bluuebunny/crossref_metadata_2025_split huggingface dataset:
P344 What our patients are looking for - the common fields of interest in IBD patients: A Google Trends Analysis
Authors: Zarchi R , Elgressy A , Ben-Horin S , Kopylov U 
Published: January 2022

Abstract

Background
Inflammatory bowel diseases are varied in the way they present, progress and respond to treatment. IBD patients frequently complain about the lack of proper knowledge and support systems, this gap leads to an extensive online search for information. The aim of our study was to characterize the trends in IBD-related Google searches by exploring the Google Trends query tool

Methods
We retrieved worldwide Google Trends data related to Crohn’s Disease and Ulcerative Colitis over the past, 10 years (Jan, 2011 - Oct, 2021). The search terms selection was based on preferences and knowledge gaps identified by an online survey by the members of the of the israeli Crohn’s Disease and Ulcerative Colitis patients association, coupled with data from available literature and Google autocompletion data. We also compared the search volume of the two diseases using the “Topic” feature in google trends, which allows us to utilize google’s search terms aggregation by a specific topic. Google trends provide RSV (Relative Search Volume) over time, and over different regions. The results are normalized on a scale of, 0–100 (100 signifying the most highly-search item).We also compared the RSV for searches related to UC and CD.

Results
Out of the, 20 domains researched over, 370 months, the, 10 most searched domains in Crohn’s disease related searches was ’diet’(41.30%), ’cancer’(14.22%), ’weight’(7.52%), ’pregnancy’(4.44%), ’disability’(4.05%), ’COVID’(3.45%), ’alcohol’ (3.22%), ’vaccine’ (3.17%), ’stress’ (2.54%) and ’smoking’ (2.47%). The, 10 most searched domain in ulcerative colitis related searches was ’diet’ (41.72%), ’cancer’ (18.69%), ’weight’ (5.47%), ’pregnancy’(4.77%), ’smoking’(3.76%), ’alcohol’(3.63%), ’probiotics(3.27%), ’disability’(2.77%), ’stress’(2.62%) and ’covid’(2.12%). When focusing at the time period between March, 2020 and October, 2021, the most searched domain in crohn’s disease was ’COVID’(22.67%) followed by ’diet’(21.81%), ’cancer’(12.52%), ’vaccine’(10.70%), ’weight’(7.07%), ’disability’ (4.34%), ’alcohol’ (2.82%), ’pregnancy’ (2.67%), ’stress’ (2.22%) and ’biologics’ (2.17%). Over the same time span, the most searched domain in ulcerative colitis was ’diet’ (29.59%) followed by ’cancer’ (18.32%), ’COVID’ (11.84%), ’weight’ (6.32%), ’vaccine’ (5.75%), ’alcohol’ (4.07%), ’pregnancy’ (3.66%), ’disability’ (3.06%), ’smoking’ (2.61%) and ’probiotics’ (2.46%).

Conclusion
Patients have numerous interests related to their IBD disease. The most searched IBD-related item is diet, with COVID-19 leading since the break of the pandemic. Our results are a surrogate representation of the patient’s knowledge gaps and needs, and we suggest that IBD healthcare providers should focus their guidance on the issues identified by the patients as such.
P345 The Effectiveness of Ustekinumab and Vedolizumab as Third-line Therapy in Patients with Refractory Crohn’s Disease
Authors: Macaluso F S , Grova M , Saladino M , Demarzo M G , Privitera A C , Giangreco E , Garufi S , Renna S , Casà A , Ventimiglia M , Cappello M , Fries W , Orlando A 
Published: January 2022

Abstract

Background
There is no head-to-head trial comparing ustekinumab (UST) and vedolizumab (VDZ) in Crohn’s disease (CD). Recently, real-world studies evaluated the two biologics in patients refractory to anti-TNF therapy, i.e. as second-line agents. Conversely, no study specifically focused on the effectiveness of UST and VDZ as third-line agents, i.e. after failure with at least one TNF-α inhibitor plus failure with VDZ or UST. We performed a multicentre, real-world assessment of the effectiveness of UST and VDZ in these highly-refractory patients with CD.

Methods
Data of consecutive patients with CD treated with UST and VDZ as third-line therapy until October, 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). The effectiveness was evaluated at, 8, 26, and, 52 weeks, and as treatment persistence at the end of follow up. The clinical outcomes were steroid-free clinical remission (SFCR - Harvey-Bradshaw Index &lt;, 5 without steroid use) and clinical response (CR - reduction of the Harvey-Bradshaw Index ≥, 3 points with a concomitant decrease of steroid dosage compared with baseline). Multiple logistic regression models were build to find independent predictors of effectiveness, including the use of UST and VDZ as candidate predictors.

Results
143 patients (UST: n=113; VDZ: n=30) were included. After, 8 weeks, SFCR was reported in, 38.1% of patients treated with UST and in, 43.3% of patients treated with VDZ (p=0.75), while CR was reported in, 61.9% of patients treated with UST and in, 60.0% patients treated with VDZ (p=1.00). After, 26 weeks, the rates of SFCR and CR were, 41.6% for UST and, 50.0% for VDZ (p=0.60), and, 61.4% for UST and, 66.7% for VDZ (p=0.81), respectively. After, 52 weeks, the rates of SFCR and CR were, 51.8% for UST and, 57.1% for VDZ (p=0.78), and, 65.9% for UST and, 71.4% for VDZ (p=0.77), respectively. Lack of difference in effectiveness between the two drugs at any time point was confirmed by multiple logistic regression models. After, 26 weeks, 88.7% of patients treated with UST and, 81.4% of patients treated with VDZ were still on treatment. Univariable Cox survival analysis showed a higher probability of treatment discontinuation for VDZ compared with UST (HR for VDZ:, 2.66; p=0.008), even if such difference was not confirmed at the multiple Cox proportional hazard regression model (HR for VDZ:, 1.94; p=0.08), where only age (HR, 0.98; p=0.04) and use of systemic steroids at baseline (HR, 3.29; p=0.003) were found to be independent predictors of treatment discontinuation.

Conclusion
This is the first real-world study assessing VDZ and UST as third-line therapy in patients with CD. Both drugs showed surprisingly high effectiveness, without significant differences between them.
P351 Allogenic adipose-derived mesenchymal stem cells (darvadstrocel) in Japanese patients with complex perianal fistulas in Crohn’s disease
Authors: Watanabe K , Mizushima T , Okita Y , Sugita A , Nakaya R , Shibata M , Yamaguchi T 
Published: January 2022

Abstract

Background
Patients with complex Crohn’s perianal fistulas were treated with allogenic mesenchymal stem cells (darvadstrocel) in pivotal studies, and in clinical practice in Europe since, 2018. However, it is unclear whether the same efficacy and safety could be expected across different ethnic groups. Moreover, it is known that perianal complications including perianal fistulas are more frequent in Asian patients with Crohn’s disease (CD).

Methods
Japanese adult patients with treatment-refractory complex perianal fistulas in CD were enrolled from, 9 sites in a phase, 3, open-label, single-arm, uncontrolled study. Patients could have, 2 internal and, 3 external openings at maximum, and their luminal disease was non-active or mildly active (CDAI ≤220) at baseline. A single dose (24mL, 120 million cells) of darvadstrocel was intralesionally injected, and results after, 24 and, 52 weeks were evaluated. Primary endpoint was combined remission (a remission rate evaluated clinically and by MRI) at Week 24.

Results
22 patients (mean age, 36.4 years, 63.6% male, mean duration of CD, 11.3 years) were enrolled. A half (11/22) had, 1 internal opening (IO) and, 2 external openings (EO) followed by, 1IO-1EO/2IO-2EO/2IO-3EO (3 each, 9/22) and, 1IO-3EO (2/22)., 59.1% and, 68.2% achieved combined remission at Week, 24 (primary endpoint) and Week, 52, respectively.
Up to Week, 52, 90.9% (20/22) experienced adverse events (AE), and, 81.8% (18/22) were mild or moderate in intensity. Proctalgia (6/22), nasopharyngitis (5/22), and anal fistula (4/22) were most frequently reported. There was no death or AE-related study discontinuation.

Conclusion
52 weeks after administrating darvadstrocel in Japanese patients with complex perianal fistulas in CD, fistula closure was confirmed in, 68% (15/22) and partial closure in, 90.0% (20/22). These findings are consistent with the pivotal study ADMIRE-CD, and real-world case-series reported from Europe. Furthermore, no new safety concerns were identified.
P366 Exclusive enteral nutrition drives protective microbiome modulation in paediatric Crohn’s Disease
Authors: Häcker D , Siebert K , Metwaly A , Hölz H , De Zen F , Köhler N , Pauling J K , Matchado M , List M , Schwerd T , Haller D 
Published: January 2022

Abstract

Background
Exclusive enteral nutrition (EEN) is a first-line induction therapy for paediatric Crohn’s disease (CD). Although the protective mechanisms remain unclear, previous studies showed substantial changes in microbiome composition in response to EEN. We aim to assess the protective function of EEN and its impact on gut microbiome signatures in paediatric CD.

Methods
We prospectively followed, 15 newly diagnosed paediatric CD patients aged, 3–18 years between, 01/2019 –, 08/2021. Patients were treated according to international guidelines including EEN therapy for, 6–8 weeks, followed by a gradual re-introduction of solid food and concomitant start of maintenance treatment. Disease activity and inflammatory biomarkers were monitored during, 12-months follow-up. 16S rRNA gene sequencing and targeted/untargeted metabolomics was performed from stool samples collected weekly during EEN and monthly thereafter (n = 261). Dietary modulation and clinical activity of patient-derived stool microbiota were studied by ex-vivo faecal fermentation and after faecal microbiota transplantation (FMT) into germ free (GF) IL10-/- mice.

Results
All patients achieved remission with EEN therapy but, 6/15 had resuming CD activity within, 6 months. Longitudinal microbial and metabolite profiling of stool samples showed highly individualized responses to EEN without coherent signatures. Integrated multi-omics data analysis showed an enrichment of long-chain fatty acids in patients under EEN, which correlated with a reduced abundance of Lachnospiraceae, compared to patients under regular diet. Faecal microbiota from CD patients with active disease (baseline or relapse) or inactive disease (EEN-induced remission) were exposed to EEN-like or dietary control formulations in continuous ex-vivo cultures. EEN-like formulation induced protective changes in the patient-derived baseline microbiota confirmed by the absence of disease activity after FMT in GF IL10-/- mice. Mice colonized with baseline microbiota after ex-vivo EEN exposure showed a decreased abundance of Bacteroides, Akkermansia, Blautia and an increase of Lachnoclostridium and Parabacteroides in comparison to those colonized directly with patient’s baseline microbiota. In contrast, EEN-like diet failed to mitigate the aggressive behaviour of relapse microbiota when transferred into GF IL10-/- mice which was in line with an inability to cause significant compositional changes.

Conclusion
Our data show that clinical efficacy of EEN in paediatric CD is accompanied by temporal and individual gut microbial and metabolite changes. The combined findings of continuous culture and gnotobiotic mouse models point towards a direct protective role of EEN-modulated patient microbiomes in regulating intestinal inflammation.
P378 Rectal bleeding and stool frequency improvement with tofacitinib dose escalation to, 10 mg BID in patients with Ulcerative Colitis following loss of response on tofacitinib, 5 mg BID maintenance therapy: Results from OCTAVE Open
Authors: Allegretti J R , Gecse K B , Chiorean M V , Argollo M , Guo X , Lawendy N , Su C , Mundayat R , Paulissen J , Salese L , Irving P M 
Published: January 2022

Abstract

Background
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In the tofacitinib UC clinical programme, patients who responded to tofacitinib, 10 mg BID during induction, and experienced treatment failure whilst receiving tofacitinib, 5 mg BID during maintenance (OCTAVE Sustain) and subsequently received tofacitinib, 10 mg BID in the open-label, long-term extension (OLE) study (OCTAVE Open; NCT01470612), comprised the dose escalation subpopulation. The efficacy and safety of tofacitinib in the dose escalation subpopulation have been previously reported.1 Here, we evaluated patient-reported outcomes to assess rectal bleeding and stool frequency improvement in the dose escalation subpopulation in OCTAVE Open.

Methods
The following efficacy endpoints based on the Mayo subscores were analysed in the overall dose escalation subpopulation and by prior tumour necrosis factor inhibitor (TNFi) failure status: rectal bleeding improvement (≥1 point decrease in rectal bleeding subscore [RBS] from OLE study baseline) and stool frequency improvement (≥1 point decrease in stool frequency subscore [SFS] from OLE study baseline), up to Month (M)6 in the OLE study (full analysis set, non-responder imputation). Changes from baseline in partial Mayo score (PMS), RBS and SFS at M1, by M2 clinical response status, were also analysed (as observed).

Results
In OCTAVE Open, 57 patients were included in the dose escalation subpopulation, of which, 28 (49.1%) had prior TNFi failure. Overall, at M1 and M6, of OCTAVE Open, 59.6% and, 66.7% of patients had rectal bleeding improvement, respectively (Figure, 1). Corresponding values for stool frequency improvement were, 50.9% and, 64.9%. At most time points, rates of rectal bleeding and stool frequency improvements were similar in patients with and without prior TNFi failure. Patients with a clinical response at M2 had a numerically greater mean decrease from baseline in PMS, RBS and SFS at M1 than those without (Figure 2).

Conclusion
In this post hoc analysis, in patients with UC who had loss of response after, 8–52 weeks of treatment with tofacitinib, 5 mg BID (following reduction from induction tofacitinib, 10 mg BID), dose escalation back to, 10 mg BID generally resulted in rectal bleeding and stool frequency improvement in the majority of patients by M1, which was maintained to M6, regardless of prior TNFi failure status. Furthermore, early improvement in RBS and/or SFS at M1 may indicate likelihood of recapturing response at M2 with dose escalation from tofacitinib, 5 to, 10 mg BID.

Reference
1. Sands BE et al. Aliment Pharmacol Ther, 2020;, 51:, 271–280.
P383 Ustekinumab as an opportunity for refractory Ulcerative Colitis patients
Authors: Iborra M , Soutullo C , Gimeno M , Bastida G , Aguas M , Cerrillo E , Sáez-González E , Garrido A , Mínguez A , Bordetas J , Nos P 
Published: January 2022

Abstract

Background
There are limited data in real-life of ustekinumab (USK) used in ulcerative colitis (UC). The aim of this study was to assess the effectiveness and safety in clinical practice of USK in UC in the medium and long-term.

Methods
Observational study in UC patients who received USK at the recommended dose based on weight ~6 mg/kg IV week, 0.90 mg SC week, 8 and maintenance, 90 mg SC every, 8 or, 12 weeks and with, 1 year of follow-up. The partial Mayo score (PMS) was used to assess clinical remission (PMS≤, 2). The PMS, C-reactive protein (CRP) and faecal calprotectin (FC) values ​​were recorded at baseline and after, 8, 16, 24 and, 52 weeks. Dose adjustment was performed by the measure of UST trough levels by ELISA, when patient lost clinical and/or biochemical response and the levels were low (&lt;1.3 µg/ml). Demographic, clinical, biochemical and endoscopic data, previous treatments, adverse events (AEs), surgeries and hospitalizations, were documented.

Results
Twenty-three patients with UC were analysed. (Table, 1). All patients had received previous biological treatment:, 52% ≥2 anti-TNF, 65% vedolizumab and, 30% JAK inhibitors. Treatment discontinuation occurred in, 3 patients (13%). The persistence was, 83% and, 79% at, 6 and, 12 months (Figure, 1). During follow-up, 12 patients (52%) maintained standard dose of USK. Dose adjustment was performed in, 13 patients (56%):, 3 (13%) required intravenous UST reinduction and, 10 (43%) required dose escalation (8 by shortening the interval between doses and, 2 by switching to intravenous USK administration). Clinical remission was reached in, 61%, 58%, 56%, 79% of the patients after, 8, 16, 24, 52 weeks, respectively. Normal CRP (&lt;5mg/L) and FC (&lt;150 µg/g) levels were achieved in, 76%, 93% and, 80% and in, 35%, 31% and, 40% of patients after, 8, 24, 52 weeks, respectively. Five of, 6 patients who had endoscopy before and after treatment showed endoscopic Mayo subscore ≤1. There were, 2 AEs, 1 hospitalization, and, 1 colectomy during follow-up.

Conclusion
This study demonstrates the safety as well as the clinical, biological and endoscopic effectiveness of USK adjusted by levels in real life in a highly refractory UC cohort.
P386 Predictive models for assessing the response to ustekinumab in Crohn’s disease patients
Authors: Hubert A , Bottieau J , Toubeau J F , Franchimont D , Vallée F , Liefferinckx C 
Published: January 2022

Abstract

Background
The loss of response to biologics remains a clinical challenge for which the discovery of predictive factors is helpful. In this direction, exploiting tree-based models on top of logistic regression (LR) allows to uncover unexpected valuable predictors. The aim of the study is to develop performant predictions of ustekinumab (USK) response at one year of follow-up in a cohort of Crohn’s disease (CD) patients using benchmark logistic regression (LR) and tailored tree-based techniques, Random forest (RF) and Gradient Boosting Decision Trees (GBDT).

Methods
This is a retrospective study based on a cohort of, 80 CD patients treated with USK. Inputs include demographic data, disease characteristics as well as pharmacokinetics, clinical and biological parameters at baseline, week, 8 and, 16. After one-year follow-up, both clinical outcome (achieved in case of USK maintenance without optimization, n=80) and endoscopic outcome (achieved in case of SES-CD&lt;10, n=52) are evaluated. The inputs are firstly ranked via the p-values for LR method and the impurity criterion for the tree-based ensemble methods. Then, the optimal subset of inputs for both methods is selected following a sequential feature selection. Due to the limited size cohort, a nested cross-validation framework was applied to avoid bias and overfitting. The performance of the final models is evaluated using the area under the ROC curve (AUC) with standard deviation (SD), sensitivity (Se) and specificity (Sp). All the analyses are performed with Python, 3.6, 6 using the packages statsmodels and Scikit-learn.

Results
Input data characterizing the CD cohort are presented in Table, 1. At one-year follow-up, clinical and endoscopic outcomes were achieved in, 56.2% (n=45/80) and, 69% (n=, 36/52), respectively. Table, 2 summarizes the predictive model characteristics at the different timepoints. Whatever the outcome, predictive models exhibited an increased accuracy over the induction timepoints. At week, 16, a multivariate LR allowed to predict endoscopic outcome with an AUC, 0.86±0.12, Se, 83% and Sp, 70%. The explanatory variables were CRP level at week, 8 and, 16, lymphocyte count at week, 8 and USK trough levels at week, 16. The best model to predict endoscopic outcome was obtained by RF with an AUC of, 0.92 ±0.08, Se, 91% and Sp, 75%. The key inputs were lymphocyte count at baseline.

Conclusion
This study highlighted the added value of applying tree-based models for the development of accurate predictive models. More specifically, the evolution of biological markers during induction as well as USK trough levels at week, 16 are relevant factors to predict endoscopic outcome among CD patients treated with USK
P391 Unpacking the different popular diets for pediatric Crohn’s disease - concerns around nutritional adequacy
Authors: Carmody E , Haskett J , Parkinson-McGraw L , Grover Z , Martinez A , Rashid M , Otley MD MSc FRCPC A 
Published: January 2022

Abstract

Background
The first line treatment for inducing remission in pediatric Crohn’s disease (CD) is Exclusive Enteral Nutrition (EEN), where a patient drinks a nutritionally complete formula exclusively for, 6 to, 12 weeks. Despite the effectiveness of EEN, some patients may experience challenges including taste fatigue, monotony, and a lack of social participation with meals. Given these challenges, patients may turn to popular or fad diets for managing their disease. These diets are often restrictive, eliminating a number of foods and exacerbating the risk of underlying nutrient deficiencies in this patient population.

Methods
These case studies involved a nutrient analysis of evidence-based and popular diets for CD, including Crohn’s Disease Exclusion Diet (CDED), CD-TREAT, Specific Carbohydrate Diet (SCD), IBD Anti-inflammatory Diet (IBD-AID), Autoimmune Protocol (AIP) Diet, Gut and Psychology Syndrome (GAPS) Diet, and low FODMAP. Four cases were selected with mild-moderate CD:, 11-year-old and, 16-year-old, both male and female. A nutrient analysis of sample menus of each diet was completed using Food Processor version of, 11.6.0 by ESHA Research. Results were compared to age and gender specific Dietary Reference Intakes (DRIs), population-based dietary intake data, and Health Canada Dietary Guidelines.

Results
Data are presented for Case, 1, 11-year-old male. Findings were comparable to other age and gender cases. As compared to Acceptable Macronutrient Distribution Ranges (AMDRs), there was a higher percentage of energy from fats and lower from carbohydrates for the SCD (% kcal, fat and carbohydrate respectively:, 59%;, 30%), IBD-AID (52%;, 37%), AIP Diet (50%;, 20%) and GAPS Diet (60%, 21%). Saturated fat intake exceeded recommendations (&gt;10% of energy intake) for CDED (% kcal, 14%) CD Treat (17%), SCD (11%), AIP Diet (15%) and GAPS Diet (20%). Both vitamin D and/or calcium intake were below the Recommended Dietary Allowance (RDA) respectively for CDED (% RDA, vitamin D and calcium respectively:, 89%;, 86%), SCD (23%;, 53%), AIP Diet (14%;, 23%), low FODMAP Diet (4%, 96%) and GAPS Diet (calcium, 58%). Adolescent females versus males between the ages of, 14–18 years may be at greater risk of inadequate nutrient intake, given the general increase in nutrient requirements yet lower caloric needs.

Conclusion
Given the increase in awareness and interest in popular diets for Crohn’s disease, it is imperative that clinicians are aware of the risks of inadequate nutrient intake with restrictive diets.