Prognostic Value of Inflammatory Bowel Disease-associated Biomarkers in Patients With Immune Checkpoint Inhibitor Enterocolitis: A Retrospective Cohort Study.

In the emerging field of immune checkpoint inhibitor enterocolitis, biomarkers to predict disease course are lacking. Select genetic polymorphisms (ATG16L1T300A) and serum amyloid A warrant further study as potential biomarkers associated with severe ICI enterocolitis.

Effects of COVID-19 on Patients with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) may take medications that affect their immune system, altering their ability to fight infection or making them less responsive to vaccines. Many of these patients were excluded from original studies regarding COVID-19, which creates a challenge for gastroenterologists to use evidence-based medicine to guide their management. We reviewed the available literature regarding patients with IBD and COVID-19 outcomes and response to vaccinations. Of all IBD patients, 0.3-24% acquired COVID-19 infection and 7-67% of those patients required hospitalization. Many studies have analyzed the effects of COVID-19 on patients with IBD. Observational studies suggest most IBD patients are not at higher risk from COVID-19 infection and that the COVID-19 vaccines are safe, effective and recommended. However, patients being treated with a TNF-α inhibitor with an immunomodulator and patients being treated with steroids should be monitored closely and efforts should be made to wean patients off of systemic steroids if possible. Patients treated with these regimens had lower antibody responses to vaccination and were at higher risk of acquiring severe COVID-19 infection. Antibody responses were robust after the second dose of mRNA vaccines with 85-100% of individuals showing seroconversion, albeit with lower levels of antibodies compared to the general population.

Analysis of Decreasing Adverse Events with Endoscopic Ultrasound in a New Advanced Endoscopy Program Over Time.

OBJECTIVE: New innovations and increasing utility of endoscopic ultrasound (EUS) are associated with rare but serious risks. We investigate the rates and risk factors for post-procedural complications over a four-year period at a new advanced endoscopy program. METHODS: We conducted a retrospective review of all adult patients who underwent upper EUS at an academic level-1 trauma center between April 2015 and November 2019. The primary outcome was the incidence of adverse events within 1 week of EUS. Secondary outcomes included emergency department visits and mortality within 30 days after EUS. Chi-square test, t test, and multivariable logistic regression were used to assess risk factors for post-procedural complications. RESULTS: A total of 968 EUS procedures were performed on 864 patients (54% female; 79% Caucasian; mean age 61 years). The overall incidence of post-procedural adverse event with EUS was 5.6%. The probability of an adverse event decreased by an average of 22% per year (p =0.01, OR 0.78). The risk for adverse events were 3.3% acute pancreatitis, 1.9% clinically significant bleeding, 0.3% bacteremia, 0.2% perforation, and 2.4% 30-day mortality. The adverse event rate was highest among low volume proceduralists (p =0.04). The 30-day mortality was more than threefolds among patients who had an adverse event within 7 days after EUS. CONCLUSION: The overall incidence of post-procedural adverse events at a new EUS program was 5.6%, with an average of 22% relative decrease in adverse events per year in the first 4 years.

Health Economic Impact of a Multicenter Quality-of-Care Initiative for Reducing Unplanned Healthcare Utilization Among Patients With Inflammatory Bowel Disease.

INTRODUCTION: A multicenter adult inflammatory bowel disease learning health system (IBD Qorus) implemented clinical care process changes for reducing unplanned emergency department visits and hospitalizations using a Breakthrough Series Collaborative approach. METHODS: Using Markov decision models, we determined the health economic impact of participating in the Collaborative from the third-party payer perspective. RESULTS: Across all 23 sites, participation in the Collaborative was associated with lower annual costs by an average of $2,528 ± $233 per patient when compared with the baseline period. DISCUSSION: Implementing clinical care process changes using a Collaborative approach was associated with overall cost savings. Future work should examine which specific interventions are most effective and whether such cost savings are sustainable.

Treatment delays during FOLFOX chemotherapy in patients with colorectal cancer: a multicenter retrospective analysis.

BACKGROUND: FOLFOX (folinic acid, 5-fluorouracil and oxaliplatin) is the most commonly used chemotherapy regimen for the treatment of colorectal cancer. FOLFOX is administered in 14-day cycles, though toxicities frequently lead to unplanned delays. We report the incidence of unplanned delays among patients receiving FOLFOX and describe the reasons for delays. METHODS: We conducted a retrospective analysis of patients receiving FOLFOX chemotherapy for colorectal cancer. Patients were treated at one of two tertiary cancer centers between January 2012 and April 2016. Cycles 2-6 were assessed for delays, and treatments were considered delayed when the interval from prior treatment was >18 days. Reasons for unplanned delays were categorized based on review of clinical records. RESULTS: We identified 214 patients receiving FOLFOX as standard-of-care therapy. The median age was 59 years, and 55% were female. Of 961 evaluable treatment cycles, 124 (13%) had unplanned delays, and 92 of 214 patients (43%) had one or more unplanned delays in cycles 2-6. Cytopenias (neutropenia and/or thrombocytopenia) were the most common cause of unplanned delays, affecting 34% of patients and accounting for 74 of 124 unplanned delays (60%). CONCLUSIONS: Delays are common during FOLFOX chemotherapy, with 43% of patients having at least one unplanned delay prior to completing cycle 6. Neutropenia and thrombocytopenia were the leading causes of unplanned delays. Our findings justify the development of systematic approaches for preventing unplanned delays, such as standardized laboratory treatment criteria and/or proactive dose adjustment strategies.

Oral, ultra-long-lasting drug delivery: Application toward malaria elimination goals.

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra-long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra-long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.