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Vedolizumab-associated adverse effects, including infusion reactions, are generally uncommon. Less than 5% of patients experience an infusion-related reaction. We report a 67-year-old male with ulcerative colitis under prolonged maintenance therapy who presented with recurring chest pain occurring immediately after consecutive vedolizumab infusions. Medical workup of possible etiologies for chest pain were investigated and excluded. Vedolizumab drug trough levels were negative, accompanied by high detectable levels of anti-vedolizumab antibodies. These findings demonstrate an uncommon case of an infusion reaction to vedolizumab infusion.

Background and aim Inflammatory bowel disease (IBD) research is extensive and increasing, with topics varying and shifting foci over time. A comprehensive analysis of the trends in IBD publications may help us grasp knowledge gaps and map future areas of interest. The aim of our study was to create a map of IBD research for the last 25 years using computational text-mining techniques. Methods We retrieved all available MEDLINE/PubMed annual datasets between 1992 and 2016. We categorized article characteristics by using word combination and title match techniques. We also assigned country of origin for each article from the first author’s affiliation. Results During the study period, 18,653 publications that appeared on PubMed were classified as IBD-related. The annual number of publications increased almost 4-fold (354 to 1361) during the study period. The United States had the highest total number of publications (n = 3179/16,358, 19.4%) and Denmark, Sweden, and Israel had the highest rate of publications per capita. There were 7986 articles successfully assigned with a main subject. Therapeutics, surgical treatment, and endoscopy were the 3 leading topics, with n = 2432/7986 (30%), 1707/7986 (21%), and 981/7986 (12%), respectively. When analyzing trends in topics over time, we found an increase in the proportion of articles on imaging (2.2% in 1992-1996 to 8% in 2012-2016) and a decrease in the proportion of articles on surgical treatment (30% in 1992-1996 to 19% in 2012-2016). Conclusions There is steady increase in the number of IBD-related publications. Although the United States is a world leader in the number of IBD publications, Denmark, Sweden, and Israel publish the most per population size. Medical therapeutics is the most popular topic, yet there is a steady increase in publications devoted to imaging and monitoring.

Extra-intestinal manifestations (EIM) are common in inflammatory bowel diseases (IBD) and may affect up to 40% of the patients during the course of the disease. Peripheral arthralgia (PA) is by far the most common EIM. To date, TNFα inhibitors are the most established treatment for EIMs in IBD. Infliximab (IFX) trough levels (TL) and anti-IFX antibodies (ATI) are correlated with multiple outcomes in IBD such as clinical response and remission, mucosal healing, fistular healing, and more. So far, a correlation between PA and IFX TL\ATI has not been evaluated. This retrospective study included IBD patients followed by the gastroenterology department of Sheba Medical Center. Patients with active PA at onset of IFX treatment were included. IFX TL and ATI were evaluated at week 6, 14, and 26 and correlated with PA persistence. Forty patients (37 Crohn’s and 3 ulcerative colitis) with IBD-related PA were included. The overall prevalence of PA was 55% (22/40), 42.5% (17/40), and 55% (22/40) after 6, 14, and 26 weeks, respectively. IFX trough drug levels were not associated with reported PA at week 6 [median, 11.8 μg/ml (IQR 6.6–15.5) vs 10.05 μg/ml (IQR 7.35–12.87), p = 0.56], week 14 [median, 4.7 μg/ml (IQR 2.3–7) vs 3.1 μg/ml (IQR 1.35–7.35), p = 0.55], and week 26 [median, 3 μg/ml (IQR 1.15–5.17) vs 3.4 μg/ml (IQR 0.13–6.75), p = 0.94]. Detectable ATI were significantly more prevalent in patients with PA than in patients without PA at week 26 [11/22 (50%) vs 3/18 (16.7%), p = 0.028]. In patients with IBD-related PA, ATI are associated with an increased risk of persistence of PA. No direct correlation was demonstrated between IFX TL and persistence of PA.

Background: Intra-abdominal abscess (IA) is an important clinical complication of Crohn’s disease (CD). A high index of clinical suspicion is needed as imaging is not routinely used during hospital admission. This study aimed to identify clinical predictors of an IA among hospitalized patients with CD using machine learning. Methods: We created an electronic data repository of all patients with CD who visited the emergency department of our tertiary medical center between 2012 and 2018. We searched for the presence of an IA on abdominal imaging within 7 days from visit. Machine learning models were trained to predict the presence of an IA. A logistic regression model was compared with a random forest model. Results: Overall, 309 patients with CD were hospitalized and underwent abdominal imaging within 7 days. Forty patients (12.9%) were diagnosed with an IA. On multivariate analysis, high C-reactive protein (CRP) [above 65 mg/l, adjusted odds ratio (aOR): 16 (95% CI: 5.51–46.18)], leukocytosis [above 10.5 K/μl, aOR: 4.47 (95% CI: 1.91–10.45)], thrombocytosis [above 322.5 K/μl, aOR: 4.1 (95% CI: 2–8.73)], and tachycardia [over 97 beats per minute, aOR: 2.7 (95% CI: 1.37–5.3)] were independently associated with an IA. Random forest model showed an area under the curve of 0.817 ± 0.065 with six features (CRP, hemoglobin, WBC, age, current biologic therapy, and BUN). Conclusion: In our large tertiary center cohort, the machine learning model identified the association of six clinical features (CRP, hemoglobin, WBC, age, BUN, and biologic therapy) with the presentation of an IA. These may assist as a decision support tool in triaging CD patients for imaging to exclude this potentially life-threatening complication.

We sought to define the effectiveness and safety of tofacitinib in a real-world (RW) cohort of Israeli patients with moderate to severe ulcerative colitis (UC).This was a multi-center retrospective observational cohort study (2019-2020) to assess the effectiveness and safety of tofacitinib induction and maintenance therapy up to 26 weeks. Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3 points, and SCCAI ≤2 or a PMS ≤1, respectively.We included 73 patients, 47% male; median age 26 years [IQR: 19.5-39.5], disease duration 7 years [IQR: 2.5-14.5], follow-up 7.1 months [IQR: 3-12], 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant corticosteroids (CS). Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months [IQR 3.4-16]. Overall, response, remission, and CS-free-remission were achieved in 47.6%, 20.6%, and 17.5% of patients, respectively. At early maintenance (week 26), response, remission, and CS-free-remission were achieved in 65%, 22.5%, and 20% of patients, respectively. At week 26, tofacitinib 10 mg BID was still used in 43%. Seventeen patients (23.2%) had an adverse event including herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%.Tofacitinib was effective in achieving CS-free-remission in about 1/5 of highly biologics -experienced patients with UC. Despite a considerable proportion of patients maintained on tofacitinib 10 mg bid, it was well tolerated and safe. Earlier positioning of tofacitinib in the therapeutic algorithm may result in improved outcomes.

Eyal Klang,1– 3 Yiftach Barash,1,3 Asaf Levartovsky,2,4 Noam Barkin Lederer,2,4 Adi Lahat2,4 1Department of Diagnostic Imaging, Chaim Sheba Medical Center, Tel Hashomer, Israel; 2Sackler Medical School, Tel Aviv University, Tel Aviv, Israel; 3DeepVision Lab (3), Chaim Sheba Medical Center, Tel Hashomer, Israel; 4Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, IsraelCorrespondence: Adi LahatDepartment of Gastroenterology, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, IsraelEmail zokadi@gmail.comBackground and Aim: Endoscopic differentiation between malignant and benign gastric ulcers (GU) affects further evaluation and prognosis. The aim of our study was to evaluate a deep learning algorithm for discrimination between benign and malignant GU in a database of endoscopic ulcer images.Methods: We retrospectively collected consecutive upper gastrointestinal endoscopy images of GU performed between 2011 and 2019 at the Sheba Medical Center. All ulcers had a corresponding histopathology result of either benign peptic ulcer or gastric adenocarcinoma. A convolutional neural network (CNN) was trained to classify the images into either benign or malignant. Endoscopies from 2011 to 2017 were used for training (2011– 2015) and validation (2016– 2017). Hyper-parameters, image augmentation and pre-training on Google images obtained images were evaluated on the validation data. Held-out data from 2018 to 2019 was used for testing the final model.Results: Overall, the Sheba dataset included 1978 GU images; 1894 images from benign GU and 84 images of malignant ulcers. The final CNN model showed an AUC 0.91 (95% CI 0.85– 0.96) for detecting malignant ulcers. For cut-off probability 0.5, the network showed a sensitivity of 92% and specificity of 75% for malignant ulcers.Conclusion: Our study displays the applicability of a CNN model for automated evaluation of gastric ulcers images for malignant potential. Following further research, the algorithm may improve accuracy of differentiating benign from malignant ulcers during endoscopies and assist in patients’ stratification, allowing accelerated patients management and individualized approach towards surveillance endoscopy.Keywords: gastric ulcer, malignant, benign, artificial intelligence, AI, deep learning

BACKGROUND Intestinal ultrasound (IUS) is an accurate tool for monitoring Crohn's disease. To date, there is no clinically used validated quantitative ultrasonographic score for assessing disease activity. For magnetic resonance enterography (MRE), the magnetic resonance index of activity (MaRIA) is most used. The goal of this study was to devise a new quantitative IUS score for assessing Crohn's disease inflammation, by using a partial MaRIA score as a reference. METHODS This was a retrospective cohort study. The study cohort included patients with Crohn's disease followed between January 2016 and December 2018. Inclusion criteria were age >18 and

Background We sought to define the effectiveness of tofacitinib in a real-world (RW) cohort of patients with moderate to severe ulcerative colitis (UC). Methods This was a multi-center retrospective observational cohort study (2017–2020). Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3, and SCCAI ≤2 or a PMS ≤1, respectively. Results We included 73 patients (47% male; median age 26 years [IQR 19.5–39.5], disease duration 7 years [IQR 2.5–14.5], follow-up 7.1 months [IQR 3–12]), 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant steroids. Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months (IQR 3.4–16). Based on per-protocol analysis, after induction (week-8–16), 33.3% achieved response, 23.3% remission, and 19% corticosteroid free remission. At early maintenance (week 26), 50% achieved response, 26.8% remission, and 24.4% corticosteroid free remission. There were no differences between biologics-experienced and naïve patients. Seventeen patients (23.2%) had an AE: herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%. Remitters had higher albumin level compared with non-remitters (4.2±0.35 Vs. 3.8±0.35, P=0.023, respectively). Conclusion In this multicenter RW cohort of highly biologics - experienced patients with UC, those who continued tofacitinib throughout induction achieved 50% response and 27% remission. Tofacitinib was well-tolerated.

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 Results: Out of over 10,000 sera, 2088 sera of 302 maintenance period stable infliximab-therapy-patients met inclusion criteria (median TL 4.1 μg/mL, interquartile range (IQR) 2.3–6.5 μg/mL). A delay beyond 3 days in infusion schedule (n > 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 Conclusion: Real-life delays of ⩽3 days from infusion protocol can probably be allowed. Delays >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.

Distinguishing between fibrotic and inflammatory strictures in Crohn’s disease (CD) is still challenging. The capacity of diffusion-weighted (DWI) magnetic resonance (MRE) to identify intestinal fibrosis was recently demonstrated; however, the therapeutic implications of this association have never been evaluated. The aim of the current study was to identify imaging features, including DWI, which can predict response to anti-inflammatory treatment in patients with stricturing CD. Consecutive CD patients with intestinal strictures that initiated treatment with anti-tumor necrosis alpha (anti-TNF) between June 2012 and April 2017 with MRE adjacent to treatment onset were retrospectively collected. The primary outcome was treatment failure, defined as drug discontinuation, CD-related surgery, or endoscopic dilatation of the stricture. Clinical, demographic, and imaging data were compared between patients who did and did not develop treatment failure within 12 months of anti-TNF treatment initiation. A total of 21 patients were included in the study; 9/21 (42.8%) developed treatment failure. None of the clinical/demographic parameters were associated with the risk of treatment failure. Among imaging parameters, only ADC value (

Background Intra-abdominal abscess is an important clinical complication of Crohn’s disease (CD), which can be diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI). However, a high index of clinical suspicion is needed to diagnose an abscess as abdominal imaging is not routinely used during hospital admission. This study aimed to identify clinical predictors of an intra-abdominal abscess among hospitalized patients with CD. Methods We created an electronic data repository of all patients with CD who visited the emergency department (ED) of our tertiary medical center between 2012 and 2018. Data included tabular demographic and clinical variables, as well as CT and MRI imaging outcomes. We searched the data repository for the presence of an abscess on abdominal imaging within seven days from the ED visit. Machine learning models were trained to predict the presence of an abscess. A logistic regression model was compared to a random forest model. The area under the receiver operator curve (AUC) was used as a metric. To establish statistical significance, bootstrapping of 100 experiments with random 80/20 training/testing splits was performed. We included only patients who were hospitalized due to complaints that can be attributed to CD exacerbation. Patients presenting within 30 days from an abdominal surgery were excluded. Results Overall, 1556 patients with CD visited the ED, of those 555 patients with a CD exacerbation. Of them, 339 patients were hospitalized and underwent abdominal imaging within 7 days from the ED visit. Forty-two patients (12.1%) were diagnosed with an abscess on abdominal imaging. The average length of the abscess was 32 mm (IQR 21.5, 43.5), mainly in the mesentery adjacent to the small bowel (38.1%). On multivariate analysis, high CRP values (64.97 mg/L, aOR 14.42 [95% CI 4.93–42.13]), high platelet count (322.5 K/microL, aOR 4.01 [95% CI 1.97–8.15]), leukocytosis (10.55 K/microL, aOR 3.83 [95% CI 1.71–8.56]) and higher heart rate (over 87.5 beats per minute, aOR 2.58 [95% CI 1.22–5.46]) were independently associated with an intra-abdominal abscess. Overall, random forest and logistic regression showed similar performance. The random forest model showed an AUC of 0.824±0.065 with eight features (CRP, Hemoglobin, WBC, age, current biologic medical treatment, BUN, current immunomodulatory medical treatment, gender). Conclusion In our large tertiary center cohort, the machine-learning model identified features associated with the presentation of an intra-abdominal abscess. Such a decision support tool may assist in triaging CD patients for imaging to exclude this potentially life-threatening complication.

Background Patients with inflammatory bowel disease (IBD) have a greater risk of venous thromboembolism (VTE) events compared with the general population especially during flares, in both hospitalised and ambulatory patients. Although VTE prophylaxis (thromboprophylaxis) is recommended in hospitalised IBD patients, the implementation is not universal, especially for non-IBD-related hospitalisations. In this study, we aimed to present the rates of VTEs and thromboprophylaxis among hospitalised IBD patients. Methods We created an electronic data repository of all IBD patients who visited the emergency department (ED) of our tertiary medical centre between 2012 and 2018. Data included tabular demographic and clinical variables (reason for referral, VTEs, clinical characteristics, hospitalisation, lab results, treatment and outcome) as well as free-text physician records. For this study, we searched the data repository for VTE cases, using ICD10 coding. Results Overall, there were 7009 ED visits of 2405 patients with IBD, 1556 (64.7%) Crohn's disease and 849 (35.3%) Ulcerative colitis patients. Thromboprophylaxis was administered in 463 hospitalisations (12.4% of IBD-related and 10.9% of non-IBD-related hospitalisations). 1.5% of patients (36/2405) who visited the ED had a new VTE. Thirty patients were diagnosed with a deep vein thrombosis (DVT), two patients with a pulmonary embolism (PE) and six additional patients were diagnosed with both a DVT and PE in the same hospitalisation. Eleven patients had a VTE during a non-IBD-related hospitalisation and six patients during an IBD-related hospitalisation (0.6% vs. 0.3%, respectively, pv = 0.12). Five patients (29.4%) developed VTEs after receiving thromboprophylaxis during hospitalisation. The majority (72.7%) of VTEs diagnosed during a non-IBD-related hospitalisation did not have additional thrombosis-related risk factors. One patient died during hospitalisation and two more patients died in the upcoming 30 days (unrelated to VTEs). Conclusion The rate of thromboprophylaxis in hospitalised IBD patients is low, despite posing life-threatening implications. Thromboprophylaxis should be implemented in IBD patients hospitalised for all indications.

Background There is an extensive and growing research effort in the field of inflammatory bowel diseases (IBD), with varying topics over the years. A comprehensive analysis of the trends in research and publications in IBD may help us grasp the gaps in knowledge and map out potential future areas of interest. Text-mining is the extraction of information from free text using computational methods. It can be applied to identify trends in a research field. The aim of our study was to create a map of IBD research of the last 25 years using text-mining techniques Methods We retrieved all available MEDLINE/PubMed annual datasets from 1992 to the end of 2017. We selected a set of relevant keywords from MeSH to include all papers relating to inflammatory bowel disease, Crohn’s disease and Ulcerative colitis. For each article we extracted the following data: article ID, title, journal, date of publication, abstract text, article type, keywords, citation frequency, and first author name and affiliation (from which we extracted the country of origin). We categorised the articles screening topics by using word combination and title match technique. We also scanned the topics in list of 100 papers (grouped by 5-year periods starting with 1992–1997) with the highest citation factor, i.e., the articles with the most citations from publish up to 2018. Results Between the years 1992 and 2017, 20,014 IBD-related publications appeared on PubMed. The annual number of publications increased almost 4-fold (from 354 in 1992 to 1361 in 2017). The USA had the highest number of papers (n = 3427/20,014, 17%) while Denmark and Israel had the highest rate of publications per population (for 2012–2017, 12 publications per 1 million in Israel and 17 in Denmark). The countries that achieved the most significant growth in publication rates were China, Egypt, Romania with growth rates of 0.0069, 0.0068 and 0.0062 respectively defined as the increase in articles per year normalised by the total amount of articles from that country. Out of 20014 papers, 5590 were successfully classified into 14 major topics. The topics that attracted the most publications over the years were medical therapeutics 1808/20014 (9% of articles from 1992 to 2017), followed by surgical treatment 1111/20014 (5.5%), endoscopy 637/20014 (3.2%) and genetics 552/20014 (2.7%), remaining stable through the study period. Conclusion There is a steady growth in the number of IBD-related publications. Although US is a world leader in the number of IBD publications overall, Denmark and Israel publish the most in relation to population size, while China, Romania and Egypt display the highest growth rate in the number of publications. Medical therapeutics is the most popular and best-cited topic.

Background Endoscopic recurrence is associated with a risk of clinical recurrence in patients with Crohn's disease after ileocecal or small bowel resection. Drug levels and presence of antidrug antibodies are associated with important clinical and endoscopic outcomes in patients with Crohn's disease treated with tumor necrosis factor inhibitors, such association was not evaluated for endoscopic postsurgical recurrence. Methods Consecutive patients with Crohn's disease treated with anti-tumor necrosis factors after surgery were identified in the databases of the participating centers. Anti-tumor necrosis factor levels and antidrug antibodies were correlated with Rutgeerts score on colonoscopy performed ≥6 months postoperatively. Significant endoscopic recurrence (SER) was defined as Rutgeerts score >2. Results Seventy-three consecutive patients (32-infliximab, 41-adalimumab) were included in the study. The colonoscopies were performed after a median of 15 (7-43) months after surgery and 8 (6-15) months from treatment onset. SER was demonstrated in 26/73 (35.6%) of the patients. The need for dose optimization, as well as trough infliximab levels (2.4 μg/mL [0.45-4.1] versus 1.1 (0-0.6), P = 0.008) and presence of antidrug antibodies (1/18 [5.6%] versus 10/14 [71.4%], P = 0.0001) were significantly associated with a risk of SER. The optimal cutoff infliximab level for prediction of SER was 1.8 μg/mL. No association between adalimumab levels and antiadalimumab antibodies was demonstrated.