scholarly journals THE ROLE OF ENDOTHELIAL DYSFUNCTION IN INFLAMMATORY BOWEL DISEASES

2021 ◽  
Vol 20 (2) ◽  
Author(s):  
A.P. Lutsyk ◽  
E.I. Shorikov

The purpose of the study – to assess the disorders’ degree of endothelium dysfunction inpatients with nonspecific ulcerative colitis (NUC) and Crohn's disease (CD), dependingon the severity of inflammation.Material and methods. 34 patients with NUC and 18 people with CD with continuousrecurrent courses, 15 patients with NUC and 15 patients with CD in remission wereobserved. The control group included 30 healthy volunteers.Results. It has been established that patients with active NUC had a significantly higherlevel of markers characterizing changes of proliferative (VEGF-165) and adhesive(VCAM-1) endothelial functions vs. control (in 4.62 and 2.01 times) and patients whohad an inactive disease (at 3.95 and 4.62) (p<0.05). In the active course of NUC, VEGF-165 level increased by 3.27 and 5.03 times, the level of VCAM by 1.83 and 2.09 times vs.inactive and control group (p<0.05).In patients with severe and moderate degrees of NUC, we have set an increase in theconcentration of VEGF-165 compared with mild degree, p<0.05. It has been proven thatin severe degree of CD, the concentration of VEGF-165 increased 21.5% vs. moderateactivity and 63.1% vs. mild activity, p<0.05.It has been established that adhesive phenotype of endothelial dysfunction with severeactivity of NUC was associated with an elevated content of adhesion molecule, dependingof activity, p<0.05. The adhesive phenotype of endothelial dysfunction is proved forpatients with severe activity of CD compared with moderate and mild activity, p<0.05.We have revealed a reliable direct regression relationship between the concentration ofthe vascular endothelial growth factor and the activity of UC according to the TrueloveWitts scale (R=0.29, p<0.05), between the CDAI index level in CD and the content ofVCAM-1 (R=0.29, p<0.05).Conclusions. Inflammatory bowel diseases - NUC and CD are accompanied withendothelium dysfunction, proliferative and adhesive phenotypes, associated with theactivity of process.

Author(s):  
O. V. Khlynova ◽  
E. A. Stepina

Aim.In this work, we set out to assess the specific features of vascular endothelium in patients suffering from severe (pan-ulcerative) and complicated forms of ulcerative colitis (UC) and Crohn’s disease (CD).Materials and methods.The research sample consisted in 65 patients with UC (n = 45) and CD (n = 20), who were either in the acute phase or had been diagnosed with such conditions for the first time. For assessing endothelial dysfunction (ED), we used such markers as levels of vascular endothelial growth factor (VEGF) in the blood serum and the number of plasma desquamated endotheliocytes (DEC).Results.The indicators of vascular endothelial dysfunction are shown to be significantly higher in patients with severe, pan-ulcerative forms of inflammatory bowel diseases (IBD). A statistically significant relationship has been established between ED indicators and the severity and localisation of the pathological process, the extra-intestinal manifestations and complications of the disease. A dependence of the endothelial dysfunction indicators on the UC endoscopic activity has been determined. A positive correlation between the levels of VEGF and DEC and the markers of systemic inflammation (ESR, CRP and fibrinogen) has been revealed.Conclusion. It is determined that, in IBD patients, endothelium dysfunction is manifested in an increase in the VEGF and DEC levels. The indicators of endothelial dysfunction are shown to be directly correlated with the serum markers of systemic inflammation. Therefore, VEGF and DEC values can be used not only as criteria for assessing the intensity of IBD, but also as predictors of a complicated disease course.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S299-S301
Author(s):  
C Le Berre ◽  
A Bourreille ◽  
M Flamant ◽  
G Bouguen ◽  
L Siproudhis ◽  
...  

Abstract Background Inflammatory bowel diseases (IBD) are disabling disorders. The IBD-Disability Index (IBD-DI) was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a shortened and visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk in a large cohort of IBD patients and to assess its variability over time. Methods From March 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3–12 months intervals (NCT03590639). Validation included concurrent validity, reproducibility, internal consistency, and evaluation of IBD-Disk correlation with IBD activity. Variability was assessed by comparing scores between baseline and follow-up visits. Results A total of 559 patients (73% Crohn’s disease, 27% ulcerative colitis) were included and 389 were followed up (Table 1). There was a good correlation between IBD-Disk and IBD-DI scores (r = 0.75, p &lt; 0.001) (Figure 1). The IBD-Disk was significantly higher in patients with active disease according to Physician/Patient Global Assessment (Figure 2), clinical scores (Figure 3), and biomarkers levels, compared with patients with inactive disease. Reproducibility was excellent (intra-class correlation coefficient = 0.90), as well as internal consistency (Cronbach’s α = 0.89). The IBD-Disk score significantly decreased in patients becoming inactive over time. Conclusion This is the first study to validate the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability in clinical practice. Further studies are warranted to assess its correlation with endoscopic activity, to explore its responsiveness to change, and to evaluate the factors associated with disability.


2020 ◽  
Vol 14 (5) ◽  
pp. 710-718 ◽  
Author(s):  
Ferdinando D’Amico ◽  
Cedric Baumann ◽  
Hélène Rousseau ◽  
Silvio Danese ◽  
Laurent Peyrin-Biroulet

Abstract In the last few decades several new molecules have been developed in the field of inflammatory bowel diseases. However, the process that leads to the approval and use of a new drug is very long, expensive and complex, consisting of various phases. There is a pre-clinical phase that is performed on animals and a clinical phase that is directed to humans. Each research phase aims to evaluate different aspects of the drug and involves a specific target group of subjects. In addition, many aspects must be considered in the evaluation of a clinical trial: randomization, presence of a control group, blind design, type of data analysis performed, and patient stratification. The objective of this review is to provide an overview of the clinical trial phases of a new drug in order to better understand and interpret their results.


2019 ◽  
Vol 38 (3) ◽  
pp. 204-210
Author(s):  
Antonio Mirijello ◽  
Maria Maddalena D’Errico ◽  
Serafino Curci ◽  
Fabrizio Bossa ◽  
Cristina d’Angelo ◽  
...  

Background: Takotsubo syndrome (TTS) is an acute cardiac dysfunction in the absence of viral causes or obstructive coronary disease completely reversible within 4–8 weeks. Inflammatory bowel diseases (IBD) are a group of diseases caused by the interaction between immune system, genetic, and environmental factors against intestinal mucosa. Both these syndromes are characterized by complex mechanisms involving endothelial dysfunction and affective disorders. Aim: To assess the possibility of an association between IBD and TTS. Methods: First, we present a case of TTS in a patient affected by active stenosing Crohn’s disease. Articles in English language were collected from PubMed and Google Scholar databases with the search terms “takotsubo,” “IBD,” “crohn disease,” “ulcerative colitis”. Results: Both TTS and IBD show multiple common features: preference for female patients, recurrent course of disease, association with endothelial dysfunction, and affective disorders. Patients affected by IBD could show specific triggers for TTS, such as malabsorption, electrolytes disturbances, and affective disorders. Conclusions: Despite pathophysiological similarities between TTS and IBD in active phase, future studies are needed to confirm this apparently possible association and to assess the presence of a pathophysiological link between these diseases.


2021 ◽  
Vol 8 ◽  
Author(s):  
Razie Kamali Dolatabadi ◽  
Awat Feizi ◽  
Mehrdad Halaji ◽  
Hossein Fazeli ◽  
Peyman Adibi

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are known as chronic gastrointestinal inflammatory disorders. The present systematic review and meta analysis was conducted to estimate the prevalence of adherent-invasive Escherichia coli (AIEC) isolates and their phylogenetic grouping among IBD patients compared with the controls. A systematic literature search was conducted among published papers by international authors until April 30, 2020 in Web of Science, Scopus, EMBASE, and PubMed databases. The pooled prevalence of AIEC isolates and their phylogenetic grouping among IBD patients as well as in controls was estimated using fixed or random effects models. Furthermore, for estimating the association of colonization by AIEC with IBD, odds ratio along with 95% confidence interval was reported. A total of 205 articles retrieved by the initial search of databases, 13 case–control studies met the eligibility criteria for inclusion in the meta analysis. There were 465 IBD cases (348 CD and 117 UC) and 307 controls. The pooled prevalence of AIEC isolates were 28% (95% CI: 18–39%), 29% (95% CI: 20–40%), 13% (95% CI: 1–30%), and 9% (95% CI: 3–19%), respectively among IBD, CD, UC, and control group, respectively. Our results revealed that the most frequent AIEC phylogroup in the IBD, CD, and control groups was B2. Fixed-effects meta analysis showed that colonization of AIEC is significantly associated with IBD (OR: 2.93; 95% CI: 1.90–4.52; P &lt; 0.001) and CD (OR: 3.07; 95% CI: 1.99–4.74; P &lt; 0.001), but not with UC (OR: 2.29; 95% CI: 0.81–6.51; P = 0.11). In summary, this meta analysis revealed that colonization by AIEC is more frequent in IBD and is associated with IBD (CD and UC). Our results suggested that the affects of IBD in patients colonized with the AIEC pathovar is not random, it is in fact a specific disease-related pathovar.


2021 ◽  
pp. 92-96
Author(s):  
А. P. Lutsyk ◽  
D. V. Shorikova

The article deals with the diagnostic value of changes in the content of interleukin-6 and D-dimer in patients with inflammatory bowel diseases (IBD) - Ulcerative Colitis (UC) and Crohn Disease (CD). Materials and methods: We have studied 34 patients with UC and 18 people with CD with continuously recurrent course. There are also analysed data of 15 patients with UC and 15 patients with CD in period of the remission. The control group included 30 healthy volunteers. Clinical, endoscopic examination, an immunoassay determination of the content of interleukin-6 (IL-6) and D-dimer, was carried out. CD activity was assessed using the Chron’s disease activity index. The localization of CD was established according to the Montreal classification. The clinical activity of the disease in patients with UC was determined using the classification according to Truelove-Witts. The value of the index consisted of the sum of points for each indicator, which allowed determining the activity of the inflammatory process. Statistical processing was performed using STATISTICA 10.0 (StatSoft. Inc., USA), at p<0.05, the discrepancies between the obtained data were considered statistically significant. Research results. According to the obtained data, mild activity was found in 7 patients with UC (20.6%) and 4 - with CD (22.3%), moderate severity - in 17 (50.0%) and 8 (44.4%) patients, severe - in 10 (29.4%) and 6 (33.3%) patients. In the remission stage, 15 patients with UC and 15 patients with CD were examined. According to the Montreal classification, lesions of the upper gastrointestinal tract (L4) were observed in 4 patients with CD (22.2%), terminal ileitis (L1) occurred in 10 patients (55.6%), 4 patients were diagnosed with ileocolitis (L3) - 22.2%. It has been established that patients with an active course of UC and CD had a higher level of proinflammatory markers and thrombosis markers (D-dimer and IL-6) compared with inactive course and control group (p<0.05). The D-dimer content in UC was 690±315 pg/l. It is confirmed the increase of the content of this marker in 2.55 times compared to control group and in 1.43 times than inactive course of the disease respectively. The level of IL-6 at active in course of UC was 3.36±1.78 pg/ml, increasing in 2.07 times against control and in 1.72 times compared with group of remission. In the active course of CD, the level of D-dimer reached 720±267 pg/ml, increasing in 2.67 times in relation to control and in 1.60 times with respect to patients under remission. The content of IL-6 in the active course of CD reached 4.07±2.17 pg/ml, increasing in 2.85 times in comparison to healthy individuals and in 2.83 times relatively patients with remission. While using the ROC-analysis, the most sensitive value as a “cut point” for the diagnosis of the active process in the course of IBD can be considered the content of the D-dimer in an amount of more than 650 pg/l. The calculated AUC in ROC-analysis for the IL-6 content was 73.7%±6.14% (61.7 - 85.7, p<0.001), indicating the prognostic value of the model. The values of the IL-6 content of more than 2.80 pg/ml are diagnostically significant to predict the active process in IBD.


2020 ◽  
Vol 9 (3) ◽  
pp. 800 ◽  
Author(s):  
Gian Caviglia ◽  
Chiara Rosso ◽  
Francesco Stalla ◽  
Martina Rizzo ◽  
Alessandro Massano ◽  
...  

In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.


2017 ◽  
Vol 41 (S1) ◽  
pp. S320-S320
Author(s):  
F. Travagliati ◽  
E. Borrelli ◽  
S. Martinelli ◽  
L. Dattoli ◽  
D. Ferrarese ◽  
...  

IntroductionInflammatory bowel diseases (IBDs) have high social impact. Aetiology is still unknown, however multifactorial genesis is surely implicated. We tried to correlate IBDs and psychological distress through evaluated psychometrical instruments and subsequently to relate subjective influences with gastroenteric clinical manifestation, defining new critical elements on which IBD are based.MethodsIn our study, we included 57 participants, selected according to their diagnosis, between those attending our gastrointestinal ambulatory: 26 had Chron's disease, while 31 had ulcerative colitis. 78 people without gastroenteric or psychiatric disorder were also included in the study as control group. Psychometric questionnaires were administered to evaluate anxiety and depressive symptoms, quality of live, self-efficacy and resilience (Fig. 1).ResultsLevels of anxiety and depression were higher in patients with IBDs than in the control group. STAI-Y highlighted higher state anxiety and trait anxiety levels in first group. HADS showed higher scores in ill patients, as well as CD-RISC showed a more impaired resilience. EQ-VAS, PGWBI and GSE revealed significant differences in health status, psychological wellness and self-efficacy between the two groups.ConclusionsIBDs seem related to psychological diseases. Affected patients have higher anxiety and depression levels than general population as well as lower self-efficacy and resilience. Those elements being strictly linked to physical discomfort contributes to develop a loop in which patients get caught. Creating a model of integrated cooperation between gastroenterologist and psychiatrist during treatment of patients with IBDs seems fundamental to grant at once all the professional figures each patient needs for better care.Disclosure of interestThe authors have not supplied their declaration of competing interest.


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