bluuebunny/crossref_metadata_2025 huggingface dataset:
P086 Sirtuin 7 inhibitor attenuates colonic mucosal immune activation in mice–potential therapeutic target in Inflammatory Bowel Disease
Authors: Kim S H , Jeen Y T , Jeon H J , Kim E S , Keum B , Chun H J
Published: January 2023

Background

Accumulating evidence has shown that sirtuin 7 (SIRT7), a mediator of various cellular activities, plays an important role in the pathogenesis of various immune-mediated inflammatory disorders. However, information remains limited regarding the role of SIRT7 in intestinal inflammation. We used a murine colitis model to investigate the role of SIRT7 in intestinal immunity and whether SIRT7 inhibitors could attenuate the intestinal inflammatory response.

Methods

Mice were divided into three groups: control, colitis-induced, and SIRT7 inhibitor-treated. A colitis mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin, as in our previous study. Quantitative analyses of inflammatory cytokines and SIRT7 levels in the colonic mucosa were performed to compare the changes in inflammatory responses between the three groups.

Results

The colitis group showed increased levels of inflammatory cytokines and SIRT7 in the colonic mucosa. The inflammatory reaction was suppressed in colitis-induced mice administered SIRT7 inhibitor. The qRT-PCR results showed normalization of inflammatory cytokines in the SIRT7 inhibitor-treated group. Histologic study revealed a decrease in the extent of inflammation after SIRT7 treatment. We also observed that the degree of clinical inflammation was improved in SIRT7-treated mice.

Conclusion

Our study demonstrated that SIRT7 inhibition attenuated the inflammatory response in the colon of mice, suggesting a possible role for SIRT7 in the pathogenesis of immune-mediated intestinal inflammation.
P090 Low-density neutrophils are higher in individuals with active ulcerative colitis
Authors: Mendieta Escalante E A , Barrera-Vargas A , Torres-Ruiz J J , Merayo-Chalico F , Dijkstra G , Faber K N , Yamamoto Furusho J K
Published: January 2023

Background

Introduction: Neutrophils and neutrophil extracellular traps (NETs) play a significant role in the pathogenesis of ulcerative colitis (UC), a chronic and relapsing inflammatory disease of the colon. Low-density neutrophils (LDNs) are a recently identified subset of neutrophils that are more prone to develop NETs and produce more pro-inflammatory cytokines and calprotectin than neutrophils of normal density. Moreover, LDNs show reduced phagocytotic activity towards bacteria. LDNs are subclassified as mature (CD15+CD14-CD10+) and immature (CD15+CD14-CD10-) based on CD10 expression, of which the immature LDNs are most pro-inflammatory. LDNs have been identified in a number of autoimmune diseases, including systemic lupus erythematosus, psoriasis, antineutrophil cytoplasmic antibody-associated vasculitis, and rheumatoid arthritis, but not yet studied in UC.

Objective

Examine the existence of LDNs in UC patients and their possible association to disease severity.

Methods

A total of 13 healthy controls and 20 patients with UC were included. Their clinical activity was evaluated with the Truelove-Witts score. LDNs and subtypes were quantified by flow cytometry in the peripheral blood mononuclear cells (PBMC).

Results

The relative abundance of LDNs was significantly higher in UC patients compared to healthy controls (1.55±1.14 vs. 0.62±0.36 respectively, P<0.05). Moreover, LDNs numbers were higher in UC patients with active disease compared to those in remission (2.67±1.36 vs. 1.09±0.55; P<0.05) (Figure 1). The abundance of immature (CD15+CD14-CD10-) LDNs positively correlated with the Truelove-Witts index (rho=.530, P<0.05) and fecal calprotectin levels (OR=1.2, P<0.05, CI=1-1.36) as illustrated in Figure 2.

Figure 1

Figure 2

Conclusion

LDNs levels are elevated in PBMCs of patients with UC and pro-inflammatory immature LDNs are associated with disease activity.
P107 Decreased epithelial keratinization contributes to defective wound healing in Crohn's disease fistula
Authors: Becker drs. M , Koelink P , Bemelman W , D'Haens G , Buskens C , Wildenberg M
Published: January 2023

Background

Up to 30% of Crohn's Disease (CD) patients suffer from perianal fistula creating a high disease burden. Treating CD fistula is challenging compared to cryptoglandular fistula, which have a significantly better wound healing response. Previous studies suggested epithelial to mesenchymal transition as an inducer of fistula formation, as markers were observed in fistula tracts. However, most studies compared CD fistula to normal mucosa, thus disregarding whether any observed difference was in fact a sign of healing (as CD fistula will have more active healing than uninjured mucosa) or a sign of pathology (as healing is not occurring effectively). Therefore, in this study we evaluated CD fistula, as well as both healthy mucosa (no active healing) and cryptoglandular fistula (effective healing) in order to determine the role of differences found.

Methods

Biopsies from the internal opening (n=20) of perianal fistula of CD patients were collected and compared to two publicly available datasets obtained from un-inflamed rectum (RISK cohort and GSE83245). In addition, curettage material of CD (n=54) and cryptoglandular fistula (n=15) was obtained. Expression profiling was performed using RNASeq.

Results

Comparing the mucosa at the internal opening of CD fistula to publicly available datasets of healthy rectum, 770 genes were differentially expressed. Pathway analysis revealed upregulation of proliferative and inflammatory processes, consistent with expected immune and wound healing responses. Interestingly, strongest upregulation was seen for processes of cornification and keratinization, including expression of IVL (involucrin) and FLGR2 (fillagrin2), involved in keratinocyte differentiation.

To evaluate whether this was contributing to active wound healing or rather to persistent disease, we analyzed the actual tract in CD and cryptoglandular fistula. Strikingly, cornification and keratinization processes were more pronounced in cryptoglandular fistula, suggesting a role in effective healing rather than the persistent pathology seen in CD. Similar data was observed for TGFb, previously detected in CD fistula and thus considered a pathological contributor. While we confirm increased TGFb activity in CD fistula compared to normal mucosa, activity in cryptoglandular fistula tracts was higher than in CD fistula tracts. Again, this would suggest TGFb signaling as part of the wound healing response rather than part of the pathogenic mechanism.

Conclusion

Perianal fistulas show upregulation of keratinization and cornification pathways compared to healthy mucosa. Comparing CD and cryptoglandular fistula, we saw more cornification in the better healing cryptoglandular fistula, suggesting involvement in effective healing rather than pathology.
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

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<2.2E-16), S1PR2 (FC 1.84, p=5.3E-7), S1PR4 (p=2.4, p<2.2E-16) and S1PR5 (FC infinite, p<2.2E-16) compared to monocytes. In contrast, circulating monocytes expressed significantly more S1PR3 (FC infinite, p<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

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 > 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 < 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 > 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

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 <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

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 <39 cm2/m2 for female and <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<0.001 and p=<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<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

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 >4, and in ulcerative colitis (UC) as a Partial Mayo index >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 < 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

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

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 <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

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: < 50 mg/g (“negative”), 50-150 mg/g (“low”) and > 150 mg/g (“high”). CRP was also divided in < 0.5 mg/dl (“negative”), 0.5-1 mg/dl (“low”) and > 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

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<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<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>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.
P205 Impact of histologic disease activity on long-term outcomes in patients with ileal pouch-anal anastomosis for ulcerative colitis
Authors: Gabbiadini R , Spaggiari P , Dal Buono A , Iuzzolino M , Furfaro F , D'Amico F , Repici A , Spinelli A , Armuzzi A
Published: January 2023

Background

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) can incur in several complications like pouchitis leading to the need of immunosuppressive therapy, hospitalization and pouch failure. Unlike non-operated UC patients, therapeutic goals are an unmet need in UC-IPAA patients and the impact of the histologic activity on the development of complications is unknown. The aim of the study was to assess the association between histology and the risk of long-term negative outcomes in UC subjects with IPAA.

Methods

This is a single-center, retrospective study which included UC adult patients with IPAA undergoing at least one pouchscopy with biopsies in the pouch body after ileostomy closure. Pouch biopsies were blindly reviewed by a gastrointestinal pathologist with expertise in IBD. Histologic disease remission was defined as a Pouchitis Disease Activity Index (PDAI) histology subscore £ 1. Negative outcomes were: IPAA related complications (acute or chronic pouchitis, hospitalization, pouch failure) and escalation of medical therapy (start of immunosuppressive or biologics). Both descriptive and inferential statistical analyses carried out

Results

A total of 66 patients were included (male n=37; 56,1%) of whom 40,9% (n=27) had histological activity at the baseline pouchscopy. The characteristics of the study population are represented in table 1. The median time of follow up was 38,5 months (range 12-151). During the study period, 27 patients (40,9%) developed acute pouchitis and 10 patients (15,2%) chronic pouchitis. Thirty-nine subjects (59,1%) required antibiotic therapy while 8 subjects required systemic steroids (12,1%). Furthermore, 15 patients (22,7%) started immunomodulatory therapy with either azathioprine or biologic agents. Six patients (9,1%) needed pouch-related hospitalization and 1 patients (1,5%) experienced pouch failure. Chronic pouchitis and the need of immunosuppressive/biology therapy was observed more frequently in patients with pouch histologic activity (29,6% vs. 5,1%, and 40,7% vs. 10,3%, respectively) (P<0.05). After adjusting for risk factors for pouchitis, the presence of histologic activity remained an independent risk factor for developing acute pouchitis (OR 4.10, 95% CI 1.39-12.04; P= 0.010), chronic pouchitis (OR 8.51, 95% CI 1.51-47.80, P=0.015) and the need for immunosuppressive or biologic therapy (OR 6.98, 95% CI 1.69-28.80; P=0.007).

Conclusion

Histologic activity was associated with an increased risk of developing both acute and chronic pouchitis and with the need for immunosuppressive/biologic therapy. Future research will clarify whether histologic remission might be considered as a therapeutic target for UC-IPAA patients developing pouchitis.
P216 Oral Budesonide and low serum albumin levels at surgery are associated with a higher risk of postoperative intra-abdominal septic complications after primary ileocecal resection for Crohn’s disease: a retrospective analysis of 853 consecutive patients treated in a tertiary centre.
Authors: Dajti G , Cardelli S , Rizzello F , Gionchetti P , Poggioli G , Rottoli M
Published: January 2023

Background

Patients undergoing ileocecal resection for Crohn’s disease (CD) are at high risk of postoperative intra-abdominal septic complications (IASC). The associated risk factors are still debated. The aim of the study was to identify the variables associated with IASC in patients treated for primary CD of the terminal ileum.

Methods

Retrospective single-centre study including consecutive patients undergoing ileocecal resection for CD between 2004-2021 and managed before surgery in a multidisciplinary IBD unit.

Outcomes

to identify the variables associated with IASC (primary aim) and severe complications, classified as Clavien-Dindo grade 3 and higher (secondary aim).

The potential independent predictors of each outcome were evaluated using logistic regression. To reduce overfitting, all models were built including only the variables that were significant at univariate analyses, except for age, gender and history of cardiovascular diseases, that were included a priori. Standard diagnostic procedures were adopted to check all models validity: influential observation analysis (Dbeta, change in Pearson chi-square), Hosmer-Lemeshow test for the goodness of fit and C statistic (area under the Receiving Operator Curve).

Results

A total of 853 patients were included. Overall sample characteristics are shown in Table 1.

Table 2 and Table 3 reported the comparison according to the primary (IASC) and secondary (severe complications) outcomes, respectively.

Table 4 showed the multivariate analyses of the potential predictors of IASC and severe complications.

The onset of IASC was associated with lower serum albumin level (OR 1.81, 95% CI 1.15-2.94, p=0.011) and the use of oral budesonide at time of surgery (OR 2.07, 95% CI 1.12-3.83, p= 0.021). The risk of severe complications was associated with a history of cardiovascular disease (OR 2.91, 95% CI 1.08-7.84, p=0.03) and lower serum albumin level (OR 1.58, 95% CI 1.02-2.50, p=0.04).

Conclusion

The present study analysed a large population of patients affected by CD of the terminal ileum who were treated homogeneously before surgery in a multidisciplinary setting and confirmed the significant impact of preoperative nutritional status on the risk of severe postoperative complications and IASC. The latter, however, was also associated with the use of oral budesonide at the time of surgery. This finding has not been previously reported in the literature. Based on the present evidence, oral budesonide should be discontinued or tapered to the lowest dose before surgery.
P224 Diagnostic delay in inflammatory bowel disease is not associated with difficult access to healthcare facilities: a clinical study on incidental cases
Authors: Cantoro L , Monterubbianesi R , Camastra C , Falasco G , Pantanella P , Cosintino R , Faggiani R , Fiorino G
Published: January 2023

Background

Diagnostic delay is a challenge in inflammatory bowel disease (IBD), more in Crohn’s disease (CD) than in ulcerative colitis (UC). Whether difficult access to healthcare facilities may be a cause of diagnostic delay is debated. Restrictions due to SARS-COV2 pandemic have impacted on the prompt access to hospitals and clinics during 2020. We aimed to investigate if those limitations impacted on diagnosis, presence of IBD-related complications, and the number of hospitalization and surgeries by the first 12 months after diagnosis.

Methods

We retrospectively analysed all consecutive patients who had access to our tertiary referral centre in Rome, Italy in the period between January 1st, 2019 and December 31st, 2021. We split all patients in three study groups: those who had diagnosis of IBD in 2019 (normal setting, control group), 2020 (severe restrictions for access to our clinic), and 2021 (intermediate restrictions). Delay from symptoms to diagnosis, presence of IBD-related complications at diagnosis, need for hospitalization and/or surgery at diagnosis, and hospitalization and surgery rates in the first 12 months since diagnosis were collected and analysed. Statistically significant differences were set as per p value <0.05.

Results

Overall, 6,125 patients accessed to our department in 2019, 4,594 in 2020, and 6,063 in 2021. In the entire period, 89 patients were diagnosed with IBD (17 CD and 14 UC in 2019, 12 and 10 in 2020, and 17 and 19 in 2021). Baseline characteristics are listed in Table 1. Median delay between symptoms and diagnosis did not statistically differ among the 3 groups (7 months in 2020, and 2 months in 2021, compared to controls, p=0.07 and p=0.24 respectively), and among CD and UC patients (p=0.30). No differences were found in hospitalisation at diagnosis (p=0.90 for 2020, and p=0.66 for 2021 compared to controls), and in the rates of IBD-related hospitalization and surgery in the following 12 months since diagnosis (p=0.41 for 2020, 0.81 for 2021 compared to controls). No significant associations were found between CD and UC patients, and no significant association was found between sex, age, type of disease, and localisation of the disease at diagnosis and 12-month outcomes.

Conclusion

Although on a small population, difficulties in accessing to hospital did not impact on diagnostic delay and further disease course in IBD patients. Further investigation on factors associated with diagnostic delay is needed.
P228 Machine learning models utilizing simple laboratory tests may assess endoscopic activity in ulcerative colitis
Authors: Kempinski R , Kraszewski S , Nizioł P , Neubauer K
Published: January 2023

Background

Together with the implementation of innovative therapies for inflammatory bowel disease, mucosal healing (MH) became the novel therapeutic goal. Currently, a golden standard for evaluation of the colonic mucosa is an invasive and expensive colonoscopy. We propose here a machine learning (ML) based model as a noninvasive tool trained on biochemical patient data. Employed random forest technique used aggregation and randomization of predictors constituted of biochemical tests to accomplish a high degree of predictive accuracy reaching 95%. SHapley Additive exPlanations (SHAP) known from cooperative game theory were used to boost the interpretability of ML model based on additive feature importance across all possible predictors in the feature space.

Methods

The study group consisted of 252 ulcerative colitis patients hospitalized in theDepartment of Gastroenterology and Hepatology, Wroclaw Medical University. Routine laboratory test results and colonoscopy reports with the Mayo scores were collected. The data were processed with different ML classifiers. The most performant model was the random forest classifier. Then the SHAP model for the importance of consecutive clinical data was calculated.

Results

We found a set of particular biochemical predictors. Total protein, C-reactive protein, creatinine, and fecal calprotectin had the most significant impact on the prediction of endoscopic Mayo score, as shown in Figure 1.

Conclusion

Novel numerical models may predict the endoscopic activity of ulcerative colitis based on simple biochemical tests.
P237 Superior predictive value of intestinal ultrasound over endoscopic severity for colectomy risk in patients with ulcerative colitis
Authors: Piazza N , Noviello D , Filippi E , Conforti F , Furfaro F , Fraquelli M , Fiorino G , Danese S , Allocca M , Caprioli F
Published: January 2023

Background

Up to 15% of patients with ulcerative colitis (UC) do not respond to medical therapies and ultimately require colectomy for disease control. Baseline endoscopic severity and failure to achieve endoscopic healing, as defined by a Mayo Endoscopic Subscore (MES) ≤ 1, following therapy have been associated with an increased risk of colectomy. Intestinal ultrasound severity, as defined by a Milan ultrasound criteria (MUC) score > 6.2, has been associated with an increased risk of colectomy. The aim of this study is to evaluate and compare MES and MUC in predicting the need for colectomy in patients with UC.

Methods

This is a double-center prospective observational cohort study. All consecutive adult UC patients between January 2016 and January 2020 requiring colonoscopy received intestinal ultrasound within 20 ± 12 days in a blinded fashion. Colectomies were evaluated during the follow-up. Univariable and multivariable Cox regression analyses were used to identify variables independently associated with colectomy risk. ROC analysis was used to compare baseline MES and MUC scores' performances in predicting colectomy.

Results

A total of 141 patients were enrolled (Table 1). Overall 13 patients underwent colectomy during 256.41 person-years of observation time. At baseline, patients requiring colectomy had increased mean values of MUC as compared to patients not undergoing surgery (6.84 ± 2.49 vs 10 ± 1.9, p <0.001). At univariate analysis, MES (HR: 3.15, 95% CI:1.18 – 8.37, p = 0.02) and MUC (HR: 1.48, 95% CI:1.19 – 1.76, p <0.001) were associated with colectomy risk. At multivariable analysis, MUC but not MES was associated with colectomy risk (HR: 1.46, 95% CI: 1.06 – 2.02, p 0.02). As compared with MES, MUC score demonstrated a higher AUROC (0.83, 95% CI: 0.75 – 0.92 vs 0.71 95% CI: 0.62 – 0.80) and better performance for assessing the need for colectomy (p = 0.02) (Figure 1). The optimal MUC score cutoff for predicting colectomy, as assessed by the Youden index, was 7.72, with a sensitivity and specificity of 1 and 0.6, respectively.

Conclusion

Ultrasound severity, as assessed by the MUC score, is superior to endoscopic severity in predicting the need for colectomy in patients with UC. A baseline MUC score of < 7.72 may rule out colectomy risk in UC patients.
P250 The impact of Primary Sclerosing Cholangitis (PSC) on fecal calprotectin assessment in individuals with Inflammatory Bowel Disease (IBD)
Authors: Arar A , Scott F , Click B , Fennimore B , Ahmed W , Oonk A , Gerich M
Published: January 2023

Background

Fecal calprotectin (FCP) is recommended as a non-invasive biomarker in ulcerative colitis (UC); however, the accuracy of FCP in individuals with concurrent primary sclerosing cholangitis (PSC) is less understood due to biliary fluid calprotectin excretion in PSC. We aimed to determine the relationship of endoscopic disease activity to FCP levels in individuals with PSC and colitis (PSC-IBD) compared to individuals with UC alone.

Methods

Individuals with PSC-IBD and UC controls who underwent colonoscopy at a large tertiary academic medical center. Controls with similar UC extent were selected in a 2:1 ratio. Mayo endoscopic scores (MES) were derived from the endoscopic database. If no prospective score was recorded, images were reviewed by two investigators with adjudicated discrepancies. Disease characteristics, baseline demographics, FCP (within 6 months of endoscopy), and C-reactive protein (CRP) were derived from the electronic medical record. Exclusion criteria included Crohn's disease or non-IBD colitis, infectious colitis, treatment change between endoscopy and FCP measurement, and colonic resection. Mean FCPs and standard deviations (SDs) were calculated, stratified by PSC status and MES. Multivariable linear regression was employed to assess the association of PSC on FCP adjusting for MES, age, alkaline phosphatase (ALP), and disease location.

Results

264 colonoscopies for 197 patients (mean age 48, 61% males, 97% extensive disease) were identified with corresponding FCP from 2013 to 2022. Compared to UC controls, there were more males in the PSC-IBD cohort; MES did not differ significantly between the two groups (Table 1). There was no significant difference in mean FCP in PSC-IBD compared to UC controls (314.7 vs 284.5, p=0.56). Mean FCP increased with increasing MES (Table 2). There was no significant difference in mean FCP between those with PSC and those without when stratified by MES (Table 3). In multivariable linear regression, left-sided disease extent, MES, and ALP were independently associated with increasing FCP (Table 4).

Conclusion

In this cohort, a diagnosis of PSC was not associated with significant differences in FCP for IBD patients when stratified by MES. These data suggest that FCP remains a reliable marker of colitis activity in IBD patients with and without PSC. Further research is required to understand the role of PSC activity in modulating FCP concentrations.