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| |  Blood Test Could Predict Which Patients Will Recover Well From Orthopaedic Surgery STANFORD, Calif -- December 2, 2009 -- The right kind of stress response in the operating room could lead to quicker recovery for patients after knee surgery, according to a new study led by Stanford University School of Medicine researchers. The results suggest that simple, inexpensive blood tests performed while patients are on the operating table could predict how well patients will have recovered months after they leave the hospital. Eventually, doctors might also be able to develop medical interventions to improve that recovery. The study, conducted with colleagues at Yale University and published in the Journal of Bone and Joint Surgery, found that patients whose immune systems responded to the stress of surgery by mobilising large numbers of pathogen-fighting cells and redistributing them to skin and other tissues recovered more quickly and completely than those patients whose immune system showed little or no reaction. The researchers also found that men were more likely than women to mount the beneficial stress response and recover more fully. “One of the beauties of the tests is that it’s so easy,” said Esther Sternberg, MD, National Institute of Mental Health, Rockville, Maryland, who was not involved in the research. “The information is completely available to any physician pre- and post-surgery.” Old models of stress and the immune system predicted that stressful situations would suppress immune activity. But Firdaus Dhabhar, PhD, Stanford University, Stanford, California, senior author of the paper, said those models didn’t differentiate between unhealthy chronic stress, which can negatively affect the immune system, and healthier short-term stress. Short-term stress, Dr. Dhabhar said, launches the fight-or flight response, which he described as “one of nature’s fundamental protective survival mechanisms.” “In nature, wounds and infections often occur during stressful situations, or cause stress soon after they occur. Therefore, we reasoned that the short-term stress response would prepare organisms for immune challenges, just as it prepares them for fight-or-flight,” said Dr. Dhabhar. In previous studies, Dhabhar found that when mice are put in stressful circumstances for just minutes to hours, their immune cells flood out of the spleen and bone marrow and into the bloodstream, causing a noticeable increase in their numbers within 5 to 10 minutes. Over the next few hours, the number of immune cells in the bloodstream decreases as the cells enter skin and other tissues, where they guard against infectious intruders. Instead of suppressing immunity, short-term stress acts like a “call to arms,” Dr. Dhabhar said, sending immune cells to at-risk tissues and preparing the body to defend itself. Dr. Dhabhar and his colleagues recruited 57 patients who were scheduled for surgery to repair damaged cartilage in their knee joints. To ensure that the surgical procedure would be as consistent as possible, all of the surgeries were performed by Peter Jokl, MD, Yale University, New Haven, Connecticut. Three to 10 days before the surgery, blood samples were obtained from patients to establish a baseline count of immune cells. Then, on the morning of surgery, the researchers took another blood sample just before administration of anaesthesia, looking for an increase in immune cells in the bloodstream. The idea, Dr. Dhabhar said, was that patients would be somewhat anxious about the impending surgery, triggering the short-term immune response. About a half-hour after surgery, the patients gave a final sample while in the recovery room. At that point, the researchers reasoned, many blood-borne immune cells should have exited the circulation and entered tissues, including the site of surgery. Using the data, the team calculated total “redistribution” numbers for lymphocytes, monocytes, and neutrophils. These numbers quantified the initial increase and subsequent decline in immune cells in the blood. The researchers then determined the median redistribution number for the group. Those with redistribution numbers higher than the median were categorised as ‘high responders.” Those whose immune-cell redistribution numbers were smaller than the median or unchanged were grouped as “low responders.” Researchers then followed up with patients for 1 year, checking knee inflammation and using the Lysholm scale to rank knee function, pain, and mobility on a scale of 1 to 100, with scores above 90 representing maximal recovery. Patients who showed the positive stress response during surgery showed increased recovery as early as 1 week post-surgery compared with low responders, an effect that carried all the way through the study period. One year later, high immune responders had average Lysholm scores of more than 90. Low responders had scores around 80 and never recovered as fully as their stress-adaptive counterparts. The researchers also uncovered a gender disparity: Women were less likely to show an adaptive response than men. On average, their lymphocyte redistribution numbers were nearly 4 times lower than that of their male counterparts. They also achieved lower overall knee recovery than men. However, when women did show adaptive immune cell redistribution, their recovery matched that of men with the same adaptive response. “It was slightly surprising to see how much in tandem the immune cell redistribution appeared to be with the overall gender recovery difference,” said Dr. Dhabhar. However, he said, the fact that patients’ immune cells showed varying degrees of redistribution during a stressful situation is evidence that the link between stress and the immune system is complex and requires more investigation. The research was funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
SOURCE: Stanford University Medical Center
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