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Introduction: We aimed to describe immune-related adverse events (irAEs) affecting multiple organs of the gastrointestinal system in patients who received immune checkpoint inhibitors., Methods: Within a 2,843 patient retrospective cohort consisting of patients with cancer treated with immune checkpoint inhibitors, we used the Electronic Medical Record Search Engine, an information retrieval system, to search free text in the medical record to identify patients with multiple gastrointestinal irAEs., Results: Thirteen patients developed multiple gastrointestinal irAEs (0.46%). The most common patterns of multisystem gastrointestinal irAE were colitis + pancreatitis and colitis + enteritis., Discussion: Multisystem gastrointestinal irAEs are rare but warrant further characterization and attention., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI)., Methods: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined., Results: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 μg/mL, P = 0.02). IFX trough levels did not differ between BMI groups., Discussion: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: After colectomy with ileoanal pouch anastomosis (IPAA), many patients develop high bowel frequency (BF) refractory to antimotility agents, despite normal IPAA morphology. Low circulating levels of glucagon-like protein-1 (GLP-1), a modulator of gastroduodenal motility, have been reported after colectomy., Methods: Double-blind crossover study of 8 IPAA patients with refractory high BF treated with daily administration of the GLP-1 receptor agonist liraglutide or placebo., Results: Liraglutide, but not placebo, reduced daily BF by more than 35% ( P < 0.03)., Discussion: Larger randomized controlled studies are warranted to delineate the treatment potential of GLP-1 receptor agonists in IPAA patients suffering from noninflammatory high BF., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objectives: Adipocytes of peripancreatic and intrapancreatic adipose tissue secret adipocytokines such as leptin, adiponectin, and resistin. For resistin, a role as an early predictor of peripancreatic necrosis and clinical severity in acute pancreatitis has been reported. It was the aim of this study to investigate whether the adipocytokine visfatin is able to serve as an early marker predicting peripancreatic necrosis and clinical severity., Methods: A total of 50 patients (20 females and 30 males) with acute pancreatitis were included in this noninterventional, prospective, and monocentric cohort study on diagnostic accuracy. Clinical severity was classified by the Ranson score and APACHE-II (Acute Physiology and Chronic Health Evaluation II) score. Pancreatic and peripancreatic necrosis were quantified by the computed tomography-based Balthazar score, the Schroeder score, and the pancreatic necrosis score. Visfatin was measured at admission and daily for 10 days by enzyme-linked immunosorbent assay (ELISA)., Results: Visfatin values were significantly and positively correlated with clinical severity (APACHE-II score and Ranson score) and with clinical end points such as death and need for interventions. Admission visfatin levels were significantly elevated in patients with higher pancreatic and extrapancreatic necrosis scores. It was shown by receiver operator characteristics that admission visfatin concentration provides a positive predictive value of 93.3% in predicting the extent of peripancreatic necrosis (area under the curve (AUC): 0.89, P<0.001, sensitivity: 93.3%, specificity: 81.8%, likelihood ratio: 5.1, post-test probability: 93%) by using a cutoff value of 1.8 ng/ml., Conclusions: Admission visfatin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Visfatin may have potential for clinical use as a new and diagnostic serum marker.

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

Objectives: Peripancreatic necrosis determines clinical severity in acute pancreatitis. Early markers predicting peripancreatic necrosis and clinical severity are lacking. Because adipocytes of peripancreatic adipose tissue secret highly active adipocytokines, the aim of the study was to investigate whether adipocytokines are able to serve as early markers predicting peripancreatic necrosis and clinical severity., Methods: A total of 50 patients (20 women, 30 men) with acute pancreatitis were included in this noninterventional, prospective, and monocentric cohort study on diagnostic accuracy. Clinical severity was classified by the Ranson score and the APACHE (Acute Physiology And Chronic Health Evaluation) II score. Pancreatic and peripancreatic necrosis were quantified by using the computed tomography-based Balthazar score, the Schroeder score, and the pancreatic necrosis score. Adiponectin, leptin, and resistin were measured at admission and daily for at least 10 days by enzyme-linked immunosorbent assay., Results: In contrast to admission C-reactive protein values, admission resistin values were significantly correlated with clinical severity and even with clinical end points such as death and need for interventions. Admission resistin levels were significantly elevated in patients with higher pancreatic and extrapancreatic necrosis scores. It was shown by receiver-operator characteristics that admission resistin concentration provides a positive predictive value of 89% in predicting the extent of peripancreatic necrosis (area under the curve, 0.8; P=0.002; sensitivity, 80%; specificity, 70%) by using a cutoff value of 11.9 ng/ml., Conclusions: Admission resistin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Resistin may have potential for clinical use as a new and diagnostic serum marker.

Objectives: The degree of diagnostic radiation exposure in children with inflammatory bowel diseases (IBD) is largely unknown. In this study, we describe this exposure in a population-based sample of children with IBD and determine the characteristics associated with moderate radiation exposure., Methods: We ascertained radiological study use, demographic characteristics, IBD medication use, and the requirement for hospitalization, emergency department (ED) encounter, or inpatient gastrointestinal surgery among children with IBD within a large insurance claims database. Characteristics associated with moderate radiation exposure (at least one computed tomography (CT) or three fluoroscopies over 2 years) were determined using logistic regression models., Results: We identified 965 children with Crohn's disease (CD) and 628 with ulcerative colitis (UC). Over 24 months, 34% of CD subjects and 23% of UC subjects were exposed to moderate diagnostic radiation (odds ratio (OR) 1.71, 95% confidence interval (CI), 1.36 - 2.14). CT accounted for 28% and 25% of all studies in CD and UC subjects, respectively. For CD subjects, moderate radiation exposure was associated with hospitalization (OR 4.89, 95% CI 3.37 - 7.09), surgery (OR 2.93, 95% CI 1.59 - 5.39), ED encounter (OR 2.65, 95% CI 1.93 - 3.64), oral steroids (OR 2.25, 95% CI 1.50 - 3.38), and budesonide (OR 1.80, 95% CI 1.10 - 3.06); an inverse association was seen with immunomodulator use (OR 0.67, 95% CI 0.47 - 0.97). Except for oral steroids and immunomodulators, similar relationships were seen in UC., Conclusions: A substantial proportion of children with IBD are exposed to moderate amounts of radiation as a result of diagnostic testing. This high utilization may impart long-term risk, given the chronic nature of the disease.

Objectives: To evaluate the efficacy and safety of purine analogs (azathioprine, 6-mercaptopurine (6-MP)) in the prevention of postoperative recurrence in Crohn's disease (CD)., Methods: We searched MEDLINE, the Cochrane Library, and EMBASE. The primary end points, clinical and endoscopic recurrence at 1 and 2 years, and safety were analyzed by the methods of Peto and Der Simonian and Laird., Results: Four controlled trials enrolled 433 patients and compared azathioprine (n=3) or (6-MP) (n=1) with control arms (placebo with or without antibiotic induction therapy or mesalamine). In the overall analysis, purine analogs were more effective than control arms in preventing clinical recurrence at 1 year (mean difference, 95% confidence interval (CI): 8, 1-15%, P=0.021, number needed to treat (NNT)=13) and 2 years (mean difference, 95% CI: 13%, 2-24%, P=0.018, NNT=8). In sensitivity analyses, the efficacy of purine analogs was superior to that of placebo for the prevention of clinical and endoscopic recurrence at 1 year (mean differences, 95% CI: 13, 1.8-25%, P=0.025, NNT=7, and 23%, 9-37%, P=0.0016, NNT=4, respectively). At 1 year, in the overall analysis, purine analogs were more effective than control arms were in preventing severe (i2-4) endoscopic recurrence (mean difference, CI 95%: 15, 1.8-29%, P=0.026, NNT=7), but they were not effective in the prevention of very severe (i3-4) recurrence. The rate of adverse events leading to drug withdrawal was higher in thiopurine-treated patients than in control arms (17.2 vs. 9.8%, respectively, P=0.021)., Conclusions: Purine analogs are more effective than placebo in preventing both clinical and endoscopic postoperative recurrence in CD, but they are associated with a higher rate of adverse events leading to drug withdrawal.

Objectives: Anemia is a frequent complication in patients with inflammatory bowel disease (IBD). The optimal route for iron supplementation to replenish iron stores has not been determined so far. We therefore evaluated the efficacy and safety of intravenous iron sucrose as compared with oral iron sulfate for the treatment of iron deficiency anemia (IDA) in patients with IBD., Methods: A randomized, prospective, open-label, multicenter study was performed in 46 patients with anemia and transferrin saturation