bluuebunny/crossref_metadata_2025_split huggingface dataset:
P900 Studying causality association of ustekinumab with cardiovascular disease outcomes using Mendelian randomization
Authors: Miguel González J A , Sánchez Mayor M , Cervera Seco L M , Gaite Reguero A , Pavlidis P , Martínez Marigorta U 
Published: January 2023

Abstract

Background
The human antibody ustekinumab targets the common p40 subunit between both pro-inflammatory interleukin-12 (IL-12) and interleukin-23 (IL-23) that upregulate T cell differentiation towards T helper 1 (TH1) and T helper 17 (TH17) respectively. The blockade of the IL12-IL23 pathway has been shown to be an effective therapeutic option for Inflammatory Bowel Disease treatment, however a recent epidemiological study has reported a potential cardiovascular risk association for ustekinumab treatment in patients at high cardiovascular risk specifically1. We use mendelian randomization (MR) to assess the reliability of this finding.

Methods
MR uses genetic variation to examine the causal effect of a risk factor (exposure) on a disease (outcome). The basis of MR relies on the use of genetic variants as instrumental variables (IVs) that are reliably related to the risk factor and that are not susceptible of reverse causation and confounding2. We use genetic variants (SNPs) detected in eQTL studies that affect gene expression levels as proxies for the IL12-IL23 pathway genes in order to simulate the biological effect of ustekinumab. A cardiovascular trait-composition composed of different groups of outcomes (acute coronary syndrome, transient ischaemic attack, unstable angina and ischemic stroke) was created to investigate further the possible association of ustekinumab with triggering cardiovascular events.

Results
Using top cis-eQTLs from the eQTLGen consortium and the Database of Immune Cell Expression (DICE) as IVs for the IL12-IL23 pathway genes, we observed non-significant associations after multiple testing correction for any of the cardiovascular traits. However, we observed a significant positive causal effect for IL12Rβ1 gene in acute coronary syndrome when using IVs from the Genotype-Tissue Expression (GTEx) project. An observation that was also obtained in a meta-analysis specifically for acute coronary syndrome. In addition, we run MR with multiple SNPs associated with IL12-IL23 genes and we did obtain similar results for IL12Rβ1 and acute coronary syndrome.

Conclusion
Our results suggest that the blockade of the IL12-IL23 pathway with ustekinumab might reduce cardiovascular risk and provide a cardioprotective effect based on the results obtained for acute coronary syndrome. As these results are not in line with previous observational studies1, further investigations are needed to clarify the biological mechanism that may account for these discrepancies.
1. Poizeau et al. JAMA Dermatol (2020).
2. Sanderson et al. Nat Rev (2022).
P908 Faecal Microbiota Transplantation refurbishes the crypt-associated microbiota in Ulcerative colitis
Authors: Markandey M , Bajaj A , Verma M , Virmani S , Singh M , Gaur P , Das P , Srikanth C , Makharia G , Kedia S , Ahuja V 
Published: January 2023

Abstract

Background
Intestinal crypts form a pristine gut biogeographical niche, homing the intestinal stem cells and being the closest neighbors to underlying lamina propria. Initially believed to be sterile, the crypt lumen was recently shown to inhabit a conserved microbial population. However, the identity of the crypt-associated microbiota (CAM) remains elusive. The present study is among the first to illustrate the CAM composition in health and its deviation during ulcerative colitis (UC), and the effect of faecal microbiota transplantation along with an anti-inflammatory diet (FMT-AID) on the structure of this community.

Methods
Recto-sigmoidal biopsies from controls, and from patients with mild-moderate UC before and after FMT-AID (n=26), were subjected to methacarn-fixation, followed by paraffin-embedding, sectioning and laser-capture microdissection-assisted crypt isolation. DNA isolated from micro-dissected samples was subjected to 16S rRNA gene sequencing. The bacterial presence in colonic crypts was confirmed using fluorescence in-situ hybridization(FISH). Microbiome data analysis was carried out by using QIIME2 and R packages.

Results
FISH performed using pan-bacterial probes revealed the presence of sparse microbial clusters in colonic crypts, distinct from the overlying layer of Mucosa-associated microbiota (MAM), in both controls as well as in UC(Fig.1a and 1b). While MAM is dominated by members of phyla Firmicutes (45%) and Bacteroidetes (26%),CAM is comprised predominantly of aerobic members of Actinobacteria(54%) and Proteobacteria(38%), followed by minor proportions of Firmicutes(4%), Acidobacteria and Cyanobacteria (2% each). The significant members of CAM included aerobic genera -Cutibacterium(35%),Sphingobium(13%), Paracoccus(11%), Micrococcus(3%), Lawsonella(3%), Rothia(2%), Prauserella(2%), Kocuria, Corynebacterium, Acinetobacter and Brevundimonas (1% each)(Fig.1c and 1d). Analysis of CAM diversity in controls, and in patients with UC before and after FMT-AID, showed no significant alterations in the α- and β diversity matrices(Fig.1e and 1f).CAM demonstrated UC-associated dysbiosis of specific taxa which was restored after FMT-AID(Fig.2a and 2b). These FMT-restored CAM taxa correlated negatively with disease-associated parameters - Fecal calprotectin (FCP), Simple Clinical Colitis Activity Index (SCCAI) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS)(Fig.2c and 2d). The positive effects of FMT-AID further refurbished the CAM-MAM interaction networks, which were obliterated in UC.(Fig.2e)

Conclusion
A gut bacterial community, enriched in aerobic bacteria, resides in the colonic crypts, and undergoes taxa-level alterations during UC and in response to FMT.
P910 Emerging role of IL-33/ST2 and Gut Microbiota axis in the inflammatory process of ulcerative colitis patients with ileal pouch-anal anastomosis
Authors: Lopetuso L R , Vetrone L , Petito V , Pugliese D , Parisio L , Laterza L , Gasbarrini A , Scaldaferri F , Papa A 
Published: January 2023

Abstract

Background
IL-33/ST2 axis and gut microbiota are important factors in the pathogenesis of IBD with a potential reciprocal influence. IL-33/ST2 axis controls the mucosal healing process during intestinal inflammation. Pouchitis, after restorative proctocolectomy with ileal pouch-anal anastomosis, is the most common complication. We aimed to explore the potential correlation between mucosal cytokines and gut microbiota in the inflammatory process of pouchitis.

Methods
23 patients with ileal pouch-anal anastomosis were enrolled. 13 showed pouchitis and 10 a normal pouch. Mucosal samples were collected from the afferent ileal loop and from the pouch. Multiplex analysis for cytokines was performed. ELISA, western blot and IHC were run to assess IL-33/ST2 axis. Microbiota was analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. Pouchitis Disease Activity Index and Pouchitis Histological Score were calculated. Multivariate analyses were run to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches.

Results
IL-1Ra, IL-6, IL-8, IL-17, IP-10, MCP-1, MIP-1a, MIP-1b were increased in the inflamed pouch vs. normal pouch. No differences were registered in samples from the afferent ileal loop. In pouchitis, IL-7 resulted reduced in the inflamed pouch vs. the ileal loop. In normal pouch, no differences were recorded. In pouchitis, IL-33 and ST2 protein levels were significantly reduced in the pouch vs. the ileal loop and resulted decreased vs. normal pouch. Full-length, bioactive IL33, ST2L and sST2 were expressed in all experimental groups; the cleaved, less active form of IL33 was increased only in pouchitis. IL-33 and ST2 stainings were less intense within the inflamed and ulcerated mucosa of pouchitis compared to the normal pouch and in close proximity to areas of re-epithelialization. Microbiota analysis showed a decreased biodiversity in pouchitis vs. normal pouch (both at pouch and ileal loop level). Lower levels of Verrucomicrobia and increased abundance of Actinobacteria were recorded in inflamed pouch vs normal pouch. In pouchitis, the ileal loop and the pouch showed decreased levels of Akkermansia muciniphila and augmented abundance of Collinsella vs. samples from the normal pouch. In pouchitis, multivariate analyses evidenced a significant inverse correlation between Collinsella e Collinsella aereofaciens abundance and ST2 levels.

Conclusion
Pouchitis and normal pouch are characterized by divergent inflammatory molecular pathways and microbial populations with a specific pattern between the pouch and afferent ileal loop. Our results suggest a potential role for IL-33/ST2 and gut microbiota axis in driving the gut mucosal wound healing in patients with ileal pouch-anal anastomosis.
P924 A unique gut microbiome signature can help differentiate Crohn`s Disease and isolated Terminal Ileitis
Authors: Raghunathan N , Joshi V , Patel R , Mekala D , Pal P , Banerjee R 
Published: January 2023

Abstract

Background
With increasing number of ileal intubations, isolated terminal ileal ulcers(TI) are often detected during colonoscopies. The etiology of these lesions have not been well-defined and differentiating TI from early Crohn’s Disease (CD) is a commonly encountered diagnostic challenge. CD is associated with significant dysbiosis; however, the gut microbiome of TI is poorly studied. We aimed to compare the gut microbial profile between CD and isolated non-specific TI.

Methods
Fecal samples were collected from treatment naïve patients (26 CD;13 TI) and healthy volunteers (29) without the use of antibiotics, probiotics, and prebiotics for at least 6 weeks. CD was confirmed by endoscopic and histological examination. TI was diagnosed based on isolated terminal ileal erosions/ulcers, normal small bowel endoscopy, non-specific inflammation with no granulomas/ cryptitis/crypt abscess on biopsy, and no history of NSAIDs. Fecal DNA was isolated and sequenced(16S-V4). Taxonomical classification was performed by Amplicon Sequence Variant approach and analysed by STAMP (Statistical Analysis of Metagenomic Profiles) using Welch`s T-Test. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used for predictive metagenomics. Significant metabolic pathways were corrected by Storey FDR (q&lt;0.05). Fecal Calprotectin (FCal) was measured using QuantOnCal rapid test.

Results
Microbiome data analysis revealed a progressive decline in α-diversity(p=0.002) in CD and different β-diversity (Bray-Curtis dissimilarity p=0.001) compared to TI and healthy(Fig1). Overall Firmicutes were lower(p=9.81e-4) while Desulfobacterota were higher(p=8.65e-3) in CD than TI(Fig2A). Faecalibacterium prausnitzii (p=0.04) and Roseburia inulinivorans (p=0.03) were markedly reduced while Parabacteroides distasonis (p=9.91e-3) and Bilophila wadsworthia (p=7.36e-3) were elevated in CD (Fig3). A microbial signature covering 8 non-overlapping taxa was deduced to distinguish CD and TI (3 taxa reduced, 5 elevated in CD compared to TI) (Fig2B). PICRUSt analysis indicated 18 significant metabolic pathways differentiating CD and TI. Bacterial stress alarmone PPGPP-MET was significantly higher in CD (p=2.04e-3) (Fig4). FCal was significantly higher in CD with mean value (±SD) as 549.12±390.4 and 167.15±191.8µg/g in TI (p=0.002).

Conclusion
A distinct gut microbiome profile was observed in TI compared to CD. Exploitation of these differences can potentiate differential diagnosis of CD and TI. Further research on the spectrum of dysbiosis is warranted. This may help in differentiating patients with early-CD who require active therapy from those with non-specific TI ulcers that resolve over time.
P927 Corticosteroid treatment in pediatric IBD patients reshapes the gut microbiota
Authors: Singh P , Sundararajan S , Terranegra A , Elawad M , Akobeng A , Al Khodor S 
Published: January 2023

Abstract

Background
Inflammatory bowel disease (IBD) in pediatric populations comprises 25% of all cases of IBD, which is a chronic immune-mediated inflammation of the intestinal tract. The clinical course of IBD is demonstrated in relapsing and remitting phases that require lifelong monitoring and treatment. The complex interactions between mucosal immunity and the intestinal microbiota are well-known in the pathogenesis of IBD. Corticosteroids are commonly administered to reduce IBD-associated mucosal inflammation and gastrointestinal symptoms. Whether or not corticosteroids beneficially modulate the mucosal microbiota to help reduce intestinal inflammation in pediatric patients with IBD has not been evaluated with interventional studies.

Methods
The objective of this study was to evaluate the effects of corticosteroids on the diversity and composition of gut microbiota in pediatric IBD patients. Ten pediatric patients diagnosed with IBD were treated with corticosteroids for 2-3 months. Stool samples were collected before and 8 weeks after treatment. The diversity and composition of gut microbiota were evaluated using 16S rRNA gene sequencing.

Results
Our results suggest that 3 months of corticosteroid treatment result in an increase in alpha diversity(p&lt;0.05). The community structure of gut bacteria was significantly different (p&lt;0.05) pre and post-treatment, with higher abundances of Bacteroides ovatus Bacteroides fragilis whereas the lower abundance of Prevotella copri and Alistipes finegoldi was observed(p&lt;0.05). In conclusion, the diversity and composition of bacteria differ as a result of corticosteroid administration. Since gut microbiota plays an important role in regulating inflammatory conditions such as IBD

Conclusion
Reshaping intestinal microbiota through corticosteroid therapy may be a viable treatment option.
N04 How to manage the concerns of patients with inflammatory bowel disease due to the transition from in-hospital to home management with oral or subcutaneous therapies: results of a survey of a cohort of patients in intravenous biologic treatment
Authors: Napolitano D , Settanni C R , Parisio L , Schiavoni E , Pugliese D , Scaldaferri F , Gasbarrini A , Papa A 
Published: January 2023

Abstract

Background
Therapeutic armamentarium of inflammatory bowel disease (IBD) has expanded, including several intravenous (IV) and subcutaneously administered biological agents and orally administered small molecules (SMs). Additionally, some biologics initially available only for IV administration also have subcutaneous (SC) formulations. However, transitioning from in-hospital IV treatment to SC or oral home therapy can lead to some patient concerns, mainly linked to the need for self-administration and managing side effects. This study aimed to evaluate the opinion of IBD patients on the transition to oral or SC treatment, considering multiple socio-demographic factors, the frequency of biologic agent infusion, and the commitments (personal, family, work) associated with the in-hospital administration of therapy. In addition, patients were asked about their knowledge of new therapeutic options and their expectations about this management modality.

Methods
We conducted a survey using a questionnaire prepared by a team of gastroenterologists and nurses working at the IBD Unit of the CEMAD-Policlinico Gemelli of Rome. The survey was administered to consecutive IBD patients in stable IV biological treatment from January to October 2022. It consists of 31 items and has been divided into four sections: descriptive, commitment, knowledge and passage mode opinion.

Results
311 patients responded to the survey from 400 questionnaires (77.7%). 49.8% favored switching from IV to oral or SC therapy, and only 25.1% disagreed. In univariate and multivariate analysis, the home therapy approval rate was significantly associated with the distance from the IBD center (Fig. 1) and work/family/personal commitments. Surprisingly, only about a quarter of the IBD patients knew that almost all the following available therapeutic agents will have an SC administration route or will be SMs (Fig. 2). Regarding patients' opinion on the efficacy of SMs or SC administration of biological agents compared to IV drugs: 63% had no definite idea, while 14% believed that the effectiveness could be reduced. 23.8% of patients would like to be reassured by their gastroenterologist or nurse on the efficacy and safety of these new therapeutic options, and 7.7% would like to know the scientific data from studies on this issue.

Conclusion
The transition from in-hospital to the home therapeutic management of biological therapy with SC or oral agents was generally viewed favorably by patients, especially if they have commitments or are residents far from the IBD center. However, to reduce patient concerns and encourage this change, it is necessary to implement a patient training and information program involving all the IBD unit care figures, including IBD nurses.
N09 Exploration of medication adherence interventions in Inflammatory Bowel Disease, Multiple Sclerosis and Rheumatoid Arthritis: A Scoping Review of Randomised Controlled Trials
Authors: King K , McGuinness S , Watson N , Norton C , Chalder T , Czuber-Dochan W ,   Bowel Research in Nursing Group
Published: January 2023

Abstract

Background
The inflammatory diseases of inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) have recognised medications to maintain remission.Yet between 53–75% of people with IBD, 30-80% with RA and up to 50% with MS do not take medications as prescribed.
Recognising and improving adherence in IBD, MS and RA is a primary treatment goal to keep symptoms quiescent.
This scoping review aims to identify effective adherence interventions for IBD, MS and RA. As there were few studies in IBD, MS and RA were included to learn lessons from other conditions.

Methods
Randomised controlled trial (RCT) medication adherence interventions for IBD, MS or RA conducted between 2012-2021, were identified in six electronic databases.
Critical Appraisal Skills Programme assessed study quality.

Results
3024 participants were included across 24 RCTs; 8(33.3%) investigating IBD, 12(50%) RA and 4(16.7%) MS.
Nine RCTs (37.5%) significantly improved medication adherence; all were rated high quality with five being delivered face to face and 1:1; all involving tailored education, advice or counselling by trained health professionals (HPs).
IBD interventions were varied; the two significantly effective were web-based; one offering education modules and “red flag” monitoring, with follow up testing versus telephone education. The other used text message reminders with tailored feedback.
Four of five effective RA interventions used psychological, behaviour change approaches.
Three integrated educational and artificial intelligence-based methods through telephone-education, viewing disease progression on a computer system or text messages.
Of the four MS interventions, only a Bluetooth bottle cap with mobile phone reminders and MI based telephone counselling led to significant adherence improvements.
Interventions using artificial intelligence were most significantly effective (see Table 1). Tools such as diaries, calendars and advice sheets were also effective in increasing adherence.
Only 10 interventions were theory based.

Conclusion
Tailored, face to face, 1:1 interaction with HPs can provide personalised, adherence support.
Integration of several therapeutic approaches can be effective, but it can be difficult to identify cause of any impact.
To improve adherence in inflammatory conditions, theoretically informed interventions should be developed and evaluated.
Online routes of intervention delivery must be accessible, user-friendly, and functional to promote self-management.
However, an adherence intervention which minimises costs, provides patient-centred, value-based care through implementation of evidence-based strategies will no doubt be welcomed by patients, HPs and services alike.
N11 Adherence, self-care and illness perception in patients with Inflammatory Bowel Disease – a qualitative study
Authors: Ljungström E , Eberhardson M , Hjortswang H , Pihl Lesnovska K 
Published: January 2023

Abstract

Background
Medical treatment (MT) is key in the management of Inflammatory Bowel Disease (IBD, ulcerative colitis [UC] and Crohn’s disease [CD]) and non-adherence is a barrier to treatment efficacy. Approximately 30 % of patients with IBD is non-adherent to MT. Self-care is defined as; the process of maintaining health through health-promoting practices and managing illness. Adherence is an important part of self-care in IBD. Illness perception relates to understanding disease and potential consequences.
The aim of this study is to add deeper understanding of adherence and non-adherence as part of self-care and explore the links to illness perception and self-efficacy in patients with IBD.

Methods
Semi-structured interviews were conducted face-to-face with 15 IBD patients (5 CD, 9 UC, 1 IBD-U, Table 1) at a university IBD-clinic in Sweden. Patients were invited to ensure richness of data and maximum variation of disease duration, age, and sex. Interviews were recorded, transcribed verbally, and analysed with inductive, latent content analysis.

Results
Analysis resulted in three main categories and ten subcategories. The first category, Disease Perception, included the observation that a majority of the informants monitors disease through bowel symptoms. However, perception of severe illness was linked to low daily function. Most informants used stress reduction and diet to reduce symptoms. Some informants struggled with acceptance of disease while others seem to have reached higher acceptance. Fear related to disease was expressed, e.g., colonoscopies, cancer and progress of disease. The second category, Health Care Perception, showed that informants highly desired a personal connection with the doctor. Some informants expressed trust issues due to delayed diagnosis, kindreds’ bad experiences from health care or emotional trauma related to disease onset or care. Unmet need of information mainly concerned the health care system, the diagnosis and MT. The third category, Treatment Perception, included the informants’ ambivalence towards MT, where worries of potential harm from MT was central. Preferences on administration of MT was a factor that influenced adherence. Many informants perceived that non-medical strategies are more or equally important as MT to decrease symptom burden.

Conclusion
The findings add understanding of reasons for adherence and non-adherence to MT and demonstrates the complex mechanisms behind this phenomenon. The informants’ evaluation of risk and benefit with MT covers considerations that are not entirely medically established. This highlights the importance of a trustful dialogue and shared decision making between patient and health care provider in order to increase adherence.