Understanding the Implications for Young Adults: Transplants, Nanomedicines, and C. difficile Infections

2023-09-19 17:29:39

(Health Rounds is published regularly on Tuesdays and Thursdays. Think your friend or colleague should know about us? Send them this newsletter. They can also subscribe here (link).) by Nancy Lapid

September 19 (Reuters) –

Hello Health Rounds readers! Today, we report the potential implications for young adults of two preliminary studies in mice: one suggests that limiting a key mechanism of cell aging could one day allow increased use of transplantable organs from from older donors, and the other shows that nanomedicines used against cancer and other diseases may be less effective in younger patients because their livers filter the drugs more efficiently. A third study showed that most patients with severe cases of highly infectious C. difficile while hospitalized carried the bacteria into the hospital rather than becoming infected during their hospital stay.

A class of drugs slows down the aging mechanism of organs from elderly donors

A class of drugs that interrupts a key aging process could one day allow surgeons to transplant more organs from older donors, experiments in mice suggest.

Using organs from older donors is essential due to the shortage. But surgeons generally try to reserve them for transplantation into older patients, because these organs tend to function less well in young adults.

The drugs, known as senolytics, prevent the transfer of so-called senescent cells, which have stopped multiplying but, instead of dying, continue to release chemicals that trigger inflammation. Cellular senescence becomes more and more common as tissues age.

On Sunday in Athens, at the 2023 Congress (link) of the European Society of Organ Transplantation, researchers reported that when they transplanted hearts from young and old donor mice into young recipient mice, the recipients of old hearts had more senescent cells in their lymph nodes, liver and muscles, as well as elevated markers of inflammation in their blood, compared to recipients of young hearts. Mice given aged hearts also had more physical and cognitive impairments afterward.

When aged donor mice were treated in advance with senolytics – Sprycel (dasatinib), Bristol Myers Squibb leukemia treatment BMY.N, and quercetin – senescent cell transfer and levels of inflammatory markers were increased. were significantly reduced, and the recipients’ fitness was comparable to that of mice that received younger organs, the researchers reported.

They hope to be able to use senolytics to prevent the transfer of senescence to humans.

“This research could not only help us improve outcomes, but also make more organs available for transplantation,” Stefan Tullius, study leader at Brigham and Women’s Hospital in Boston, said in a statement.

Nanomedicines may be less effective in young cancer patients

Modern cancer drugs, known as nanomedicines, may be less effective in younger patients, whose livers are able to filter a significant amount of drugs from the bloodstream, preventing them from reaching tumors, such as studies carried out on mice suggest this.

“Our liver is designed to protect us (from toxins in the blood), but in young people it may also protect them in a way that limits the effectiveness of nanotherapies,” Dr. Wen Jiang of the MD Anderson Cancer Center at the University of Texas, leader of the study.

Nanomedicines use tiny particles to carry drugs. Benefits may be reduced toxicity, improved target specificity, and safe delivery of higher doses.

In laboratory experiments, Jiang’s team administered the same doses of nanodrug formulations of the chemotherapies paclitaxel or doxorubicin to young and old mice with breast tumors.

In aged mice, the treatment led to better tumor control because the animals’ livers contained fewer filtering cells, known as Kupffer cells, which trap drugs and toxins, allowing a greater amount of drugs to reach the tumor, according to a report published Monday in Nature Nanotechnology (link).

Blocking the activity of a specific protein found in greater quantities in Kupffer cells of young livers reduced drug filtering and improved the therapeutic effectiveness of drugs, but only in young mice, they also found. Researchers.

“These results show that there is not always a single drug delivery strategy that is effective for diverse patient populations, and that personalized design is warranted for future nanomedicines,” said Jiang.

Around 100 nanotechnology-based therapies have been approved by US and European regulators. Although this study focused on cancer, filtering by the liver represents a potential obstacle for all nanomedicines, Jiang said.

Most C. difficile infections may not be acquired in the hospital

Hospitalized patients who develop highly infectious severe bacterial diarrhea known as Clostridioides difficile are likely to have been infected before their admission rather than having acquired the infection during their stay, according to new research that appears to point to the against conventional wisdom.

Seeking to understand how C. difficile infections spread, researchers at Rush University Medical Center in Chicago analyzed daily fecal samples from more than 1,100 patients treated in their intensive care unit (ICU) over a nine-month period .

Based on the genetics of the strains identified, intensive infection control efforts already in place have helped limit transmission at the hospital.

Only 1% of patients who did not have pathogenic C. difficile bacteria when admitted to the intensive care unit acquired it from another patient, researchers reported Monday in Nature Medicine (link) .

Patients who had tested positive for the so-called toxigenic C. difficile bacteria during their admission to intensive care, without symptoms, had a 24 times higher risk of developing a serious infection during their hospitalization, compared to patients without the disease. bacterium.

“Something happened in these patients that we don’t yet understand that triggered the transition from the C. difficile hanging around in the gut to the organism that causes diarrhea and other complications resulting from the infection,” Evan Snitkin, study leader at the University of Michigan Medical School, said in a press release.

“These data suggest that interventions focused on preventing the transition from colonization to overt infection will have a greater impact than investing additional resources aimed at interrupting cross-transmission

#Health #rounds #class #drugs #organs #older #donors #younger #patients #p.m

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