bluuebunny/crossref_metadata_2025_split huggingface dataset:
P663 Mild COVID-19 disease and breakthrough cases among children with inflammatory bowel disease: An update from an international registry
Authors: Brenner E , Zhang X , Agrawal M , Ungaro R , Colombel J F , Kappelman M 
Published: January 2022

Abstract

Background
Coronavirus disease 2019 (COVID-19) tends to cause mild disease in children, although severe disease occurs rarely. Children with inflammatory bowel disease (IBD) often receive immunosuppressive medications that may increase risk of infectious complications. Little is known about the severity of breakthrough infection after COVID-19 vaccination in children with IBD. We describe COVID-19 outcomes among children with IBD, including those with breakthrough infection.

Methods
The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a database created to evaluate COVID-19 outcomes in IBD patients. We included children (age ≤18) from the SECURE-IBD database through November 17th, 2021. We used descriptive statistics to summarize demographic/disease characteristics of the study population, both overall and stratified by hospitalization status, and performed bivariate comparisons. We reported demographic and clinical details of patients requiring an intensive care unit stay and those with breakthrough infection (defined as ≥1 COVID-19 vaccination prior to infection), respectively.

Results
We analyzed 606 pediatric IBD COVID-19 cases from 37 countries. The most common IBD medications were tumor necrosis factor (TNF) antagonist monotherapy (48%) and sulfasalazine/mesalamine (20%). Most patients (85%) had no non-IBD comorbidities. No patients died, and 28 children (5%) were hospitalized. Factors associated with hospitalization included non-IBD comorbid conditions (43% hospitalized vs 13% not; p &lt;0.01), moderate/severe IBD disease activity (61% vs 15%; p &lt;0.01 overall), gastrointestinal symptoms (68% vs 16%, p &lt;0.01), and steroid use (29% vs 6%, p &lt;0.01). TNF antagonist monotherapy was associated with a decreased likelihood of hospitalization (29% vs 49%; p value 0.03) (Table 1). Seven patients needed intensive care, and three (0.5%) required mechanical ventilation (Table 2). There were nine fully vaccinated and five partially vaccinated patients who developed breakthrough infection, of whom only one required hospitalization but did not need a ventilator (Table 3). The majority of patients with breakthrough infection (13/14) were on systemic immunosuppressants at the time of COVID-19 infection (10/14 on TNF antagonists).

Conclusion
We found that children with IBD have a relatively low risk of severe COVID-19 outcomes. Among children with IBD who developed COVID-19 after vaccination, the majority were on immunosuppressants and had mild disease that did not require hospitalization. These data may reassure families and providers of children with IBD during the COVID-19 pandemic and support public health recommendations for COVID-19 vaccination among eligible children with IBD.
P678 Rare and severe complications in paediatric Inflammatory Bowel Disease: results of 5 years of international collaboration through the PIBD-SETQuality Safety Registry
Authors: Klomberg R , Kemos P , Chondrou P , Croft N , de Ridder L 
Published: January 2022

Abstract

Background
In addition to development of complicated disease behavior itself, children with Inflammatory Bowel Disease (IBD) are at risk of several complications, including malignancies, severe sepsis, or venous thrombosis, which can ultimately even cause death. Due of the rareness of these events, little evidence exists on underlying causes and risk factors, and little experience with these events in clinics hampers development of management guidelines.

Methods
In the ongoing international PIBD-SETQuality Safety Registry, participating paediatric gastroenterologists monthly completed an electronic survey since September 2016. In this survey, they indicated whether or not they had seen any predefined rare and severe complication of paediatric IBD (PIBD) or related treatment in a PIBD patient &lt;19 years. In an annual denominator survey, participants also reported the number of PIBD patients under their care. Together with the duration of participation, this number was used to calculate incidence rates of each complication in the registry. Upon report of a complication, specific follow-up forms were sent, collecting patient demographics, complication details (diagnostics, management, outcome) and IBD details (Paris classification, disease severity, IBD treatment).

Results
From September 2016 to October 2021, the registry reached an all-time number of 222 participants. Currently, 139 paediatric gastroenterologists actively report from 127 international pediatric IBD centers in 30 countries, covering a total of 23,239 PIBD patients. The average duration of participation per center was 39.7 (IQR (29 – 55) months, resulting in a total study population of 65,099 patient-years. In total, 245 complications were reported, including 78 classified as other rare and severe complications (Figure 1). Incidence rates for some complications (e.g. renal failure, venous thrombosis, opportunistic infection) were relatively increased, while other complications, (e.g. hemophagocytic lymphohistiocytosis (HLH)) were rare. Among reported malignancies were Hodgkin lymphoma (n = 6) and hepatosplenic T-cell lymphoma (n = 2). Causes of death were IBD-related in 73% of cases and included cancer (n=2), cerebrosinus venous thrombosis (n=2) and severe sepsis (n=2).

Conclusion
After 5 years of international collaboration of more than 200 PIBD specialists, the Safety Registry project has confirmed several complications in PIBD have increased incidence over the general paediatric population. HLH and HSTCL were rarely reported. Clinical phenotyping of patients has resulted in better understanding of underlying aetiologies and outcome of complications. Ultimately, in partnership with PIBD experts, this project will develop and share management guidelines to improve patient care.
P701 Compositional and functional alterations of the gut microbiome are associated with impaired intestinal permeability in healthy relatives of patients with Crohn’s disease
Authors: Leibovitzh H , Lee S H , Xue M , Raygoza Garay J A , Hernandez-Rocha C , Madsen K L , Meddings J B , Guttman D S , Espin-Garcia O , Smith M I , Goethel A , Moayyedi P , Steinhart A H , Panancionne R , Huynh H , Jacobson K , Aumais G , Mack D R , Abreu M , Bernstein C N , Marshall J K , Turner D , Xu W , Turpin W , Croitoru K 
Published: January 2022

Abstract

Background
The gut microbiome may play a role in gut barrier homeostasis including epithelial barrier integrity and function. However, data are scarce and limited to animal studies. We aimed to assess if alterations in the gut microbiome are associated with altered intestinal permeability.

Methods
We utilized the Genetic Environmental Microbial (CCC GEM) cohort of healthy first-degree relatives of patients with Crohn’s disease. Gut barrier function was assessed using the ratio of urinary fractional excretion of lactulose to mannitol (LMR). Stool bacterial DNA was extracted and sequenced for the V4 hypervariable region of the 16S rDNA gene using MiSeq and processed using QIIME2. PICRUSt2 was used to impute Microbial functions. In order to identify robust associations, the overall cohort was divided based on geographic region into a North American discovery cohort (n=2,472) and non-North American external validation cohort (n=655). LMR&gt;0.025 was defined as abnormal. LMR-microbiome associations were assessed using generalized estimating equation multivariable regression model and Random Forest (RF) classifier algorithm. q&lt;0.05 was considered significant when multiple tests were performed.

Results
The median age of the entire cohort was 17.0 years [IQR 12.0; 24.0], 52.6% were females and 25.4% had LMR&gt;0.025. In the discovery cohort, subjects with LMR&gt;0.025 had markedly reduced alpha diversity (Chao1 index, estimate= -0.0037, p=4.0e-04) and altered beta diversity (Bray-Curtis dissimilarity index, PERMANOVA: pseudo-F statistic = 2.99, p=1.0e-03). Eight bacterial genera and 52 microbial pathways were identified to be associated with LMR&gt;0.025 (q&lt;0.05). The compositional associations were replicated in four genera (Adlercreutzia [odds ratio(OR)=0.74, 95% confidence interval (CI) 0.6–0.91], Clostridia-UCG-014 [OR=0.71, 95%CI 0.59–0.86], Clostridium-sensu-stricto-1 [OR=0.75, 95%CI 0.61–0.92] and Colidextribacter [OR=1.65, 95%CI 1.2–2.26]). The pathway associations were replicated in eight pathways (biosynthesis of glutamate [OR=0.4, 95%CI 0.21–0.74], tryptophan [OR=0.06, 95%CI 0.01–0.27] and threonine [OR=0.038, 95%CI 0.003–0.41], among others). Bacterial community composition was associated with gut barrier homeostasis as defined by the RF analysis (p= 1.4e-6).

Conclusion
Gut microbiome community composition and microbial pathways are associated with gut barrier function. These findings may identify microbial targets that enhance barrier function.
P707 Microbial signature of the colon is not associated with response to vedolizumab in Crohn’s disease
Authors: Hageman I , Joustra V , Li Yim A , Davids M , Henneman P , Hakvoort T , Probert F , Satsangi J , D’Haens G , De Jonge W 
Published: January 2022

Abstract

Background
Crohn’s disease (CD) is a complex disease where the gut microbiome plays an important role. One of the established treatments in CD is Vedolizumab (VDZ), an alpha(4)beta(7) integrin antibody. Finding biomarkers to predict therapy response is still a clinical unmet need, since this treatment has shown endoscopic remission in only a third of CD patients. Ananthakrishnan et al. demonstrated a strong relationship between microbial metagenomics signature and therapy response to VDZ in CD based on the metagenomics composition of baseline fecal samples. While the majority of studies focus on fecal samples, mucosa-adherent bacterial signature could bring forth stable biomarkers. In this study, we sought to identify the signature of the adherent microbiome in intestinal biopies to differentiate responders (R) from non-responders (NR) to VDZ treatment at baseline.

Methods
We prospectively collected ileal and colonic biopsies from adult CD patients scheduled to start VDZ treatment during baseline- and follow-up (FU) endoscopies. After median 27 weeks of follow-up, patients were classified as either R or NR based on endoscopic response (≥50% reduction in SES-CD score), steroid-free clinical response (≥3 point drop in HBI or HBI ≤4, no systemic steroids) and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a basal CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Microbiome composition of the biopsies was determined using 16S RNA gene V3V4 amplicon sequencing. We measured alpha and beta diversity using Wilcoxon and Adonis metrics.

Results
In total, 44 CD patients were included in the baseline cohort (28 R and 16 NR) and 53 CD patients were included in the follow up cohort (37 R and 20 NR), for which 21 patients overlap between baseline and follow up. When comparing alpha-diversity between R and NR, we did not find significant differences in ileal (Wilcoxon, p=0.78) and colonic (Wilcoxon, p=0.70) samples at baseline nor at follow up (ileal Wilcoxon, p=0. 27 and colonic Wilcoxon, p=0. 63). Next, comparing the beta-diversity, we demonstrated no significant differences between R and NR in ileal (baseline p=0.96, follow up p=0.11) and colonic (baseline p=0.11, follow up p=0.4). Microbiome profiles did show high inter-individual variation but were highly similar intra-individually both between body site and over time.

Conclusion

Here, we investigated the microbial signature of VDZ R and NR and demonstrated mucosa-associated microbiome is mostly stable after resolution/non-resolution of inflammation in CD and does not predict response to VDZ therapy. Further analyses on data of infliximab, adalimumab and ustekinumab treated patients, as part of the EPIC Pioneer study, are ongoing.
P721 Faecal microbiota analysis with body composition and nutritional habits simultaneously amongst Crohn’s disease patients
Authors: Bálint A , Bacsur P , Resál T , Jójárt B , Gyuris Z , Jaksa G , Pintér L , Takács B , Pál S , Gácser A , Szántó K J , Rutka M , Bor R , Fábián A , Farkas K , Maléth J , Szepes Z , Molnár T 
Published: January 2022

Abstract

Background
Changes in microbiome of the gut and decreased diversity in inflammatory bowel disease(IBD) is the subject of intense researches. The exact pathophysiological connection is lacking, but the systemic inflammation due to the microbial alterations are assumed. This study aimed to perform analysis of faecal microbiota composition simultaneously with body composition by bioelectrical impedance and nutrition habits in Crohn’s disease(CD) patients to find specific microbiota profiles connected with obesity, mesenterial fat, signs of systemic inflammation, nutritional and body composition characteristics.

Methods
In our prospective cohort study, CD patients were enrolled. At the inclusion, demographic and clinical data, blood, and faecal samples were obtained. Clinical disease activity was assessed by CDAI, and SES-CD. Laboratory tests were made including C-reactive protein(CRP), albumin and lipids (triglyceride, cholesterol). Faecal bacterial composition was assessed using shotgun metagenomics sequencing technique. Each patient underwent a body composition analysis via bioelectrical impedance analysis. A nutritional questionnaire was filled by each subject.

Results
Data of 27 CD patients with different localisation was analysed in this study (mean age was 35±11 years). According to the gut inflammation, some Blautia species correlated positively with SES-CD (p=0,004), and correlated with faecal calprotectin negatively (p=0,02), while Roseburia hominis negatively with CDAI scores(p=0,01). High CDAI scores were also associated with dysbiosis. Adlercreutzia equolifaciens and Blautia hansenii associated with triglyceride(negatively p=0,04, positively p=0,05). Firmicutes has a lower, while Bacteroidetes has a higher abundance at high cholesterol level(p=0,001, p=0,023). Lower Adlercreutzia and Lactobacillus abundance were seen in patients with high visceral fat area(p=0,05, p=0,01), while Clostridia correlated with percent body fat(p=0,025).Bifidobacterium bifidum were associated in people with low body weight or low skeletal muscle mass(p=0,01, p=0,03). Beside Clostridia, Eubacteriales also correlated with waist-hip ratio(p=0,04, p=0,04).

Conclusion
To our knowledge this is the first study to analyse microbiota profiles by shotgun sequencing technique in CD patients depending on body composition via bioelectrical impedance and nutrition. Changes in Blautia, Lactobacillus, Adlercreutzia, Roseburia and Bifidobacterium abundances in patients with CD and obesity highlight the importance of correlations between lipid metabolism, adipose tissue mass, and chronic inflammation. Through this, it helps to develop new therapeutic approaches, such as personalized pre- or probiotics or faecal microbiota transplantation.
N06 Assessing stakeholder identified barriers and enablers to Ultrasound implementation for assessment of Crohn’s Disease in the UK: A qualitative interview study
Authors: Radford S , Leighton P , Coad J , Moran G 
Published: January 2022

Abstract

Background
Data from the METRIC trial (PMID:29914843) has shown that small bowel ultrasound (US) has very good diagnostic accuracy for disease extent, presence and activity in Crohn’s Disease, is well tolerated by patients and is cheaper when compared to MRI. A recent survey (unpublished) undertaken by the authors via the British Society of Gastroenterology indicated that there is enthusiasm for the use of US in IBD care in the UK. However, uptake of US in the UK is limited, however it is unclear why this is the case.

Methods
A qualitative semi-structured interview study, utilising template analysis using the Normalisation Process Theory (NPT) codebook, was undertaken. NPT was used to guide the analysis framing the findings in relation to the implementation processes related to integrating US into daily IBD care. Interviews were undertaken utilising virtual meeting software.

Results
Fourteen participants were enrolled in the interview study (table #). Participants were enrolled between 02/06/2021-and 06/09/2021, with interviews taking place during the same time period. Enrolled were three patients living with CD (21.4%), two IBD Nurse specialists (14.3%), two IBD Nurse consultants (14.3%), one surgical IBD nurse specialist (7.1%), two consultant gastroenterologists (14.3%), two consultant radiologists (14.3%) and two gastroenterology service managers (14.3%). Participants reported that perceived barriers included reliance on MRI and established care pathways, reluctance to change, lack of trust in US in relation to perceived lack of precision when compared to MRI and the initial financial and time outlay in establishing a US service (buying equipment and training staff). Participants were enthusiastic for the uptake of US and discussed enablers to US uptake being the benefits to patients in terms of reduction in waiting times and earlier diagnosis and treatment allocation (leading to improved clinical outcomes), reduced hospital appointments, reduced costs to the NHS, patients having better understanding of their health and improvements in the therapeutic relationships between patients and healthcare professionals.

Conclusion
There is an enthusiasm to establish and utilise US in IBD care in the UK, however there are perceived barriers in achieving this. There is scant literature to effectively assess these reported barriers and enablers. Therefore there is further research required in the areas of the impact of the use of US on the confidence of clinical decision making of healthcare professionals and the relative cost effectiveness when compared to MRI use for the assessment of IBD in the UK.
N07 Current practices of Ultrasound for assessment of Crohn’s Disease in the UK
Authors: Radford S , Moran G 
Published: January 2022

Abstract

Background
Data from the METRIC trial (PMID:29914843) has shown that small bowel ultrasound (US) has very good diagnostic accuracy for disease extent, presence and activity in Crohn’s Disease (CD), is well tolerated by patients and is cheaper when compared to MRI. However, Uptake of US in the UK is limited

Methods
We designed and conducted an online survey to assess the current usage of US throughout the UK. The survey was undertaken by BSG IBD group members between 9 June 2021 - 25 June 2021. Responses were anonymous, respondents were able to skip questions.

Results
103 responses were included in the data analysis Responses came from 14 different regions of the UK, from 66 individual NHS trusts. 99.03% (n=103) respondents reported that they currently have an MRI service for Crohn’s disease, where only 30.1% (31) had access to US service. Numbers of MRIs per month was reported as an average of 15.14, with a range of 3–75. The average number of US undertaken was reported as 7.67 per month, with a range of 0–50. Average time for results to be reported for MRI scans was reported as between 4–6 weeks, with a range of 2 days to 28 weeks. The average time for an US to be reported was stated as 1–4 weeks, with a range of 0–8 weeks. 48.51% of respondents reported that they were ‘very confident’ when using MRI data to make clinical decisions. 25.24% were ‘extremely confident’, 22.33% were somewhat confident and 2.91% were not so confident. 11% of respondents stated they would be extremely confident in using US to make clinical decisions, 22% stated they would be very confident, 27% somewhat confident, 20% not so confident and 20% not at all confident. Of those respondents who did not have access to an US service, 92.31% (72) stated that they would be interested in developing an US service.

Conclusion
There is an appetite for the uptake of US in the UK for assessment of CD, however there remains a significant number of UK centres with little or no access to an US service. There is a difference in the levels of confidence that clinicians have in using US as a diagnostic tool in the UK. Further research is necessary to understand why this is the case. Results from this survey will go on to inform our future work in developing an implementation package for US in the UK in the NHS.
N08 The influence of the Covid-19 epidemic on access to medical advice for children with Inflammatory Bowel Disease (IBD), based on patients from The Children’s Memorial Health Institute, Warsaw (IPCZD)
Authors: Kotkowicz Szczur M , Matuszczyk M , Kierkuś J 
Published: January 2022

Abstract

Background
COVID -19 significantly affected all levels of medical care as well as access to medical care for children with Inflammatory Bowel Diseases (IBD).The purpose of the study was to investigate how the Covid-19 epidemic influenced on the access to medical care for children with IBD, on the quality of medical care during this period and on the health of young patients.

Methods
The analysis was based on the results of the questionnaire containing 15 questions addressed to the parents of children with IBD. The questions concerned mainly access to GP consultations and gastroenterology consultations, but also access to medicines and parents’ concerns about the health of children during the pandemic.
Since December 2020, 150 questionnaires have been sent to parents of children with IBD. 72 completed questionnaires were returned and 60 of them were included into the analysis (12 were excluded due to lack of complete data). The T-Student test was used for statistical analysis.

Results
Only 5 % of respondents (n=3) stated that the pandemic had no impact on access to a GP, as many as 83% (n = 50) indicated that the epidemic made access to primary care physicians very difficult.
Changes in access to health care during the Covid-19 epidemic caused anxiety about further treatment of the child in 96.7% (n = 58, p&lt;0,05) of the surveyed parents.
In The Children’s Memorial Health Institute due to the limitations of visits related to the development of the pandemic, telemedicine was introduced on a large scale. Due to the easy access to medical telepaths and the resulting, if necessary, outpatient visits, the respondents assessed the access to medical consultations of doctors from the IBD team in IPCZD as much better than before the pandemic 58% (n = 35, p&lt;0,05) or no changes compared to the time before the pandemic 42% (n = 25). 90% (n=54) of the surveyed parents indicated that they would also like to use telemedicine after the epidemic as an alternative to some hospital visits.
Statistical analysis also showed a correlation between difficulties with access to specialized medications during a pandemic and the occurrence of an exacerbation of the disease in a child during that period.
Out of the 40 (67%) group of parents who showed difficulties in purchasing medicines for their children in the survey, as many as 75% (n = 30, p &lt;0.05) reported exacerbation of the disease during the epidemic.

Conclusion
Based on the above results, we concluded that the pandemic had a major impact on access to medical care as well as on access to specialized medications. In The Children’s Memorial Health Institute, thanks to the development of telemedicine, access to specialist care in the IBD team has not changed.