bluuebunny/crossref_metadata_2025_split huggingface dataset:
P251 Endoscopic and pathologic findings of the esophago-gastroduodenal involvement of Crohn’s disease in Korea: a prospective cohort study
Authors: Kim G H , Kim J , Park S H , Ahn J Y , Ye B D , Jung H Y , Yang S K 
Published: January 2022

Abstract

Background
The characteristics and incidence of esophago-gastroduodenal involvement of Crohn’s disease (CD) are unclear in Korea. We aim to investigate the prevalence and clinicopathological characteristics of CD with esophago-gastroduodenal involvement.

Methods
A total of 115 patients with CD who underwent esophagogastroduodenoscopy (EGD) including esophageal, gastric and duodenal biopsies were enrolled prospectively between 2020 and 2021 at a tertiary care center. Total of five specimens obtained from the esophagus, gastric body and antrum, and duodenal bulb and second portion respectively during endoscopy were histologically reviewed. The presence of Helicobater pylori was evaluated by immunohistochemical analysis.

Results
The median age was 30.0 (interquartile range [IQR] 25.0–37.0) years and 74.8% were male. Of total, 32.2% had were symptoms including epigastric pain (29.7%), bloating (27.0%) and dyspepsia (13.5%). Based on histological features, 56 patients (48.7%) were identified as having UGI involvement (15 esophageal, 44 gastric, and 36 duodenal). Of 115 included patients, bamboo- joint-like appearance in the stomach was founded in 81 (70.4%) and their histologic findings were mostly revealed as non-specific feature. Notable histopathological findings included non-caseating granulomas in 8 cases (7.0%), focally enhanced gastritis in 38 cases (33.0%), and lymphocytic esophagitis in 13 cases (10.7%). Among 115 cases, 6 cases (5.2%) were H. pylori positive and 109 cases (94.8%) were H. pylori negative.

Conclusion
The prevalence of esophago-gastroduodenal involvement of CD was relatively high among CD patients who underwent EGD in Korea. A high suspicion of CD with esophago-gastroduodenal involvement with endoscopic biopsy is warranted when patients have abnormal endoscopic findings.
P259 Metabolic associated Liver Disease and sex as key factors of cardiovascular risk in Inflammatory Bowel Disease
Authors: García Mateo S , Martínez-Domínguez S J , Ballesta Martínez S , Espinosa Rueda J , Tejero Justes C , Aso Gonzalvo M C , Gallego Llera B , Alfambra Cabreja E , Baptista P M , Nocito Colón M M L , Gargallo-Puyuelo C J , Gomollón F 
Published: January 2022

Abstract

Background
Atherosclerosis is the main factor for the development of cardiovascular (CV) events. Patients with systemic inflammatory conditions such as inflammatory bowel disease (IBD) are supposed to be at risk of early atherosclerosis. However, data are still contentious. IBD patients are also at risk of other comorbidities such as metabolic associated fatty liver disease (MAFLD), a well-recognised entity associated with increased CV risk. The aim of this study is to demonstrate the impact of MAFLD on CV risk for IBD patients.

Methods
Prospective cohort study of consecutive IBD outpatients (Leonnard-Jones criteria, &gt; 1 year) was performed from October 2020 to April 2021. Of 947 patients, 50 with IBD who met criteria for MAFLD and 50 with IBD and without MAFLD were matched by sex, age and IBD location. Patients with a previous diagnosis of CV disease, type II diabetes mellitus and under treatment for dyslipidaemia were excluded. Fatty liver disease (FLD) was diagnosed by ultrasonography, controlled attenuation parameter (CAP TM), fatty liver index (FLI), hepatic steatosis index (HSI) and lipid accumulation product (LAP). To assess early atherosclerosis, alterations in carotid artery intima-media thickness (CIMT) and SCORE as non-invasive CV risk test were performed in both groups. Statistical analysis was performed using SPSS, a binomial generalized linear model with logistic regression was performed, with CIMT alteration as dependent variable. For all tests a two-sided p value &lt;0.05 was considered significant.

Results
Of 100 IBD patients included 51 (51%) were women with median age of 51.0 (41–59). There were 49 (49%) patients diagnosed of ulcerative colitis (UC) and 51 (51%) of Crohn’s disease (CD). Comorbidities and disease patient’s characteristics are shown in table 1. Most of the patients had an abnormal CIMT (58 (58%)). Of all the variables obtained, only female sex (OR (CI 95%) 3.322 (1.03–10); p=0.033) and MAFLD (OR (CI 95%) 5.05 (1.71–14.92); p=0.003)) were significatively associated with CIMT alterations. SCORE test did not associate with a significatively CIMT alteration. Among the different options to assess FLD, only ultrasonography and CAP were statisticaly associated with CIMT alterations (specificity 66%, sensibility 62%, p=0.005).

Conclusion
Female sex and MAFLD are associated with early atherosclerosis defined by CIMT alterations in IBD patients. Ultrasonography and CAP are better than biochemical test not only to predict FLD but also to assess CV risk.
P290 Therapeutic requirements in patients with Ulcerative Proctitis. Is it necessary immunosuppressive therapy in these patients?
Authors: Ferreiro Iglesias R , Porto Silva M S , Marín S , Casanova M J , Mañosa M , González-Muñoza C , de Francisco R , Caballol B , Arias L , Piqueras M , Zabana Y , Rivero M , Calvet X , Mesonero F , Varela Trastoy P , Busta Nistal R , Gomez Perosanz R , Vega P , Gonzalez Vivo M , Iborra M , Jimenez Marquez L , Madero L , Rodríguez-Lago I , Rodriguez Gonzalez M , Vera I , Ponferrada Diaz A , Vela M , Torrealba L , Van Domselaar M , Iglesias E , Gisbert J P , Calafat M , García-Planella E , Perez-Martinez I , Ricart E , Sicilia B , Mena R , Nieto L , Domenech E , Barreiro-de Acosta M 
Published: January 2022

Abstract

Background
Ulcerative proctitis may have a mild and less aggressive course, although evidence is scarce because these patients are excluded from participation in randomized controlled clinical trials. The aim is to identify clinical characteristics and complications associated with ulcerative proctitis refractory to conventional therapy.

Methods
Patients included in the prospectively maintained ENEIDA registry from GETECCU with ulcerative proctitis were included. Socio-demographic data were evaluated. We defined ulcerative proctitis based on ECCO guidelines and immunosuppression as the use of immunomodulators and/or biologics. Logistic regression was used to identify the independent factors associated with immunosuppressive therapy among the different socio-demographic data.

Results
From a total of 34.716 patients with ulcerative colitis, 6281 (18%) patients with ulcerative proctitis were identified. Mean age was 53 ±15 years and mean duration of illness was 12 ± 9 years. Surgery was necessary only in 2% of patients, 31 (0.5%) panprotocolectomy or subtotal colectomy. The clinical characteristics of the patients with and without immunosupressive therapy are summarized at table 1. A total of 3691 patients received oral 5-ASA (58.8%) and 4652 (74.1%) topic 5ASA. 636 (10.1%) were refractory to 5-ASA and corticosteroids, necessitating immunosuppression: 459 patients with azathioprine (7%), 28 with 6-mercaptopurine (0.4%), 49 with methothrexate (0.8%), 191 with infliximab (9%), 125 with adalimumab (2%), 50 with golimumab (0.8%), 57 with vedolizumab (0.9%), 6 with ustekinumab (0.1%) and 3 with tofacitinib (0.0). 316 (5%) patients needed one biologic therapy, 95 (1.5%) needed 2 biologics and 40 (0.6%) at least three different biologics. Longer duration of illness and use of corticosteroids were associated with higher risk of immunosuppression.

Conclusion
Good clinical outcomes were recorded in ulcerative proctitis, with only 10% of patients treated with immunosuppression therapy. The risk factors of immunosuppression were longer duration of illness and use of corticosteroids.
P296 vedolizumab Does Not Increase Risk of Clostridium Difficile Infection in Patients with Inflammatory Bowel Disease Using vedolizumab: a Retrospective Cohort Study
Authors: Alshahrani A 
Published: January 2022

Abstract

Background
Several studies have demonstrated that there is increased incidence, recurrence, and severity of Clostridium difficile (CDI) infection over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies.

Methods
This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5-ASA therapy) were enrolled from January 2015 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using the three different classes of therapy. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI.

Results
There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). No difference was seen in the number of patients with CDI; CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group (p=0.36). The Cox PH model revealed current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model.

Conclusion
Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have a high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.
P299 Prediction model for steroid-free clinical remission with vedolizumab at week 22 in patients with Ulcerative Colitis: Machine learning using clinical data at baseline
Authors: Miyoshi J , Maeda T , Matsuoka K , Saito D , Morikubo H , Matsuura M , Tamura S , Hisamatsu T 
Published: January 2022

Abstract

Background
Predicting the response of patients with ulcerative colitis (UC) to a molecular targeted drug before administration is an unmet need for optimizing individual patient care. We hypothesized that a new machine-learning approach could identify predictors of therapeutic efficacy that have not been reported as statistically significant factors using the conventional statistical approaches. As a proof-of-concept study, we explored predictors and a prediction model for the efficacy of vedolizumab (VDZ) for UC.

Methods
The clinical data at baseline (week 0) of 34 UC patients who started VDZ at Kyorin University Hospital was collected (Cohort 1; training cohort). The collected data contained 49 clinical features; patient background (e.g. sex, age, disease phenotype, etc.), treatment history, clinical/endoscopic activity, and blood examination items. Random forest (RF) was employed to investigate clinical features that affect steroid-free clinical remission (SFCR) with VDZ at week 22 in UC. A prediction model was developed using logistic regression based on the results of RF. The prediction ability of the prediction model was evaluated with the data of 35 patients who started VDZ at Toho University Sakura Medical Center (Cohort 2; extra-facility test cohort). The prediction ability of the VDZ prediction model for ustekinumab (UST) was examined using the data of 22 patients who started UST at Kyorin University Hospital (Cohort 3).

Results
RF computed the contribution of each clinical feature to achievement/no-achievement of SFCR at week 22. When the top 8 features (partial Mayo score, MCH, BMI, BUN, concomitant use of AZA, lymphocyte fraction, height, and CRP) were employed for logistic regression, the prediction accuracy of the prediction model was 100% and 68.6% for Cohorts 1 and 2, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in Cohort 2 were 92.3%, 54.5%, 54.5%, and 92.3%, respectively. Meanwhile, in Cohort 3 with UST, sensitivity, specificity, PPV and NPV were 70.0%, 45.5%, 53.4%, and 62.5%, respectively.

Conclusion
Our machine-learning approach detected clinical features at baseline that impact the achievement of SFCR at week 22 in patients who received VDZ for UC and developed a prediction model that appears to be useful to screen non-responders to VDZ. Given the low prediction ability in Cohort 3, our findings support the notion that a prediction model for each molecular targeted drug is needed for optimizing the drug selection for individual patients. This study provides the proof-of-concept that machine learning on clinical data could open a new era of personalized medicine for UC.
P316 Ozanimod is an efficacious oral therapy after, 5-ASA failure in immunomodulator- and biologic-naive patients with ulcerative colitis: post hoc analysis from True North
Authors: Sands B E , Dignass A , Irving P , Chiorean M , Long M , Eren D , Ahmad H A , Osterman M T , Petersen A , Elegbe A , Ritter T , Danese S 
Published: January 2022

Abstract

Background
Oral, 5-aminosalicylates (5-ASA) and corticosteroids (CS) are often the first-line treatment for ulcerative colitis (UC), and patients (pts) who fail these agents typically advance to chronic immunosuppressives. Ozanimod, an oral sphingosine, 1-phosphate receptor modulator, is approved for treating adults with moderately to severely active UC in the US. This post-hoc analysis from the pivotal phase, 3 True North randomised controlled trial evaluated the efficacy of ozanimod at week (wk), 10 (end of induction) in immunomodulator- and biologic-naive pts with moderate to severe UC who failed, 5-ASA with or without concomitant CS.

Methods
True North consisted of a, 10-wk induction period. Pts in Cohort, 1, stratified by CS use at screening, were randomised to either ozanimod, 0.92 mg (equivalent to ozanimod HCl, 1 mg; n=429) or placebo (n=216) once daily in a double-blind manner; pts in Cohort, 2 (n=367) received open-label daily ozanimod, 0.92 mg. At enrollment, pts were required to be on stable doses of oral, 5-ASA and/or CS for &gt;2 wk and continued on the same dose throughout induction. Pts who received tofacitinib within, 2 wk of screening were excluded. This analysis focused on clinical remission, clinical response, endoscopic improvement, and mucosal healing efficacy outcomes in immunomodulator- and biologic-naive, 5-ASA exposed pts.

Results
Of, 464 pts treated with, 5-ASA and were immunomodulator- and biologic-naive, with or without CS, 205 were on ozanimod and, 105 were on placebo in Cohort, 1;, 158 received open-label ozanimod in Cohort, 2. Baseline characteristics were similar between groups in Cohort, 1. Compared with placebo at wk, 10, a higher proportion of ozanimod-treated patients achieved clinical remission (23.4% vs, 8.9%), clinical response (53.7% vs, 30.7%), endoscopic improvement (35.6% vs, 14.9%), and mucosal healing (18.0% vs, 5.0%; Figure, 1) in this subgroup. These results are consistent with previously published results of the overall study population,1 which demonstrated significantly greater proportions of patients receiving ozanimod vs placebo achieving clinical remission (18.4% vs, 6.0%), clinical response (47.8% vs, 25.9%), endoscopic improvement (27.3% vs, 11.6%), and mucosal healing (12.6% vs, 3.7%). Additionally, all efficacy endpoints were achieved by a greater proportion of patients on ozanimod vs placebo regardless of CS use at baseline (Figure, 2). Results were similar for open-label ozanimod-treated patients in Cohort 2.

Conclusion
Ozanimod demonstrated efficacy at wk, 10 in immunomodulator- and biologic-naive patients with UC who had failed, 5-ASA, regardless of CS use at baseline.

Reference
1. N Engl J Med, 2021;385:1280.
P317 Ustekinumab Trough Concentrations Associated with Biochemical Outcomes in Patients with Crohn’s Disease
Authors: Straatmijer T , Biemans V B C , Moes D J A R , Hoentjen F , ter Heine R , Maljaars P W J , Theeuwen R , Pierik M , Duijvestein M , van der Meulen A E 
Published: January 2022

Abstract

Background
Ustekinumab (UST) is a monoclonal antibody which binds to the p40 subunit of interleukins-12/23 and is an effective and safe treatment for patients with Crohn’s disease (CD). An association between serum drug concentrations and therapeutic outcomes is required to justify Therapeutic Drug Monitoring (TDM). However, it is currently unknown if TDM is of additional value in UST treatment. We assessed the exposure-biochemical response relationship of UST trough concentrations at week, 8 in a prospective, real-world setting.

Methods
We performed a prospective study in CD patients with biochemical, radiologic or endoscopic disease activity in four academic centers in the Netherlands. All patients (n=90) received weight adjusted intravenously (IV) UST induction. First subcutaneous (SC), 90 mg induction dose was administered at week, 8 followed by a maintenance dose of, 90 mg SC every, 8 or, 12 weeks, at the discretion of the physician. Blood for drug levels were drawn at different time points during follow up (median follow up was, 52 weeks (IQR, 50–52)) with a median amount of, 2 measurements (IQR, 1–4) per patient. Plasma concentrations of UST were determined by means of a validated enzyme-linked immune assay. A population pharmacokinetic (PK) model was developed based on these measurements and the UST FDA review documents. Subsequently, the individual UST concentration time course during treatment were predicted using the developed model. Corticosteroid-free clinical remission (HBI ≤, 4) and biochemical remission (C-reactive protein (CRP) ≤5 mg/L or faecal calprotectin (FC) ≤, 250) were assessed at week, 12 and, 24. Quartile analysis and logistic regression was performed to analyse if UST concentration at week, 8 was associated with biochemical remission rates at week, 24. An independent cohort of, 34 patients was used to validate the primary outcomes.

Results
Basis characteristics of all patients are shown in table 1. Median estimated trough concentrations of UST were, 4.23 µg/mL (IQR, 2.79–5.83) and, 7.19 µg/mL (IQR, 3.30–10.67) at week, 8 in the primary and validation cohort respectively. Patients achieving biochemical remission at week, 12 and, 24 had statistically significantly higher UST levels at week, 8 (P&lt;0.01) compared to patients without biochemical remission (fig, 1). Also, higher UST levels at week, 8 were associated with better biochemical remission rates at week, 12 and, 24 in quartile analysis and logistic regression (fig, 2,3). Associations of UST levels at week, 8 and biochemical remission at week, 12 and, 24 were confirmed in the validation cohort. No UST antibodies were detected.

Conclusion
In this real-world cohort of CD patients, ustekinumab levels of ≥5.9 µg/mL at week, 8 were associated with higher biochemical remission rates at week, 12 and, 24.
P326 The effect of compliance during exclusive enteral nutrition on faecal calprotectin levels in children with Crohn’s disease
Authors: Mckirdy S , Russell R , Hansen R , Svolos V , Gkikas K , Logan M , Gerasimidis K 
Published: January 2022

Abstract

Background
It is yet unclear whether suboptimal response to exclusive enteral nutrition (EEN), in some children with Crohn’s disease (CD), is explained by poor compliance. All proprietary feeds used for EEN are gluten-free; hence patients’ compliance to EEN could be determined by detecting gluten immunogenic peptide (GIP), a biomarker of gluten intake, in faeces.

Methods
The concentration of GIP was measured in the faeces of, 45 children (3–17 years) with CD prior to and during (33 &, 54 days) treatment with EEN. Associations with GIP and faecal calprotectin (FCAL) levels were explored at, 33 and, 54 days of EEN.

Results
GIP was present in, 37 of the, 40 (93%) patients who provided stool samples prior to starting EEN, indicating typical gluten consumption in CD patients. In patients with undetectable GIP at both, 33 and, 54 days of EEN, FCAL significantly decreased from baseline (mean decrease, 33 days: -743mg/kg, 54 days: -1043mg/kg, p&lt;0.001), but not in patients who had detectable GIP. At EEN completion, patients with undetectable GIP had a lower FCAL by, 763mg/kg than patients with a positive GIP result (p=0.041) and demonstrated a greater decline from baseline FCAL (-69% vs +5.%, p=0.021).

Conclusion
Poor response to EEN might be explained at least in part by diminished compliance and dietary transgressions. Faecal GIP might be useful as a proxy biomarker of EEN compliance.
P336 Can Mesenchymal Stem Cell (MSC) apoptosis be used as a biomarker for treatment success in perianal fistulising Crohn’s Disease (pCD)? Findings from a prospective pilot study
Authors: Iqbal N , Constable L , Tozer P , Lung P , Hart A , Powell N 
Published: January 2022

Abstract

Background
Mesenchymal Stem Cells (MSC) demonstrated promising results in patients with refractory perianal fistulising Crohn’s Disease (pCD) in the ADMIRE-CD trial, however their use is limited by treatment cost. Studies of Graft vs. Host Disease (GvHD) patients receiving MSCs for steroid refractory disease have shown that in vitro Peripheral Blood Mononuclear Cell (PBMC) induced MSC apoptosis correlates with clinical response. We conducted a pilot prospective study to investigate the clinical and radiological outcome of MSC treatment and determine whether in vitro MSC apoptosis correlates with clinical response in patients with pCD.

Methods
Patient eligibility and MSC administration mirrored that in ADMIRE-CD. Prior to treatment, patient PBMCs were isolated and co-cultured with MSCs and the proportion of apoptotic MSCs identified using flow cytometry (Annexin V+, 7AAD- MSCs). Patients were followed up at, 6-monthly intervals and clinical indices including the Perianal Disease Activity Index (PDAI) and Fistula Drainage Assessment (FDA) were recorded in addition to MRI response. Clinical response categories were determined according to ADMIRE-CD as well as new criteria accounting for radiological healing (Table 1).

Results
Ten patients underwent MSC treatment (M=4, median age, 35, range, 22–73 years). At final follow up (median, 24 months, range, 18–30 months), there was a significant improvement in mean FDA (baseline, 1.3, final follow up, 0.5, p&lt;0.01) but not in PDAI. The apoptosis assay was performed in, 9 patients. A greater proportion of MSC apoptosis was demonstrated when co-cultured with pCD patient PBMCs than with PBMCs from healthy controls (Figure, 1). Patients with a percentage of apoptotic MSCs greater than the group median (22.3%) were classed as apoptosishigh. At final follow up, apoptosishigh patients were also those who demonstrated a response to MSC treatment according to both St Mark’s (Figure, 2) and ADMIRE CD criteria (Figure 3).

Conclusion
The ability of patient PBMCs to induce the highest proportions of MSC apoptosis correlates with clinical response to MSC treatment in this small sample of patients. An adequately powered prospective study is required to determine the potential use of MSC apoptosis as a biomarker of clinical response.