bluuebunny/crossref_metadata_2025_split huggingface dataset:
P622 Comparison of long-term outcomes of infliximab and adalimumab in biologic-naïve patients with ulcerative colitis
Authors: Durak M B , Baspınar B , Guven I E , Kivrakoglu F , Kilic V , Kosar K , Erdogan C , Yüksel I 
Published: January 2022

Abstract

Background
The comparative efficacy and safety of infliximab (IFX) and adalimumab (ADA) have revealed variable results in biologic-naïve patients with ulcerative colitis (UC), and long-term comparison studies between IFX and ADA with or without immunomodulator therapy are still needed in patients with UC.

Methods
The aim of this study was to evaluate the long-term effectiveness and safety of IFX compared to ADA in biologic-naïve adult patients with UC. All data of patients between June 2007 and March 2021 were collected retrospectively. We compared UC-related hospitalisation, colectomy, steroid use, and serious infections leading to treatment cessation.

Results
Out of 86 UC patients, 41 started IFX first (mean age at onset: 34.4 years, 61.0% male) and 45 started ADA first (mean age at onset: 31.4 years, 60.0% male). Disease duration was 7.2 years for IFX and 8.1 years for ADA. There were no significant differences between the two groups with respect to age, gender, smoking, extraintestinal manifestations, immunomodulator usage, or disease extent at the onset of anti-TNF therapy (p &gt; 0.05). Concomitant rates of medication including mesalazine, sulphapyridine, thiopurine, and steroids were the same in both groups (p &gt; 0.05). In the IFX group, baseline haemoglobin (11.7 vs 13.2, p = 0.05) and albumin (3.8 vs 4.2, p = 0.02) levels were lower than those of the ADA group, while C-reactive protein was higher (14.0 vs 6.0, p = 0.04) than in the ADA group. Total MAYO score at baseline was similar in both groups (p = 0.10).
During anti-TNF therapy, steroid use was significantly higher in the ADA group (44.4%) compared to IFX (14.6%, p = 0.003). The rates of UC-related hospitalisation (IFX 9.8% vs ADA 13.3%, p=0.74) and colectomy (IFX 4.9% vs ADA 2.2%, p = 0.60) were similar in IFX and ADA groups. Serious infection leading to treatment cessation was not different between the two groups (IFX 2.4% vs ADA 4.4%, p=0.54). These outcomes were similar in UC patients treated with IFX or ADA monotherapy or in combination with an immunomodulator within each group, and there was no significant difference between IFX and ADA in combination with an immunomodulator regarding those outcomes (p &gt; 0.05).

Conclusion
In this study, steroid use in the ADA group was significantly higher than in the IFX group, although UC-related hospitalisation, colectomy, and serious infections were not different in biologic-naïve adult patients with UC. We also observed that outcomes were similar in patients treated with IFX and ADA monotherapy or in combination with an immunomodulator. In the present study, IFX revealed better long-term outcomes for first-time treatment of UC patients.
P630 Systematic review and meta-analysis: Diagnostic delay and the subsequent impact on the disease course of adult Inflammatory Bowel Disease
Authors: Jayasooriya N , Ballie S , Blackwell J , Creese H , Bottle R , Petersen I , Saxena S , Pollok R C 
Published: January 2022

Abstract

Background
Diagnosis of inflammatory Bowel disease (IBD) can be challenging and time consuming. There is substantial variation in the reported time to diagnosis and the impact of diagnostic delay on disease course. We therefore conducted a systematic review to evaluate the length of time to diagnosis and a meta-analysis of the impact of delay on the disease course of IBD.

Methods
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and final papers were assessed for risk of bias. We searched MEDLINE and Embase for retrospective and prospective studies, published up to December 2020, that reported diagnostic interval, from the time of symptom onset or first consultation to a confirmed diagnosis of IBD, in adults (age ≥18 years). We extracted data from published studies and calculated the weighted median and interquartile range (IQR) of the reported diagnosis interval. Delay was defined as a time period greater than the 75th centile. From eligible studies, we extracted risk estimates and, using random-effects meta-analysis, calculated the pooled odds ratios (OR) and 95% confidence intervals (CI) of studies that examined the association of diagnostic delay with subsequent clinical outcomes, including disease phenotype and surgical intervention. Statistical heterogeneity was assessed, I2 &gt;50% indicating substantial heterogeneity.

Results
Of 1,533 studies identified, 28 fulfilled the eligibility criteria, including 25,764 patients diagnosed with IBD: Crohn’s disease (CD) = 13,206 and ulcerative colitis (UC) = 12,558. In CD, the pooled weighted median for the diagnostic interval was 8.8 months (IQR 3.0–61.1 months). In UC, the pooled weighted median was 15.2 months (IQR 2.4–62.8). Considering studies from high income countries alone, the pooled weighted median was 6.4 months (IQR 1.7–46.7) in CD, and 2.5 months (IQR 0.3–23.0) in UC.
11 studies were eligible for inclusion in the meta-analysis, representing 6,403 patients diagnosed with IBD (CD; n = 4,902 and UC; n = 1,501). In CD, pooled analysis showed an association between delayed diagnosis and stricturing disease (OR:1.77, CI 1.28–2.46; I2 =61%), penetrating disease (OR: 1.48, CI 1.21–1.82; I2=0%) and intestinal surgery (OR:1.88, CI 1.45–2.44; I2 =34%; figure 1a). In UC, delayed diagnosis was associated with an increased risk of colectomy (OR:4.13, CI 1.04–16.40; I2 =0%; figure 1b).

Conclusion
Measures are required to reduce delay in the diagnosis of IBD, which is associated with an increase in stricturing and penetrating disease phenotype in CD and a substantially increased risk of surgery in both CD and UC.
P650 IBD care from the patient perspective: The patient’s turn
Authors: Creemers R , van der Horst D , Raats I , Romberg-Camps M , Scherpenzeel M , van Bodegraven A 
Published: January 2022

Abstract

Background
There is an increased focus on patient reported outcomes and patient reported experiences as means to optimize provided care. Both are considered essential in improving quality and service. Zuyderland Medical Centre (ZMC) is transforming its inflammatory bowel disease (IBD) care into a patient oriented IBD Centre (PGC IBD) as a way to provide modern patient centred care.
The project ‘Patient aan zet’ is an initiative of Crohn & Colitis NL (CCNL) and takes place in several hospitals. The aim of the project is to optimize quality of care for adult patients with IBD by ensuring that the patient is properly and unambiguously informed and the patients involvement increases in treatment.

Methods
A cross-sectional survey using a questionnaire was performed to map out expectations and experiences of patients with the IBD outpatient clinic of ZMC. This questionnaire (part of the project ‘Patient aan zet’) was developed by CCNL as an online self-completion instrument. The results of this questionnaire were assessed in a subsequent discussion group.
All IBD-patients presenting for an outpatient appointment at ZMC in March 2021, received an e-mail with a link to the questionnaire. In total, 500 e-mails were sent. After completing the questionnaire, patients were given the opportunity to sign up for a discussion group.

Results
In total, 198 participants completed the questionnaire fully or partially (40%) (Table 1). We found patients were satisfied with health care in general and with the information supply concerning IBD specifically. Use of the online monitoring tool MyIBDCoach and response time in the online monitoring tool contributed to positive judgment.
In the discussion group emerged that continued attention must be paid to the impact of endoscopic procedures from the patient perspective as endoscopic procedures (as part of the mucosal healing concept) may induce lasting and major impact on patients disease experience. In line with the ongoing corona pandemic developments, patient prefer a combination of check-up appointments by phone and at the outpatient clinic depending on (burden of) disease activity. Finally, specific attention is necessary for patients with a longstanding disease history. Needs concerning dietary advice and psychosocial support appear to vary over time.

Conclusion
ZMC is transforming its IBD care into a PGC IBD as a way to provide optimal and patient centred care. Involving patient in this process has given direction to optimizing patient information and patient involvement. The experiences gained from this process will be used to evaluate the PGC IBD after implementation and, together with the patient association, to develop a PREM that can be used to optimize IBD care.
P654 Clinical outcomes in familial versus sporadic inflammatory bowel disease diagnosed in the era of biological therapies. Prospective data from the ENEIDA registry
Authors: González Muñoza C , Calafat M , Gisbert J P , Iglesias E , Minguez M , Sicilia B , Esteve M , Gomollon F , Calvet X , Ricart E , Carpio D , Rivero M , Lopez-Sanroman A , Marquez L , Nos P , Cabriada J L , Guardiola J , Garcia-Sepulcre M F , Garcia-Lopez S , Lorente Poyatos R , Taxonera C , Barrio Andres J , Vera I , Domenech E , Garcia-Planella E 
Published: January 2022

Abstract

Background
It has been reported that familial aggregation occurs in 10–20% of inflammatory bowel disease (IBD) patients1. Familial IBD has been associated with disease anticipation2 and with an increased need for immunosuppressants3 and surgery4. However, most studies were performed before the widespread use of biological agents and this may impact on the need for surgery.
We aimed to compare the clinical outcomes of IBD (by means of the need for biological therapy and abdominal surgery) between familial and sporadic forms of IBD in the era of biological therapies.

Methods
Data were extracted from the ENEIDA registry by GETECCU, a Spanish, prospectively-maintained, IBD database in which more than 80 centers are participating.
Only adult patients diagnosed with IBD since 2005 and prospectively followed in the registry since diagnosis were included.
Familial IBD was defined as those cases with at least one first-degree relative diagnosed with IBD. Sporadic IBD was defined as those cases with no familial relative (of any degree) with IBD.
Kaplan-Meier survival curves were performed to evaluate the cumulative probabilities of remaining biologic-free and surgery-free. Log-rank test was performed to compare them between familial and sporadic IBD forms. Chi-square test was performed for the rest of variables.

Results
A total of 5,263 patients (2,627 Crohn’s disease [CD]; 2,636 ulcerative colitis [UC]) were included. Of them, 507 (10%) were familial cases (274 CD, 233 UC; P=0.05). The median follow-up was 38,4 and 35.5 months, respectively (P=0.086).
Familial cases were younger (P=0.022) and had a higher proportion of females among UC cases (P=0.048).
No differences were observed in the need for biological therapy in both CD and UC between familial and sporadic IBD. Regarding surgery, no differences were observed in the cumulative probabilities of a first intestinal resection for CD and colectomy for UC. Similar results were obtained when all the analyses were restricted to those subgroups at high-risk for surgery (i.e. CD with ileal involvement and extensive UC).

Conclusion
In patients diagnosed with IBD in the era of biological therapies, familial forms have the same requirements for biological agents and resectional surgery as sporadic forms. Therefore, familial aggregation does not seem to be a factor for a more aggressive disease.
P659 No decrease in number of new Inflammatory Bowel Disease diagnoses in children in the Netherlands during the Covid-19 pandemic: a nationwide retrospective cohort study
Authors: Klomberg R , Joling A R , te Groen M , Kuijpers C , Escher H , Nagtegaal I , de Ridder L 
Published: January 2022

Abstract

Background
The COVID-19 pandemic has had a large impact on regular healthcare provision in the Netherlands. During the first wave, healthcare in children was strongly reduced due to safety regulations and reduced hospital capacity for non-COVID care. This, and fear of COVID-19 could have led to delayed inflammatory bowel disease (IBD) healthcare, and delayed or even missed diagnoses. This has already been demonstrated in adult IBD patients in the Netherlands1, but not yet in the paediatric population. This is of importance, as in children, diagnostic delay is associated with higher rates of strictures, fistulising complications, and growth delay2. Therefore, this study aims to determine the impact of COVID-19 on IBD-related procedures and new IBD diagnoses in children in the Netherlands.

Methods
In this nationwide retrospective cohort study, a search was conducted in the nationwide pseudonymized pathology registry of the Netherlands (PALGA), with complete national coverage. Using retrieval terms for ulcerative colitis, Crohn’s disease, IBD unclassified and corresponding synonyms, all IBD related pathology reports (resection specimens or intestinal biopsies) from January 2018 to December 2020 in children age 1–18 were selected. Patients with a recognized diagnosis of IBD were eligible for inclusion, which was scored independently by two authors based on all reports. All IBD-related procedures (endoscopies and intestinal resections) were identified. Monthly frequencies of procedures and new IBD diagnoses during the COVID-19 pandemic in the Netherlands (March 11, 2020 – December 31, 2020) were compared to the average monthly frequencies of 2018–2019.

Results
After exclusion of non-IBD related reports, 2161 IBD-related procedures were identified between January 2018 and December 2020. The average number of monthly IBD procedures in 2018–2019 was 59.8, whereas in 2020 this was 60.6 procedures per month, reflecting a 0.8% increase (Figure 1). In 2020, the number of new IBD diagnoses was 456, similar to the 458 new IBD diagnoses in 2018–2019. During the COVID-19 pandemic the weekly number of new diagnoses was 8.8, while between January 2018 and March 2020 this was 8.5 (Figure 2). A slight reduction in monthly IBD-related resections was observed (2.7 vs. 3.5).

Conclusion
Despite the reduction in regular healthcare in children in the Netherlands due to the COVID-19 pandemic, no reduction was observed in IBD-related endoscopies and surgeries during the pandemic in the Netherlands. This reassuring evidence demonstrates that pediatric IBD healthcare remained unchanged, thus not delaying diagnosis of new IBD patients or treatment of severe disease flares.
References
1. Groen M.T., et al. Gastroenterology, 2020.
2. Ricciuto, A., et al. J Crohns Colitis, 2021.
P679 Inflammatory Bowel Disease and cancer risk in the IBSEN study after 30 years of follow-up
Authors: Follin-Arbelet B , Småstuen Cvancarova M , Hovde Ø , Jelsness-Jørgensen L P , Moum B 
Published: January 2022

Abstract

Background
Inflammatory Bowel Diseases (IBD) are chronic diseases with a heterogeneous clinical course, which often cause serious complications. Previously our group has reported that male ulcerative colitis (UC) patients have an increased risk for developing colorectal cancer 20 years after diagnosis, compared to the general Norwegian population. This study aims to estimate the risk of cancer after 30 years.

Methods
Data from the Inflammatory Bowel disease in South-Eastern Norway (IBSEN) study, in which all patients diagnosed from 1990 to 1994 were included, as well as data on all cancer cases from the Norwegian Cancer Registry and mortality from the Norwegian Cause of Death Registry, were used. All IBD patients were age- and gender-matched with five controls and followed up from the date of IBD diagnosis to the date of first cancer diagnosis, death or end of follow-up (31.12.2020) whichever came first. We computed hazard ratios (HR) for all cancers combined and for cancers of digestive organs using conditional Cox regression model stratified by gender and IBD diagnosis.

Results
In total, 756 IBD patients were included, 519 with UC and 237 with Crohn’s disease (CD). Of these, 82 UC and 35 CD patients were diagnosed with cancer during the follow-up. The most frequent cancer diagnoses were intestinal, breast and prostate cancers (Table 1). For all cancers combined, males with UC and females with CD had slightly higher risk of developing cancer compared to matched controls, however, the increased risks were not statistically significant. The same pattern was observed for cancers of digestive organs (Table 2).
Table1.

Table 2.

Conclusion
Our data did not reveal significant differences in risk of developing cancer 30 years after diagnosis between IBD patients and age-and gender-matched controls.
P702 Faecal Microbiota Transplantation Sculpts the faecal and mucosal microbial and metabolomic profiles in patients with Ulcerative Colitis
Authors: Bajaj A , Markandey M , Singh M , Virmani S , Vuyyuru S K , Kante B , Thirunavukkarasu R , Verma M , Kumar P , Kshetrapal P , Makharia G , Gupta D , Kedia S , Ahuja V 
Published: January 2022

Abstract

Background
Gut microbiota modulation via faecal microbiota transplantation (FMT)is known to induce long lasting clinical as well as endoscopic remission in patients with UC. The present study aims to identify microbial and metabolomic changes in the faecal as well mucosal niches, in response to FMT in patients with UC.

Methods
28 patients with mild-moderate UC and 16 non-IBD controls were enrolled. Patients were given a weekly infusion of pooled-multidonor-FMT, for 8 weeks, while maintaining a uniform dietary pattern. We collected paired stool and recto-sigmoidal biopsysamples from patients with UC pre-FMT (n=28), post-FMT (n=10) and controls (n=16). 16S (V3-V4) rRNA sequencing and LC-MS based untargeted metabolomics was performed. α and β diversity analysis and differential abundance (DA) analysis of microbiota was performed using DeSeq2 R package. Differential metabolite peaks between the three groups were identified via volcano plot and annotated using LipidMaps, HMDB, Kegg and Metlin databases. (Fig.1)

Results

α-diversity of patients with UC was not significantly different from that of controls, in both sample matrices. Post-FMT α-diversity of faecal samples differed significantly from the Pre-FMT group, however in mucosal tissue, the difference was non-significant. β-diversity indices were significant in UC pre-FMT vs post-FMT populations for both matrices (Fig.2A and B). DA analysis identified faecal and mucosal controls and UC post-FMT samples to be significantly similar [ANOSIM R=0.07; p=0.1 (faecal) and R=0.02; p=0.315 (mucosal)]. Analysis of core microbiota revealed diminished faecal microbial core in UC, with no major UC-associated loss of mucosal core members, showing relatively conserved nature of mucosal microbiota. FMT restored microbial core along both niches.
UC pre-FMT samples displayed increased abundance of Firmicutes (Limosilactobacillus, Lactobacillus, Streptococcus, Veilonella and Sphingomonas) and Proteobacteria (Methylobacterium) in faecal samples, while mucosa-associated microbiota displayed increased abundances of Firmicutes (Streptococcus, Limosilactobacillus, Ligilactobacillus, Eubacterium, Enterococcus, etc), Bacteroidetes (Parabacteroides and Alistipes) and Proteobacteria (Burkholderia)(Fig.3). Distinct functional classes of metabolites, including bacterial cell wall and QS molecules, membrane lipids, metabolism of vitamins, long and medium chain fatty acids, bile acids, and tryptophan etc, were also found to be altered between the three groups in both sample matrices(Fig.4)

Conclusion
FMT efficiently restores beneficial bacterial populations and related metabolic pathways in faecal as well the relatively reserved mucosal microbial niches, which may pave way for induction of remission in patients with UC.
P706 A distinct subset of tissue-resident Th17 cells expands in the inflamed intestines of Crohn’s Disease patients and responds to colitogenic bacteria
Authors: Paroni M , Leccese G , Ranzani V , Pagani M , Landini P , Vecchi M , Abrignani S , Facciotti F , Caprioli F , Geginat J 
Published: January 2022

Abstract

Background
Inflammatory bowel diseases (IBDs) are characterized by excessive inflammatory T-cell responses to intestinal microbes. Th17-derived Th1 cells (“Th1/17”) are pathogenic in mice, and might also drive inflammation in IBDs.Here, we characterized the role of a novel subset of human intestinal-resident Th17 cells, which produced very high levels of IL-17, together with IFN-γ, in intestinal inflammation in Crohn’s Disease.

Methods
CD4+T-cell subsets from IBD patients and controls were analysed by RNA sequencing and flow cytometry. They were monitored pre/post-therapies in different tissues, and analysed for antigen specificities.

Results
CCR6+CCR5+CXCR3-T-helper cells co-expressed RORC and T-bet, and co-produced IL-17 and IFN-γ. These CCR5+Th17-cells were associated with intestinal inflammation in Crohn’s Disease (CD), but not in ulcerative colitis, and contracted upon Infliximab-induced mucosal healing. Conversely, CXCR3+CCR6+Th1/17 cells, which also co-produced IL-17 and IFN-γ, were unaltered. Intestinal CCR5+Th17-cells had up-regulated genes of pro-inflammatory Th17-effector cells, and down-regulated genes involved in recirculation. Consistently, CCR5+Th17-cells were rare in peripheral blood and lymph nodes, displayed a tissue-resident phenotype in the gut and were enriched in the intra-epithelial compartment of CD patients. Conversely, CCR5-Th17-cells were abundant in the circulation, had an increased gut-homing potential in IBDs, and decreased post-Vedolizumab treatment in the intestine. Moreover, they up-regulated CCR5 with IL-23, which was abundant in the guts of CD patients. Importantly, intestinal CCR5+Th17 cells were selectively activated by adherent-invasive Escherichia coli (AIEC), but not by a commensal/probiotic strain. Th1/17-cells responded instead to Cytomegalovirus. Notably, AIEC induced also IL-23 and the CCR5 ligand RANTES from dendritic cells (DCs).

Conclusion
We identified a gut-resident Th17-cell subset that was activated by CD-associated bacteria, suggesting a key role in pathogenesis. They could differentiate from conventional, circulating Th17-cells that are recruited to the gut and activated by AIEC-infected DCs. Conversely, intestinal Th1/17-cells may protect CD patients from CMV-induced colitis.