New findings show improved recovery after injury or illness

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 healing process goes awry after the reaction, it’s a sign that harm is coming – and the wound can become more damaged, 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 Communications, provide important clues.

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 studies 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 in first.

It’s an ancient practice

Disease is a common response to all diseases – and, therefore, people have been trying to explain it for decades. In ancient Rome, the medical writer Aulus Celsus described the four main symptoms of inflammation: redness, heat, swelling, and pain – and later, the physician and surgeon Galen added loss. of doing 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 have inflammation based on symptoms such as high white blood cell count or fever, “there are no guidelines for diagnosis.” “It’s about the type of cancer, and whether it’s shrinking in the right way,” said senior author John. Higgins, professor of systems biology at the Blavatnik Institute at HMS. “As doctors, we are surprisingly unprepared to see patients who are going to have a good response 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 separate the normal features, 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 a similar stimulus at a specific time,” said first author Brody a research associate in systems biology at HMS and Mass General.

They decided on nonemergency cardiovascular surgery – more specifically, coronary artery bypass grafting, valve replacement, or a 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 find out the features of the healing process, the researchers worked with the author Thoralf Sundt, the HMS Edward D. Churchill Professor of Surgery at Mass General, reviewed medical record data from 4,693 patients at Mass General who underwent cardiovascular surgery. 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 to find out the ways to heal the disease: the white blood cell count, which is not surprising, increases during inflammation, and the number platelet count, which decreases when platelets are used 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 be able to define a good recovery in terms of a small number of measurements that were already known by doctors and patients,” said author Jonathan a hematologist and researcher at HMS and MGH.

The team then expanded the study to look at other types of surgery that cause significant pain, including amputations, laparoscopic surgeries, cesarean sections, segmental amputations, and with a complicated pancreas surgery called a Whipple procedure. They also looked at infections such as COVID-19 and Clostridium difficile colitis, as well as sepsis, an immune response to 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 the same patterns of white blood cell count and platelet count returning to normal levels as their cardiovascular disease counterparts — and do so regardless 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 pain-healing methods evoked the so-called Anna Karenina sentiment popularized by Jared Diamond in his book Guns, Germs, and Steel: There’s only one way things can go right, but there are many ways it can go wrong. Well-healed patients usually follow a predictable pattern of decline and rise in white blood cell and platelet counts, but poorly-healed patients may have numbers that are high or low – and not only the expected fees.

It compares to child growth charts, where each child starts out at a different place but must follow the same path of growth – and thus stay in the same percentile – 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 was higher than the healthy range defined by the researchers – and continued to increase over the next few days, as he switched to bad. 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 actually identify advanced cancers,” 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 look at when white blood cell counts peak during inflammation, and look for processes in the body that lead to exponential decay afterward. 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 good healing from the beginning will allow us to identify diseases at an early stage, and plan interventions to improve outcomes,” said by writer Aaron AguirreHMS assistant professor of medicine at Mass General.

The research was supported by the One Brave Idea InitiativeAccelerated grants to 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 Foundation.

/ Public release. This may be a point-in-time version from the original team/author, edited for clarity, style and length. The views and opinions expressed are those of the author. Check it out in full here.

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