Blue Notes
Authors: Charles J. Kahi
Journal: Clinical Gastroenterology and Hepatology (2024)

Immune-mediated inflammatory disorders (IMIDs) including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis/psoriatic arthritis (PSO), and ankylosing spondylitis (AS), are associated with increased risk of major adverse cardiovascular events (MACE). There is uncertainty regarding the cardiovascular safety of newer medications for IMIDs such as biologics and small molecules (anti-IL-23, anti-IL-12/23, anti-TNFs, and JAKi). This network meta-analysis pooled 40 studies (36 RCTs) that reported MACE (myocardial infarction, cerebrovascular accident, unstable angina, cardiovascular death, or heart failure) in patients with IMIDs. The study included nearly 127,000 patients with IMID, most commonly PSO (70%), followed by RA (16%), and IBD (6%). On network meta-analysis, anti-TNF-α (OR, 2.49, 95% credible interval [CrI]: 1.14-5.62), JAKi (OR, 2.64, 95% CrI: 1.26-5.99), and anti-IL-12/23 (OR, 3.15, 95% CrI: 1.01-13.35) were associated with increased risk of MACE compared with placebo. There was no significant difference between these agents in the magnitude of the MACE risk. Anti-IL-23 was not associated with increased MACE risk. The magnitude of risk of MACE with anti-TNF, JAKi, anti-IL12/23, or anti-IL-23 versus placebo was not statistically different based on IMID type on direct and network comparisons. Comment: The increased risk of MACE with anti-IL-12/23, JAKi, and anti-TNF-α is concerning and warrants vigilance especially in younger individuals. Still, the risk appears independent of IMID or medication type, and thus MACE risk should not be the foremost factor guiding treatment selection. See page 961. Several randomized controlled trials and meta-analyses of these trials show that computer-aided detection (CADe) can improve adenoma detection by about 10%. However, these positive results have not been consistently replicated in less controlled settings. This systematic review and meta-analysis aimed to assess the benefits and harms of CADe in real-world practice. A total of 8 non-randomized studies (4 prospective, 4 retrospective) comprising 9,782 patients were included. There was no significant difference between CADe-assisted and standard colonoscopy with regards to adenoma detection rate (44% vs 38%; RR 1.11 [95% CI 0.97 – 1.28]), mean adenoma per colonoscopy (0.93 vs 0.79; MD 0.14 [-0.04 – 0.32]), or advanced adenoma detection rate (RR 0.84 [95% CI 0.59 – 1.20]. There was also no difference in mean non-neoplastic lesions per colonoscopy (0.52 vs 0.47; MD 0.14 [-0.07 – 0.34]) and withdrawal time (14.3 vs 13.4 minutes; MD 0.8 minutes [-0.18 – 1.90]). There was a slight advantage in favor of CADe in leave-one-study out analysis and when considering only prospective studies, but stratification by colonoscopy indication did not affect the main findings. Comment: There is a clear performance gap of CADe between randomized controlled trials and pragmatic, real-world settings. Therefore, the answer to the broad question of whether CADe is helpful is a nuanced "it depends"-on the practice setting in which it is deployed, and also very importantly on individual endoscopists and their engagement with the technology. See page 971. Established modifiable risk factors for diverticulitis include diet, physical inactivity, and obesity, but little is known about the effect of smoking and alcohol consumption. To address this knowledge gap, investigators identified over 84,000 women in the Nurses' Health Study II who were 39-52 years old and without known diverticulitis at baseline in 2003. Smoking was ascertained every 2 years and alcohol use every 4 years, and participants self-reported diverticulitis on questionnaires (92% accuracy of self-report compared to medical record review). Multivariable models adjusted for age, menopausal hormone status and hormone use, BMI, physical activity, smoking status, alcohol intake, aspirin use, NSAID use, fiber intake, and red/processed meat intake. There were 3,018 incident diverticulitis cases. Compared to never smoking, current smoking (HR 1.20, 95% CI 1.04-1.39) and past smoking (HR 1.20, 95% CI 1.11-1.30) were both associated increased risk of incident diverticulitis. No dose-response relationship was found when smoking was assessed in pack-years. For alcohol, compared to non-drinkers, women who consumed 30 or more g/d of alcohol (more than 2 drinks/d) had an HR of 1.26 (95% CI, 1.05-1.50; P trend = 0.04). A joint analysis of smoking and alcohol found that individuals who smoked and consumed more than 2 alcoholic beverages daily were at the highest risk. Comment: Patients with incidental findings of diverticulosis at colonoscopy often ask for advice on what to do about it and how to prevent complications. In addition to healthy diet and exercise, stopping smoking and avoiding heavy alcohol use may also help mitigate the risk of diverticulitis. See page 1108. Screening for certain GI disorders, such as colorectal cancer, has been shown to be associated with "teachable moments" where patients adopt beneficial lifestyle changes. There are few studies that have investigated the effect of knowledge about liver disease status can lead to beneficial lifestyle changes. This study aimed to evaluate short- and long-term consequences after screening for liver fibrosis with transient elastography (TE) in individuals at risk of alcohol related liver disease (ALD, n=1850) and metabolic dysfunction-associated steatotic liver disease (MASLD, n=2946). Among nearly 4800 participants, 10% in the ALD group and 7% in the MASLD group had TE ≥8 kPa. In patients in the ALD group, median drinks decreased by 4 units/week after 6 months, and this was most pronounced in those with a positive screening TE (10 units/week). After 6 months, the prevalence of alcohol overuse decreased from 46% to 32%, 45% reported abstinence/decreased use, and only 15% reported increased drinking. The number of individuals with abstinence/decreased use was significantly higher in screening positive, but there was no difference between screening status and increased alcohol use. The reduction in weekly drinks was sustained at 2-year reassessment, and the association of a positive screening test with abstinence/decreased alcohol use was still present (OR=1.84, 95% CI 1.09-3.11). In patients in the MASLD group, 35% reported decreased caloric intake/healthier diet at 6 months, which was also more pronounced among those with a positive screening TE. In addition, 22% reported that they exercised more, and 13% reported a weight loss ≥5%. These observations were sustained in a smaller subgroup that completed repeat interview after a median of 33 months. Comment: In at-risk individuals, screening for liver fibrosis can itself be part of the treatment, as it can lead to sustained reductions in alcohol consumption and weight, and improved dietary and exercise habits. See page 1037. Screening for Fibrosis Promotes Lifestyle Changes: A Prospective Cohort Study in 4796 IndividualsClinical Gastroenterology and HepatologyVol. 22Issue 5PreviewEarly detection of liver fibrosis is believed to promote lifestyle changes. We evaluated self-reported changes in alcohol intake, diet, exercise, and weight after participating in a screening study for liver fibrosis. Full-Text PDF Open AccessRisk of Major Adverse Cardiovascular Events in Immune-Mediated Inflammatory Disorders on Biologics and Small Molecules: Network Meta-AnalysisClinical Gastroenterology and HepatologyVol. 22Issue 5PreviewRecent studies raise concern for increased risk of major adverse cardiovascular events (MACE) with Janus kinase (JAK) inhibitors used to treat immune-mediated inflammatory disorders (IMIDs). We aimed to examine MACE risk with licensed biologics and small molecules used commonly between IMIDs: inflammatory bowel disease, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis. Full-Text PDF Lack of Effectiveness of Computer Aided Detection for Colorectal Neoplasia: A Systematic Review and Meta-Analysis of Nonrandomized StudiesClinical Gastroenterology and HepatologyVol. 22Issue 5PreviewBenefits of computer-aided detection (CADe) in detecting colorectal neoplasia were shown in many randomized trials in which endoscopists' behavior was strictly controlled. However, the effect of CADe on endoscopists' performance in less-controlled setting is unclear. This systematic review and meta-analyses were aimed at clarifying benefits and harms of using CADe in real-world colonoscopy. Full-Text PDF Smoking and Alcohol Consumption and Risk of Incident Diverticulitis in WomenClinical Gastroenterology and HepatologyVol. 22Issue 5PreviewMuch of what is known about the effects of alcohol and tobacco use on diverticular disease derives from studies of asymptomatic diverticulosis or complicated diverticulitis. We examined smoking and alcohol consumption and risk of incident diverticulitis in a large cohort of women. Full-Text PDF