week 14 and with GPA = 0 (p = 0,019) and FC &lt;150 mg/ kg (p = 0,027) in week 30. IFX levels &gt; 3 µg/mL at 12 months follow-up were associated with FC &lt; 150 mg/kg (p = 0,001). PRO was used to evaluate patients’evolution, and progressive improvement in scores at weeks 0, 14 and 30 was observed (p &gt; 0.001). IFX levels &gt; 7 µg/mL at week 14 were associated with a better PRO score at week 14. Discontinuation (40%) within the first year linked to higher CRP and FC at week 0 and active disease at weeks 6, 14, and 30.

Conclusion
Early IFX monitoring at weeks 6 and 14 optimizes IBD management. IFX levels &gt; 7 µg/mL indicate better short and long-term clinical outcomes and drug durability, irrespective of HLA-QDA1*05 status.
P264 The utility of ANCA in Ulcerative Colitis and Crohn’s Disease: A Retrospective Cohort Study in Taiwan
Authors: Wu Y H , Wang C P , Huang P J , Lai H C , Cheng K S , Chou J W 
Published: January 2024

Abstract

Background
Inflammatory bowel disease (IBD) includes two chronic idiopathic inflammatory diseases: ulcerative colitis (UC) and Crohn disease (CD). The diagnosis of IBD depends on clinical, endoscopic, histological, radiological and biochemical criteria, which may be invasive, time consuming and usually not accepted by patients with IBD. Antineutrophil cytoplasmic antibodies (ANCAs) is believed to be related to IBD. The aim of this study was to investigate these serological markers and the evidence for their use in the diagnosis and management of IBD in Taiwan.

Methods
We conducted a retrospective cohort study in adult IBD patients who had received the serum examinations using the medical records of China Medical University Hospital between 1 January 1980 and 31 October. 2023.

Results
A total of 301 IBD patients (194 with UC, 107 with CD) were included in this current study. A high proportion were male (IBD 70.41%; UC 65.63%, and CD 76.71%). The mean diagnostic age of these enrolled patients was 42.9 years. In our patients, the prevalence of positive anti-HCV Ab is 0.0% in UC patients and 0.96% in CD patients. However, the prevalence of positive HBsAg was 14.5% in UC patients and 9.4% in CD patients.
The prevalence of pANCA was 21.2% in UC patients and 1.4% in CD patients, respectively. The prevalence of cANCA was 3.1% in UC patients and 0.0% in CD patients. This pattern of low sensitivity and high specificity for pANCA is also seen in UC patients in various cohort studies. The serum positivity of p-ANCA was significantly higher in UC patients (Figure 1). UC patients with positive p-ANCA were older than CD patients with positive p-ANCA (44.9 vs. 37.3 years). Furthermore, we found that the incidence of positive p-ANCA in UC patients with E1, E2, and E3 at diagnosis was 3.5%, 39.2%, and 57.1%, respectively (Table 1). The serum levels of ANCA-IgG were indeed higher in patients in the severe group than those in the moderate and mild groups.

Conclusion
Serological biomarkers have been demonstrated to be a series of rapid, non-invasive approaches for assessments of early diagnosis, disease activity and prognosis for IBD. ANCA may be helpful in the early diagnosis of UC and in differentiating it from CD. UC patients with positive ANCA have a higher rate of intestinal mucosal vasculitis than UC patients with negative ANCA. Furthermore, ANCA may also contributes to the pathogenesis of HBV-related systemic vasculitis. Therefore, the management of HBV-related vasculitis includes control the immune complex formation and reaction as well as antiviral agents to reduce the antigenic load resulting in reduction of inflammation. Moreover, effective biomarkers with high sensitivity and specificity need to be investigated in the future.
P276 Predictive value of changes in 3D volumetry in perianal fistulas in patients with Crohn’s disease under biologic therapy. A pilot study
Authors: Ordás Jiménez I , Caballol B , Saavedra C , Fernández-Clotet A , Masamunt M , Ricart E , Rimola J 
Published: January 2024

Abstract

Background
Changes in the 3D volumetry of perianal fistulas measured by magnetic resonance (MR) could be an imaging biomarker of interest. The objective of the study is to determine the value of volumetric changes in perianal fistulas in patients with Crohn's disease (CD) after biological treatment to predict subsequent clinical outcomes.

Methods
Retrospective single-center pilot study. We have included CD patients with perianal fistulas who started biological therapy between 2012-2020 and have 1) both pre- and post-treatment (3-18 months) pelvic MR and 2) follow-up after post-treatment MR of at least 2 to 5 years. According to the last visit, patients were categorized as clinically active (perianal discharge) or in remission (absence of draining). Using an specific software (vEUA, Motilent, London), we calculated the 3D volumetry of the fistulas, the active component (hypersignal on T2) and the fibrotic component (hyposignal on T2). We compared MR volumetric changes between both pre and post treatment MRs and calculated the value of MR volumetric changes in predicting clinical remission using a multivariate stepwise logistic regression analysis.

Results
Among the 24 patients included, 13 were in perianal clinical remission in the last follow-up. The percentage (%) of volumetric changes in the active component was significantly higher in patients achieving perianal clinical remission compared to non-responder patients (82.5% vs 38.7%, p=0.007). The % of change of the fibrotic component was also significantly higher in patients achieving perianal remission (120% vs 34%, p=0.03). The % of change of the active component was identified as predictor of clinical remission (OR 1.06 [1.02-1.11] P=0.008). A reduction of ≥16% of the active MR component has a sensitivity of 85% and specificity of 82% to predict clinical perianal remission on the long-term.

Conclusion
Changes in the 3D volumetry on MR of perianal fistulas have value in predicting clinical response. The decrease in the active component could be therefore a good biomarker to define therapeutic targets in fistulizing perianal CD.
P295 Early sonographic improvement predicts the middle-term efficacy of molecular-targeted medications for Ulcerative Colitis
Authors: Miyoshi J , Kimura Y , Morikubo H , Komatsu H , Yonezawa H , Matsuura M , Hisamatsu T 
Published: January 2024

Abstract

Background
Today molecular-targeted medications (MTMs) are widely used for ulcerative colitis (UC). Predicting the efficacy of MTMs early after induction remains a crucial clinical challenge. Intestinal ultrasound (IUS) is now considered a non-invasive, promising monitoring tool for UC. It can assess the disease activity of UC in the whole colon safely and repeatedly. Here, we hypothesized that over time IUS assessment can predict the MTM efficacy early, contribute to early clinical decision-making on whether to continue or switch MTMs, and reduce the burden of colonoscopy (CS) recommended to be scheduled at around 6 months after the induction.

Methods
We analyzed 44 patients who started an MTM for active UC, underwent IUS at baseline and 3 months, and took CS at 6 months after the induction. The clinical disease activity and endoscopic activity at 6 months were assessed with Lichtiger index (LI) and Mayo endoscopic subscore (MES), respectively. Clinical remission was defined as a LI ≤ 3. Endoscopic improvement (EI) was defined as a MES = 0 or 1. In addition to the assessment of sonographic findings, such as bowel wall thickness (BWT), bowel wall stratification including submucosa index (SMI), bowel wall flow with modified Limberg score (mLS), Milan Ultrasound Criteria (MUC), UC-IUS index (UII), Kyorin Ultrasound Criterion for UC (KUC-UC; BWT&lt;3.8mm with SMI&lt;50%) were evaluated.

Results
Patients who achieved steroid-free clinical remission (SFCR) showed better improvement in BWT, %BWT, and mLS in 3 months compared to those who did not achieve SFCR (p&lt;0.01 for each). The improvement in MUC and UII was also observed in patients who achieved SFCR at 6 months (p&lt;0.001 for both). In ROC analyses, the area under the curve for SFCR at 6 months was 0.80 with BWT, 0.80 with %BWT, 0.81 with mLS, 0.85 with MUC, and 0.85 with UII. Among the 44 patients, 7 patients achieved MUC≤ 6.2, estimating MES=0/1, at 3 months, and 6 out of 7 patients demonstrated EI at 6 months (positive predictive value [PPV]=87.5%). Meanwhile, 4 patients satisfied KUC-UC at 3 months and all of them achieved SFCR and EI at 6 months (PPV=100%).

Conclusion
Our study suggests that patients who achieved sonographic improvement in 3 months can continue an ongoing MTM therapy and that patients who demonstrated sonographic findings estimating EI at 3 months can postpone CS at 6 months.