bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt;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

Abstract

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&gt;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

Abstract

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 (&lt; 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&lt;0.05). UC patients had a 0.16 mm thinner BWT than CD (p&lt;0.05). Mean BWT in patients on VDZ was thinner than those on anti-TNF monotherapy (-0.19mm, p&lt;0.05). BWT in patients on anti-TNF combination therapy was thicker than patients on anti-TNF monotherapy (0.21mm, p&lt;0.05). There was no BWT difference between patients on IM, 5-ASA and UST compared to anti-TNF (p&gt;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

Abstract

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: &lt; 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

Abstract

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 &lt; 250mcg/g, 250 – 999mcg/g, 1000 – 1999mcg/g and &gt;= 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 &gt;= 2000mcg/g were significantly less likely than those with FCP &lt;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.
P384 Serum biomarkers of proteolytic type III and type IV collagen remodeling differentiate patients with Inflammatory Bowel Disease according to infliximab treatment response or non-response
Authors: Pehrsson M , Alexdottir M S , Steenholdt C , Boye T L , Karsdal M A , Bay-Jensen A C , Ainsworth M , Mortensen J H 
Published: January 2024

Abstract

Background
Characterized by chronic inflammation, patients with Inflammatory Bowel Disease experience detrimental remodeling of their intestinal extracellular matrix (ECM). Treatment with anti-inflammatory drugs can reduce the inflammation, leading to remission and tissue healing. However, adequate monitoring of patients is critical to ensure and maintain treatment response. As potential surrogate markers of ECM remodeling, we investigated blood-based neoepitope biomarkers of type III and type IV collagen in patients with IBD. We aimed to determine the value of the biomarkers for monitoring and predicting response to infliximab (IFX).

Methods
A total of 160 IBD patients initiating IFX treatment at visit 1 were included, having blood drawn at visits 1, 2, and 3, with treatment response evaluated at visit 3 using the Physicians Global Assessment (PGA) score. The response was defined as a PGA of 0 at Visit 3. Measuring the biomarkers C3M (MMP-9 degraded type III collagen) and C4A3-HNE (neutrophil elastase degraded type IV collagen α-3 chain) in the blood, we evaluated their ability to differentiate responders and non-responders to IFX induction therapy. The serum biomarker levels at each visit between responders and non-responders were statistically assessed using a mixed-effects model correction applying Bonferroni’s multiple comparison test and receiver operating characteristics (ROC).

Results
At all three visits, patients not responding to IFX treatment had significantly elevated C3M levels (p&lt;0.001, &lt;0.01, and &lt;0.01) (Figure 1A). Quantifying serum C4A3-HNE demonstrated an elevation in responders at visits 1, 2, and 3, with a significant biomarker increase at visit 2 compared to non-responders (p&lt;0.05) (Figure 1B). Determining the serum C3M levels at Visit 3 resulted in identifying non-responders with an area under the curve of 0.695 (sensitivity: 74.4% and specificity: 60.0%, p=0.009).

Conclusion
Quantifying the MMP-9 degraded C3M biomarker in the serum of IBD patients could differentiate responders and non-responders at visit 1 upon initiating IFX treatment. Serum C3M remained elevated in non-responders throughout the study period and applying ROC analysis quantifying C3M at Visit 3 could assist in identifying non-responders to IFX treatment. The C4A3-HNE biomarker was elevated in responders at all three visits, being statistically elevated at visit 2, indicating potential as a surrogate marker of IFX treatment response. Our data suggest differences in the proteolytic remodeling of type III and IV collagen quantified by neoepitope biomarkers between responders and non-responders to IFX treatment. The differences were quantifiable already at treatment initiation (visit 1).
P398 The Burden of Psychiatric Manifestations in Inflammatory Bowel Diseases: A Systematic Review with Meta-analysis
Authors: Massironi S , Pigoni A , Vegni E A M , Keefer L , Dubinski M C , Brambilla P , Delvecchio G , Danese S 
Published: January 2024

Abstract

Background
Psychiatric manifestation in individuals with inflammatory bowel disease (IBD) has been the subject of extensive research, but uncertainties remain regarding its precise magnitude, its impact on intestinal disease, and the whole burden of psychiatric manifestations.This systematic review aims to synthesize available evidence on the prevalence and impact of psychiatric disorders in patients with IBD.

Methods
A systematic search of PubMed/MEDLINE, EMBASE, and SCOPUS databases was performed to identify relevant studies published between January 2010 and January 2023. Cross-sectional, case-control, cohort, registry, and population studies that addressed the prevalence of depression, anxiety, bipolar disorder, and schizophrenia in patients with IBDs and that met the specific inclusion criteria were selected. A meta-analysis to assess the strength of association between IBD and selected psychiatric disorders was also performed. Data extraction and quality assessment were performed.

Results
The search yielded a total of 3209 articles. 193 met the inclusion criteria, but only 26 studies provided the complete data for the analysis (Table 1).
Overall, the prevalence of psychiatric comorbidities was found to be significantly higher in IBD compared with the general population. The analysis revealed a moderate but significant association between IBD and depression, with a pooled odds ratio (OR) of 1.42 (95%CI 1.33-1.52). (Fig.1)
Also, anxiety emerged as a prevalent comorbidity in IBD with a pooled OR of 1.3 (95%CI =1.22-1.44). Evidence on the relationship between bipolar disorders and IBD was limited and mixed, with a pooled OR of 1.64 (95%CI=1.20-2.24), despite a substantial heterogeneity (I2=94.01%). Only three studies examined the association between schizophrenia and IBD, providing widely heterogeneous results, with an inconclusive OR (p= 0,73), estimated at 0.93 (95%CI=0.62-1.39).

Conclusion
This systematic review with meta-analysis highlights that patients with IBD, both CD and UC, frequently experience psychiatric comorbidities such as depression, anxiety, bipolar disorders, and, to a lesser extent, schizophrenia. These disorders are more prevalent in IBD patients than in the general population. Depression and anxiety are particularly prevalent. Bipolar disorder is still an underexplored area in the context of IBD. Data on the relationship between schizophrenia and IBD is sparse and inconclusive and requires further research. Given the high prevalence of psychiatric comorbidities in IBD patients, the results of this systematic review underscore the need for a deeper understanding of these associations and early identification and tailored interventions for mental health in patients with IBD to improve their quality of life.
P411 Is transmural healing better than mucosal healing in pediatric Crohn’s disease?
Authors: D'Arcangelo G , Carnevale L , Oliva S , Maccioni F , Russo G , Busato L , Aloi M 
Published: January 2024

Abstract

Background
While the long-term benefit of achieving mucosal healing (MH) in Crohn’s disease (CD) has been demonstrated, data on transmural healing (TH), assessed by non-invasive imaging modalities (i.e. magnetic resonance enterography, MRE) are scarce, particularly in the pediatric setting. Nonetheless it has been deemed as an adjunctive target for CD by the STRIDEII consensus. We aimed to investigate the outcomes of pediatric CD patients with TH comparing them to those with MH and with “no healing”.

Methods
Prospective, single-center, observational study conducted at the Pediatric Gastroenterology and Liver Unit of the Umberto I Hospital, Sapienza University of Rome. Children with an established diagnosis of CD and under biological therapy undergoing an MRE and an ileocolonoscopy performed within a 3-month interval were consecutively enrolled. Transmural healing was defined as the complete healing of both the mucosa at endoscopy (absence of ulceration) and of the bowel layers at the MRE. In the presence of a normal colonoscopy but an active MRE children were deemed as MH. The group “no healing” (NH) included children with an active endoscopy, regardless of the MRE classification. At 6, 12, and 24 months, the following outcomes were evaluated and compared in the three groups: disease flares, CD-related hospitalization, CD-related surgery, need for step-up treatment, and occurrence of complications.

Results
93 children were included (30% female, mean age 11,2±3,8). Twenty-three (25%) were classified as TH, 27 (29%) as MH and 43 (46%) as NH. Overall, at the Kaplan Meier analysis, the risk of any unfavorable outcome was significantly lower in both TH and MH patients compared to NH (Log Rank p&lt;0.0001 and p=0.002, respectively). Specifically, children with TH were at lower risk of hospitalization (p=0.02), and complications (p=0.007) compared to those with NH. No difference was found between MH and NH children for the same outcomes. Both TH and MH children were at lower risk of step-up treatment (p&lt;0.0001 and p=0.0.0002, respectively) compared to NH. No difference was found between TH and MH patients for all the outcomes evaluated.

Conclusion
Achieving transmural healing in pediatric CD is associated with better long-term outcomes, although the additional benefit compared to reaching MH alone does not appear significant. However, the persistence of inflammation is associated with worse outcomes in all patients.