Research Round-up

From the Spring 2020 edition of Vanderbilt Medicine Magazine

Less inflammation = better healing

Myocardial infarction remains a leading cause of mortality and morbidity worldwide, raising an urgent need for novel therapies.

Acute MI provokes an inflammatory response in the heart that removes damaged tissue to promote repair and regeneration. Overactive and/or prolonged inflammation impedes healing, however, suggesting that reducing inflammation may lead to better outcomes.

Previously Lan Wu, MD, Luc Van Kaer, PhD, and colleagues identified a subpopulation of regulatory B lymphocytes in the fat tissue of obese mice that secretes interleukin-10 (IL-10), an anti-inflammatory cytokine which protects against obesity-associated insulin resistance.

Reporting in the Proceedings of the National Academy of Sciences, they found IL-10-producing B cells in mice also are highly enriched in fat tissue around the heart. Following MI, the cells increase in number and move to the damaged heart, where they terminate inflammation and protect against further injury and dysfunction.

IL-10-producing B cells thus are novel targets to improve the outcome of MI, the researchers concluded.

 

AI maps routes to heart disease

A study in the Journal of Biomedical Informatics uses machine learning on unlabeled electronic health record (EHR) data to shed light on the emergence of cardiovascular disease (CVD).

The study hinges on automated patient phenotyping and ample longitudinal data. Juan Zhao, PhD, Wei-Qi Wei, MD, PhD, and colleagues gathered 12,380 de-identified patient records that reached back at least 10 years prior to a CVD diagnosis. An automated scan found some 1,068 distinct patient phenotypes in this dataset.

Aided by a technique called tensor decomposition, unsupervised machine learning revealed the long-term emergence of 14 distinct CVD patient subtypes. Across the six most prevalent subtypes, the risk of heart attack was markedly different, indicating the scan had struck meaningful distinctions.

Certain phenotypes that came forth prominently in the scan — urinary infection, vitamin D deficiency, depression — would appear to challenge current understanding of the routes by which CVD emerges.

 

Treating C. diff: new purpose for an old drug?

Clostridioides difficile infection (CDI) is a major health threat, particularly for older patients. In the U.S. the infection claims 15,000 lives per year. Certain antibiotics, by disrupting normal gut microorganisms (microbiota), create an opening for the infection.

Developed in the early 1970s, misoprostol is an inexpensive generic drug once used to prevent gastrointestinal ulcers in people taking daily NSAIDs — that is, aspirin, ibuprofen, etc. — but it has since been replaced for that purpose by newer alternatives.

Based partly on the detrimental impact of NSAIDs during CDI, David Aronoff, MD, reasoned that misoprostol may have promise as a treatment for severe CDI.

In a study in Anaerobe, Aronoff and colleagues show that misoprostol protects mice against severe CDI and promotes the recovery of mouse gut microbiota following antibiotic perturbation. With misoprostol, survival from severe CDI increased threefold.

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