bluuebunny/crossref_metadata_2025_split huggingface dataset:
P150 Increased risk of ibd flare after sars-cov-2 infection. who’s the more guilty: viral infection or therapy withdrawal?
Authors: Bezzio C , Guarino A D , Fiorino G , Armuzzi A , Ribaldone D G , Furfaro F , Pugliese D , Vernero M , Variola A , Gerardi V , Scucchi L , Viganò C , Caprioli F A , Roselli J , Coppini F , Ardizzone S , Onali S , Zingone F , Daperno M , Cortellezzi C , Carparelli S , Soriano A , Manes G , Saibeni S 
Published: January 2022

Abstract

Background
In the last year, the severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has spread rapidly around the world. The interactions between SARS-CoV-2 and inflammatory bowel disease (IBD) are so far not fully understood. In particular, no studies evaluated the potential role of SARS-CoV-2 on IBD course. Indeed, it is known that viral infections can be act as triggers for IBD flare and it is reasonable that the possible drug discontinuation during SARS-CoV-2 infection could in turn lead to an IBD flare.

Methods
This was a prospective, observational case-control study. From March 11th 2020 to June 30th 2020 we enrolled IBD patients with proven SARS-Cov-2 infection (“cases”) and IBD patients without SARS-CoV-2 infection matched for sex, age, diagnosis, therapy and clinical activity (“controls”). Cases and controls were followed-up at least for 6 months. Differences between case and control group were tested for significance using the Student’s t test and Fisher’s test, as appropriate. A two-tailed p value &lt; 0.05 was indicative of statistical significance.

Results
219 IBD patients (127 UC, 58.0%) with SARS-CoV-2 infection and 219 IBD patients without SARS-CoV-2 infection were enrolled. Table 1 shows baseline features of the population. Among the 122 cases in clinical remission at the time of viral infection, 28 (22.9%) showed a disease flare; this percentage was significantly higher than that observed in controls: 12/137 (8.8%)(p=0.0018). Among patients with disease flare, there were no significant differences between cases and controls group in terms of age (42.3 ± 16.0 vs. 43.1 ± 15.4 years, p=0.44), gender (female 45.7% vs. 48.2%, p= 0.54), use of biologic therapies (p=0.83) and UC or CD diagnosis (p=0.06). Biologic therapy was temporary withdrawn more significantly in cases than in controls (68/202, 33.6% vs. 14/204, 6.9%) (p&lt;0.001) and overall biologic therapy discontinuation was significantly associated with disease flare (OR 2.56, 95% CI 1.02–6.41, p=0.04).

Conclusion
IBD patients with SARS-CoV-2 infection have an increased risk to have a clinical recurrence in short-term in comparison with IBD patients without SARS-CoV-2 infection. This increased risk could be due to the viral infection and/or to the temporary discontinuation of biologic therapies, because of infection.
P168 Matrix Gla protein, a potential marker of tissue remodelling and physiological ageing of the gut in Crohn’s Disease
Authors: Vieujean S , Delanaye P , Seidel L , Cavalier E , Pierre N , Louis E 
Published: January 2022

Abstract

Background
Matrix Gla protein (MGP) is an extracellular matrix protein. The inactive dephosphorylated and uncarboxylated form of this protein, called dp-ucMGP, has been shown to be increased in plasma of Crohn’s disease (CD) patients compared to non IBD patients (Brnic et al., 2020). Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity and could be a potential marker of mucosal healing in CD.

Methods
The plasmatic level of dp-ucMGP was measured in a blood sample collected the same day as the ileocolonoscopy by CLIA method using IDS-iSYS InaKtif MGP. In addition to classical clinical data (gender, age, body mass index or BMI, disease duration, IBD treatment), endoscopic (disease localisation, Crohn’s Disease endoscopic index or CDEIS, as well as the presence of erythema, ulcer, oedema, pseudopolyp, stricture) and biological (C-reactive protein or CRP) parameters were collected as well as faecal calprotectin to assess CD activity.

Results
A total of 82 colonoscopies and dp-ucMGP assays were performed in 75 CD patients (44 females and 31 males; 43 colonic diseases, 22 ileal diseases and 19 ileocolic diseases) between October 2012 and November 2019. Out of the 82 performed colonoscopies, 22 showed a mucosal healing. Although MGP level was significantly correlated with CDEIS (r=0.21, p=0.040), it was neither associated with endoscopic remission (737 ± 205 pmol/L for patients in endoscopic remission vs 809 ± 332 pmol/L for those who were not, p=0.37), nor correlated with faecal calprotectin (r=0.074, p=0.51) or with CRP (r=0.12, p=0.27) levels. Plasma MGP levels increased significantly with age (r=0.38, p=0.0004) and disease duration (r=0.37, p=0.0006) but not with the BMI (r=0.045, p=0.69). Patients on corticosteroids at the time of colonoscopy had a higher level of MGP (1065 ± 531 pmol/L vs 729 ± 179 pmol/L, p=0.0003). There was no association with other treatments (5-ASA, immunomodulators, anti-TNF, anti-α4β7 integrin or anti-IL-12/IL-23 p40 monoclonal antibody). Regarding endoscopic CD lesions, MGP values were significantly higher in cases of oedema (1153 ± 628 pmol/L vs 766 ± 261 pmol/L, p=0.019) and pseudopolyps (1099 ± 569 pmol/L vs 766 ± 264 pmol/L, p=0.018) but there was no association with the presence of other lesions.

Conclusion
The significant increase of plasmatic MGP levels with age, disease duration but also in patients with pseudopolyps suggests that this extracellular matrix protein could rather be a marker of tissue remodelling (not necessarily stricturing) and physiological ageing of the gut in CD than a marker of disease activity. The relevance of the plasmatic dosage of this protein to assess CD bowel damages deserves to be further investigated.
P179 Distinct ultrasound characteristics of the appendix in patients with ulcerative colitis: a prospective, cross-sectional cohort study
Authors: Reijntjes M , de Voogd F , Bemelman W , d’Haens G , Buskens C , Gecse K 
Published: January 2022

Abstract

Background
Increasing evidence suggests a role for the vermiform appendix in onset and relapse of ulcerative colitis (UC). Consequently, appendectomy is increasingly being seen as a potential alternative treatment. As a recent study suggests that patients with histological appendiceal inflammation are most likely to respond, pre-operative identification of ulcerative appendicitis could be beneficial1. Intestinal ultrasound (IUS) is increasingly utilized in the diagnosis and follow-up of patients with UC. The objective of this study was to characterize the appendix by IUS in UC patients with active and quiescent disease and healthy controls.

Methods
In this cross-sectional prospective observational cohort study, we performed appendiceal IUS on UC patients with active (A) disease (FCP&gt;250 and SCCAI&gt;5) and quiescent (Q) disease (FCP&lt;150 and SCCAI&lt;5), followed by age-, body mass index- and gender- matched healthy (H) controls. During IUS, the appendix was identified as a bowel structure with cecal origin and a blind-ending tip. IUS still images and cineloops were centrally and blindly read by an IUS expert (&gt;1000 examinations). Primary outcomes were signs of appendicitis on IUS, defined as a &lt;6 mm transverse appendiceal diameter3 (average of a cross-sectional and longitudinal measurement), hyperaemia (using the modified Limberg score2), presence of peri-appendiceal fat and fluid, and compressibility.

Results
Out of 95 (A n=35, Q n=30, H n=30) included patients, the majority (n=58, 61.1%) had a visible appendix on IUS, which was similar among cohorts (p=0.56). The appendiceal diameter measured &gt;6.0mm in a significantly higher proportion of active UC patients (A: 45.5%, Q: 5.6%, H: 0.0%, p=0.01). An increased diameter occurred irrespective of disease extent (42.9% of E1/E2 endoscopic active patients). Although the appendiceal diameter was higher for UC patients (Q-H p= 0.02, A-H p&lt; 0.01), no significant difference between A and Q patients was found (p=0.15, Fig. 1). A higher proportion of UC patients had incompressibility when compared to healthy controls (Fig. 2a, p= 0.02). Hypervascularity was present in 54.5% of active UC (Fig. 2b, p= 0.02).
Fig 1. Box plot of appendiceal diameter (mm) among cohorts

Fig 2 (a, b). Bar charts of incompressibility (a) and hypervascularity (b) among cohorts
a

b

Conclusion
Appendiceal IUS was feasible in UC patients. Characteristics of appendiceal inflammation of IUS were reported for UC patients, as both the transverse appendiceal diameter and incompressibility rates were significantly higher in UC patients when compared to healthy controls. Correlating appendiceal IUS findings to histological inflammation could contribute to identifying UC patients most likely to benefit from appendectomy.
P184 Relationship Between Patient Sex and Serum Tumor Necrosis Factor Antagonist Drug and Anti-Drug Antibody Concentrations in Inflammatory Bowel Disease; A Nationwide Cohort Study
Authors: Shehab M , Alasfour H , Abdullah I , Alhendi G , Alhadab A , Alfadhli A , Ziyab A , Battat R 
Published: January 2022

Abstract

Background
Anti-drug antibodies to infliximab (ATI) and adalimumab (ATA) are associated with loss of response to tumor necrosis factor antagonist (anti-TNF) therapy in inflammatory bowel disease (IBD). We evaluated the relationship between patient sex and serum TNF antagonist drug and antibody concentrations in inflammatory bowel disease

Methods
A nationwide multicenter retrospective cohort study was conducted by evaluating patients’ charts from July 2018 until September 2021. The effect of patient sex on anti-drug antibodies and serum drug concentration in patients with IBD across 7 hospitals was investigated. A subgroup analysis also investigated the effect of anti-TNF combination therapy. Geometric means were calculated, and multiple linear regression was used to estimate the adjusted ratio of geometric means (RoGM) and their 95% confidence intervals (CI).

Results
In the total study sample (n = 1093), males receiving infliximab had higher anti-drug antibody concentrations (38.3 vs. 22.3 AU/ml; aRoGM = 1.72, 95% CI: 1.30–2.27, p-value &lt;0.001) compared to females. Additionally, infliximab serum drug concentrations among males were lower compared to females (2.6 vs. 4.1 ug/ml; aRoGM = 0.62, 95% CI: 0.44–0.88, p-value = 0.007). In the subgroup analysis (n = 359), male compared to female patients on combination therapy with infliximab and immunomodulators had similar anti-drug antibody concentrations (30.2 vs. 21.9 AU/ml; aRoGM = 1.38, 95% CI: 0.79–2.40, p-value = 0.254). There was no difference in the anti-drug antibody and serum drug concentrations among males and females on adalimumab.

Conclusion
In patients receiving infliximab, anti-drug antibodies were higher in males than females. Consistent with this, serum drug concentrations were lower in males than females on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among males and females on adalimumab. In addition, no difference in anti-drug antibodies between males and females receiving anti-TNF combination therapy was observed
P196 Pre-treatment antibodies to infliximab and adalimumab are common but are not associated with anti-TNF treatment failure
Authors: Nice R , Goodhand J R , Kennedy N , Ahmad T , Winyard P , McDonald T J 
Published: January 2022

Abstract

Background
Anti-TNF treatment failure is common. Primary non-response and loss of response are frequently caused by low anti-TNF drug levels mediated, principally, by the formation of anti-drug antibodies which can be mitigated by concomitant immunomodulator use.
Previous small studies in patients with IBD suggest that antibodies formed prior to treatment can bind drug and impair the pharmacokinetics, efficacy and safety of the anti-TNF drugs.
We sought to determine the prevalence, neutralising capacity and clinical relevance of pre-treatment antibodies to infliximab and adalimumab in in anti-TNF-naïve patients with active luminal Crohn’s disease.

Methods
The Personalised Anti-TNF Therapy in Crohn’s Disease study (PANTS) is a UK-wide, multicentre, prospective observational cohort reporting treatment failure rates of the anti-TNF drugs infliximab and adalimumab in Crohn’s disease.
The prevalence of antibodies to infliximab and adalimumab at baseline in all patients were measured using IDKmonitor ELISA assays and neutralising capacity in positive cases was determined using the iLite™ cell-based assays. Associations between baseline antibody status, subsequent immunogenicity and drug levels, and response status were assessed using Mann-Whitney U tests and chi-squared analyses, respectively.

Results
In the PANTS cohort, at baseline, pre-treatment anti-TNF antibodies were detected in 7.3% (112/1525) patients. Pre-treatment antibodies to infliximab were more common (6.3% 96/1525 vs 2.4% 36/1525, p&lt;0.01) and of higher levels (median (IQR) infliximab: 23.9 (14.2 – 55.2) AU/ml vs adalimumab: 7.2 (6.3 – 10.4) AU/ml, p&lt;0.0001) than adalimumab. A minority (1.3% (20/1525)) of patients had anti-drug antibody reactivity to both drugs. None of the detected anti-drug antibodies had demonstrable anti-TNF neutralising capacity detected by our iLite™ cell-based assay. No associations were seen between baseline antibody reactivity, subsequent immunogenicity, drug levels or response status at week 14 or week 52.

Conclusion
Pre-treatment anti-drug antibodies are common. However, they do not neutralise anti-TNF drug activity invitro, promote drug clearance or influence clinical response to anti-TNF drugs. Further work is required to understand this cross-reactivity and to determine the exact nature of the antibodies detected in drug naïve individuals.
P214 Plasma fatty acid binding protein 2, interleukin-10 and lipopolysaccharides as biomarkers for microscopic colitis
Authors: Vytautas K , Varkalaite G , Vaitkeviciute E , Arstikyte J , Skieceviciene J , Kupcinskas J 
Published: January 2022

Abstract

Background
The pathogenesis of microscopic colitis (MC) is still poorly understood and there are no non-invasive diagnostic markers to aid in disease diagnosis. Fatty acid binding protein 2 (FABP2) is expressed in enterocytes and colonocytes (although to a lesser extent) and is released after intestinal injury. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is reduced in inflammatory bowel diseases. Lipopolysaccharides (LPS) are bacterial endotoxins that promote inflammation and their presence in systemic circulation represents impaired intestinal barrier function. Our aim was to investigate these compounds as possible non-invasive diagnostic biomarkers for MC and compare their profile between MC and ulcerative colitis (UC).

Methods
63 patients with active MC, 52 healthy controls (HCs), 43 patients with active and 43 with inactive UC were recruited for the study. The presence of active disease was assessed using the Hjortswang criteria in MC and Mayo score in UC patients. Plasma concentrations of FABP2, IL-10 and LPS were measured using Human FABP2/I-FABP Quantikine ELISA Kit (DFBP20; R&D systems, MN, USA), Human IL-10 Quantikine ELISA KIT (D1000B; R&D systems, MN, USA), and Human Lipopolysaccharides (LPS) ELISA Kit (CSB-E09945h; Cusabio, China). Statistical significance of concentration differences between groups was determined using the Mann-Whitney U test.

Results
No significant difference was discovered when comparing the plasma FABP2, IL-10 and LPS concentrations between MC patients and HCs. However, FABP2 concentrations were significantly lower in the plasma of UC patients, both active (median 1272 pg/ml, p = 0,004) and inactive (median 1334 pg/ml, p = 0,001) when compared with MC patients (median 1680 pg/ml). The difference in FABP2 concentration between HCs (median 1365 mg/ml) and active or inactive UC patients did not reach statistical significance.
IL-10 concentrations were significantly lower in patients with active UC (median 2,58 pg/ml) than in MC patients (3,89 pg/ml, p = 0,006) and HCs (median 4,79 pg/ml, p = 0,005). There was no significant difference between MC patients or HCs when compared with inactive UC patients (median 3,04 pg/ml).
The plasma concentrations of LPS were similar across all the patient groups and no significant difference was observed.

Conclusion
Plasma FABP2, IL-10 and LPS did not distinguish MC patients from HCs in our study and did not show potential as biomarkers. Our results of lower plasma IL-10 concentration in patients with active UC show that it could be a useful biomarker for disease activity. It is unclear whether the lower plasma concentration of FABP2 in active UC patients compared to MC patients is important since neither group differed significantly from HCs.
P217 Prevalence of COVID-19 in IBD patients treated with infliximab and vedolizumab in Croatian tertiary center – clinical observation of a case series
Authors: Domislović V , Brinar M , Čukovic-Čavka S , Turk N , Grgić D , Barišić A , Jelaković M , Krznarić Ž 
Published: January 2022

Abstract

Background
The risk of COVID-19 in patients with IBD is considered comparable to general population. However, it has been hypothesized that patients on immunosuppressive therapy could be more susceptible to SARS-CoV-2, mainly due to well-known association of immunosuppressive therapy and increased risk of viral infections. Our aim was to examine the frequency of COVID-19 infection among tertiary center IBD patients treated with biological therapy.

Methods
These are descriptive data including IBD patients on biological therapy which are regularly followed in Croatian referral IBD center at the University Hospital Centre Zagreb, Croatia. Patients on adalimumab were excluded since they are not regularly followed and are receiving therapy at home. SARS-CoV-2 infection was identified as RNA positive nasopharyngeal swab. Disease activity was measured using Harvey-Bradshaw Index (HBI) in CD, partial Mayo score (pMayo) in UC, and CRP. COVID-19 was defined as mild as any of the symptoms consistent with COVID-19 without shortness of breath, dyspnea, abnormal chest imaging and room SpO2&gt;=97%.

Results
Out of total 234 patients on infliximab 15 (6.4%) had COVID-19, which was the case for 3 out of 48 (6.2%) patients on vedolizumab. We have not documented COVID-19 among 67 patients on ustekinumab and 10 on golimumab. Among infected there were 9 patients with CD, 8 UC and 1 IBD unclassified, 61.1% were male and average age was 37 (SD 12). All patients had mild clinical picture with symptoms lasting around 3 days. Overall, 3 UC patients on infliximab had worsening of IBD symptoms (bloody stools and diarrhea) in approximate time to and after COVID infection (increase of pMayo by &gt;=2 points) with only 1 patient requiring glucocorticoid therapy. One male patient had prolonged post-COVID syndrome in terms of fatigue and mild dyspnea over 4 months, but suffered from bronchial asthma. There was no difference in HB index, pMayo or CRP before and after COVID-19 infection (p&gt;0.05). Loss of smell and taste was present 3 patients.

Conclusion
Our analysis was limited to IBD patients scheduled to receive a visit; hence it could not represent general IBD population. However, according to the results of other studies, we did not gain the impression of increased risk of infection or poorer clinical outcome in IBD patients on biological therapy. In addition, study from Singh AK et al. reported worse outcomes of COVID-19 IBD patients in UC, but not on biological therapy, which is also in line with our observation (1).

Reference
1. Singh AK et al. Risk and outcomes of coronavirus disease in patients with inflammatory bowel disease: A systematic review and meta-analysis. United European Gastroenterol J. 2021;9:159–176.
P226 Nuclear magnetic resonance spectroscopy measure of protein glycosylation is a biomarker of activity and metabolic complications in Inflammatory Bowel Disease
Authors: García Mateo S , Martínez-Dominguez S J , Aso Gonzalvo M C , Refaie E , Gallego Llera B , Alfambra Cabrejas E , Sanz B , Amigó Grau N , Ribalta J , Martínez-Micaelo N , Gargallo-Puyuelo C J , Gomollón F 
Published: January 2022

Abstract

Background
Plasma glycoproteins are acute-phase proteins, which can contribute to the development of many complex inflammatory diseases as Inflammatory Bowel Disease (IBD). Glycoprotein concentration as measured by nuclear magnetic resonance (NMR) spectroscopy has been proposed as a biomarker for monitoring activity of IBD, but has been also related to metabolic syndrome. Our goal is to further define the role of this new biomarker in IBD patients with MAFLD.

Methods
Prospective cohort study of consecutive IBD outpatients (Leonnard-Jones criteria, &gt; 1 year) seen at reference centre, was performed from October 2020 to April 2021. Of 947 outpatients, 50 patients with IBD who met criteria for MAFLD and 50 patients with IBD and without MAFLD were matched by sex, age and IBD severity. Every IBD patient was also matched with 4 controls without IBD. Patients and controls with a previous diagnosis of CV disease, type II diabetes mellitus and under treatment for dyslipidaemia were excluded. Serum samples were analysed by NRM Spectroscopy with glycoprotein (Glyc-B, Glyc-F and Glyc-A) analysis by Biosfer Teslab, Spain. Demographic, clinical, biochemical and anthropomorphic variables were obtained prospectively in all cases. Wilcoxon Rank-sum test was used for comparison between groups with R (v 4.1.1).

Results
A total of 100 IBD patients and 400 controls were included. The median age were 51.0 (41–59) years old for each group. There were no differences in body mass index (BMI) between groups (26.4 (23.1–29.9) for IBD and 27.1 (24.4–30.4) for controls p=0.130). Regarding IBD patients, 49 (49%) had ulcerative colitis (UC) and 51(51%) Crohn’s disease (CD). Both IBD groups (with or without MAFLD) were well-matched excepting BMI as expected (table 1). Glycoprotein concentrations were significatively higher in IBD when compared to controls (table 2, p&lt;0.001). In IBD patients with MAFLD glycoprotein concentrations were the highest (p&lt;0.001) with no overlap with controls (table 3).

Conclusion
This prospective study confirms that glycoprotein concentrations can be a biomarker in IBD and for the first time suggests that it can be a very useful biomarker to identify MAFLD.