Study provides important clues for better inflammatory response

The immune system is the body’s first line of defense, where immune cells rush to the site of an injury or infection to repair and prevent further damage.

When active, inflammation helps the body recover and heal after injury. However, when the recovery goes wrong after the response, it signals that disaster is about to happen -; and the neck itself can cause further injury, leading to serious illness or death.

But what separates a good recovery from a bad one?

A new study, led by researchers at Harvard Medical School and Massachusetts General Hospital, was published on August 22 in Nature Communicationsgive important indications.

Scientists have identified broad patterns of pain responses in patients who have successfully recovered after surgery or serious illnesses such as COVID-19, heart attacks, and sepsis. . These patterns, they found, depend on the precise paths that white blood and platelet counts follow as they return to normal.

If confirmed in further research and adopted as a clinical guide, the findings could help doctors quickly identify when a patient’s recovery is not going well, allowing them to intervene used to.

It’s an ancient practice

Yeast is a common response to all diseases-; and so people have tried to explain it for thousands of years. In ancient Rome, the medical writer Aulus Celsus described the four main symptoms of inflammation: redness, warmth, swelling, and pain -; and later, the physician and surgeon Galen added loss of function to the list. Today, scientists know that symptoms of inflammation arise when the immune system mounts a response to an injury or infection, sending out protective white blood cells, proteins, and chemicals that cause physiological changes in the body.

Although doctors today are good at identifying patients who are experiencing inflammation based on symptoms such as high white blood cell count or fever, “there is no guide to looking at the type of cancer, and the type of fit,” said senior author John. Higgins, professor of systems biology at the Blavatnik Institute at HMS. “As doctors, we are not equipped to separate patients whose inflammatory response is going well from patients who are not responding.”

However, it is important to know if the inflammation is responding well to the disease and progressing in healing, because it can help doctors decide whether to stand back and let the body of the patient who heals himself or enters.

Higgins and his team began to understand the recovery of the disease to determine if there are common characteristics in successful recovery.

Signs of success

Because inflammation develops in patients who are already sick, learning can be difficult. Therefore, researchers have found that in order to distinguish between normal patterns, they need to study the inflammatory response in a controlled setting.

“We need to find a situation where everyone starts out in a normal state of health, and then they all get the same stimulus at a specific time,” explained first author Brody Foy. , a research associate in systems biology at HMS and Nui Nui.

They recorded nonemergency cardiovascular surgery -; More specifically, coronary artery bypass grafting, coronary artery bypass grafting, or any other combination. These procedures are often used in medical patients who have heart problems but are stable and do not have complications that require immediate treatment. However, all cardiovascular surgeries involve trauma and serious damage when doctors enter the heart to correct the procedure, requiring a significant pain response.

To identify recovery patterns, researchers worked with co-author Thoralf Sundt, the HMS Edward D. Churchill Professor of Surgery at Mass General, to review clinical data from 4,693 patients at Mass General who underwent cardiovascular disease. After looking at multiple measures at the same time, they found common patterns in the trajectories of patients who survived well. They lived in two ways that clearly know the trajectories for the better healing of the disease: the number of white blood cells, which is not surprising, increases during inflammation, and the number of platelets, which decreases measures the use of platelets for clotting and healing.

Among patients who recovered well after surgery, the number of white blood cells decreased in a precise point, while the platelet count increased in a different point, but also correctly. These trajectories, the researchers said, can be used to monitor recovery in a personal way.

Doctors can’t look at changes in 20 different things at once. We really wanted to explain the positive recovery in terms of the small measures already known by doctors and patients. “

Jonathan Carlson, author, hematologist and researcher at HMS and MGH

The team then expanded the study to look at other types of surgery that cause severe inflammation, including amputations, laparoscopic surgeries, cesarean sections, segmental amputations, and with a complicated pancreas surgery called a Whipple procedure. They also looked at infectious diseases like COVID-19 and Clostridium difficile colitis, and sepsis, a life-threatening inflammatory response triggered by an infection. Finally, they looked at methods of recovery after events such as heart attacks and strokes that deprive the muscles of oxygen and can cause aberrant inflammation.

The researchers found that patients who recovered followed similar trajectories for white blood cell count and platelet count returning to the normal range as their cardiovascular surgery -; and did so because of their status or age. These characteristics were also stable regardless of the speed of recovery of the patients, or the levels at which their white blood and platelet count started.

In addition, scientists can mathematically describe the exact paths that show a positive recovery: The white blood cell count went through an exponential decay, but the platelet count increased after a short delay.

“What’s interesting about this study is that it shows that there are common patterns of recovery for a wide range of diseases, and if we know how to heal well, then we can We see a bad disease,” Higgins said.

Translate the results

For Higgins, these inflammatory healing methods gave rise to the idea called Anna Karenina that Jared Diamond published in his book. Guns, disease, and steel: There is only one way things can go right, but many ways things can go wrong. Patients who recover well follow a predictable pattern of decline and rise in white blood cell and platelet counts, while patients who recover poorly may have high or low counts. -; or simply change the estimated costs.

It compares to child development charts, where each child starts at a different place but must follow the same path of development -; and thus remain in a similar percentage -; for weight and height. He believes that his team can create personalized treatment plans to personalize health pathways for each patient with a wide range of illnesses.

Higgins and his team are working to get their knowledge into the hands of doctors to help them better understand how patients heal from inflammation.

To illustrate this point, Higgins presented the case of a 78-year-old woman who was hospitalized after a heart attack. On the fourth day of his recovery, his white blood cell count dropped to the normal range, indicating that he was recovering well. However, his white blood cell count is higher than the healthy range that researchers have defined -; and increased over the next few days, as the storm worsened. In other words, the whole sample provided a more valuable diagnostic signal than a complete blood count, Higgins said, by signaling a day earlier that something was wrong in recovery. of the patient.

Higgins, however, kept it to be seen whether the result will improve before these harbingers of a bad return. It is a topic for further research.

“Our approach is to really identify serious diseases,” Higgins said. “We need to learn if knowing something earlier really helps, but at least we have a chance to get involved.”

Higgins and his team are also interested in studying the biological mechanism by which white blood cell and platelet counts return to normal after injury or illness.

“These findings help create some hypotheses for the mechanisms,” Higgins said. For example, it led researchers to observe when white blood cell counts peak during inflammation, and to look for processes in the body that lead to exponential decay later. of the peak.

The researchers also wanted to change their focus before the procedure to see if they could identify common patterns of positive response when patients first started to experience inflammation after injury. or illness.

“Understanding the importance of a successful recovery from the start allows us to identify patients who are at risk earlier, and plan interventions to improve outcomes, ” said author Aaron Aguirre, HMS professor of medicine at Mass General. .

The research was supported by the One Brave Idea Initiative, Fast Grants at the Mercatus Center, George Mason University, the NIH (DP2DK098087), the Partnership for Clean Competition Research Collaborative, the MGH Hassenfeld award, and the Controlled Risk Insurance Company/ Risk Management. site.


Book reference:

Foy, BH, et al. (2022) Human Regeneration Explained by Co-Regulatory Dynamics of White Blood and Platelet Populations. Nature Communications.


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