bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1182 Risk of surgery in patients with newly diagnosed Crohn's disease is declining along the 21st century
Authors: Kontola K , Oksanen P , Huhtala H , Helavirta I , Ilus T 
Published: January 2025

Abstract

Background
The repertoire of biological medication for Crohn’s disease (CD) has expanded in the past two decades. The impacts of these new therapies on surgery rates are still under investigation. Our aim was to analyse the surgery rates in newly diagnosed CD patients in the biological era in all age groups.

Methods
Newly diagnosed CD patients were collected from the registry of Social Insurance Institution of Finland and data on surgeries from the Finnish Institute for Health and Welfare. Patients were stratified according to the diagnosis year and the availability of medication to three groups: 2000-2006 (infliximab era), 2007-2013 (anti-TNF era with infliximab and adalimumab available) and 2014-2020 (multiple biologicals available). The subgroups were defined as paediatric (aged &lt;20), adults (aged 20-59), and the elderly (aged ≥60).

Results
We identified 11,329 newly diagnosed CD patients, of whom 1,959 were operated. The cumulative risk of surgery was 8.2%, 13.8%, and 18.7% in 1, 5, and 10 years postdiagnosis, respectively. Overall, the 1- and 5-year risks were declining (incidence rate ratio (IRR) 0.97, CI 0.96-0.98 and IRR 0.98, CI 0.97-0.99, respectively), yet the 10-year risk showed no change (IRR 0.99, CI 0.98-1.01). The paediatric group (IRR 1.24, CI 1.10-1.39) and the elderly (IRR 1.20, CI 1.07-1.34) had higher risk of surgery compared to the adults. Also, men had higher risk of operation (IRR 1.20, CI 1.10-1.32). Adults had lower operation risk in later eras compared to infliximab era (IRR 0.55, CI 0.49-0.619). However, the paediatric group demonstrated reduction only in the last era (IRR 0.25, CI 0.18-0.34), and the elderly had stable risk (IRR 1.04, CI 0.82-1.31). The most common operation type in the primary operation was ileocecal resection (39%), followed by procedures in colon (32%) and small bowel (23%). Only in the elderly subgroup the most frequent procedure was colon resection (37%), followed by small bowel (32%) and ileocecal procedure (26%).

Conclusion
The risk of surgery among newly diagnosed CD patients is declining along the 21st century. Risk is also declining in the paediatric population, whereas the risk of the elderly has stayed constant.
P1183 Multivariable analysis of baseline variables associated with efficacy outcomes in the ELEVATE UC clinical programme
Authors: Feagan B G , Kayal M , Schreiber S , Abreu M T , Banerjee R , Fellmann M , Abbatemarco A M , Woolcott J C , Wu J , Goetsch M , Keating M , Rubin D T 
Published: January 2025

Abstract

Background
Baseline (BL) variables that accurately predict responses to advanced therapies have potential to improve ulcerative colitis (UC) management. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. BL data from patients in the ELEVATE UC clinical programme were used to identify variables associated with etrasimod response.

Methods
In this post hoc analysis of ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369),1 efficacy endpoints of clinical remission and endoscopic improvement, and change from BL in modified Mayo score (MMS) and endoscopic subscore (ES), were analysed using logistic or linear regression models, respectively, at Weeks 12 (pooled data) and 52 (ELEVATE UC 52 only). BL variables pre-selected by univariate regression analyses (≥1 comparison p&lt;0.1) associated with efficacy outcomes were further assessed using multivariable logistic/linear regression using backward selection (stay criterion p&lt;0.05).

Results
At Week 12, BL corticosteroid use (no vs yes, odds ratio; 95% confidence interval: 0.61; 0.41, 0.90), a BL ES of 3 vs 2 (0.44; 0.30, 0.64) and higher high-sensitivity C-reactive protein (hsCRP) (≥0.5 to &lt;3 vs &lt;0.5 mg/L: 0.43; 0.24, 0.77) were independently associated with lower odds of achieving clinical remission. Biologic/Janus kinase inhibitor (bio/JAKi) naïve vs experienced was associated with higher odds of achieving clinical remission at Week 52 (2.02: 1.13, 3.61). Similar variables were associated with endoscopic improvement at Week 12. At Week 52, a BL MMS 4–6 vs 7–9 (2.23; 1.38, 3.60) was linked with increased odds of achieving endoscopic improvement (Figure). At Week 12, higher hsCRP (≥0.5 to &lt;3 vs 0.5 mg/L, least squares mean difference: 0.62), a BL ES of 3 vs 2 (0.48) and bio/JAKi exposure (naïve vs experienced: -0.42) were associated with change from BL in MMS, and higher disease activity (hsCRP ≥0.5 to &lt;3 vs &lt;0.5 mg/L: 0.27; ES 3 vs 2: -0.43) with change from BL in ES; most associations were not observed at Week 52 (Table).

Conclusion
In this analysis, BL variables related to higher disease activity were associated with lower odds of achieving efficacy endpoints at Week 12. These were not associated with all efficacy endpoints at Week 52, suggesting some patients may require more time to achieve clinical outcomes.

References
1.Sandborn WJ et al. Lancet 2023; 401: 1159–1171.
Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.
P1191 Early Clinical, Biological, and Sonographic Response in Ileal Crohn’s Disease Patients Treated with Upadacitinib: A Single-Centre Real-World Experience
Authors: Maria A , Laura C , David R D L C , cristina O , Carmen G , Berta D L H , Francisco L , Ángeles M , carmen Y , Begoña C , Yago G L 
Published: January 2025

Abstract

Background
Upadacitinib (UPA), a selective JAK1 inhibitor, has shown efficacy in moderate-to-severe Crohn’s disease (CD), even in patients refractory to advanced therapies. This study aimed to evaluate the effectiveness, safety, and durability of UPA in refractory CD in real-world settings, with a focus on early objective assessment using biological markers and intestinal ultrasound (IUS).

Methods
A retrospective analysis was conducted on 41 CD patients (61% male, median age 40 years [SD: 33–53], mean disease duration 11 years [SD: 6–17]). Disease characteristics and prior treatments, including anti-TNF (100%), ustekinumab (70.7%), vedolizumab (19.5%), and risankizumab (9.8%), were recorded. Clinical (Harvey-Bradshaw Index [HBI]), biological (C-reactive protein [CRP], fecal calprotectin [FCP]), and IUS parameters (wall thickness, affected segment length, Limberg score) were assessed at 1, 2, 3, 6, and 12 months. Median follow-up was 8.2 months (SD: 4.8–12.3). Treatment patterns included standard induction (46.3%), extended induction (29.3%), and sustained high-dose (24.4%).

Results
Clinical response (≥2-point HBI reduction) was significant from week 4 and sustained throughout follow-up. Baseline CRP was 0.60 mg/dL (SD: 0.28–1.30), decreasing to 0.30 (SD: 0.05–0.80) at 1 month, 0.14 (SD: 0.04–0.64) at 3 months, and 0.10 (SD: 0.04–0.42) at 12 months, showing a non-significant downward trend. FCP dropped from 860 µg/g (SD: 270–1700) to 506 (SD: 186–2343) at 1 month, 260 (SD: 121–1200) at 3 months, and 205 (SD: 120–382) at 12 months, with a similar non-significant trend.
Of 31 patients with baseline IUS, 55.6% showed radiological improvement in at least two IUS parameters at 12 months, though not statistically significant.
Nine patients (22%) discontinued UPA due to adverse events (7.3%) or lack of response (17%). Non-severe adverse effects were reported in 53.7%, predominantly dermatological, without requiring dose adjustments or discontinuation. No severe infections, thromboembolic events, or cardiovascular complications were observed.

Conclusion
UPA demonstrated rapid, effective, and safe treatment for refractory CD in clinical practice. Trends toward early clinical, biological, and sonographic improvements were observed, highlighting its potential in real-world management of refractory CD.
P1194 Evaluating the Cost-Utility of Intestinal Resection Before Anti-Tumor Necrosis Factor Therapy for Strictures in Crohn's Disease in China
Authors: Tang X , Bai X , Yang H , Han W 
Published: January 2025

Abstract

Background
Crohn's disease is a chronic, relapsing immune-mediated disorder. Stricturing Crohn's disease is severe and frequent complication. The therapeutic landscape has been revolutionized with the advent of biologic agents.

Methods
A hybrid model was used. The model consisted of a decision tree model component and a Markov model component with 10-year follow-up for assessing the different therapies. Quality-adjusted life-years and costs were discounted at an annual rate of 5%. A sensitivity analysis was performed to evaluate the resilience of the results in the face of parameter uncertainty.

Results
According to our base-case analysis results, maintenance treatment with adalimumab after enterectomy is the most cost-effective (more quality-adjusted life-years gained and less cost incurred), followed by adalimumab ($47,709.37/QALY vs. $45,986.53/QALY vs. $66,526.40/QALY vs. $46,186.51/QALY). The results of one-way sensitivity analysis and probabilistic sensitivity analysis demonstrated the robustness of the model and base-case analysis accounting for the uncertainty of parameters.

Conclusion
In patients treated surgically after an initial diagnosis of intestinal stricture, adalimumab is a biologic agent that should be recommended for later maintenance therapy. In contrast, surgery may be recommended later in patients who were not treated surgically at the outset.

References
Knowles, S., et al., Quality of Life in Inflammatory Bowel Disease: A Systematic Review and Meta-analyses-Part II. Inflammatory bowel diseases, 2018. 24(5): p. 966-976.
Rieder, F., C. Fiocchi, and G. Rogler, Mechanisms, Management, and Treatment of Fibrosis in Patients With Inflammatory Bowel Diseases. Elsevier, 2017(2).
Mak, J.W.Y. and S.C. Ng, Epidemiology of fibrostenosing inflammatory bowel disease. Journal of digestive diseases, 2020. 21(6): p. 332-335.
Lin SN, M.R., Qian C, Bettenworth D, Wang J, Li J, Bruining DH, Jairath V, Feagan BG, Chen MH, Stenosis Therapy and Antifibrotic Research (STAR) Consortium; Rieder F. Development of antifibrotic therapy for stricturing Crohn's disease: lessons from randomized trials in other fibrotic diseases. Physiol Rev, 2022.
P1201 Pre- and postnatal metal exposures impact Crohn’s Disease risk and intestinal inflammation in an analysis of deciduous teeth
Authors: Tinoco da Silva Torres J , Midya V , Picker M , Martinez M , Moreira-Barbosa C , Kim T , H Allin K , Jess T , Saraiva S , Gouveia C , Talamini R , Brand E , Oldenburg B , Amil Dias J , Amorim R , Trindade E , Colombel J F , Peter I , Arora M , Agrawal M 
Published: January 2025

Abstract

Background
Early-life exposures influence long-term health, including the risk of IBD, however measuring these exposures is challenging. A prior pilot study showed that deciduous teeth could quantify environmental exposures. Here we analyzed essential and toxic metals in baby teeth to explore their impact on Crohn’s Disease (CD) risk during pre- and early postnatal periods.

Methods
We obtained deciduous teeth from 2 cohorts:1) individuals with CD and controls who had their baby teeth stored (IBD Tooth Fairy Study), and 2) offspring of women with and without IBD, followed since birth (MECONIUM Study). Essential [magnesium, calcium, chromium, manganese, cobalt, nickel, copper, zinc, molybdenum] and non-essential [lithium, aluminum, arsenic, strontium, cadmium, tin, lead, bismuth] metals were measured using laser ablation-inductively coupled plasma mass spectrometry. Teeth neonatal line was used as a reference to differentiate pre- and postnatal exposures. Data were analyzed using metal-to-calcium ratios to evaluate metal content variations over time. Weighted quantile regression analyses determined the relationship between metal mixtures (essential and non-essential) pre- and postnatally with incident CD (IBD Tooth Fairy Study) and with fecal calprotectin (Fcal) level at 2 years of age (MECONIUM Study).

Results
Sixty teeth were analyzed from the IBD Tooth Fairy cohort (27 CD, mean age at diagnosis 17y (range 5-32); 33 controls; mean age at recruitment 21.6y (range 7-48). Pre- and postnatal mixture of essential metals was associated with lower adjusted odds ratio (aOR) of CD, with manganese as the primary contributor (aOR [95%CI]: 0.51 [0.28, 0.91] and 0.69 [0.43, 1.12], respectively). Conversely, a mixture of non-essential metals was linked to increased odds of CD, with cadmium as the main contributor (aOR [95%CI]: 3.23 [1.11, 9.41] and 2.46 [1.24, 4.88], respectively) (Figure 1A).
From the MECONIUM Study, 29 teeth were analyzed (6, 6, and 17 from offspring of women with CD, UC, and controls, respectively). Median Fcal (mcg/gm) at age 2 years was 243.5 in offspring of women with IBD and 111 in offspring of women without IBD. A mixture of essential metals (pre- and postnatal) was associated with lower Fcal levels at age 2 years, with manganese being the highest contributor in both periods (Figure 1B).

Conclusion
Pre- and postnatal exposures to essential and non-essential metals, measured in baby teeth, were associated with the risk of developing CD and higher Fcal levels in babies at risk for IBD, with manganese being the top contributor in both cohorts. Future research should expand these findings and explore the mechanistic pathways through which these exposures affect IBD risk.
P1343 Impact of Biologic Therapy on Gut Microbiome in Crohn's Disease: An Indian Patient Cohort Study
Authors: Raghunathan N , Gunala N , Thakur M , Mekala D , Patel R , Bharath P , Kumari V , Gavate R , Banerjee R 
Published: January 2025

Abstract

Background
The advent of biologic therapy has revolutionized the treatment paradigm in IBD. In developing countries including India, where affordability and accessibility drive the treatment choice, it is important to understand the mechanisms behind biologic therapy and pave way to the future to predict response rates. This prospective study examines the impact of biologic therapy on the gut microbiome in moderate-to severe CD patients in India.

Methods
Fecal samples were collected from healthy controls(n=36) and 39 CD patients at baseline and after completing induction doze [Infliximab (n=16), Vedolizumab (n=6), and Ustekinumab (n=17)]. Individuals on recent antibiotics(&lt;8weeks)/probiotics/NSAIDs were excluded. Clinical response was assessed at 6-weeks, with follow-up at 6 months to classify responders (CDAI&lt;150) and non-responders(CDAI&gt;150). DNA was isolated from 114 fecal samples and subjected to whole-genome shotgun metagenomics to generate a minimum of 6GB data per sample. After removal of human DNA read contamination, taxonomy and functional annotation was assigned using Kraken2, Bracken, and Human3 tools and statistical significance by using Wilcoxon Test (R-Studio).

Results
The gut microbiome in CD at baseline exhibited reduced diversity, lower SCFA-producing bacteria and increased pro-inflammatory bacteria like Collinsella and Escherichia compared to healthy cohort. The human DNA content in fecal samples was significantly higher in CD compared to healthy cohort with mean of 19.2% and 0.06% respectively. Post biologic therapy, there was significant restoration of the gut microbiome with increase in bacterial diversity, increased abundance of SCFA-producing Firmicutes and Phascolaractobacterium , probiotic Bifidobacterium species and reduction in pathogenic bacteria Enterococcus gallinarium. The average human DNA content also decreased to 9.6%. On sub-analysis, between responders (n=31) and non-responders; pathogenic Klebsiella pneumonia, Fusobacterium and Corynebacterium were found to be higher in non-responders compared to responders (Fig2A). Further, 19 metabolic pathways significantly differed between responders and non-responders, which included those pathways responsible for degradation of carbohydrates and generation of precursor metabolites and energy higher in the former (Fig2B).

Conclusion
There is increased gut dysbiosis in CD relative to healthy cohort which appears to get restored upon biologic therapy. The findings suggest the biologic therapy may play a role in restoring the compromised intestinal barrier in CD. A microbiome-based signature to predict response rates on biologic therapy can be seen in future.
P1348 Unique gut microbiome profile can distinguish Intestinal Tuberculosis and Crohn`s Disease: An Indian patient cohort study
Authors: Raghunathan N , Thakur M , Gunala N , Mekala D , Patel R , Bharath P , Banerjee R 
Published: January 2025

Abstract

Background
The rising IBD in the Tuberculosis(TB) endemic zones of Asia poses diagnostic challenges. TB and Crohn`s Disease (CD) have overlapping clinical symptoms, radiologic and histopathology features. Here, we aimed to study the gut dysbiosis in CD and ITB and use a machine-learning(ML)-based algorithm to identify a microbiome-based signature to distinguish the two conditions.

Methods
We recruited 26 confirmed ITB, 28 CD and 26 healthy controls. Fecal samples were collected from treatment-naive patients. Individuals on recent antibiotics(&lt;8weeks)/probiotics/NSAIDs were excluded. Fecal DNA was extracted for 16SrRNA-V4 sequencing. Taxonomy(LEfSe) and functional pathway predictions (PICRUSt) were generated and analysed. Microbial taxa were classified based on Amplicon Sequence Variant Approach. Statistical analyses were performed using Wilcoxon Test (R-Studio). Seven ML-models were tested for performance to differentiate CD-ITB and identify a microbial signature using Gini index.

Results
Bacterial alpha diversity; both Shannon and Simpson indices were significantly lower in CD compared to ITB (Fig1A). The CD cohort showed reduced Firmicutes, but higher abundance of Bacteroidota and Desulfobacterota relative to ITB. The median Firmcutes: Bacteroidota ratio (F:B) was the least in CD (2.15), followed by ITB (4.4) and healthy (6.4) (Fig1B&C). Accuracies of KNN and XGBoost algorithms for differentiation between CD-ITB were 88% and 85%, respectively(Fig2A). Butyrate-producers Faecalibacterium, Lachnoclostridium, and Eubacterium hallii were lower in CD (Fig2B) with reduced abundance of 3 butyrate-production pathways (HEXITOLDEGSUPER-PWY,PWY-6628,PWY-5677). ML-based unique microbial signature of 6 taxa, including Escherichia coli, Romboutsia Streptococcus and Bifidobacterium was identified (Fig2C).

Conclusion
CD and ITB demonstrate significant differences in bacterial diversity and F:B ratio suggesting severe dysbiosis in CD relative to ITB. Reduced butyrate producers in CD and increased pathogens were key features. These findings highlight microbiome analysis as a promising non-invasive diagnostic tool for differentiating CD-ITB.
P1350 The Role of oral Porphyromonas gingivalis and Its Outer Membrane Vesicles in Inflammatory Bowel Disease
Authors: Yang C , Zhao Y , Chen J , Chen N 
Published: January 2025

Abstract

Background
The etiology of Inflammatory bowel disease (IBD) remains elusive, but emerging evidence suggests a potential link between oral microbiota and IBD. Porphyromonas gingivalis(Pg.), a major pathogen in periodontal disease, and its outer membrane vesicles(OMVs) may play significant roles in the development and progression of IBD.

Methods
Animal models of IBD were established to observe the impact of Pg. and its OMVs on intestinal inflammation. In vitro cell culture was conducted to explore the interaction between Pg.-OMVs and intestinal epithelial cells and immune cells.

Results
Through the analysis of salivary microbiota in IBD patients and healthy individuals, we observed a significant increase in the abundance of Pg. in the saliva of IBD patients. OMVs may serve as a novel medium for oral bacteria to communicate with the gut. Our findings indicate that Pg.-OMVs can promote the development of IBD through various mechanisms. Firstly, they can disrupt intestinal barrier function by promoting inflammation in intestinal epithelial cells and degrading tight junction proteins. Additionally, Pg.-OMVs carry pathogenic factors and pro-inflammatory molecules, which activate intestinal macrophages to polarize towards the M1 phenotype, inducing inflammatory responses. Beyond systemic effects, we discovered that the key virulence factor LPS of Pg. can stimulate oral epithelial cells to secrete exosomes. These exosomes exhibit pro-inflammatory properties, including the disruption of the intestinal mucosal barrier and the promotion of macrophage polarization towards the M1 phenotype, with subsequent secretion of inflammatory factors.

Conclusion
Porphyromonas gingivalis and its outer membrane vesicles play important roles in the pathogenesis of IBD. Understanding these mechanisms provides new insights into the relationship between oral health and IBD and may lead to the development of novel diagnostic and therapeutic strategies for IBD.
P1356 Comparison of different diagnostic test for detection of CMV colitis in hospitalized patients with ulcerative colitis: an interim analysis
Authors: Melotti L , Rinaldi M , Gabrielli L , Rosini F , Salice M , Scaioli E , Calabrese C , Dussias N , Vanigli N , Gionchetti P , Rizzello F 
Published: January 2025

Abstract

Background
Cytomegalovirus (CMV) colitis is a serious concern worsening the prognosis of patients with ulcerative colitis (UC) as an independent risk factor for hospitalization and surgery. European guidelines indicate that immunohistochemistry [IHC], tissue polymerase chain reaction [PCR], or possibly both, are essential for confirming active CMV colitis in IBD and should be considered as standard tests. The aim of our study is to evaluate the diagnostic performance of different tests used for diagnosis of CMV infection in comparison with the gold standard in hospitalized patients for UC flare.

Methods
We prospectively included consecutive UC patients hospitalized for a UC flare since March 2024. UC activity was assessed according to the Truelove&Witts score together with CMV-DNA PCR on blood, stool, tissue and IHC on colonic biopsies were all performed within 5 days from admission. Demographic data, history of medications, lab test at admission were collected for every patient. Patients were treated for UC according to guidelines; in case of CMV positivity on IHC or tissue CMV PCR &gt; 250 cp/mg (qPCR) they received either ganciclovir or vanganciclovir if useful according to investigators. We registered clinical remission and need of surgery within 30-days from hospitalization.

Results
In this interim analysis we collected data on 51 patients. Of these, 70.6% were admitted with severe UC according to the Truelove&Witts score, with a median endoscopic Mayo score of 3, and 49% of the patients were steroid-refractory at hospital admission. 63% of patients achieved clinical remission 30 days after admission, whereas 37% did not show signs of response, including 4 patients who needed surgery within this time frame. In our cohort 16/51patients (31.4%) were diagnosed with CMV colitis according to IHC or qPCR &gt; 250 cp/mg, while only 3/51 patients (5.8%) confirmed the diagnosis according to IHC criteria. Only 8 patients received antiviral treatment; in the remaining 8 cases antiviral treatment was not indicated due to lack of presumed clinical benefit. Blood positive CMV-DNA was found in 8 patients; among them 5 were confirmed with CMV colitis. Only 3 patients tested positive for stool CMV-DNA, however all of them received a subsequent confirmation of CMV colitis.

Conclusion
Concordance between diagnostic criteria (qPCR vs IHC criteria) was low confirming the unreliability of currently accepted diagnostic test. Preliminary data about alternative sources of CMV DNA testing looks promising and more reliable. Further data are needed to attain definite conclusions.