ADC Values for Detecting Bowel Inflammation and Biologic Therapy Response in Patients With Crohn Disease: A Post Hoc Prospective Trial Analysis.

BACKGROUND. New biologic agents for Crohn disease (CD) create a need for noninvasive disease markers. DWI may assess bowel inflammation without contrast agents. OBJECTIVE. The purpose of this study was to evaluate ADC values for identifying bowel inflammation and therapeutic response in patients with CD treated with biologic therapy. METHODS. This study entailed post hoc analysis of prospective trial data. Analysis included 89 patients (median age, 37 years; 49 women, 40 men) with CD treated by biologic therapy who underwent MR enterography (MRE) at baseline and 46 weeks after therapy, from March 2013 to April 2021; 43 patients underwent ileocolonoscopy at both time points. Analysis was conducted at the level of small-bowel and colorectal segments (586 segments analyzed). MR index of activity (MaRIA) score and presence of endoscopic ulcers were determined at both time points. One observer measured bowel wall ADC. Diagnostic performance was evaluated. Dichotomous ADC assessments used a threshold of 1301 × 10-6 mm2/s based on initial ROC analysis; dichotomous MaRIA score assessments used a threshold of 11 (moderate to severe inflammation). A second observer repeated ADC measurements in 15 patients. RESULTS. At baseline, ADC had AUC of 0.92, sensitivity of 78.6%, specificity of 91.4%, and accuracy of 88.2% for detecting segments with MaRIA score 11 or greater. At baseline, AUC for detecting endoscopic ulcers was 0.96 for MaRIA score versus 0.87 for ADC (p < .001); sensitivity, specificity, and accuracy were 70.8%, 90.2%, and 85.1% for ADC and 86.2%, 96.2%, and 93.6% for MaRIA score. At follow-up, ADC had AUC of 0.87, sensitivity of 75.4%, specificity of 83.6%, and accuracy of 80.0% for detecting improvement in MaRIA score to less than 11. At follow-up, AUC for detecting endoscopic ulcer healing was 0.94 for MaRIA score versus 0.84 for ADC (p = .01); sensitivity, specificity, and accuracy were 70.7%, 95.8%, and 84.4% for ADC and 90.2%, 100.0%, and 95.6% for MaRIA score. Interobserver agreement for ADC, based on intraclass correlation coefficient, was 0.70 at baseline and 0.65 at follow-up. CONCLUSION. The findings do not support use of ADC rather than MaRIA scores for detecting biologic therapy response. CLINICAL IMPACT. ADC may have an adjunct role in assessing bowel inflammation in CD, but showed limited performance for detecting biologic therapy response.

Inflammatory bowel disease integral care units: Evaluation of a nationwide quality certification programme. The GETECCU experience.

BACKGROUND: One of the most valued targets in inflammatory bowel disease (IBD) is for physicians to provide and patients to receive a high-level quality of care. This study aimed to evaluate the implementation of a nationwide quality certification programme for IBD units. METHODS: Identification of quality indicators (QI) for IBD Unit certification was based on Delphi methodology that selected 53 QI, which were subjected to a normalisation process. Selected QI were then used in the certification process. Coordinated by GETECCU, this process began with a consulting round and an audit drill followed by a formal audit carried out by an independent certifying agency. This audit involved the scrutiny of the selected QI in medical records. If 80%-90% compliance was achieved, the IBD unit audited received the qualification of "advanced", and if it exceeded 90% the rating was "excellence". Afterwards, an anonymous survey was conducted among certified units to assess satisfaction with the programme for IBD units. RESULTS: As of January 2021, 66 IBD units adhere to the nationwide certification programme. Among the 53 units already audited by January 2021, 31 achieved the certification of excellence, 20 the advanced certification, and two did not obtain the certification. The main survey results indicated high satisfaction with an average score of 8.5 out of 10. CONCLUSION: Certification of inflammatory bowel disease units by GETECCU is the largest nationwide certification programme for IBD units reported. More than 90% of IBD units adhered to the programme achieved the certification.

Can we Monitor a Patient with Inflammatory Bowel Disease and Adapt Treatment without Endoscopy?

BACKGROUND: While predictors of disease course in inflammatory bowel diseases (IBD) are not accurate, we adapt therapies reactively, after objective demonstration of the presence of active disease, complications, or an inadequate response to a therapeutic intervention. In this context, adequate monitoring is essential to make timely management decisions. OBJECTIVE: To review the role of clinical assessment, biomarkers, radiology and endoscopy in monitoring patients with IBD. RESULTS: Assessment of clinical symptoms is the cornerstone of monitoring in IBD; in ulcerative colitis (UC) there is acceptable correspondence between mucosal lesions and presence of symptoms, but in Crohn's disease (CD) there is a considerable disconnection between these two, and monitoring requires complementary tests. Blood and stool markers such as C-reactive protein and fecal calprotectin are increasingly used. However, the operating properties of these biomarkers are different according to disease type (UC vs. CD), age (pediatric or adult), and disease location (small bowel vs. colonic disease). Cross-sectional imaging has a similar accuracy to endoscopy to detect inflammation in CD, and a higher accuracy to detect stenosing and penetrating complications. It has also been shown that magnetic resonance imaging is accurate for measuring response to therapeutic interventions. CONCLUSION: Cross-sectional imaging is one of the preferred monitoring options in patients with CD. Endoscopy continues to be the preferred examination for assessing UC, and should still be considered in patients with CD who have symptoms or altered biomarkers and cross-sectional imaging is negative.

Cell therapies for IBD: what works?

The inflammatory response in patients with inflammatory bowel disease is a complex self-amplifying process with multiple cellular and molecular pathways controlling activation and shut-off of the process. Available therapeutic interventions with drugs that have a very selective action, such as anti-tumor necrosis factor antibodies, or broader effects such as corticosteroids still leave a significant proportion of patients with Crohn's disease and ulcerative colitis insufficiently treated. Cellular therapies are emerging as promising new approaches to treat inflammatory bowel diseases and in particular Crohn's disease. Experimental and clinical data are the origin of the increasing utilization of cell therapies for severe immune-mediated diseases including inflammatory bowel disease. The types of cell therapies for these diseases can be divided into two different areas: hematopoietic stem cell therapies, and selected/conditioned immune cell therapy, the latter including mesenchymal stem cells and T-regulatory cells-based therapies.

Protective effect of superoxide dismutase in radiation-induced intestinal inflammation.

PURPOSE: To analyze the therapeutic value of Cu/Zn-superoxide dismutase (SOD1) supplementation in an experimental model of radiation-induced intestinal inflammation and explore its mechanistic effects. METHODS AND MATERIALS: Mice were subjected to abdominal irradiation with 10 Gy or sham irradiation and studied 24 or 72 hours after radiation. Groups of mice were treated with 0.1, 4, or 6 mg/kg/day of SOD1 or vehicle. Leukocyte-endothelial cell interactions in intestinal venules were assessed by intravital microscopy. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was determined with radiolabeled antibodies. Effects of SOD1 on histologic damage and levels of lipid hydroperoxides were also measured. RESULTS: A significant increase in the flux of rolling leukocytes and number of firmly adherent leukocytes in intestinal venules was observed at 24 and 72 hours after irradiation. Treatment with SOD1 had no effect on leukocyte rolling but significantly and dose-dependently decreased firm leukocyte adhesion to intestinal venules. Treatment with SOD1 at doses that reduced leukocyte recruitment abrogated the increase in hydroperoxides in intestinal tissue and ICAM-1 upregulation in intestinal endothelial cells. The inflammatory score, but not a combined histology damage score, was also significantly reduced by SOD1. CONCLUSIONS: Treatment with SOD1 decreases oxidative stress and adhesion molecule upregulation in response to abdominal irradiation. This is associated with an attenuation of the radiation-induced intestinal inflammatory response.

Trefoil peptide TFF2 treatment reduces VCAM-1 expression and leukocyte recruitment in experimental intestinal inflammation.

There is evidence for a beneficial effect of trefoil peptides in animal models of gastric damage and intestinal inflammation, but the optimal treatment strategy and the mechanistic basis have not been explored thoroughly. It has been suggested that these proteins may modulate the inflammatory response. The aims of this study were to compare the protective and curative value of systemic and topical trefoil factor family (TFF)2 administration in dextran sulfate sodium-induced experimental colitis and to investigate the relationship between the therapeutic effects of TFF2 and modulation of leukocyte recruitment and expression of cell adhesion molecules. Clinical and morphologic severity of colitis was evaluated at the end of the study (Day 10). Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. The expression of cell adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was measured by the dual radiolabeled monoclonal antibody technique. Pretreatment with TFF2 by subcutaneous or intracolonic (ic) route ameliorated the clinical course of colitis, and the luminal route had a significantly superior effect. This beneficial effect was correlated with significant reductions in endothelial VCAM-1 but not MAdCAM-1 expression and leukocyte adhesion to intestinal venules, which returned to levels similar to those of controls. In established colitis, ic TFF2 treatment did not modify the severity of colonic lesions. In conclusion, TFF2 is useful in the treatment of colitis, and topical administration is superior to the systemic route. Reduction in adhesion molecule expression and leukocyte recruitment into the inflamed intestine contributes to the beneficial effect of this treatment.