The prognostic value of histology in ulcerative colitis in clinical remission with mesalazine

Frieri, Giuseppe; Galletti, B.; Ruscio, Mirko Di; Tittoni, Rachele; Capannolo, Annalisa; Serva, Donatella; Latella, Giovanni; Sollima, Laura; Leocata, Pietro; Necozione, Stefano; Frieri, Rosamarie; Viscido, Angelo

doi:10.1177/1756283x17722926

Cited by 29 publications

(28 citation statements)

References 37 publications

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“…In a prospective observational study, 87.1% of patients with histological remission at initial assessment remained in clinical remission after 1 year (53). In addition, histological remission in patients with UC was a strong predictor of steroid-free remission and clinical recurrence after 3 years of follow-up and was associated with lower hospitalization and corticosteroid use rates over a median follow-up period of 6 years (47,54,55). In a retrospective study, histological normalization was associated with increased odds of relapse-free survival compared with endoscopic healing or histological quiescence (56).…”

Section: Resultsmentioning

confidence: 94%

A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review

et al. 2019

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OBJECTIVES: In 2015, the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program proposed shifting the therapeutic focus on ulcerative colitis (UC) toward altering the natural history of the disease course by regularly monitoring objective measurements of disease activity and tailoring treatment accordingly. The therapeutic paradigm shift was well received in the research community and is often cited. However, new evidence on optimal UC treatment targets continues to accumulate since the time of the STRIDE guidelines. This systematic review summarizes the evidence accrued since the STRIDE UC recommendations, discusses the barriers for adoption of treat-to-target approaches in clinical practice in UC, and suggests directions for future research. METHODS: We systematically reviewed MEDLINE for studies from the time of the STRIDE systematic review up to March 31, 2018, that assessed the potential treatment targets identified by the STRIDE recommendations. RESULTS: Each potential treatment target literature search returned > 200 articles, which were then reviewed by 2 independent investigators for relevant studies. Selected studies of clinical factors, patient-reported outcomes, endoscopy, histology, imaging, and biomarkers and implications on treatment targets are summarized. CONCLUSIONS: It appears that the relative weight given to different therapeutic targets in the development and improvement of UC treatments could be optimized, with an increased emphasis on endoscopic and histological targets over clinical or symptomatic targets. For this evolution to occur, however, new research has to demonstrate that the treat-to-target approach will deliver on the promise of better long-term outcomes compared with current approaches.

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Section: Resultsmentioning

confidence: 94%

A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review

et al. 2019

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“…Since metformin has previously been demonstrated to active AMPK and is considered as a safe drug in clinical application, we use metformin to further study the role of AMPK in colitis. Mesalazine, a cyclooxygenase (COX) inhibitor, is widely used for IBD treatment ( Frieri et al, 2017 ). In the present study, we used mesalazine (200 mg/kg) as a positive control.…”

Section: Resultsmentioning

confidence: 99%

Activating AMPK to Restore Tight Junction Assembly in Intestinal Epithelium and to Attenuate Experimental Colitis by Metformin

et al. 2018

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Adenosine monophosphate-activated protein kinase (AMPK), a crucial molecule in energy metabolism, is reported to play a potential role in gut epithelial differentiation and barrier function recently; however, its performance and mechanisms in the pathological process of inflammatory bowel diseases remain unidentified. In this study, we have found that the phosphorylation of AMPK in colonic tissues is negatively correlated with severity of disease during the initiation and development of experimental colitis induced by dextran sulfate sodium. Activation of AMPK by metformin significantly controls the progression of colitis, which is associated with the maintenance of tight junction in colonic epithelium in mice. Moreover, our in vitro data in colonic epithelial Caco2 cells shows that metformin promotes expression and assembly of tight junctions via an AMPK-dependent way. Overall, our results suggested that activating AMPK by a clinically safe drug metformin could be a beneficial choice for colitis treatment.

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“…Mice were orally treated with 2.5% DSS for nine consecutive days and then normal water for 2 days, inducing a model of acute colitis that was characterized by severe weight loss, evident diarrhea, rectal bleeding, and shortened colon length. Mesalazine, a cyclooxygenase (COX) inhibitor, which reduces the risk of recurrence of IBD, is by far the most frequently used drug in IBD treatment ( 19 ), and in this study, we used mesalazine as a positive control in mice ( 20 , 21 ). As shown in Figure 5 A, compared to the vehicle-treated group, oral treatment of procyanidin, especially at a dose of 40 mg/kg, markedly attenuated weight reduction.…”

Section: Resultsmentioning

confidence: 99%

The Antioxidant Procyanidin Reduces Reactive Oxygen Species Signaling in Macrophages and Ameliorates Experimental Colitis in Mice

Chen

You

et al. 2018

Front. Immunol.

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Management of inflammatory bowel disease (IBD) is a real clinical challenge. Despite intense investigation, the mechanisms of IBD remain substantially unidentified. Some inflammatory conditions, such as matrix metalloproteinases (MMPs) and the nuclear factor-κB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathways, are reported to contribute to the development and maintenance of IBD. Regulation of their common upstream signaling, that is, reactive oxygen species (ROS), may be important to control the progression of IBD. In the present study, we found that procyanidin, a powerful antioxidation flavonoid, has a significant effect on ROS clearance on THP-1 macrophages after lipopolysaccharide (LPS) or LPS-combined adenosine triphosphate stimulation, thus downregulating MMP9 expression, suppressing NF-κB signaling, and interrupting the formation of the NLRP3 inflammasome. Moreover, our in vivo data showed that procyanidin attenuated Dextran sulfate sodium-induced experimental colitis in a dose-dependent fashion by suppressing the expression of MMP9, NF-κB, and NLRP3 inflammasome signaling in colonic tissues in mice. Overall, our results suggested that targeting ROS could be a potential therapeutic choice for colonic inflammation.

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The prognostic value of histology in ulcerative colitis in clinical remission with mesalazine

Abstract: Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.

Cited by 29 publications

References 37 publications

A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review

A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review

Activating AMPK to Restore Tight Junction Assembly in Intestinal Epithelium and to Attenuate Experimental Colitis by Metformin

The Antioxidant Procyanidin Reduces Reactive Oxygen Species Signaling in Macrophages and Ameliorates Experimental Colitis in Mice

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