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Aim: Assess the characteristics of break through COVID-19 in Inflammatory Bowel Disease (IBD) patients, despite complete vaccination., Methods: Patients who reported a COVID-19 at least 3 weeks after complete vaccination were asked to answer an on-line anonymous questionnaire which included patient and disease characteristics, vaccination history, and the evolution of COVID-19., Results: Among 3240 IBD patients who reported complete vaccination between 1st May 2021 and 30thJune 2022, 402 (12.4%) were infected by SARS Cov-2 [223 male, 216 Crohn's disease (CD), 186 Ulcerative Colitis (UC), mean (SD) age 42.3 (14.9) years, mean (SD) IBD duration 10.1 (9.7) years]. Three hundred and sixty-nine patients (91.8%) were infected once and 33 (8.2%) twice. The mean (SD) time between last vaccination and infection was 4.1 (1.6) months. Overall, 351 (87.3%) patients reported mild constitutional and/or respiratory symptoms, 34 (8.4%) were asymptomatic and only 17 patients (4.2%) required hospitalization. Of hospitalized patients, 2 UC patients died of COVID-19 pneumonia. The remaining hospitalized patients did not need high flow oxygen supply or ICU admission., Conclusions: A minority of completely vaccinated IBD patients developed COVID-19 which evolved with mild symptoms and a favorable outcome. These results reinforce the importance of vaccination especially in vulnerable populations., Competing Interests: Conflict of Interest There are no conflicts of interest to declare regarding this study, (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic diseases, such as IBD, can lead to anxiety and depression which can have a significant impact on productivity at work [presenteeism]. The aim of this study was to assess the prevalence of depression/anxiety, presenteeism and exercise levels among IBD patients., Methods: This was a multicentre study whereby adult IBD patients, in clinical remission, were asked to answer a questionnaire anonymously. Hospital Anxiety and Depression Score [HADS], Stanford Presenteeism Scale [SPS-6] and Godin Exercise Score were also collected., Results: A total of 585 patients were recruited. The majority had Crohn's disease [CD, 62.2%] and were male [53.0%], with a median age of 39 years [IQR 30-49]. A psychiatric diagnosis was present in 10.8% of patients prior to their IBD diagnosis. A further 14.2% of patients were psychiatrically diagnosed after IBD diagnosis, this being commoner in CD patients [41.6% of CD, p <0.01]. A raised HADS-Anxiety or a HADS-Depression score ≥8 was present in 46.1% of patients, with 27.4% having a score ≥11. Low presenteeism at work was present in 34.0%. Patients diagnosed with depression/anxiety had a more sedentary lifestyle [p <0.01], lower presenteeism at work [p <0.01] and a higher rate of unemployment [p <0.01]., Conclusions: A significant percentage of IBD patients in remission suffer from anxiety and/or depression. Risk factors for these are CD, female gender, use of biologic medications, long-standing and/or perianal disease. Depression/anxiety was associated with a sedentary lifestyle, lower presenteeism at work and unemployment. Validated screening tools and appropriate referrals to psychologists and/or psychiatrists should be employed within IBD clinics., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Anti-SARS-CoV-2 vaccine clinical trials did not include patients with immune-mediated conditions such as inflammatory bowel disease [IBD]. We aimed to describe the implementation of anti-SARS-CoV-2 vaccination among IBD patients, patients' concerns, and the side effect profile of the anti-SARS-CoV-2 vaccines, using real-world data., Methods: An anonymous web-based self-completed survey was distributed in 36 European countries between June and July 2021. The results of the patient characteristics, concerns, vaccination status, and side effect profile were analysed., Results: In all 3272 IBD patients completed the survey, 79.6% had received at least one dose of anti-SARS-CoV-2 vaccine, and 71.7% had completed the vaccination process. Patients over 60 years old had a significantly higher rate of vaccination [p < 0.001]. Patients' main concerns before vaccination were the possibility of having worse vaccine-related adverse events due to their IBD [24.6%], an IBD flare after vaccination [21.1%], and reduced vaccine efficacy due to IBD or associated immunosuppression [17.6%]. After the first dose of the vaccine, 72.4% had local symptoms and 51.4% had systemic symptoms [five patients had non-specified thrombosis]. Adverse events were less frequent after the second dose of the vaccine and in older patients. Only a minority of the patients were hospitalised [0.3%], needed a consultation [3.6%], or had to change IBD therapy [13.4%] after anti-SARS-CoV-2 vaccination., Conclusions: Although IBD patients raised concerns about the safety and efficacy of anti-SARS-CoV-2 vaccines, the implementation of vaccination in those responding to our survey was high and the adverse events were comparable to the general population, with minimal impact on their IBD., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Interstitial lung [ILD] disease and granulomatous lung disease [GLD] are rare respiratory disorders that have been associated with inflammatory bowel disease [IBD]. Clinical presentation is polymorphic and aetiology is unclear., Methods: This was an ECCO-CONFER project. Cases of concomitant ILD or GLD and IBD, or drug-induced ILD/GLD, were collected. The criteria for diagnosing ILD and GLD were based on definitions from the American Thoracic Society and the European Respiratory Society and on the discretion of reporting clinician., Results: We identified 31 patients with ILD. The majority had ulcerative colitis [UC] [n = 22]. Drug-related ILD was found in 64% of these patients, 25 patients [80.6%] required hospitalisation, and one required non-invasive ventilation. The causative drug was stopped in all drug-related ILD, and 87% of patients received systemic steroids. At follow-up, 16% of patients had no respiratory symptoms, 16% had partial improvement, 55% had ongoing symptoms, and there were no data in 13%. One patient was referred for lung transplantation, and one death from lung fibrosis was reported. We also identified 22 GLD patients: most had Crohn's disease [CD] [n = 17]. Drug-related GLD was found in 36% of patients and 10 patients [45.4%] required hospitalisation. The causative drug was stopped in all drug-related GLD, and 81% of patients received systemic steroids. Remission of both conditions was achieved in almost all patients., Conclusions: ILD and GLD, although rare, can cause significant morbidity. In our series, over half of cases were drug-related and therefore focused pharmacovigilance is needed to identify and manage these cases., (© Crown copyright 2019.)

Background and Aims: Inflammatory bowel disease [IBD] can impair patients' functional capacity with significant negative effects on their quality of life. Our aim was to determine the impact of IBD diagnosis on fitness levels and to assess the levels of engagement in physical activity and fatigue in IBD patient before and after diagnosis., Methods: A prospective multi-centre cross-sectional study was performed. Patients diagnosed with IBD in the previous 18 months were recruited. Inclusion criteria included clinical remission and/or no treatment changes within the previous 6 months. Physical exercise levels were assessed by the Godin score and fatigue levels was assessed by the functional assessment of chronic illness therapy [FACIT] score., Results: In total, 158 patients (100 Crohn's disease [CD]) were recruited. Mean age was 35.1 years (95% confidence interval [CI] ± 2.0). Gender distribution was approximately equal [51.3% male]. The Mean Harvey Bradshaw and Simple Clinical Colitis Activity indices were 2.25 [95% CI ± 0.40] and 1.64 [95% CI ± 0.49], respectively. The mean Godin score difference before and after IBD diagnosis was 6.94 [p = 0.002]. Patients with ulcerative colitis [UC] [41.8%] were more likely than patients with CD [23.0%] to reduce their exercise levels [p = 0.04]. FACIT scores were lower in patients who had experienced relapses [p = 0.012] and had severe disease [p = 0.011]. Approximately one-third of patients reduced their activity level following IBD diagnosis., Conclusions: Patients were significantly less physically active after a diagnosis of IBD and this was more apparent in UC. Identification of the risk factors associated with loss of fitness levels would help to address the reduced patient quality of life., (Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The main objective is to determine the overall prevalence of anemia in inflammatory bowel diseases (IBD) in Europe., Methods: A systematic literature search in PubMed and Embase was performed for studies published between January 2007 and May 2012. Eligible studies were included if they were original full-paper publications originated from Europe and if the authors agreed to provide their data. An overall prevalence of anemia in IBD, disease specific, and age-gender stratified basis prevalences were estimated. The influence of disease entity (Crohn's disease/ulcerative colitis), gender, age, disease activity (remission/active disease), and IBD-specific treatment strategies on the prevalence of anemia was analyzed by a mixed logistic regression model. Thereby, the factor country of origin was included as a random effect., Results: Data were available for 2192 patients, mainly treated in tertiary referral centers. The overall prevalence of anemia in IBD patients was 24% (95% confidence interval, 18-31). Age-gender stratified prevalences were estimated for the age strata 18 to 29, 30 to 39, 40 to 49, 50 to 64, 65 to 74, >74 years and ranged from 18% to 35%. Patients receiving IBD-specific medication (P = 0.0002, odds ratio 1.54), and patients with active disease status (P < 0.0001, odds ratio 2.72) were significantly more likely to have anemia compared with patients not receiving IBD-specific medication or being in remission. Patients with ulcerative colitis tended to have anemia less likely than patients with Crohn's disease (P = 0.01, odds ratio 0.77)., Conclusions: The overall prevalence of anemia in patients with Crohn's disease was 27% (95% confidence interval, 19-35) and 21% (95% confidence interval, 15-27) in patients with ulcerative colitis. Thereby, 57% of the anemic patients were iron deficient.

Anemia is a common complication of inflammatory bowel diseases. An international working party has formed and developed guidelines for evaluation and treatment of anemia and iron deficiency that should serve practicing gastroenterologists. Within a total of 16 statements, recommendations are made regarding diagnostic measures to screen for iron- and other anemia-related deficiencies regarding the triggers for medical intervention, treatment goals, and appropriate therapies. Anemia is a common cause of hospitalization, prevents physicians from discharging hospitalized patients, and is one of the most frequent comorbid conditions in patients with inflammatory bowel disease. It therefore needs appropriate attention and specific care.

Background: Inherited risk factors have been suggested to play an important role in the pathogenesis of vascular complications of inflammatory bowel disease (IBD). The aim of the present study was to investigate the role of mutations associated with cardiovascular disease in IBD patients with or without vascular complications compared with thrombotic and healthy controls (HC)., Methods: Twelve polymorphisms of thrombophilic and vasoactive genes were evaluated in a group of 30 IBD patients with vascular complications (IBD-VC) compared with 60 IBD patients without vascular complications, 30 thrombotic controls (TC), and 54 healthy controls, using a commercially available kit., Results: No significant differences between IBD-VC and TC concerning the carriage of these mutations were found. The frequencies of the factor V (FV) 506 RQ (Leiden) genotype and the 506Q allele were significantly higher in these groups than in HC (P < 0.05) but not IBD controls (P > 0.05). The allele frequency of the mutant 4G allele of the plasminogen activator inhibitor (PAI) polymorphism, similar in the IBD-VC and TC groups, was significantly higher in these groups compared with the IBD group (P = 0.03) and the HC (P = 0.001). It is noteworthy that there was a trend of association of FV R506Q polymorphism with venous thrombosis and PAI-1 gene polymorphism with arterial thrombosis., Conclusions: Our results suggest that the investigated gene polymorphisms do not differ in patients with IBD-VC and TC. FV R506Q and PAI-1 gene polymorphisms might be associated with the increased risk of development of vascular complications in IBD.

Background: Angiogenesis has been suggested to play an important role in inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD)., Materials and Methods: Serum Ang-2 and Tie-2 serum levels were measured in 160 IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2 levels were correlated with the disease activity, as well as the type, localization and treatment of the disease., Results: Median serum Ang-2 and Tie-2 levels were significantly higher in both the UC patients and the CD patients compared with the healthy controls (P < 0.05 and P < 0.001, respectively). The IBD patients with early disease (diagnosis < 2 years) had significantly higher (P = 0.04) median serum Ang-2 levels but significantly lower (P = 0.02) median serum Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2 years). The CD patients with active disease had significantly higher levels of Ang-2 compared with non-active disease (P = 0.02). Serum levels of both Ang-2 and Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood cell count, platelet count and albumin., Conclusions: Serum Ang-2 and Tie-2 levels are elevated in patients with IBD. These markers may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD.

Background: /, Aims: Laminin and collagen IV have been proposed as extracellular matrix serum markers. Because fibrosis is a major complication of inflammatory bowel disease, serum concentrations of laminin and collagen IV were measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared with inflammatory and healthy controls., Methods: Laminin and collagen IV serum concentrations were measured in 170 patients with inflammatory bowel disease (86 UC and 84 CD), in 23 patients with other causes of intestinal inflammation, and in 80 matched healthy controls using commercially available enzyme linked immunosorbent assays. Laminin and collagen IV concentrations were correlated with disease activity, type, localisation, and treatment., Results: Mean (SD) serum laminin concentrations were 281.0 (110.1) ng/ml in patients with UC, 275.6 (106.7) ng/ml in patients with CD, 192.0 (17.8) ng/ml in healthy controls, and 198.5 (32.5) ng/ml in inflammatory controls. Mean (SD) serum collagen IV concentrations were 72.8 (22.9) ng/ml in patients with UC, 71.0 (18.2) in patients with CD, 79.8 (12.2) ng/ml in healthy controls, and 88.9 (24.6) ng/ml in inflammatory controls. There was a significant difference among the four groups (p < 0.0001) for both markers. There was a strong correlation between serum laminin, but not collagen IV, and disease activity in both diseases. No significant association was found between these markers and disease localisation or disease type., Conclusions: Serum concentrations of laminin are increased, whereas serum concentrations of collagen IV are decreased, in patients with inflammatory bowel disease. They may be useful surrogate markers for sustained inflammation and tissue remodelling.

Objectives: We investigated whether the mean platelet volume would be a useful marker in the evaluation of inflammatory bowel disease activity., Methods: Complete blood count, C-reactive protein, erythrocyte sedimentation rate, serum thrombopoietin and erythropoietin, plasma beta-thromboglobulin, and platelet factor 4 were measured in 93 patients with ulcerative colitis, 66 patients with Crohn's disease, and 38 healthy blood donors. Disease activity was assessed by the Clinical Colitis Activity Index in patients with ulcerative colitis and by the Crohn's Disease Activity Index in patients with Crohn's disease., Results: Mean platelet count was increased in patients with active compared to inactive ulcerative colitis (p < 0.05), and in patients with active compared to inactive Crohn's disease (p = 0.0002) or healthy controls (p < 0.0001). On the other hand, mean platelet volume was significantly decreased in patients with active compared to inactive ulcerative colitis (p = 0.02) or healthy controls (p < 0.0001), and in patients with active compared to inactive Crohn's disease (p = 0.0005) or healthy controls (p < 0.0001). Mean platelet volume was inversely correlated with the white blood cell count (r = -0.17, p = 0.02), C-reactive protein (r = -0.46, p = 0.009) and erythrocyte sedimentation rate (r = -0.28, p = 0.008). No significant correlations were found between mean platelet volume and serum thrombopoietin or erythropoietin levels; however, a strong negative correlation between mean platelet volume and beta-thromboglobulin (r = -0.34, p < 0.0001) and platelet factor 4 (r = -0.30, p = 0.0002) was observed., Conclusions: Mean platelet volume is significantly reduced in active inflammatory bowel disease and is negatively correlated with the known inflammatory bowel disease activity markers and the platelet activation products. We propose that mean platelet volume provides a useful marker of activity in inflammatory bowel disease.

Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). It is recognized that a hypercoagulable state exists in IBD which involves all components of the clotting system. It has been suggested that this hypercoagulable state is closely linked to the disease pathogenesis. Recent studies have shown that genetic defects such as factor V Leiden mutation and C677T methylenetetrahydrofolate reductase polymorphism associated with hyperhomocysteinemia seem to interfere in the thrombotic manifestations of IBD. Acquired factors such as antiphospholipid antibodies could also participate in the development of the thrombotic process. Deficiencies of other anticoagulant factors play a less important role in the thrombosis, and therefore it is not surprising that the results on these factors in IBD are contradictory. In conclusion the resultant gene-gene and gene-environment interactions between risk factors are the key to the understanding of why an IBD patient develops thrombosis at a specific point in time.

Objective: Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. A recently identified mechanism for thrombophilia, the poor anticoagulant response to activated protein C, has been suggested as one of the leading risk factors for thrombosis. The aim of this study was to evaluate the frequency of thrombophilic abnormalities, including activated protein C-resistance (APCR), in Greek patients with ulcerative colitis (UC) and Crohn's disease (CD)., Methods: Forty-eight patients with UC, 36 with CD, and 61 matched healthy controls (HC) were studied. Cases with presence of lupus anticoagulant, use of anticoagulants or heparin, and pregnancy were excluded. Disease activity in CD was evaluated by use of the Crohns Disease Activity Index (CDAI) score and in UC by the Truelove-Witts grading system. Plasma levels of protein C, free protein S, antithrombin III (AT-III), activated protein C resistance (APCR), and fibrinogen were determined in IBD patients, as well as in HC. All the cases and controls with abnormal APCR were further studied by genetic testing for the factor V Leiden mutation., Results: Mean fibrinogen levels in UC and CD patients were significantly elevated (p<0.0001), compared with HC. The mean values of free protein S, as well as mean APCR, were significantly lower in UC and CD patients than in the HC (p<0.0001). Seven (five UC and two CD) of 84 IBD patients (8.3%) and three of the HC (4.9%) had the factor V Leiden mutation. No significant difference was observed for the other thrombophilic parameters. Fibrinogen levels and profound free protein S deficiency were found related to disease activity., Conclusions: Thrombophilic defects are common in Greek patients with IBD and they could interfere either in the disease manifestation or in the thrombotic complications.

Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Anti-cardiolipin (aCL) antibodies have been shown to be associated with thrombosis. Recently, the antibodies against the anti-cardiolipin cofactor beta2-glycoprotein I (a(beta2)GPI) have been found with higher specificity for thrombosis. The presence of these antibodies was assessed in 128 patients with IBD [83 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)] and 100 healthy controls (blood donors). Patients with UC and CD had a significantly higher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (HC) (3%). Eleven IBD patients (8.6%) but no HC had a(beta2)GPI. None of the IBD patients with a history of thrombosis had aCL and only one of them (a UC patient with deep vein thrombosis of the right leg) had a high titer of IgG a(beta2)GPI. In conclusion, these data show that both aCL and a(beta2)GPI are significantly associated with IBD but further studies are needed to determine the significance of our findings.

Patients with ulcerative colitis have an increased risk for developing colon cancer compared to the general population. The risk is related to the extension of the disease and its duration. This risk is the same for Crohn's colitis patients of equal extension and duration. By chemoprevention we mean the use of specific natural or synthetic chemical agents to reverse, suppress or prevent progression to invasive cancer. The chemopreventive agents for colon cancer are either of natural origin (vitamins, minerals, food constituents) or synthetic chemicals (difluoromethyl ornithine) and pharmaceutical agents (aspirin, oltipraz). Apart from folate, no other agent has so far been used in vivo for the prevention of colon cancer in long-standing inflammatory bowel disease. The use of folate was, however, not primarily intended to prevent cancer but to enhance folate absorption in ulcerative colitis. From retrospective studies, within the framework of cancer surveillance programmes, it became evident that folate supplementation may play a positive role as a chemopreventive agent against colorectal cancer in patients with long-standing, extensive ulcerative colitis. There is also evidence suggesting that folate supplementation may contribute to regulation of rectal cell proliferation in ulcerative colitis patients. There is a real need for multicentre, randomized, prospective clinical studies in order to evaluate the promising role of folate in preventing colorectal cancer in patients with long-standing inflammatory bowel disease.

In 153 patients with IBD, 64 with Crohn's disease (CD), and 89 with ulcerative colitis (UC), as well as in 54 healthy controls (HC), the frequencies of four known di-allelic polymorphisms in the genes for TNF-alpha and lymphotoxin alpha (LTalpha) were investigated. In the Dutch population, the alleles of these four polymorphisms are present in only five combinations, called TNF haplotypes: TNF-C, -E, -H, -I, -P. Furthermore, the relation with the presence of perinuclear anti-neutrophil cytoplasmic autoantibodies (P-ANCA) was studied. A small, but statistically significant, association between the polymorphism at position -308 in the promoter region of the TNF-alpha gene and UC was found. The frequency of the uncommon TNF-alpha -308 allele 2 was found to be decreased in patients with UC compared with HC (allele frequency of allele 2 in UC patients 0-15 versus 0.25 in HC, P=0.044). No significant differences in distribution of the TNF haplotypes were found between IBD patients and HC, although there was a tendency towards a higher frequency of the TNF-C haplotype in UC patients compared with controls (haplotype frequency 22% versus 13%; P=0.19). No statistically significant differences in distribution of the TNF haplotypes were observed between P-ANCA-positive and P-ANCA-negative UC patients. The strength of the associations indicates that TNF genes are not markers for the predisposition to suffer from IBD. They may, however, be markers of subsets of patients with UC and CD.

Recent reports have shown that allele 2 of the IL-1 receptor antagonist (IL-1Ra) gene is over-represented in ulcerative colitis (UC). Healthy individuals carrying allele 2 of this gene have increased production of IL-lRa protein. Since the final outcome of the biological effects of IL-β may depend on the relative proportion of these two cytokines, we have studied if a Taq1 polymorphism in the IL-1β gene, which is relevant to IL-1β protein production, may be involved in the genetic susceptibility to UC and Crohn's disease (CD), in association with the established IL-1Ra gene polymorphism. Polymorphisms in the closely linked genes for IL-1β and IL-1Ra were typed in 100 unrelated Dutch patients with UC, 79 with CD, and 71 healthy controls. The polymorphic regions in exon 5 of the IL-lβ gene and in intron 2 of the IL-1Ra gene, were studied by polymerase chain reaction (PCR)-based methods. The IL-lβ allele frequencies in UC and CD patients did not differ from those in healthy controls. In order to study if the IL-1β gene polymorphism might participate synergistically with the IL-1Ra gene polymorphism in susceptibility to UC and CD, individuals were distributed into carriers and non-carriers of allele 2 of the genes encoding IL-1β and IL-1Ra, in each of the patient groups and controls. Results indicated a significant association of this pair of genes, estimated by the odds ratio (OR) after performing Fisher's exact test, in the UC group (P = 0.023, OR = 2.81), as well as in the CD group (P = 0.01, OR = 3.79). Thus, non-carriers of IL-lβ allele 2 were more often present in the subgroup of patients carrying the IL-1Ra allele 2. By contrast, no association of these alleles was detected in the group of healthy controls (P = 1.00, OR = 0.92). These results suggest that the IL-1β/IL-1Ra allelic cluster may participate in defining the biological basis of predisposition to chronic inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]