Publications

BACKGROUND: Women remain underrepresented in gastroenterology (GI). Studies have identified that a lack of formal mentorship for women contributes to this underrepresentation. While many GI divisions have adopted models for supporting GI fellows and faculty, there is a gap in our knowledge regarding mentorship options for internal medicine (IM) residents interested in GI.

AIMS: To evaluate representation of women at each level of their career (resident, fellow, and attending) and examine trends in representation of women in GI compared to other IM subspecialties.

METHODS: We analyzed AAMC Physician Specialty Data Reports to compare gender representation and growth of women representation across all IM subspecialties and residencies from 2007 to 2021.

RESULTS: In 2021, 44.3% of IM residents, 37.8% of GI fellows, and 19.7% of actively practicing attending gastroenterologists were women. Since 2007, GI comprised significantly lower proportions of women attendings except for cardiology, and lower representation in fellows, except for cardiology and nephrology, than other IM subspecialties (p < 0.001). There was a consistently higher proportion of women GI fellows than attendings over the past 14 years (p < 0.01).

CONCLUSIONS: GI has among the lowest representation of women at each career level compared to other IM subspecialties. Given the previously reported preference of gender congruent mentoring, the underrepresentation of senior academic gastroenterologists who are women may be a contributing factor to lower proportions of women trainees choosing to pursue GI.

Extracellular ATP and its derivates mediate a signaling pathway that might be pharmacologically targeted to treat inflammatory conditions. Extracellular adenosine, the product of ATP hydrolysis by ectonucleotidase enzymes, plays a key role in halting inflammation while promoting immune tolerance. The rate-limiting ectoenzyme ENTPD1/CD39 and the ecto-5'-nucleotidase/CD73 are the prototype members of the ectonucleotidase family, being responsible for ATP degradation into immunosuppressive adenosine. The biological effects of adenosine are mediated via adenosine receptors, a family of G protein-coupled receptors largely expressed on immune cells where they modulate innate and adaptive immune responses. Inflammatory bowel disease (IBD) is a serious inflammatory condition of the gastrointestinal tract, associated with substantial morbidity and often refractory to currently available medications. IBD is linked to altered interactions between the gut microbiota and the immune system in genetically predisposed individuals. A wealth of studies conducted in patients and animal models highlighted the role of various adenosine receptors in the modulation of chronic inflammatory diseases like IBD. In this review, we will discuss the most recent findings on adenosine-mediated immune responses in different cell types, with a focus on IBD and its most common manifestations, Crohn's disease and ulcerative colitis.

The Brain Sciences Editorial Office retracts the article, "Sex-Based Differences in Plasma Autoantibodies to Central Nervous System Proteins in Gulf War Veterans versus Healthy and Symptomatic Controls" [...].

The Brain Sciences Editorial Office retracts the article "Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls" [...].

INTRODUCTION: A need for better treatment options for moderate to severe ulcerative colitis (UC) persists because of the efficacy and safety limitations of current therapies. Neutrophil epithelial transmigration is associated with the characteristic colonic mucosal inflammation in and very likely involved with the pathogenesis and clinical symptoms of UC. ADS051 is a small-molecule inhibiting neutrophil migration and activation, which are potentially important therapeutic targets in UC. The phase 1 single ascending dose study evaluated ADS051's safety, tolerability, and pharmacokinetics in healthy volunteers.

METHODS: Fifty healthy adults were randomized 4:1 into 5 ascending dose cohorts to receive a single oral dose of ADS051 100 mg, 300 mg, 700 mg, 1,500 mg, 3,500 mg, or placebo. Participants were followed until 30 days after dosing. Safety and pharmacokinetics of ADS051 in stool, blood, and urine were evaluated.

RESULTS: ADS051 was safe and well-tolerated. Adverse events (AEs) of constipation were reported by 2 participants (5.0%) in the ADS051 1,500 mg group vs none in the placebo group. No serious AEs reported and no discontinuations due to AEs. In all dose groups, a cumulative average of 10%-24% of the ADS051 dose was recovered in stool, mostly within 48 hours after dosing. ADS051 was quantifiable in only 2 of 440 blood samples (7.64 and 69.8 ng/mL). On average, <0.035% of the ADS051 dose was excreted in urine.

DISCUSSION: ADS051 was safe, well-tolerated, and achieved high stool concentrations with minimal systemic exposure. ADS051 could be a safe and effective, locally acting, neutrophil-targeting agent for the treatment of UC.

In this article we comment on the article by Agatsuma et al. Our article focuses on the use of screening for colon cancer increases the likelihood of early diagnosis of colorectal cancer compared to those presenting after symptoms develop. Patients with symptoms were more likely to have left-sided lesions with resultant hematochezia and/or changes in bowel habits. In this study almost all patients in the screen group were first screened with immunochemical fecal occult blood testing. Colonoscopy was used either if it was thought to be the more appropriate initial screening modality or if the non-invasive test was positive. The exact timing when an initial screening colonoscopy should be performed is not totally clear from this study. However, early screening for colon cancer does reduce the risk of cancer diagnosis and more advanced cancer diagnoses.

Objectives: Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract, comprising ulcerative colitis (UC) and Crohn's disease (CD). Earlier onset of IBD symptoms has been linked to a higher prevalence of depression and anxiety. Evidence supports that cortisol abnormalities correlate with the development and severity of autoimmune diseases. The primary aim of this study was to investigate the correlation of morning salivary cortisol levels with self-reported mood (depression and anxiety) and quality of life in patients with IBD. Methods: This was a prospective, single-center study including outpatients with IBD. Enrolled patients provided a one-time morning salivary cortisol sample and electronically completed a one-time survey encompassing self-reported quality of life (Short Inflammatory Bowel Disease Questionnaire (SIBDQ)) and mood (Patient Health Questionnaire 8 (PHQ-8), General Anxiety Disorder-7 (GAD-7)). Results: A total of 36 patients (UC, n = 21) were included in the study. There was no correlation between morning salivary cortisol and depressive symptoms (PHQ-8: r = 0.007, p = 0.968) or quality of life (SIBDQ: r = -0.095, p = 0.606). However, there was a trend towards a positive correlation between self-reported anxiety symptoms by GAD-7 and salivary cortisol (r = 0.347, p = 0.052). A subgroup analysis showed a positive correlation between morning salivary cortisol and GAD-7 scores in patients with UC (r = 0.535, p = 0.015), but not in patients with CD (r = 0.064, p = 0.843). Conclusions: This pilot study is the first to associate cortisol with anxiety symptom severity in UC. Further research is needed to investigate the link between salivary cortisol, neuropsychiatric disease, and IBD outcomes.

INTRODUCTION: Ulcerative colitis (UC) is characterized by colonic inflammation, with neutrophils playing a key role in UC activity, prognosis, and response to therapies. Current UC therapeutics can have significant side effects and limited efficacy. ADS051 is a novel, oral, gut-restricted small molecule that modulates neutrophil migration and activation without in vitro suppression of T-cell activation. The primary objective of this Phase 1b multidose trial was to evaluate the safety of ADS051. Secondary objectives were clinical activity and pharmacokinetics assessment.

METHODS: This trial enrolled 24 patients with moderate-to-severe UC in 3 sequential ascending dose cohorts with 3:1 randomization to ADS051 200 mg, 800 mg, or 3,200 mg, or placebo, administered orally once daily for 28 days. Safety, tolerability, and pharmacokinetics were assessed weekly, with clinical activity end points of clinical remission, endoscopic improvement, and histologic remission evaluated at Day 28.

RESULTS: ADS051 was well tolerated without severe or serious adverse events. High fecal concentrations were achieved with low systemic exposure, with <1% of the daily dose of ADS051 excreted in urine. On Day 28 of the trial, clinical remission was achieved in 22.2% of the pooled ADS051 group vs 0% of the pooled placebo group. Endoscopic response was achieved in 50.0% of ADS051-dosed vs 16.7% of placebo, and endoscopic improvement was achieved in 33.3% of ADS051-dosed vs 0% of placebo.

DISCUSSION: Phase 1b data in patients with UC indicate a favorable safety profile for ADS051 with encouraging signals of clinical activity, supporting the advancement to a Phase 2 trial.