bluuebunny/crossref_metadata_2025_split huggingface dataset:
P125 MIG (CXCL9) and IL22 are key biomarkers that discriminates between paediatric IBD patients and non-IBD patients in a novel biomarker model
Authors: Eindor A , Tsai K , Jacobson K 
Published: January 2024

Abstract

Background
The current gold standard for diagnosis of Inflammatory bowel disease (IBD) is based on clinical and endoscopic evaluation as well as histologic and radiologic evaluation. However, endoscopic evaluation can be uncomfortable and carry some risks, especially in the paediatric population that requires general anesthesia in order to perform the procedure. Our aim was to investigate whether serum biomarkers can differentiate between paediatric patients with and without IBD. Secondary aims were to determine whether there are biomarkers that can differentiate between Crohn's disease (CD) and Ulcerative colitis (UC), and whether we can predict progression to biologic treatment within one year from diagnosis using these biomarkers.

Methods
Paediatric patients undergoing a first diagnostic colonoscopy at British Columbia Children's Hospital (BCCH) between December 2019 and June 2022 were invited to participate in the study. A 2 ml blood sample was taken from each participant at the time of colonoscopy. Demographic and clinical data were collected from each patient. Blood samples were analyzed using the LegendplexTM flow cytometry kits investigating 12 different inflammatory cytokines and chemokines associated with IBD. Eleven of them were found most significant in an initial analysis performed on 100 patients using 50 biomarkers, and CCL7 was added due to significance in previous studies. A prediction model was built via a supervised learning method to determine how well we can predict the different groups.

Results
Two hundred and forty-six paediatric patients participated in the study. Median age was 13.03 years, 92 were females (37.4%) and 155 (63.01%) were diagnosed with IBD, with 103 (66.45%) diagnosed with Crohn's disease. The AUROC using SPLS-DA classification was 0.805. MIG and Il22 were found to be the key biomarkers to discriminate between pediatric IBD patients and non-IBD patients. In a random forest analysis MIG, Il8 and Il22 were found most important for discrimination.
On a univariate analysis MIG and Il18 were found statistically significant as a predictor of CD (p=0.016 for both). CXCL1 was predictive to progression to biologic treatment within one year of diagnosis (p=0.039). However, the prediction model did not predict well the subclasses nor progression to biologic treatment.

Conclusion
Using serum biomarkers can predict the diagnosis of Paediatric IBD. MIG and Il22 were found to be the key biomarkers in the prediction model.
P165 Guselkumab binding to CD64+ IL-23–producing myeloid cells enhances potency for neutralizing IL-23 signaling
Authors: Atreya R , Abreu M T , Krueger J G , Eyerich K , Greving C , Hammaker D , Stoveken B , Hartman J , Leppard K , Sarabia I , Wertheimer J , Deming J , Kohler K , Li H , Freeman T , Hart A , Keyes B , Ritchlin C , McInnes I B , Allez M , Fourie A , Sachen K 
Published: January 2024

Abstract

Background
IL-23 is implicated in the pathogenesis of inflammatory bowel disease (IBD) and myeloid cells that express FcγRI (CD64) have been identified as the primary cellular source of IL-23 in inflamed IBD gut tissue. Guselkumab (GUS) and risankizumab (RZB) are monoclonal antibodies (mAbs) specifically directed against the IL-23p19 subunit. GUS is a fully human IgG1 mAb with a native Fc region while RZB is a humanized IgG1 mAb with a mutated Fc region. Here, we evaluated CD64 and IL-23 expression in IBD patient gut biopsies, binding of GUS and RZB to CD64, and the functional consequences of CD64 binding by IL-23p19 subunit mAbs, in in vitro assays.

Methods
IL23A and FCGR1A (CD64) expression was analyzed from bulk and single-cell RNAseq datasets. Binding of mAbs to IFNγ-primed human monocytes, as well as binding to IL-23–secreting inflammatory monocytes and capture of endogenously secreted IL-23, were assessed by flow cytometry. Internalization of IL-23, GUS, and RZB within CD64+ macrophages was evaluated using live cell confocal imaging. Potency of GUS and RZB for inhibiting IL-23 signaling was determined in a co-culture of THP-1 (a CD64+ monocyte cell line activated to produce IL-23) and an IL-23 reporter cell line (measuring biologically active IL-23).

Results
Analysis of RNAseq datasets showed that FCGR1A, IL23A, and IL12B were significantly increased in inflamed versus non-inflamed IBD gut biopsies and that IL23A was predominantly expressed by FCGR1A-expressing myeloid cells. In in vitro assays GUS, but not RZB, showed Fc-mediated binding to CD64 on IFNγ-primed monocytes. CD64-bound GUS simultaneously captured IL-23 secreted from the same cells. GUS, but not RZB, bound to the surface of CD64+ macrophages and mediated internalization of IL-23 to low pH intracellular compartments. GUS and RZB demonstrated similar potency for inhibiting signaling by IL-23 present in THP-1–conditioned media. However, in a co-culture of IL-23–producing THP-1 cells with an IL-23–responsive reporter cell line, GUS demonstrated enhanced potency compared to RZB for inhibition of IL-23 signaling.

Conclusion
Our transcriptomic analysis supported previous observations of CD64+ myeloid cells as a key source of IL-23 production in inflamed IBD gut tissue. GUS binding to CD64 on IL-23–producing cells likely contributed to the enhanced functional potency of GUS compared to RZB for inhibition of IL-23 signaling in the co-culture assay. These in vitro data support a hypothesis for optimal enrichment of GUS in inflamed tissues where CD64+ IL-23–producing myeloid cells are increased and in proximity to IL-23–responsive lymphoid cells, enabling GUS to more potently neutralize IL-23 by targeting IL-23 at its source of production.
P174 Treg Cell and Human Intestinal Myoﬁbroblast-Derived Amphiregulin induced by TGF-β Promotes Colitis-Associated Intestinal Fibrosis
Authors: Wang L , Zhang H , Zhao X 
Published: January 2024

Abstract

Background
Intestinal fibrosis is one of the most threatening complications of Crohn’s disease (CD). Intestinal fibrosis is usually the result of chronic inflammation, and T cell response is the main driver of intestinal inflammation. At present, there are few researches on the mechanism of Treg cells in intestinal fibrosis, and the role of Treg-derived Areg in intestinal fibrosis has not been studied.

Methods
AREG and TGF-β expression was assessed in patients with CD with or without intestinal ﬁbrosis by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). In this study, dextran sulfate sodium (DSS)-induced chronic colitis model in wild-type (WT) and Areg-/- mice and T-cell transfer model with WT and Areg-/- Treg cells were used. CD4+ T cell expression of AREG induced by Treg cell differentiation-related cytokines and self-secreted cytokines was determined by Western blotting. Human intestinal myoﬁbroblasts expression of AREG induced by different cytokines was determined by qRT-PCR. The effect of AREG on proliferation/migration in human intestinal myoﬁbroblasts was determined.

Results
AREG and TGF-β expression was increased in ﬁbrotic sites compared with nonﬁbrotic sites from patients with CD. Although DSS-induced more severe colitis in Areg-/- mice, which developed less severe intestinal fibrosis compared with WT mice on DSS insults. Transfer of Areg-/- Treg cells induced less severe ﬁbrosis in Rag-/- mice compared with WT Treg cells. TGF-β promoted AREG expression in Treg cells by activating Smad3. In addition, TGF-β promoted the AREG expression in Treg cells in a time and dose dependent manner. TGF-β also promoted the AREG expression in human intestinal myoﬁbroblastss from CD patients with fibrosis. AREG promoted human intestinal myoﬁbroblast proliferation and motility.

Conclusion
These findings revealed that Treg and human intestinal myoﬁbroblast-derived AREG induced by TGF-β promotes intestinal fibrotic responses in experimental colitis and human patients with CD.
P187 Validation of Disease Severity Index for Predicting Complicated Disease in Crohn’s Disease: A comparison study with Lémann Index
Authors: Zhou L , Qiu Y , Lu B , Lin X , Chen B , He Y , Zeng Z , Chen M , Li X , Mao R 
Published: January 2024

Abstract

Background
The recently developed Disease Severity Index (DSI) provides a comprehensive assessment of structural bowel damage (BD) in addition to short-term signs and symptoms. We aimed to evaluate DSI in identifying patients with Crohn’s disease (CD) at high risk of disease progression, compared to Lémann Index (LI).

Methods
This was a retrospective observational study. The consecutive patients with CD in a referral center between 2017 and 2019 were reviewed. DSI and LI were calculated at diagnosis. A complicated CD course (composite outcome of corticosteroid dependency, treatment escalation, CD-related hospitalization, and surgery) and associated risk factors were further analyzed.

Results
The median LI and DSI of included 300 patients were 1.63 (interquartile ranges [IQR], 1.25-3.13) and 42 (IQR 32-51), respectively. 152 patients (50.7%) experienced a complicated disease course (median 5.1 months; IQR 1.1-20.2). DSI (AUC 0.67; 95% CI 0.60-0.72) showed a better performance in predicting a complicated course of CD over LI (AUC 0.57; 95% CI 0.50-0.62; P=0.01). The cumulative probability of complicated CD course in severe patients was higher compared to those with ‘mild CD’ (P&lt;0.001) when stratified by a cut-off value (DSI&gt;43). The Cox analysis identified DSI&gt;43 (HR 2.18; 95% CI 1.54-3.09; P&lt;0.001), B2/3 vs. B1 (HR 2.80; 95% CI 1.99-3.94; P&lt;0.001), and a higher level of CRP (HR 1.01; 95% CI 1.00-1.02; P=0.005) as independent prognostic factors for complicated CD. In contrast, LI was not associated with complicated CD (P=0.164).

Conclusion
Higher DSI was validated to be associated with a complicated disease outcome. DSI might play a better role than LI in identifying patients at high risk of disease progression.
P190 Identification of clinical risk factors for postoperative endoscopic recurrence in Crohn’s disease: a prospective, multicenter cohort study
Authors: Bak M , Beelen E , van der Bilt J , Camps M , Dijkstra G , van der Marel S , Stassens L , Maljaars J , Buskens C , Jansen S , Jharap B , Horjus C , van Schaik F , West R , de Boer N , van der Woude J , van Ruler O , de Vries A 
Published: January 2024

Abstract

Background
Further refinement of clinical risk stratification for postoperative endoscopic recurrence in patients with Crohn’s disease is required to identify patients who will benefit from prophylactic therapy. Therefore, we aimed to assess risk factors for endoscopic recurrence in a large prospective, multicenter cohort study.

Methods
CD patients (≥16 years) scheduled for ileocolic (re-)resection (ICR) and those who underwent an ileocolonoscopy at 6 months following ICR were included. Primary outcome of the study was endoscopic recurrence (modified Rutgeerts’ score ≥ i2b at 6 months). Multivariable logistic regression was performed to identify clinical risk factors. The model included a random effect for the study center to correct for potential correlation between treating center and the outcome.

Results
In total, 298 patients underwent ICR (79.2% primary ICR, 20.8% re-resection) after a median disease duration of 5.3 years (IQR 1.0 – 12.4). 60.4% of patients were female with a median age at surgery of 34.1 years (IQR 25.7 – 50.5). 67.8% of the patients were exposed to ≥1 biological prior to surgery. Postoperative prophylactic medication (&lt;12 weeks to ICR) was initiated in 85/298 (28.5%) patients; 24.7% immunomodulator, 29.4% anti-TNF, 27.1% combination therapy [immunomodulator with anti-TNF agent], 4.7% vedolizumab, 14.1% ustekinumab. Mean time to postoperative ileocolonoscopy was 6.2 months (SD 1.3). Endoscopic recurrence was diagnosed in 37.9% of the patients. Multivariable logistic regression identified active smoking (adjusted OR [aOR] 3.12; 95% CI 1.63 – 5.98) and penetrating disease behaviour (aOR 1.92; 95% CI 1.04 – 3.57) as risk factors for endoscopic recurrence, whilst ileocolic disease (versus ileal disease; aOR 0.27; 95% CI 0.15 – 0.49) and postoperative prophylactic medication (aOR 0.24; 95% CI 0.12 – 0.47) were identified as protective factors for endoscopic recurrence (Table 1).

Conclusion
Active smoking and penetrating disease behaviour at time of surgery were identified as risk factors for early postoperative recurrence in Crohn’s disease. Reversely, ileocolic disease at time of surgery and initiation of postoperative prophylactic medication were identified as protective factors for early endoscopic recurrence. Young age at surgery, perianal disease and a prior intestinal resection, included as risk factors in the current international guidelines, were not associated with early endoscopic postoperative recurrence in this large prospective cohort study.
P216 Urine Metabolomic Characteristics of Anxiety and Depression Disorders in Patients with Inflammatory Bowel Disease
Authors: Huang X P , Zhou M S , Dang Y , Xu F , Xu C Y , Wang Z , Xu X Y , Wang C S E , Zhu S Y , Li P , Wu J , Shi H Y 
Published: January 2024

Abstract

Background
Up to 25%-35% of patients with inflammatory bowel disease (IBD) suffer from anxiety or depression. We aimed to depict the urine metabolic profile of IBD patients with anxiety and depression disorders and investigate the urinary metabolites that could characterize the mental disorders in IBD patients.

Methods
Urine samples were collected from IBD patients, and the Liquid Chromatography-Mass Spectrometry (LC-MS) was used to detect the metabolites. The Hospital Anxiety and Depression Scale (HADS) was used to assess the anxiety and depression symptoms. Least absolute shrinkage and selection operator (LASSO) regression model with 10-fold cross-validation was used to establish a metabolite-based prediction model for mental disorders in patients with IBD.

Results
Among the involved IBD patients (n=23, median age 41, women 61%), 35% had anxiety and 35% had depression. The urine metabolic profiles of IBD patients with anxiety or depression disorders were largely separated from those without mental symptoms (Figure 1 a-b). There were 36 metabolites up-regulated and 25 metabolites down-regulated in the anxiety group, while 10 metabolites up-regulated and 35 metabolites down-regulated in the depression group (Figure 1 c-d). The LASSO model identified the metabolites predicting IBD patients with mental disorders (Figure 2 a-b). Six metabolites (L-Carnitine, Riboflavin-5-phosphate, 2-Ethyl-2-phenylmalonamide, 3-Indoxyl sulphate, Sodium cholate, Tritylalcohol) were selected to construct the prediction model for anxiety, and another six metabolites (D-(-)-Glutamine, dAMP, DL-Stachydrine, dCMP, 5'-Deoxy-5'-(Methylthio)Adenosine, Sakuranin) were selected to construct the prediction model for depression in IBD patients. Both models showed excellent performances with an AUC of 0.992 (95%CI:0.97-1.00) and 0.933 (95%CI: 0.83-1.00) for predicting anxiety and depression, respectively, among patients with IBD (Figure 2 c-d).

Conclusion
We found significantly different urine metabolic profiles between IBD patients with and without anxiety and depression disorders. The specific urinary metabolites panel may become effective biomarkers for the prediction of anxiety and depression disorders in IBD patients.
P231 Impact of the depth of mucosal healing on the burden of ulcerative colitis : a cross-sectional study
Authors: Yzet C , Brazier F , Robert C , Moreau C , Meudjo E , Richard N , Chatelain D , Fumery M 
Published: January 2024

Abstract

Background
Ulcerative colitis (UC) is a major cause of disability, affecting physical, emotional and social well-being. The recent STRIDE II international guidelines consider disability-free and normal quality of life as therapeutic targets. Today, the degree of mucosal healing required to reduce disability, incontinence and bowel urgencies is poorly known.

Methods
We conducted a single-center cross-sectional study between January 2021 and June 2023. All consecutive patients with UC and endoscopic healing (Mayo ≤ 1) underwent IBD-disk disability assessment the day of the colonoscopy. Histological healing was defined as Nancy score 0 or 1 (2 biopsies per segment from rectum to right colon). Moderate to severe disability was defined as an overall score ≥ 40. Incontinence was defined by a Wexner score &gt;5 and bowel urgency by an NRS urgency score &gt; 1).

Results
A total of 57 patients were included, with 34 (59.6%) women. Median age and disease duration were 47.4 (interquartile range [IQR] [43.5; 51.2]) and 13.0 years (IQR, 13.1-18.4), respectively. 37/57 (65%) patients had complete endoscopic healing Mayo 0 and 43/54 (80%) histological healing. The median overall IBD-Disk score was 29 [25.5; 37.5] and 27 (47%) had moderate to severe disability. There were no differences in terms of age, gender, body mass index, smoking status, disease extension and treatment for the 3 groups Mayo 1, Mayo 0 and histological healing. The rate of moderate to severe disability was not different among patients with Mayo 0 (7/20, 35%) vs. Mayo 1 (20/37, 54%) patients (p=0.26), or in patients with (22/43, 51%) or without histological healing (4/11,36%) (p =0.51). Of the 35 patients assessed, bowel urgency were reported in 11 (31.4%), with no difference between the two definitions of endoscopic healing (p=0.72) or histological healing (p=0.37). Among the 35 patients with a Wexner score evaluation, incontinence was observed in 19% (4/21) and 14% (2/14) of Mayo 0 and Mayo 1 patients respectively (p=0.99), and 24% (6/25) vs. 0% (0/7) of patients with or without histological healing (p=0.3).

Conclusion
Half of patients with UC who achieved endoscopic healing reported a moderate to severe disability. Mayo 0 (vs. 1) endoscopic healing and histological healing do not appear to provide any short-term benefit in terms of disability, fecal incontinence or bowel urgency.
P233 Cytomegalovirus colitis in patients with moderate-to-severe Ulcerative Colitis: diagnosis, clinical impact and treatment efficacy
Authors: Melotti L , Salice M , Rinaldi M , Dussias N , Vanigli N , Scaioli E , Privitera Hrustemovic H , Rizzello F , Gionchetti P 
Published: January 2024

Abstract

Background
Cytomegalovirus (CMV) colitis is a serious concern worsening the prognosis of patients with ulcerative colitis (UC), involving mainly those who are not responding to immunosuppressive therapy. CMV colitis is an independent predictor of hospitalisation and surgery. Diagnosis of CMV colitis can be obtained either via immunohistochemistry (ICH) or tissue polymerase chain reaction (PCR), possibly both.
We aimed to assess the prognostic impact of CMV colitis in patients with UC and the clinical utility of testing for CMV plasma-DNA reactivation.

Methods
We conducted a retrospective, observational, monocentric study in our IBD center in Bologna.
Consecutive patients hospitalized for moderate-to-severe ulcerative colitis from January 2020 to June 2023 were included. Patients were tested for CMV colitis at hospitalization, along with other concomitant infections. Diagnosis of CMV-colitis was made either by ICH on colonic mucosa histological samples or on resected colon specimens. Need of surgery was evaluated at 28, 180 and 365 days.
Basal characteristics of patients according to the presence or absence of CMV organ disease were compared with Mann-Whitney, X2 or Fischer tests, as appropriate.
A Kaplan-Meier survival analysis was calculated to verify whether antiviral treatment for CMV organ disease had an impact on avoiding surgery.

Results
A total of 135 patients were included. CMV organ disease was present in 37 (27.4%). Around half (51.4%) were diagnosed endoscopically, and 62.2% had evidence of plasma reactivation with a median of 1008 cp/mL CMV-DNA viral load (IQR 318-2980).
Differences between the two groups (CMV colitis vs non CMV) included age (p = 0.004), Charlson Comorbidity Index (CCI) (p = 0.003), refractory disease (p = 0.007), and median CMV-DNA viral load (p &lt; 0.001).
Patients with CMV colitis needed surgery in 24/37 cases within 1 year from the diagnosis, compared to 41/98 in the non-CMV group. Interestingly, among the first group, 54% of cases underwent colectomy within 28 days, whereas only 34.1% underwent colectomy in the non-CMV group (p = 0.049).
At multivariable analysis, steroid refractory disease, CCI and serum CMV-DNA reactivation were associated with CMV colitis. The latter had the highest OR (17.7 p &lt; 0.001).
Kaplan-Meier showed that patients who were treated with anti-viral therapy had a significant reduction of the risk of receive surgical treatment (p&lt;0.001) [Table 1].

Conclusion
CMV-DNA plasma reactivation is independently associated to CMV colitis. The use of anti-viral treatment is able to reduce the risk to underwent surgery, suggesting that screening of CMV colitis is mandatory in patients with moderate-to-severe UC.
P271 Impact of Biologics on Surgical Trends in Inflammatory Bowel Disease: Insights from a Lower-endemic Region
Authors: Chuang C H , Yang E H , Chen N Y , Po-Jun C , Kang J W , Chang Y C , Cheng C L 
Published: January 2024

Abstract

Background
Biologics have revolutionized inflammatory bowel disease (IBD) treatment, yet their impact on surgery rates remains variable in real-world studies. This nationwide cohort study in Taiwan aims to investigate the influence of biologics on surgery trends and identify associated risk factors in a region with lower IBD endemicity.

Methods
A retrospective population-based cohort study was conducted using data from Taiwan's National Health Insurance Database, spanning from January 1, 2003, to December 31, 2018. The cohort included 2676 eligible IBD patients, 725 Crohn's Disease (CD) and 1951 ulcerative Colitis (UC). Patient characteristics, surgery outcomes, and the related risk factors were analyzed.

Results
During the study period, 292 CD and 186 UC patients underwent surgery, with 245 in the pre-biologic era and 233 in the post-biologic era. Cumulative probabilities of intestinal surgery (IS) for CD patients were 20%, 35%, and 44% at 1st, 5th, and 10th years, while anal surgery (AS) rates were 3%, 5%, and 7%, respectively (Figure 1). UC patients exhibited lower surgery rates. Cox model analysis revealed age at diagnosis &gt; 60 years as a significant risk factor for IS, but not AS, in both CD and UC groups. Gender and biologics era showed no association (Table 1). After the first IS, CD and UC patients had high 2nd IS rates of 31% and 24%, respectively.

Conclusion
This nationwide study in a lower endemic area provides insights into IBD surgery trends. The first 7 years of the biologics era did not alter surgery rates, but age at diagnosis &gt; 60 years was associated with a higher IS rate. After the initial operation, IBD patients demonstrated a higher rate of subsequent surgeries.