Publications

GOALS: The aim was to assess patient adherence to multitarget stool DNA testing as well as factors associated with adherence.

BACKGROUND: In the United States, disparities in colorectal cancer screening exist along racial and socioeconomic lines. While some studies suggest that stool-based screening tests may help reduce the screening gap, the data for multitarget stool DNA testing is unclear.

STUDY: We conducted a single-center retrospective cohort study on multitarget stool DNA testing ordered between April 2020 and July 2021. We calculated the proportion of patients who completed testing and used multivariate logistic regression to identify covariates associated with test adherence.

RESULTS: Among 797 patients ordered for multitarget stool DNA testing, 481 patients (60.4%) completed testing. Adherence rates by patient subgroups ranged from 35.8% to 78.1%. Higher test adherence was found in Asian patients (odds ratio 2.65, 95% CI 1.36-5.18) and those who previously completed colorectal cancer screening (OR 1.45, 95% CI 1.01-2.09), while Black patients (OR 0.58, 95% CI 0.39-0.87), patients with resident primary care physicians (OR 0.34, 95% CI 0.21-0.56), and patients contacted through an outreach program (OR 0.47, 95% CI 0.25-0.87) had lower adherence.

CONCLUSIONS: A significant proportion of patients ordered for multitarget stool DNA testing did not complete testing. Differences in adherence rates among patient subgroups may be reflective of underlying disparities in health care access.

Th17-cells play a key role in the pathogenesis of autoimmune hepatitis (AIH). Dysregulation of Th17-cells in AIH is linked to defective response to aryl-hydrocarbon-receptor (AhR) activation. AhR modulates adaptive immunity and is regulated by aryl-hydrocarbon-receptor-repressor (AHRR), which inhibits AhR transcriptional activity. In this study, we investigated whether defective Th17-cell response to AhR derives from aberrant AHRR regulation in AIH. Th17-cells, obtained from the peripheral blood of AIH patients (n = 30) and healthy controls (n = 30) were exposed to AhR endogenous ligands, and their response assessed in the absence or presence of AHRR silencing. Therapeutic effects of AHRR blockade were tested in a model of Concanavalin-A (Con-A)-induced liver injury in humanized mice. AHRR was markedly upregulated in AIH Th17-cells, following exposure to l-kynurenine, an AhR endogenous ligand. In patients, silencing of AHRR boosted Th17-cell response to l-kynurenine, as reflected by increased levels of CYP1A1, the main gene controlled by AhR; and decreased IL17A expression. Blockade of AHRR limited the differentiation of naïve CD4-cells into Th17 lymphocytes; and modulated Th17-cell metabolic profile by increasing the levels of uridine via ATP depletion or pyrimidine salvage. Treatment with 2'-deoxy-2'-fluoro-d-arabinonucleic acid (FANA) oligonucleotides to silence human AHRR in vivo, reduced ALT levels, attenuated lymphocyte infiltration on histology, and heightened frequencies of regulatory immune subsets in NOD/scid/gamma mice, reconstituted with human CD4 cells, and exposed to Con-A. In conclusion, blockade of AHRR in AIH restores Th17-cell response to AHR, and limits Th17-cell differentiation through generation of uridine. In vivo, silencing of AHRR attenuates liver damage in NOD/scid/gamma mice. Blockade of AHRR might therefore represent a novel therapeutic strategy to modulate effector Th17-cell immunity and restore homeostasis in AIH.

BACKGROUND & AIMS: Chronic gastrointestinal (GI) symptoms are a common reason for seeking medical care. We aim to determine the rates of ambulatory care use and to characterize demographics, work-up, and treatment (pharmacologic and nonpharmacologic) for patients with chronic upper GI symptoms and conditions in the United States.

METHODS: Estimates of annual visits for the most common upper GI symptoms and diagnoses including gastroesophageal reflux disease, dyspepsia, nausea and vomiting, and gastroparesis were recorded from the 2007-2015 National Ambulatory Medical Care Surveys. Only chronic conditions, defined as >3 months, were included. We calculated the weighted proportion of ambulatory visits associated with pharmacologic, nonpharmacologic treatment (eg, diet, complementary and alternative medicine), or both.

RESULTS: A total of 116,184,475 weighted ambulatory visits were identified between the years of 2007 and 2015 for adults (average of 12,909,386 annual visits) with chronic upper GI symptoms and diagnoses. Gastroesophageal reflux disease was the most common reason for an ambulatory visit (n = 11,200,193), followed by dyspepsia (n = 1,232,598), nausea and vomiting (n = 714,834), and gastroparesis (n = 140,312). Pharmacologic treatment was more common than nonpharmacologic treatment (44.7% vs 28.5%). A total of 37.6% of patients were not receiving treatment at the time of the visit. These treatment patterns did not significantly change over the time of our study. Upper endoscopies were the most ordered test, representing 7.5% of all investigated upper GI symptoms.

CONCLUSIONS: Chronic upper GI symptoms and diagnoses account for a high number of annual health care visits, both in primary care and specialty care. Although there are several treatments, many of these patients are not on any treatments.

In recent years, legislation targeting the sexual and gender minority (SGM) community has been passed at an increasingly alarming rate, affecting access to safe and effective gender-affirming care and forcing many SGM patients, including those with inflammatory bowel disease (IBD), to withhold their identities and health concerns. Additionally, SGM patients with IBD may have unique health considerations that have not yet been well-studied OBJECTIVE: This article aims to explore the intersection of IBD and sexual health in patients who identify as SGM and to identify limitations for gastroenterologists in caring for SGM patients. The article also aims to provide suggestions for improvement in SGM-competent care within gastroenterology METHODS: A thorough literature review was conducted regarding sexual health and the SGM community with IBD. This included a review of surgical considerations in SGM patients, sexually transmitted infections (STIs) and prevention, and sexual dysfunction RESULTS: Overall, little is known about the impact of IBD on patients who identify as sexual and gender minorities. Surgery, medications, and STIs continue to be a concern in the SGM community with IBD and these areas represent opportunities to improve SGM-competent IBD care. Additionally, implementation of an SGM-focused curriculum is urgently needed in medical education to improve provider knowledge and care for this unique group of patients CONCLUSIONS: Patients with IBD who identify as SGM experience challenges that are not well described in prior literature. More research is needed and is actively being pursued to guide provider awareness and improve sexual health for this patient population.

INTRODUCTION: Moderate-to-severe inflammatory bowel disease treatment transitioned from step-up therapy to induction of remission with a biologic agent, but insurance coverage varies.

METHODS: Top 50 insurance companies were searched for publicly available policies for 5 biologic/small molecule agents. Data regarding coverage requirements were compared with American College of Gastroenterology/American Gastroenterological Association guidelines.

RESULTS: Thirty-four insurers had public policies. Adherence to American College of Gastroenterology/American Gastroenterological Association guidelines ranged from 5.8% to 58.8%. Only 14.71% and 17.65% of policies permitted any first-line biologic therapy in Crohn's disease and in ulcerative colitis.

DISCUSSION: Nearly every insurance company required failure of steroids and immunomodulators before biologic therapy. Further work is required to improve patient access to standard-of-care treatment.

BACKGROUND: Infliximab (IFX) use is limited by loss of response often due to the development of anti-IFX antibodies and low drug levels.

METHODS: We performed a single center prospective observational cohort study of pediatric and young adult subjects with inflammatory bowel disease (IBD) on IFX with over 3 years of follow-up. Infliximab levels (IFXL) and antibodies to infliximab (ATI) were measured throughout the study. Subjects were followed until IFX was discontinued.

RESULTS: We enrolled 219 subjects with IBD (184: Crohn's disease; 33: Ulcerative colitis; and 2 Indeterminant colitis; 84 female, median age 14.4 years, 37% on concomitant immunomodulator). Nine hundred and nineteen serum samples (mean 4.2 ± 2.1 per patient) were tested for IFXL and ATI. During the study, 31 (14%) subjects discontinued IFX. Sixty patients had ATI. Twenty-two of those 60 patients with ATI discontinued IFX; 14 of 31 patients who discontinued IFX had detectable ATI at study onset. The combination of ATI and IFXL < 5 µg/mL at study entry was associated with the highest risk of drug discontinuation (hazard ratios [HR] ATI 4.27 [p < 0.001] and IFXL < 5 µg/mL [HR]: 3.2 p = 0.001). Patients with IFXL 5-10 µg/mL had the lowest rate of discontinuation (6%). IFX dose escalation eliminated ATI in 21 of 60 subjects.

CONCLUSIONS: ATI is a strong predictor of needing to stop IFX use and inversely correlates with IFXL. Detection of ATI during therapeutic drug monitoring postinduction but also periodically during maintenance therapy identifies individuals who may benefit from IFX dose escalation and/or the addition of an immunomodulator, as these interventions may reduce or eliminate ATI.

Chen H, Wu S, Tang M, et al. Thalidomide for recurrent bleeding due to small-intestinal angiodysplasia. N Engl J Med. 2023;389:1649-1659. 37913505.

BACKGROUND AND AIMS: Substantial differences exist in pancreatic cancer outcomes across ethnoracial stratifications. We sought to assess racial, ethnic, sex, and age reporting and inclusion of participants in pancreatic cancer screening studies.

METHODS: A systematic search of Cochrane Library, Ovid Embase, Google Scholar, Ovid MEDLINE, PubMed, Scopus, and Web of Science Core Collection from inception to 2022 was conducted. Original studies on pancreatic cancer screening were identified and assessed for reporting and inclusion on race, ethnicity, sex, and age. The pooled proportions of study participants for these characteristics were calculated and compared with population-based benchmarks.

RESULTS: Among 27 eligible pancreatic cancer screening studies, 26 reported data on either sex, race, or ethnicity, with a total of 5273 participants. Information on participant sex was reported by 26, race by 12, and ethnicity by 8 studies. Participants in these studies were almost all white (pooled proportion, 93.1%; 95% confidence interval [CI], 89.7-96.4) and non-Latino (pooled proportion, 97.4%; 95% CI, 94.0-100), and these groups were over-represented when compared with the general population. Female participants were well represented, with a pooled proportion of 63.2% (95% CI, 59.9-66.6). When reported, mean or median participant age was <60 years. Meta-regression revealed higher proportions of female participants in studies from the United States (P = .002). No association between increasing participation of racial or ethnic under-represented populations and study quality, ascending year of publication, or source of study funding was noted.

CONCLUSIONS: Substantial disparities in race, ethnicity, sex, and age reporting and inclusion in pancreatic cancer studies were noted, even among high-quality and publicly funded studies.