Reply to comment on "Ultrasonographic scores for ileal Crohn's disease assessment: better, worse or the same as contrast­enhanced ultrasound?

We read the comments by Nylund K et al. regarding our paper "Ultrasonographic scores for ileal Crohn's disease assessment: Better, worse or the same as contrast­enhanced ultrasound?". Intestinal ultrasound has become one of the most valuable developments in the past decade, a non-invasive, well-tolerated exam, with an easy repeatability, and absence of sedation, ionizing radiation, or preparation. Particularly for inflammatory bowel disease, where there is a lack of agreement of patient's symptoms with disease activity, in an era where the paradigm of mucosal healing is changing to transmural healing, and with the emergence of several therapies leading to repeated imaging surveillance, it is essential to highlight the role of intestinal ultrasound. Although intestinal ultrasound is an increasingly used tool to monitor inflammatory bowel disease activity, there is no widely accepted reproducible activity index, since the methodology for the development of the scores was shown to be insufficient in most studies and none have been adequately validated (Bots et al., J Crohns Colitis 12:920-9, 2018). In our study, we showed that the contrast-enhanced ultrasound (CEUS) peak enhancement derived from the time-intensity curve (TIC) is a promising non-invasive emerging method with a good accuracy to correlate clinical and endoscopic activity in the terminal ileum, superior to intestinal ultrasound scores relying on bowel wall thickness and colour Doppler.

Stepping it up: Physical activity is associated with a lower incidence of prolonged gastric transit time in capsule endoscopy.

BACKGROUND AND AIM: Physical activity has been proposed as a potential factor influencing capsule endoscopy (CE) gastric transit time (GTT). However, there is no reported factual evidence confirming this association. We aimed to prospectively assess the effect of physical activity in the first hour of CE in the occurrence of prolonged GTT. METHODS: This is a prospective study including consecutive patients undergoing CE. For each patient, a step counter was attached to the CE register. The number of steps during the first hour of the procedure was registered. The main outcome was prolonged GTT (CE remaining in the stomach for > 1 h). Outcomes were adjusted for possible confounders by multivariate analysis. RESULTS: We included 100 patients, 60% undergoing small bowel CE and 40% colon CE. The mean number of steps in the first hour was significantly lower in patients with prolonged GTT (2009 ± 1578 steps) comparatively with those without prolonged GTT (3597 ± 1889 steps) (P < 0.001). On multivariate analysis including significant confounders, steps in the first hour were an independent predictor of prolonged GTT (P = 0.018). Single-handedly, the number of steps taken in the first hour had a good acuity for predicting prolonged GTT (area under the curve = 0.74; P < 0.001), with an optimal cut-off of 2000 steps (sensitivity 81.3% and specificity 70%). CONCLUSIONS: Physical activity during the first hour of CE significantly decreased the occurrence of prolonged GTT. These findings pave the way for further definition of clear instructions to give to patients undergoing CE.

Small Bowel CLEansing Assessment and Report (SB-CLEAR): Standardizing bowel preparation report in capsule endoscopy.

BACKGROUND AND AIM: Small-bowel (SB) cleansing is crucial to assess the reliability of capsule endoscopy (CE) findings. However, the presence of multiple grading systems is hampering their use in clinical practice. In 2020, Colon CLeansing Assessment and Report (CC-CLEAR) was created and validated. We sought to develop and validate a new score for the evaluation of the SB cleansing, adapted from CC-CLEAR, aiming to standardize CE reporting regarding the quality of preparation. METHODS: The new grading score, SB CLeansing Assessment and Report (SB-CLEAR), divided the SB into three tertiles, each being scored depending on the percentage of visualized mucosa (0, < 50%; 1, 50%-75%; 2, > 75%; 3, > 90%). The overall classification was a sum of each segment score, graded between excellent, good, and inadequate (0-5). Any segment scoring ≤1 resulted in inadequate overall classification. CE videos were prospectively evaluated by two experienced CE readers blinded to each other. RESULTS: We included 52 CEs, 41(78.8%) female, with a mean age of 57.9 ± 17.9 years. Inter-observer agreement was very strong for each tertile (first: r = 0.863; second: r = 0.865; third: r = 0.861; P < 0.001), which resulted in overall excellent correlation when considering the quality of preparation in all tertiles (r = 0.940; P < 0.001). By applying final classifications of "inadequate," "good," and "excellent," correlation between observers was also very strong (r = 0.875; P < 0.001). CONCLUSIONS: SB-CLEAR is an innovative and reproducible grading score for evaluation of SB preparation quality in CE, with overall excellent inter-observer agreement. Along with CC-CLEAR, this may become a valuable tool to uniformize reporting of bowel preparation quality in CE.

Direct oral anticoagulants are associated with potentially bleeding lesions in suspected mid-gastrointestinal bleeding.

BACKGROUND AND AIM: Direct oral anticoagulants (DOACs) became a widespread alternative in anticoagulant therapy. Nevertheless, concerns are raised about their safety, with increased gastrointestinal bleeding rates being described. There are scarce studies regarding DOACs effect on small-bowel capsule endoscopy (SBCE) findings. We aimed to assess if the detection of lesions with high bleeding potential on SBCE was significantly different in patients treated with DOACs when compared to non-anticoagulated patients and to patients anticoagulated with other agents. METHODS: Cohort study including consecutive patients who underwent SBCE for suspected mid-gastrointestinal bleeding (MGIB) in 2019 and 2020. RESULTS: From 148 patients, 38 (25.7%) were anticoagulated, of which 26 (68.4%) with DOACs. P2 lesions were detected in 36.5% (n = 54) of the patients. These lesions were more frequently detected in patients under DOACs treatment when compared to non-anticoagulated patients (69.2% vs. 29.1%; p=.001), and also when compared to patients treated with other anticoagulants (69.2% vs. 33.3%; p=.037). No differences in P2 lesions detection were observed between patients treated with other anticoagulants and non-anticoagulated patients (33.3% vs. 29.1%; p=.747). In multivariate analysis, DOACs usage was significantly associated with higher detection rates of P2 lesions on SBCE, when adjusted for classical risk factors for MGIB (OR: 3.38; 95%CI = 1.23-9.26; p=.018). CONCLUSIONS: Despite their undeniable cardiovascular benefits and easy applicability, DOACs should still be considered with caution. These drugs were significantly associated with higher risk of potentially bleeding lesions on SBCE when compared to other anticoagulants and represent an independent risk factor for MGIB when adjusted for other variables.

RHEMITT score: Predicting the risk of mid gastrointestinal rebleeding after small bowel capsule endoscopy: A prospective validation.

BACKGROUND AND AIM: The RHEMITT score (Renal disease; Heart failure; Endoscopic findings; Major bleeding; Incomplete SBCE; Tobacco; Treatment by enteroscopy) was the first score to accurately predict the individual risk of small bowel rebleeding after capsule endoscopy (SBCE). The aim of the study is on the prospective validation of the RHEMITT score. METHODS: Cohort of consecutive patients with mid-gastrointestinal bleeding (MGIB) submitted to SBCE and followed prospectively, during at least 12 months, since 2017 until 2020. Rebleeding was defined as an overt bleeding event (melena or hematochezia) or a hemoglobin decrease of at least 2 g/dL. The RHEMITT score was calculated for each patient and the rebleeding rates compared. The performance of the score was tested by calculating the area under curve of the receiver operator characteristic curve. A rebleeding-free survival was assessed, corresponding to the period between the date of SBCE and the date of the first post-SBCE rebleeding event. RESULTS: We included 162 patients, 102 (62.9%) were female, with a mean age of 64 years old. The sensitivities and specificities of the score grades for predicting rebleeding were as following: for low-risk patients, 0% (0-10%) and 28.8% (21.1-36.5%); for intermediate-risk patients, 23.3% (8.2-38.4%) and 72% (64.3-79.7%); for high-risk patients, 76.7% (61.6-91.8%) and 99.2% (97.7-100%), corresponding to an area under curve of the receiver operator characteristic of 0.988 (P < 0.001). Kaplan-Meyer plots were statistically different according to the attributed risk (log-rank P value <0.001; Breslow-Wilcoxon P value <0.001). CONCLUSION: The RHEMITT score performed with excellent discriminative power in predicting rebleeding risk, and we herewith propose a surveillance of MGIB patients guided by the RHEMITT score.

Apex Score: Predicting Flares in Small-Bowel Crohn's Disease After Mucosal Healing.

BACKGROUND: Optimal strategies for using small-bowel capsule endoscopy (SBCE) in established small-bowel Crohn's disease (CD) remain uncertain. Mucosal healing (MH) has emerged as a valuable predictor of a flare-free disease. We aimed to evaluate the occurrence of disease flare on patients with small-bowel CD and MH, as well as to create a score identifying patients in higher risk for this outcome. METHODS: We analyzed consecutive patients submitted to SBCE for assessment of MH and included those where MH was confirmed. The incidence of disease flare was assessed during follow-up (minimum 12 months). A score predicting disease flare was created from several analyzed variables. RESULTS: From 47 patients with MH, 12 (25.5%) had a flare (versus 48.3% in excluded patients without MH; p = 0.01). Age ≤ 30 years (OR  = 70; p  = 0.048), platelet count ≥ 280 × 103/L (OR  = 12.24; p  =  0.045) and extra-intestinal manifestations (OR  =  11.76; p  =  0.033) were associated with increased risk of CD flare during the first year after SBCE with MH. These variables were used to compute a risk-predicting score-the APEX score-which assigned the patients to having low (0-3 points) or high-risk (4-7 points) of disease flare and had excellent accuracy toward predicting disease relapse (AUC  =  0.82; 95%CI 0.64-0.99). CONCLUSION: Patients with small-bowel CD and MH were not free of disease flares on the subsequent year, despite presenting lower rates when compared to those without MH. The APEX score demonstrated excellent accuracy at stratifying patients relapse risk and guiding further therapeutic options for patients achieving MH.

P020 Proton Pump Inhibitor Therapy: Providing "Acid" Outcomes in Patients With Inflammatory Bowel Disease Under Infliximab Treatment.

BACKGROUND: A recent meta-analysis has suggested that proton pump inhibitor (PPI) therapy is associated with lower clinical remission rates and a higher number of hospitalizations in patients with inflammatory bowel disease (IBD) under infliximab therapy. We aimed to assess if these differences kept their significance when adjusted for other possible confounders. METHODS: Cohort study of consecutive patients with Crohn's disease (CD) and Ulcerative Colitis (UC) under infliximab therapy. A minimum follow-up of 54 weeks after introduction of infliximab treatment was required. The analyzed outcomes were deep remission at week 54 and the need of IBD-related hospitalization, corticosteroid treatment or abdominal surgery under infliximab treatment. Collected possible confounders were age, gender, smoking habits, perianal disease, extra-intestinal manifestations, familiar history of IBD and concomitant use of immunomodulators. RESULTS: Our final sample included 104 patients, 56 (53.8%) of them females, with a mean age of 38.2±13.1 years. From these, 77 (74.0%) had CD and 27 (26.0%) had UC. PPI therapy was described in 21 (20.2%) of the patients under infliximab treatment. On univariate analysis, PPI users were found to have significantly lower rates of deep remission at week 54 (7.7 vs 28.3%; p = 0.034) and higher IBD-related hospitalization rates (47.6 vs 21.7%; p = 0.034). No differences were found regarding the need of corticosteroid therapy (4.8 vs 10.8%; p = 0.398) or abdominal surgery (33.7 vs 21.7; p = 0.201). When adjusted for the collected confounders by multivariate analysis, while not significantly influencing deep remission at week 54 (OR = 0.16; 95%CI = 0.02-1.63; p = 0.121), concomitant PPI therapy was a significant independent risk factor for IBD-related hospitalization (OR = 3.22; 95%CI = 1.11-9.34; p = 0.04). CONCLUSION: Despite not conducting to significantly different deep remission rates, concomitant PPI therapy was associated with a three-fold increase in hospitalization rates in IBD patients under infliximab treatment, even when adjusted for classical risk factors for adverse outcomes in IBD. These findings emphasize the importance of restricting PPI treatment to those with a clear clinical indication, especially in this set of patients.

P051 Identifying High-Risk Patients With Acute Severe Ulcerative Colitis: Is the ACE Index Useful?

BACKGROUND: Treatment delay in patients admitted with acute severe ulcerative colitis (ASUC) are associated with increased mortality. Therefore, it is essential to identify on admission patients at high-risk of steroid nonresponse who may benefit from earlier second-line treatment or surgical intervention. Recently, the ACE index was developed and includes 3 variables at admission: C-reactive protein (CRP) ≥50mg/dL, albumin ≤30g/L and endoscopic severity (Mayo endoscopic score=3), and ranges between 0-3 points. An index of 3 has been shown to be useful to identify patients with acute ulcerative colitis with high-risk of steroid nonresponse. OBJECTIVES: To assess the ACE index performance in predicting steroids response in ASUC. METHODS: Retrospective study including consecutive admissions for ASUC according to Truelove and Witts definition between January 2005 and December 2020. The ACE index was calculated and its accuracy for predicting response to steroids on admission in ASUC was assessed through the area under the curve (AUC). RESULTS: Sixty-five patients were included of whom 78.5% responded to steroids. Mean CRP (p = 0.01), albumin (p=0.02) and endoscopic severity score (p < 0.001) at admission were significantly different between responders and nonresponders, as opposed to Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score (p = 0.32). Median ACE index was 2. The ACE index was a predictor of steroids response (AUC 0.789; p = 0.001); 50.0% of patients with an index of 3 did not respond to steroids, and 86.3% of patients with an index inferior to 3 responded to steroids (positive predictive value 50.0%; negative predictive value of 86.3%). CONCLUSION: The ACE index is an accurate predictor of steroids response on admission in ASUC. However, in our study, the ACE index doesn´t discriminate whose high-risk patients would benefit from earlier therapeutic escalation, since only 50.0% of patients with an index of 3 did not respond to steroids.

Colon Capsule CLEansing Assessment and Report (CC-CLEAR): a new approach for evaluation of the quality of bowel preparation in capsule colonoscopy.

BACKGROUND AND AIMS: Current colon capsule (CC) cleansing grading scales rely on subjective parameters and lack proper interobserver agreement. We should strive for higher intra- and interobserver agreement for the evaluation of the cleansing quality of CCs. Here we sought to validate a new grading scale for the evaluation of CC cleansing. METHODS: For the new grading scale, named Colon Capsule CLEansing Assessment and Report (CC-CLEAR), the colon was divided in 3 segments: right-sided, transverse, and left-sided colon. Each segment was scored according to an estimation of the percentage of visualized mucosa (0, <50%; 1, 50%-75%; 2, >75%; 3, >90%). The overall cleansing classification was a sum of each segment score, grading between excellent (8-9), good (6-7), and inadequate (0-5). Any segment scoring ≤1 resulted in inadequate overall classification. Videos were reviewed and scored using CC-CLEAR and the Leighton-Rex grading scale by 2 experienced operators blinded to each other. Kendall's coefficient evaluated inter- and intraobserver agreement. RESULTS: We included 58 consecutive CCs, corresponding to 75.9% women, with a mean age of 65 years. Overall cleansing CC-CLEAR classifications were as follows: reader A, 22.4% (n = 13) excellent, 31% (n = 18) good, and 46.5% (n = 27) inadequate; and reader B, 24.1% (n = 14) excellent, 22.4% (n = 13) good, and 53.4% (n = 31) inadequate. CC-CLEAR interobserver agreement was superior to the Leighton-Rex scale (Kendall's W .911 vs .806, respectively; P < .01). The intraobserver agreement for CC-CLEAR was excellent for both readers (P > .01). CONCLUSIONS: CC-CLEAR is a new practical and reliable grading scale for the evaluation of bowel preparation quality using a CC, with excellent inter- and intraobserver agreement.

Does Perianal Disease Influence the Efficacy of Combination Therapy in Crohn's Disease?

BACKGROUND: Perianal disease is associated with a disabling course of Crohn's disease (CD). We aim to study the impact of perianal disease on CD remission rates, after a 1-year course of infliximab in combination therapy with azathioprine. METHODS: This was a retrospective, single-center cohort study, including consecutive CD patients on combination therapy, followed for 1 year since induction. The outcome variable was split into clinical and endoscopic remissions. The correlation toward the outcome variable was assessed with univariate and multivariate analysis and a survival assessment, using SPSS software. RESULTS: We assessed 74 CD patients, of whom 41 (55.4%) were female, with a mean age of 36 years. Thirty-nine percent of the patients presented perianal disease at diagnosis (n = 29). We documented 70.3% clinical and 47.2% endoscopic remissions. Several variables had statistical significance toward the outcomes (endoscopic and clinical remissions) in the univariate analysis. After adjusting for confoundment, patients with perianal disease presented an odds ratio (OR) of 0.201 for achieving endoscopic remission (CI: 0.054-0.75, p value 0.017) and an OR of 0.203 for achieving clinical remission (CI: 0.048-0.862, p value 0.031). Sixty-six patients (89.2%) presented an initial response to treatment, from whom, 20 (30.3%) exhibited at least 1 disease relapse (clinical and/or endoscopic). Patients with perianal disease presented higher probability of disease relapse, displaying statistically significant difference on Kaplan-Meier curves (Breslow p value 0.043). CONCLUSION: In the first year of combination therapy, perianal disease is associated with an 80% decrease in endoscopic and clinical remission rates and higher ratio of disease relapse.

Small Bowel Angioectasias Rebleeding and the Identification of Higher Risk Patients.

BACKGROUND: Small bowel capsule endoscopy (SBCE) is the gold standard for suspected small bowel bleeding (SBB). Angioectasias are the most common vascular anomalies in the gastrointestinal tract and have been reported as the source of SBB in up to 80% of patients. Considering their frequency, their usual intermittent bleeding nature, and their risk of rebleeding, the aim of this study was to identify some features and possible predictors of rebleeding in the presence of these lesions. METHODS: This is a retrospective study, which included consecutive SBCE with angioectasias between April 2008 and December 2017 with a minimum follow-up of 12 months. Rebleeding was defined as a drop of hemoglobin ≥ 2 g/dl and/or in the presence of hematochezia or melenas with negative esophagogastroduodenoscopy and ileocolonoscopy. Data were collected from medical records, and angioectasias were classified by number, location, size, and type. Univariate and multivariable statistical analysis was performed to identify possible predictors of rebleeding. RESULTS: From a total of 630 patients submitted to SBCE for suspected SBB, 129 with angioectasias were included; 59.7% were female, with a median age of 72 (19-91) years old and a mean follow-up of 44.0 ± 31.9 months. In 32.6% (n = 42) of the patients, at least one episode of rebleeding was documented. The presence of heart failure (OR 3.41; IC95% 1.18-9.89; p = 0.024), the size of the angioectasias (OR 5.41; IC95% 2.15-13.6; p < 0.001), and smoking status (OR 3.15; IC95% 1.07-9.27; p = 0.038) were independent predictor factors of rebleeding. CONCLUSION: Heart failure, smoking status, and angioectasias with a size superior to 5 mm are independent predictor factors of rebleeding in a population with angioectasias diagnosed by SBCE.

Small-bowel transit time in capsule endoscopy: a determinant factor for the diagnosis of small-bowel bleeding.

BACKGROUND: small-bowel capsule endoscopy (SBCE) is the gold standard for the study of small-bowel bleeding (SBB). Recent studies suggest that longer small-bowel transit times (SBTT) may be associated with a higher diagnostic yield of SBCE. AIM: the aim of the study was to investigate if longer SBTT is a predictive factor of positive findings on SBCE in a population that underwent SBCE for suspected SBB. METHODS: a retrospective single-center study including consecutive SBCEs between May 2012 and May 2019, due to suspected SBB. A positive SBCE was considered in the presence of lesions with high bleeding potential such as ulcers, angioectasias, and tumors (P2 lesions, according to the Saurin classification). RESULTS: we included 372 patients, 65.9 % female, with a median age of 67 (IQR: 19-97) years. We observed that patients with P2 lesions (n = 131; 35.2 %) in SBCE exhibited a longer SBTT (p = 0.01), were older (p < 0.001), were more frequently male (p = 0.019), and suffered more frequently from arterial blood hypertension (p = 0.011), diabetes (p = 0.042), chronic kidney disease (p = 0.003), and heart failure (p = 0.001). In the logistic analysis, significant predictive factors for the presence of P2 lesions included age (OR: 1.027; 95 % CI: 1.009-1.045; p = 0.004), SBTT (OR: 1.002; 95 % CI: 1.001-1.005; p = 0.029), and male gender (OR: 1.588; 95 % CI: 1.001-2.534; p = 0.049). CONCLUSIONS: patients with longer SBTT had higher rates of lesions with high bleeding potential (P2). SBTT along with previously well-defined factors such as age and male gender were the only independent predictive factors for the presence of P2 lesions. These findings may suggest that a slower passage of the capsule through the small bowel may allow a better diagnostic yield for significant lesions.

Simplify to improve in capsule endoscopy - TOP 100 is a swift and reliable evaluation tool for the small bowel inflammatory activity in Crohn's disease.

Background: Capsule endoscopy is a widely recognized method to study the small bowel, including in patients with Crohn's disease (CD). The Lewis score (LS) is a valuable tool in this setting, able to assess inflammatory activity. TOP100, a new software tool of the RAPID Reader®, emerged to assist in the time-consuming capsule reading process, by automatically selecting 100 images that will most likely contain abnormalities.Aim: Evaluate the agreement between TOP100 and classic reading (CR) in determining LS in the setting of CD.Methods: Retrospective study including consecutive patients undergoing small bowel capsule endoscopy (SBCE) for suspected or established CD. One experienced reader performed CR and calculated the LS. Another experienced reader, blinded to the CR results, reviewed all SBCE videos using TOP100 and calculated the LS.Results: One hundred and fifteen patients were included. SBCE detected significant inflammatory activity (LS ≥135) in 64 patients (55.7%). We verified a strong agreement between the two methods of capsule reading (Kappa = 0.83, p < .001), with an agreement on 89.6% of the cases. The agreement was superior in moderate-to-severe inflammatory activity (Kappa = 0.92, p < .001). All cases of moderate-to-severe activity detected by CR were identified by TOP100 as significant inflammatory activity. A good agreement was verified in all tertiles (p < .001).Conclusions: Although the classical review of the entire video remains the gold standard, the TOP100 has been shown to be a useful tool in assisting the reader in a prompt calculation of LS, in particular for identifying patients with moderate-to-severe inflammatory disease.

RHEMITT Score: Predicting the Risk of Rebleeding for Patients with Mid-Gastrointestinal Bleeding Submitted to Small Bowel Capsule Endoscopy.

INTRODUCTION: Small bowel capsule endoscopy (SBCE) is the gold standard for mid-gastrointestinal bleeding (MGIB). No score has been developed to predict the risk of small bowel rebleeding after SBCE. OBJECTIVE: Creating a predictive small bowel rebleeding risk score for MGIB, after initial SBCE. METHODS: Retrospective, single center study, including SBCEs for MGIB, from June 2006 to October 2016. The minimum follow-up was 12 months. Univariate analysis and a multivariable Cox regression model tested the association with rebleeding. Statistically significant variables were used to compute the score. The score's accuracy was tested through a receiver operating characteristic (ROC) curve. A classification tree identified risk groups. For internal validation, we performed a 5-fold cross validation. RESULTS: We assessed 357 SBCEs for MGIB, of which 88 (24.6%) presented rebleeding during follow-up. Seven variables were used to compute a risk-predicting score - the RHEMITT score - namely, renal disease; heart failure; endoscopic capsule P1/P2 lesions; major bleeding; incomplete capsule; tobacco consumption; and endoscopic treatment. The score presented good accuracy toward the outcome (area under the curve ROC 0.842, 95% CI 0.757-0.927). We established 3 rebleeding risk groups: low (0-3 points); intermediate (4-10 points); and high (+11 points). CONCLUSION: A new MGIB score, named RHEMITT, accurately anticipates the individual risk of small bowel rebleeding after initial SBCE.

Low fecal calprotectin predicts clinical remission in Crohn's disease patients: the simple answer to a challenging question.

BACKGROUND AND AIM: Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation. Predicting relapses in Crohn's disease (CD) patients can allow earlier changes in therapy. The aim of this study was to evaluate the role of FC in predicting relapse in CD patients in clinical remission within six months follow-up. METHODS: Patients with CD who were in clinical remission at least ≥3 months were included in this study. The first FC sample during the remission period was evaluated and was used as the baseline value. Relapse was defined as an unexpected escalation in therapy, hospitalization or need for surgery for active CD. The accuracy and optimal cutoff FC values for predicting clinical relapse at six months were assessed by the area under the ROC curve (AUC). RESULTS: One hundred and forty-four patients were evaluated, with mean age of 38.4 years. Of these, 13 (9%) had a relapse during the follow-up period. The mean FC value was significantly lower for non-relapsers (203.2 µg/g) than for relapsers (871.3 µg/g), p < .001. The AUC for predicting relapse by using FC values was 0.924. The optimal cutoff FC value to predict relapse was 327 µg/g; with values of sensitivity, specificity, negative predictive value and positive predictive value were 92.3%, 82.4%, 99.1% and 34.3%, respectively. CONCLUSIONS: FC is more useful in predicting remission maintenance than relapse in patients with CD in clinical remission. Values of FC ≤327 µg/g can exclude relapse at least at six months follow-up period.

CECDAIic - a new useful tool in pan-intestinal evaluation of Crohn's disease patients in the era of mucosal healing.

Background: Pan-intestinal capsule endoscopy (Pan-CE) has been used to assess both the small and large bowel inflammation in Crohn's disease (CD) patients in a single examination. The capsule endoscopy Crohn's disease activity index (CECDAI) was initially developed to measure mucosal disease activity in the small bowel, although in 2018, it was extended to the colon for standardization of inflammatory activity (CECDAIic). The aim of this study was to apply the CECDAIic in a cohort of CD patients that underwent Pan-CE to evaluate the inter-observer agreement and the correlation between this score and inflammatory parameters.Methods: The videos were read and scored using the CECDAIic by three independent experienced operators, blinded to the results of the standard workup. Statistical analysis was performed with SPSS®, using Kendall's coefficient to evaluate the inter-observer agreement. Spearman correlation (rs) was used to access the correlation between the score and inflammatory biomarkers.Results: Included 22 patients, 59.1% males with mean age of 30.7 ± 11.1 years. The median CECDAIic score was 9.17 (0-37). The overall CECDAIic score Kendall coefficient was 0.94, demonstrating a statistically significant (p < .001) and excellent agreement between the three observers. In addition, we found a very good correlation between CECDAIic and calprotectin (rs = 0.82; p = .012) and a moderate correlation with C-reactive protein (CRP, rs = 0.50; p = .019).Conclusions: CECDAIic is a new score with excellent inter-observer agreement and strong correlation with calprotectin levels.

ORBIT score: an useful predictor of small bowel rebleeding in patients under chronic anticoagulation.

BACKGROUND AND STUDY AIMS: Available scoring systems to assess the risk for major bleeding in patients on chronic anticoagulation seem inadequate in predicting higher diagnostic yields of small bowel capsule endoscopy (SBCE) or higher rebleeding rates in patients with suspected small bowel bleeding. The aim of this study was to evaluate the ability of the new ORBIT score in predicting positive findings of SBCE or higher rebleeding rates in chronically anticoagulated patients with suspected small bowel bleeding. PATIENTS AND METHODS: Retrospective analysis of 570 patients who consecutively underwent SBCE for the study of suspected small bowel bleeding. For each of the 67 patients who were on chronic anticoagulation, ORBIT score (Older age, Reduced hemoglobin/hematocrit, Bleeding history, Insufficient kidney function and Treatment with antiplatelets) was calculated. Patients were classified as high-risk (ORBIT score ≥4) or low/intermediate-risk (ORBIT score <4). Data on SBCE findings, diagnostic yield and rebleeding were compared between groups. RESULTS: When ORBIT score was calculated, 41 and 26 patients were classified as low/intermediate-risk and high-risk, respectively. When low/intermediate-risk and high-risk groups were compared, no differences were found in the diagnostic yield of SBCE (39.0% vs. 23.1%; p = .176). However, in high-risk patients, rebleeding was significantly more common than in low/intermediate-risk patients (80.0% vs. 36.6%; p = .003). CONCLUSIONS: In patients presenting with suspected small bowel bleeding and on chronic anticoagulation, the new ORBIT score seems promising in identifying those with a higher risk of rebleeding, in whom a closer follow-up and a more aggressive diagnostic and therapeutic strategy is advisable.

Perianal Crohn's disease - association with significant inflammatory activity in proximal small bowel segments.

OBJECTIVES: Perianal Crohn's disease (CD) prevalence varies according to the disease location, being particularly frequent in patients with colonic involvement. We aimed to evaluate small bowel involvement and compare small bowel capsule endoscopy findings and inflammatory activity between patients with and without perianal disease. MATERIALS AND METHODS: Retrospective single-center study including 71 patients - all patients with perianal CD (17 patients) who performed a small bowel capsule endoscopy were included, and non-perianal CD patients were randomly selected (54 patients). Clinical and analytical variables at diagnosis were reviewed. Statistical analysis was performed with SPSS v21.0 and a two-tailed p value <.05 was defined as indicating statistical significance. RESULTS: Patients had a median age of 30 ± 16 years with 52.1% females. Perianal disease was present in 23.9%. Patients with perianal disease had significantly more relevant findings (94.1% vs 66.6%, p = .03) and erosions (70.6% vs 42.6%, p = .04), however, no differences were found between the two groups regarding ulcer, villous edema and stenosis detection. Overall, patients with perianal disease had more frequently significant small bowel inflammatory activity, defined as a Lewis Score ≥135 (94.1% vs 64.8%, p = .03), and higher Lewis scores in the first and second tertiles (450 ± 1129 vs 0 ± 169, p = .02 and 675 ± 1941 vs 0 ± 478, p = .04, respectively). No differences were found between the two groups regarding third tertile inflammatory activity assessed with the Lewis Score. CONCLUSION: Patients with perianal CD have significantly higher inflammatory activity in the small bowel, particularly in proximal small bowel segments, when compared with patients without perianal disease.

Capsule endoscopy with PillCamSB2 versus PillCamSB3: has the improvement in technology resulted in a step forward?

AIM: To compare the findings and completion rate of PillCam® SB2 and SB3. METHODS: This was a retrospective single-center study that included 357 consecutive small bowel capsule endoscopies (SBCE), 173 SB2 and 184 SB3. The data collected included age, gender, capsule type (PillCam® SB2 or SB3), quality of bowel preparation, completion of the examination, gastric and small bowel transit time, small bowel findings, findings in segments other than the small bowel and the detection of specific anatomical markers, such as the Z line and papilla. RESULTS: The mean age of the patients was 48 years and 66.9% were female. The two main indications were suspicion/staging of inflammatory bowel disease (IBD) and obscure gastrointestinal bleeding (OGIB) (43.7% and 40.3%, respectively). Endoscopic findings were reported in 76.2% of examinations and 53.5% were relevant findings. No significant differences were found between SB2 and SB3 with regard to completion rate (93.6% vs 96.2%, p = 0.27), overall endoscopic findings (73.4% vs 78.8%, p = 0.23), relevant findings (54.3% vs 52.7%, p = 0.76), first tertile findings (43.9% vs 48.9%, p = 0.35), extra-SB findings (23.7% vs 17.3%, p = 0.14), Z line and papilla detection rate (35.9% vs 35.7%, p = 0.97 and 27.1% vs 32.6%, p = 0.32, respectively). With regard to the patient subgroups with suspicion/staging of IBD, significant differences were found in relation to the detection of villous edema and the 3rd tertile findings, thus favoring SB3 (26.3% vs 43.8%, p = 0.02 and 47.4% vs 66.3%, p = 0.02, respectively). Mucosal atrophy was significantly more frequently diagnosed with the PillCam® SB3 in patients with anemia/OGIB (0% vs 8%, p = 0.03). CONCLUSIONS: Overall, PillCam® SB3 did not improve the diagnostic yield compared to SB2, although it improved the detection of villous atrophy and segmental edema.

Can we rely on inflammatory biomarkers for the diagnosis and monitoring Crohn's disease activity?

BACKGROUND: Small bowel capsule endoscopy (SBCE) is a very important tool in the diagnosis and monitoring of Crohn's disease (CD). The Lewis score (LS) and Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) are used to quantify and standardize inflammatory activity observed in the SBCE. AIM: To evaluate the correlation between the LS and CECDAI scores and inflammation biomarkers (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]). A secondary goal was to define thresholds for CECDAI based on thresholds already established for LS. METHODS: This was a retrospective study of 110 patients with suspect or known CD, with involvement of small bowel. Linear regression was used to calculate thresholds of CECDAI corresponding to the thresholds already established for LS. A Pearson correlation (r) was used to calculate the correlation between the LS and CECDAI scores and biomarker levels. Only patients with exclusive involvement of the small bowel were selected (n = 78). RESULTS: A moderate correlation was found between the endoscopic scores (r = 0.59, p < 0.001). CECDAI scores of 5.57 and 7.53 corresponded to scores of 135 and 790 in LS, respectively. There was a statistically significant correlation between CRP and the LS (r = 0.28, p = 0.014) and CECDAI (r = 0.29, p = 0.009). There was also a significant correlation between ESR and CECDAI (r = 0.29, p = 0.019), but not with LS. CONCLUSION: There is a moderate correlation between the two scores. This study allowed the calculation of thresholds for CECDAI based on those defined for LS. We found a weak correlation between SBCE endoscopic activity and inflammatory biomarkers.