Medical Bulletin 14/ February/ 2025 - Video

A new study in experimental animals reveals a critical difference in how macrophages — a part of the immune system — help repair the heart in newborns versus adults after a heart attack. The study highlights a fundamental difference in how the immune system drives healing based on age. The study was published in the journal Immunity.

In newborns, macrophages perform a process called efferocytosis, which recognizes and eats dying cells. This process triggers the production of a bioactive lipid called thromboxane, signaling nearby heart muscle cells to divide, and allowing the heart to regenerate damaged heart muscle, the study found. In adults, macrophages produce much less thromboxane, leading to a weaker repair signal.

The study examined how the immune system responds to heart injury in mice of different ages, including newborn mice (one-day old) and adult mice (eight weeks old). The researchers found the ability of macrophages to engulf dying cells was enhanced in newborn mice due to increased expression of MerTK, a receptor that recognizes dying cells. Therefore, when the scientists blocked this key receptor, newborn mice lost their ability to regenerate their hearts, resembling adult hearts after a heart attack.

Engulfment of dying cells by newborn macrophages triggered a chemical chain reaction that produced a molecule called thromboxane A2, which unexpectedly stimulated heart muscle cells to multiply and repair the damage, the study found. Additionally, nearby muscle heart cells in newborns are primed to respond to thromboxane A2, leading them to change their metabolism to support their growth and healing. But in adults, this process did not work the same way — after an injury, their macrophages did not produce enough thromboxane A2, limiting their ability to regenerate heart tissue.

Reference: Connor Lantz, Amanda Becker, Matthew DeBerge, Mallory Filipp, Kristofor Glinton, Aparnaa Ananthakrishnan, Jessica Urbanczyk, Madeline Cetlin, Afnan Alzamroon, Ahmed Abdel-Latif, Matthew Spite, Zhi-Dong Ge, Edward B. Thorp, Early-age efferocytosis directs macrophage arachidonic acid metabolism for tissue regeneration, Immunity, Volume 58, Issue 2, 2025, Pages 344-361.e7, ISSN 1074-7613, https://doi.org/10.1016/j.immuni.2024.11.018.

Patients aged between 50 to 70 years with a mechanical heart valve replacement had better long-term survival compared to those with a biological valve, new research led by the University of Bristol has found. The study is published in the European Journal of Cardio-Thoracic Surgery.

Existing guidelines support the use of mechanical valves made of synthetic materials in patients below the age of 50, while biological valves made of animal tissue are favoured for those above the age of 65 or 70. The guidelines leave the choice to the decision of surgeons and patients who are 50 to 70 years old.

A total of 1,708 (61% male) patients with an average age of 63 years were included with 1,191 (69.7%) receiving a biological valve replacement.

The research found there were no short-term differences when comparing patients receiving biological and mechanical valves. However, patients who received mechanical valves had better long-term survival up to 13 years after having surgery.

Patients with a size 19 mm biological valve replacement had the worse long-term survival. Patients with a size 21 mm mechanical valve had better survival compared to both size 19 and 21 mm biological valves. The study confirmed that severe patient prosthesis mismatch is a significant risk factor for poor long-term survival.

Gianni Angelini, BHF Professor of Cardiac Surgery at the Bristol Medical School: Translational Health Sciences (THS), Director of the Bristol Heart Institute and corresponding author, said: “Our study has implications for decision-making in surgical heart valve replacements for patients aged between 50 and 70 years old. The evidence supporting better long-term survival in patients receiving a mechanical heart valve suggests the current trend favouring biological valves in this age bracket should be urgently reconsidered. The survival benefit is especially clear in smaller sized valves.”

The research team recommends the evaluation of the long-term benefits associated with mechanical valves, especially in smaller sizes, despite long-term blood thinners not being needed with biological valves.

Reference: Jeremy Chan, Pradeep Narayan, Daniel P Fudulu, Tim Dong, Hunaid A Vohra, Gianni D Angelini, Long-term clinical outcomes in patients between the age of 50-70 years receiving biological versus mechanical aortic valve prostheses, European Journal of Cardio-Thoracic Surgery, 2025;, ezaf033, https://doi.org/10.1093/ejcts/ezaf033

Researchers have been able to decipher the mechanism behind the dietary therapy also known as exclusive enteral nutrition for crohn’s disease. Based on the results, they are launching a clinical study combining dietary therapy with faecal microbiome transfer to further enhance treatment outcomes.

Vitamins, minerals, proteins, carbohydrates, and fatty acids: the formula for exclusive enteral nutrition (EEN) contains all essential nutrients and is highly effective for managing Crohn's disease, often improving symptoms within a few days and without additional medical treatment.

The researchers demonstrated how the gut microbiome -- the complex community of all microbes in the intestine -- changes as a result of dietary therapy and contributes to the treatment success.

They found that the medium-chain fatty acids in the diet positively affect certain gut bacteria, which proliferate and reduce inflammation. The study reveals even more: in an artificial intestinal model, researchers treated patients' stool with the formula, thus adapting the microbiome. When this adapted microbiome was transferred to mice, no inflammation developed. However, when the microbiome was not pre-adapted by the formula, the mice developed typical inflammatory symptoms.

The team is now conducting a clinical study to investigate whether this mechanism also works in humans -- meaning whether a healthier microbiome can be established following the "microbiome reboot." The aim is to sustain the inflammation-free state for as long as possible. To achieve this, the researchers are utilizing fecal microbiome transfer, commonly referred to as "fecal transplant," following dietary therapy.

Reference: https://www.tum.de/en/news-and-events/all-news/press-releases/details/clinical-study-on-new-therapy-for-crohns-disease