Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists.

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.

Efficacy and Safety of Hyperbaric Oxygen Therapy in Fistulizing Crohn's Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen in a pressurized chamber, increasing tissue oxygen levels and regulating inflammatory pathways. Mounting evidence suggests that HBOT may be effective for inflammatory bowel disease. Our systematic review and meta-analysis aimed to quantify the efficacy and safety of HBOT in fistulizing Crohn's disease (CD). METHODS: A systematic review was conducted using the EMBASE, Web of Science, Pubmed, and Cochrane Library databases according to the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" criteria. Study bias was assessed using the Cochrane Handbook guidelines. RESULTS: Sixteen studies with 164 patients were included in the analysis. For all fistula subtypes, the pooled overall clinical response was 87% (95% CI: 0.70-0.95, I2 = 0) and the pooled clinical remission was 59% (95% CI: 0.35-0.80, I2 = 0). The overall clinical response was 89%, 84%, and 29% for perianal, enterocutaneous, and rectovaginal fistulas, respectively. On meta-regression, hours in the chamber and the number of HBOT sessions were not found to correlate with clinical response. The pooled number of adverse events was low at 51.7 per 10,000 HBOT sessions for all fistula types (95% CI: 16.8-159.3, I2 = 0). The risk of bias was observed across all studies. CONCLUSION: HBOT is a safe and potentially effective treatment option for fistulizing CD. Randomized control trials are needed to substantiate the benefit of HBOT in fistulizing CD.

Comparison of viscous budesonide and fluticasone in the treatment of patients with eosinophilic esophagitis: a systematic review and meta-analysis.

Background: Steroids are an important pharmacologic treatment in patients with eosinophilic esophagitis (EoE). Fluticasone and budesonide are the 2 main steroid medications used in EOE treatment, but current United States (US) guidelines do not recommend one agent over the other. In this study, we conducted a meta-analysis to compare important patient outcomes when both agents are used. Methods: A comprehensive search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was performed from each database's inception to March 29th, 2023. Two independent reviewers systematically identified trials that compared the effect of budesonide vs. fluticasone in the management of EoE. A meta-analysis was performed using a fixed-effects model. The primary outcome was the histologic response (defined as an eosinophil count <15 per high-power field) which reflects the response to treatment. Results: Three studies met our inclusion criteria and were included in the analysis, with a total of 272 patients. All studies were carried out in the US and 1 was a randomized controlled trial. Our meta-analysis showed no statistically significant difference with the use of budesonide compared to fluticasone in achieving a histologic response (odds ratio 1.29, 95% confidence interval 0.77-2.14; P=0.34; I2=0%). Conclusion: Our systematic review and meta-analysis indicated no difference between budesonide and fluticasone in achieving a histologic response in patients with EoE.

Predictive Model for Positive Video Capsule Endoscopy in Iron Deficiency Anemia.

BACKGROUND AND AIMS: Bleeding from the gastrointestinal tract can contribute to the development of iron deficiency anemia (IDA) among individuals without another obvious source of bleeding. In order to identify patients most likely to benefit from examination of the small bowel, our aim was to create a risk score for positive video capsule endoscopy (VCE) in IDA utilizing a multicenter collection of studies. METHODS: We performed a retrospective multicenter study utilizing VCE studies performed for an indication of IDA between 1/1/2005 and 7/31/2018. VCE findings were graded based on the P0-P2 grading system. The primary outcome of interest was a positive (P2) VCE. Data were analyzed with Student's t test for continuous variables and the Fisher's exact test for categorical variables. Logistic regression was used to identify independent associations with positive VCE. RESULTS: In total, 765 VCE procedures were included with 355 (46.5%) male subjects and a median age of 63.2 (SD 15.3) years. One hundred ninety studies (24.8%) were positive (P2) for small bowel bleeding. Four variables associated with positive VCE which were incorporated into a point scoring system: (+) 1 for age ≥ 66 years, active smoking and cardiac arrythmia and (-) 1 for preceding hemoglobin level ≥ 8.5. The risk probabilities for positive VCE-assigned scores - 1, 0, 1, and 2 + were 12.3% (95% CI 7.3-17.3%), 20% (14.9-25.1%), 34.8% (28.6-41%), and 39% (30-47.8%). CONCLUSION: In order to improve the diagnostic yield of capsule examinations, risk factors should be applied to clinical decision-making. We created a risk score for positive VCE in IDA, including the risk factors of age, smoking, history of cardiac arrythmia, and preceding hemoglobin level.

The Feasibility, Safety, and Long-term Outcomes of Endoscopic Submucosal Dissection for Colorectal Neoplasia in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Evidence regarding the utility of endoscopic submucosal dissection (ESD) for neoplasia in patients with inflammatory bowel disease (IBD) is limited. This meta-analysis aims to understand the feasibility, safety, and long-term outcomes of ESD in IBD patients. METHODS: Electronic databases were searched for observational and case-controlled studies. Primary endpoints were en bloc resection and margin-negative resection of neoplastic lesions. Secondary endpoints included procedure-related bleeding and perforation, local recurrence, and metachronous neoplasia. RESULTS: We analyzed 25 studies with a total of 585 neoplastic lesions in 552 patients. The rates of en bloc resection and margin-negative resection were 0.88 [95% confidence interval (CI) 0.82-0.92] and 0.78 (95% CI 0.72-0.83), respectively. Meta-regression analysis showed longer disease duration was significantly associated with the higher rate of en bloc resection. The rates of procedure-related bleeding and perforation were 0.080 (95% CI 0.057-0.11) and 0.055 (95% CI 0.038-0.081), respectively. The rates of local recurrence and metachronous neoplasia were 0.008 events/person-year (95% CI 0.002-0.013) and 0.031 event/person-year (95% CI 0.016-0.046), respectively. Meta-analysis of case-controlled studies found no significant differences in the endpoints between IBD patients treated by ESD and those treated by endoscopic mucosal resection, or non-IBD patients treated by ESD. CONCLUSIONS: ESD is a feasible and safe procedure to remove neoplastic lesions in IBD patients. Given there is a considerable risk of metachronous neoplasia development, postoperative surveillance colonoscopy with an appropriate consultation with surgeons is essential to monitor not only local recurrence but also neoplastic changes in the remaining colon.

Prevalence and clinical features of patients with autoimmune pancreatitis and inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) are categorized into immune-mediated inflammatory disorders (IMIDs). While AIP is a pancreato-biliary IMID with an increased incidence and prevalence among patients with IBD, its features are still unclear. This systematic review and meta-analysis aims to assess the prevalence and clinical characteristics of AIP-IBD patients. METHODS: Electronic databases were searched to identify observational studies assessing AIP and IBD. The primary outcome was the prevalence of IBD among AIP patients, and vice versa. Secondary outcomes included clinical findings and outcomes of each IMID in AIP-IBD patients. The pooled rate of each outcome was determined using a random effects model. RESULTS: For primary outcomes, 40 observational studies with 4031 AIP patients were included and the pooled prevalence of IBD was 10.5% (95% CI 7.2-15.0%). Meanwhile, five studies with 10,551 IBD patients were included and the pooled prevalence of AIP was 0.6% (95% CI 0.2-1.9%). For secondary outcomes, 53 observational studies with 469 AIP-IBD patients were assessed. The rates of type 2 AIP and ulcerative colitis were 79.2% (95% CI 69.1-86.6%) and 74.8% (95% CI 68.2-80.4%), respectively. We also demonstrated AIP-IBD patients were at a significant increased risk of AIP recurrence and colectomy compared with patients with either AIP or IBD (RR = 1.9, 95% CI 1.1-3.1 and P = 0.014 and RR = 3.7, 95% CI 1.9-6.9, P < 0.001, respectively). CONCLUSIONS: Our meta-analysis reported the prevalence of AIP-IBD patients and demonstrated patients with both IMIDs had a high risk of poor outcomes.

Pregnancy and neonatal outcomes in women receiving calcineurin inhibitors: A systematic review and meta-analysis.

AIMS: Calcineurin inhibitors (CNIs) are often used for solid organ transplantation recipients or patients with immune-mediated diseases. This systematic review and meta-analysis aims to understand how CNIs affect pregnancy and neonatal outcomes. METHODS: Electronic databases were searched for observational studies assessing pregnancy and neonatal outcomes in CNI-treated patients. The pooled rate of each outcome was determined. Metaregression was conducted to identify contributing factors to the outcomes. RESULTS: We analysed 98 studies with a total of 5355 pregnancies in 4450 CNI-treated patients. The pooled rates of live birth and spontaneous abortion were 82.1% (95% confidence interval [CI] 76.7-86.4%) and 11.7% (95% CI 8.7-15.5%), respectively. The rates of preterm delivery (33.2%, 95% CI 29.2-37.5%), low birth weight (35.8%, 95% CI 27.7-44.8%) and preeclampsia (13.5%, 95% CI 9.4-19.2%) were 3-4 times higher than the rates of general population. Nearly half of the CNI-treated patients required caesarean delivery (43.5%, 95% CI 36.9-50.3%). The rates of stillbirth, neonatal and maternal death were 4.2% (95% CI 2.8-6.2%), 2.9% (95% CI 1.8-4.8%) and 2.3% (95% CI 1.3-4.1%), respectively. Metaregression showed that preeclampsia was significantly associated with the risks of preterm delivery and low birth weight. Older maternal age, prepregnancy hypertension and cyclosporine use increased the risk of preeclampsia. CONCLUSION: Given the higher mortalities in CNI-treated patients and their children than the general averages, their pregnancy is considered high risk. The risks of preterm delivery and low birth weight were primarily attributed to preeclampsia. Since prepregnancy hypertension increased its risk, an appropriate preconception blood pressure management may improve their outcomes.

Review article: drug-induced small bowel injury.

BACKGROUND: Drug-induced gastrointestinal injury has been increasingly reported, but its exact incidence is not known. The small and large intestines represent the most affected sites of injury, accounting for 20%-40% of all gastrointestinal side effects. AIM: To provide an updated literature review detailing medications linked to the development of small bowel injury. METHODS: We conducted a literature search on PubMed from its inception to May 1, 2021. We included English-language original studies, meta-analyses, systematic reviews, review articles and case reports. RESULTS: Drug-induced enteropathy can range from asymptomatic histological changes resulting in a subtle, self-limited disease to a chronic inflammatory condition mimicking inflammatory bowel disease, or bowel perforation. Endoscopy can demonstrate erythema, mucosal friability, oedema, erosions, ulcers or strictures in severe cases. Histology may include mucosal erosions and ulcerations, focal active enteritis, villous atrophy, epithelial apoptosis or necrotising enteritis. A well-established association has been found with the use of nonsteroidal anti-inflammatory drugs, immunosuppressants, chemotherapeutic agents, antibiotics, immunotherapies, etanercept and olmesartan. Possible associations have been reported with other biologic agents, medications used for glycemic control, antihypertensives, cholinesterase inhibitors, potassium and iron supplements, with conflicting data regarding contraceptives/hormonal therapy and isotretinoin. CONCLUSION: Physicians should be aware of the manifestations of drug-induced enteropathy as early recognition can lead to prompt discontinuation of the offending therapy and, therefore, a reduced risk of future complications.

P014 Postoperative Recurrence in Crohn's Disease Patients Treated with Adalimumab versus Infliximab: A Systematic Review and Meta-Analysis.

BACKGROUND: Up to 80% of patients with Crohn's disease (CD) undergo intestinal resection at one point. However, the risk of post-operative recurrence (POR) increases with time, with half of these patients developing recurrence at five years after surgery. Treatment with anti-tumor necrosis factor (anti-TNF) agents has been shown to decrease the risk of clinical and endoscopic recurrence post-operatively. This meta-analysis aims to compare the rate of the two mostly commonly used anti-TNF agents (infliximab (IFX) and adalimumab (ADA)) and their efficacy in maintaining clinical and endoscopic remission in CD patients who were treated with adalimumab versus infliximab after surgery. METHODS: A comprehensive search of Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus was conducted from each database's inception to May 29th 2021. Comparative studies assessing the efficacy and safety of infliximab and adalimumab for postoperative CD patients were included. Primary outcomes included postoperative clinical and endoscopic remission. Secondary outcome was the risk of adverse events due to anti-TNF agents. Pooled event rates were calculated per person-year of follow-up. RESULTS: Four studies with total of 361 CD patients were included in the final analysis. Our meta-analysis showed no statistically significant difference in maintaining clinical and endoscopic remission rates between patients treated with infliximab and those with adalimumab (Pooled incidence rate ratio of 0.75 (95% CI 0.43-1.3), and 0.94 (95% CI 0.71-1.2), respectively) (Figure 1A, 2A). There were low to moderate heterogeneities (I2 = 57.1% for clinical remission and I2 = 0% for endoscopic remission). The funnel plot in each analysis indicated no publication bias, which was supported by Begg's and Egger's tests (Figure 1B, 2B). There was also no significant difference in the risk of adverse events between the two groups (RR= 0.56, 95% CI 0.068-4.5) (Figure 3). CONCLUSION: Our meta-analysis demonstrated comparable efficacy of infliximab and adalimumab in maintaining post-operative clinical and endoscopic remission in Crohn's disease, with similar rates of adverse events. Our meta-analysis was limited by the small number of total studies and patients included and the lack of randomized controlled trials.

Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis.

OBJECTIVES: The prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases who are frequently treated with disease modifying therapies remains poorly understood. This meta-analysis aims to assess the prevalence and clinical outcomes of COVID-19 in autoimmune diseases. METHODS: Electronic databases were searched for observational and case-controlled studies. We sorted medications into glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic or targeted synthetic DMARDs (b/tsDMARDs), which was also divided into monotherapy and b/tsDMARDs-csDMARDs combination therapy. RESULTS: We analysed 62 observational studies with a total of 319 025 patients with autoimmune diseases. The prevalence of COVID-19 was 0.011 (95% CI: 0.005 to 0.025). Meta-analysis of seven case-controlled studies demonstrated that the risk of COVID-19 in autoimmune diseases was significantly higher than in control patients (OR: 2.19, 95% CI: 1.05 to 4.58, p=0.038). Meta-regression analysis showed glucocorticoids were significantly associated with the risk of COVID-19. For clinical outcomes, we assessed 65 studies with 2766 patients with autoimmune diseases diagnosed with COVID-19. The rates of hospitalisation and mortality were 0.35 (95% CI: 0.23 to 0.50) and 0.066 (95% CI: 0.036 to 0.12), respectively. Glucocorticoids, csDMARDs and b/tsDMARDs-csDMARDs combination therapy increased the risk of these outcomes, whereas b/tsDMARDs monotherapy, particularly antitumour necrosis factor agents, were associated with a lower risk of hospitalisation and death. CONCLUSIONS: Our meta-analysis demonstrated that patients with autoimmune diseases had an increased risk of COVID-19, primarily attributed to glucocorticoid use. b/tsDMARDs monotherapy was associated with a lower risk of severe COVID-19 suggesting its safety in the COVID-19 pandemic.

Drug-Induced Colitis.

Drug-induced colitis encompasses a wide spectrum of colon disorders that can manifest microscopically or macroscopically. Patients present with new-onset colitis or exacerbations of inflammatory bowel diseases; in some cases, colitis resolves with discontinuation of medication. Mucosal injury can be focal or extensive, involving the entire colonic mucosa, and sometimes involves other parts of the gastrointestinal tract. It has been a challenge to determine the proportion of new-onset colitis caused by medication and there are few data on the overall prevalence. We review the drugs that have been linked with development of drug-induced colitis and strategies for physicians who believe their patients have this disorder-usually discontinuation of the drug believed to cause colitis and treatment with steroids or immune-modulating therapies. Physicians must be aware of medications that can cause colitis.

Early vs Late Use of Anti-TNFa Therapy in Adult Patients With Crohn Disease: A Systematic Review and Meta-Analysis.

OBJECTIVES: While anti-tumor necrosis factor alpha (anti-TNFa) therapies for Crohn disease (CD) were initially introduced in 1998 for biologic therapies are often introduced after a minimum of 6 years after diagnosis. The benefit of anti-TNFa early in the course of CD is still controversial, with some studies showing better outcomes but others not. To determine whether earlier introduction of anti-TNFa therapy improves efficacy in clinical trials or clinical series, we aimed to perform a meta-analysis comparing early vs late anti-TNFa use in the management of CD. METHODS: A comprehensive search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database's inception to November 3, 2019. We included comparative studies of early vs late use of anti-TNFa therapy in adult patients with CD. RESULTS: Eleven studies were included in the analysis, with a total of 2501 patients. Meta-analysis demonstrated that the early use of anti-TNFa was associated with a statistically significant decrease in the need for surgery (relative risk [RR] = 0.43; 95% confidence interval [CI], 0.26-0.69; I2 = 68%) and disease progression (RR = 0.51; 95% CI, 0.35-0.75; I2 = 61%). Early use also showed an increase in early remission (RR = 1.94; 95% CI, 1.54-2.46; I2 = 0%) and clinical response. There was no statistically significant difference in achieving late remission (RR = 1.39; 95% CI, 0.94-2.05; I2 = 65%) or mucosal healing (RR = 1.10; 95% CI, 0.63-1.91; I2 = 0%). CONCLUSION: This systematic review suggests that using anti-TNFa earlier in the treatment of CD (within 3 years) may improve clinical outcomes compared to late administration in terms of achieving early clinical remission, clinical response, disease progression, and the need for surgery.

Rates of and Factors Associated With Placebo Response in Trials of Pharmacotherapies for Nonalcoholic Steatohepatitis: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: It is important to know the extent of the placebo effect in designing randomized controlled trials for patients with nonalcoholic steatohepatitis (NASH), to accurately calculate sample size and define treatment endpoints. METHODS: We performed a systematic review and meta-analysis of the placebo groups from randomized controlled trials of adults with NASH that provided histologic and/or magnetic resonance image-based assessments. We identified trials through a comprehensive search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus, from each database's inception through January 2, 2018. RESULTS: We identified 39 randomized controlled trials, comprising 1463 patients who received placebo. Histologic assessment data (the nonalcoholic fatty liver disease activity scores, NAS) were available from 956 patients; magnetic resonance spectroscopy data were available from 295 patients and magnetic resonance proton density fat fraction measurements from 61 patients. Overall, 25% of patients given placebo had an improvement in NAS by 2 or more points (95% CI, 21%-29%) with a small amount of heterogeneity (I2 = 27%). There were improvements by at least 1 point in steatosis scores of 33% ± 3% of patients, in hepatocyte ballooning scores of 30% ± 3% of patients, in lobular inflammation scores of 32% ± 3% of patients, and in fibrosis scores of 21% ± 3% of patients, with a moderate amount of heterogeneity among trials (I2 range, 51%-63%). Patients given placebo had a statistically significant improvement in NAS (by 0.72 ± 0.19), with a large amount of heterogeneity (I2 = 96%). Univariate and multivariate meta-regression showed that trials with a higher baseline NAS, those conducted in South America, and those in which patients had a decrease in body mass index, were associated with greater improvements in NAS among patients given placebo. Patients given placebo had significant reductions in intrahepatic triglyceride, measured by magnetic resonance spectroscopy (by 1.45% ± 0.54%) with moderate heterogeneity (I2 = 40%), and in magnetic resonance proton density fat fraction (by 2.43 ± 0.89), without heterogeneity (I2 = 0). Mean serum levels of alanine and aspartate aminotransferases decreased significantly (by 11.7 ± 3.8 U/L and 5.9 ± 2.1 U/L, respectively; P < .01 for both). CONCLUSIONS: In a meta-analysis of randomized controlled trials of NASH, patients given placebo have significant histologic, radiologic, and biochemical responses. The placebo response should be considered in designing trials of agents for treatment of NASH.

Nonalcoholic fatty liver disease and the risk of clinical cardiovascular events: A systematic review and meta-analysis.

OBJECTIVE: Numerous studies have assessed the association between Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However, results have been conflicting due to variability in definitions of NAFLD and ascertainment of CVD, often combining clinical and surrogate endpoints. We therefore systematically reviewed published literature to assess the association between NAFLD and clinical cardiovascular events (CVE) and performed a meta-analysis. METHODS: We searched PubMed, Medline, Cochrane, CINAHL, and Web of Science databases using terms "nonalcoholic fatty liver disease", "nonalcoholic steatohepatitis", "cardiovascular disease", and their combinations to identify prospective studies published from inception through March 2016. Data from selected studies was extracted and meta-analysis was then performed using random effects model. RESULTS: A total of six studies with 25,837 patients (NAFLD: 5953; controls: 19,884) were included in the final analysis. Patients with NAFLD had a significantly higher risk of clinical CVE compared to controls (RR: 1.77; 95% CI: 1.26-2.48, p<0.001). Exclusion sensitivity analysis did not alter the above results. The association remained consistent for subgroups with clinical coronary artery disease (RR: 2.26; 95% CI: 1.04-4.92, p<0.001) and ischemic stroke (RR: 2.09; 95% CI: 1.46-2.98, p<0.001). The risk of cardiovascular mortality was also increased in the NAFLD group (RR 1.46, 95% CI 1.31-1.64, p<0.001). CONCLUSION: NAFLD patients have a significantly higher risk for clinical CVE compared to those without. These results need to be confirmed in large prospective studies.