scholarly journals Mucosal Healing in Crohn’s Disease: Bull’s Eye or Bust? “The Pro Position”

2021 ◽  
pp. 1-6
Author(s):  
Neil O’Moráin ◽  
Jayne Doherty ◽  
Roisin Stack ◽  
Glen A. Doherty
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Injury ◽  
Mucosal Healing ◽  
Inflammatory Disorder ◽  
Stricture Formation ◽  
Chronic Inflammatory Disorder ◽  
Non Invasive ◽  
Appropriate Treatment ◽  
Bull's Eye

<b><i>Background:</i></b> Crohn’s disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. <b><i>Summary:</i></b> Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. <b><i>Key Messages:</i></b> Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.

scholarly journals P138 Platelet-to-lymphocyte ratio index: a reliable tool for non-invasive assessment of endoscopic activity in small bowel Crohn’s Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S225-S225
Author(s):  
V Macedo Silva ◽  
M Freitas ◽  
S Xavier ◽  
T Cúrdia Gonçalves ◽  
P Boal Carvalho ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Small Bowel ◽  
Crohn's Disease ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
C Reactive Protein ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Reactive Protein ◽  
Non Invasive

Abstract Background The platelet-to-lymphocyte ratio (PLR) index has been a recent focus of investigation as a reliable marker of inflammation. This score was recently shown to have a good accuracy upon predicting endoscopic remission in patients with colonic Crohn’s Disease (CD). We aimed to assess the discriminative power of PLR index in patients with isolated small bowel CD. Methods Single center study of consecutive patients with isolated small bowel CD (L1 ± L4 disease according to Montreal classification) who underwent small bowel capsule endoscopy (SBCE) for assessment of endoscopic activity between January 2019 and December 2020. Only complete SBCEs were considered. CD endoscopic activity was classified according to the Lewis score (LS) value. Complete blood count, C-reactive protein and fecal calprotectin values were collected within 1 month of SBCE. Results Final sample included 49 patients, 35 (71.4%) of them females, with a mean age of 35.1±11.8 years. SBCE reported mucosal healing (LS&lt;135) in 30.6% of the patients; mild activity (135≤LS&lt;790) in 42.9% and moderate-to-severe activity (LS≥790) in 26.5% of the patients. PLR index positive correlation with LS was significant and moderate (k=0.597; p&lt;0.001). This correlation was stronger than the one seen between fecal calprotectin (k=0.525; p=0.001) or C-reactive protein (k=0.321; p=0.029) and the LS score. In particular, PLR index presented an excellent accuracy for predicting patients with a moderate-to-severe endoscopic activity (AUC=0.908; 95%CI=0.816–0.999; p&lt;0.001), with an optimal cut-off of PLR above 157 (sensitivity 92.3%; specificity 82.9%). The accuracy for prediction of mucosal healing was good (AUC=0.743; 95%CI=0.600–0.887; p=0.007), with an optimal cut-off of PLR below 126 (sensitivity 66.7%; specificity 80.0%). Conclusion PLR index demonstrated an excellent acuity for predicting patients with moderate to severe disease in small bowel CD. Moreover, it also demonstrated good acuity for predicting mucosal healing on this set of patients. These results come from a significant correlation of PLR index with endoscopic activity in small bowel CD. Our findings establish this index as a promising and easy-to-apply tool for non-invasive and regular follow-up of patients with small bowel CD.

scholarly journals Profiling Non-Coding RNA Levels With Clinical Classifiers in Pediatric Crohn’s Disease

2020 ◽  
Author(s):  
Ranjit S. Pelia ◽  
Suresh Venkateswaran ◽  
Jason D. Matthews ◽  
Yael Haberman ◽  
David J. Cutler ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Progression ◽  
Protein Function ◽  
Inflammatory Disorder ◽  
Substantial Impact ◽  
Chronic Inflammatory Disorder ◽  
Inflammatory Status ◽  
Disease Behavior ◽  
Non Coding Rnas

Abstract Background: Crohn’s disease (CD) is a heritable chronic inflammatory disorder. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression, but can also directly affect protein function, thus having a substantial impact on biological processes. We investigated whether non-coding RNAs (ncRNA) at diagnosis are dysregulated during CD at different CD locations and future disease behaviors to determine if ncRNA signatures can serve as an index to outcomes. Methods: Using subjects belonging to the RISK cohort, we analyzed ncRNA from the ileal biopsies of 345 CD and 71 non-IBD controls, and ncRNA from rectal biopsies of 329 CD and 61 non-IBD controls. Sequence alignment was done (STAR package) using Human Genome version 38 (hg38) as reference panel. The differential expression (DE) analysis was performed with EdgeR package and DE ncRNAs were identified with a threshold of fold change (FC) >2 and FDR < 0.05 after multiple test corrections. Results: In total, we identified 130 CD specific DE ncRNAs (89 in ileum and 41 in rectum) when compared to non-IBD controls. Similarly, 35 DE ncRNAs were identified between B1 and B2 in ileum, whereas no differences among CD disease behaviors were noticed in rectum. We also found inflammation specific ncRNAs between inflamed and non-inflamed groups in ileal biopsies. Overall, we observed that expression of mir1244-2, mir1244-3, mir1244-4, and RN7SL2 were increased during CD, regardless of disease behavior, location, or inflammatory status. Lastly, we tested ncRNA expression at baseline as potential tool to predict the disease status, disease behaviors and disease inflammation at 3-year follow up.Conclusions: We have identified ncRNAs that are specific to disease location, disease behavior, and disease inflammation in CD. Both ileal and rectal specific ncRNA are changing over the course of CD, specifically during the disease progression in the intestinal mucosa. Collectively, our findings show changes in ncRNA during CD and may have a clinical utility in early identification and characterization of disease progression.

scholarly journals Panenteric capsule endoscopy identifies proximal small bowel disease guiding upstaging and treatment intensification in Crohn’s disease: A European multicentre observational cohort study

2020 ◽  
pp. 205064062094866 ◽  
Author(s):  
Foong Way D Tai ◽  
Pierre Ellul ◽  
Alfonso Elosua ◽  
Ignacio Fernandez-Urien ◽  
Gian E Tontini ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Small Bowel ◽  
Crohn's Disease ◽  
Capsule Endoscopy ◽  
Bowel Disease ◽  
Mucosal Healing ◽  
Small Bowel Disease ◽  
Treatment Intensification ◽  
Non Invasive ◽  
Proximal Small Bowel

Background Endoscopically defined mucosal healing in Crohn’s disease is associated with improved outcomes. Panenteric capsule endoscopy enables a single non-invasive assessment of small and large bowel mucosal inflammation. Aims and methods: This multicentre observational study of patients with suspected and established Crohn’s disease examined the feasibility, safety and impact on patient outcomes of panenteric capsule endoscopy in routine clinical practice. The potential role in assessment of disease severity and extent by a comparison with existing clinical and biochemical markers is examined. Results Panenteric capsule endoscopy was performed on 93 patients (71 with established and 22 with suspected Crohn’s disease). A complete examination occurred in 85% (79/93). Two cases (2.8%) of capsule retention occurred in patients with established Crohn’s disease. Panenteric capsule resulted in management change in 38.7% (36/93) patients, including 64.6% (32/48) of those with an established diagnosis whose disease was active, and all three patients with newly diagnosed Crohn’s disease. Montreal classification was upstaged in 33.8% of patients with established Crohn’s disease and mucosal healing was demonstrated in 15.5%. Proximal small bowel disease upstaged disease in 12.7% and predicted escalation of therapy (odds ratio 40.3, 95% confidence interval 3.6–450.2). Raised C-reactive protein and faecal calprotectin were poorly sensitive in detecting active disease (0.48 and 0.59 respectively). Conclusions Panenteric capsule endoscopy was feasible in routine practice and the ability to detect proximal small bowel disease may allow better estimation of prognosis and guide treatment intensification. Panenteric capsule endoscopy may be a suitable non-invasive endoscopic investigation in determining disease activity and supporting management decisions.

scholarly journals Mesenchymal Stromal Cell Therapy in the Management of Perianal Fistulas in Crohn’s Disease: An Up-To-Date Review

Medicina ◽  
2020 ◽  
Vol 56 (11) ◽  
pp. 563
Author(s):  
Gaetano Gallo ◽  
Vincenzo Tiesi ◽  
Serena Fulginiti ◽  
Gilda De Paola ◽  
Giuseppina Vescio ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Negative Impact ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Entire Gastrointestinal Tract

Crohn’s Disease (CD) is a chronic inflammatory disorder that potentially involves the entire gastrointestinal tract. Perianal fistulizing CD (pCD) is a serious and frequent complication associated with significant morbidities and a heavy negative impact on quality of life. The aim of CD treatment is to induce and maintain disease remission and to promote mucosal repair. Unfortunately, even the best therapeutic regimens in pCD do not have long-term efficacy and cause a significant number of side effects. Therefore, it is mandatory to study new therapeutical options such as the use of mesenchymal stromal cells (MSCs). These cells promote tissue repair via the induction of immunomodulation. The present review aims to analyze the existing updated scientific literature on MSCs adoption in the treatment of pCD to evaluate its efficacy and safety and to compare the use of bone marrow and adipose tissue derived MSCs, type of administration, and dose required for recovery.

scholarly journals Transcriptional and Molecular Pathways Activated in Mesenteric Adipose Tissue and Intestinal Mucosa of Crohn’s Disease Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Andressa Coope ◽  
Lívia Bitencourt Pascoal ◽  
Francesca Aparecida Ramos da Silva ◽  
José Diego Botezelli ◽  
Maria de Lourdes Setsuko Ayrizono ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Signaling Pathways ◽  
Intestinal Mucosa ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Mesenteric Adipose Tissue ◽  
Immune Mediated ◽  
First Time

Crohn’s disease (CD) is a chronic inflammatory disorder, characterized by cytokine imbalance and transcription signaling pathways activation. In addition, the increase of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Therefore, we evaluated the transcription signaling pathways and cytokines expression in intestinal mucosa and MAT of active CD patients. Ten patients with ileocecal CD and eight with noninflammatory diseases were studied. The biopsies of intestinal mucosa and MAT were snap-frozen and protein expression was determined by immunoblotting. RNA levels were measured by qPCR. The pIkB/IkB ratio and TNFαlevel were significantly higher in intestinal mucosa of CD when compared to controls. However, STAT1 expression was similar between intestinal mucosa of CD and controls. Considering the MAT, the pIkB/IkB ratio was significantly lower and the anti-inflammatory cytokine IL10 was significantly higher in CD when compared to controls. Finally, the protein content of pSTAT1 was higher in MAT of CD compared to controls. These findings reinforce the predominance of the proinflammatory NF-kB pathway in CD intestinal mucosa. For the first time, we showed the activation of STAT1 pathway in MAT of CD patients, which may help to understand the physiopathology of this immune mediated disease.

scholarly journals Mucosal Healing in Crohn’s Disease: Bull’s Eye or Bust? The “Relative” Con Position

2021 ◽  
pp. 1-8
Author(s):  
Mahmoud Mosli ◽  
Turki Alameel ◽  
Ala I. Sharara
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Treatment Plan ◽  
Immunosuppressive Treatment ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
Inflammatory Bowel ◽  
Noninvasive Markers ◽  
Endoscopic Assessment ◽  
Bull's Eye

<b><i>Background:</i></b> Crohn’s disease is a progressive inflammatory bowel disease. Persistent untreated inflammation can cumulatively result in bowel damage in the form of strictures, fistulas, and fibrosis, which can ultimately result in the need for major abdominal surgery. Mucosal healing has emerged as an attractive, yet ambitious goal in the hope of preventing long-term complications. <b><i>Summary:</i></b> Clinical remission is an inadequate measure of disease activity. Noninvasive markers such as fecal calprotectin, CRP, or small bowel ultrasound are useful adjunct tools. However, endoscopic assessment remains the cornerstone in building a treatment plan. Achieving complete mucosal healing has proved to be an elusive goal even in the ideal setting of a clinical trial. <b><i>Key Messages:</i></b> Aiming for complete mucosal healing in all patients may result in overuse of medications, higher costs, and potential side effects of aggressive immunosuppressive treatment. More practical goals such as relative or partial healing, for example, 50% improvement in inflammation and reduction in size of ulcers, ought to be considered, particularly in difficult-to-treat populations.

scholarly journals Journey through Crohn’s Disease Complication: From Fistula Formation to Future Therapies

2021 ◽  
Vol 10 (23) ◽  
pp. 5548
Author(s):  
Federica Rubbino ◽  
Luana Greco ◽  
Alessio di Cristofaro ◽  
Federica Gaiani ◽  
Stefania Vetrano ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Fistula ◽  
Fistula Formation ◽  
Surgical Approaches ◽  
Molecular Characteristics ◽  
Inflammatory Disorder ◽  
Mesenchymal Transition ◽  
Chronic Inflammatory Disorder ◽  
Increased Risk

Crohn’s Disease (CD) is a chronic inflammatory disorder in which up to 50% of patients develop fistula within 20 years after the initial diagnosis, and half of these patients suffer perianal fistulizing disease. The etiopathogenesis of CD-related perianal fistula is still unclear, and its phenotypical and molecular characteristics are even more indefinite. A better understanding would be crucial to develop targeted and more effective therapeutic strategies. At present, the most accredited theory for the formation of CD-related fistula identifies the epithelial-to-mesenchymal transition (EMT) as the driving force. It has been well recognized that CD carries an increased risk of malignancy, particularly mucinous adenocarcinoma is often associated with long-standing fistula in CD patients. Despite the availability of multiple treatment options, perianal fistulizing CD represents a therapeutic challenge and is associated with an important impact on patients’ quality of life. To date, the most effective management is multidisciplinary with the cooperation of gastroenterologists, surgeons, radiologists, and nutritionists and the best recommended treatment is a combination of medical and surgical approaches.

XI. Novel mouse models to study pathogenic mechanisms of Crohn's disease

2000 ◽  
Vol 278 (5) ◽  
pp. G665-G669 ◽  
Author(s):  
Theresa T. Pizarro ◽  
Kristen O. Arseneau ◽  
Fabio Cominelli
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mouse Models ◽  
Intestinal Inflammation ◽  
The United States ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Therapeutic Modalities ◽  
Genetically Manipulated ◽  
Chronic Intestinal Inflammation

Crohn's Disease (CD) affects more than 500,000 individuals in the United States and represents the second most common chronic inflammatory disorder after rheumatoid arthritis. Although major advances have been made in defining the basic mechanisms underlying chronic intestinal inflammation, the precise etiopathogenesis of CD remains unknown. We have recently characterized two novel mouse models of enteritis that express a CD-like phenotype, namely the TNF ΔARE model of tumor necrosis factor (TNF) overexpression and the SAMP1/Yit model of spontaneous ileitis. The unique feature of these models is that they closely resemble CD for location and histopathology. These genetically manipulated new models of intestinal inflammation offer a powerful tool to investigate potential causes of human disease and may allow the development of novel disease-modifying therapeutic modalities for the treatment of CD.

scholarly journals Roles of IL-17A and IL-23 in the Pathogenesis of Ulcerative Colitis and Crohn’s Disease

2021 ◽  
pp. 2526-2535
Author(s):  
Sarah S. Abdul-Hussein ◽  
Ekhlass N. Ali ◽  
Nawal M. F. Alkhalidi ◽  
Neihaya H. Zaki ◽  
Ali H. Ad'hiah
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Family History ◽  
Crohn's Disease ◽  
Smoking Status ◽  
Serum Levels ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
History Of ◽  
Disease Extension

     Inflammatory bowel disease (IBD) is a chronic inflammatory disorder,  the etiology and pathogenesis of which have been suggested to be influenced by cytokines. Two main clinical types of IBD are recognized, namely ulcerative colitis (UC) and Crohn's disease (CD). The present study examined serum levels of two cytokines (IL-17A and IL-23) in 60 IBD patients (30 UC and 30 CD) and 30 healthy controls. The levels were correlated with age, gender, cigarette-smoking status, disease duration, family history, disease extension, symptoms, extra-intestinal manifestations, and medication. The results depicted that IL-17A level was significantly higher in UC and CD patients compared to control (45.2 ± 23.3 and 47.5 ± 34.4 vs. 15.6 ± 7.5 pg/ml, respectively; p < 0.001). Serum level of IL-23 was similarly increased in UC and CD patients compared to control (64.1± 23.7 and 62.5 ± 27.3 vs. 25.2 ± 11.1 pg/ml, respectively). However, the level of both cytokines showed no significant variation between UC and CD patients (p = 0.713 and 0.777, respectively). Distributing UC and CD patients into subgroups according to some characteristics revealed that IL-17A level was significantly increased in UC male compared to female patients (57.3 ± 18.2 vs. 34.5 ± 22.5 pg/ml; p = 0.005). It was also significantly increased in smoker UC patients compared with non-smoker patients (51.9 ± 19.4 vs. 31.6 ± 25.5 pg/ml; p = 0.022). Smoker CD patients also showed a significantly increased level of IL-23 compared to non-smoker patients (72.7 ± 28.5 vs. 52.2 ± 22.6 pg/ml; p = 0.038). In the case of family history, IL-23 level was significantly decreased in UC patients with a family history of IBD compared to CD patients with a family history (84.5 ± 24.3 vs. 50.4 ± 17.0 pg/ml.; p = 0.042). In conclusion, the present data suggest a role for IL-17A and IL-23 in the etiology and pathogenesis of UC and CD.

scholarly journals Capsule Endoscopy in Crohn’s Disease—From a Relative Contraindication to Habitual Monitoring Tool

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1737
Author(s):  
Adi Lahat ◽  
Ido Veisman
Keyword(s):  
Crohn’S Disease ◽  
Small Bowel ◽  
Crohn's Disease ◽  
Capsule Endoscopy ◽  
Invasive Procedure ◽  
Disease Diagnosis ◽  
Inflammatory Disorder ◽  
Disease Extent ◽  
Chronic Inflammatory Disorder ◽  
Relative Contraindication

Crohn’s disease (CD) is a chronic inflammatory disorder that may involve the gastrointestinal tract from the mouth to the anus. Habitual disease monitoring is highly important during disease management, aiming to identify and treat disease exacerbations, in order to avoid immediate and future complications. Currently, ilio-clonoscopy is the gold standard for mucosal assessment. However, the procedure is invasive, involves sedation and allows for visualization of the colon and only a small part of the terminal ileum, while most of the small bowel is not visualized. Since CD may involve the whole length of the small bowel, the disease extent might be underestimated. Capsule endoscopy (CE) provides a technology that can screen the entire bowel in a non-invasive procedure, with minimal side effects. In recent years, this technique has gained in popularity for CD evaluation and monitoring. When CE was first introduced, two decades ago, the fear of possible capsule retention in the narrowed inflamed bowel lumen limited its use in CD patients, and a known CD located at the small bowel was even regarded as a relative contraindication for capsule examination. However, at present, as experience using CE in CD patients has accumulated, this procedure has become one of the accepted tools for disease diagnosis and monitoring. In our current review, we summarize the historic change in the indications and contraindications for the usage of capsule endoscopy for the evaluation of CD, and discuss international recommendations regarding CE’s role in CD diagnosis and monitoring.

Sign in / Sign up

Export Citation Format

Share Document