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The investigation of small bowel (SB) intussusception is variable, reflecting the lack of existing standards. The aim of this study was to understand the role of small bowel capsule endoscopy (SBCE) to investigate this pathology. This was a retrospective multi-centre study. Patients with intussusception on SBCE and those where SBCE was carried out due to findings of intussusception on radiological investigations were included. Relevant information was collected. Ninety-five patients (median age 39+/-SD19.1 years, IQR 30) were included. Radiological investigations were carried out in 71 patients (74.7%) prior to SBCE with intussusception being present in 60 patients on radiological investigations (84.5%). Thirty patients (42.2%) had intussusception on radiological investigations followed by a normal SBCE. Ten patients (14.1%) had findings of intussusception on radiological investigations, a normal SBCE and repeat radiological investigations that were also normal. Abnormal findings were noted on SBCE that could explain intussusception on imaging in (16 patients) 22.5% of patients. Five patients (5.3%) underwent radiological investigations and SBCE to investigate coeliac disease and intussusception. None had associated malignancy. Four patients (4.2%) underwent SBCE to investigate familial polyposis syndromes and went on to SB enteroscopy and surgery accordingly. Most patients (n = 14; 14.8%) with intussusception on initial SBCE (without prior radiological imaging) had suspected SB bleeding (n = 10, 10.5%). Four patients (4.2%) had additional findings of a mass on CT scan and went on to have surgery. SBCE should be used to complement radiology when investigating intussusception. It is a safe non-invasive test that will minimise unnecessary surgery. Additional radiological investigations following a negative SBCE in cases of intussusception noted on initial radiological investigations are unlikely to yield positive findings. Radiological investigations following intussusception noted on SBCE in case of patients presenting with obscure gastrointestinal bleeding, may yield additional findings. [ABSTRACT FROM AUTHOR]

Extraintestinal manifestations (EIM) are associated with diminished quality of life. The efficacy of Ustekinumab and vedolizumab for EIM treatment is not well established. The aim was to compare the effectiveness of ustekinumab and vedolizumab for treatment of EIM in IBD. We included IBD patients treated with vedolizumab or ustekinumab in the Gastroenterology department, Sheba Medical Center, for up to 52 weeks between 2015 and 2021. Patients with active EIM before treatment initiation were included. 111 patients were included. 53 patients (48%) were treated with ustekinumab; 88% (n-99) had CD. The most common EIM was arthralgia (95/111, 84%). Patients treated with ustekinumab were more likely to be anti-TNF experienced (n-51/53 [96%] compared with vedolizumab n = 36/58 [62%], p < 0.001). Clinical response of EIM at week 52 was achieved in 36% of patients treated with ustekinumab (n-18/50) and 34% of patients (n-19/54) treated with vedolizumab, with no statistically significant difference (p = 0.9). No statistical significance was achieved for patients presented with arthralgia. Clinical response of arthralgia at week 52 was seen in 34% (n-19/55) and 36% (n-18/46) of the patients treated with vedolizumab and ustekinumab, respectively, (p = 0.3). In this study, no difference was found between vedolizumab and ustekinumab regarding their effect on EIM in IBD patients for up to 52 weeks. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Routine screening for establishing Lynch syndrome (LS) in young individuals diagnosed with adenomas is not recommended due to its low yield, and limited sensitivity of the employment of immunohistochemistry for DNA mismatch-repair proteins on polyps. Hence we aimed to evaluate the yield of germline mutational analysis in diagnosis of LS in a young Israeli cohort with colorectal adenomatous polyps. Data were retrospectively collected on consecutive patients, age ≤ 45 years, who underwent colonoscopy with removal of at least one adenoma during 2015–2020, and subsequently genetic testing by multigene panel or LS-Jewish founder mutation panel. Overall, 92 patients were included (median age 35 years, range 23–45 years), of whom 79 (85.8%) underwent multigene panel genotyping, and 13 (14.2%) analysis for Jewish founder LS gene mutations. Altogether, 18 patients were identified with pathogenic mutations in actionable genes, including LS-associated genes in 6 (6.5%), BRCA2 in 2 (2.5%), GREM1 in 1(1.2%), and low-penetrance genes- APC I1307K and CHEK2- in 9 (11.4%) patients. Compared with non-LS patients, LS-carriers had a significantly higher median PREMM5 score (2.6 vs. 1.3; P = 0.04). Young individuals diagnosed with adenomatous polyps should be offered genetic testing when fulfilling clinical guidelines for LS, but weight should also be given to adenoma characteristics in the PREMM5 score. [ABSTRACT FROM AUTHOR]

We evaluated the efficacy of herbal combination of curcumin-QingDai (CurQD) in active ulcerative colitis (UC). Part I was an open-label trial of CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index score of 5 or higher and a Mayo endoscopic subscore of 2 or higher. Part II was a placebo-controlled trial conducted in Israel and Greece, randomizing active UC patients at a 2:1 ratio to enteric-coated CurQD 3 g/d or placebo for 8 weeks. The co-primary outcome was clinical response (reduction in the Simple Clinical Colitis Activity Index of ≥3 points) and an objective response (Mayo endoscopic subscore improvement of ≥1 or a 50% fecal calprotectin reduction). Responding patients continued either maintenance curcumin or placebo alone for an additional 8 weeks. Aryl-hydrocarbon receptor activation was assessed by cytochrome P450 1A1 (CYP1A1) mucosal expression. In part I, 7 of 10 patients responded and 3 of 10 achieved clinical remission. Of 42 patients in part II, the week 8 co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (P =.033). Clinical response was observed in 85.7% vs 30.7% (P <.001), clinical remission in 14 of 28 (50%) vs 1 of 13 (8%; P =.01), a 50% calprotectin reduction in 46.4% vs 15.4% (P =.08), and endoscopic improvement in 75% vs 20% (P =.036) in the CurQD and placebo groups, respectively. Adverse events were comparable between groups. By week 16, curcumin-maintained clinical response, clinical remission, and clinical biomarker response rates were 93%, 80%, and 40%, respectively. CurQD uniquely up-regulated mucosal CYP1A1 expression, which was not observed among patients receiving placebo, mesalamine, or biologics. In this placebo-controlled trial, CurQD was effective for inducing response and remission in active UC patients. The aryl-hydrocarbon receptor pathway may merit further study as a potential UC treatment target. ClinicalTrials.gov ID: NCT03720002. [Display omitted] [ABSTRACT FROM AUTHOR]

Capsule endoscopy (CE) is an important modality for diagnosis and follow-up of Crohn's disease (CD). The severity of ulcers at endoscopy is significant for predicting the course of CD. Deep learning has been proven accurate in detecting ulcers on CE. However, endoscopic classification of ulcers by deep learning has not been attempted. The aim of our study was to develop a deep learning algorithm for automated grading of CD ulcers on CE. We retrospectively collected CE images of CD ulcers from our CE database. In experiment 1, the severity of each ulcer was graded by 2 capsule readers based on the PillCam CD classification (grades 1-3 from mild to severe), and the inter-reader variability was evaluated. In experiment 2, a consensus reading by 3 capsule readers was used to train an ordinal convolutional neural network (CNN) to automatically grade images of ulcers, and the resulting algorithm was tested against the consensus reading. A pretraining stage included training the network on images of normal mucosa and ulcerated mucosa. Overall, our dataset included 17,640 CE images from 49 patients; 7391 images with mucosal ulcers and 10,249 normal images. A total of 2598 randomly selected pathologic images were further graded from 1 to 3 according to ulcer severity in the 2 different experiments. In experiment 1, overall inter-reader agreement occurred for 31% of the images (345 of 1108) and 76% (752 of 989) for distinction of grades 1 and 3. In experiment 2, the algorithm was trained on 1242 images. It achieved an overall agreement for consensus reading of 67% (166 of 248) and 91% (158 of 173) for distinction of grades 1 and 3. The classification accuracy of the algorithm was 0.91 (95% confidence interval, 0.867-0.954) for grade 1 versus grade 3 ulcers, 0.78 (95% confidence interval, 0.716-0.844) for grade 2 versus grade 3, and 0.624 (95% confidence interval, 0.547-0.701) for grade 1 versus grade 2. CNN achieved high accuracy in detecting severe CD ulcerations. CNN-assisted CE readings in patients with CD can potentially facilitate and improve diagnosis and monitoring in these patients. [ABSTRACT FROM AUTHOR]

Lynch syndrome carries an increased risk of colorectal neoplasia, hence annual surveillance colonoscopy is recommended. This study aimed to compare the diagnostic yields of image enhancement modalities for colorectal neoplasia in patients with Lynch syndrome. Meta-analysis of pooled ratios of lesion detection rates (RRs) and odds ratios (ORs) with 95% confidence intervals (CIS), comparing white light endoscopy (WLE) and chromoendoscopy (ChE). Four studies comparing WLE to ChE were analyzed. ChE fared better than WLE in overall lesion detection (RR 1.97, 95% CI 1.63–2.38) and detection of adenomas (RR 1.53, 95% CI 1.07–2.17), flat lesions (RR 3.4, 95% CI 2.47–4.67) and proximally-located lesions (RR 2.93, 95% CI 1.91–4.5). The odds of a patient having any lesion found were higher in ChE compared to WLE (OR 2.42, 95% CI 1.56–3.75). The odds of a patient having adenoma(s) found on endoscopy were not significantly higher in chromoendoscopy compared to white light endoscopy (OR 1.81, 95% CI 0.65–5.01). Using standard definition technology, ChE allows detection of more lesions, especially adenomas, flat lesions and proximal lesions in Lynch syndrome patients, compared to WLE. The results show that surveillance colonoscopy of Lynch syndrome patients should be performed using ChE. [ABSTRACT FROM AUTHOR]

Ustekinumab [UST] is effective in Crohn's disease (CD) in the UNITI studies. Several real-world experience (RWE) studies with UST have been published to date. Our aim was to summarize the available RWE data for UST effectiveness and safety. A systematic review of the available RWE studies of UST for CD and pooled analysis of the available effectiveness and safety data was performed. Eight relevant studies of 6 RWE were included for analysis. Data from 578 patients were pooled for analysis. Most patients (97.7%) were anti-TNF experienced. Pooled clinical response rate was 60%, 62%, 49% at 12, 24 and 52 weeks respectively (95% CI (0.42–0.77), (0.48–0.75), (0.37–0.62)). Pooled remission rate was 39% (95% CI (0.18–0.65)) at 24 weeks and pooled endoscopic response rate was 63% (95% CI (0.53–0.72)) after approximately one year of UST; 134 adverse events (AE) were reported in total, pooled proportion 21% (95% CI (0.12–0.35)). Serious AE were reported in 19 patients, pooled proportion 5% (95% CI (0.03–0.08)). Infections were reported in 38, pooled proportion 6% (95% CI (0.04–0.11)). Pooled analysis of the RWE data suggests that the real-world effectiveness and safety are comparable to that reported in the randomized control trials. [ABSTRACT FROM AUTHOR]

Loss of response (LOR) to infliximab occurs in ∼30% of IBD patients. At time of LOR, lower infliximab-trough-levels (TL), in the absence of anti-drug-antibodies (ATI), have been associated with the need for therapy escalation. Nevertheless, few studies have examined the outcome of infliximab-therapy intensification, based on different TL. To evaluate the impact of infliximab-TL on efficacy of therapy intensification (dose-elevation/interval-shortening). This was a retrospective observational study performed at two tertiary-centers between 2013–2017. Study population included IBD patients who underwent infliximab therapy escalation (dose elevation/interval shortening) due to clinical LOR. Patients with TL < 3 μg/ml or positive ATI were excluded. TL and clinical scores before intensification and after 6, 12 months were obtained prospectively. Forty-eight IBD patients were included; 23(49%), and 29(60%) reached clinical remission by 6, 12 months before intensification. TL among patients in clinical remission were significantly lower than among those clinically active, both at 6 (p = 0.001, median TL 4.7,8.7 μg/ml, IQR 3.6–8.1, 5.9–16 μg/ml) and 12 months (p = 0.005, median TL 4.6,8.7 μg/ml, IQR 3.6–8, 5.3–16 μg/ml), respectively. In IBD patients experiencing clinical LOR to infliximab in the absence of ATI, success of doubling the dose was inversely associated with baseline TL. Patients with baseline TL above 9 mcg/ml were very unlikely to reach clinical remission. [ABSTRACT FROM AUTHOR]

Abstract Introduction Several real-world experience (RWE) studies with vedolizumab (VDZ) for induction of remission in inflammatory bowel diseases (IBD) have been published; however, long-term RWE data is scarce. Aims To describe the effectiveness and safety of VDZ in maintenance treatment of IBD. Methods A multicenter retrospective national study. The primary outcome of was clinical response at week 52; main secondary aims included clinical remission at week 52, rates of secondary loss of response and treatment discontinuation. Results We included 193 (133—CD; 60—UC) patients from 9 Israeli IBD centers. At week 52, response was observed in 62/133 (46.7%) CD patients, including 28 (21%) in clinical remission; 71 (53.3%) discontinued treatment or did not respond. For UC, response at week 52 was observed in 27/60 (45%), including 20 (33%) in clinical remission; 33 (55%) discontinued treatment or did not respond. Secondary non-response by week 52 occurred in 19.4% and 23.5% of week 14 responders in CD and UC, respectively. Week 14 response was associated with treatment continuation at week 52: no predictors of secondary loss of response were identified. Summary VDZ is safe and effective for maintenance of response and remission in IBD; week 14 response is positively associated with long-term response in both UC and CD. [ABSTRACT FROM AUTHOR]

Background and aims Capsule endoscopy (CE), magnetic resonance enterography (MRE) and small bowel (SB) intestinal contrast ultrasound (SICUS) are the modalities of choice for SB evaluation. This study aimed to compare the diagnostic yield (DY) of CE to MRE and SICUS in detection and monitoring of SB CD through meta-analysis of the available literature. Methods We performed a systematic literature search for trials comparing the accuracy of CE, MRE and SICUS for detection of active SB inflammation in patients with suspected and/or established CD. Only prospective studies comparing CE with another additional diagnostic modality were included in the final analysis. Pooled odds ratios (ORs) for the DY of the three modalities were calculated. Results A total of 112 studies were retrieved; following selection, 13 studies were eligible for analysis. The DY of CE for detection of active SB CD was similar to that of MRE (10 studies, 400 patients, OR 1.17; 95% CI 0.83–1.67) and SICUS (5 studies, 142 patients, OR 0.88; 95% CI 0.51–1.53). The outcomes were similar for the subgroups of suspected versus established CD and adult versus pediatric patients. CE was superior to MRE for proximal SB CD (7 studies, 251 patients, OR 2.79; 95% CI 1.2–6.48); the difference vs SICUS was not significant. Conclusion CE, MRE and SICUS have similar DY for detection of SB CD in both suspected and established CD. CE is superior to MRE for detection of proximal SB disease, however the risk of capsule retention should be considered. [ABSTRACT FROM AUTHOR]

Background Crohn’s disease is associated with accumulation of progressive structural bowel damage (SBD) leading to the development of stenotic and penetrating complications. The data pertaining to the course of progression of SBD is scarce. The Lemann index (LI) is a novel tool for evaluation of SBD that incorporates pan-enteric clinical, endoscopic and imaging data. Aims To evaluate the progression of SBD in quiescent CD patients. Methods Patients with known quiescent small bowel Crohn’s disease (CD) for at least 3 months (CDAI < 220) were prospectively recruited and underwent repeated magnetic resonance enterographies (MRE) and video capsule endoscopies (VCE). Patients were assessed for SBD on initial and follow-up evaluation using relevant clinicopathological data, MRE and VCE results. Significant structural bowel damage (SBD) was identified as LI > 4.8, and progression of SBD as LI > 0.3. Results Sixty one patients were enrolled in the study. Significant SBD was detected 13 (21.4%) on enrollment. Duration of disease (p = 0.036) and history of CD-related surgery (p = 0.0001) were associated with significant BD. Forty one patients underwent a follow-up MRE (14.8 ± 2.5 months apart). LI was similar at baseline and follow-up. There was a negligible change in LI between the evaluations. Conclusions In patients with quiescent Crohn’s disease, structural bowel damage was stable over a median of 14 months follow-up. [ABSTRACT FROM AUTHOR]

Background and Aims Evaluation of small-bowel patency is recommended before swallowing video capsule endoscopy to prevent capsule retention. This study aimed to evaluate the ability of magnetic resonance enterography (MRE) to predict patency capsule (PC) retention in patients with Crohn’s disease and to identify the most predictive imaging features for retention. Methods Fifty-seven patients prospectively underwent MRE and PC. Two radiologists predicted PC retention. Interrater reliability was determined by using Cohen’s κ coefficient. The sensitivity, specificity, and positive and negative predictive values were calculated for the predictions. Evaluation of the imaging features was done using the t test and receiver-operating characteristics; t-tests were also performed on the clinical parameters. Results The κ value for interrater reliability was 0.58. The sensitivity, specificity, PPV, and NPV for the predictions by the 2 radiologists were 92.3%, 59%, 40%, 96.3%, and 100%, 52.3%, 38.2%, 100%, respectively. The maximal stricture length (9.7 ± 3.66 cm vs 7.0 ± 3.08 cm, P = .04) and the number of prestenotic dilations (1.9 ± 1.07 vs 1.0 ± 1.38, P = .03) were associated with PC retention. The area under the receiver-operating characteristic curves was 0.69 for the maximal stricture length and 0.751 for the number of prestenotic dilations. The phenotype of the disease was the only clinical parameter significantly correlated with PC retention. Conclusions MRE has a high NPV and sensitivity for PC retention. When capsule retention is suggested by MRE, PC should be performed before the video capsule endoscopy examination. The maximal stricture length and the number of prestenotic dilations were found to be the most predictive imaging features for PC retention. [ABSTRACT FROM AUTHOR]

Abstract: Background: Subjects maintained on infliximab scheduled therapy for inflammatory bowel disease may require dose optimization due to secondary loss of response. There are limited data on infliximab dose optimization for ulcerative colitis. Aims: To investigate dose optimization in ulcerative colitis patients with secondary loss of response. Methods: This was a retrospective multicentre study. Primary outcome was rapid clinical response assessed at the next administration of infliximab after dose intensification. Secondary outcomes were rapid clinical remission, and clinical response, remission and colectomy rate by week 52. Doubling the dose (10mg/kg q8 weeks) vs. shortening the dose interval (5mg/kg every 6 or 4 weeks) were compared. Results: Forty-one patients from eight centres were enrolled (15 for double dose and 26 for interval shortening). Rapid response was achieved in 37/41 patients (90.2%), while 19/41 (46.3%) achieved rapid clinical remission. At week 52, 28/41 patients were maintained in clinical remission, but 4 (9.8%) underwent colectomy. No difference was found between the two optimization strategies. Subjects achieving rapid clinical response had a significantly higher colectomy-free rate at week 52 (p =0.002). Conclusion: Dose optimization of infliximab was effective to restore clinical response or remission and to prevent colectomy in ulcerative colitis patients with secondary loss of response. [Copyright &y& Elsevier]

Abstract: Background: Failure of anti-TNF treatment in inflammatory bowel disease (IBD) patients can take on several forms, each posing distinct etio-pathogenic considerations and management dilemmas. Aim: The aim of this study is to review the mechanisms responsible for the various forms of anti-TNF failures in IBD and to elucidate strategies for optimizing clinical efficacy. Results: Primary failures of anti-TNF induction therapy occur in up to 40% of patients in clinical trials and in 10–20% in clinical series. Longer disease duration, smoking and several genetic mutations are predisposing factors for primary failures. Curiously, primary non-response is probably not a class-effect phenomenon since switching to another anti-TNF is effective in over 50% of such patients. Secondary loss of response is also a common clinical problem with incidence ranging between 23 and 46% at 12months after anti-TNF initiation. Underlying mechanisms are often related to increased anti-TNF clearance by anti-drug antibodies, but may also include other causes for recalcitrant IBD activity as well as disorders that are unrelated to IBD itself. Astute management begins with verifying the presence of uncontrolled inflammatory IBD activity as a cause for patient's symptoms. Next, it is prudent to consider a trial of wait-and-see approach, since in some patients with mild-moderate symptoms, loss of response may resolve without alteration of therapy. If it does not, measuring anti-TNF trough levels and anti-drug antibodies may clarify the underlying mechanism in individual patients although there are still limited and conflicting data regarding the role of these measurements in guiding the choice between dose-intensification, switch to another anti-TNF or to another immuno-modulator, and the addition of an immuno-modulator as a combination therapy with the failing anti-TNF. Anti-TNF re-induction after prior drug-holiday is a distinct clinical scenario and scarce evidence suggests re-induction outcome to be dependent on the circumstances when drug-holiday was commenced. Finally, discontinuation of anti-TNF in patients with stable deep clinico-biologic and mucosal remission may be a viable option, as in these carefully selected patients the majority may enjoy long-term remission without the need for continued anti-TNF treatment. [Copyright &y& Elsevier]

There are few therapeutic options for patients with inflammatory bowel disease who lose response to infliximab because they produced antibodies against the drug. We performed a retrospective analysis to investigate whether administration of immune modulators to 5 patients who developed antibodies to infliximab (ATI) restored response to this drug; 3 patients were given azathioprine/6-mercaptopurine and 2 patients were given methotrexate. Concentrations of infliximab and ATIs, and antitumor necrosis factor (TNF) activity, were analyzed using enzyme-linked immunosorbent assay–based competition assays of serum samples collected before and after patients were given the immunomodulator. In all patients, levels of ATIs gradually decreased and trough levels of infliximab increased; clinical responses were restored to all patients. In competition assays, immunomodulator-induced elimination of ATIs was associated with increased anti-TNF activity in serum. The addition of immunomodulators to therapy might be helpful to patients who have lost response to anti-TNF agents owing to formation of antidrug antibodies. [ABSTRACT FROM AUTHOR]

The early stages of Crohn's disease (CD) course are heterogeneous, and it is a challenge to predict the course of disease in patients with new diagnosis. We performed an observational longitudinal study of 156 adults (79 male; median age, 27.7 years; 57 treatment naïve) with newly diagnosed CD (within 6 months of enrollment), referred from medical centers and community clinics in Israel from 2013 through 2017. Study participants each received semi-annual scheduled evaluations. Indolent disease was defined as a disease course without need for strict interventions to control complicated course of CD (hospitalization or surgery, or decision to start steroid, immunomodulator, or biologic therapy). Cox regression and receiver operating characteristic analyses were used to identify factors associated with early indolent or complicated course of CD. We validated our findings in an independent cohort of patients with CD from a separate medical center in Israel in 2018. Over a median follow-up period of 17.2 months (interquartile range, 8.8–23.8 months), 52 patients (33.3%) had an indolent course of CD, 29 (18.5%) required hospitalizations, and 75 (48%) were recommended to start steroid, immunomodulator, or biologic therapies. The median time to first intervention was 3.4 months (95% CI, 2.4–4.4). We developed a model based on clinical factors that identified 4 factors associated with complicated course in treatment-naïve patients: body mass index <25 kg/m2 (hazard ratio [HR], 2.45; 95% CI, 1.07–5.43; P =.033), serum level of vitamin B12 <350 pg/mL (HR, 2.78; 95% CI, 1.21–6.41; P =.016), white blood cells ≥7 × 103/μL (HR, 2.419; 95% CI, 1.026–5.703; P =.044), and serum level of ALT ≥25 IU/L (HR, 2.680; 95% CI, 1.186–6.058; P =.018). This model discriminated between patients with vs without a complicated course of disease with 90% and 89% accuracy at 6 and 12 months after diagnosis, respectively. A validation cohort demonstrated a discriminatory ability of 79% at 3 months after diagnosis, and a nomogram was constructed. In an observational longitudinal study of 156 patients with newly diagnosed CD, we found that one third have an early indolent course of disease. We identified factors that can be measured at diagnosis to identify patients at risk for an early complicated course—these might be used in patient management and selection of treatment. [ABSTRACT FROM AUTHOR]

Deep learning is an innovative algorithm based on neural networks. Wireless capsule endoscopy (WCE) is considered the criterion standard for detecting small-bowel diseases. Manual examination of WCE is time-consuming and can benefit from automatic detection using artificial intelligence (AI). We aimed to perform a systematic review of the current literature pertaining to deep learning implementation in WCE. We conducted a search in PubMed for all original publications on the subject of deep learning applications in WCE published between January 1, 2016 and December 15, 2019. Evaluation of the risk of bias was performed using tailored Quality Assessment of Diagnostic Accuracy Studies-2. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curves were plotted. Of the 45 studies retrieved, 19 studies were included. All studies were retrospective. Deep learning applications for WCE included detection of ulcers, polyps, celiac disease, bleeding, and hookworm. Detection accuracy was above 90% for most studies and diseases. Pooled sensitivity and specificity for ulcer detection were.95 (95% confidence interval [CI],.89-.98) and.94 (95% CI,.90-.96), respectively. Pooled sensitivity and specificity for bleeding or bleeding source were.98 (95% CI,.96-.99) and.99 (95% CI,.97-.99), respectively. Deep learning has achieved excellent performance for the detection of a range of diseases in WCE. Notwithstanding, current research is based on retrospective studies with a high risk of bias. Thus, future prospective, multicenter studies are necessary for this technology to be implemented in the clinical use of WCE. [ABSTRACT FROM AUTHOR]

The aim of our study was to develop and evaluate a deep learning algorithm for the automated detection of small-bowel ulcers in Crohn's disease (CD) on capsule endoscopy (CE) images of individual patients. We retrospectively collected CE images of known CD patients and control subjects. Each image was labeled by an expert gastroenterologist as either normal mucosa or containing mucosal ulcers. A convolutional neural network was trained to classify images into either normal mucosa or mucosal ulcers. First, we trained the network on 5-fold randomly split images (each fold with 80% training images and 20% images testing). We then conducted 10 experiments in which images from n – 1 patients were used to train a network and images from a different individual patient were used to test the network. Results of the networks were compared for randomly split images and for individual patients. Area under the curves (AUCs) and accuracies were computed for each individual network. Overall, our dataset included 17,640 CE images from 49 patients: 7391 images with mucosal ulcers and 10,249 images of normal mucosa. For randomly split images results were excellent, with AUCs of.99 and accuracies ranging from 95.4% to 96.7%. For individual patient-level experiments, the AUCs were also excellent (.94-.99). Deep learning technology provides accurate and fast automated detection of mucosal ulcers on CE images. Individual patient-level analysis provided high and consistent diagnostic accuracy with shortened reading time; in the future, deep learning algorithms may augment and facilitate CE reading. [ABSTRACT FROM AUTHOR]

Background & Aims There are few data available on the real-life pharmacokinetic and pharmacodynamics features of vedolizumab, a monoclonal antibody against integrin α4β7. We performed a prospective study of patients with inflammatory bowel diseases (IBDs) treated with vedolizumab to determine serum drug concentrations, formation of antivedolizumab antibodies (AVAs), and integrin α4β7 saturation. Methods We performed a prospective study of 106 patients with IBD (67 with Crohn’s disease and 39 with ulcerative colitis) treated with vedolizumab from September 2014 through March 2017 at 2 tertiary medical centers in Israel. Clinical data and serum samples were collected before and during induction and maintenance therapy. Clinical remission was defined as Harvey–Bradshaw index scores below 5 or as Simple Clinical Colitis Activity Index scores of 3 or less. We measured serum levels of vedolizumab, AVAs, and markers of inflammation. Peripheral blood mononuclear cells were obtained from some patients at designated trough time points and CD3+ CD45RO+ T cells were isolated from 36 samples. Cells were incubated with fluorescent-conjugated vedolizumab and flow cytometry was used to quantify α4β7 integrin saturation. We also performed flow cytometry analyses of CD3+ CD45RO+ lamina propria T cells isolated from intestinal mucosa of patients without IBD (non-IBD controls, n = 6), patients with IBD not treated with vedolizumab (untreated IBD controls, n = 8), and patients with IBD treated with vedolizumab (n = 15). Results Clinical remission was achieved by 48 of 106 patients (45%) by week 6 and 50 of 106 patients (48%) by week 14 of treatment. The median level of vedolizumab at week 6 was higher in patients in clinical remission (40.2 μg/mL) than in patients with active disease (29.7 μg/mL; P = .05). The median serum level of vedolizumab was significantly higher in patients with a normal level of C-reactive protein (21.8 μg/mL vedolizumab) vs the level in those with a high level of C-reactive protein (11.9 μg/mL vedolizumab) during maintenance treatment ( P = .0006). The other clinical outcomes measured were not associated with median serum level of vedolizumab at any time point examined. AVAs were detected in 17% of patients during induction therapy and 3% of patients during maintenance therapy, but did not correlate with clinical outcomes. Flow-cytometry analysis of peripheral blood memory T cells (n = 36) showed near-complete occupancy of α4β7 integrin at weeks 2 and 14 and during the maintenance phase, regardless of response status or drug levels. Most intestinal CD3+CD45RO+ memory T cells of healthy and IBD controls expressed α4β7 (72%; interquartile range, 56%–81%). In contrast, free α4β7 was detectable on only 5.6% of intestinal memory cells (interquartile range, 4.4%–11.2%) ( P < .0001) from vedolizumab-treated patients, regardless of response. Conclusions In a prospective study of real-life patients with IBD, we associated vedolizumab drug levels with remission and inflammatory marker level. Integrin α4β7 was blocked in almost all T cells from patients treated with vedolizumab, regardless of serum level of the drug or response to treatment. These findings indicate a need to explore alternative mechanisms that prevent response to vedolizumab. [ABSTRACT FROM AUTHOR]

Background & Aims Ustekinumab, an inhibitor of the p40 subunit of interleukins 12 and 23, is an effective treatment for patients with Crohn's disease (CD). Trough concentrations of tumor necrosis factor (TNF) antagonists and presence of anti-drug antibodies are associated with important clinical and endoscopic outcomes. We investigated associations between trough concentrations of ustekinumab and clinical, biomarker, and endoscopic outcomes of real-world patients with CD. Methods We recruited 62 patients with CD who were either refractory or intolerant to TNF antagonists, treated with ustekinumab from April 2014 to September 2015. Patients received 90 mg of ustekinumab subcutaneously at weeks 0, 1, and 2 during induction and 90 mg every 4 or 8 weeks during maintenance. Clinical, biomarker, and endoscopic outcomes, trough concentrations of ustekinumab, and anti-drug antibodies were assessed at both week 10 postinduction therapy and at week 26 or later during maintenance therapy in a prospective longitudinal patient cohort or at week 26 or later during maintenance therapy in a cross-sectional patient cohort. Analysis was performed on data combined from both maintenance cohorts, which had similar outcomes at week 26 or later. A primary analysis determined if ustekinumab drug trough concentrations were associated with clinical response (reduction in Harvey Bradshaw Index score of 3 or greater), clinical remission (Harvey Bradshaw Index score <5), steroid-free clinical remission, biomarker (serum level of C-reactive protein [CRP] or level of fecal calprotectin) reduction, biomarker normalization (serum level of CRP below 5 mg/L or level of fecal calprotectin below 200 μg/g), endoscopic response (simple endoscopic score for CD reduced by 50% or more), or endoscopic remission (simple endoscopic score for CD of 2 or less). Results At week 26 or beyond, 80.7% of patients had a clinical response, 66.1% were in clinical remission, 50.0% were in steroid-free clinical remission, 58.9% had an endoscopic response, and 19.6% were in endoscopic remission. The mean trough concentration of ustekinumab at this time point was higher in patients with an endoscopic response (4.7 μg/mL) than without (3.8 ug/mL; P = .03). An optimal ustekinumab threshold trough concentration at week 26 or later was found to be 4.5 μg/mL (area under the curve, 0.67). A greater proportion of patients with trough concentrations of ustekinumab above 4.5 μg/mL at week 26 or later had an endoscopic response (75.9%) than did patients with trough concentrations below this level (40.7%; P = .008). Patients with trough concentrations of ustekinumab above 4.5 μg/mL at week 26 or later also had a lower mean level of CRP (12.6 mg/L) than did patients with trough concentrations below this level (mean level of CRP, 23.9 mg/L; P = .04). We did not detect antibodies against ustekinumab in any patient. Conclusions Ustekinumab therapy was effective in patients with CD who had not responded to or were intolerant to treatment with a TNF antagonist. Maintenance trough concentrations of ustekinumab above 4.5 μg/mL at 26 weeks or later were associated with biomarker reduction and endoscopic response. [ABSTRACT FROM AUTHOR]

Background and Aims Small-bowel bleeding is the primary indication for capsule endoscopy (CE). Many experts advocate a “watch-and-wait” policy in negative CE. This meta-analysis examines the odds of rebleeding after negative index CE and the impact on long-term follow-up. Methods A comprehensive literature search identified articles examining the rebleeding rate after negative CE. Demographic and clinical information with emphasis on outcomes was retrieved, pooled, and analyzed. Heterogeneity among studies was assessed using the I 2 statistic. A random effects model was used as the pooling method because of high heterogeneity. Risk of bias was assessed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. The primary outcome evaluated was the pooled odds ratios (ORs) for rebleeding after a negative CE for obscure GI bleeding (OGIB). Results Twenty-six studies with 3657 patients were included. The pooled rate of rebleeding after negative CE was .19 (95% CI, .14-.25; P < .0001). The pooled OR of rebleeding was .59 (95% CI, .37-.95; P < .001). The effect was more pronounced in studies with a short follow-up (OR, .47; 95% CI, .24-.94; P < .001). There was no statistically significant difference in rebleeding after CE for occult and overt OGIB. Prospective studies showed a lower OR of rebleeding of .24 (95% CI, .08-.73; P = .01). Most studies were high quality. Conclusions Our analysis shows that negative CE provides adequate evidence of a subsequently low risk of rebleeding. Such patients can therefore be safely managed with watchful waiting. However, patients who rebleed after 2 years may need to be investigated for a new source of blood loss. [ABSTRACT FROM AUTHOR]

Background & Aims Infliximab is a safe and effective therapy for ulcerative colitis (UC). We conducted a multicenter retrospective cohort study that included 7 European countries and Israel to examine whether infliximab discontinuation can be considered for patients who achieve sustained remission. Methods We performed a retrospective cohort study, collecting medical records from 13 tertiary care referral inflammatory bowel disease centers of all patients with UC treated with infliximab (n = 193). We compared the disease course of patients with at least 12 months of clinical remission who discontinued infliximab (n = 111) with that of patients who continued scheduled treatment (controls, n = 82). We examined the incidence rates of relapse, hospitalization and colectomy, the comparative effectiveness of different therapeutic strategies after discontinuation, and assessed the rates of response, remission, and adverse effects after infliximab re-initiation. Statistical analyses used time-to-event methods. Results In the entire cohort, 67 patients (34.7%) relapsed during the follow-up period. The incidence rate of relapse was significantly higher after discontinuation (23.3 per 100 person-years) compared with the control group (7.2 per 100 person-years) in univariable analysis (log-rank P < .001; hazard ratio, 3.41; 95% confidence interval, 1.88–6.20) and multivariable analysis (hazard ratio, 3.70; 95% confidence interval, 2.02–6.77). Rates of hospitalization and colectomy did not differ between groups. Thiopurines appeared to be the best treatment option after infliximab discontinuation (incidence of relapse: 15.0 per 100 person-years for thiopurines, 27.4 per 100 person-years for thiopurines plus aminosalicylates, and 31.2 per 100 person-years for aminosalicylates alone; log-rank P = .032). Response was regained in 77.1% of patients and remission in 51.4% of patients who re-initiated infliximab. However, 17.1% had infusion reactions and 17.1% reported other adverse events. Conclusions In a multinational retrospective cohort study of patients with UC in sustained clinical remission, we associated discontinuation of infliximab with an increased risk of relapse. Treatment re-initiation is effective and safe. [ABSTRACT FROM AUTHOR]