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Video capsule endoscopy (VCE) of the small-bowel has been proven to accurately diagnose small-bowel inflammation and to predict future clinical flares among patients with Crohn’s disease (CD). In 2017, the panenteric capsule (PillCam Crohn’s system) was introduced for the first time, enabling a reliable evaluation of the whole small and large intestines. The great advantage of visualization of both parts of the gastrointestinal tract in a feasible and single procedure, holds a significant promise for patients with CD, enabling determination of the disease extent and severity, and potentially optimize disease management. In recent years, applications of machine learning, for VCE have been well studied, demonstrating impressive performance and high accuracy for the detection of various gastrointestinal pathologies, among them inflammatory bowel disease lesions. The use of artificial neural network models has been proven to accurately detect/classify and grade CD lesions, and shorten the VCE reading time, resulting in a less tedious process with a potential to minimize missed diagnosis and better predict clinical outcomes. Nevertheless, prospective, and real-world studies are essential to precisely examine artificial intelligence applications in real-life inflammatory bowel disease practice.

Background: Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn’s disease (CD). However, data regarding its predictive role in this population over an extended follow-up are scarce. Objectives: To predict clinical exacerbation and to assess the yield of Lewis score in identifying CD patients with future clinical exacerbation during an extended follow-up (>24 months). Design: A post hoc analysis study. Methods: Adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography in a prospective study (between 2013 and 2018). We extracted extended clinical data (up to April 2022). The primary composite outcome (i.e. clinical exacerbation) was defined as intestinal surgery, endoscopic dilation, CD-related admission, corticosteroid administration, or biological/immunomodulator treatment change during follow-up. Results: Of the 61 patients in the study [median age 29 (24–37) years, male 57.4%, biologic treatment 46.7%], 18 patients met the primary outcome during an extended follow-up [median 58.0 (34.5–93.0) months]. On univariable analysis, complicated [hazard ratio (HR) 7.348, p = 0.002] and stricturing disease phenotype (HR 5.305, p = 0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) ⩾ 135 identified patients with future exacerbation [AUC (area under the curve) 0.767, 95% confidence interval (CI) 0.633–0.902, p = 0.001, HR 6.317, 93% negative predictive value], whereas the AUC of the conventional Lewis score was 0.734 (95% CI: 0.589–0.879, p = 0.004). Sensitivity analysis restricted to patients with either complicated ( n = 34) or stricturing ( n = 26) disease phenotype revealed that midLS still predicted clinical exacerbation during follow-up (AUC 0.747/0.753, respectively), in these patients. Conclusion: MidLS predicts treatment failure in quiescent CD patients (median follow-up of 5 years) independently of disease phenotype.

Background: Deep learning techniques can accurately detect and grade inflammatory findings on images from capsule endoscopy (CE) in Crohn’s disease (CD). However, the predictive utility of deep learning of CE in CD for disease outcomes has not been examined. Objectives: We aimed to develop a deep learning model that can predict the need for biological therapy based on complete CE videos of newly-diagnosed CD patients. Design: This was a retrospective cohort study. The study cohort included treatment-naïve CD patients that have performed CE (SB3, Medtronic) within 6 months of diagnosis. Complete small bowel videos were extracted using the RAPID Reader software. Methods: CE videos were scored using the Lewis score (LS). Clinical, endoscopic, and laboratory data were extracted from electronic medical records. Machine learning analysis was performed using the TimeSformer computer vision algorithm developed to capture spatiotemporal characteristics for video analysis. Results: The patient cohort included 101 patients. The median duration of follow-up was 902 (354–1626) days. Biological therapy was initiated by 37 (36.6%) out of 101 patients. TimeSformer algorithm achieved training and testing accuracy of 82% and 81%, respectively, with an Area under the ROC Curve (AUC) of 0.86 to predict the need for biological therapy. In comparison, the AUC for LS was 0.70 and for fecal calprotectin 0.74. Conclusion: Spatiotemporal analysis of complete CE videos of newly-diagnosed CD patients achieved accurate prediction of the need for biological therapy. The accuracy was superior to that of the human reader index or fecal calprotectin. Following future validation studies, this approach will allow for fast and accurate personalization of treatment decisions in CD.

Background: Artificial intelligence (AI) is rapidly infiltrating multiple areas in medicine, with gastrointestinal endoscopy paving the way in both research and clinical applications. Multiple challenges associated with the incorporation of AI in endoscopy are being addressed in recent consensus documents. Objectives: In the current paper, we aimed to map future challenges and areas of research for the incorporation of AI in capsule endoscopy (CE) practice. Design: Modified three-round Delphi consensus online survey. Methods: The study design was based on a modified three-round Delphi consensus online survey distributed to a group of CE and AI experts. Round one aimed to map out key research statements and challenges for the implementation of AI in CE. All queries addressing the same questions were merged into a single issue. The second round aimed to rank all generated questions during round one and to identify the top-ranked statements with the highest total score. Finally, the third round aimed to redistribute and rescore the top-ranked statements. Results: Twenty-one (16 gastroenterologists and 5 data scientists) experts participated in the survey. In the first round, 48 statements divided into seven themes were generated. After scoring all statements and rescoring the top 12, the question of AI use for identification and grading of small bowel pathologies was scored the highest (mean score 9.15), correlation of AI and human expert reading-second (9.05), and real-life feasibility-third (9.0). Conclusion: In summary, our current study points out a roadmap for future challenges and research areas on our way to fully incorporating AI in CE reading.

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population.

Background: The diagnosis of proximal small bowel involvement in Crohn’s disease (CD) can be challenging at magnetic resonance enterography (MRE). The inflammatory process in CD can be associated with peri-intestinal inflammatory reactions, including the presence of inflamed mesenteric lymph nodes. Objectives: To evaluate the significance of inflamed mesenteric lymph nodes adjacent to the jejunum at MRE in CD and the association with proximal bowel disease as detected by video capsule endoscopy (VCE). Design: This retrospective study was performed in two tertiary medical centres, and included 64 patients with CD who underwent MRE as well as VCE within 1 year. Methods: Data were collected for examinations performed between August 2013 and February 2021. MRE images were independently reviewed by radiologists who were blinded to the clinical data. Association between the presence of mesenteric lymph nodes adjacent to jejunum at MRE and disease activity according to VCE Lewis scores of proximal small bowel was examined. Results: VCE detected proximal disease in 24/64 patients (37.5%). Presence of regional lymph nodes in the jejunal mesentery was significantly associated with jejunal disease as seen on VCE ( p

Background and aimAnti-TNFα is measurable in infants exposed in utero up to 12 months of age. Data about the exposure effect on the infant’s adaptive immunity are limited. We aimed to prospectively evaluate the distribution and function of T and B cells, in infants of females with inflammatory bowel disease, in utero exposed to anti-TNFα or azathioprine.MethodsA prospective multi-center study conducted 2014–2017. Anti-TNFα levels were measured in cord blood, and at 3 and 12 months. T-cell repertoire and function were analyzed at 3 and 12 months by flow-cytometry, expression of diverse T cell receptors (TCR) and T-cell receptor excision circles (TREC) quantification assay. Serum immunoglobulins and antibodies for inactivated vaccines were measured at 12 months. Baseline clinical data were retrieved, and 2-monthly telephonic interviews were performed regarding child infections and growth.Results24 pregnant females, age 30.6 (IQR 26.5–34.5) years were recruited, 20 with anti-TNFα (infliximab 8, adalimumab 12), and 4 with azathioprine treatment. Cord blood anti-TNFα was higher than maternal blood levels [4.3 (IQR 2.3–9.2) vs. 2.5 (IQR 1.3–9.7) mcg/ml], declining at 3 and 12 months. All infants had normal number of B-cells (n = 17), adequate levels of immunoglobulins (n = 14), and protecting antibody levels to Tetanus, Diphtheria, Hemophilus influenza-B and hepatitis B (n = 17). All had normal CD4+, CD8+ T-cells, and TREC numbers. TCR repertoire was polyclonal in 18/20 and slightly skewed in 2/20 infants. No serious infections requiring hospitalization were recorded.ConclusionWe found that T-cell and B-cell immunity is fully mature and immune function is normal in infants exposed in utero to anti-TNFα, as in those exposed to azathioprine. Untreated controls and large-scale studies are needed to confirm these results.

Crohn’s disease (CD) is a chronic inflammatory disorder characterized by a transmural inflammation that may involve any part of the gastrointestinal tract. An evaluation of small bowel involvement, allowing recognition of disease extent and severity, is important for disease management. Current guidelines recommend the use of capsule endoscopy (CE) as a first-line diagnosis method for suspected small bowel CD. CE has an essential role in monitoring disease activity in established CD patients, as it can assess response to treatment and identify high-risk patients for disease exacerbation and post-operative relapse. Moreover, several studies have shown that CE is the best tool to assess mucosal healing as part of the treat-to-target strategy in CD patients. The PillCam Crohn’s capsule is a novel pan-enteric capsule which enables visualization of the whole gastrointestinal tract. It is useful to monitor pan-enteric disease activity, mucosal healing and accordingly allows for the prediction of relapse and response using a single procedure. In addition, the integration of artificial intelligence algorithms has showed improved accuracy rates for automatic ulcer detection and the ability to shorten reading times. In this review, we summarize the main indications and virtue for using CE for the evaluation of CD, as well as its implementation in clinical practice.

Background: Higher infliximab trough levels (TLs) correlate with better clinical, inflammatory, and endoscopic outcomes among inflammatory bowel disease (IBD) patients. Although standard scheduled infliximab therapy regimen consists of infusions at pre-defined time-points (weeks 0, 2, 6, and every 8 weeks), short-period deviations from therapeutic schedule are common in ‘real life’, but the pharmacokinetic impact of these deviations has not been explored. In this study, we aim to determine whether short-period deviations from infusion schedule affect infliximab-TL. Methods: A retrospective analysis of all IBD patients receiving infliximab maintenance therapy every 8 weeks was conducted in a tertiary medical center. Patients with anti-drug antibodies, deliberate interval shortening and 59 days since last infusion) was found to significantly affect TL (mean difference in TL 0.9 μg/mL, 95% confidence interval (CI): 0.03–1.9 μg/mL, p 3 days culminate in measurable decrease of TL, although effect on clinical outcome is unclear. This needs to be taken into account when interpreting drug-level test results. Summary: A total of 2088 sera of 302 maintenance period inflammatory bowel disease (IBD) patients treated with infliximab were analyzed, to assess effect of small deviations from infusion schedule on TLs. A significant decline in patients’ trough level (TL) was noted as early as 3 days after scheduled infusion.

Background and Aims: The aim of our study was to create an accurate patient-level combined algorithm for the identification of ulcers on CE images from two different capsules. Methods: We retrospectively collected CE images from PillCam-SB3′s capsule and PillCam-Crohn’s capsule. ML algorithms were trained to classify small bowel CE images into either normal or ulcerated mucosa: a separate model for each capsule type, a cross-domain model (training the model on one capsule type and testing on the other), and a combined model. Results: The dataset included 33,100 CE images: 20,621 PillCam-SB3 images and 12,479 PillCam-Crohn’s images, of which 3582 were colonic images. There were 15,684 normal mucosa images and 17,416 ulcerated mucosa images. While the separate model for each capsule type achieved excellent accuracy (average AUC 0.95 and 0.98, respectively), the cross-domain model achieved a wide range of accuracies (0.569–0.88) with an AUC of 0.93. The combined model achieved the best results with an average AUC of 0.99 and average mean patient accuracy of 0.974. Conclusions: A combined model for two different capsules provided high and consistent diagnostic accuracy. Creating a holistic AI model for automated capsule reading is an essential part of the refinement required in ML models on the way to adapting them to clinical practice.

Background and Study Aims: Deep learning (DL) for video capsule endoscopy (VCE) is an emerging research field. It has shown high accuracy for the detection of Crohn's disease (CD) ulcers. Non-steroidal anti-inflammatory drugs (NSAIDS) are commonly used medications. In the small bowel, NSAIDs may cause a variety of gastrointestinal adverse events including NSAID-induced ulcers. These ulcers are the most important differential diagnosis for small bowel ulcers in patients evaluated for suspected CD. We evaluated a DL network that was trained using CD VCE ulcer images and evaluated its performance for NSAID ulcers.Patients and Methods: The network was trained using CD ulcers and normal mucosa from a large image bank created from VCE of diagnosed CD patients. NSAIDs-induced enteropathy images were extracted from the prospective Bifidobacterium breve (BIf95) trial dataset. All images were acquired from studies performed using PillCam SBIII. The area under the receiver operating curve (AUC) was used as a metric. We compared the network's AUC for detecting NSAID ulcers to that of detecting CD ulcers.Results: Overall, the CD training dataset included 17,640 CE images. The NSAIDs testing dataset included 1,605 CE images. The DL network exhibited an AUC of 0.97 (95% CI 0.97–0.98) for identifying images with NSAID mucosal ulcers. The diagnostic accuracy was similar to that obtained for CD related ulcers (AUC 0.94–0.99).Conclusions: A network trained on VCE CD ulcers similarly identified NSAID findings. As deep learning is transforming gastrointestinal endoscopy, this result should be taken into consideration in the future design and analysis of VCE deep learning applications.

(1) Background: Villous atrophy is an indication for small bowel capsule endoscopy (SBCE). However, SBCE findings are not described uniformly and atrophic features are sometimes not recognized; (2) Methods: The Delphi technique was employed to reach agreement among a panel of SBCE experts. The nomenclature and definitions of SBCE lesions suggesting the presence of atrophy were decided in a core group of 10 experts. Four images of each lesion were chosen from a large SBCE database and agreement on the correspondence between the picture and the definition was evaluated using the Delphi method in a broadened group of 36 experts. All images corresponded to histologically proven mucosal atrophy; (3) Results: Four types of atrophic lesions were identified: mosaicism, scalloping, folds reduction, and granular mucosa. The core group succeeded in reaching agreement on the nomenclature and the descriptions of these items. Consensus in matching the agreed definitions for the proposed set of images was met for mosaicism (88.9% in the first round), scalloping (97.2% in the first round), and folds reduction (94.4% in the first round), but granular mucosa failed to achieve consensus (75.0% in the third round); (4) Conclusions: Consensus among SBCE experts on atrophic lesions was met for the first time. Mosaicism, scalloping, and folds reduction are the most reliable signs, while the description of granular mucosa remains uncertain.

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

Background: Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. Objective: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. Methods: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. Results: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. Conclusion: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

Background: Matrix metalloproteinase-9 (MMP-9) is a novel marker of intestinal inflammation. The aim of this study was to assess if serum MMP-9 levels predict clinical flare in patients with quiescent Crohn’s disease (CD). Methods: This study was a post hoc analysis of a prospective observational study in which quiescent CD patients were included and followed until clinical relapse or the end of a 2-year follow-up period. Serial C-reactive protein (CRP) and fecal calprotectin (FC) levels were measured, and the patients underwent repeated capsule endoscopies (CEs) every 6 months. Small bowel inflammation was quantified by Lewis score (LS) for CE. A baseline magnetic resonance enterography was also performed, and MaRIA score was calculated. Serum MMP-9 levels in baseline blood samples were quantified by ELISA. Results: Out of 58 eligible enrolled patients, 16 had a flare. Higher levels of baseline MMP-9 were found in patients who developed subsequent symptomatic flare compared with patients who did not [median 661 ng/ml, 25–75 interquartile range (IQR; 478.2–1441.3) versus 525.5 ng/ ml (339–662.7), respectively, p = 0.01]. Patients with serum MMP-9 levels of 945 ng/ ml or higher were at increased risk for relapse within 24 months [area under the curve (AUC) of 0.72 [95% confidence interval (CI): 0.56–0.88]; hazard ratio 8.1 (95% CI 3.0–21.9, p

Background and study aims Nomenclature and descriptions of small bowel (SB) vascular lesions in capsule endoscopy (CE) are scarce in the medical literature. They are mostly based on the reader's opinion and thus differ between experts, with a potential negative impact on clinical care, teaching and research regarding SBCE. Our aim was to better define a nomenclature and to give a description of the most frequent vascular lesions in SBCE. Methods A panel of 18 European expert SBCE readers was formed during the UEGW 2016 meeting. Three experts constructed an Internet-based four-round Delphi consensus, but did not participate in the voting process. They built questionnaires that included various still frames of vascular lesions obtained with a third-generation SBCE system. The 15 remaining participants were asked to rate different proposals and description of the most common SB vascular lesions. A 6-point rating scale (varying from ‘strongly disagree’ to ‘strongly agree’) was used successive rounds. The consensus was reached when at least 80 % voting members scored the statement within the ‘agree’ or ‘strongly agree’. Results Consensual terms and descriptions were reached for angiectasia/angiodysplasia, erythematous patch, red spot/dot, and phlebectasia. A consensual description was reached for more subtle vascular lesions tentatively named “diminutive angiectasia” but no consensus was reached for this term. Conclusion An international group has reached a consensus on the nomenclature and descriptions of the most frequent and relevant SB vascular lesions in CE. These terms and descriptions are useful in daily practice, for teaching and for medical research purposes.

Background and study aims Inflammatory bowel disease (IBD) affects the small bowel and colon. Endoscopic evaluation of these organs is essential. The new pan-enteric Crohn’s capsule (PCC) system is customized for complete coverage of IBD lesions in the entire bowel, allowing assessment and follow-up of disease severity and extent. The aim of this study was to evaluate the functionality of the PCC system in patients with suspected or established IBD. Patients and methods This was a prospective five-center feasibility study assessing the performance of PCC. Subjects ingested PCC after patency assurance with standard bowel preparation plus boosts. The primary endpoint was successful procedure, that is, video creation and report generation in accordance with methodology. Secondary endpoints were subjective coverage of the entire bowel, duration of reading time, video quality and occurrence of adverse events. Results Forty-one patients were included in the study with a mean age of 40.8 years ± 15.5, 46 % of whom were males. Seventy-one percent of patients had established Crohn’s disease (CD) and 53 % had active disease. Cleansing was graded good/excellent in 95 %. All 41 videos met the primary endpoint. There was no retention, 83 % reached the toilet while still recording. Thirty-one percent of patients with CD had proximal disease. Bowel coverage was graded 6.7 ± 0.6 and 6.1 ± 1.3 (1 – 7, unconfident – confident), image quality 6.1 ± 0.8 (1 – 7, poor – excellent), and reading time 3.7 ± 1.4 (1 – 7, very short to very long). Conclusions The PCC system is a minimally invasive system allowing extensive evaluation of the entire bowel in patients with IBD.

Background: Anastomotic recurrence is frequent in patients with Crohn’s disease (CD) following ileocecal resection. The degree of endoscopic recurrence, quantified by the Rutgeerts score (RS), correlates with risk of clinical and surgical recurrence. Several studies demonstrate the accuracy of fecal calprotectin (FC) for detection of endoscopic recurrence, however the optimal threshold FC value remains to be established. The aim of our meta-analysis was to evaluate the accuracy of common FC cut-offs for detection of endoscopic recurrence. Methods: We performed a systematic literature search for studies evaluating postoperative recurrence in CD which reported RS and FC levels. Endoscopic recurrence was defined as RS = 2–4 (or RS ⩾ 2). We calculated pooled diagnostic sensitivity, specificity, diagnostic odds ratio (DOR) and constructed summary receiver operating characteristic (SROC) curves for each available FC cut-off value. Results: A total of 54 studies were retrieved; 9 studies were eligible for analysis. Diagnostic accuracy was calculated for FC values of 50, 100, 150 and 200 µg/g. A significant threshold effect was observed for all FC values. The optimal diagnostic accuracy was obtained for FC value of 150 µg/g, with a pooled sensitivity of 70% [95% confidence interval (CI) 59–81%], specificity 69% (95% CI 61–77%), and DOR 5.92 (95% CI 2.61–12.17). The area under the SROC curve was 0.73. Conclusion: FC is an accurate surrogate marker of postoperative endoscopic recurrence in CD patients. The FC cut-off 150 μg/g appears to have the best overall accuracy. Serial FC evaluations may eliminate or defer the need for colonoscopic evaluation in up to 70% of postoperative CD patients.

Background: The Montreal classification defines L4 Crohn’s disease (CD) as any disease location proximal to the terminal ileum, which anatomically includes L4-esophagogastroduodenal (EGD), L4-jejunal, and L4-proximal ileal involvement. L4-jejunal disease was established to be associated with poor prognosis. However, the outcome of patients with L4-proximal ileal disease or L4-EGD remains to be clarified. Our study aimed to investigate whether the outcome differs among CD patients with L4-EGD, L4-jejunal, and L4-proximal ileal disease. Methods: In our retrospective cohort study, 483 patients with confirmed CD were included. The primary outcome was intestinal surgery. Demographic features and outcomes were compared among L4-EGD, L4-jejunal, and L4-proximal ileal disease. Results: Thirty-nine (8.1%) patients had isolated L4 disease, whereas 146 patients had L4 as well as concomitant L1, L2, or L3 disease. During a median follow up of 5.8 years, L4 patients were more likely to have intestinal surgeries compared to non-L4 patients (31% versus 16%, p < 0.001). The percentage of L4-jejunal patients who underwent surgery was higher than that of L4-proximal ileal (66% versus 28%, p < 0.001), and both of these subtypes of L4 were at higher risk for intestinal resection compared to L4-EGD patients (66% and 28% versus 9%, respectively, p < 0.001 and p < 0.05). On multi-variable analysis, L4-jejunal (HR 3.08; 95% CI 1.30–7.31) and L4-proximal ileal disease (HR 1.83; 95% CI 1.07–3.15) were independent predictors for intestinal resection. Conclusions: L4 disease had worse prognosis compared to non-L4 disease. Within L4 disease, phenotype of L4-jejunal and L4-proximal ileal disease indicated higher risk for intestinal surgery. It might be justified to further characterize the L4 phenotype of the Montreal classification into three specific subgroups including L4-EGD, L4-jejunal, and L4-proximal ileal disease, similar to the Paris classification of pediatric patients.

Background: Small bowel involvement in Crohn’s disease (CD) is frequently proximal to the ileocecal valve and inaccessible by conventional ileocolonoscopy (IC). Small bowel capsule endoscopy (SBCE) is among the prime modalities for assessment of small bowel disease in these patients. Intestinal ultrasound (IUS) is an accurate bedside fast and low-cost diagnostic modality utilized in CD for both diagnosis and monitoring. The aim of this study was to examine the accuracy of IUS in patients with suspected CD after a negative IC, and to evaluate the correlation of IUS with SBCE, inflammatory biomarkers and other cross-sectional imaging techniques. Methods: Prospective single center study in which patients with suspected CD underwent IUS and SBCE examinations within 3 days. IUS results were blindly compared with SBCE that served as the gold standard. A post hoc comparison was performed of IUS and SBCE results and available cross-sectional imaging results (computed tomography or magnetic resonance enterography) as well as inflammatory biomarkers if measured. The study cohort was followed for 1 year. In case of discordance between the IUS and SBCE results, the diagnosis at 1 year was reported. Results: Fifty patients were included in the study. The diagnostic yield of both IUS and SBCE for the diagnosis of small bowel CD was 38%. The IUS findings significantly correlated to small bowel inflammation detected by SBCE ( r = 0.532, p < 0.001), with fair sensitivity and specificity (72% and 84%). Cross-sectional imaging results significantly correlated to IUS as well ( r = 0.46, p = 0.018). Follow up was available in 8 of the 10 cases of discordance between IUS and SBCE. In all of these cases, diagnosis of CD was not fully established at the end of the follow up. Conclusions: The diagnostic yield of CE and IUS for detection of CD in patients with negative ileocolonoscopy was similar. IUS can be a useful diagnostic tool in suspected CD when IC is negative.

Background Small-bowel capsule endoscopy (CE) is a prime modality for evaluation of the small bowel. The Lewis score (LS) and the Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI) are validated endoscopic indices for quantification of small-bowel inflammation on CE. It is unclear whether these indexes are interchangeable for the evaluation of mucosal inflammation in established Crohn’s disease (CD). The aim of this study was to compare the quantitative evaluation of small- bowel inflammation by LS and CECDAI. Methods Patients with known quiescent small-bowel CD for at least 3 months (Crohn’s disease activity index < 150) were prospectively recruited and underwent CE. The LS was calculated using RAPID 8 capsule-reading software and the CECDAI was calculated manually. Cumulative LS (C-LS) was calculated by summation of individual tertile LS. Fecal calprotectin (FCP) and C-reactive protein (CRP) levels were measured and correlated with the scores. Results A total of 50 patients were included in the study. There was a moderate correlation between the worst segment LS and CECDAI (Pearson’s r = 0.66, p = 0.001), and a strong correlation between C-LS and CECDAI ( r = 0.81, p = 0.0001). CECDAI < 5.4 corresponded to mucosal healing (LS < 135), while CECDAI > 9.2 corresponded to moderate-to-severe inflammation (LS ⩾ 790). There was a moderate correlation between capsule scores and FCP levels ( r = 0.39, p = 0.002 for LS, r = 0.48, p = 0.001 for C-LS, and r = 0.53, p = 0.001 for CECDAI, respectively). CRP levels were not significantly correlated with either score. Conclusions CECDAI and C-LS are strongly correlated and perform similarly for quantitative assessment of mucosal inflammation in established CD.

Crohn’s disease (CD) is a chronic inflammatory disease, in most patients involving the small and large bowel. In recent years, with the use of small bowel video capsule endoscopy (SBCE), it has become clear that in 50% or more of adults with established CD there is not only distal but also proximal small bowel involvement that suggests poor prognosis. A great deal of effort has been put into early diagnosis and stratification of patients into low versus high risk, thus directing treatment from step-up, or accelerated step-up, to top-down therapies. SBCE has been used for assessment of small bowel pathologies for over 15 years, mainly for occult gastrointestinal bleeding and suspected CD. In recent years, a colonic capsule, with cameras on both sides and a wider angle of view, has been developed and is used by some to survey both small and large bowel. Recently the same capsule, with adjustments, has been released in Europe, concentrating (with specialized software) on inflammatory bowel disease. In this review I summarize the new data regarding the use of SBCE as well as the small bowel colon (SBC) versions of capsule endoscopy in established CD and the ways these could alter the management of such patients.

Background: Video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) are the prime modalities for the evaluation of small bowel (SB) Crohn’s disease (CD). Mucosal inflammation on VCE is quantified using the Lewis score (LS). Diffusion-weighted (DW) magnetic resonance imaging (MRI) allows for accurate assessment of SB inflammation without administration of intravenous contrast material. The Magnetic Resonance Index of Activity (MaRiA) and the Clermont index are quantitative activity indices validated for contrast-enhanced MRE and DW-MRE, respectively. The aim of this study was to compare the quantification of distal SB inflammation by VCE and MR-related activity indices. Methods: Patients with known quiescent SB CD were prospectively recruited and underwent MRE and VCE. LS, MaRIA and Clermont scores were calculated for the distal SB. Results: Both MRI-based indices significantly correlated with the LS and the Clermont index ( r = 0.50, p = 0.001 and r = 0.53, p = 0.001, respectively). Both MaRIA and Clermont scores were significantly lower in patients with mucosal healing (LS < 135). The area under the curve (AUC) with both MR scores was moderate for prediction of any mucosal inflammation (LS ⩾ 135) and excellent for prediction of moderate-to-severe inflammation (LS ⩾ 790) (0.71 and 0.74 versus 0.93 and 0.91 for MaRIA and Clermont score, respectively). Conclusions: Modest correlation between VCE- and MRE-based quantitative indices of inflammation in patients with quiescent SB CD was observed. Between-modality correlation was higher in patients with endoscopically severe disease. DW-MRE gauged by Clermont score was at least as accurate as contrast-enhanced MRE for quantification of SB inflammation.

Background and aims: The patency capsule is designed to evaluate the patency of the small bowel before administration of small-bowel capsule endoscopy (SBCE) in patients at high risk of retention. The utilization of a patency capsule may be associated with a risk of symptomatic retention, but very few cases have been reported to date. The aim of our study was to describe our experience with this rare complication of a patency capsule. Methods: This was a multicenter retrospective case series. The medical records of patients who underwent a patency capsule test were scanned and all cases of symptomatic retention were collected. Results: In total, 20 symptomatic cases of retention out of 1615 (1.2 %) patency capsule tests were identified; in one patient, the patency capsule was retained in the esophagus, in the rest, the capsule was detected in the small bowel resulting in abdominal pain or small-bowel obstruction. One patient (5 %) required surgery; all other patients resolved spontaneously or after corticosteroid therapy. Conclusions: Symptomatic patency capsule retention is a very rare complication with a favorable prognosis. It should be recognized but its use in patients with suspected small-bowel stenosis should not be discouraged.

Inflammatory Bowel Diseases (IBD) are an immune mediated chronic or relapsing disorders of the gastrointestinal (GI) tract. IBD is characterized by a chronic intestinal inflammatory process with various components contributing to the pathogenesis of the disease including environmental factors such as smoking or use of Non Steroidal Anti-Inflammatory Drugs (NSAIDS). NSAIDS are among the most commonly used medications for the treatment of various inflammatory conditions. The main factor limiting NSAIDS use is the concern for the development of gastrointestinal toxicity including mucosal injury. A possible association between the use of NSAIDS and the onset or relapse of IBD has been repeatedly suggested. This article will review the current concepts and evidence of the relationship between IBD and NSAIDS.

Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2-4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p