Crohn's Disease Endoscopic Index Of Severity Research Articles

COMPARING MAGNETIC RESONANCE ENTEROGRAPHY AND ENDOSCOPY FINDINGS TO QUANTATATIVE MAGENTIC RESONANCE IMAGING IN PEDIATRIC CROHN’S DISEASE

Abstract BACKGROUND In pediatric Crohn’s disease, endoscopy has remained the gold standard for diagnosis; however, Magnetic Resonance Enterography (MRE) is able to show inflammation of the bowel that a gastroenterologist cannot reach with endoscopy. For a standard MRE, a patient needs to ingest oral contrast, receive intravenous (IV) contrast and a spasmolytic agent, and hold his/her breath during portions of the study, which can be challenging in younger children. As shown in previous studies, quantitative Magnetic Resonance Imaging (MRI) can evaluate bowel motility in children with Crohn’s disease, showing that as motility decreases in the bowel, inflammation increases. A motility score obtained from GIQuant software (Motilent, UK) may allow existing MRE protocols to be shortened and can be done with free-breathing techniques and without IV contrast and the spasmolytic agent. AIM Our primary aim is to demonstrate that quantitative MRI, which uses the cine image to develop a motility score from GIQuant software, is as effective as standard MRE in assessing inflammation of the bowel. We secondarily hypothesize that the motility score will inversely correlate to the Endoscopic Biopsy Acute Histologic Inflammatory Score (eAIS), the Crohn’s Disease Endoscopic Index of Severity (CDEIS) score, and the MR Index of Activity (MaRIA) score. METHODS This was a retrospective study of 50 pediatric patients from Children’s Wisconsin with ileal and/ or cecal Crohn’s disease who underwent endoscopy and MRE within 7 days of each other without exposure to therapy. Cine images were used from patients’ previously obtained MREs to obtain a motility score using GIQuant. A cine image and GIQuant map example is shown in Figure 1. The relationships between motility score and MaRIA, eAIS, and CDEIS were then calculated by Spearman’s rank correlation coefficient (ρ). RESULTS MaRIA and motility scores inversely correlated (ρ = -0.66, p <.0001), which is seen in Figure 2. MaRIA positively correlated with CDEIS (ρ = 0.30, p= 0.03) and eAIS (ρ = 0.26, p = 0.07). The motility score showed a non-significant negative correlation with CDEIS (ρ = -0.17, p = 0.24) and eAIS (ρ = -0.23, p =0.11). CONCLUSION Quantitative MRI is as effective as standard MRE in identifying inflammation of the bowel in Crohn’s disease. The cine image is obtained much faster than standard MRE and without the use of intravenous contrast, spasmolytic agent, and breath-holding techniques, which is crucial for children who are too young to cooperate with current MRE protocols. Figure 1 MRE cine image with the Region of Interest in the terminal ileum identified via the polygon and the resulting Motility Map produced by GIQuant Figure 2 MaRIA and Motility scores of each patient in our cohort

Matrix gla protein, a potential marker of tissue remodelling and physiological ageing of the gut in crohn’s disease

Background The inactive dephosphorylated and uncarboxylated form of the matrix Gla protein (dp-ucMGP) has been shown to be increased in plasma of inflammatory bowel disease (IBD) patients. Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity, presence of strictures and cumulative structural bowel damage in Crohn’s disease (CD) patients. Methods The plasmatic level of dp-ucMGP was measured in a monocentric cohort of prospectively recruited patients. The analysis was done by chemiluminescent immunoassay on blood samples collected the day of a planned ileocolonoscopy. In addition to classical clinical data (gender, age, body mass index (BMI), disease duration, current treatment), endoscopic data (disease location, Crohn’s Disease Endoscopic Index of Severity (CDEIS), mucosal healing (MH), presence of 9 CD lesion types) and biological markers (faecal calprotectin and C-reactive protein (CRP)) were collected. The association between dp-ucMGP level and Lémann index was also investigated. Univariate linear regression was used to investigate the relationship between dp-ucMGP level and different parameters collected. Results A total of 82 ileocolonoscopies and dp-ucMGP assays were performed in 75 CD patients (45 females; 37 ileocolonic, 19 ileal and 19 colonic diseases) between October 2012 and November 2019. A total of 24 patients (29.3%) showed MH. The dp-ucMGP levels were not associated with MH, CDEIS, faecal calprotectin or CRP levels. Plasmatic dp-ucMGP levels increased significantly with age (p = 0.0032), disease duration (p = 0.0033), corticosteroids use (p = 0.019) and tended to increase in patients with intestinal strictures (p = 0.086) but not with the Lémann index. Conclusion The significant increase of plasmatic dp-ucMGP levels with age, disease duration and the trend observed in patients with non-ulcerated strictures may suggest that this extracellular matrix protein could be a marker of tissue remodelling and physiological ageing of the gut.

Endoscopy in IBD: When and How?

Endoscopy is an essential tool supporting inflammatory bowel disease diagnosis, and ileocolonoscopy is essential to the diagnostic process because it allows for histological sampling. A decent description of endoscopic lesions may lead to a correct final diagnosis up to 89% of the time. Moreover, endoscopy is key to evaluating endoscopic severity, which in both Crohn's disease and ulcerative colitis is associated with worse disease outcomes (e.g., more frequent advanced therapy requirements or more frequent hospitalizations and surgeries). Endoscopic severity should be reported according to validated endoscopic scores, such as the Mayo endoscopic subscore (MES) or the ulcerative colitis endoscopic index of severity (UCEIS) for ulcerative colitis, the Rutgeerts score for postoperative Crohn's recurrence, and the Crohn's disease endoscopic index of severity (CDEIS) or the simplified endoscopic score for Crohn's disease (SES-CD) for luminal Crohn's disease activity. The measuring of endoscopic activity has become a regulatory agency requirement to increase the objective evaluation of disease activity and drug response. In recent years, the central reviewing of endoscopic videos has become a standard for clinical trials. However, the adjudication paradigm and the type of endoscopic reading may substantially affect trial outcomes, and the reproducibility of all endoscopic scores is not perfect as they require the interpretation of intrinsically subjective images. This paper reviews and discusses the available evidence on inflammatory bowel disease endoscopy.

Tumor Necrosis Factor-α, Fecal Calprotectin, and Disease Activity in Inflammatory Bowel Disease Patients

INTRODUCTION: Inflammatory bowel disease (IBD) has increased incidence and the lack of effective long-term therapeutic options has resulted in mortality from intestinal complications and also significant costs to the country’s health-care system. Evaluation of disease activity in IBD patients is beneficial for establishing clinical judgments, especially in giving therapy and knowing the response of the given therapy. Tumor necrosis factor (TNF)-α, fecal calprotectin (FC), Lichtiger index, and Crohn’s Disease Endoscopic Index of Severity (CDEIS) are useful tools for evaluating disease activity. This study wants to know the relationship between biomarkers with disease activity. METHODS: A cross-sectional retrospective study was conducted on IBD patients. The diagnosis of IBD was based on findings from the gastrointestinal tract during colonoscopy and biopsy that showed features of IBD. TNF-α _was taken from the patient’s serum, while FC was from the patient’s stool sample. Lichtiger index was taken from anamneses, while CDEIS from endoscopy. The data will be analyzed using SPSS 22.0. RESULTS: A total of 35 patients with IBD met the inclusion criteria. This study found a 0.7-fold risk in IBD patients to have moderate-severe activity if they had TNF-α _levels of ≥ 1.14 pg/mL, although it was not significant (p = 0.581; OR:0.68; 95%CI 0.18-2.66). A significant relationship was found in the value of FC with disease activity in IBD patients, with a six-fold risk of having IBD with moderate-to-severe activity if FC levels ≥254 μg/g (p=0,011, OR:6,24, 95%CI 1,44-27,06). CONCLUSION: Fecal calprotectin levels have significant relationship with disease activity in IBD patients, both clinically and endoscopically. Fecal calprotectin is a decent marker for assessing disease activity in IBD patients.

Motility Mapping Quantification Using the Classical Optical Flow Algorithm for Small Bowel Crohn's Disease: Comparison with Balloon-assisted Enteroscopy Findings.

To quantify bowel motility shown on cine MRI using the classical optical flow algorithm and compare it with balloon-assisted enteroscopy (BAE) findings in patients with Crohn's disease (CD). This retrospective study included 29 consecutive patients with CD who had undergone MR enterocolonography (MREC) and BAE between March and May 2017. We developed computer software to present motion vector magnitudes between consecutive cine MR images as bowel motility maps via a classical optical flow algorithm using the Horn-Schunck method. Cine MR images were acquired with a balanced steady-state free precession sequence in the coronal direction to capture small bowel motility. The small bowels were divided into three segments. In total, 63 bowel segments were assessed via BAE and MREC. Motility scores on the maps, simplified MR index of activity (sMaRIA), and MREC score derived from a 5-point MR classification were assessed independently by two radiologists and compared with the CD endoscopic index of severity (CDEIS). Correlations were assessed using Spearman's rank coefficient. The areas under the receiver-operating characteristic curve (AUCs) of motility score for differentiating CDEIS was calculated; a P value < 0.05 was considered statistically significant. Motility score was negatively correlated with CDEIS (r = -0.59 [P < 0.001] and -0.54 [P < 0.001]), and the AUCs of motility scores for detecting CDEIS ≥ 3 were 88.2% and 78.6% for observers 1 and 2, respectively. There were no significant differences in the AUC for detecting CDEIS ≥ 3 and CDEIS ≥ 12 between motility and sMaRIA or MREC score. The motility map was feasible for locally quantifying the bowel motility. In addition, the motility score on the map reflected the endoscopic inflammatory activity of each small bowel segment in patients with CD; hence, it could be used as a tool in objectively interpreting cine MREC to predict inflammatory activity in CD.

Outcomes of Pediatric Patients with Crohn's Disease Received Infliximab or Exclusive Enteral Nutrition during Induction Remission.

Background Both exclusive enteral nutrition (EEN) and infliximab (IFX) are recommended as induction therapy for pediatric Crohn's disease (CD). Our aim was to compare long-term disease outcomes of patients initially received with either IFX or EEN. Methods Medical records of newly diagnosed, therapy naïve pediatric patients with CD received with IFX or EEN as induction therapy were retrospectively enrolled. Pediatric Crohn's disease activity index (PCDAI), Crohn's disease endoscopic index of severity (CDEIS), and other clinical data were compared pre- and postinduction therapy in two groups. The sustained remission rates and time coupled with body mass index (BMI) and height for age (HFA) changes were evaluated during more than 2-year long-term follow-up. Results We collected data from 58 children with CD used IFX (23) or EEN (35) as induction remission therapy from January 2015 through June 2021 in our single-center. The median follow-up after starting IFX or EEN was 12.2 months (6.5–18.0months) and 18.9 months (7.1–30.7months), respectively. The proportion clinical and endoscopic remission in EEN (88.57% and 68.75%) was similar with that of IFX (73.91% and 80.77%) after induction therapy. No significant differences were also observed in BMI and HFA recovery between two groups. Among those who achieved clinical or endoscopic remission or endoscopic response, the sustained remission rates and time did not reveal any significant differences for those 10 patients who used 6-mercaptopurine/methotrexate (6-MP/MTX) or 14 patients who used IFX as maintenance treatment during longitudinal follow-up. Conclusions Our study suggested that EEN treatment is similar with IFX therapy in short-term outcomes, and EEN+6-MP/MTX treatment is comparable with IFX+IFX therapy in long-term outcomes.

Distinct alterations of fecal microbiota refer to the efficacy of adalimumab in Crohn's disease.

Background and Aims: Anti-tumor necrosis factor mAb (i.e., adalimumab, ADA) is currently used in the treatment of patients with Crohn’s disease (CD). However, its regulation on fecal microbiota is still not fully understood. Methods: A retrospective analysis was conducted on 115 patients with CD who received treatment with ADA for 12 weeks at the Inflammatory Bowel Disease Center in Shanghai Tenth People’s Hospital and Department of Gastroenterology in Shanghai General Hospital. The Crohn’s disease activity index (CDAI) evaluation was applied to patients before ADA therapy at week 0, 4, 8, and 12. Clinical remission (CR) was defined as the CDAI < 150. All patients underwent ileocolonoscopy or enteroscopy at baseline (week 0) and week 12. Crohn’s Disease Endoscopic Index of Severity (CDEIS) scores were calculated by two experienced physicians to assess endoscopic activity. Mucosal healing (MH) was assigned a CDEIS score between 0 and 3. Fecal samples were collected from eight CD patients at baseline and week 12, and the microbiota was analyzed by using 16S RNA sequencing. Results: At week 12, CR was achieved in 70.6% (72/102) of the patients with active CD. A total of 47.1% (48/102) of the patients with active CD attained MH, among which, 56.6% (30/53) of the patients with mildly active CD (3 ≤ CDEIS <9) and 48.0% (12/25) of the moderately active CD patients (9 ≤ CDEIS <12) attained MH, but only 25.0% (6/24) achieved MH in severely active CD patients (CDEIS ≥12). The efficacy of ADA was not associated with lesion locations (χ 2 = 0.409, p = 0.815). Unexpectedly, we found an increase in protective microbiota at the genus level (e.g., Barnesiella, Anaerostipes, Tyzzerella, Lachnoclostridium, and Lachnospiraceae_unclassified) but a decrease in pathogenic bacteria (Escherichia–Shigella) in fecal samples of the ADA-responsive group (ADA-R) when compared with those in the ADA-nonresponsive group (ADA-NR). Notably, the gene bglX coding β-glucosidase and gph encoding phosphoglycolate phosphatase were enriched in fecal samples of ADA-R. Conversely, the abundance of genes coding ATP-binding cassette (ABC) transporter system proteins was significantly enriched in fecal samples of ADA-NR when compared with that of the ADA-R. Conclusion: This study reveals that ADA markedly improves clinical remission and induces MH in mildly to moderately active CD patients and that distinct changes in the gut microbiota can be used to predict the efficacy of ADA.

CT enterography for evaluation of disease activity in patients with ileocolonic Crohn's disease

BackgroundCT enterography (CTE) is used routinely for assessment of activity and severity in Crohn's disease (CD), but there are few CTE scoring systems. The aim of this study was to develop a quantitative CTE scoring system for ileocolonic Crohn's disease activity.MethodsForty-nine CD patients with ileocolonic involvement were retrospectively included between March 2015 and May 2018. All patients underwent CTE and ileocolonoscopy. Mural hyperenhancement and mural thickening at CTE were scored quantitatively, while mural stratification, submucosal fat deposition, comb sign, perienteric fat hypertrophy and mesenteric fibrofatty proliferation were qualitative variables. A Tobit regression model was applied for assessing the association between Crohn's disease endoscopic index of severity (CDEIS) and CTE variables.ResultsA total of 280 intestinal segments were evaluated. Independent predictors for CDEIS were mural thickness (p < 0.001), mural stratification (p < 0.001) and comb sign (p = 0.002). In order to quantify disease activity based on CTE findings in each segment, a simplified CT enterography index of activity (CTEIA) was derived from logistic regression analysis. The formula was as follows: CTEIA (segment) = 2.1 mural thickness(mm) + 9.7 mural stratification + 5.2 comb sign. There was a high and significant correlation coefficient between CDEIS and CTEIA (r = 0.779, p < 0.001) for per-segment analysis. The model for the detection of ulcerative lesions in the colon and terminal ileum achieved an area under the receiver-operating curve of 0.901 using a cut-off point of 6.25.ConclusionsCTEIA is a new qualitative tool for evaluation of ileocolonic Crohn’s disease, which need to be validated in further studies.

Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: A randomized controlled trial.

SummaryBackgroundThe efficacy and mechanisms of acupuncture for Crohn's disease (CD) are not well understood. We investigated its effects on symptoms, intestinal microbiota, and circulating inflammatory markers in CD patients.MethodsThis 48-week, randomized, sham controlled, parallel-group clinical trial was performed at a tertiary outpatient clinic in China. From April 2015 to November 2019, 66 patients (mean age 40·4, 62·1% were male, all were Han Chinese) with mild to moderate active CD and unresponsive to drug treatment were enrolled and randomly assigned equally to an acupuncture group or a sham group. The treatment group received 3 sessions of acupuncture plus moxibustion per week for 12 weeks and a follow-up of 36 weeks. Clinicaltrials.gov: NCT02559037.FindingsAt week 12, the clinical remission rate (the primary outcome) and clinical response rate of acupuncture group were significantly higher than that of sham group, with a difference of 42·4% (95% CI: 20·1%-64·0%) and 45·5% (95% CI: 24·0%-66·9%), respectively, both of which maintained at week 48. The acupuncture group had significantly lower CD activity index and C-reactive protein level at week 12, which maintained at 36-week follow-up. The CD endoscopic index of severity, histopathological score, and recurrence rate at week 48 were significantly lower in acupuncture group. The number of operational taxonomic unit of intestinal microbiota and relative abundance of Faecalibacterium prausnitzii and Roseburia faecis were increased. Plasma diamine oxidase, lipopolysaccharide, and Th1/Th17 related cytokines were decreased in 12-week after acupuncture.InterpretationAcupuncture was effective in inducing and maintaining remission in patients with active CD, which was associated with increased abundance of intestinal anti-inflammatory bacteria, enhanced intestinal barrier, and regulation of circulating Th1/Th17-related cytokines.FundingNational Key Basic Research Program of China (2015CB554500 and 2009CB522900), Shanghai Rising-Star Program (19QA1408100).

DOP89 Infliximab and ustekinumab clearance during induction predicts post-induction endoscopic outcomes in patients with Crohn’s Disease

Abstract Background Monitoring of monoclonal antibody clearance has been hypothesised to be an appealing approach for predicting treatment outcomes in patients with inflammatory bowel diseases. We aimed to investigate the benefits of monitoring infliximab and ustekinumab clearance in patients with Crohn’s disease (CD) based on data from clinical trials. Methods Data were obtained from patients with moderate-to-severe CD starting infliximab (n=108)1 or ustekinumab (n=80)2 therapy. Endoscopic remission (CD Endoscopic Index of Severity &amp;lt;3) and endoscopic response (≥50% decrease from baseline in simple endoscopic score for CD) were assessed at week (w)12 and w24 of infliximab and ustekinumab therapy, respectively. A priori prediction (based on covariate data only; at w0) and a posteriori prediction (Bayesian forecasting using measured drug concentrations; during treatment) were performed using previously built population pharmacokinetic models (NONMEM 7.5).3,4 Covariates of fecal calprotectin, albumin, CD activity index, and antibodies towards infliximab (ATIs) were used to estimate infliximab clearance. Albumin and body weight were used to estimate ustekinumab clearance. Results Patients achieving endoscopic remission at w12 had significantly lower infliximab clearance and higher infliximab serum concentration at w2 and w6 of treatment (P &amp;lt;0.05, Table 1). Patients achieving endoscopic response at w24 had significantly lower ustekinumab clearance at w4 and w8, as well as a significantly larger reduction in clearance relative to w0 (P &amp;lt;0.05, Table 1). However, ustekinumab serum concentrations at w4 and w8 were similar between patients with and without endoscopic response (P &amp;gt;0.2, Table 1). Most patients with an early increase in infliximab clearance (16/22; 73%) and ustekinumab clearance (27/29; 93%) did not reach the endoscopic endpoint (P &amp;lt;0.05; Table 2). However, a decrease in clearance was no guarantee for endoscopic remission during infliximab therapy (false predictive rate 46%) and response during ustekinumab therapy (false predictive rate 69%). The infliximab clearance after start of induction therapy (at w2 and w6) was significantly higher in patients who developed ATIs during induction therapy (Figure 1). Conclusion Lower infliximab and ustekinumab clearance (absolute as well as relative to w0) early during induction predict more favourable endoscopic outcomes. In patients treated with ustekinumab, clearance monitoring may better predict endoscopic response at w24 as compared to standard therapeutic drug monitoring.

Assessment of endoscopic response using pan-enteric capsule endoscopy in Crohn’s disease; the Sensitivity to Change (STOC) study

Background The potential use of pan-enteric capsule endoscopy (pan-CE) to evaluate mucosal changes during treatment has not been evaluated. We aimed to assess the ability of pan-CE to measure changes in mucosal disease activity before and after starting biologic treatment in Crohn’s disease patients. Methods In this two-center prospective study, patients with clinical and biochemical signs of active Crohn’s disease underwent pan-CE before and 8 to 12 weeks after treatment initiation with infliximab, adalimumab or vedolizumab. Endoscopic disease activity was assessed using the simple endoscopic score for Crohn’s disease (SES-CD) and the Crohn’s disease endoscopic index of severity (CDEIS), expanded with two segments (i.e., the jejunum and pre-terminal ileum). Occurrence of endoscopic remission (i.e., absence of ulcers) and endoscopic response (i.e., 50% decrease in SES-CD and CDEIS scores compared to baseline) was assessed and the standardized effect size was calculated. Results Twenty-two patients (50% females) completed the study. Endoscopic remission was observed in 6 out of 22 (27%) patients and 13/22 patients (59%) showed an endoscopic response for both the SES-CD and CDEIS score. Median SES-CD and CDEIS scores decreased from 16.0 (IQR 10.0 − 24.0) to 6.0 (IQR 2.8 − 12.0, p = .001) and from 7.1 (IQR 4.6 − 11.2) to 3.0 (IQR 0.9 − 6.0, p = .001), respectively. The standardized effect size was 1.44 and 1.24 for the SES-CD and CDEIS, respectively. No adverse events related to pan-CE were reported. Conclusion Pan-CE was a useful technique to assess changes in mucosal disease activity in Crohn’s disease patients.

P353 Pan-enteric capsule endoscopy enables assessment of mucosal healing after biologic treatment initiation in Crohn’s disease

Abstract Background Pan-enteric capsule endoscopy (pan-CE) visualizes the entire gastrointestinal tract and provides an attractive alternative to conventional ileocolonoscopy to evaluate luminal disease activity in Crohn’s disease (CD). An earlier study showed that pan-CE is feasible, safe and well tolerated by CD patients. The aim of the present study was to assess the Sensitivity TO measure Change (STOC) in mucosal disease activity using pan-CE in CD. Methods Patients with CD and active disease based on symptoms (i.e. Crohn’s disease activity index (CDAI) &amp;gt;150) and inflammatory biomarkers (i.e. C-reactive protein (CRP) &amp;gt;5 mg/L and/or fecal calprotectin (fCal) levels &amp;gt;250 mg/kg) underwent pan-CE, using the second-generation Pillcam colon capsule, prior to and 8-12 weeks after treatment initiation with infliximab, adalimumab or vedolizumab. Luminal disease activity was assessed using the Crohn’s disease endoscopic index of severity (CDEIS) and the simple endoscopic score for Crohn’s disease (SES-CD), expanded with two segments for the jejunum and pre-terminal ileum. Sensitivity to detect mucosal change was assumed if the standardized effect size was &amp;gt;0.8. Correlations between the evolution in CDAI, CRP and fCal with endoscopic activity scores before and after treatment initiation were calculated. Results Twenty-eight patients underwent pan-CE of whom two withdrew consent and four did not start biologic therapy. Twenty-two patients (78.6%) started biologic treatment and underwent pan-CE twice. Median duration between treatment initiation and pan-CE was 11 weeks (IQR: 9.8-12 weeks). Half of patients (11/22) were female and the median age was 24 years (IQR=22-38 years). The standardized effect size was 1.11 for CDEIS and 1.36 for SES-CD. Median CDEIS scores decreased from 6.8 (IQR=4.6-11.2) to 3 (IQR=0.9-6.0, p=0.01). Median SES-CD scores decreased from 15.5 (IQR=9.8-22.5) to 6 (IQR=2.8-11.3, p=0.001). SES-CD score per segment decreased significantly for colon segments, not for small bowel segments (figure 1). The difference in CDAI, CRP and fCal outcomes before and after treatment did not correlate with the change in CDEIS and SES-CD. Conclusion Pan-CE is useful to assess luminal disease activity in CD patients who embark on biological treatment. Pan-CE is sensitive to monitor mucosal healing outcomes and might therefore replace ileocolonoscopy for this indication in CD patients.

P081 Resolvin D2 attenuates colonic inflammation of Crohn’s disease patients

Abstract Background Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Usually, the clinical management are based on sulphasalazine, corticosteroid, immunomodulators, biologics therapy and bioactive small molecules. However, new therapeutic strategies involving the inflammatory process are being proposed as the use of pro-resolution lipid mediators. This study aimed to investigate the potential therapeutical role of Resolvin D2 (RvD2) in the intestinal mucosa of CD patients and its therapeutic potential. Methods The study included 16 CD patients, 8 patients in remission (CDR) and 8 with active disease (CDA) and 6 healthy subjects in the control group (CTR); all were followed up in tertiary referral hospital. Blood sample and colonic biopsies were collected during colonoscopy. Disease activity was determined by the Crohn’s Disease Endoscopic Index of Severity (CDEIS). The serum blood level of RvD2 was determined by enzymatic immunosorption assay (ELISA). Intestinal biopsies were submitted to cell culture and treated with Infliximab (IFX) or RvD2. The expression of inflammatory cytokines was evaluated by real-time PCR and RvD2 levels through the ELISA. A nonparametric test was used for statistical analysis, with adopted p&amp;lt;0.05. The study was approved by the University of Campinas research ethics committee. Results The intestinal mucosa of the CDA group showed higher levels of pro-inflammatory markers, such as, IL1β (p=0.008 and p=0.01), IL6 (p=0.002), IL23 (p=0.03) and S100A8 (p=0.004 and p=0.01), compared to CTR and CDR groups, respectively. Although serum RvD2 levels of CDA (p=0.002) and CDR (p=0.004) groups were increased when compared to the CTR group, there is no differences between CDA and CDR groups (p&amp;gt;0.05). However, intestinal explants of the CDA group treated with RvD2 showed a significantly decrease of IL1β expression (p&amp;lt;0.05) when compared to the non-treated biopsies in the ex vivo culture experiments, similar to what was as verified by IFX treatment (p&amp;lt;0.05). Conclusion The results suggest the participation of RvD2 in the modulation of colonic inflammation associated with CD. RvD2 showed to be as effective as IFX in attenuating the pro-inflammatory response present in the intestinal mucosa of patients with CD and provide insights into pro-resolution lipid mediators approaches to modulate chronic inflammation.

Poor Concordance Between Clinical Activity and Endoscopic Severity in Pediatric Crohn's Disease: Before and After Induction Therapy.

Endoscopic assessments of disease activity are important to diagnose and evaluate treatment responses in patients with Crohn's disease (CD). However, the invasiveness of endoscopy limits the application of this technique in routine examination. Thus, interest has been increasing in identifying noninvasive surrogate markers to predict endoscopic CD activity. We retrospectively analyzed pediatric patients with new-onset CD from January 2013 to December 2018 at Zhejiang University Affiliated Children's Hospital. The disease severity was scored according to the Crohn's Disease Endoscopic Index of Severity (CDEIS). Routine blood tests were determined individually. Clinical activity was assessed based on the Pediatric Crohn's Disease Activity Index (PCDAI). A total of 91 patients with CD had undergone one or more ileocolonoscopies (n = 146), the mean CDEIS for all the pediatric patients with CD was 7.0 (95% CI 5.7-8.2), and the mean PCDAI was 20.9 (95% CI 18.3-23.5). Pearson's linear analysis of the CDEIS and PCDAI in pediatric patients with CD showed a moderate correlation (r = 0.508, P < 0.001). Weak correlations were found between the PCDAI and CDEIS at the first diagnosis (r = 0.408, P < 0.001) and after completing induction therapy (r = 0.286, P < 0.05). Routine blood tests also did not correlate well with the CDEIS. This study identified weak correlations between the PCDAI and CDEIS in assessing pediatric patients with CD severity both at first diagnosis and after induction therapy. A comprehensive assessment of PCDAI, CDEIS and multiple laboratory factors should be performed at diagnosis and during the follow-up of patients with CD.

Hepatic mosaic enhancement pattern correlates with increased inflammatory activity and adverse therapeutic outcomes in patients with Crohn's disease.

This study aimed to evaluate the role of hepatic mosaic enhancement pattern (HMEP) on computed tomography images in the disease activity and therapeutic outcome of Crohn's Disease (CD). Twenty-five CD patients with HMEP comprised the HMEP group, and 25 CD patients without HMEP, who had a similar onset age, sex, and disease course with those in the HMEP group, comprised the non-HMEP group. No underlying liver/biliary disease was observed in any of the patients. Clinical characteristics, laboratory test results, Lémann index, and CD endoscopic index of severity (CDEIS) were compared between the groups using the Student t-, Mann-Whitney U, Chi square, or Fisher's exact tests. Patients received top-down, step-up, or traditional treatment during the follow-up period. After the 1-year follow-up, therapeutic outcomes (active inflammation [CDEIS > 3.5 if the endoscopic data were available, or C-reactive protein level > 5mg/L if the endoscopic data were unavailable] or remission) were evaluated. The occurrence rate of fistulas/abscesses was higher in the HMEP group (84%, 21/25) than in the non-HMEP group (48%, 12/25) with no statistical significance (P = 0.056). The HMEP group showed a higher C-reactive protein level (P = 0.001), erythrocyte sedimentation rate (P = 0.013), and blood platelet count (P = 0.005). There was no significant difference in therapeutic strategies between the groups (P = 0.509). The HMEP group showed a significantly lower remission ratio after anti-inflammatory treatment than the non-HMEP group (P = 0.045). HMEP was correlated with increased inflammatory activity and adverse therapeutic outcomes in CD. This finding provided insights regarding novel markers of CD diagnosis and treatment.

The endoscopic diagnosis of mucosal healing and deep remission in inflammatory bowel disease.

The therapeutic goal in inflammatory bowel disease (IBD) patients has shifted from controlling the clinical activity alone to managing other associated problems. The concept of mucosal healing (MH) and deep remission (DR) are advocated and regarded as new therapeutic goals in IBD. However, the definition of MH still remains controversial. It is unclear whether or not the histological structures or functional factors should be included in the definition of DR in addition to clinical remission and MH. The classifications of white-light imaging (e.g. Mayo endoscopic subscore, UCEIS, CD Endoscopic Index of Severity, simple Endoscopic Score-CD) have been proposed and are now widely used to assess the severity as well as the MH of inflammation in IBD. In ulcerative colitis, magnifying chromoendoscopy has been shown to be useful to assess the MH of inflammation while other types of image-enhanced endoscopy, such as narrow-band imaging, have not. Endocytoscopy and confocal laser endomicroscopy (CLE) are also applied to assess the activity in IBD. These endoscopic procedures can estimate MH with more precision through observing the details of superficial structures, such as crypt openings. In addition, CLE can partially assess the mucosal function by detecting fluorescence leakage. Molecular imaging can possibly detect the molecules associated with inflammation, intestinal regeneration and differentiation, and various functions including the intestinal barrier and mucus secretion. These novel procedures may improve the diagnosis strategy of DR through the assessment of DR-associated factors such as the histological structures and functional factors in the near future.

Location but Not Severity of Endoscopic Lesions Influences Endoscopic Remission Rates in Crohn's Disease: A Post Hoc Analysis of TAILORIX.

The impact of severity and location of Crohn's disease (CD) endoscopic ulcers on endoscopic remission in patients treated with antitumor necrosis factor is poorly known. We aimed to describe the endoscopic evolution of CD lesions in a prospective cohort of patients treated with infliximab (IFX) in combo therapy. We conducted a post hoc analysis of the TAILORIX randomized controlled trial, which studied biologic-naïve patients with active CD and endoscopic ulcers receiving IFX combo therapy. Ileocolonoscopies were performed at week 0, 12, and 54. Endoscopic healing was defined as the absence of ulcers and complete endoscopic remission as CD Endoscopic Index of Severity (CDEIS) <3. Ileocolonic segments were scored separately for remission by blinded readers. A total of 122 (median disease duration: 7 months) patients were included, corresponding with 379 diseased segments. The median (IQR) CDEIS scores at week 0, 12, and 54 were 9.9 (6.1-14.4), 2.4 (0.2-4.6), and 0.2 (0.0-3.7), respectively. At weeks 12 and 54, the rates of endoscopic healing and complete endoscopic remission were 41% and 61% and 61% and 73%, respectively. Median CDEIS scores were similar among patients with deep ulcers at baseline and those with only superficial ulcers at week 12 and 54. Segmental remission rates were lower both at week 12 and 54 in the ileum compared with colonic segments (P < 0.01 all comparisons) and in the rectum (P = 0.02 and P = 0.03). In biologic-naive patients with CD treated with IFX combo therapy, the severity of endoscopic lesions at the baseline did not influence healing rates. Endoscopic remission occurs less frequently in the ileum compared with the colon.

Dynamic contrast-enhanced magnetic resonance imaging and diffusion-weighted imaging in the activity staging of terminal ileum Crohn's disease.

BACKGROUNDThe activity staging of Crohn’s disease (CD) in the terminal ileum is critical in developing an accurate clinical treatment plan. The activity of terminal ileum CD is associated with the microcirculation of involved bowel walls. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) can reflect perfusion and permeability of bowel walls by providing microcirculation information. As such, we hypothesize that DCE-MRI and DWI parameters can assess terminal ileum CD, thereby providing an opportunity to stage CD activity.AIMTo evaluate the value of DCE-MRI and DWI in assessing activity of terminal ileum CD. METHODSForty-eight patients with CD who underwent DCE-MRI and DWI were enrolled. The patients’ activity was graded as remission, mild and moderate-severe. The transfer constant (Ktrans), wash-out constant (Kep), and extravascular extracellular volume fraction (Ve) were calculated from DCE-MRI and the apparent diffusion coefficient (ADC) was obtained from DWI. Magnetic Resonance Index of Activity (MaRIA) was calculated from magnetic resonance enterography. Differences in these quantitative parameters were compared between normal ileal loop (NIL) and inflamed terminal ileum (ITI) and among different activity grades. The correlations between these parameters, MaRIA, the Crohn’s Disease Activity Index (CDAI), and Crohn’s Disease Endoscopic Index of Severity (CDEIS) were examined. Receiver operating characteristic curve analyses were used to determine the diagnostic performance of these parameters in differentiating between CD activity levels.RESULTSHigher Ktrans (0.07 ± 0.04 vs 0.01 ± 0.01), Kep (0.24 ± 0.11 vs 0.15 ± 0.05) and Ve (0.27 ± 0.07 vs 0.08 ± 0.03), but lower ADC (1.41 ± 0.26 vs 2.41 ± 0.30) values were found in ITI than in NIL (all P < 0.001). The Ktrans, Kep, Ve and MaRIA increased with disease activity, whereas the ADC decreased (all P < 0.001). The Ktrans, Kep, Ve and MaRIA showed positive correlations with the CDAI (r = 0.866 for Ktrans, 0.870 for Kep, 0.858 for Ve, 0.890 for MaRIA, all P < 0.001) and CDEIS (r = 0.563 for Ktrans, 0.567 for Kep, 0.571 for Ve, 0.842 for MaRIA, all P < 0.001), while the ADC showed negative correlations with the CDAI (r = -0.857, P < 0.001) and CDEIS (r = -0.536, P < 0.001). The areas under the curve (AUC) for the Ktrans, Kep, Ve, ADC and MaRIA values ranged from 0.68 to 0.91 for differentiating inactive CD (CD remission) from active CD (mild to severe CD). The AUC when combining the Ktrans, Kep and Ve was 0.80, while combining DCE-MRI parameters and ADC values yielded the highest AUC of 0.95.CONCLUSIONDCE-MRI and DWI parameters all serve as measures to stage CD activity. When they are combined, the assessment performance is improved and better than MaRIA.

Defining Endpoints and Biomarkers in Inflammatory Bowel Disease: Moving the Needle Through Clinical Trial Design

Defining Endpoints and Biomarkers in Inflammatory Bowel Disease: Moving the Needle Through Clinical Trial Design

Diffusion-weighted magnetic resonance enterocolonography in assessing Crohn disease activity.

Diffusion‑weighted magnetic resonance imaging has the potential to identify inflamed bowel segments in patients with Crohn disease (CD). We aimed to determine diffusion‑weighted imaging (DWI) value to predict active CD and compare apparent diffusion coefficients (ADCs) with endoscopic and conventional indices of magnetic resonance imaging of CD activity. Overall, 229 patients with suspected and diagnosed CD prospectively underwent magnetic resonance enterocolonography (MR‑EC) with DWI sequence and ileocolonoscopy. The magnetic resonance activity index (MaRIA), Clermont index, and CD endoscopic index of severity (CDEIS) were calculated. The clinical diagnosis of CD was confirmed in 100 out of 229 patients. A DWI score of 2 or higher had 96.9% sensitivity and 82.3% specificity for diagnosing CD. A threshold ADC value of 1.3 × 10-3 mm2/s could distinguish between normal and inflamed bowel segments with a sensitivity of 73.8% and a specificity of 98%. For the MaRIA, a threshold ADC value of 1.32 × 10-3 mm2/s with a sensitivity of 97.9% and a specificity of 97.8% was established. There were significant differences in the DWI scores and ADC values comparing patients with inactive, mild, and moderate-to-severe disease (P <0.01). ADCs inversely correlated with the MaRIAglobal (r = -0.69; P = 0.001), Clermontglobal (r = -0.722; P = 0.001), and CDEIS (r = -0.69; P = 0.001). DWI is a valuable tool that is capable of identifying inflamed bowel segments as accurately as the conventional MaRIA score and of discriminating between mild and moderate-to-severe CD.