bluuebunny/crossref_metadata_2025_split huggingface dataset:
P650 Integrin expression patterns of patients with IBD treated with vedolizumab.
Authors: Kokkotis G , Chalakatevaki K , Papathanasiou E , Tzanoudaki M , Kane R , Liatsis M , Zampeli E , Michopoulos S , Bamias G 
Published: January 2023

Abstract

Background
Anti-α4β7 integrin monoclinic antibody vedolizumab is an effective treatment for moderate and severe Ulcerative Colitis and Crohn’s Disease. Occasionally vedolizumab-treated patients experience articular extraintestinal manifestations, in the form of arthralgias, which could be attributed to lymphocyte tracking modification caused by vedolizumab. This study aims to describe α4β7 andα4β1 integrin expression on circulating lymphocytes and the effect of vedolizumab on integrin expression, as well asto identify expression patterns associated with arthralgias under vedolizumab.

Methods
A cross-sectional study was conducted. Peripheral blood was collected in EDTA-coated bottles before a scheduled drug administration. Expression of α4β7 and α4β1 integrins on CD4+T, CD8+T, B and plasma cells was studied by flow cytometry (DX Flex, BC), using CD3, CD4, CD8, CD19,CD138, CD49d (α4), β7, CD29 (β1). Kaluza C software and SPSS23 were used for analysis.

Results
In total, 40 IBD patients (16 of them treated withvedolizumab) and 8 healthy controls were included. There was a higher percentage of α4β1expressing lymphocytes compared to α4β7+ ones (P&lt;0.001) (figure 1).

Vedolizumab-treated patients had lower percentages of integrin-expressing B cells (α4β7 P=0.001 vs controls, α4β7 P=0.052 vs non-vedolizumab IBD, α4β1 P=0.002 vs controls, α4β1 P=0.015 vs non-vedolizumab IBD) and α4β1 plasma cells (P=0.013 vs non-vedolizumab IBD) (figure 2).

In patients treated with vedolizumab with arthralgias, α4β7 expression on B-cells was more suppressed, whereas α4β1 expression on plasma cells was less suppressed, compared to those that had not developed arthralgias, but not in a statistically significant level (figure 3).

Conclusion
Patients treated with vedolizumab presented different patterns of integrin expression on circulating B cells. Manifestation of arthralgias under vedolizumab may be associated with a disruption of α4β7/α4β1 proportion.
Funding: This study was funded through a research grant from the Greek IBD study group (EOMIFNE) to G.B. EOMIFNE Grant: 2020EOMIFNEp1
P652 Therapeutic drug monitoring during induction therapy with Ustekinumab in patients with Crohn’s disease: the key to early identification of patients with inadequate response.
Authors: Mínguez A , Bastida G , Terol I , Argumánez V , Iborra M , Aguas M , Moret I , Cerrillo E , Garrido A , Tortosa L , Nos P 
Published: January 2023

Abstract

Background
Ustekinumab (UST), an inhibitor of the p40 subunit of interleukins 12 and 23, is approved for the treatment of moderate and severe Crohn disease (CD) but a significant number of patients either partially respond or do not benefit at all. Therapeutic drug monitoring can be used to optimize the efficacy of biological drugs by ensuring adequate exposure to these drugs.
The aim of our research was to identify the relationship between serum concentrations of UST during the induction and biochemical remission at week 16 in patients with CD.

Methods
All CD patients treated with UST included in a local database were identified. Only patients with a fecal calprotectin (FCP) &gt; 250 mg/g were selected. All patients were treated with an initial intravenous induction therapy of UST, followed by subcutaneous maintenance therapy. Disease activity was assessed retrospectively by clinical (Harvey–Bradshaw Index [HBI]) and biochemical parameters (FCP; C-reactive protein (CRP) and Albumin) at Week 0, Week 4, week 8 and week 16. UST trough levels were measured at 4, 8 and 16 weeks using a commercially available validated enzyme-linked immunosorbent assay (ELISA).
Main outcome was biochemical remission, defined by a decreased of calprotectin levels more than 80% or an absolute value less than 200 mg/g at week 16.

Results
Seventy-six patients were included. Patients’ Characteristics at baseline are listed in table 1. Median [IQR] HBI was 5,5 [3-8] at the beginning of treatment. Evolution of biochemical parameters throughout induction is showed in table 2. At the end of the induction phase (week 16), HBI, CRP and FCP decreased significantly from baseline. At this moment HBI was less than 2 in 51% of patients. FCP was available in 63 patients. Biochemical remission was observed in 26/63 (41,3%) patients. Median [IQR] UST serum concentrations were 20,9 μg/mL [13,7–26,3] at w4, 10,1 μg/mL [3,5–7,4] at w8 and 4,1 μg/mL [1,4–3,9] at w16. Quartile analysis demonstrated that 100% and 66% with an UST serum concentration in the highest quartile [Q4], at w4 and w8, achieved a biochemical remission by w16 [p = 0.05 and p &lt;0,02 respectively]. The area under the receiving operating characteristic curve (AUROC) of UST levels to predict biochemical remission at week 4 and week 8 were 0,84 CI95% (0,62-1) and 0,74 CI95% (0,57-0,91) respectively.

Conclusion
Serum concentrations of UST at week 4 and 8 after intravenous infusion could be used to stratify patients according to the probability of achieving remission. This measurements during induction could be used to optimize treatment of CD.
P653 Tight control and Treat to target increase the rates of Transmural remission and Transmural response in Crohn’s disease
Authors: Fernandes S R , Bernardo S , Rita Gonçalves A , Moura dos Santos P , Valente A , Tato Marinho R , Correia L 
Published: January 2023

Abstract

Background
increasing evidence support the use of Transmural remission as a treatment target in Crohn’s disease (CD) but few patients can reach it with currently available therapies. Treat-To-Target (T2T) and Tight-Control (TC) strategies may potentially improve these results.

Methods
Methods: single-center retrospective study including 123 CD patients with active colonoscopy (CN) and magnetic resonance enterography (MRE) at baseline and with available follow-up CN and MRE for reassessment of remission. We evaluated the effects of T2T and TC strategies on the rates of Transmural remission and Transmural response. Patient submitted to bowel surgery between examinations were excluded.

Definitions
CN activity: ulcers in non-operated patients or Rutgeerts score&gt; i1 in operated patients; MRE activity: bowel thickness &gt;3 mm and enhancement on T1/T2 sequences. Transmural remission: inactive CN and MRE at reassessment; Transmural response: improvement from baseline in either examination. T2T: treatment decisions resulting in both clinical remission (Harvey-Bradshaw &lt;5) and fecal calprotectin remission (Fc &lt;250 ug/g) at reassessment. TC: treatment decisions resulting in persistent Fc remission (≥ 2 consecutive results, including reassessment).

Results
48.0% and 42.3% of patients followed a T2T and TC strategy, respectively. Transmural remission and Transmural response were reached by 33.3% and 69.1% of patients, respectively. T2T resulted in higher rates of Transmural remission (55.9% vs 12.5%, P&lt;0.001) and Transmural response (91.5% vs 48.4%, P&lt;0.001). TC was also associated with higher rates of Transmural remission (51.9% vs 19.7%, P&lt;0.001) and Transmural response (90.4% vs 53.5%, P&lt;0.001). In multivariate regression, T2T (OR 9.30 95%CI 2.85-30.30, P&lt;0.001), TC (OR 3.85 95%CI 1.18-12.54, P=0.025) and starting biologic treatment (OR 3.63 95%CI 1.36-9.70, P=0.010) were independent predictors of reaching Transmural response. T2T was the only independent predictor of reaching Transmural remission (OR 6.540 95%CI 2.41-17.74, P&lt;0.001).

Conclusion
Patients following a T2T and TC strategy presented higher rates of Transmural remission and Transmural response.
P657 Current landscape of the real-world utilization of Interleukins 22, 23 and Interleukin 22 binding protein as biomarkers for Inflammatory Bowel Disease (IBD): A targeted literature review
Authors: Dolin P , Evans K , Castañeda J , Udayachalerm S , Cabrera C 
Published: January 2023

Abstract

Background
Precision medicine is an active area of IBD research. Evidence underpinning the role of IL-22, IL-23, and IL-22 binding protein (BP) as biomarkers of mechanistic pathways, diagnosis, disease severity, and treatment response has been accumulating. Little is known about the applications of these ILs as biomarkers in real-world studies. The aim of this literature review was to describe the current landscape of assessing IL-22, IL-23 and IL-22BP in real-world studies.

Methods
A search was undertaken in MEDLINE and Embase to identify English-language manuscripts (2018-2021) and conference abstracts (2019-2021) of real-world studies in adult IBD, measuring IL-22, IL-23, or IL-22BP. One reviewer screened titles/abstracts for eligibility using a standardized form. A second reviewer independently screened a random sample of publications and disagreements were resolved by a third reviewer.

Results
Titles and abstracts of 369 studies were screened. Forty-two studies met the eligibility criteria and were included for full-text screening. Seventeen studies were then excluded because they lacked key information such as the study design or the clinical application. A total of 25 studies were included. Of those, three were conference abstracts. Nine (36%), eight (32%), and eight (32%) studies included patients with CD only, UC only, and both CD and UC with/without their comparison groups, respectively. Eleven studies (44%) were conducted in Europe, 10 (40%) in Asia, two (8%) in North America, and one (4%) each in Africa and the Middle East.
Twelve (48.0%) studies reported on IL-23, 11 (44.0%) on IL-22 and one (4.0%) on IL-22BP. Most publications reported on more than one IL with multiple applications. Eight (28%) studies examined diagnostic applications, 11 (38%) prediction of severity, and 10 (34%) prediction of treatment response. Multiple sampling sources were used, including tissue (38%), serum (34%), cell (16%), blood(9%), and plasma (3%). IL-23 levels were consistently correlated with IBD severity when comparing IBD with healthy controls, but the data was less consistent for IL-23 as a diagnostic test or predictor of treatment response. The reported correlations for IL-22 and IL-22BP varied across studies. This was potentially due to heterogeneous study methodologies.

Conclusion
This literature review shows that IL-22, IL-22BP and IL-23 have been studied in the real world for diagnosis, prediction of disease severity, and treatment response in IBD; however, there was heterogeneity in methodologies, ethnic composition, and sample types across studies. The correlation of IL-22 level with the studied outcomes was qualitatively inconsistent across studies and applications, whereas IL-23 was found to be consistently associated with IBD severity.
P662 Pre-treatment vitamin D concentrations do not predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease
Authors: Lin S , Chanchlani N , Smith R , Roberts C , Nice R , McDonald T J , Hamilton B , Bewshea C , Kennedy N A , Goodhand J R , Ahmad T ,   PANTS consortium
Published: January 2023

Abstract

Background
Vitamin D has a regulatory role in innate and adaptive immune processes. Previous small studies have reported that low pre-treatment vitamin D concentrations are associated with primary non-response and shorter drug persistence to anti-TNF therapy. We sought to assess whether pre-treatment 25-hydroxyvitamin D concentrations predicted primary non-response and non-remission to infliximab and adalimumab in patients with Crohn’s disease recruited to the PANTS (Personalised Anti-TNF Therapy in Crohn’s disease) study.

Methods
We used composite endpoints using the Harvey Bradshaw Index (HBI) in adults and the short paediatric Crohn’s disease activity index (sPCDAI) in children, corticosteroid use, and C-reactive protein (CRP) to define primary non-response (Figure 1). Remission was defined as CRP of ≤3 mg/L and HBI of ≤4 points (short paediatric Crohn’s disease activity index ≤15 in children), without corticosteroid therapy or exit for treatment failure. 25-hydroxyvitamin D concentrations were measured in stored baseline serum samples and cut-offs for vitamin D status were: deficiency &lt; 25nmol/L, insufficiency 25-50nmol/L and adequacy/sufficiency &gt; 50nmol/L.

Results
Samples from 659/898 infliximab (526 Remicade; 133 biosimilar CT-P13) and 448/605 adalimumab (448 Humira) treated patients included in the effectiveness analysis of the PANTS study were included. Overall, 17.1% (189/1107; 95% confidence interval [CI] 15.0 - 19.4%) and 47.7% (528/1107; 95% CI 44.8 - 50.6%) patients had vitamin D deficiency and insufficiency, respectively. At baseline, 22.2% (246/1107) patients were receiving some form of vitamin D supplementation.
Multivariable linear regression analysis confirmed that baseline sampling during non-summer months (Figure 2), South Asian ethnicity, lower serum albumin concentrations, higher HBI and nontreatment with vitamin D supplements were independently associated with lower vitamin D concentrations (Figure 3).
Primary non-response at week 14 and non-remission at week 54 occurred in 19.3% (116/600; 95% CI 16.4 - 22.7%) and 58.8% (351/597; 95% CI 54.8- 62.7%) patients treated with infliximab and 25.3% (100/396; 95% CI 21.2- 29.8%) and 65.3% (246/377; 95% CI 60.3- 69.9%) of patients treated with adalimumab, respectively.
Pre-treatment vitamin D status did not predict response or remission status to anti-TNF therapy at week 14 (infliximab Ppnr = 0.87, adalimumab Ppnr = 0.18) or non-remission at week 54 (infliximab P = 0.12, adalimumab P = 0.59) (Figure 4).

Conclusion
Vitamin D deficiency is common in patients with active Crohn’s disease. Unlike previous studies, pre-treatment serum 25-hydroxyvitamin D concentration did not predict primary non-response to anti-TNF treatment at week 14 or non-remission at week 54.
P665 Social Media Listening to better Understand the Lived Experience of Individuals With Ulcerative Colitis
Authors: Auriat O , Lucats L , Badalamenti S , Kruger A , Wiekowski M , Glotfelty L , Van Hoogstraten H , Coulouvrat C 
Published: January 2023

Abstract

Background
Lived experience is a depiction of a person’s experiences and decisions, as well as the knowledge gained from these experiences and choices. Despite a wealth of clinical studies and real-world data on ulcerative colitis, large-scale and comprehensive insights into the lived experience are lacking. This study aimed to explore how the lived experience of UC is described on social media.

Methods
All English-language posts from the UC open-access forums of Reddit.com, Inspire.com and Everyday Health.com were extracted and anonymized with Synthesio. Concept occurrence and sentiment analysis were performed using Luminoso, a natural language processing (NLP) platform. NLP is the ability of a computer program to interpret human language as it is spoken and written.

Results
A total of 29,250 comments posted between July 01, 2018 and January 01, 2021 were extracted and analyzed. The first 40 concepts were manually reviewed to remove the synonyms of UC and high level health-related concepts (e.g., illness, doctor, treat…) and several concepts were manually merged (eg, stomach and gut). The most common topic expressed in the posts was feeling (n=4,749, 16%), two thirds reporting negative sentiment (68%). Symptom analysis revealed the highest occurrence in pain (n = 4,085, 14%), rectal bleeding (n = 3,385, 12%), toilet frequency (n = 2,003, 7%) and fatigue (n = 626, 2%). These symptoms were associated with negative sentiments (58% to 89%). Among pain, a quarter of the posts were related to stomach or intestinal pain (n = 1,097, 27%). Further sub-concept analysis related to pain revealed topics on pain related to disease flare (n = 711, 17%), joint pain (n = 394, 10%) and bone pain (n = 124, 3%). Notably, patients did not post frequently about their medication (&lt;1%), but surgery was mentioned in 1,494 posts (5%). Sentiment analysis again outlined the dominance of negative feelings whether the comment was related to fear of this definitive procedure or to life post-surgery. Lastly, anxiety (n = 1,019, 3%) and concerns about sleep (n = 857, 3%) were less frequently identified, but still meaningful, concepts.

Conclusion
NLP analysis of posts on UC in unmonitored social media forums demonstrates that patients are firstly concerned by pain and its impact that is strikingly not part of the Mayo score and not routinely assessed in large clinical trials. While social media-based retrospective data collection inherently limits the amount of demographic or clinical description, social media listening studies offer the potential to sample spontaneous patient concerns from large numbers of individuals. Analysis of these data may lead to the development of patient-centered endpoints to be incorporated into clinical studies in the future.
P666 Effect of anastomotic configuration on Crohn’s Disease recurrence after primary ileocolic resection. A comparative monocentric study of end-to-end versus side-to-side anastomosis.
Authors: Bislenghi G , Vancoillie P J , Fieuws S , Verstockt B , Sabino J , Wolthuis A , D'Hoore A 
Published: January 2023

Abstract

Background
There is an ongoing debate whether the type of anastomosis following intestinal resection for Crohn’s disease (CD) can have an impact on complications and postoperative recurrence. The aim of the present study is to describe the outcome of side-to-side (S-S) versus end-to-end (E-E) anastomosis after ileocolic resection for CD.

Methods
A retrospective single center comparative study was conducted in consecutive CD patients who underwent primary ileocecal resection between 2005 and 2013. All patients underwent colonoscopy 6-months postoperatively to assess endoscopic recurrence, defined as modified Rutgeerts’ score &gt;i2b. Surgical recurrence implied reoperation due to CD activity at the anastomotic site. Modified surgical recurrences was defined as the need for re-operation or balloon-dilation. Perioperative factors related to recurrence were evaluated.

Results
Of the128 patients included, 52 (40.6%) received an E-E anastomosis. Median follow-up was longer in the E-E group (8.62 vs 13.68 years, p&lt;0.001). Apart from the primary anastomosis, patient, disease and surgical characteristics were similar between both groups. Postoperative complications and anastomotic leak were comparable (S-S 6.6% vs E-E 7.7%, p=1.00). During the entire postoperative follow-up, biologicals were used in 55.3% and 63.5% (p=0.37) in S-S and E-E patients, respectively. Endoscopic recurrence did not differ between S-S and E-E patients (40.8% vs 49.0%, p=0.37). However, at ten years follow-up, surgical and modified surgical recurrence rate were significantly higher in the E-E group (19.7% vs 7.4%, p=0.02 and 39.2% vs 14.1%, p=0.001). Type of anastomosis was the only independent risk factor for surgical and modified surgical recurrence.

Conclusion
The type of anastomosis did not influence endoscopic recurrence and immediate postoperative disease complications. However, the wide diameter and the morphologic characteristic of the stapled S-S anastomosis result in a lower risk for balloon dilatation and surgical reintervention in the long-term.
P673 The safety of rapid versus standard infliximab infusions in children with inflammatory bowel disease: a multi-centre retrospective cohort study
Authors: Jagt J , Galestin S , Benninga M , de Boer N , de Meij T 
Published: January 2023

Abstract

Background
Rapid infliximab (IFX) infusions have shown to be safe in adults with inflammatory bowel disease (IBD), but data on its safety in paediatric IBD is limited. This study aimed to assess the frequency and timing of infusion reactions (IR) in children with IBD who received rapid (1-h) vs. standard (2-h) IFX infusions.

Methods
This retrospective cohort study included IBD patients 4-18 years old, treated with IFX between January 2006 - November 2021 at two tertiary centres (AMC and VUmc) in Amsterdam, the Netherlands. The AMC protocol was adjusted from standard to rapid infusions with a 1-h post-infusion observation period in July 2019, whereas in VUmc only standard infusions were administered without a post-infusion observation period. After merging both departments in 2022, VUmc patients were allocated from standard to rapid infusions. The primary outcome was the frequency of acute IR amongst rapid vs. standard infusions. Secondary outcomes were the timing, severity and management of IR.

Results
Totally, 297 (150 VUmc, 147 AMC) patients (221 Crohn’s disease; 65 ulcerative colitis; 11 IBD-unclassified) were included, with a total of 7500 maintenance IFX-infusions. No differences were found in the frequency of IR between the patients receiving standard infusions (16/115, 13.9% of patients), rapid infusions (1/31, 3.2%) and both infusion rates (11/151, 7.3%) (p= 0.105). No difference in the frequency of IR was found between standard infusions (26/4383, 0.6% of infusions) and rapid infusions (9/3117, 0.3%) (p= 0.083). Twenty-six of 35 IR (74.3%) occurred during infusion, while nine occurred post-infusion (25.7%). All post-infusion IR were mild, requiring no intervention or oral medication.

Conclusion
Rapid IFX infusions did not result in an increased frequency of IR compared to standard infusions. The IR that occurred post-infusion were mild. Our data have resulted in adjustment of the protocol to rapid infusion without a post-infusion observation period for all IFX patients.
P676 Intestinal ultrasound accurately predicts therapy failure in Crohn's disease patients during a biologics-induced remission
Authors: Albshesh A , Abend A , Margalit Yehuda R , Mahajna H , Ben-Horin S , Kopylov U , Carter D 
Published: January 2023

Abstract

Background
Intestinal Ultrasound (IUS) is a non-invasive modality that can assess disease activity, complications, and treatment follow-up in Crohn's disease (CD) patients. IUS is reliable, patient-friendly, and allows frequent monitoring of disease activity. While 3mm bowel wall thickness (BWT) was repeatedly found to correlate with intestinal inflammation, whether this threshold also best predicts clinically relevant future outcomes is still largely unknown.
We aim to investigate the role of IUS to predict the risk of therapy failure in biologics-treated CD patients in clinical remission.

Methods
Our analysis included a retrospective cohort of CD patients in clinical remission (HBI≤4) induces by biologic drugs, who underwent IUS 12 (±2) months after induction. We examined the correlation of IUS activity parameters with future therapy failure (defined as drug discontinuation, dose escalation, new corticosteroid use, CD-related hospitalization, or surgery).

Results
A total of 57 patients (58% male), with ileal (65%) or ileocolonic (35%) CD, on biological therapy (28% infliximab, 51% adalimumab, 10.5% vedolizumab, 10.5% ustekinumab) were included. Therapy failure occurred in 54.3% (32.2% drug discontinuation, 45.2% dose escalation, 16.2% corticosteroid use and 6.4% hospitalization) during a median follow-up of 12 (IQR 5-22) months after IUS. Of all IUS parameters examined, therapy failure was associated only with increased BWT; BWT &gt; 5mm (hazard ratio (HR) 2.3 [confidence interval (CI) 1.03-5.3], p= 0.041). Interestingly, there was risk plateauing with increased BWT above this cutoff (&gt;5.5 mm (HR 2.2 [CI 1-5.10], p=0.048); &gt;6mm (HR 2.6 [CI 1.17-6.12], p=0.019); &gt;6.5 mm (HR 2.5 [CI 1.08-5.83], p=0.032)) (Figure 1). A BWT cutoff of 3mm could not discriminate patients with future treatment failure.

Conclusion
Our findings suggest that BWT of &gt; 5 mm during clinical remission can predict subsequent treatment failure in CD patients treated with biologics. Our results support the use of IUS in monitoring CD during remission, and may point to a novel threshold predicting disease reactivation.