bluuebunny/crossref_metadata_2025_split huggingface dataset:
P221 Intestinal ultrasound is predictive of disease relapse in asymptomatic Inflammatory Bowel Disease patients
Authors: Picker E A , Choi N K , Reddy N , Rubin D T , Krugliak Cleveland N 
Published: January 2024

Abstract

Background
Intestinal ultrasound (IUS) is a non-invasive, repeatable, and accurate disease monitoring modality that provides real-time assessment of inflammatory bowel disease (IBD). There are few data on the utility of IUS monitoring of asymptomatic patients. We assessed the ability of IUS to predict disease relapse in asymptomatic patients.

Methods
We maintain a prospectively maintained registry and database of IUS cases at our institution. We used this database to perform a retrospective analysis of IBD patients who were asymptomatic (HBI4, SCCAI2) but who had signs of active inflammation on IUS, defined by bowel wall thickness (BWT) &gt; 3mm and/or colour Doppler signal (CDS) (modified Limberg score (mLimberg) &gt; 0). We assessed the prevalence and time to clinical (symptomatic) relapse (HBI&gt;4, SCCAI&gt;2). IUS parameters and treatment change (defined as addition of steroids, immunomodulators, treatment escalation, therapy cycle or swap) were evaluated as predictors of disease relapse.

Results
40 patients (47 CD, 5 UC, 1 IBD-U; 53 IUS exams) were included. 10 patients (18.9%) relapsed within an average of 107.0 (±108.2) days. The relapsed group had a mean BWT of 4.5 (±0.3) mm vs. 3.9 (±0.5) mm in the non-relapsed group (p = 0.112), and a mean mLimberg of 1.7 (±0.3) vs. 1.3 (±0.1) (p = 0.503). Of the 53 IUS exams included in this study, 40 exams resulted in treatment change after the IUS (28 due to IUS findings alone, 12 due to other indications at a later time including elevated faecal calprotectin (FCP), breakthrough symptoms, drug level, perianal symptoms, psoriasis, allergic reaction, and bowel obstruction). Of the 40 patients who had treatment change (including dose escalation (n=16), dose de-escalation (n=4), therapy cycle or swap (n=14), or addition of steroids (n=5) or immunomodulators (n=1)), 9 (22.5%) experienced a clinical relapse, and of the other 13 patients who did not have a treatment change, 1 (7.7%) experience a clinical relapse (p = 0.257).

Conclusion
Silent inflammation identified by IUS in asymptomatic patients is associated with disease relapse in nearly 20% of patients within an average of 3.5 months. The degree of inflammation by BWT and CDS was numerically higher in the relapse group compared to those who did not relapse, although this was not statistically significant. The treatment changes incorporated in this cohort did not lead to lower rates of disease relapse. However, these findings demonstrate the prognostic value of silent inflammation as detected by IUS and the need for future prospective treat-to-target type studies using IUS.
P225 Mucosal transcriptomic profiles associated with clinical response in patients with Ulcerative Colitis receiving filgotinib
Authors: Magro F , Feagan B G , Rogler G , Peyrin-Biroulet L , Bauer Y , Cougnaud L , Oortwijn A , Randall M , Rudolph C , Reinisch W 
Published: January 2024

Abstract

Background
Filgotinib (FIL) is an oral, once-daily, JAK1 preferential inhibitor approved for the treatment of Ulcerative Colitis (UC). In the phase 2b/3 SELECTION trial (NCT02914522), FIL had a high level of efficacy in inducing and maintaining histological remission and endoscopic response, relative to placebo (PBO). Here, we described the changes in the mucosal transcriptomic profiles associated with histologic and endoscopic responses following FIL or PBO treatment.

Methods
Patients with moderately to severely active UC were enrolled into one of two cohorts (biologic-naive or biologic-experienced) and randomized 2:2:1 to receive FIL 200 mg (FIL200), FIL 100 mg (FIL100) or PBO from baseline to week 10. RNA was extracted from colon biopsies collected at baseline and week 10, and RNA sequencing (RNA-seq) was performed according to standard protocols. Clinical responses of interest included histological remission (assessed by categorical Geboes score) and endoscopic response (both defined in Figure legend) at week 10.
To assess transcriptional variability, RNA-Seq data were analyzed by a spectral map separately for baseline and week 10. Differentially expressed gene (DEG) analysis was used to explore differences in transcriptional expression for multiple comparators: from baseline to week 10 between patients with or without clinical response, separately, by treatment arm and cohort.

Results
RNA-Seq data were available for 1086 patients across treatment arms at baseline and/or week 10. Spectral map analysis showed no visual association between baseline transcriptional variability (principal component [PC]1: 26%) and achieving either histological remission or endoscopic response at week 10, nor with the treatment arm. At week 10, the main source of transcriptional variability (PC1: 32%) was visually associated with achieving histological remission or endoscopic response, but not with the treatment arm. From the DEG analysis, more significant genes were associated with histological remission in the FIL200 arm compared with either the FIL100 or PBO arms, especially for biologic-naive compared with biologic-experienced patients (Figure A). Furthermore, more significant genes were associated with endoscopic response in the FIL arms compared with PBO (Figure B).

Conclusion
The overall transcriptional response associated with histological remission or endoscopic response was greater in FIL treatment arms than the PBO arm. This transcriptional response differed between biologic-naive and experienced patients, suggesting that transcriptional changes associated with clinical response were influenced by both FIL treatment and previous biologic use. Preliminary data suggests these transcriptional changes occur in pathways related to UC pathogenesis.
P227 The learning curve for using intestinal ultrasonography
Authors: Bezzio C , Saibeni S , Vernero M , Furfaro F , Monteleone M , Ribaldone D , Fiorino G , Brinch D , Friedman A B , Scalvini D , Maconi G 
Published: January 2024

Abstract

Background
The use of intestinal ultrasonography (IUS) is recommended for suspected or known inflammatory bowel disease (IBD), but the technique is challenging to learn. This prospective study examined how the accuracy of IUS increases with operator experience (“learning curve”) and if prior abdominal ultrasound experience facilitates the learning process.

Methods
The study included five gastroenterologists: four trainees and one expert sonographer. Two trainees had limited abdominal ultrasound experience (&lt; 50 exams) and two had extensive experience (&gt; 500 exams); none had IUS experience. The trainees received an eight-hour course on IUS and one week of hands-on training with the expert sonographer on approximately 50 IUS exams. Thereafter, over a four-week period, each trainee performed 99 examinations and reported four IUS findings. The expert sonographer repeated the exam, and concordance (k) between the expert and trainees was assessed in three consecutive testing periods of 33 exams each.

Results
A progressive improvement in concordance was observed for all IUS findings from Period 1 to Period 3, overall and for both groups of trainees, although those with experience in abdominal ultrasound had faster learning curves. The minimum number of examinations required to achieve concordance with the expert operator (after the initial 50 exams) for detecting increased bowel wall thickness was 34 and detecting bowel dilatation was 29. However, a minimum of 47 examinations was necessary to achieve concordance for detecting intra-abdominal complications, considered an advanced IUS competence. The number of examinations required to achieve concordance was higher for trainees without than with abdominal ultrasound experience.

Conclusion
Basic competence in IUS can be acquired with relatively few examinations, while advanced competence requires more extensive training, particularly for gastroenterologists without abdominal ultrasound experience. These findings have implications for the development of training programs and the establishment of proficiency levels in IUS.
P228 Predictors of steroid therapy refractoriness in admitted Acute Severe Ulcerative Colitis patients
Authors: Abdelmeguid A , Elbanna A , Ibrahim F A E , Whitehead E , Fitzgerald A , Turnbull J , Robertson H , Elsheikh W , Ellakany A , Sebastian S 
Published: January 2024

Abstract

Background
One third of acute severe ulcerative colitis (ASUC) patients are steroid refractory and require colectomy or rescue therapy. Risk stratifying ASUC patients who are steroid non responders to facilitate early initiation of rescue therapy or consideration of colectomy remains an unmet needs in the management of ASUC.

Methods
Records of admitted patients with ASUC over a 5-year period were included. Clinical (diagnosis history, previous medications, disease extent) laboratory (FBC, CRP and albumin at admission and day 3, CRP/albumin ratio) and endoscopic scores (Mayo and UCEIS) at admission were recorded. The primary outcome was response to IV steroids. Secondary outcomes were the proportion of patients requiring re admission or initiation of advanced therapy (biologics or small molecules) within 1 year.

Results
Our study included 103 ASUC patients (44/103 male, median age: 41 years(Min:18, Max:84, range:66, IQR:27). 53 patients were steroid responders, 50 patients were non responders. Among non responders 48 had rescue therapy and 5 had colectomy at index admission (3 after rescue therapy and 2 without rescue therapy). There was no statistical significant difference between both groups in age, gender, disease extent and duration, haemoglobin level, platelets, CRP level, Mayo score of sigmoid, UCEIS score of rectum and sigmoid. There was statistically significant difference between both groups in being on oral steroids at entry, duration of hospital stay, albumin at admission, day 3 albumin, CRP/Albumin ratio at day 3 and Mayo score of rectum.
On univariate analysis, albumin at admission and at day 3, CRP/Albumin ratio at day 3 and being on oral steroids at entry predicted non response to steroids while on multivariate analysis, being on steroids at admission was the only factor independently associated with steroid non-response(OR= 4.695, 95% CI: 1.79-12.34, P=0.002).
Among steroid responders, 13(24.5%) required readmission within 1 year while only 3(6.7%) of the steroid non responders who received rescue therapy required readmission.
Twenty five(47.2%) of steroid responders required initiation of advanced therapies within 1 year of index admission while 28 didn’t. Patients who required initiation of advanced therapy have statistically significant lower hemoglobin and higher platelets than who didn’t. Hemoglobin was the only factor to predict initiation of advanced therapy in multivariate regression analysis(-0.043, P=0.029)

Conclusion
Being on oral steroids at admission for ASUC can predict non response to IV steroids with majority may benefit from upfront advanced therapies at Day 1 of admission. Nearly half of the admitted ASUC patients who respond to steroids require treatment escalation to advanced therapies at 1 year.
P242 Immune-cell specific biomarker of early intestinal inflammation: Neutrophil elastase degraded fragment of type III collagen is elevated in patients with Inflammatory Bowel Disease
Authors: Tsapanou Katranara T , Pehrsson M , Alexdottir M S , Domislović V , Krznarić Ž , Ainsworth M A , Boye T L , Steenholdt C , Bay-Jensen A C , Karsdal M A , Mortensen J H 
Published: January 2024

Abstract

Background
Inflammatory Bowel Disease (IBD) is characterized by epithelial barrier injury of the gastrointestinal (GI) tract. The disease course encompasses abnormal immune responses and excessive secretion of proteases from immune cells. Neutrophils are the first to migrate into the inflamed interstitial matrix, where type III collagen is significantly deposited. Detection of mucosal inflammation in early stages is crucial to prevent cumulative clinical damage, as a delayed diagnosis can hinder effective treatment. Thus, we aimed to develop a biomarker that reflects early intestinal inflammation prior to it becoming medically evident; allowing us to distinguish patients that would respond to an anti-inflammatory treatment.

Methods
A competitive enzyme-linked immunosorbent assay targeting a human neutrophil elastase derived fragment of type III collagen was developed (C3-HNE). The validation was conducted by assessing its dilution recovery, matrix spiking, interference, and inter- and intra-assay variation. The biological relevance was evaluated in commercial samples, one preclinical, and two clinical studies. In the preclinical study, C3-HNE was measured in serum samples from a dextran sodium sulfate (DSS)-induced colitis rat model. In the commercial samples and clinical cohorts, C3-HNE was measured in serum from patients with IBD and healthy donors (HD). To compare the biomarker levels between groups, two-way ANOVA with a Fisher's LSD, and Mann-Whitney U-tests or Kruskal-Wallis (Dunn’s corrected) were conducted.

Results
The novel biomarker C3-HNE was successfully validated, resulting in a technically robust assay with acceptable technical parameters (Table 1). In the preclinical study, the analysis revealed significant difference in the C3-HNE levels between the control and DSS groups on day 4 (p=0.01) (Figure 1A). Additionally, C3-HNE was released earlier (day 1) in the timeline than the elevation of the current disease activity (DAI) score (day 7) (Figure 1A-B). In both clinical cohorts and commercial samples, C3-HNE levels were significantly higher in patients with Crohn's disease (CD), ulcerative colitis (UC) and IBD than in HD (p&lt;0.01, p&lt;0.05 and p&lt;0.05) (Figure 1C-E). Based on the ROC analysis, the biomarker can significantly discriminate between HD and CD, UC or IBD (Table 1).

Conclusion
C3-HNE is elevated in patients with CD, UC and IBD compared with HD. Furthermore, C3-HNE reflects early stages of clinically apparent mucosal damage during experimental colitis. This biomarker holds the potential to identify early mucosal damage or acute inflammation in the GI tract; nevertheless, additional studies are needed to evaluate its clinical validity.
P244 The first step to IBD prevention exploring rate of pre-clinical inflammation in subset of asymptomatic subjects at risk of IBD: screening stage of the PIONIR trial
Authors: Kenigsberg S , Turpin W , Lee S H , Ledder O , Shimhlash Y , Griffiths A , Huynh H Q , El-Matary W , Otley A , Avni-Biron I , Jacobson K , Panaccione R , Bitton A , Croitoru K , Turner D 
Published: January 2024

Abstract

Background
With the increasing prevalence of inflammatory bowel diseases (IBD) globally, it is necessary to start focusing efforts on prevention of the diseases. The Genetic, Environmental, Microbial (GEM) study identified biological signatures predictive of developing IBD in first degree relatives (FDR) of patients with Crohn’s disease (CD). The ongoing PIONIR (Preventing IBD ONset in Individuals at Risk) study is a randomized controlled trial aimed to explore whether the Tasty & Healthy diet can change the CD-risk associated biomarkers of healthy FDRs who are particularly high risk of developing CD, originally followed in the GEM cohort. We report here the rate of IBD and pre-IBD inflammation in a subset cohort.

Methods
Subjects, 6-35 years of age from the GEM cohort who were identified by a combination of predictors at recruitment to GEM to have an increased risk for persistently elevated fecal calprotectin (FC) (i.e. Microbiome Risk Score (MRS), increased gut permeability and/or multiplex family of CD) were approached to perform a new FC test. Subjects who had FC&gt;70µg/g, confirmed by a second sample, were offered a panenteric video capsule endoscopy (VCE), but some elected to proceed to ileocolonoscopy instead.

Results
For the PIONIR recruitment, a total of 450 subjects were approached from 7 sites in Israel and Canada, of whom 183 consented and provided a stool sample for FC (Figure). FC was elevated in 57 (31%) subjects, confirmed by re-testing in 36 (20%); 25/36 underwent VCE/ileocolonoscopy (Figure). In total, 8 (4.4% of the screened cohort) had normal-appearing mucosa, in 10 (5.5%) there were non-specific mucosal changes (e.g. several erosions or erythema), 6 (3.3%) had ulcers compatible with CD and 1 (0.6%) was inconclusive. The median FC of those eventually diagnosed with CD (816 [IQR 361-1123) was higher than the remaining 30 without IBD with elevated FC (175 [111-281], p=0.003). FC&gt;275µg/g was highly predictive of CD in the entire cohort (AUROC 0.97 (95%CI 0.93-0.99); sensitivity 83%, specificity 94%).

Conclusion
Preclinical mucosal inflammation in VCE/ileocolonoscopy was found in 18 of 183 (9.8%) screened subjects (i.e. elevated FC with either normal or nonspecific mucosal findings), 134 (73%) had normal FC and 11 (6%) with elevated FC had missing VCE/ileocolonoscopy data. Six had CD (3.3%, or 17% of the 36 with elevated FC). Detecting subjects at risk at their preclinical stages, possibly with FC&gt;275µg/g, is the first necessary step in developing preventive strategies for IBD.
P248 Feasibility, accuracy and reproducibility of the ultrasound measurement of psoas muscle compared to bioelectrical impedance analysis for the evaluation of skeletal muscle mass in patients with IBD
Authors: Fichera A , Costantino A , Piagnani A , Baldrighi S , Roncoroni L , Vecchi M , Caprioli F , Fraquelli M 
Published: January 2024

Abstract

Background
Sarcopenia is characterized by the loss of muscle mass and it is a strong predictor of disability and poor outcomes in several chronic gastrointestinal diseases such as inflammatory bowel diseases (IBD). Therefore, it is useful to evaluate muscle mass in patients with chronic gastrointestinal diseases at risk for sarcopenia. Radiological evaluation of muscle mass is obtained with computed tomography (CT), magnetic resonance (MRI) and bioelectrical impedance (BIA).
We aimed at assessing the feasibility, reproducibility and diagnostic accuracy of ultrasound (US) measurement of psoas muscle thickness adjusted for body mass index (BMI) compared to skeletal muscle mass (SMM) evaluated with BIA normalized to height2 in the quantification of muscle mass among patients with IBD.

Methods
We enrolled a total of 86 consecutive patients with IBD (males 68.6%, mean age 50.4 ± 17.6, 7.4% with Crohn’s disease) who underwent US evaluation of psoas muscle thickness and BIA during the same day.
US measurement (Philips Epiq, Bothell, USA) was performed by two sonographers, blind to each other. BIA was performed with the Seca mBCA 525 (Hamburg, Germany).
A cut-off of 6.68 and 8.97 of SMM normalized to height2 was considered as normal value for women and men respectively.
Sensitivity, specificity, positive and negative predictive values(PPV and NPV), positive and negative likelihood ratios (LR+ andLR−) were calculated, all with the respective 95% confidence inter-vals (95% CI).
The reproducibility between the US operators was evaluated by intra-class correlation coefficient(ICC) for the quantitative variables of psoas muscle.
The study was approved by our local ethics committee and partially funded by the Italian Ministry of Health.

Results
US psoas muscle thickness measurement was feasible in all the 86 enrolled patients.
There was a significant correlation between US measurement and BIA with a Pearson r coefficient of 0.54 (p= &lt;0.0001). Among men a cut off of 108.18 cmxkg/m*2 showed a sensitivity of 93.5% and a specificity of 53,6% in the detection of low SMM at BIA (Figure 1). Among women a cut off of 66.9 cmxkg/m*2 showed a sensitivity of 78.5% and a specificity of 69.2% in the detection of low SMM at BIA (Figure 2).
Reproducibility among the operators had an ICC of 0.95 (CI 0.93-0.96).

Conclusion
Sarcopenia is a prognostic factor of poor outcomes in IBD, therefore it is important to identify patients at risk for it. Nowadays, assessment of muscle mass and eventually sarcopenia relies on radiological techniques (CT/MRI and BIA). At this purpose we propose a simple, non-ionizing, fast and reproducible US technique that compared to BIA showed a high sensitivity and thus can be used in clinical ractice to screen for muscle mass reduction in IBD patients.
P254 Outcomes of endoscopic and histologic remission in ulcerative colitis under advanced therapy
Authors: Rodrigues I , Bronze S , Fernandes S , Saraiva S , Bernardo S , Gonçalves A R , Moura Santos P , Valente A , Araújo Correia L 
Published: January 2024

Abstract

Background
Current expert-based recommendations suggest that clinical and endoscopic remission should be pursued as treatment targets in ulcerative colitis (UC). However, combined endoscopic and histologic remission may be associated with improved outcomes.

Methods
Retrospective single-center cohort study including consecutive patients with UC under advanced therapy (biologics and small molecules) with endoscopic and histologic evaluation. We evaluated the rates of hospitalization, surgery, steroid-free remission, and treatment discontinuation after 1-year of follow-up according to the type of remission. Endoscopic remission was defined as a Mayo endoscopic subscore of 0. Histologic remission was defined as the absence of ulcers, erosions and neutrophils in the lamina propria.

Results
One hundred and six patients were included. Thirty-five patients (33.0%) achieved combined endoscopic and histologic remission, 21 patients (19.8%) endoscopic but not histologic remission and 50 patients (47.2%) did not achieve endoscopic remission. At the end of 1-year, 85 patients (79.4%) achieved steroid-free remission, 14 (13.0%) required hospitalization, 4 (3.7%) surgery, 15 (14.1%) discontinued treatment. A compound outcome was reached by 31 (29.2%) patients.
In multivariate analysis including age at diagnosis, age at biologic, type of advanced treatment, disease duration, immunomodulation, previous biologic exposure and type of remission, only the type of remission was associated with a lower chance of reaching any unfavourable outcome (reference no remission) - combined endoscopic and histologic remission (OR 0.162 95%CI 0.05-0.528, P=0.003) and isolated endoscopic remission (OR 0.286 95%CI 0.084-0.971, P=0.045). Kaplan-Meier analysis showed longer outcome-free survival in patients with combined endoscopic and histologic remission.

Conclusion
Achieving combined endoscopic and histologic remission is associated with better clinical outcomes after 1 year of advanced treatment compared to no remission. However, we could not confirm a significant advantage of combined endoscopic and histologic remission over endoscopic remission alone.