Hashash, Jana G.

Background: The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn’s disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. Study: Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. Results: Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. Conclusions: Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.

AbstractBackground and AimAlthough fidaxomicin is an effective first‐line treatment for Clostridioides difficile infection, it has not been well studied in patients with inflammatory bowel disease. We aimed to assess the effectiveness of fidaxomicin for the treatment of C. difficile infection in patients with inflammatory bowel disease.MethodsThis was a multicenter retrospective study of adults with inflammatory bowel disease and C. difficile infection treated with fidaxomicin with at least 3 months of follow up. The primary outcomes were treatment response, defined as resolution of C. difficile infection‐attributed diarrhea and/or negative C. difficile infection stool test, and time to C. difficile infection recurrence after fidaxomicin.ResultsThirty‐three patients (median age 42 years; 60.6% female) were included. Most patients had ulcerative colitis (26, 78.8%), were receiving treatment with a biologic or small molecule medication (19, 57.6%), and had a prior episode of C. difficile infection (26, 78.8%, median 2 episodes, range 0–15). Fidaxomicin led to resolution of C. difficile infection in 20 (60.6%) patients, with 6/20 (30.0%) developing a recurrence at a median of 55 days. Most patients who failed to respond to fidaxomicin underwent fecal microbiota transplantation (10/13, 76.9%) with resolution.ConclusionsIn this cohort of patients with inflammatory bowel disease and C. difficile infection, 60.6% responded to treatment with fidaxomicin. Of those who did not respond, fecal microbiota transplantation was an effective therapy.

Lay Summary It is unknown if immune checkpoint inhibitor therapy increases risk of pouch-related complications in patients with inflammatory bowel disease after ileal-pouch anal anastomosis. In our study, pembrolizumab therapy was not associated with significant gastrointestinal immune-related adverse events or pouch-related complications.

Abstract Introduction The COVID-19 pandemic caused by SARS-CoV-2 continues to result in significant morbidity and mortality on a global scale. Prior studies have examined the effectiveness of non-COVID vaccines in setting of sleep disturbances. This study evaluated data from a large national database to examine the relationship between the risk of breakthrough COVID-19 infections in patients with certain sleep related disturbances. Methods Real-time search and analysis using the TriNetX platform to evaluate risk of COVID-19 breakthrough infections (BTI) for patients having ICD-10 diagnoses relating to insomnia, circadian rhythm disorders, and inadequate sleep. The sleep disorder and control cohorts underwent propensity matching including factors for age, gender, race, ethnicity, and multiple co-morbid conditions. Results Of 24,720 patients identified as having a sleep disturbance relating to insomnia, circadian rhythm disorder, or inadequate sleep, 815 (3.2%) were found to have a developed a BTI. There was a significant increased risk of BTI noted between the sleep disorder and control cohorts (adjusted odds ratio (aOR) of 1.40, 95% confidence interval (CI) of 1.23-1.58). Subgroup analysis showed an elevated risk for BTI receiving two doses (aOR 1.53, 95% CI 1.24 – 1.89) versus three doses (aOR 1.45, 95% CI 1.24 – 1.69). Patients with the sleep disturbance were not found to be at an increased risk of hospitalization, intubation, death, or composite outcome of death and intubation. Conclusion The presence of having a diagnosis of insomnia, circadian rhythm disorder, or inadequate sleep was associated with increased risk of COVID-19 breakthrough infection. Support (if any)

Abstract: Background and Aims The BNT162b2 and mRNA-1273 COVID-19 vaccines are efficacious in patients with inflammatory bowel disease; but there is a lack of data examining if holding immunosuppressive therapy around vaccination improves immune response. We studied the effect of holding IBD medications around the time of vaccination on antibody response and breakthrough COVID-19 infection. Methods Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID is a prospective cohort of individuals with IBD receiving COVID-19 vaccination. Quantitative measurement of anti-receptor binding domain IgG antibodies to SARS-CoV-2 was performed 8 weeks after completing a vaccination series. Results A total of 1854 patients were included; 59% were on anti-tumour necrosis factor [TNF] [10% of these on combination therapy], 11% on vedolizumab, and 14% on ustekinumab; 11% of participants held therapy before or after vaccine administration for at least 2 weeks. Antibody levels were similar in participants continuing versus holding anti-TNF monotherapy before or after the second vaccine [BNT162b2: 10 μg/mL vs 8.9 μg/mL; mRNA-1273: 17.5 μg/mL vs 14.5 μg/mL]. Comparable results were seen in those on combination therapy. Antibody titres in those on ustekinumab or vedolizumab were higher compared with anti-TNF users, but there was no significant difference if the drug was held or continued [BNT162b2: 22.5 μg/mL vs 23 μg/mL; mRNA-1273: 88 μg/mL vs 51 μg/mL]. Holding therapy was not associated with decreased rate of COVID-19 infection compared with those not holding therapy [BNT162b2: 28% vs 29%; mRNA-1273: 19% vs 31%]. Conclusion We recommend continuing IBD medications while receiving mRNA COVID-19 vaccination without interruption.

INTRODUCTION: Use of the electronic health record (EHR) has become increasingly widespread. Higher EHR burden is associated with burnout, but this has not been specifically investigated among gastroenterology (GI) providers. METHODS: We retrospectively collected measures of EHR use for outpatient GI providers during a 6-month period. We compared metrics across provider sex, subspecialty, and training (physicians vs nonphysician providers [NPPs]). RESULTS: Data collected represented more than 16,000 appointments from 41 providers across the Division of Gastroenterology and Hepatology. Inflammatory bowel disease (IBD) and hepatology specialists spent more time per appointment in the EHR, clinical review, and outside regular hours compared with other subspecialists. NPPs spent more EHR time than physicians. DISCUSSION: IBD and hepatology specialists and NPPs may have disproportionally high EHR burden. More work is needed to understand differences in provider workload to combat burnout.

Abstract Background Despite the growing therapeutic armamentarium, at least half of the patients with Crohn’s disease will require surgery during their lifetime. Current evidence for the prevention and treatment of postoperative Crohn’s disease supports the use of anti-tumor necrosis factor agents with limited data about the use of the newer biologics, vedolizumab and ustekinumab. Methods We performed a systematic review of available data to determine the efficacy of the newer biologics in the management of postoperative Crohn’s disease. We included noncomparative and comparative studies. The main outcomes of interest were clinical and endoscopic postoperative recurrence rates. Results The search strategy identified 1231 citations, with 32 eligible for review. Several studies showed that the postoperative Crohn’s disease recurrence rates with the use of the newer biologics were comparable to previously published results with the use of anti-tumor necrosis factor agents, while other studies failed to show their efficacy. It is important to note that the studies were heterogeneous and included a relatively small sample size, making it difficult to draw a definite conclusion about the efficacy of the newer biologics in the management of postoperative Crohn’s disease. Conclusion The newer biologics do play a role in the management of postoperative Crohn’s disease. After our review, we proposed an updated algorithm on the role of newer biologics in the approach to patients with postoperative Crohn’s disease. Yet, until we have better-designed studies, their definite positioning remains to be determined.