bluuebunny/crossref_metadata_2025_split huggingface dataset:
P112 S1PR expression on circulating immune cells is not limited to lymphocytes in patients with inflammatory bowel disease
Authors: Verstockt . B , Verstockt S , Cremer J , Sabino J , Ferrante M , Vermeire S 
Published: January 2023

Abstract

Background
With the recent approval of ozanimod in ulcerative colitis (UC) and promising data of etrasimod, S1P receptor (S1PR) modulators are entering the therapeutic landscape. Besides differences in receptor selectivity (ozanimod S1PR1/5, etrasimod S1PR1/4/5), both compounds induce a drop in circulating B/T-lymphocytes, without affecting monocyte counts. This lymphocyte drop seems independent of treatment response, suggesting that other cell types – like monocytes, implicated in IBD pathogenesis - might contribute to efficacy. Furthermore, very little is known about the expression of S1PR on circulating lymphocytes/monocytes in the context of IBD.

Methods
Peripheral blood mononuclear cells were isolated from 135 IBD patients with active endoscopic disease (Table 1), and subsequently FACS sorted (CD14 monocytes and CD4 T-cells). RNA was extracted from lysed cells, and single-end sequenced using Illumina HiSeq4000.

Results
All S1PR were identified on both CD4 T-cells and monocytes, though with hardly any S1PR5 expression on circulating monocytes and hardly any S1PR3 expression on T-cells. Receptor expression on both monocytes and T-cells correlated significantly only for S1PR1 (r0.25, p=0.003) and S1PR4 (r 0.19, p=0.02). Circulating T-cells had substantial higher expression of S1PR1 (fold change [FC] 1092.0, p&lt;2.2E-16), S1PR2 (FC 1.84, p=5.3E-7), S1PR4 (p=2.4, p&lt;2.2E-16) and S1PR5 (FC infinite, p&lt;2.2E-16) compared to monocytes. In contrast, circulating monocytes expressed significantly more S1PR3 (FC infinite, p&lt;2.2E-16). Receptor expression on T-cells did not differ between patients with Crohn’s disease (CD) and UC, whereas monocyte S1PR1 was significantly elevated in CD as compared to UC (FC 4.5, p=0.006) (Figure 1). Previous anti-TNF was not associated with any difference in S1PR1, but was associated with a slight increase in S1PR4 (FC=1.26, p=0.02). No association was observed in relation to previous vedolizumab exposure, whereas concomitant steroid use was linked to a decrease in S1PR5 on T-cells (FC 0.35, p=0.007). Disease duration or inflammatory burden (CRP) were not associated with any S1PR, though S1PR1 positively correlated with age in T-cells (r 0.23, p=0.008). In UC, S1PR1 on monocytes was significantly elevated in proctitis compared to left-sided and pancolitis (p=0.02); in CD, L1 disease was linked to elevated S1PR1 monocyte expression as compared to patients with L2/L3 (p=0.002). No link with CD disease behaviour could be demonstrated.

Conclusion
Besides lymphocytes, monocytes do express S1PR in patients with IBD. The clinical consequences and the potential link with efficacy of S1PR modulators should therefore be further explored, especially given the heterogeneity of S1PR expression on circulating cells in IBD patients.
P129 Intestinal ultrasound at week 12 predicts long-term endoscopic response to biologics in ulcerative colitis
Authors: Allocca M , Dell'Avalle C , Furfaro F , Zilli A , Radice S , D'Amico F , Peyrin-Biroulet L , Fiorino G , Danese S 
Published: January 2023

Abstract

Background
Intestinal ultrasound (IUS) is accurate to assess endoscopic activity in ulcerative colitis (UC). The Milan ultrasound criteria (MUC) is a validated scoring system to assess and grade endoscopic activity in UC. The most accurate cutoff value for MUC was &gt; 6.2 for endoscopic activity (defined as a Mayo endoscopic score, MES ≥ 2). The aim of this study was to assess the predictive value of IUS and MUC for treatment response in a longitudinal cohort, using colonoscopy (CS) as reference standard.

Methods
Consecutive active UC patients starting biologic therapy were included. All patients underwent CS, IUS, clinical and faecal calprotectin (FC) evaluations prior commencing a biological therapy, and within one year (mean 9.4 months). In addition, patients were evaluated by IUS, clinical and FC assessments at week 12. The primary objective was to evaluate whether ultrasound improvement (defined as MUC ≤ 6.2) at week 12 predicted endoscopic improvement at reassessment (defined as MES ≤ 1). Endoscopic remission was defined as MES = 0.

Results
Forty-nine patients were included (59% under infliximab, 29% under vedolizumab, 8% under adalimumab, 4% under ustekinumab). MUC and MES correlated at reassessment (r= 0.767, p &lt; 0.001). Ultrasound improvement at week 12 was the only independent predictor for MES ≤ 1 and MES = 0 at reassessment (OR 5.80, p = 0.010; OR 10.41, p = 0.041; respectively). Ultrasound improvement at week 12 showed NPV of 96% for detecting MES = 0. A ≥ 2 reduction of the MUC score predicted MES=0 (area under the curve, AUC 0.816). MUC ≤ 4.3 was the most accurate cut-off value for MES = 0 (AUC 0.876). The responsiveness ratio of Guyatt for the MUC was 1.73 and the standardized effect size ratio was 1.6. Both these values &gt; 0.8 indicate a large effect of responsiveness for the MUC.

Conclusion
MUC is highly accurate to monitor treatment response. Ultrasound improvement after the induction period may predict long-term endoscopic response. The MUC may be used both in clinical trials and routine practice.
P145 Phenotypic progression of Crohn’s disease : assessment of risk factors in a Tunisian population
Authors: Ben Safta N , Ben Mustpha N , Khemiri W , Serghini M , Laabidi S , Fekih M , Labidi A , Boubaker J 
Published: January 2023

Abstract

Background
Phenotype progression in patients with Crohn’s disease (CD) is common, but its risk factors vary between studies. The knowledge of these factors at diagnosis help to identify patients with high risk to progression. These patients should be given aggressive treatments given early in the disease course. The aim of our study was to evaluate the long-term behavioral course of Crohn's disease and to determine predictive factors for phenotypic progression.

Methods
We conducted a retrospective, descriptive study including patients with Crohn's disease that were managed at our department, over a 9-year period [January 2011 - January 2020]. Patients with less than 2 years of follow-up were excluded. We screened for factors associated with phenotypic progression during follow-up by a univariate study. By binary logistic regression, we sought for factors independently related to phenotypic progression, including variables that had a p &lt;0.2 in univariate study.

Results
We included 341 patients with a sex ratio of 1.05. The median age at diagnosis of CD was 31 years. Smoking was observed in 36.4% of patients and 16.5% were alcohol users. Forty-four patients (12.9%) had a family history of Inflammatory Bowel Disease and 5.3% had associated autoimmune diseases. The mean BMI of the patients was 20.57 ± 4.5 kg/m². Seventy-six patients were at least overweighted at the time of diagnosis. The disease was classified as ileal, colonic and ileocolic in 150, 86 and 99 patients respectively. The involvement of the upper gastrointestinal (GI) tract was noted in 49 patients (14.36%) and 84 patients (24.6%) had perineal lesions mainly complex fistulas (17.3%). CD was initially classified as inflammatory, stricturing and fistulizing in 71%, 17% and 11% respectively. Phenotypic progression during follow-up was observed in 33 patients (9.6%), finally classifying the disease as inflammatory in 41%, stricturing in 22% and fistulizing in 35% of cases. In univariate study, the factors associated with phenotypic progression were represented by isolated ileal location (p=0.028, OR=2.28), the presence of perineal fistulas (p=0.006, OR=3.07) and hypoalbuminemia at diagnosis of less than 27.94g/L (p=0.035). Extensive ileal involvement and the presence of granuloma on histology were not associated with phenotypic progression. In multivariate study, only initial upper GI tract’s involvement was an independent predictor of phenotypic progression (p=0.024. OR=0.11, IC[0.18-0.75]).

Conclusion
Our study showed that upper GI tract’s involvement was the main predictor of phenotypic progression in CD.
P160 Influence of sarcopenia on perioperative management and postoperative outcome in patients with Crohn’s Disease undergoing intestinal surgery: a retrospective study
Authors: O'Neill C , Haenen S , Coudyzer W , Bislenghi G , D'Hoore A , Verstockt B , Ferrante M , Vermeire S , Sabino J 
Published: January 2023

Abstract

Background
Sarcopenia (loss of skeletal muscle mass and/or strength) is a predictor of postoperative morbidity in various surgical populations. We evaluated the impact of sarcopenia in postoperative outcomes after intestinal surgery in patients with Crohn’s disease (CD) at a tertiary referral centre.

Methods
This is a retrospective analysis of all patients with CD undergoing intestinal surgery at our centre, between January 2013 and September 2019 with available abdominal computed tomography images within 90 days before surgery. The images were assessed for sarcopenia according EWGSOP2 criteria (Skeletal Muscle Index &lt;39 cm2/m2 for female and &lt;55 cm2/m2 for male) and visceral and subcutaneous fat areas. All patients were coded for postoperative complications using the Clavien–Dindo classification system.

Results
A total of 114 patients with Crohn’s disease were included (table 1 and 2). The prevalence of sarcopenia was 67.5%. Common intestinal procedures were ileocecal resections (49%), segmental small-bowel resections/stricturoplasty (6.1%), and colon resection (8.8%). Sarcopenic patients have more frequently penetrating phenotype than patients without sarcopenia (p=0.007). Body mass index and serum albumin levels were significantly lower (p&lt;0.001 and p=&lt;0.037, respectively) and C-reactive protein levels were significantly higher (p=0.014) in sarcopenic patients compared to non-sarcopenic patients. Furthermore, both visceral and subcutaneous fat were significantly lower (both p&lt;0.001) in patients with sarcopenia. ICU admission, rates of postoperative complications within 30 days, infections, reoperation and re-hospitalization were not significantly different between sarcopenia and non-sarcopenia groups. However, there was a trend of a longer length of hospital stay (p= 0.062) in patients with sarcopenia. Sarcopenic patients received significantly more preoperative and postoperative parenteral nutrition (p=0.006 and p=0.035, respectively) and protective ileostomy (p=0.025) compared with patients without sarcopenia.

Conclusion
The prevalence of sarcopenia based on EWGSOP2 criteria is high in patients with CD requiring bowel resection. In this cohort, sarcopenia was not linked to higher rate of postoperative complications, although this might be explained by different surgical procedures and nutrition management before and after surgery for CD.
P174 Uncontrolled depression and female gender increase the risk of severe fatigue in patients with inflammatory bowel disease under infliximab therapy.
Authors: Ferreiro Iglesias R , Calvino-Suarez C , Baston-Rey I , Mauriz-Barreiro V , Dominguez-Munoz J E , Barreiro-de Acosta M 
Published: January 2023

Abstract

Background
Fatigue is a significant predictor of worst health-related qualify of life in inflammatory bowel disease (IBD) patients. Nevertheless, the role of fatigue in IBD patients under infliximab (IFX) therapy has been poorly investigated. The aim of the study was to evaluate the potential factors associated with fatigue in patients under maintenance treatment with IFX.

Methods
A prospective observational cohort study was designed. All IBD patients aged 18 and over under maintenance treatment with intravenous (IV) infliximab were consecutively included at the infusion day. Patients completed 3 self administered questionnaires. Fatigue was assessed with the Fatigue Impact Scale (FIS), quality of life with the Inflammatory Bowel Disease Questionnaire-Short From (IBDQ-9) and anxiety and depression using the Hospital Anxiety and Depression scale (HAD). We considered the maximum total FIS as the highest fatigue perception. Disease activity was defined in Crohn’s disease as a Harvey-Bradshaw index &gt;4, and in ulcerative colitis (UC) as a Partial Mayo index &gt;2. Patient demographics and disease characteristics were also collected: age, sex, disease duration, smoking habit, type of IBD, extra-intestinal manifestations, clinical activity, prior surgery, obesity, anemia, treatments (steroids, immunosuppressants, anxiolytics, antidepressants) and presence of anxiety or depression. Multiple linear regression was used to identify the variables associated with the presence of fatigue.

Results
Ninety patients were consecutively included (49 female, median age 42 years, interquartile range 19). Sixty three patients (70%) had Crohn’s disease (46.8% fistulising and 25.8% stenosing behaviour) and twenty seven ulcerative colitis (30%). Nearly 27% were smokers, 35 (39%) presented anxiety and 18 (21%) depression. Approximately, 8% of the patients and 7% received treatment for anxiety and depression, respectively, but only 2/18 patients with current depression received antidepressants. Combotherapy was present in 41% of the patients and 75.6% were in clinical remission. Mean fatigue was 32.74 ± SD 17.27. The highest scores for fatigue were associated with female gender (B = 10.936; P= 0.009) and the presence of depression (B = 11.114; P = 0.029). Activity disease almost increased significantly the severity of the fatigue(B = 8.995; P= 0.063). The use of antidepressants not increased the risk (B = -4.995; P = 0.555). Patients with fatigue had significantly reduced the quality of life (r = -0.638; p &lt; 0.001) (Figure 1).

Conclusion
Uncontrolled depression and female gender increased the risk of severe fatigue more than disease activity in patients under maintenance treatment with IFX. Fatigue is related to worst health-related qualify of life.
P180 Ileorectal anastomosis preserves female fertility after colectomy in Ulcerative Colitis
Authors: Druvefors E , Myrelid P , Andersson R E , Landerholm K 
Published: January 2023

Abstract

Background
Colectomy and reconstruction in patients with inflammatory bowel disease (IBD) may adversely affect fertility, but few population-based studies are available.

Methods
Fertility was assessed in 2,989 women and 3,771 men with IBD and prior colectomy 1964-2014, identified from the Swedish National Patient Register, and 35,092 matched population-based individuals.

Results
Reconstruction with ileoanal pouch anastomosis (IPAA) was as common as ileorectal anastomosis (IRA) in ulcerative colitis (UC) and IBD-unclassified (IBD-U) while rare in Crohn’s disease (CD). Compared with the matched non-IBD cohort, women with IBD had lower fertility overall post colectomy (HR 0.65, CI 0.61-0.69). The impact was least in patients with colectomy only with the rectum left intact (HR 0.79, CI 0.70–0.90) and more pronounced after reconstructive surgery. Comparing the surgical options within the cohort of women with colectomy for IBD using colectomy only as reference, fertility in female patients remained unaffected after IRA (HR 0.86, CI 0.63-1.17 for UC, 0.86, CI 0.68-1.08 for IBD-U and 1.07, CI 0.70-1.63 for CD), but was impaired after IPAA, especially in UC (HR 0.67 CI 0.50-0.88), and after completion proctectomy (HR 0.65, CI 0.49-0.85 for UC, 0.68, CI 0.55-0.85 for IBD-U and 0.61, CI 0.38-0.96 for CD). In men, fertility was marginally reduced in the entire cohort post colectomy (HR 0.89, CI 0.85-0.94), regardless of reconstruction.

Conclusion
Fertility was reduced in women after colectomy for IBD. The least impact was seen with a deviated rectum left in situ. IRA was associated with no further reduction in fertility, whereas proctectomy with or without IPAA were associated with the strongest impairment. IRA therefore seems to be the preferred reconstruction to preserve fertility in selected female patients. Fertility in men was only moderately reduced after colectomy and reconstructive choice.
P193 Predicting the middle-term efficacy of molecular-targeted medications for Ulcerative Colitis based on the intestinal ultrasound findings
Authors: Miyoshi J , Morikubo H , Yonezawa H , Kimura Y , Moue C , Komatsu H , Matsuura M , Hisamatsu T 
Published: January 2023

Abstract

Background
Intestinal ultrasound (IUS) is non-invasive and can assess all segments of the colon even in severe ulcerative colitis (UC). While IUS can estimate the endoscopic findings of UC, in terms of the Treat to Target strategy, it remains a crucial clinical question whether the changes in IUS findings with therapeutic interventions can predict the treatment efficacy and the patient prognosis. Here, we investigated if comparing IUS findings at baseline and 3 months after starting a molecular-targeted medication (MTM) can predict the steroid-free clinical remission (SFCR) of UC at 6 months.

Methods
Inclusion criteria were (1) patients with UC who started an MTM as the induction therapy by March 2022 in Kyorin University Hospital, (2) IUS was performed at baseline and 3 months after starting the medication, and (3) patients could be tracked until 6 months after starting the medication. SFCR was defined as Lichtiger index &lt;4 without changing the MTM, performing surgery, and using steroids. The bowel wall thickness (BWT, mm), bowel wall flow (BWF, scored with Limberg score), bowel wall stratification (BWS, intact/unclear/loss), increased echoic level of mesenteric fat around the colon (i-fat, yes/no), and haustration (normal/abnormal) were assessed at the most severely affected segment of the colon. The change of each parameter (Δ) was evaluated based on the sonographic findings at baseline and 3 months. The changing rate of BWT (ΔBWT%) was calculated as ΔBWT%=100 X ([BWT at 3 months]-[BWT at the baseline])/(BWT at the baseline). Milan ultrasound criteria (MUC) and UC-IUS index (UII) were scored based on the sonographic findings. This study was approved by the Institutional Review Board of Kyorin University School of Medicine (IRB No. 1668).

Results
In total 18 cases (ustekinumab: 7, infliximab: 5, vedolizumab: 4, adalimumab: 1, and tofacitinib: 1) were analyzed. IUS was performed at 0 and 88.5 days (median) after starting the molecular-target medications. Fourteen subjects achieved SFCR at 6 months (SFCR+ group). ΔBWT was significantly better in the SFCR+ group (-1.41±2.90) compared to the SFCR- group (1.20±1.31) (p=0.023). The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of ΔBWT for SFCR at 6 months was 0.875. ΔBWT% showed a similar predicting capacity. Apparent sonographic improvements, (1) BWS became intact, (2) i-fat disappeared, and (3) haustration became normal, were observed only in the SFCR+ group. MUC and UII decreased more in the SFCR+ group compared to the SFCR- group, but not statistically significant in the present analysis.

Conclusion
Assessing BWT over time at baseline and 3 months can be a promising index to predict the efficacy of the molecular-targeted medications at 6 months.
P195 Is fecal calprotectin truly valuable in the management of isolated small bowel Crohn’s disease?
Authors: Rafael M A , Bordalo Ferreira F , Oliveira A M , Nassauer Mónica A , Santos L 
Published: January 2023

Abstract

Background
Crohn’s disease (CD) is a complex inflammatory bowel disease (IBD) with different locations and behaviors. Although fecal calprotectin (FC) is recommended [1, 2] and has been used to monitor IBD, clinical practice has raised doubts about its utility in small bowel (SB) CD.
Even though initial studies did not find a role for FC in SB CD, recent literature confirmed its acuity in SB active inflammation [2]. In fact, recent studies have confirmed a correlation between FC values and the degree in inflammatory activity in magnetic resonance enterography (MRE) [3, 4, 5, 6]. However, all these studies included patients with simultaneous colonic disease.
Therefore, we evaluated the role of FC in predicting active inflammation in patients with isolated SB CD.

Methods
40 patients with L1 CD according to Montreal classification [7] who underwent MRE, FC and C-reactive protein (CRP) assessment [maximum time between all exams was 60 days] were included. MRE data included disease location and extension, SB wall thickness and contrast enhancement, presence of SB dilation, fistulous tracts, inflammatory masses or abscesses, mesenteric findings. FC was both evaluated as a continuous variable and divided into 3 categorical variables: &lt; 50 mg/g (“negative”), 50-150 mg/g (“low”) and &gt; 150 mg/g (“high”). CRP was also divided in &lt; 0.5 mg/dl (“negative”), 0.5-1 mg/dl (“low”) and &gt; 1 mg/dl (“high”).
Non parametric tests were used to correlate MRE findings with continuous FC and CRP values and Pearson’s chi-squared test was used to correlate categorical FC and CRP values.

Results
FC values ranged from 0 to 2872 mg/g, with an average of 301 mg/g. 31.7% had “negative”, 24.4% “low” and 43.9% “high” FC values. Table 1 represents MRE findings.
We found a significant statistical correlation between both continuous and categorical FC values with positive mesenteric findings (p=0.0283 and p=0.037), increased bowel wall thickness (p=0.0455 and p=0.039) and presence of stenotic segments (p=0.0193 and p=0.05). All stenosis had signs of active inflammation. We did not find any correlation between FC and disease location or extension, bowel wall contrast enhancement or presence of penetrating disease. CRP values did not correlate with any of MRE findings.

Conclusion
Although imaging exams are essential for initial evaluation and treatment response in ileal disease, FC is a useful tool to evaluate active disease in isolated SB CD with both inflammatory (B1) and stenotic (B2) disease, in predominantly inflammatory stenosis. Our results do not support FC use to monitor penetrating (B3) disease.
P200 Hepatic Steatosis but not Fibrosis is independently associated with poor outcomes in patients with Inflammatory Bowel Disease
Authors: Hyun H K , Lee H W , Jihye P , Park S J , Park J J , Kim T I , Kim W H , Lee J S , Kim B K , Park J Y , Kim D Y , Ahn S H , Kim S U , Cheon J H 
Published: January 2023

Abstract

Background
Increased prevalence of nonalcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) has been reported; however, the effects of NAFLD on the outcome of IBD remains unclear. We investigated whether the presence of NAFLD could influence the outcomes of patients with IBD.

Methods
We recruited 3,356 eligible patients with IBD into our study between November 2005 and November 2020. Hepatic steatosis and fibrosis were diagnosed using hepatic steatosis index (HSI) of ≥30 and fibrosis-4 (FIB-4) of ≥1.45, respectively. Primary outcome was clinical relapse, defined based on the following: IBD-related admission, surgery, or first use of corticosteroids, immunomodulators, or biologics agents for IBD.

Results
Prevalence of NAFLD in patients with IBD was 16.7%. Patients with hepatic steatosis and advanced fibrosis were older, had a higher body mass index, and were more likely to have diabetes (all p&lt;0.05). Multivariate cox regression analysis revealed that hepatic steatosis was independently associated with an increased risk of relapse in patients with ulcerative colitis (UC) (hazard ratio [HR] 1.697, 95% confidence interval [CI] 1.291-2.230; p&lt;0.001) and Crohn’s disease (CD) (HR 1.536, 95% CI 1.130-2.087; p=0.006). Advanced liver fibrosis was not associated with an increased risk of clinical relapse in patients with UC or CD (all p&gt;0.05).

Conclusion
Hepatic steatosis was independently associated with increased risks of clinical relapse in patients with UC and CD, whereas fibrotic burden in the liver was not. Future studies should investigate whether the assessment and therapeutic intervention of NAFLD will improve clinical outcomes of patients with IBD.