After surgery, some patients rebound quickly, and some endure weeks of fatigue or pain.
What if a blood test could predict which path recovery will take? Surgery could be planned better, and recuperation strategies could be made more effective or less expensive.
A new study opens a door to such prediction tools. By analyzing blood from patients having hip replacements, scientists and doctors found that certain activity in patients' immune systems correlated to different recovery times.
In the study, published in the journal Science Translational Medicine, scientists tagged proteins in patients' blood with isotopes and analyzed thousands of signals using a tool related to a mass spectrometer, called a mass cytometer. Changes in levels of three proteins appeared to correlate with how long it took patients to walk proficiently, recover from pain, and regain energy.
The study was small, with 32 patients, and recovery times varied from virtually immediate to six weeks. The protein levels did not tell the whole story, but they seemed to account for about half the variation in recovery time, researchers reported.
Capturing such a fine-grained picture of blood cell activity and linking it to patient outcomes marks a new milestone along the road toward individualizing medical treatment, experts said.
"This is by far the most detailed and deep analysis of what's going on in your blood, which is in essence the highway of a whole country," said Tak W. Mak, a biochemist at the University of Toronto, who was not involved in the study. "I think the promise is in the future, that we can get one complete synopsis of all the cars and trucks and bicycles and people on the highway and profile all their characteristics."
He said much more work remains, including testing the "immunological signature" theory on more patients and seeing if predicted outcomes hold true. In this study, "the data does not blow me away," he said, "but the potential of what it can do is enormous."
The study involved 20 men and 12 women ages 54 to 68 who had a hip replaced. They were otherwise relatively healthy. Researchers sampled blood from patients one hour before surgery, and one hour, 24 hours, 72 hours, and six weeks afterward.
The immune signals scientists measured were like pulses along an earthquake's path, or the incremental mobilization of a National Guard reserve unit, said Garry Nolan, a Stanford microbiologist and a study author. He is an inventor of the mass cytometer and earns proceeds from it.
"Most cells in the immune system are in a state of quiescence, not running around with their hair on fire all the time," he said. But when trauma or illness strikes, some cells mobilize, and the scientists could assess "what they are thinking on their way to the invasion site, what they are preparing to do."
Patients answered questions every three days for six weeks to gauge how long it took to reach three milestones: regaining most of their hip function, eliminating most of their pain and regaining half their energy. The researchers found that three proteins, transcription factors that switch genes on or off, rose or fell to correlate with these milestones.
For example, said Dr. Martin Angst, a Stanford anesthesiologist and a study author, if the signal from the protein CREB, measured an hour before surgery, increased by 60 percent an hour after surgery, the patient took about 32 days to regain most hip function. If the signal decreased by 60 percent, it took about 12 days. If the signal did not change, it took about 17 days.
Levels of another protein, STAT 3, correlated to recovery from fatigue, which ranged from zero to 36 days. And levels of a protein called NF-kB correlated with lessening of pain, which took two days for some patients and 36 for others.
Patients' age, body mass index, pain medication or type of anesthesia made no difference. On average, for unclear reasons, women regained energy about twice as fast as men, Dr. Angst said.
One study participant, Michael Hall, 69, a retired teacher in Merced, Calif., used a walker for two weeks and a cane for two more, and took Vicodin for pain for about a month.
But Sam Salmon, 64, a lawyer in Windsor, Calif., who described himself as "healthy, but not a dude," needed one crutch for little more than a week, had virtually no fatigue and was "pain-free after about 10 days."
Now, though, Mr. Salmon is recovering from rotator cuff surgery and says "it's just the opposite," with pain and fatigue having lasted for nine weeks so far.
The researchers speculate that some differences between patients might reflect immunological variation caused by genetic, environmental or health factors. Differences in the same patient's reaction to different operations might relate to immunological activity beforehand. If tests show someone's immune system is battling an invisible infection, for example, perhaps surgery should be delayed.
Dr. Jon Hyman, an orthopedic surgeon in Atlanta not involved in the study, said the research "deserves a lot more investigation." But he said clinical use would require the precision to predict when patients could stop physical therapy, return to work or quit painkillers, to "show that having this information results in saving money somewhere."
Dr. Brice Gaudilliere, an anesthesiologist and study author, said studies that were underway aimed to "expand these results to other types of surgery and other types of trauma."
Ultimately, before surgery, a blood sample could be exposed to stress or trauma in a test -tube, and its response could help predict a patient's recovery or whether surgery is even advised, the researchers said. Dr. Mak said the technology might eventually be used as a prediction tool in conditions besides surgery: to anticipate a relapse, for example, of cancer, septic shock or embolism.
"It's a new frontier," said Dr. Laurie Glimcher, dean of Weill Cornell Medical College, who was not involved in the research. If such a "signaling fingerprint" could predict recovery or relapse, "it's an interesting and unusual example of what I would call precision medicine."
An article on Tuesday about using the results of a blood test to try to predict how patients will recover from surgery referred incorrectly to aspects of the method used to analyze the patients' blood. The proteins were tagged with isotopes, not with fluorescent molecules, and while the tool used was a type of mass spectrometer called a mass cytometer, it did not use lasers.
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