Jefferson Investigates: Discrimination’s Impact on Recovery, Cannabis for Chronic Pain, and Cancer’s Blood Supply

Does discrimination slow recovery from brain trauma, can patients with long-term pain use cannabis to reduce opioid use, will blocking blood flow to cancer slow its growth?
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Discrimination Linked to Worse Outcomes after Traumatic Brain Injury

Moderate and severe traumatic brain injuries (TBIs) can lead to lifelong disability and require long-term medical care. While drugs and surgery can treat TBI, new research also shows that conditions in a patient’s life outside the doctor’s office — like educational level, economic status and neighborhood environment — can all play a role to help or hinder TBI recovery.

Umesh Venkatesan, director of the Brain Trauma and Behavior Laboratory at the Moss Rehabilitation Research Institute, was interested in how one specific life experience — societal discrimination — could impact health outcomes after a TBI. Discrimination has been shown to cause psychological distress that can lead to downstream health problems. Individuals with TBI are especially at risk for discrimination, as people from marginalized communities are more likely to sustain a TBI, and because TBIs can cause disabilities that are subject to discrimination.

Dr. Venkatesan and colleagues surveyed how often individuals with moderate and severe TBI felt discriminated against for any reason, related or unrelated to their injury. The results, published in The Journal of Head Trauma Rehabilitation, show that discrimination is linked to a range of adverse effects. Individuals experiencing discrimination measured higher on scales of anxiety and depression, showed more signs of frontal lobe brain damage, like lack of inhibition, and even reported worse quality of life.

Dr. Venkatesan says he hopes this research pushes healthcare professionals to pay attention to individual patient’s experiences in TBI care. “You have to really consider people holistically, taking into account their whole lives completely” he says.

The results also underscore how social determinants of health may shape rehabilitation outcomes. “It makes it particularly important that we study these social factors and experiences in our patients,” says Dr. Venkatesan, “Because social issues like discrimination may have been negatively influencing their whole lives, there’s no reason to believe these factors are going to stop influencing patients’ health after brain injury. If anything, the injury might make tough situations worse.”

Dr. Venkatesan plans to expand his work to other social, economic, and environmental “life course” factors that can affect rehabilitation recovery and long-term functioning after a TBI.

By Marilyn Perkins

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Medical cannabis can help chronic pain patients reduce opioid use

The downsides of relying on opioids for chronic pain conditions are clear — the drugs become less effective over time and patients have to increase how much they take, while excessive use or abuse can be lethal. Researchers at Jefferson and clinicians at the Rothman Orthopaedic Institute wondered if medical cannabis, studied for its pain-relieving properties and recently legalized in Pennsylvania, might help.

Patients in Pennsylvania can now be certified to access medical cannabis, says Dr. Asif Ilyas, an orthopedic surgeon at Rothman. “We began actively certifying patients,” he says, for those with chronic pain conditions such as neuropathies, arthritis and cancer pain, “so we wanted to follow them to assess their outcomes.”

Dr. Ilyas and his team designed a study to monitor any change in opioid use before and after patients had been certified for medical cannabis. The findings were promising: Patients cut their opioid daily dose by nearly half over six months, on average, and a third of people stopped filling their opioids prescriptions completely. Overall, patients experienced less pain and reported improved quality of life.

“We were very pleased with these initial positive findings,” Dr. Ilyas says, because of the clear and profound change in their primary measure: opioid use. Still, he knows there’s much more to learn, as there are many forms of medical cannabis and many delivery routes. “We’re still in the infancy of understanding all the dynamics of medical cannabis in the management of pain.”

Dr. Ilyas and his research team hope to build on these initial findings and intend to pursue more investigations around medical cannabis, he says, “with more granularity and with more controlled studies.”

By Jill Adams

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Cutting Off the Blood Supply to Breast Cancer

One way to slow tumor growth in cancer is by impeding the tumor’s ability to make new blood vessels. Current anti-cancer drugs that use this strategy, such as bevacizumab, have been used clinically for nearly 20 years, but in many cases the drugs don’t provide enough benefit to counter their risks.

Researchers at Jefferson Health are exploring alternative pathways to starve tumors by blocking blood vessel formation, also called angiogenesis. Renato Iozzo’s laboratory discovered a key molecule called endorepellin, which occurs naturally in the body and can interfere with blood vessel growth. The researchers thought if they could boost endorepellin levels, they might have an alternative way of preventing angiogenesis in tumors.

To test their idea, the team created transgenic mice that, when stimulated, would over-produce endorepellin. In cells from the mice, boosting endorepellin inhibited the angiogenesis pathway and sprouting of new blood vessels, says Carolyn Chen, an MD-PhD student in Dr. Iozzo’s laboratory. Next they needed to see if it works in living animals with implanted breast cancer tumors. “There are so many more compounding factors in the whole animal,” Chen says.

The results were positive: Stimulating endorepellin significantly decreased tumor volume in the mice. “It’s a proof of principle study,” says Chen, which means they’re testing their idea with tools that cannot be tested in humans. There’s a long way to go before this knowledge can be translated into clinical treatment.

Chen says the shortcomings of current anti-angiogenesis drugs in cancer has forced the field to dig deeper and find these new pathways. Even with this promising anti-tumor intervention, there’s plenty to learn, such as the most effective time to trigger action and what other molecular processes are involved.

By Jill Adams

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