Alanyl-glutamine supplementation for Clostridioides difficile infection treatment (ACT): a double-blind randomised controlled trial study protocol.

INTRODUCTION: Clostridioides difficile is the leading cause of healthcare-associated infections in the USA, with an estimated 1 billion dollars in excess cost to the healthcare system annually. C. difficile infection (CDI) has high recurrence rate, up to 25% after first episode and up to 60% for succeeding episodes. Preliminary in vitro and in vivo studies indicate that alanyl-glutamine (AQ) may be beneficial in treating CDI by its effect on restoring intestinal integrity in the epithelial barrier, ameliorating inflammation and decreasing relapse. METHODS AND ANALYSIS: This study is a randomised, placebo-controlled, double-blind, phase II clinical trial. The trial is designed to determine optimal dose and safety of oral AQ at 4, 24 and 44 g doses administered daily for 10 days concurrent with standard treatment of non-severe or severe uncomplicated CDI in persons age 18 and older. The primary outcome of interest is CDI recurrence during 60 days post-treatment follow-up, with the secondary outcome of mortality during 60 days post-treatment follow-up. Exploratory analysis will be done to determine the impact of AQ supplementation on intestinal and systemic inflammation, as well as intestinal microbial and metabolic profiles. ETHICS AND DISSEMINATION: The study has received University of Virginia Institutional Review Board approval (HSR200046, Protocol v9, April 2023). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04305769.

Effect of alcohol and tobacco use on vascular dementia: a matched case control study.

BACKGROUND: Vascular dementia is the second most common type of dementia in the United States. The underlying association of tobacco and alcohol with vascular dementia is not completely understood. PURPOSE: Determine the relationship of tobacco and alcohol use with the development of vascular dementia (VaD). METHODS: This was a matched case-control study of subjects living in Olmsted County, MN. Cases of VaD were identified through medical record abstraction using conventionally accepted definitions of VaD, using the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Ensignement en Neurosicences ( NINDS-AIRENS) criteria and were matched to controls by gender and age within 3 years among persons free of dementia on the index date. Exposure data for alcohol and tobacco use were abstracted by trained nurses, along with demographic, lifestyle, cerebrovascular, cardiovascular, and vascular comorbid disease characteristics. Matched conditional logistic regression for univariate and multivariate evaluation of the association of tobacco and alcohol use with VaD was utilized. RESULTS: Current alcohol exposure was associated with a decreased risk of VaD with an odds ratio of 0.48 (95% confidence interval: 0.31-0.74). This protective effect of alcohol was seen in men, women, and subjects under 80 years of age. Tobacco use was not associated with VaD in univariate and multivariate analysis, and stratified analysis did not reveal any subgroup-specific associations between tobacco use and VaD in the study population. CONCLUSION: Current alcohol use appears to have protective effects against the development of vascular dementia. The effects are more pronounced in subjects under age 80. This may reflect the direct vascular effects of alcohol on the vascular system or may represent a surrogate for better social or functional status. Previous alcohol use was not protective. Tobacco use was not a risk factor for VaD status, which was possibly an indication of survivorship bias in the cohort.

Immunosenescence: role and measurement in influenza vaccine response among the elderly.

Immunosenescence refers to the inability of an aging immune system to produce an appropriate and effective response to challenge. This immune dysfunction may manifest as increased susceptibility to infection, cancer, autoimmune disease, and vaccine failure. Mounting biological evidence supports the potential clinical relevance and impact of immunosenenscence. We briefly review immunosenescence with a focus on replicative senescence in cytotoxic T cells and recent clinical studies examining its association with influenza and infectious disease outcomes.