bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP06 The influence of different prednisolone tapering algorithms on the effectiveness of infliximab in patients with Ulcerative Colitis – A real-world cohort study
Authors: Ovesen P D , Ilvemark J F K F , Attauabi M , Seidelin J B 
Published: January 2022

Abstract

Background
Data regarding the influence of prednisolone tapering on clinical outcomes among patients with ulcerative colitis (UC) are limited. We aimed to investigate the influence of different prednisolone tapering algorithms on the effectiveness of infliximab (IFX) among patients with UC.

Methods
This Danish retrospective single-center study included all patients with UC who were treated with IFX between 2009 and 2019 at Herlev University Hospital. The patients were grouped according to the prednisolone tapering: standard (≤5 mg/week), fast (&gt;5 mg/week), or direct discontinuation after an initial course of less than one week. Finally, we included a control group of patients treated with IFX monotherapy. The primary outcome was corticosteroid-free clinical remission at weeks 14 and 52 defined as a partial Mayo score ≤1. Variables with a p-value ≤0.20 in univariable regression analysis were included in multivariable analysis. A subgroup analysis containing patients with acute severe ulcerative colitis (ASUC) treated with at least 40 mg of prednisolone at initiation of IFX was performed.

Results
The study included 148 patients with UC of whom 81 (54.7%) were treated with prednisolone at the initiation of IFX. No association between prednisolone tapering and corticosteroid-free clinical remission with IFX at weeks 14 or 52 was observed (Figure 1 and Table 2). However, a higher proportion of patients in the standard tapering group achieved a C-reactive protein (CRP) level less than 5 mg/L at week 14 as compared with the fast-tapering group (23/23 (100%) vs. 14/18 (77.8%); p=0.03) and directly discontinuation group (6/10 (60%); p=0.03). This difference was not explained by prednisolone usage. In addition, none of the patients within the standard tapering regime (0/24; 0%) had severe activity at week 14 whereas this was seen in 4/19 (21.1%) in the fast tapering regime (p=0.03). In the subgroup analysis of 33 patients with ASUC, the standard tapering algorithm was associated with higher clinical remission as compared with the fast tapering regime at week 14 (9/14 (64.3%) vs. 5/19 (27.8%); p=0.02) and clinical response or remission at week 52 (12/14 (85.7%) vs. 7/19 (36.8%); p=0.01, Figure 2).

Conclusion
This study demonstrated no overall impact of prednisolone tapering algorithms on short and long-term effectiveness of IFX in patients with UC. However, standard tapering resulted in lower CRP levels and fewer cases of severe disease activity in the overall cohort and higher rate of short and long-term clinical response among ASUC patients, as compared with fast tapering regimes. Taken together, the data indicate that longer corticosteroid exposure in patients with high disease burden might improve IFX responses.
OP31 Dietary and Multi-Omic characterization of new onset treatment naive Crohn Disease identifies factors that may contribute to disease pathogenesis
Authors: Haberman Ziv Y , Braun T , Amir A , Levhar N , Malik A , Neuman S , Picard O , Yavzuri M , Efroni G , Hadar R , Ben-Horin S 
Published: January 2022

Abstract

Background
Crohn Disease (CD) prevalence is rising worldwide. As altered genetics are improbable, this phenomenon likely relates to environmental-dietary changes linked with gut microbiome. We aimed to define host and microbial factors at CD diagnosis.

Methods
Multiomics analyses of SOURCE cohort including clinical, biomarkers (CRP, fecal calprotectin), food frequency questionnaire (FFQ), serum metabolomics, mucosal terminal ileum (TI) transcriptomics, and fecal and mucosal biopsy samples for 16S microbial amplicon sequencing.

Results
25 newly-diagnosed CD and 33 controls (median age 28 years, 50% males). Gender, age, and BMI did not differ between groups, but CRP (p=0.001) and calprotectin (p=E-10) were significantly higher in CD. FFQ results showed that compared to controls, pre-diagnosis CD patients consumed significantly more added sugar (g/day), starch (g/day) nitrite (mg/day), and significantly less vitamin K, D, vegetables, and olive oil (Fig 1). Microbial analyses highlighted significant differences (FDR&lt;0.1) in amplicon sequence variants (ASVs) abundance between stool and biopsies samples (73 ASVs) and between CD and Controls samples (82 ASVs). Biopsy vs. stool samples were enriched for Veillonella, Fusobacterium, Neisseria, and Ruminococcus gnavus. CD showed higher abundance of Enterobacteriaceae and Ruminococcus gnavus with reduction of several Ruminococcaceae and Lachnospiraceae taxa (Fig. 1). Ileal transcriptomics differential expression (FC&gt;1.5, FDR&lt;0.05) replicated previous results with significant induction in CD of DUOX2, CXCL9, and DEFB4A and pathways linked to innate and adaptive immunity, and to extracellular matrix. CD down regulated genes included GUCA2B, SLC10A2, and GSTA1, and pathways linked with epithelial transporters. Serum metabolomics highlighted significant variations (FDR&lt;0.25) in Linoleic acid, aKG, Tryptophan, nicotinamide, Docosahexaenoic acid, oxalate, and GABA between CD and controls. We next tested for significant association (FDR&lt;0.25) between diet and multi-OMICs (Fig. 2). Associations between gut microbiome and TI transcriptomics, and serum metabolomics showed that Erysipelotrichacea taxa positivity correlated with serum oxalate, and TI expression of CEACAM6 and DUOX2. Associations between diet and TI transcriptomics and serum metabolomics indicated that B12, tryptophan and riboflavin consumptions were negatively associated with the bile acid transporter SLC10A2 in the TI, and vegetables consumption was positively associated with oxalate degrading Oxalobacter.

Conclusion
Conclusions: FFQ identifies difference in diet at the onset of CD that may contribute to pathogenesis. Integration between dietary and OMICs layers disclosed novel correlations warranting further exploration.
DOP19 Myeloid and lymphoid cell abnormalities persist in the intestinal mucosa of patients who recover from COVID-19 infection
Authors: Meringer H , Tokuyama M , Tankelevich M , Martinez-Delgado G , Jha D , Livanos A E , Canales-Herrerias P , Cossarini F , Mehandru S 
Published: January 2022

Abstract

Background
Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (Gl) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, in-vitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SAR-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19.

Methods
Individuals with previous COVID-19 diagnosis (by either RT–PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1,2). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells). Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody.

Results
Thirty subjects with a previous history of COVID-19 (post-COVID), median of 4 months from diagnosis (range 1–10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14+) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC) 1 (lin-HLA-DRhiCD14-CD11c+CD141+) and cDC2 (lin-HLA-DRhiCD14--CD11c+CD1c+) were noted in the colon only. Among T cell subsets, CD8+ tissue resident memory T cells (CD8+CD69+CD103+) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3-CD27+CD38hi) trended higher (p=0.06), while mucosal B cells (CD3-CD19+) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1). There were no significant correlations of these cell populations with either time after the infection or IF positivity.

Conclusion
Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long term sequela of COVID-19, including long-haul COVID.
DOP21 Potential mechanisms linking biological therapies on SARS-CoV-2 susceptibility in Inflammatory Bowel Disease patients
Authors: Pisani L F , Mola S , Crespi G , Caprioli F , Pastorelli L , Annunziata M L , Manfredi M , Porta C 
Published: January 2022

Abstract

Background
The current novel coronavirus (SARS-CoV-2) pandemic is an ongoing global health crisis, which represents an important challenge for the whole society and mankind. Patients with inflammatory bowel disease (IBD) are treated with immunosuppressive drugs that are usually associated with more severe viral infections. However, the effects of the different therapies on the risk of SARS-CoV-2 infection and Covid-19 severity in IBD patients are still under investigation.

Methods
Between April 2020 and April 2021, 238 IBD patients (N=145 with Crohn disease and N=93 with Ulcerative colitis) of the North Italy area have been enrolled. Both serum samples (N=238 IBD patients and N=45 healthy donors) and colon biopsies from inflamed and non-inflamed mucosa (N=88 IBD patients N=20 non-IBD control) have been collected. To evaluate the exposure to SARS-CoV-2, both clinical data and seroprevalence of anti-SARS-CoV-2 Ab have been analyzed. Serum samples were analyzed by untargeted metabolomics analysis and the frequency of a serum metabolomics signature associated with protection were evaluated in IBD versus healthy donors. Moreover, gene expression analysis of key proteins for virus entry (ACE2, TMPRSS2, TMPRSS4, ADAM17) were analyzed by qPCR in the gut mucosa biopsies of IBD patients.

Results
The seroprevalence of anti-SARS-CoV-2 Ab in our cohort of IBD patients (10/238) indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy. Accordingly, we observed that the serum metabolomics signature associated with protection was more frequent in IBD patients treated with anti-TNF (N=50, 70%), than healthy controls (N=45, 50%). Gene expression analysis of the proteins involved in SARS-CoV-2 entry also indicated that IBD patients treated with anti-TNF (N=14) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4. Moreover, vedolizumab-treated patients (N=7) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar.

Conclusion
Our study indicates that IBD population treated with biologics has an overall lower risk to contract SARS-CoV-2 infection. Future studies to gather the mechanisms underpinning the effects of biologics on the expression of the proteins involved in SARS-CoV-2 viral entry in association with the specific metabolomics signature of viral susceptibility might shed light on potential targets to increase resistance in higher risk subgroups of patients.
DOP29 A novel predictive scoring system of venous thromboembolism after surgery for Inflammatory Bowel Disease: A NSQIP-IBD registry analysis
Authors: Cheong J Y , Connelly T , Prien C , Jia X , Valente M , Bhama A , Lightner A , Holubar MD- MS S 
Published: January 2022

Abstract

Background
Patients undergoing colorectal surgery for inflammatory bowel disease (IBD) are recognized to have an increased risk of venous thromboembolism (VTE). The aim of this study was to determine the perioperative risk factors for VTE and to create a predictive scoring system for VTE in the IBD cohort.

Methods
The NSQIP-IBD registry from 2017–2020 was used to identify patients for the study. Demographics, operative and outcomes data of IBD patients undergoing colectomies for IBD were analyzed. Student t and χ 2 tests were used for univariate analysis. A logistic multivariate regression model was performed using all significant variables to develop a predictive scoring system of VTE.

Results
5003 patients (51.9% male, mean age 42.7, 57.3% Crohn’s / 42.7% ulcerative colitis) were included in the study. 125 (2.49%) developed VTE. The univariate analysis is presented in Table 1. On multivariate analysis ASA grade, ulcerative colitis, sepsis, serum sodium &lt;139 mmol/L, an open abdomen and preoperative inter hospital transfer were associated with greater risk of VTE. An open abdomen postoperatively was associated with the highest odds of developing a VTE [2.69 (1.20 – 5.39, p=.009)]. Using these 6 significant factors, a risk model was created. The risk of VTE with one risk factor was 0.7% and 1.8% with two risk factors. The risk of VTE increased to 3.6% and 4.5% with three and four risk factors respectively. With five and six risk factors, the risk of VTE increased exponentially to 10.9%, 25% respectively (Figure 1).

Conclusion
This study affirms that multiple perioperative and operative factors increase the risk of VTE after surgery for IBD. We present a novel model which demonstrates a cumulative risk increasing exponentially when more than five risk factors are present.
DOP32 Biologic treatment does not reduce the risk of postoperative peristomal pyoderma gangrenosum in Crohn’s Disease patients
Authors: Iesalnieks I 
Published: January 2022

Abstract

Background
To assess the risk of postoperative peristomal pyoderma gangrenosum in Crohn’s disease patients undergoing bowel resection with formation of an ostomy.

Methods
All patients with Crohn’s disease undergoing intestinal resection with formation of an ostomy were included in the present retrospective analysis. The data collection was performed prospectively. All cases of pyoderma gangrenosum were identified by clinical examination and documented on photographs. “Extended colectomies” were total colectomy and proctocolectomy.

Results
Between 2009 and 2021, 99 patients underwent intestinal resections with formation of an ostomy – 95 ileostomies and 4 colostomies. Ileocolic resections were performed in 62 patients, small bowel resections in 2 and colorectal resections in 35 patients. Additional abdominoperineal rectal resections were performed in 19 out of latter 35 patients. At the time of surgery, 31 patients were on biological treatment, 19 on steroids. Postoperatively, 10 patients (10%) developed peristomal pyoderma gangrenosum – all during first 3 postoperative months and all in presence of an ileostomy. By univariate analysis, abdominoperineal resection (26% vs. 9%, p=0.03), presence of colonic disease (20% vs. 2%, p=0.005), preoperative biological treatment (24% vs. 4%, p=0.008), extended colectomy (27% vs. 5%, p=0.008), non-stricturing/non-penetrating disease (35% vs. 5%, p=0.002) were associated with an increased risk of peristomal pyoderma gangrenosum. By multivariate analysis, preoperative intake of biologic treatment (Hazard Ratio 5.5, p=0.03), and non-stricturing/non-penetrating disease (HR 8.3, p=0.006) were associated with the risk of postoperative pyoderma gangrenosum.

Conclusion
Crohn’s disease patients with colonic disease undergoing bowel resections for non-stricturing/non-penetrating disease are at high risk to develop peristomal pyoderma gangrenosum during the early postoperative period. Preoperative biological treatment does not decrease the risk of pyoderma formation; moreover, it might even increase it.
DOP39 Effect of baseline disease characteristics on clinical outcomes in moderate-to-severe Ulcerative Colitis treated with upadacitinib: Results from a Phase 3 trials programme
Authors: Higgins P , Colombel J F , Reguiero M , Parkes G , Ilo D , Philips C , Yao X , Cheng E , Schreiber S 
Published: January 2022

Abstract

Background
Upadacitinib (UPA) is an oral, once-daily (QD), selective Janus kinase inhibitor that has demonstrated efficacy in the induction and maintenance treatment of Ulcerative Colitis (UC). This analysis aimed to assess the impact of baseline UC characteristics on clinical outcomes following UPA therapy.

Methods
Patients (pts) with moderately to severely active UC who had failed conventional or biological treatment were enrolled in two randomised, double-blind (DB), placebo (PBO)-controlled, Phase 3, 8-week induction studies of UPA 45 mg QD vs PBO. Pts achieving a clinical response (decrease from baseline in Adapted Mayo score ≥2 points and ≥30% from baseline, plus a decrease in rectal bleeding score [RBS] ≥1 or an absolute RBS ≤1) at Week (Wk) 8 entered a 52-week, randomised, DB, PBO-controlled, Phase 3 maintenance study, and received UPA 15 mg QD, UPA 30 mg QD, or PBO. The primary efficacy endpoint was clinical remission per Adapted Mayo score at Wk 8 (induction) and at Wk 52 (maintenance). Pre-specified (PS) and post hoc (PH) analyses were conducted by baseline disease activity (full Mayo score ≤9 or &gt;9) (PS), extent (PS), duration (&lt;2, 2–5, &gt;5–10, &gt;10 years [yrs]) (PH), and high-sensitivity C-reactive protein (hs-CRP) level (≤5 or &gt;5 mg/L) (PH).

Results
988 pts were included in the induction studies, and 451 in the maintenance study. The treatment difference between UPA 45 mg QD and PBO excluded zero for all subgroups at Wk 8 (Figure 1). Wk 8 remission rates were lower for full Mayo score &gt;9 vs ≤9, and for CRP &gt;5 vs ≤5 mg/dL, with minimal effects of disease extent or duration. Wk 52 maintenance of remission rates were greater with UPA 15 mg and 30 mg QD vs PBO (16–44% and 30–50% difference, respectively), and with UPA 30 vs UPA 15 mg QD. This incremental benefit of the 30 mg dose was greater in pts with severely (full Mayo score &gt;9) vs moderately active disease (Figure 2); 15 mg and 30 mg demonstrated similar efficacy in pts with Mayo score &lt;9. Statistically non-significant numerical advantages for UPA 30 mg vs UPA 15 mg maintenance were seen in all subgroups, with the exception of hs-CRP &gt;5 mg/L.

Conclusion
UPA 45 mg QD is an effective induction treatment for UC, regardless of baseline disease characteristics. Both 15 and 30 mg UPA doses are effective maintenance regimens, regardless of baseline disease characteristics. However, the 30 mg dose shows a trend towards increased benefit vs 15 mg in pts with Mayo score &gt;9 and extensive disease. This analysis suggests that while UPA 15 mg may be most appropriate for patients with UC with a low inflammatory burden (per full Mayo score and extent), the 30 mg dose may be more appropriate for those with a high one.
DOP59 Development of a novel Ulcerative Colitis (UC) endoscopic activity prediction model using machine learning (ML)
Authors: Colombel J F , Rubin D , Schott J P , Gottlieb K , Erisson L , Prucka B , Phillips S , Kwon J , Ng J , McGill J 
Published: January 2022

Abstract

Background
Previous studies have described machine learning (ML) models to predict how human readers would score disease activity in UC using the endoscopic Mayo Score (eMS). So far, none employed deep human annotation that considers all the endoscopic features making up the eMS. Here we report the results of an ML model that is trained on eMS features using centrally read endoscopies.

Methods
793 full-length videos were obtained from 249 patients with UC who participated in NCT02589665, a phase 2 trial with mirikizumab in patients with UC and associated with centrally read (single reader) eMS (CReMS) as the primary dataset. After cleaning for usable frames, the data were split into training, validation and testing subsets. The ML workflow consisted of annotation, segmentation, and classification (e.g., erosions, ulcers, erythema, vascular pattern, and bleeding). Human image classification and segmentation with bounding boxes and was subjected to quality control adjudicated by one of three IBD specialists, generating more than 60,000 eMS-relevant annotation labels. The model was evaluated on a test set of 147 videos using the CReMS, and a consensus set of 94 test videos, where CReMS and annotator reported eMS (AReMS) were in agreement without adjudication. The primary objective of the model was a categorical prediction of endoscopically inactive disease (eMS 0 & 1) compared with active disease (eMS 2 & 3). The secondary objectives of the model were to predict endoscopic healing (eMS 0) and to predict severe disease (eMS 3).

Results
The model performances are in Table 1. On the full test set of 147 videos, the model predicted inactive disease compared with active disease with an accuracy of 84%, positive predictive value (PPV) of 80%, and negative predictive value (NPV) of 85%. In the subset of 94 videos with CreMS and AReMS consensus, the model predicted inactive disease compared with active disease with an accuracy of 89%, PPV 87%, and NPV of 90%. In this same subset, the model predicted endoscopic healing and severe disease with an accuracy of 95% and 85%, PPVs of 86% and 82% and NPVs of 95% and 87%, respectively. For the secondary objectives in the full set of 147 videos, the model predicted endoscopic healing and severe disease with an accuracy of 90% and 80%, PPVs of 44% and 86%, and NPVs of 95% and 86%, respectively.

Conclusion
We have developed a ML predictive model of the eMS in UC using centrally read videos and demonstrate excellent distinction between active and inactive disease, and clear discrimination between other levels of endoscopic activity. We propose that this unique ML approach to endoscopic assessment be considered as a substitute to human central reading in future clinical trials.