Executive Editor

Therapeutic exercise lessens lung injury and

muscle wasting in critically ill patients

Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that affects approximately 200,000 people a year in the U.S. and has a higher mortality rate than breast and prostate cancer combined. The condition most often occurs in people who are critically ill or who have significant injuries; those who do survive it often experience profound skeletal muscle weakness.

Over the past 30 years, efforts to fight ARDS with various drug therapies aimed at the lungs have failed. However, doctors at Wake Forest Baptist Medical Center (Winston Salem, North Carolina) have tried a different approach – exercise.

"Based on some earlier work done here, we've known that getting critically ill patients up and moving around as soon as it's medically feasible helps them get off of ventilators sooner, increases their strength when they get out of intensive care and improves overall outcomes," said D. Clark Files, assistant professor of pulmonary, critical care, allergy and immunologic medicine at Wake Forest Baptist. "What we haven't understood is why it helps."

Using an animal model that mimics what happens in people with ARDS, Files and a team of researchers worked to understand how the mechanisms underlying early mobility therapy improve the outcomes of patients with this illness. The study is published in Science Translational Medicine.

In the study, mice with acute lung injury and the resulting muscle weakness were exercised for two days. The researchers found that a short duration of moderate- intensity exercise led to marked improvements in lung, limb and respiratory muscle function.

"We looked at specific pathways involved in muscle wasting and found that early exercise turns these pathways off," Files said. "There is a complex immune response to injury and it appears that exercise is acting on multiple different proteins that involve the innate immune system and dampen this over-exuberant immune response."

The researchers then confirmed their findings from the animal model by comparing them to banked plasma from patients who were enrolled in an earlier clinical trial at Wake Forest Baptist in which patients were randomized to early mobility versus usual control. They confirmed that at least one of the markers most significantly changed in the regulation of the immune response in mice also occurs in humans.

"This study gives a lot of biological relevance to how and why early mobility tends to work," Files said. "We've identified some mechanisms that we think are very important."

Files said the next step will be to duplicate this study in older animals (instead of young mice used in the current study) because most people with ARDS are older with higher mortality.

"We want to know if therapies that work for younger ICU patients should be the same or different for older patients," he said.

First blood test for osteoarthritis could soon be available

The first blood test for osteoarthritis could soon be developed, thanks to research by the University of Warwick.

The research findings could potentially lead to patients being tested for osteoarthritis and diagnosed several years before the onset of physical symptoms.

Conducted by the University's medical school, the research identified a biomarker linked to both rheumatoid and osteoarthritis.

While there are established tests for rheumatoid arthritis (RA), the newly identified biomarker could lead to one which can diagnose both rheumatoid arthritis and osteoarthritis (OA).

The research's focus was citrullinated proteins (CPs), a biomarker suspected to be present in blood of people with early stage rheumatoid arthritis. It had previously been established that patients with RA have antibodies to CPs, but it was not thought that this was the same for those with OA.

However, the Warwick researchers found for the first time increased CPs levels in both early-stage OA and RA.

They then produced an algorithm of three biomarkers, CPs, anti-CP antibodies along with, the bone-derived substance, hydroxyproline.

Using the algorithm the researchers found that with a single test they could potentially detect and discriminate between the major types of arthritis at the early stages, before joint damage has occurred.

Commenting on the findings, lead researcher, Naila Rabbani said, "This is a remarkable and unexpected finding. It could help bring early-stage and appropriate treatment for arthritis which gives the best chance of effective treatment."

Explaining the role of CPs in relation to both RA and OA and the importance of the algorithm to the research Rabbani said, "It has been long established that the autoimmunity of early-stage RA leads to antibodies to CPs, but the autoimmunity, and hence antibodies, are absent in early-stage OA. Using this knowledge and applying the algorithm of biomarkers we developed provides the basis to discriminate between these two major types of arthritis at an early stage."

The ability to discriminate between RA and OA could provide a number of benefits to patients, including early diagnosis. Dr Rabbani said:

"Detection of early stage-OA made the study very promising and we would have been satisfied with this only – but beyond this we also found we could detect and discriminate early-stage RA and other inflammatory joint diseases at the same.

"This discovery raises the potential of a blood test that can help diagnose both RA and OA several years before the onset of physical symptoms."

The research, Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health, is published by Nature Scientific Reports.

Spinal surgery diminishes low back
pain, improves sexual function

Chronic low back pain can limit everyday activities, including sex. New research presented today at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS; Rosemont, Ilinois), found that 70% of patients consider sexual activity "relevant" to their life quality, and patients who receive surgical treatment for spinal spondylolisthesis (DS) and spinal stenosis (SS)—common degenerative conditions most often occurring in older adults—were twice as likely to report no pain during sex.

"Our current research sheds light on the effect that spinal surgery has on a patient's sex life and begins to describe the impact spinal disease has on this very important aspect of life," said senior study author Shane Burch, an orthopedic surgeon at the University of California, San Francisco.

Researchers reviewed data from the Spine Patients Outcomes Research Trial (SPORT) of 1,235 patients diagnosed with DS or SS. Patient responses to the question, "In the past week, how has pain affected your sex life?" were used to determine sex-life relevance. Patients selecting the options, "unable to answer" or "does not apply to me," were placed in the sex-life non relevant (NR) group. Patients selecting other options were placed into the sex-life relevant (SLR) group. The mean age of patients in the NR and SLR groups were 68 and 63 years, respectively. Seventy percent of patients were in the SLR group.

There was a higher association of being in the NR group for patients who were female or unmarried, or had a coexisting joint problem or hypertension. At baseline, 40 percent of SLR patients reported having some level of pain related to sex.

The study included 825 patients, 449 with SS and 376 with DS. A total of 294 patients received nonoperative treatment, and 531, surgical treatment. The nonoperative patients were more likely to report pain related to sex at all follow-up time frames (from 41% compared to 20%). The percentages remained constant during annual visits at one year, two years, three years and four years after surgery. Prior studies found that 41% of physicians routinely question patients with lumbar disc herniation about sexual problems.

"Our current research has two important findings," said Horst. "The first is that sexual activity and sexual function is an important consideration for patients with degenerative spine conditions. The study also shows that sexual function is a more relevant consideration for patients who are married, younger, and male. The second important finding of our study is that patients with degenerative conditions of the spine treated with surgery reported less pain with their sex-life compared to patients treated without surgery. This finding lasted throughout the four years of follow-up."

Study identifies low back pain risk factors

New research presented today at the 2015 AAOS annual meeting identified nicotine dependence, obesity, alcohol abuse and depressive disorders as risk factors for low back pain, a common condition causing disability, missed work, high medical costs and diminished life quality.

According to the U.S. Centers for Disease Control and Prevention's (CDC) 2012 National Health Survey, nearly one-third of U.S. adults reported that they had suffered from low back pain during the previous three months. For many adults, low back pain is debilitating and chronic. Determining modifiable risk factors for low back pain could help avoid or diminish the financial and emotional costs of this condition.

Researchers reviewed electronic records of more than 26 million patients from 13 health care systems across the U.S., including 1.2 million patients diagnosed with low back pain (approximately 4.54 percent of the patient records).

The review found that 19.3% of the patients diagnosed with a depressive disorder reported lower back pain, as did 16.75% of patients diagnosed as obese (a body mass index, or BMI, >30kg/m²), 16.53% of the patients diagnosed with nicotine dependence, and 14.66% with reported alcohol abuse. Patients with nicotine dependence, obesity, depressive disorders, and alcohol abuse were had "statistically significant" relative risks of 4.489, 6.007, 5.511 and 3.326 for low back pain, respectively, when compared to other patients.

"This study used an electronic healthcare database to identify modifiable risk factors—obesity, depressive disorders, alcohol and tobacco use—in patients with low back pain," said lead study author and orthopaedic surgeon Scott Shemory, "The findings will allow physicians to better counsel and more closely follow their high-risk patients."