bluuebunny/crossref_metadata_2025 huggingface dataset:
P179 Decrease in Butyric Acid in fecal matter in patients with Inflammatory Bowel Disease is associated with the levels of secretory Immunoglobulin A and fecal calprotectin
Authors: Parra Izquierdo L V , de Avila J , Ramos A , Chila-Moreno L , Bello-Gualtero J M , Valdes A , Morantes S , Madroñero J , Bautista-Molano W , Delgado F , Florez-Sarmiento C , Romero-Sanchez C
Published: January 2024

Background

Accumulating evidence shows that the development of IBD is always accompanied by dysbiosis of the intestinal microbiota. Short-chain fatty acids (SCFAs) are produced by prebiotic intestinal bacteria, with mportant anti-inflammatory functions, delaying the clinical progression of IBD. The aim of this study is to compare SCFA levels in fecal matter in patients with IBD versus patients with Spondyloarthritis (SpA) and healthy controls.

Methods

24 patients were evaluated for the presence of gastrointestinal symptoms, demographic data and inflammatory markers: fecal calprotectin, C-reactive protein (CRP), secretory IgA (SIgA) and erythrocyte sedimentation rate (ESR). The quantification of SCFAs (acetic-AC, propionic-AP, butyric-AB and total SCFAs-ACCC-T) from fecal matter was analyzed by ultra-high pressure liquid chromatography coupled to mass spectrometry (UHPLC-Q/ TOFMS).

Results

33.3% of patients with IBD were men, with body mass index >25 in 16.7%; 83.3% presented more than 2 gastrointestinal symptoms at the time of sample collection, 33.3% had high levels of fecal calprotectin, 50% had CRP levels higher than 3mg/L and high ESR in 33.3% and a mean SIgA. of 27.73±5.03 g/mL. Very decreased levels of butyric acid (BA)ug/mL and T-SCFA were observed in IBD (9.45±4.89 and 121.73±65.94, respectively), compared to CS (BA 20.84±8.83 and total SCFA.12±122.09)., SpA SG (AB 13.35±10.44 and total AGCC 150.73±128.52) and SpA without OS (AB 21.13±5.68 and AGCC-T 219.51±229.65). Significant differences were found in fecal BA levels between the study groups (p=0.027). Interestingly, this metabolite in the CS group and the SpA group without OS did not show differences between them, but compared to the IBD group p=0.015 and 0.009 respectively, with a decrease in IBD. And interestingly, no differences were evident between fecal SCFA levels between the IBD group and the SpA group with OS even without a diagnosis of IBD. A principal component analysis was performed for the IBD group where two components were identified that group where COMP.1 was defined by a high correlation between the levels of each of the ACCC (AB CCF= 0.994, AA CCF= 0.935, AP= 0.610 and AGCC-TCCF= 0.910) that had an inverse relationship with COMP.2 which was made up of SIgA (CCF=0.988) and fecal calprotectin (CCF= 0.988).

Conclusion

SCFAs play a key role in maintaining immune homeostasis both locally and systemically. BA levels were significantly lower in patients with IBD compared to CS and those with SpA. This evidence clearly supports the hypothesis that relates the lack of BA with an exacerbated inflammatory response that could give rise to a dysfunctional intestinal epithelial barrier by regulating the production of mucosal antibodies such as SIgA.
P191 Inflammatory bowel disease type unclassified in paediatric-onset IBD: A nationwide cohort study in Scotland with up to 20 years follow-up shows reclassification in the majority and mild course in those remaining as IBDU
Authors: Wands D , Gianolio L , Cameron F , Hansen R , Russell R , Wilson D
Published: January 2024

Background

Inflammatory bowel disease type unclassified (IBDU) is the least common subtype of IBD accounting for around 10% of incident cases in children. There are a lack of long-term longitudinal data to fully elucidate both disease course and reclassification rate in IBDU. Our aim is to clarify disease course and reclassification rate by presenting nationwide data of an IBDU cohort with long-term (9-20 years) follow-up.

Methods

In a nationwide study, we analysed our prospectively identified 11 year cohort of IBDU patients diagnosed 01/01/03-31/12/13 via all Scottish paediatric IBD centres (Aberdeen, Edinburgh, Glasgow) and followed-up into adult services until 01/01/23. All had a diagnosis of IBDU based on the Porto diagnostic criteria and Paris PIBD phenotypic classification using a combination of clinical, endoscopic, histological and radiological findings. Follow-up data were obtained retrospectively from electronic medical records (demographics, diagnostic plus all repeat endoscopic and radiological assessments, longitudinal disease severity based on defined global clinician assessment, medical treatment and surgical outcomes) at fixed time points (5 and 10 years post-diagnosis) and at the last follow-up.

Results

A total of 116 patients were initially identified as IBDU, with 14 patients excluded as they emigrated out of the area before the first time point. 102 patients were included in the analysis (57/102 (56%) male, median (IQR) age at diagnosis 11.5 (9.1-13.2) years) with a median (IQR) length of follow-up of 10.5 (8.6-14.0) years. A change of diagnosis was made in 61/102 (60%) patients with 30/102 (29%) reclassified as Crohn’s disease (CD) and 31/102 (30%) as ulcerative colitis (UC) after a median (IQR) disease duration of 5.0 (2.0-8.2) and 4.7 (1.8 – 7.7) years respectively. Patients who remained as IBDU had a milder disease course compared to those reclassified as CD/UC with higher 1-5 year remission rates (30/39 (77%) in IBDU vs 16/57 (28%) in CD/UC-reclassified, p<0.05), lower rates of moderate-to-severe disease (3/39 (8%) in IBDU vs 31/57 (54%) in CD/UC-reclassified, p<0.05), less need for biologics across all time points (all p<0.05) and a higher proportion managed on aminosalicylates or no medication (all p<0.05). Higher rates of surgical resections were observed by last documented FU in CD/UC-reclassified patients (IBDU 1/41 (2%) vs CD/UC-reclassified 11/61 (18%), p=0.02).

Conclusion

In our nationwide paediatric IBDU cohort the majority (60%) of patients were reclassified as either UC or CD over the longest published median follow-up (10.5 years); those who remained with an IBDU classification had a milder disease course and decreased need of biologic escalation.
P214 Effects of rectal stump proctitis on short-term postoperative complications after proctectomy and ileal pouch-anal anastomosis for Ulcerative Colitis
Authors: Calini G , Catalioto C , Dajti G , Cardelli S , Rizzello F , Gionchetti P , Poggioli G , Rottoli M
Published: January 2024

Background

Inflammation of the rectal stump (proctitis) after subtotal colectomy with ileostomy for ulcerative colitis (UC) is common. Proctitis may affect the postoperative outcomes of ileal pouch-anal anastomosis (IPAA). This study aims to explore associations between rectal stump proctitis and short-term postoperative complications (POCs) after proctectomy and IPAA for UC.

Methods

This retrospective single-centre study included patients who underwent proctectomy, IPAA and protective ileostomy for UC from 2000-2023. Data were retrieved from our prospectively-maintained database. Exclusion criteria were dysplasia or cancer (103 pts), missing pathology results (50 pts), undetermined colitis or Crohn’s Disease features at proctectomy (18 pts). All patients underwent three-staged IPAA and were divided into four groups according to the rectal stump proctitis status at pathology: remission, mild, moderate, and severe proctitis. A stepwise binary logistic regression analysis was performed for each short-term outcome. Models included variables with a different distribution according to the outcome (p-value ≤0.1).

Results

We included 785 patients who underwent proctectomy and IPAA. At pathology, remission was achieved by 162 (20.6%) patients, while proctitis of the rectal stump was mild in 211 (26.9%), moderate in 246 (31.3%), and severe in 166 (21.1%) patients, respectively. Table 1 details population characteristics and outcomes according to the proctitis status. Patients with moderate and severe proctitis received more preoperative biologics and ongoing systemic steroids at surgery. While they underwent previous abdominal surgery less frequently, the laparoscopy rate was lower with a longer postoperative length of stay. At multivariate (Table 2), Medical POCs were independently associated with ongoing antibiotics (OR 2.29 [1.01-5.20] p=0.047) and ASA score≥3 (OR 1.93 [1.11-3.35] p=0.019). Surgical POCs were independently associated with ongoing systemic steroids (OR 2.09 [1.19-3.68] p=0.011, while ongoing antibiotics (OR 0.2 [0.04-0.86] p=0.031) and laparoscopy (OR 0.53 [0.28-1.00] p=0.049) were protective. Intra-abdominal septic complications (IASCs) and abdominal/pelvic abscesses were independently associated with the proctitis status (OR 1.1 [1.06-2] p=0.018 and OR 1.56 [1.08-2.25] p=0.017, respectively).

Conclusion

Rectal stump proctitis was independently associated with postoperative abdominal and pelvic abscesses and IASCs after proctectomy and IPAA for UC. The association between proctitis and IPAA’s long-term outcomes and pouch failure need to be further explored.
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

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 >2 courses of corticosteroids, or a cumulative dose of >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

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<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

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) >16) or as a composite of both high clinical disease activity (Simple Clinical Colitis Activity Index >10 or Harvey-Bradshaw Index>7) and biochemical inflammation (C-reactive protein >10 mg/L or fecal calprotectin >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

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<0.001) and moderate (κ: 0.56, p<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

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 > 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 > 7 µg/mL correlated with improved disease outcomes in week 6, 14 and 30. In this way, IFX levels > 7 µg/mL in week 6 were associated with CRP < 5 mg/L (p = 0.008), FC <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 > 7 µg/mL in week 14 were associated with GPA = 0 (p = 0,001) and FC <150 mg/kg (p = 0,0015) in week 14 and with GPA = 0 (p = 0,019) and FC <150 mg/ kg (p = 0,027) in week 30. IFX levels > 3 µg/mL at 12 months follow-up were associated with FC < 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 > 0.001). IFX levels > 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 > 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

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

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

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<3.8mm with SMI<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<0.01 for each). The improvement in MUC and UII was also observed in patients who achieved SFCR at 6 months (p<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.
P301 Distinct plasma proteomic biomarkers associate with disease progression in patients with Inflammatory Bowel Diseases
Authors: Veenstra F E , Hu S , van Dullemen H M , Visschedijk M C , Faber K N , Dijkstra G , Samsom J N , Festen E A M , Weersma R K , Spekhorst L M , Bourgonje A R
Published: January 2024

Background

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by complex pathophysiology, phenotypic heterogeneity and disease progression. Patients with IBD show distinct shifts in circulating inflammatory proteins, which may be suggestive of biological mechanisms behind clinical disease progression. Thus far, proteomics studies in IBD have primarily focused on changes in the plasma proteome at pre- and post-diagnostic stages, as well as its genetic and phenotypic determinants. However, studies focusing on proteomic biomarkers for predicting the risk of disease progression are lacking. Here we aimed to identify plasma proteomic biomarkers associated with disease progression in patients with IBD.

Methods

In this study, a total of 83 inflammation-related plasma proteins were quantified in a cohort of 452 patients with IBD (267 with CD, 185 with UC) who participated in the 1000IBD project and had available follow-up data. Proximity extension assay technology was leveraged to measure these proteins. Disease progression outcomes, including the development of intestinal stenosis, IBD-related surgical interventions, and extraintestinal manifestations (EIMs), were extracted from electronic health records. Logistic regression analyses and Cox proportional hazards regression models were used to investigate associations between plasma proteins and the risk of disease progression outcomes.

Results

During a median follow-up of 10.3 (interquartile range [IQR] 7.6-11.1) years, 63 (23.6%) patients with CD developed intestinal stenosis, 53 (19.9%) patients with CD and 14 (7.6%) patients with UC underwent IBD-related surgery, and 120 (44.9%) patients with CD and 45 (24.3%) patients with UC developed EIMs. On multivariable analysis, macrophage colony-stimulating factor-1 (CSF-1) was most strongly associated with the presence of stricturing disease (Montreal B2 phenotype) (odds ratio [OR] per doubling in protein level 4.5, 95%CI: 1.6-12.9, P=0.005) and with a shorter stenosis-free survival (hazard ratio [HR] per doubling 4.2, 95%CI: 1.5-11.6, P=0.006). Furthermore, interferon-gamma (IFN-γ) was most strongly associated with surgery in CD (OR per doubling 1.6, 95%CI: 1.2-2.2, P=0.003) and with shorter surgery-free survival in CD (HR per doubling 1.4, 95%CI: 1.2-1.7, P<0.001) in multivariable analysis.

Conclusion

This study highlights that disease progression in IBD is associated with elevated levels of specific inflammatory plasma proteins. Specifically, CSF-1 and IFN-γ show most promise as possible proteomic biomarkers for the future development of intestinal stenosis and the risk of surgical interventions in patients with CD, respectively.
P315 Comparable un-passed patency capsule rates among Crohn’s disease patients during Clinical remission using different preparation protocols
Authors: Ukashi O , Dotan A , Borkovsky T , Talan Asher A , Thurm T , Hirsch A , Maharshak N , Eliakim R , Ben-Horin S , Kopylov U , Deutsch L
Published: January 2024

Background

Patency capsule (PC) ingestion has been proven to be a useful tool in assessing small-bowel patency before ingestion of capsule endoscope. However, false positive results of un-passed PC due to colonic hypomotility/constipation, may wrongfully preclude the use of CE in this population. Therefore, we aimed to evaluate the efficacy of intense bowel-preparation protocol before PC ingestion versus standard clear fluid-diet to reduce un-passed PC rates in patients with Crohn’s disease (CD) in clinical remission.

Methods

This was a bicenter cohort of adult patients (≥18 years-old) with small-bowel CD (L1/L3) in clinical remission, who underwent PC ingestion before CE procedure. Each center regularly follows a different preparation protocol. Patients in the intense-protocol group adhered to a low-residue diet followed by a clear fluid diet for 12 hours and fasting for 12 hours before ingestion. During capsule ingestion they were also given 10mg of Bisacodyl. Drinking and eating were resumed after 2- and 4-hours post-ingestion, respectively. Clear fluids were consumed by the control group. Propensity-score matching (PSM) in a 1:1.75 ratio was performed with adjustment for age, sex, CD-duration>1year and B2/B3 disease-phenotype, with regards to the intense preparation-protocol. The primary outcome was defined as un-passed PC (i.e., the absence of PC excretion in the stool or its presence in the abdomen by abdominal X-ray within 30 hours from ingestion).

Results

269 patients were included (intense group-79, control group-190). The cohort following the PSM comprised of 212 patients (intense group-77, control group-135). Current biologic use was less common in the intense-protocol group compared to the controls (37.7% vs. 61.2%, p=0.001). Un-passed PC rates were 13.0% (10/77 patients) vs. 19.3% (26/135 patients) in the intense-protocol and the control groups, respectively (p=0.242). On univariable analysis longer disease-duration (OR 1.042, 95% CI 1.002-1.085, p=0.040) was the only variable to be associated with un-passed PC. Age≥40 was associated with increased risk for un-passed PC as well, however only borderline significance was achieved (OR 1.917, 95% CI 0.927-3.967, p=0.085). Upon multivariate logistic regression analysis, there was no clinico-demographic/disease-related variable that was independently associated with the probability for un-passed PC. Of 269 patients, there was a single subsequent CE retention in the control group, which has resolved spontaneously (0.4%).

Conclusion

Intense-preparation protocol based on low-residue diet and laxatives was not superior to clear fluid diet alone, for reducing the rates of un-passed PC and for increasing successful patency test of small-bowel, among CD patients in clinical remission.
P323 Defining Normal Bowel Wall Thickness on Intestinal Ultrasound in an International Multicenter Cohort of Children with Inflammatory Bowel Disease in Sustained Deep Remission
Authors: Kellar A , Chavannes M , Huynh H , Aronskyy I , DeBruyn J , Kim J , Dolinger M
Published: January 2024

Background

Intestinal ultrasound (IUS) is a non-invasive, patient-centric tool for detecting and monitoring activity in patients with inflammatory bowel disease (IBD). Bowel wall thickness (BWT) is the most important parameter for assessing IBD activity, however, normal values are extrapolated from adults. We aimed to define normal BWT in children with IBD who achieved sustained deep remission.

Methods

International, multicentre, retrospective, pediatric IUS database including IBD patients (< 18 years) without a prior history of surgery or complications who underwent IUS after achieving sustained deep remission: absence of ulcerations on ileocolonoscopy and/or transmural healing on magnetic resonance enterography or computed tomography enterography and steroid-free clinical remission from 2020-2023. Descriptive statistics summarized data as percentages for categorical variables and median [IQR] for continuous variables. Primary outcome was median BWT by segment: sigmoid colon (SC), descending colon (DC), transverse colon (TC), ascending colon (AC), and terminal ileum (TI), assessed using Kruskall Wallis. Secondary outcomes included univariate association of BWT and age, sex, disease duration, diagnosis (Crohn’s disease (CD) vs. ulcerative colitis (UC)/IBD-unspecified (IBD-U) and medication exposure.

Results

80 patients (33 (41%) female; 51 (64%) CD:26 (33%)UC:3 (4%)IBD-U, median age 15.2 [14-16.6] years) with 400 bowel segments were included. Forty (50%) received anti-tumor necrosis factor therapy (anti-TNF), 18 (23%) ustekinumab (UST), 10 (12%) mesalamine(5-ASA), 6 (8%) vedolizumab (VDZ), 5 (6%) immunomodulator monotherapy (IM), and 1 (1%) upadacitinib (UPA) (Table 1). Median BWT was 1.3 [1.0-1.6]mm for SC, 1.3 [1.1-1.7]mm for DC, 1.3 [1.0-1.6] mm for TC, 1.3 [1.0-1.6]mm for AC, and 1.3 [1.1-1.5]mm for TI (Figure 1). There was no difference in BWT between segments (p=0.7952), age (p=0.1952) or sex (p=0.781). BWT was negatively associated with disease duration (p<0.05). UC patients had a 0.16 mm thinner BWT than CD (p<0.05). Mean BWT in patients on VDZ was thinner than those on anti-TNF monotherapy (-0.19mm, p<0.05). BWT in patients on anti-TNF combination therapy was thicker than patients on anti-TNF monotherapy (0.21mm, p<0.05). There was no BWT difference between patients on IM, 5-ASA and UST compared to anti-TNF (p>0.05).

Conclusion

Normal BWT for children with IBD in deep remission is less than adults, and unaffected by age, sex and bowel segment. BWT may be affected by disease duration, phenotype and medication exposure. These findings are crucial to the standardized assessment of transmural healing in children with IBD.
P338 The dependence of the level of Glycoprotein type 2 on the level of Zonulin in Crohn's disease
Authors: Knyazev O , Kagramanova A V , Lishchinskaya A , Kulakov D
Published: January 2024

Background

Introduction. Type 2 glycoprotein (GP2) is a quantitatively predominant membrane protein of excretory granules of pancreatic acinar cells. In a number of studies, it has been demonstrated that this protein is the main antigen for pancreatic antibodies associated with Crohn's disease Zonulin – a protein that can reversibly increase the permeability of the intestinal wall by changing the structure of tight junctions of the lateral surfaces of intestinal epithelial cells. The determination of fecal zonulin is used for noninvasive assessment of increased intestinal permeability. Normal values of zonulin in stool (≤ 110 ng/ml) indicate the absence of damage to the villous surface of the intestinal mucosa and normal density of intercellular contacts

The aim of the study was to establish the dependence of the level of type 2 glycoprotein on the level of fecal zonulin (FZ) in the feces of CD patients with exacerbation of the disease.

Methods

122 patients with CD in the form of ilekolitis with exacerbation of the disease (Me age — 32 years) were examined. FZ was evaluated by ELISA (IDK ® Zonulin ELISA Kit, Immunodiagnostik AG, Germany) in ng/ml. Reference values: < 83.15 ng/ml is a variant of the norm, 83.15-110 ng/ml is an elevated level, 110 ng/ml is a high level.

The level of IgG and IgA to GP2 (antibodies to glycoprotein) antigen of pancreatic centroacinar cells (Anti-GP2, IgG, IgA) was determined by ELISA. Reference values: IgG GP-2 less than 10 units/ml, Ig and GP-2 less than 5 units/ml – positive values.

Results

In the stool samples of CD patients during the period of exacerbation in 92 patients, an increase in FZ was detected, the average value was 333.4 ±16.9 ng/ml. In the blood samples of 87 patients with CD during the period of exacerbation, an increase in Ig A GP-2 was detected, the average value was 43.4±6.9 units/ml. In the blood samples of 107 CD patients during the period of exacerbation, an increase in Ig G GP-2 was detected, the average value was 17.1 ± 1.3 units/ml. There is a high correlation force between the concentration of FZ and the concentration of Ig A GP-2 (r-0.760) (p=0.010). There is a moderate correlation force (r-0.490) (p=0.023) between the concentration of FZ and the concentration of Ig G GP-2.

Conclusion

An increase in the concentration of FZ in the feces of CD patients during exacerbation significantly correlates with an increase in the concentration of Ig A GP-2 and Ig G GP-2.
P348 Increased pre-treatment faecal calprotectin concentration predicts resistance to ustekinumab induction in ulcerative colitis
Authors: Saifuddin A , Powell N
Published: January 2024

Background

Rates of resistance to advanced therapy remain high in ulcerative colitis (UC). Pre-treatment predictors of poor outcomes would provide valuable information for treating clinicians so other therapies could be given or early treatment switches could be considered if response is inadequate. We investigated whether baseline, pre-treatment faecal calprotectin (FCP) can predict resistance to ustekinumab.

Methods

Clinical outcomes at week 8, including clinical remission, endoscopic healing and mucosal healing were determined in patients enrolled in the UNIFI phase 3 placebo-controlled trial program, investigating the efficacy of ustekinumab for moderate-to-severe UC (GSE206285), in whom FCP concentrations were available at baseline, prior to initiation of treatment. Clinical outcomes were defined in patients with FCP < 250mcg/g, 250 – 999mcg/g, 1000 – 1999mcg/g and >= 2000mcg/g. Chi-squared test was used to assess statistical significance. Area under the receiver operating characteristics curve (AUROC) analyses were used to determine the ability of faecal calprotectin level to predict treatment resistance. Analyses were performed using R 4.2.3 (Vienna, Austria) and GraphPad Prism 10.0.3 (Massachusetts, United States).

Results

Outcome data and linked faecal calprotectin levels were available for 340 patients. FCP values ranged from 15 – 25249mcg/g. The median FCP value was 1402mcg/g (interquartile range: 600.8 – 2772.0mcg/g). In general, all clinical outcome measures were progressively worse with increasing FCP concentrations. For the respective FCP cut-offs, 22.0%, 19.3%, 11.3% and 6.7% achieved clinical remission; 39.0%, 24.1%, 20.6% and 16.0% achieved endoscopic healing; and 29.3%, 16.9%, 15.5% and 7.6% achieved mucosal healing (Figure 1). ROC analyses revealed that pre-treatment FCP predicts resistance to ustekinumab therapy for all stated outcomes, including clinical remission (AUROC: 0.66, P=0.001), endoscopic healing (AUROC: 0.63, P=0.0013) and mucosal healing (AUROC: 0.65, P=0.0005).

Conclusion

Increasing concentrations of pre-treatment FCP predicts resistance to ustekinumab therapy in moderate-to-severe UC. Patients with FCP >= 2000mcg/g were significantly less likely than those with FCP <1000 mcg/g to achieve clinical remission or mucosal healing. Since neutrophils are the main producers of FCP, these data build on other emerging data indicating that excessive accumulation of mucosal neutrophils is associated with treatment resistance in IBD.