Publications by authors named "Bruce Yacyshyn"

Dried blood spot (DBS) analysis has existed for >50 years, but application of this technique to fecal analysis remains limited. To address whether dried fecal spots (DFS) could be used to measure fecal bile acids, we collected feces from five subjects for each of the following cohorts: ) healthy individuals, ) individuals with diarrhea, and ) infected patients. Homogenized fecal extracts were loaded onto quantitative DBS (qDBS) devices, dried overnight, and shipped to the bioanalytical lab at ambient temperature.

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Background & Aims: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease.

Methods: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews.

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Background & Aims: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms.

Methods: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet.

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Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated diseases of the gastrointestinal (GI) tract. Their etiology is complex and involves immune (eg, cytokines) and nonimmune (eg, environment) mediated contributions, causing inflammatory damage to the GI tract. Though cytokines contribute a major role in the inflammatory process of both CD and UC, there are some key differences in which cytokines are involved in the pathobiology of CD and UC.

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Objective: Transition to adult IBD care continues to be a challenge. Efficacious models of improving transition to adult care in the United States are lacking. We present data from a pilot, prospective, non-randomized, intervention implemented at IBD centers in the Midwest and Southeast United States.

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Background & Aims: Although Clostridioides difficile infection (CDI) is known to involve the disruption of the gut microbiota, little is understood regarding how mucus-associated microbes interact with C difficile. We hypothesized that select mucus-associated bacteria would promote C difficile colonization and biofilm formation.

Methods: To create a model of the human intestinal mucus layer and gut microbiota, we used bioreactors inoculated with healthy human feces, treated with clindamycin and infected with C difficile with the addition of human MUC2-coated coverslips.

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Background: This randomized, open-label phase 2a study investigated the safety/tolerability, pharmacokinetics, and efficacy of olorinab-a highly selective, peripherally acting, full agonist of the cannabinoid receptor 2-in patients with Crohn's disease (CD) experiencing abdominal pain.

Methods: Eligible subjects 18-80 years of age with quiescent to mildly active CD were randomized to receive olorinab 25 or 100 mg three times daily for 8 weeks. The primary objective was to assess safety/tolerability.

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Recurrent and acute bleeding from intestinal tract angioectasia (AEC) presents a major challenge for clinical intervention. Current treatments are empiric, with frequent poor clinical outcomes. Improvements in understanding the pathophysiology of these lesions will help guide treatment.

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Background: A large number of studies have evaluated the pharmacology, safety, and/or efficacy of bismuth subsalicylate for the relief of common gastrointestinal symptoms, diarrhea and vomiting due to acute gastroenteritis. In addition, short-term (48 h) medication with bismuth subsalicylate is known to be effective against infectious gastroenteritis such as travelers' diarrhea.

Aims: Previous studies have documented the bacteriostatic/bactericidal effects of bismuth subsalicylate against a variety of pathogenic gastrointestinal bacteria.

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Article Synopsis
  • Etrasimod is an oral medication being tested for treating ulcerative colitis, a serious inflammatory bowel disease, in a phase 2 study.
  • The study involved 156 patients, who were given either 1 mg or 2 mg of etrasimod or a placebo for 12 weeks, measuring improvements in symptoms and endoscopic findings.
  • Results showed that the 2 mg dose of etrasimod significantly improved clinical scores and endoscopic outcomes compared to placebo, with most side effects being mild or moderate.
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Obesity is a global pandemic with immense health consequences for individuals and societies. Multiple factors, including environmental influences and genetic predispositions, are known to affect the development of obesity. Despite an increasing understanding of the factors driving the obesity epidemic, therapeutic interventions to prevent or reverse obesity are limited in their impact.

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Clostridium difficile infection (CDI) is the primary cause of nosocomial diarrhea in the United States. Although C. difficile toxins A and B are the primary mediators of CDI, the overall pathophysiology underlying C.

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Article Synopsis
  • Bezlotoxumab is a monoclonal antibody designed to prevent the recurrence of Clostridium difficile infections (CDI) in high-risk adults, based on a thorough analysis of data from the MODIFY I/II trials.
  • The study focused on a modified intent-to-treat population, evaluating how well bezlotoxumab worked in participants with specific risk factors such as age, prior CDI history, and severe CDI cases.
  • Results showed that bezlotoxumab significantly reduced the rate of CDI recurrence, the need for fecal microbiota transplants, and hospital readmissions related to CDI for participants with these risk factors, particularly benefiting those with three or more risk factors.
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Background: Clostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment of C difficile infection.

Methods: We did a phase 2, randomised, double-blind, active-controlled, non-inferiority study.

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Although intestinal homeostasis is maintained by intestinal stem cells (ISCs), regeneration is impaired upon aging. Here, we first uncover changes in intestinal architecture, cell number, and cell composition upon aging. Second, we identify a decline in the regenerative capacity of ISCs upon aging because of a decline in canonical Wnt signaling in ISCs.

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Background & Aims: The peptic ulcer heals through a complex process, although the ulcer relapse often occurs several years later after healing. Our hypothesis is that even after visual evidence of healing of gastric ulceration, the regenerated epithelium is aberrant for an extended interval, increasing susceptibility of the regenerated epithelium to damage and further diseases.

Methods: Gastric ulcers were induced in mice by serosal topical application of acetic acid.

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Background: 5-aminosalicylic acid (5-ASA) is a classic anti-inflammatory drug for the treatment of ulcerative colitis. N-acetyltransferase (NAT) enzymes convert 5-ASA to its metabolite N-acetyl-5-ASA, and it is unresolved whether 5-ASA or N-acetyl-5-ASA is the effective therapeutic molecule. We previously demonstrated that colonic production of N-acetyl-5-ASA (NAT activity) is decreased in dextran sulfate sodium-induced colitis.

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Background And Aims: To determine whether clinical information influences endoscopic scoring by central readers using the Ulcerative Colitis Endoscopic Index of Severity [UCEIS; comprising 'vascular pattern', 'bleeding', 'erosions and ulcers'].

Methods: Forty central readers performed 28 evaluations, including 2 repeats, from a library of 44 video sigmoidoscopies stratified by Mayo Clinic Score. Following training, readers were randomised to scoring with ['unblinded', n = 20, including 4 control videos with misleading information] or without ['blinded', n 20] clinical information.

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Article Synopsis
  • The rise of Clostridium difficile (C. difficile) infections (CDI) has led to increased hospitalizations, highlighting the need to understand how it colonizes the intestine and causes disease.
  • Research found that CDI patients produce less MUC2 and have altered mucus compositions compared to healthy individuals, particularly showing differences in sugar components relevant to C. difficile's interaction with mucus.
  • The study indicates that C. difficile can reduce MUC2 production and shows a preference for mucus from CDI patients, suggesting potential new targets for therapeutic strategies against CDI.
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Clostridium difficile infection (CDI) is principally responsible for hospital acquired, antibiotic-induced diarrhea and colitis and represents a significant financial burden on our healthcare system. Little is known about C. difficile proliferation requirements, and a better understanding of these parameters is critical for development of new therapeutic targets.

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