Tag: Pain

Different pain types in multiple sclerosis can cause difficulty staying active

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BYLINE: Valerie Goodwin

Newswise — For patients with multiple sclerosis, a regular exercise routine is important for managing symptoms. But due to different causes of chronic pain, physical exercise can be more difficult for some.

Research published in the Journal of Pain from the University of Michigan found that widespread pain with nociplastic features can make engaging in physical activity a painful task for patients with MS.

“Widespread pain with nociplastic features is a chronic and diffuse pain which can be challenging to localize or describe precisely,” said Libak Abou, Ph.D., research assistant professor and lead author of the paper.

“In a person with MS, this type of pain arises from altered processing signals within the central nervous system. This is opposed to pain that arises from specific tissue damage, classified as nociceptive pain, or pain related to demyelination and axonal damage, classified as neuropathic pain.”

Abou and fellow researchers surveyed patients with MS to see if those with a higher indication of widespread pain with nociplastic features were more likely to be insufficiently active or sedentary when compared to their MS counterparts with no chronic pain, nociceptive pain, or neuropathic pain.

Each of the participants was self-reporting with their data.

The results of the survey showed that those who experienced WPNF in addition to their MS were not sufficiently active due to the chronic pain they were experiencing.

“There is a growing need to consider what type of pain MS patients are experiencing before giving them an exercise plan,” said Abou.

“The concept of considering widespread pain with nociplastic features when creating exercise plans for MS is newer but could help many patients get to an activity level that will help ease symptoms without causing them intense pain.”

For the future, Abou hopes that clinicians can begin doing screenings for underlying pain mechanisms in patients with MS that are struggling to stay active to help further tailor their physical routines to their personal needs.

“The end goal is to help those with MS maintain their functional independence,” said Abou.

“It is also important to remember that these patients will likely need extra support from their physical therapy team to keep them on a path with less pain.”

Additional authors: Libak Abou, Daniel Whibley, and Anna L. Kratz from the Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, Michigan as well as the Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan. Daniel J. Clauw from the Department of Anesthesiology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan.

Paper cited: “Widespread Pain With Nociplastic Features is an Independent Predictor of Low Physical Activity in People with Multiple Sclerosis,” The Journal of Pain. DOI: 10.1016/j.jpain.2023.09.005

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Michigan Medicine – University of Michigan

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November 1, 2023
Black and Hispanic patients much more likely to die after surgery than white patients

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Newswise — SAN FRANCISCO — About 12,000 Black and Hispanic patients who died after surgery the past two decades may have lived if there were no racial and ethnic disparities among Americans having surgery, suggests a study of more than 1.5 million inpatient procedures presented at the ANESTHESIOLOGY® 2023 annual meeting. This estimate draws attention to the human toll of disparities in surgical outcomes, with Black patients being 42% more likely and Hispanic patients 21% more likely to die after surgery compared to white patients.

Unless efforts to narrow the racial and ethnic gap in surgical outcomes intensify, preventable deaths will continue among minority patients, the researchers said. The development of equity policies to address disparity gaps can make a difference, with even a 2% reduction in projected excess mortality rates among Black patients averting roughly 3,000 post-surgery deaths in the next decade, they determined.

“This study represents the first effort to move beyond merely documenting the ongoing disparities in surgical outcomes in the U.S. by quantifying the aggregate human toll of these disparities,” said Christian Mpody, M.D., Ph.D., MBA, lead author of the study and assistant professor of anesthesiology and pediatrics at The Ohio State University College of Medicine, Columbus. “We should not become used to reading statistics about people dying. It’s essential to remember that beyond the statistics, odds ratios and p-values, these are real people — brothers, sisters, mothers and fathers.”

“The findings bring to light the deaths that may have been preventable if people of various racial and ethnic backgrounds had comparable mortality rates to white patients,” he said. “That’s important for conveying the gravity of the issue to policymakers, health care professionals and the general public.”

Researchers analyzed the Nationwide Inpatient Sample data of more than a million surgical procedures performed at 7,740 U.S. hospitals between 2000 and 2020. They determined Black patients were 42% more likely than white patients to die within 30 days of surgery, driven by higher mortality in the Northeast (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island and Vermont). Hispanic patients were 21% more likely than white patients to die within 30 days of surgery, driven by higher mortality in the West (Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington and Wyoming).

Although death rates declined for all groups over the 20-year period, the disparity gaps did not narrow over time. The study did not identify causes of death.

“It’s important to note that disparities in these regions do not necessarily mean that the surgical care is inferior. It may reflect overall population health and socioeconomic conditions,” said Dr. Mpody. “Our team is currently investigating the underlying causes of these regional variations.”

Dr. Mpody said the study didn’t assess the effectiveness of specific interventions or policies, noting that addressing the problem requires a three-pronged approach involving research, education and service. Suggested interventions by the authors include increasing investment in disparity research and incorporating race and racism lectures in medical and nursing school curricula. Health systems should: provide cultural competency training; focus on diversity in grand rounds; invest in patient education and health literacy; develop personalized medicine approaches that take into account individual patients’ needs and race-sensitive protocols; and increase the number of minority providers.

THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/MadeforThisMoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook, follow ASALifeline on Twitter and use the hashtag #ANES23.

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American Society of Anesthesiologists (ASA)

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October 15, 2023
Anesthesiologist-led blood management programs save hospitals significant amounts of blood and reduce costs with same or better patient outcomes
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Newswise — SAN FRANCISCO — Blood management programs that reduced or avoided transfusions saved a health system millions of dollars annually, with a return on investment of more than $7 for every dollar spent, while achieving the same or better outcomes, suggests research presented at the ANESTHESIOLOGY® 2023 annual meeting.

Over the past 10 years, the Johns Hopkins Health System established a comprehensive blood management program with two primary goals: 1) to reduce unnecessary transfusions across the five-hospital health system, and 2) to provide specialized care that avoids transfusions in patients who decline them. Together these efforts save blood and reduce costs, making more blood available for those who really need it, such as trauma patients. Transfusions are routinely used for emergencies and trauma, but also are needed in heart, transplant, hip or knee replacement, spine, vascular, liver and pancreatic surgery. Nonsurgical patients also need blood, for example those with cancer (leukemia, lymphoma), sickle cell anemia or gastrointestinal bleeding.

“Since we are always dealing with blood shortages, doing more with less is critically important,” said Steven M. Frank, M.D., lead author of the study and professor in the Department of Anesthesiology and Critical Care Medicine at Johns Hopkins Medicine, Baltimore. “We like to say that blood saves lives when you need it, but only increases risks and costs when you don’t. Our results showed that a comprehensive blood management program can substantially help the bottom line — for every dollar spent, we received $7.50 in return.”

Starting in 2012, two anesthesiologist-led, multidisciplinary blood management programs were run side by side.
- The Patient Blood Management Clinical Community program was designed to reduce unnecessary transfusions using several methods. The methods include evidence-based transfusion triggers, a “Why Give 2 When 1 Will Do?” single unit of blood transfusion campaign, and other anesthesiology-led before, during or after surgery measures of “keeping blood in the patient” such as using medications or intentionally lowering blood pressure to reduce bleeding and using smaller tubes to collect blood for lab tests. Over a 10-year period, the annual blood acquisition cost reduction was $2.9 million, a 10.9% decrease and a 9.6-fold return on investment.
- The Center for Bloodless Medicine and Surgery program was designed to avoid transfusions entirely for those who don’t accept them, primarily Jehovah’s Witness patients. The program brings in revenue by attracting patients who are often turned down by other hospitals. Over 10 years, the program brought in approximately $5 million a year (after subtracting the direct cost of care), representing a 6.6-fold return on investment.
Clinical outcomes such as infection, blood clots, kidney injury, heart attack or stroke were the same before and after the Patient Blood Management Clinical Community program was instituted. Clinical outcomes were the same or better for the Center for Bloodless Medicine and Surgery program, as the incidence of hospital-acquired infection was significantly lower when transfusions were avoided.

“By reducing unnecessary medical procedures, we are actually doing more with less and providing higher value care,” said Dr. Frank. “Since clinical outcomes are either the same or better while giving less blood, the patients benefit from reduced risks and costs.”

THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/MadeforThisMoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook, follow ASALifeline on Twitter and use the hashtag #ANES23.

# # #
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American Society of Anesthesiologists (ASA)

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October 14, 2023
I'm A PT: This Program Has Revolutionized The Way I Provide Care

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HCC has shown me another way to administer health care—one that’s better for both patients and practitioners.

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Carly Egrie, DPT

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October 4, 2023
Doctors Told Me To ‘Just Lose Weight’ And My Pain Would Go Away. It Only Got Worse.

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My voluptuous pear shape is common among the women in my family. Our trademark big thighs and wide hips appeared early on my adolescent body, though, and worried my parents, who had also questioned doctors as to how a toddler could have cellulite.

“If she just loses weight, it’ll go away.” That was the reverberating collective opinion of the medical community as I attempted WeightWatchers, Herbalife, summer fat camp and numerous other diets, all by the time I entered puberty, none with lasting results.

I entered my teens determined to “fit in.” I pushed myself to keep up with the stride of my friends, not sway too much or walk too heavily. Determined not to be that fat kid. I danced and exercised for hours on end at home, to the annoyance of my mother, whose room was beneath mine.

As the years progressed, however, I began experiencing pain. It was a pain that, by my teens, I had become accustomed to pushing to the back of my mind to avoid embarrassment. During high school, however, it became excruciating.

When I finally took this to my doctor, he responded that my body was carrying extra weight “like a backpack” and that if I lost it, the pain would go away. Though I felt like the doctor didn’t take the time to properly evaluate my condition, I attempted fad diets, resulting in more weight gain than loss.

By college and early adulthood, I had given up hope and became determined to be successful despite my weight. I overexerted myself in an attempt to prove that fat people weren’t lazy. I rarely ate sweets, shunned bread and skipped meals religiously. I was obsessed with not letting the world see me “acting fat.” I refused to mention my pain.

“Grin and bear it” became my battle cry. On the outside, I was successfully wearing the look of happiness, but internally I was living in misery, afraid to tell anyone how bad the pain was or how tired and heavy my body felt. I knew what their response would be: “If you’d just lose weight, it’ll go away.”

“I rarely ate sweets, shunned bread and skipped meals religiously. I was obsessed with not letting the world see me ‘acting fat.’ I refused to mention my pain.”

They didn’t understand. They couldn’t. This fat was different. This fat was painful, and it wasn’t responding to diet or exercise.

Frustrated and now with decreasing mobility, I started quietly searching the internet for answers. I knew I couldn’t be the only person to ever experience this. I needed help, and the general medical community offered very little more than judgment. At times, what they offered felt more like an insult than help:

“You are a pretty girl. You should lose weight and get your education and make something out of yourself.” (I have three degrees.)

“Nothing is wrong with you other than you are morbidly obese. You need to eat just a small amount of lettuce and half of a boiled egg with no dressing for all of your meals.”

“I know that you came in here for a UTI, but I came down to talk to you about losing weight.”

These are a few of the things said to me by the medical community as I searched for answers to my pain. It was typical for doctors to scoff at my attempts to explain how diets affected my body. Desperate, I took the advice of medical professionals and opted for weight loss surgery. The result of that was weight loss only in my upper body. My lower body continued to get larger, and my mobility continued to decline.

I was depleted. My last resort had failed. It was getting exceedingly difficult to function in life. Driving became hazardous, work was near impossible, and the pain permeated every part of my life, even sleep. That’s when a doctor finally agreed that it might be lymphedema that was affecting my limbs.

Lymphedema is swelling that occurs due to either a blockage or an overload in the lymphatic system, causing lymphatic fluid to accumulate in certain areas. This diagnosis was only the beginning of understanding what my body was experiencing, and it came too late in my journey.

One month into lymphedema treatment, I lost complete mobility, and have been working to regain it ever since. However, this was the beginning of me getting the answers that I truly needed. I was blessed to meet a few specialized doctors and therapists who were able to immediately diagnose my condition accurately. It was lipedema.

“Finally, a diagnosis. Finally, hope. Finally, not feeling like the doctor is looking at me with scathing judgment and ridicule.”

According to The Lipedema Foundation, “Lipedema is a chronic medical condition characterized by a symmetric buildup of adipose tissue (fat) in the legs and arms. A common but underrecognized disorder, Lipedema may cause pain, swelling, and easy bruising. It may be accompanied by an unusual texture within the fat that can feel like rice, peas, or walnuts beneath the surface of the skin. The intensity of pain may range from none to severe, and its frequency may be constant, come and go, or only occur when the fat is pushed on. Limited public awareness of Lipedema, coupled with few research-backed treatments, can lead to exacerbation of symptoms as well as physical and emotional distress. Common symptoms include fatigue, muscle pain, or easy bruising.”

Finally, a diagnosis. Finally, hope. Finally, not feeling like the doctor is looking at me with scathing judgment and ridicule. Someone understood that losing weight wasn’t going to simply make the pain go away and that my fat wasn’t normal.

They understood that I had been through a lot just to get a diagnosis, and they helped me learn how to care for my lipedema body. More specifically, in my case, lipo-lymphedema, or lipedema that has progressed to the point of affecting your lymph system as well. It was late, but it’s not ever too late to initiate positive changes.

I now know lipedema has been shown to be resistant to dietary and exercise interventions. And while research suggests bariatric surgery may result in a reduction of total fat mass, this loss of mass is less likely to reduce volume in lipedema-affected areas or ease other symptoms such as pain.

I began learning techniques to help my lymphatic system. Certain foods and exercises affect my body more positively than others. I learned that certain activities cause my body greater stress than others. I am learning to take care of my lipedema body overall, instead of just focusing on weight loss.

But what about the rest? If I “just lose weight,” will the emotional damage go away?

Shedding the internal critic has been as hard as it is to get rid of an addiction. I beat myself up for every “cheat day,” every day that I don’t make it to the gym, every time my stamina won’t endure as long as a smaller person. I have to intentionally change the internal dialogue and remind myself that I am a human who is combating a medical condition.

Instead of losing weight, I focus on dealing with lipedema. I also focus on connecting with others who are treating or suffering from the same condition. This has resulted in the most sustainable reduction in my weight yet. But the result that mattered the most was finally gaining hope.

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August 11, 2023
Best Shoes For Arthritic Feet + What Shoes To Avoid

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Cunha describes arthritis as acute or chronic inflammation of a joint and its surrounding soft tissues.

Osteoarthritis, rheumatoid arthritis, and post-traumatic arthritis are all the three major types of arthritis that commonly affect the foot and ankle.

Osteoarthritis is most commonly experienced in those middle-age and older, but can sometimes occur in younger people. Also known as degenerative arthritis, this is when the cartilage in the joint begins to wear away gradually, which can cause the painful sensation of bone rubbing on bone. In osteoarthritis, pain and stiffness worsens with time.

Rhematoid arthritis, on the other hand, is a chronic autoimmune disease, meaning it occurs from the immune system attacking its own tissues. It can affect multiple joints throughout the body but commonly begins in the foot and ankle. While the exact cause is not known, rheumatoid arthritis is typically triggered by an infection or environmental factor.

Posttraumatic arthritis can emerge after a specific injury in the foot or ankle, such as dislocation or a fracture. The impact is similar to osteoarthritis, with the cartilage wearing away between the joints. Even with proper treatment, an injured joint is almost seven times more likely than an uninjured joint to develop arthritis.

Per Cunha, arthritis in your feet can cause discomfort or pain that can eventually lead to limited motion, loss of joint function, and deformities in your affected joints.

“In arthritis, progressive joint deterioration occurs and the smooth, gliding surface covering the ends of bones (cartilage), which serves to cushion the joint, is gradually lost, resulting in the bones wearing against each other,” he explains.

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Renee Cherry

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August 9, 2023
Advances in Physical Therapy Offer Unexpected Paths to Recovery

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Newswise — At LifeBridge Health Physical Therapy in collaboration with NovaCare Rehabilitation, individuals are discovering new and unexpected ways that physical therapy can transform their quality of life.

“The majority of our patients are orthopedic patients, injured athletes, and people living with general aches and pains,” says Market Manager Todd Shrager, P.T., A.T.C. “But our collaboration with a national leader like NovaCare keeps us at the forefront of physical therapy research and enables the therapy team to bring an entire roster of unique services and specialists to the community.”
The roster is indeed diverse, with services ranging from concussion management and aquatics therapy to hand therapy and vestibular rehabilitation (for patients living with inner ear disorders). But perhaps the most unique service is ReVital, the industry’s first cancer rehabilitation program, which is specially designed to help patients manage and recuperate from the often-harsh side effects of chemotherapy, radiation and surgery.

“Our ReVital therapists are trained and certified to understand not only what cancer can do to the body, but also what cancer treatment can do,” explains Shrager. “It’s a holistic, full-body approach that’s focused on survivorship and wellness even after the patient’s treatment ends.”

As part of the ReVital program, physical therapists work closely with the cancer care teams at Carroll, Northwest and Sinai hospitals to create a seamless, comprehensive
care plan for each patient. It’s a level of collaboration that Shrager says is true of all LifeBridge Health Physical Therapy services.

“There’s a wonderful continuity of care between us and our patients’ physicians at all of our locations because we are part of the LifeBridge Health family,” he says.

Collaborative Care for Athletes
NovaCare and LifeBridge Health have expanded their collaboration to bring medical resources to local athletes throughout the region. In addition to LifeBridge Health’s ongoing partnerships with Loyola University and Carroll County High School Athletics, the LifeBridge Health Sports Medicine team has recently become the official medical provider for The Baseball Warehouse, Pipeline Soccer Club and Baltimore Celtic Soccer Club. Together, NovaCare and LifeBridge Health will help athletes with injury prevention and treatment through physician access, athletic training, physical therapy and education.

Heal Without the Hassle
LifeBridge Health Physical Therapy makes recovery easier with 18 full-service locations throughout the community. Click here to find the location nearest you.

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LifeBridge Health

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August 4, 2023
Structure of Opioid Receptors May Reveal How to Better Design Pain Relievers, Addiction Therapies

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Newswise — Opioids remain the most potent and effective pain relievers in medicine, but they’re also among the most addictive drugs that can halt a person’s ability to breathe during an overdose — which can be deadly. Researchers have been racing to develop safer pain reliever drugs that target a specific opioid receptor, called the kappa opioid receptor, that is only found in the central nervous system and not elsewhere in the body, like other opioid receptors. Previous research suggests that such drugs may not lead to addiction or death due to overdose, but the currently known drugs that target these kappa opioid receptors have their own set of unacceptable side effects, including depression and psychosis.

In one of the first steps towards eventually developing a new wave of kappa opioid receptor drugs without these side effects, researchers at the University of Maryland School of Medicine and Washington University have mapped the 3D structure of the central nervous system specific kappa opioid receptor and figured out how it differs from the other opioid receptors. In this new study, they discovered what instructs the kappa opioid receptor to change its shape, which uniquely binds to opioid drugs, akin to a lock fitting with a specific key.

They published their results in the May issue of Nature.

Aside from relieving pain, opioid receptors are also involved in everything from sensing taste and smell to digestion and breathing, as well as responding to many of the body’s hormones. The way that opioid receptors can influence so many functions around the body is by acting with one of seven cell activity proteins, known as G-alpha proteins, that each help to specialize the function they suppress in the cell.

“Knowing how these drugs interact with opioid receptors and having a clear view of this molecular snapshot is critical for allowing researchers to develop more effective pain-relieving drugs. This requires a drug that binds to the right type of opioid receptor, such as one in the central nervous system to reduce pain versus the ones that interact in the gut, causing side effects like constipation,” said study corresponding author Jonathan Fay, PhD, Assistant Professor of Biochemistry and Molecular Biology at UMSOM. “Additionally, these next generation medications will need to be designed with the appropriate kind of G-alpha protein in mind, as this will help to precisely target location and cell function by determining the specific shape of the opioid receptor — so the drug only reduces pain without affecting other body functions.”

The known kappa opioid receptor drugs do not produce the same euphoria as traditional opioid drugs, making these kappa opioid receptor drugs less likely to be addictive.

For the current study, the researchers used cryogenic electron microscopy in order to visualize the structure of the kappa opioid receptor. They first needed to flash freeze the receptors, which were bound to a hallucinogenic drug with one of two of the traditional G-alpha proteins. They then used a different drug to see how the kappa opioid receptor interacted with two other types of G-alpha proteins; one of these G-alpha proteins is found only in the central nervous system and the other is used to detect taste and smell.

Dr. Fay described the G-protein as shaped like a chainsaw with a handle and a ripcord. Each G-protein had a slightly different position of its chainsaw handle when bound to the kappa opioid receptor. This change in position played an active role in determining the shape of the kappa opioid receptor and thus what drug bound the best to it. These findings ultimately could have implications for how new drugs will be designed.

UMSOM Dean Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor, said, “Researchers face an enormous challenge in developing safer pain-reliever drugs since they will need to target both the correct opioid receptor as well as the appropriate G-alpha protein. Studies like these reinforce the mission of our new Kahlert Institute for Addiction Medicine, which aims to help develop this next generation of engineered small molecule drugs that are less addictive.

The research was supported by National Institutes of Health grants from the National Institute of General Medical Sciences (R35GM143061) and the National Institute of Neurological Disorders and Stroke (R01NS099341). The Titan X Pascal graphics card used for this research was donated by NVIDIA.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world — with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

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University of Maryland School of Medicine

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July 27, 2023
6 Ways to Improve Your Back Pain
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When Deanne Bhamgara took a tumble off her electric scooter on a pier in San Diego, she didn’t make much of it at first. The fall left her sore, but she felt only little pain.

But over the next several days, she slowly began to hurt more and more.

“What started as a tingling sensation in my thighs had soon become sensitive to touch,” says Bhamgara, 28. The San Francisco resident later learned that the fall affected her lower back, tailbone, pelvic areas, and her hip joints. In a few days, Bhamgara’s pain had radiated to the rest of her back and to the thighs as well.

Almost all Americans get back problems at one time or another. You might sleep awkwardly or wrench your back while lifting something heavy. Or, like Bhamgara, you might hurt your back in an accident. But often, says physical therapist Eric Robertson, DPT, the culprit is too much sitting and not enough moving.

“We’re largely a sedentary society, and so that sedentary lifestyle is the primary thing that we have to work on,” says Robertson, who also is a spokesperson for the American Physical Therapy Association (APTA). “So any sort of movement exercise, walking, working with a physical therapist to give you an individualized customized program is a great idea.”

When Bhamgara went to doctors, physical therapists, and chiropractors about what to expect with her recovery, they gave her conflicting opinions. It might take 6-12 weeks, she heard, or it could take a full year before she was back to normal.

“I was mostly in bed after the pain started,” Bhamgara says. She had inflammation on her thighs right up to behind the knees, groin, butt, lower back, and sometimes in her shoulders.

Confused and worried, Bhamgara tried a host of treatments to ease her pain. She went to physical therapy twice a week. She got trigger point massage and acupuncture, which she said helped.

Bhamgara is now on the mend. She understands it’ll take time and effort to fully heal and to keep her inflammation in check.
Robertson of the APTA says feeling better with back pain doesn’t have to be complicated. Here are some effective steps:

Avoid bed rest. Studies show that lying down too much can slow recovery and raise the pain.

“Over the last 25 years or so, probably the one thing we’ve learned definitively about back pain and bed rest is that is not OK,” says William Lauretti, DC, an associate professor at New York Chiropractic College and a spokesperson for the American Chiropractic Association. Instead, “you want to be as active as you can be with your back pain.”

Move. You may not want to move when you’re in pain, but it’s important to do as much as you can handle.

Robertson says most back pain isn’t serious, even if it may be very painful. “So not being afraid of motion and continuing to move despite the pain is something that’s really important,” he says. Walking is a good choice you can do on your own. You also can work with a physical therapist to learn how to spot dangerous levels of pain and which moves are best for you.
Keep good posture. Pay attention to the way you hold your back when you sit, stand, walk, sleep, or do day-to-day activities. Good posture is when all the bones in your spine are correctly aligned. Poor posture can leave your back stiff and tense. This often to leads to back pain.

Lauretti offers these tips on posture:

Don’t sit up in your bed hunched over your laptop. That’s a surefire recipe for back pain over time.

If you must sit for a long time, use cushioned chairs. Hard seats won’t support your back and may prevent you from sitting up straight.

Use a comfortable desk and chair if you need them while working.

Here are some general tips to maintain good posture:

Keep your feet shoulder-width apart.

Tuck your stomach in when you’re standing.

If you’re standing for too long, regularly shift your weight from one foot to the other and from your toes to heels.

Roll your shoulders back.

Let your arms hang naturally on the sides of your body.
Sleep smart. The ideal bed, Lauretti says, is one that’s “comfortable for you.” As for the best sleep posture, he says on your side or back is easier on your back than sleeping on your belly. If you’re face down, your head will be turned all night so you can breathe, which can lead to neck pain.

Bhamgara says tucking a pillow between her legs to help align her hips lessens her back pain.

Relax. Back pain can be linked to stress, tension, and other non-physical problems, Robertson says. Massages and acupuncture may help loosen muscles. Yoga, meditation, and other mindfulness practices may help lift your mood, stretch your muscles, and make you relax so you can better manage your back pain.

Bhamgara says mediation made her feel alive, especially when her back pain made it painful to move freely.

“I would think about healing every inch of my body,” she says. “There were times I would imagine myself walking in a park with my headphones on and just dancing! That brought me life.”

Call your doctor. If your back pain doesn’t go away after 4 weeks or if you have long-term pain that lasts beyond 12 weeks and keeps you from carrying on with your daily activities, see your doctor. They can help pinpoint the cause of your pain and may suggest new therapies. Get medical attention right away if your legs tingle, feel numb, or weak.

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July 25, 2023

Anesthesiologists Denounce Another Year of Medicare Payment Cuts, Urge Immediate Reforms

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Newswise — The American Society of Anesthesiologists (ASA) condemned yet another year of cuts to Medicare payments for critically important anesthesia and pain medicine services. The proposed cuts, announced in the Centers for Medicare & Medicaid Services’ (CMS) 2024 Physician Fee Schedule (PFS), represent the fifth consecutive year of either a pay freeze or payment cut for the services anesthesiologists provide to their patients as shown in the table below. The CMS-proposed Medicare payment cuts will compound the financial strain anesthesia practices are already facing.

“Yet another year of Medicare payment cuts shows that the Medicare physician payment system is completely broken and unsustainable. A comprehensive overhaul of the Medicare payment system for physicians is long overdue,” said ASA President Michael W. Champeau, M.D., FAAP, FASA. “The Medicare payment rates are grossly inadequate due to egregious flaws in the government formula used to calculate physician payment rates. These inadequate payment rates, rising practice costs, and COVID-19 pandemic-related financial pressures seriously threaten physicians’ practice survival and patient access to care. Congress must act.”

Within the fee schedule, CMS has proposed an anesthesia conversion factor (CF) of $20.370, representing a decrease of 3.26% from the 2023 anesthesia CF of $21.1249. The 2024 proposed Resource-Based Relative Value Scale (RBRVS) CF is $ 32.7476. This represents a decrease of 3.36% from the 2023 CF of $33.8872. CMS established this decrease due to a statutorily mandated budget neutrality adjustment for changes in work relative value units (RVUs) and practice expense updates.

Anesthesia and Resource-Based Relative Value Scale (RBRVS) Conversion Factor Trends

	Anesthesia CF	% Change	RBRVS CF	% Change
2017	$22.0454	–	$35.8887	–
2018	$22.1887	0.7%	$35.9996	0.3%
2019	$22.2730	0.4%	$36.0391	0.1%
2020	$22.2016	-0.3%	$36.0896	0.1%
2021	$21.5600	-2.9%	$34.8931	-3.3%
2022	$21.5623	0.0%	$34.6062	-0.8%
2023	$21.1249	-2.0 %	$33.8872	-2.1%
2024*	$20.4370	-3.3%	$32.7476	3.4%

* CY 2024 Proposed CF

Each of these cuts compounds the financial hurt anesthesiologists and their practices are facing with Medicare payments. Although legislation passed in 2023 provided for a 1.25% update to the conversion factor for CY 2024, this is less than the 2.5% update Congress approved for CY 2023. Absent congressional action, new cuts will be effective January 1, 2024.

ASA is committed to advocating for changes to the broken Medicare payment system to ensure anesthesiologists and other pain medicine physicians are paid fairly for the services they provide to their patients. ASA has strongly endorsed a legislative effort – H.R. 2474, the Strengthening Medicare for Patients and Providers Act, that would provide an inflationary adjustment to Medicare payments so that compensation for physicians and other clinicians matches the rising cost of the health care services they are providing. ASA has also strongly encouraged Congress and policymakers to re-evaluate the flawed budget neutrality clauses of the PFS that greatly restrict payment increases and cause continued payment cuts for many critical health care services. ASA looks forward to advocating our position before Congress and in working with CMS and other government stakeholders on proposed solutions.

Finalized provisions will become effective on January 1, 2024.

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July 13, 2023

CBD exposure during pregnancy can potentially harm a developing fetus – Medical Marijuana Program Connection

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Researchers at the University of Colorado Anschutz Medical Campus have found that cannabidiol (CBD), often used to treat anxiety and nausea, can potentially harm a developing fetus.

The paper was published in Molecular Psychiatry today.

People consume cannabis or a non-psychoactive component cannabidiol (CBD) to help with nausea and anxiety during pregnancy because they think it is safe and healthy. But CBD crosses the placenta and accumulates in the fetal brain.

Until now, no one knew how fetal exposure to CBD affected brain development, said Emily Bates, PhD, an associate professor at the University of Colorado School of Medicine and lead author of the study.

“We found oral consumption of a high dose of CBD during pregnancy impaired problem solving in female mice,” said Bates, who worked with Karli Swenson, a graduate student in her lab.

Along with fellow researchers, Won Chan Oh, PhD, Luis Gomez-Wulschner and Victoria Hoelscher, the team discovered that fetal exposure to CBD reduced the excitability of the pre-frontal cortex, a part of the brain important for learning.

They also found that increased pain sensitivity occurred only in male mice while cognitive impairments happened only in females. Bates said more research is needed to understand why the effects of CBD are sex-specific.

The perceived benefits of CBD are widely accepted in the U.S. where many view it as a safe alternative for treating the nausea, anxiety, and pain associated with…

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July 11, 2023
Tip Sheet: Understanding cancer-related pain, newborn screening for deadly immune disorder — and new Fred Hutch leadership

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Newswise — SEATTLE — July 6, 2023 — Below are summaries of recent Fred Hutchinson Cancer Center research findings and other news.

If you’re looking for resources who can comment on skin cancer awareness and skin protection during the summer months, see our list of experts and reach out to [email protected] to set up interviews.

Cancer research and care

Pinpointing pain: Is it cancer or cancer treatment? Distinguishing side effects of cancer treatment from potential metastatic recurrence can be difficult. In a Q&A, Dr. Hanna Hunter, medical director of cancer rehabilitation at Fred Hutch, s best practices on how doctors and patients can work together to manage pain symptoms.

American Society of Clinical Oncology Annual Meeting 2023 highlights: Fine-tuning cancer care Fred Hutch researchers at ASCO’s annual meeting d their latest findings in cellular immunotherapy, early detection cancer screening tests, interplays between the microbiome and genetics in colorectal cancer and more.

Cancer Health Equity Podcast: Nurses in cancer care The latest episode of Fred Hutch’s Office of Community Outreach and Engagement’s monthly podcast explores the role of nurses in cancer care and how they’re part of working toward health and well-being for everyone. Two Fred Hutch nurses on the blood and bone marrow transplant team — Arlyce Coumar and Jennifer Lynch — their stories of working with patients and families, as well as educating other nurses. They also discussed how nurses are getting more engaged in advocating for policies in health care. Fred Hutch community health educators Aden Afework, who works with African-American populations, and Snowy Johnson, who works with Indigenous populations, moderated the discussion.

Severe combined immunodeficiency A new analysis published in The Lancet shows that newborn screening is the biggest factor in preventing deaths from the rare inherited disorder called severe combined immunodeficiency, also known as “bubble boy disease.” Babies born with SCID appear healthy at birth but are vulnerable to infections and usually die within the first two years of life unless they’re treated with immune-restoring treatment, such as stem cell transplant. Dr. Monica Thakar, pediatric bone marrow transplant physician, led the analysis which was published June 20. Read more in a National Institute of Allergy and Infectious Disease news release .

Diversity, equity and inclusion

Me Loving You: Themes of healing and moving forward Fred Hutch celebrated the start of Pride month with its fourth art installation as part of the Public Art & Community Dialogue Program featuring artist Ariadne Campanella. Initiated by Fred Hutch’s DEI Core, the program commissions artwork from artists representing diverse communities with the aim of engaging Fred Hutch employees and the broader community in conversations of solidarity with underrepresented groups. Campanella, a queer, non-binary trans woman and mixed media artist, was selected to create a piece focusing on LGBTQIA+ communities as they reflect on healing and moving from surviving to thriving.

New Fred Hutch leaders

Dr. Sara Hurvitz joins Fred Hutch, University of Washington Breast oncologist Dr. Sara Hurvitz has been named the new senior vice president of the Clinical Research Division at Fred Hutch and head of the Division of Hematology and Oncology at the University of Washington Department of Medicine. She will begin her role Aug. 1. Currently at UCLA, Hurvitz is an international expert in breast oncology and a leader in clinical and laboratory-based oncology research, with extensive experience in leading clinical trials spanning all phases.

Fred Hutch announces new member, leadership on board of directors Fred Hutch announced one new member of its board of directors and its newly elected chair and vice chair. Pete Shimer, chief operating officer at Deloitte, will join the board. Leigh Morgan, chief strategy and operating officer at the Nia Tero Foundation, has been appointed the new chair of the board of directors, and Sean Boyle, chief operating officer at Omniva, has been appointed vice chair.

Awards and grants

Dr. Mroj Alassaf named a 2023 Helen Hay Whitney Fellow Dr. Mroj Alassaf, postdoctoral fellow in Dr. Akhila Rajan’s lab, received a 3 year $215,000 Helen Hay Whitney foundation fellowship. Her work focuses on how mitochondrial components from fat can reach the brain and what influence they have on its health. A neurobiologist by training, Alassaf joined Rajan’s team after showing in her graduate work how a new mitochondrial protein contributes to neuronal health.

Dr. Sita Kugel receives V Foundation Translational Research Award Pancreatic cancer researcher Dr. Sita Kugel has received an inaugural Translational Research Award from the V Foundation for Cancer Research. The $800,000, four-year grant will allow Kugel to pursue an innovative Phase 1b clinical trial to translate from the lab to the clinic breakthroughs her group has made in developing a tailored treatment for a subtype of pancreatic cancer.

Dr. Cecilia Moens elected inaugural member of the Society for Developmental Biology Academy Developmental biologist Dr. Cecilia Moens joins nine other scientists elected to the newly created Society for Developmental Biology Academy. Moens work focuses on using zebrafish as a model to study the genes that control the brain’s early development. Her current research looks at how immature neurons make their connections to muscles and other neurons in the process of building functional circuits.

Lung cancer expert Dr. McGarry Houghton receives Satya and Rao Remala Family Endowed Chair Dr. McGarry Houghton, a pulmonary physician-scientist, studies the immune system’s role in cancer and lung cancer early detection. He was named the first recipient of the Satya and Rao Remala Family Endowed Chair, which provides support for a researcher working on both lung cancer and the promotion of equitable access to health and education. Houghton is pursuing a plasma-based diagnostic tool that would be used in conjunction with CT screening for lung cancer early detection.

Virus researchers Cohn and Blanco-Melo win coveted grants Drs. Lillian Cohn and Daniel Blanco-Melo are both early career scientists studying viruses and recently received support for their work through scholar programs. Cohn was named a biomedical scholar by the Pew Charitable Trust and Blanco-Melo was named a Searle scholar. Cohn’s research focuses on finding ways to cure HIV/AIDS by eradicating reservoirs of latently infected blood cells that persist despite continuous therapy with antiviral drugs. Blanco-Melo focuses on exploring how viruses evolve and how the human immune response to them changes over time.

Science spotlight Sci ence Spotlight is a monthly installment of articles written by postdoctoral fellows at Fred Hutch that summarize new research papers from Fred Hutch scientists. If you’re interested in learning more or covering these topics, contact: [email protected]

# # #

Fred Hutchinson Cancer Center unites individualized care and advanced research to provide the latest cancer treatment options and accelerate discoveries that prevent, treat and cure cancer and infectious diseases worldwide.

Based in Seattle, Fred Hutch is an independent, nonprofit organization and the only National Cancer Institute-designated cancer center in Washington. We have earned a global reputation for our track record of discoveries in cancer, infectious disease and basic research, including important advances in bone marrow transplantation, immunotherapy, HIV/AIDS prevention, and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services and has network affiliations with hospitals in four states. Fred Hutch also serves as UW Medicine’s cancer program.

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July 7, 2023
Best Lumbar Support Pillows Of 2023, Medically Reviewed

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If you’ve ever experienced lower back pain, you know how persistent (and, well, incredibly painful) it can be. You can try your best to ignore it, but chances are, you’ll find the pain affecting your everyday life—especially when sitting down. To find some reprieve in your day to day, the best lumbar support pillows can make all the difference.

Ideally made from memory foam—or another material that cradles the natural curvatures of the body—these types of pillows support your lower back while you’re sitting in your home, office, car, or public transportation. Research shows that a lumbar support pillow can ease back pain 1, essentially ensuring a better posture and relieving discomfort at the source.

Below, find our selections for the best lumbar support pillows of 2023, in addition to expert advice from physical therapists and sleep specialists on what to look for and how to get the most out of your pillow.

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Caitlyn Martyn

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June 15, 2023
Women exhibit greater loss sensitivity in risky choices: study

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Newswise — Women are less willing to take risks than men because they are more sensitive to the pain of any losses they might incur than any gains they might make, new research from the University of Bath School of Management shows.

Published in the British Psychological Society’s British Journal of Psychology, the study – “Gender differences in optimism, loss aversion and attitudes toward risk” – also finds that men are ‘significantly’ more optimistic than women, making them more willing to take risks.

Researcher Dr Chris Dawson, associate professor in business economics at the University of Bath School of Management, said the findings were significant and could help explain sex-specific outcomes in different employment sectors, and in financial markets.

‘It is widely acknowledged that men, across many domains, take more risks than women. These differences in how the sexes view risk can have significant effects,” Dr Dawson says.

‘For instance, differences between the sexes in risk taking can explain why women are less likely to be entrepreneurs, are underrepresented in high-paying jobs and upper management, and less likely to invest their wealth in equities markets than men. Despite these important implications, we still know very little about why women take fewer risks than men.

“My research attempts to fill that gap. When thinking about risky choices, people tend to assess the probability of losing something alongside an evaluation of how painful that loss would be. I found that women take less risks than men as they focus more on the possibility of losing and anticipate experiencing more pain from potential losses,” he adds.

Previous research suggests that women are more risk averse than men, and this study investigated the joint role of two psychological characteristics to explain the differences – loss aversion, the idea that losses loom larger than gains, and optimism.

To measure loss aversion, Dr Dawson used data from 13,575 people from the UK British Household Panel Survey to assess how changes in household income from one year to the next predict changes in psychological wellbeing.

He found that income losses are less painful for men than for women with no difference in the psychological responses to income gains between the sexes.

When asked how they saw themselves financially a year from now with expectations about outcomes under the individual’s control, men were significantly more optimistic than women.

The research indicates that this optimism may be linked to men’s overconfidence about their abilities compared to women which previous studies have highlighted.

If women are both less optimistic about the probability of favourable outcomes occurring and less confident in their abilities than men, they will naturally evaluate a given gamble as being riskier, the research says.

Overall, the study finds that women report a lower willingness to take risks than men with 53 percent of this gap accounted for by the higher levels of loss aversion amongst women and a further 3 per cent attributable to the lower levels of financial optimism amongst women.

Loss aversion and optimism still have significant effects on risk attitudes even after controlling for the personality traits such as openness, neuroticism and extraversion.

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June 9, 2023
Mattress For Side Sleepers: 6 Best For Alignment & Pain, From PTs

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Side sleeping is the most common sleep position, and experts agree that it’s typically also the healthiest. chiropractor Kevin Lees, D.C., of The Joint Corp, explains that sleeping on one’s side provides relief from back pain and may reduce one’s risk of breathing problems like sleep apnea, while Park notes that it tends to promote good circulation. However, the sleeping position also comes with some potential downsides.

The key to restful, restorative sleep is to keep your spine, neck, and shoulders all in good alignment. But picture the shape of someone sleeping on their side: The widest parts of their body, their shoulders and hips, will naturally want to sink deeper into a mattress.

If your mattress is super firm and doesn’t have enough give, you might wake up with shoulders and hips that feel sore or stiff in the morning. If it’s really soft, your shoulders and hips may sink too far into your mattress and throw off that ever-important alignment, which can irritate your joints and ligaments and contribute to low back pain.

“If you have too soft of a mattress, regardless of your sleep position, your body kind of gets absorbed into that,” physical therapist and founder of Aletha Health Christine Koth, PT says. “It might feel good, but your body has to do absolutely no work. Without a little bit of muscle contraction to stabilize you, you actually lose some of the support that your body needs.”

From head to toe, experts say side sleepers should aim for the following alignment when sleeping:

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Emma Loewe

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June 6, 2023
Reasons To Make This Soothing THC Topical Gel Your New Daily Ritual

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To better understand the reasons for adopting a THC topical into our wellness routine, we connected with Jessie Kater, Sr. Vice President of Innovation, Research & Development at Curaleaf. “Topicals can be a good alternative route of administration for some people that maybe less inclined to inhale or ingest cannabis. The Plant Precision Relieve Topical Gel is a great choice for those looking for some localized relief, and as some of it gets absorbed into the bloodstream, it can also help provide systemic relief and relaxation, making it a great multi-functional option.”

Another benefit of Plant Precision Relieve Topical Gel is that it’s lightweight on your skin, whereas many THC topicals out there feel heavy. THC is a highly lipophilic compound, meaning it has an affinity for lipid environments and dissolves more easily in fat than it does water. Because of this, many gels have a hard time permeating beyond the watery layers of our skin. But according to Jessie Kater, Sr. Vice President of Innovation, Research & Development at Curaleaf, their Plant Precision Relieve Topical Gel includes food grade ethanol and permeation enhancers. In-house proprietary research indicates that these enhancers assist in carrying cannabinoids across the layers of skin into deeper tissue and blood vessels where it is then circulated systemically. This doesn’t just imply a lighter gel, it also means you’ll start to feel a calming “body high” tingle.

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Devon Barrow

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June 5, 2023
New Research Reveals How Exercise Can Increase Pain Tolerance

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Published in the latest version of PLoS ONE, this study 1 was performed on a group of more than 10,000 adults in Norway from the University Hospital in Tromsø.The researchers had the participants self-report their activity levels and then measured their pain tolerance.

How’d they do that? Each participant submerged their hand in freezing cold ice water and then ranked their pain on a scale. Researchers measured pain tolerance two times across eight years.

In the end, participants that reported a more active lifestyle ranked the pain of the icy water lower. More frequent exercisers were also able to keep their hand in the water for about 20 seconds longer than the mostly sedentary group.

There was a dose-response trend too, which means the more often they exercised, the more this resilience to pain grew. Interestingly, participants who increased their activity level over the eight-year study period also showed increased tolerance to pain over time.

RELATED: The Best Workouts For Longevity & How Often To Do Them, From An MD

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Gretchen Lidicker, M.S.

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June 2, 2023
MD Anderson Research Highlights for May 24, 2023

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Newswise — HOUSTON ― The University of Texas MD Anderson Cancer Center’s Research Highlights showcases the latest breakthroughs in cancer care, research and prevention. These advances are made possible through seamless collaboration between MD Anderson’s world-leading clinicians and scientists, bringing discoveries from the lab to the clinic and back.

Recent developments include a new treatment option for relapsed/refractory mantle cell lymphoma, a better understanding of protein variants that trigger tumor cell death and activate antitumor immunity, insights into the relationship between sickle cell trait and renal medullary carcinoma, clearer awareness of the clinical relevance of CD8 T cell state in acute myeloid leukemia, and an understanding of the distinct neuronal pathways triggered by chemotherapy and nerve injury.

Phase I/II trial shows safety and efficacy of pirtobrutinib in advanced MCL
Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) – an aggressive subtype of B-cell non-Hodgkin lymphoma – initially respond well to covalent Bruton tyrosine kinase inhibitors (cBTKis) but eventually develop resistance, underscoring the need for more effective therapeutic strategies. Pirtobrutinib – a highly selective non-covalent BTKi – inhibits both normal and mutant BTK, providing a potential alternative. In a first-in-human Phase I/II clinical trial, researchers led by Michael Wang, M.D., examined the safety and efficacy of pirtobrutinib monotherapy in 90 patients with R/R MCL who previously received cBTKi treatment. The objective response rate was 57.8%, including 20% with complete responses, and the 12-month estimated duration of response rate was 57.1%. The most common side effects were fatigue, diarrhea and dyspnea. Grade 3 adverse events were infrequent and only 3% of patients discontinued treatment. The study demonstrated that pirtobrutinib was safe and showed durable efficacy in R/R MCL. Based on this data, the Food and Drug Administration granted accelerated approval for pirtobrutinib in R/R MCL in Jan. 2023. Learn more in the Journal of Clinical Oncology.

Specific protein variants trigger cancer cell death and improve antitumor response
The gasdermin B (GSDMB) protein can trigger cancer-associated pyroptosis – a form of programmed cell death that activates antitumor immune responses – but its exact role is controversial. The protein has multiple variants created from mRNA splicing, and these can have either anti- or pro-tumor functions. In this study, researchers led by Qing Kong, Ph.D., and Zhibin Zhang, Ph.D., examined six GSDMB splicing variants to provide insights into which are involved in pyroptosis. Relative to other variants, isoforms 3/4 were cytotoxic for tumor cells, triggering pyroptosis and resulting in better antitumor outcomes in bladder and cervical cancer models. The study suggests that tumors may be preferentially generating non-cytotoxic GSDMB variants in order to protect against pyroptosis. It also highlights the potential for therapeutic strategies that can increase production of cytotoxic GSDMB variants to improve antitumor immunity and enhance immunotherapy response. Learn more in Science Immunology.

Link between sickle cell trait and SMARCB1 loss observed in renal medullary carcinoma
Renal medullary carcinoma (RMC) is a rare and aggressive form of kidney cancer that typically develops in young adults with sickle cell trait (SCT). Loss of the SMARCB1 tumor suppressor is a defining characteristic of RMC tumors. To better understand the mechanisms driving RMC and to improve treatment options, researchers led by Giannicola Genovese, M.D., Ph.D., Pavlos Msaouel M.D., Ph.D., and Melinda Soeung, Ph.D., investigated whether the loss of SMARCB1 provides a survival advantage in the presence of SCT. They demonstrated that a lack of oxygen induced by SCT leads to SMARCB1 degradation, protecting cells from hypoxic stress. The results suggest that SMARCB1 loss improves the survival of RMC cells under hypoxia, potentially explaining why SMARCB1-deficient tumors are resistant to therapeutic agents targeting hypoxia pathways. These insights may help researchers develop more effective treatments against RMC. Learn more in Proceedings of the National Academy of Sciences.

CD8 T Cells in AML display continuous differentiation and clonal hyperexpansion
Limited research is available on CD8 T cell exhaustion in hematologic cancers, specifically acute myeloid leukemia (AML). In a study led by Hussein Abbas, M.D, Ph.D., researchers characterized CD8 T cells from healthy donors as well as newly diagnosed (NewlyDx) and relapsed/refractory (R/R) AML patients. They discovered very few “exhausted” cells, with effector CD8 T cells from NewlyDx and R/R patients having different cytokine and metabolic profiles than the classic exhaustion signature seen in solid tumors. Researchers refined a 25-gene signature associated with poor outcomes in previously untreated AML patients, suggesting that the CD8 cell state may be clinically relevant. Analysis of T cell receptor sequencing data also revealed an increase in clonal hyperexpansion in R/R patient cells. The study highlights shared characteristics between CD8 cells in AML and those in solid cancer, suggesting that immune-based therapy in AML is likely to be most successful in earlier stages when CD8 T cells can afford plasticity. Learn more in Cancer Immunology Research.

Chemotherapy and nerve injury induces chronic pain via different sensory neurons
Treatment with chemotherapy is necessary for many patients with cancer, but it can sometimes cause chronic pain similar to traumatic nerve injuries. Studies have shown chemotherapy-induced neuropathy augments glutamate NMDA receptor (NMDAR) activity in the spinal cord, but little is known about the pathways involved. Researchers led by Yuying Huang, Ph.D., Shao Rui-Chen, M.D., and Hui-Lin Pan, M.D., Ph.D., found that chemotherapy triggers NMDAR activity in specific excitatory neurons. Removing NMDAR from these primary sensory neurons diminished chemotherapy-induced pain in laboratory models. Alternatively, chronic pain from traumatic nerve injury mainly resulted from the NMDAR expressed in different spinal neurons. The results suggest that chronic pain following nerve injury and chemotherapy is triggered by the NMDAR in different neurons and pathways, highlighting potential cellular targets to help treat these separate conditions. Learn more in The Journal of Neuroscience.

In case you missed it
Read below to catch up on recent MD Anderson press releases.

– 30 –

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May 24, 2023
Study reveals unique molecular machinery of woman who can’t feel pain

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Newswise — The biology underpinning a rare genetic mutation that allows its carrier to live virtually pain-free, heal more rapidly and experience reduced anxiety and fear, has been uncovered by new research from UCL.

The study, published in Brain, follows up the team’s discovery in 2019 of the FAAH-OUT gene and the rare mutations that cause Jo Cameron to feel virtually no pain and never feel anxious or afraid. The new research describes how the mutation in FAAH-OUT ‘turns down’ FAAH gene expression, as well as the knock-on effects on other molecular pathways linked to wound healing and mood. It is hoped the findings will lead to new drug targets and open up new avenues of research in these areas.

Jo, who lives in Scotland, was first referred to pain geneticists at UCL in 2013, after her doctor noticed that she experienced no pain after major surgeries on her hip and hand. After six years of searching, they identified a new gene that they named FAAH-OUT, which contained a rare genetic mutation. In combination with another, more common mutation in FAAH, it was found to be the cause of Jo’s unique characteristics.

The area of the genome containing FAAH-OUT had previously been assumed to be ‘junk’ DNA¹ that had no function, but it was found to mediate the expression of FAAH, a gene that is part of the endocannabinoid system and that is well-known for its involvement in pain, mood and memory.

In this study, the team from UCL sought to understand how FAAH-OUT works at a molecular level, the first step towards being able to take advantage of this unique biology for applications like drug discovery.

This included a range of approaches, such as CRISPR-Cas9 experiments on cell lines to mimic the effect of the mutation on other genes, as well as analysing the expression of genes to see which were active in molecular pathways involved with pain, mood and healing.

The team observed that FAAH-OUT regulates the expression of FAAH. When it is significantly turned down as a result of the mutation carried by Jo Cameron, FAAH enzyme activity levels are significantly reduced.

Dr Andrei Okorokov (UCL Medicine), a senior author of the study, said: “The FAAH-OUT gene is just one small corner of a vast continent, which this study has begun to map. As well as the molecular basis for painlessness, these explorations have identified molecular pathways affecting wound healing and mood, all influenced by the FAAH-OUT mutation. As scientists it is our duty to explore and I think these findings will have important implications for areas of research such as wound healing, depression and more.”

The authors looked at fibroblasts taken from patients to study the effects of the FAAH-OUT-FAAH axis on other molecular pathways. While the mutations that Jo Cameron carries turn down FAAH, they also found a further 797 genes that were turned up and 348 that were turned down. This included alterations to the WNT pathway that is associated with wound healing, with increased activity in the WNT16 gene that has been previously linked to bone regeneration.

Two other key genes that were altered were BDNF, which has previously been linked to mood regulation and ACKR3, which helps to regulate opioid levels. These gene changes may contribute to Jo Cameron’s low anxiety, fear and painlessness.

Professor James Cox (UCL Medicine), a senior author of the study, said: “The initial discovery of the genetic root of Jo Cameron’s unique phenotype was a eureka moment and hugely exciting, but these current findings are where things really start to get interesting. By understanding precisely what is happening at a molecular level, we can start to understand the biology involved and that opens up possibilities for drug discovery that could one day have far-reaching positive impacts for patients.”

This research was supported by the Medical Research Council (MRC) and Wellcome.

¹So called ‘junk’ DNA describes regions of the genome or non-coding genes that don’t create proteins. They were once thought redundant, but in recent years researchers have begun to discover the role of ‘dark’ regions of the genome in regulating coding genes.

Publication:

Hajar Mikaeili et al. ‘Molecular basis of FAAH-OUT-associated human pain insensitivity’ will be published in Brain and is strictly embargoed until 24 May 2023 01:01 BST / 23 May 2023 20:01 ET.

The DOI for this paper will be: https://doi.org/10.1093/brain/awad098

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May 23, 2023
In 2050, over 800 million people globally estimated to be living with back pain

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EMBARGOED: 08:30 hrs Australian Eastern Standard Time (AEST) Tuesday 23 May 2023 / 23:30 hrs UK (UK) Monday 22^nd May

Study estimates there will be over 800 million cases of low back pain in 2050, a 36 percent increase from 2020. With an ageing population, researchers say we must ‘put the brakes’ on low back pain cases before the burden becomes too great for our healthcare system.

Analysis of over 30 years of the GBD data has shown the number of cases of low back pain is growing, with modelling suggesting by 2050, 843 million people will be affected by the condition largely due to population increases and ageing of populations.

The continued lack of a consistent approach on back pain treatment, and limited treatment options have researchers concerned that this will lead to a healthcare crisis, as low back pain is the leading cause of disability in the world.

In Australia, there will be a nearly 50 percent increase in cases by 2050. The landscape of back pain cases is set to shift, with the biggest increases in back pain cases to be in Asia and Africa.

The findings are published in Lancet Rheumatology today.

“Our analysis paints a picture of growing low back pain cases globally, putting enormous pressure on our healthcare system. We need to establish a national, consistent approach to managing low back pain that is informed by research,” says lead author, Professor Manuela Ferreira from Sydney Musculoskeletal Health, an initiative of the University of Sydney, Sydney Local Health District and Northern Sydney Local Health District.

“Currently, how we have been responding to back pain has been reactive. Australia is a global leader in back pain research; we can be proactive and lead by example on back pain prevention”, said Professor Ferreira who is based at Sydney’s Kolling Institute.

The study reveals several milestones in back pain cases. Since 2017, the number of low back pain cases has ticked over to more than half a billion people.

In 2020, there were approximately 619 million cases of back pain.

At least one third of the disability burden associated with backpain was attributable to occupational factors, smoking and being overweight.

A widespread misconception is that low back pain mostly affects adults of working age. But researchers say this study has confirmed that low back pain is more common among older people. Low back pain cases were also higher among females compared to males.

This is the most comprehensive and up-to-date available data that includes for the first time global projections and the contribution of GBD risk factors to low back pain. The work was made possible by the joint efforts of The University of Sydney, the Institute for Health Metrics and Evaluation (IHME) at the University of Washington’s School of Medicine (healthdata.org), IHME’s international collaborators, and the Global Alliance for Musculoskeletal Health (gmusc.com).

“We also know that most available data come from high-income countries, making it sometimes hard to interpret these results for low to mid-income countries. We urgently need more population-based back pain and musculoskeletal data from countries of low to mid-income,” said senior author Professor Lyn March from Sydney Musculoskeletal Health and the Kolling Institute.

The study analysed GBD data from 1990 to 2020 from over 204 countries and territories to map the landscape of back pain cases over time. The GBD is the most comprehensive picture of mortality and disability across countries, time, age, and sex.

It is also the first study to be used for modelling the future prevalence of back pain cases.

“Health systems need to respond to this enormous and rising burden of low back pain that is affecting people globally. Much more needs to be done to prevent low back pain and ensure timely access to care, as there are effective ways of helping people in pain” said Prof Anthony Woolf, co-chair of the Global Alliance for Musculoskeletal Health which is calling for priority to be given to addressing the growing burden of musculoskeletal conditions.

“Ministries of health cannot continue ignoring the high prevalence of musculoskeletal conditions including low back pain. These conditions have important social and economic consequences, especially considering the cost of care. Now is the time to learn about effective strategies to address the high burden and to act” said Dr Alarcos Cieza, Unit Head, World Health Organization, Headquarters, Geneva

National guidelines will form basis of back pain prevention

In 2018, experts (independent to this study) voiced their concerns in The Lancet and gave recommendations, especially regarding exercise and education, about the need for a change in global policy on the best way to prevent and manage low back pain to stop the rise of inappropriate treatments.

However, since then, there has been little change. Common treatments recommended for low back pain have been found to have unknown effectiveness or to be ineffective – this includes some surgeries and opioids.

Professor Ferreira says there is a lack of consistency in how health professionals manage back pain cases and how the healthcare system needs to adapt.

“It may come as a surprise to some that current clinical guidelines for back pain treatment and management do not provide specific recommendations for older people.”

“Older people have more complex medical histories and are more likely to be prescribed strong medication, including opioids for back pain management, compared to younger adults. But this is not ideal and can have a negative impact on their function and quality of life, especially as these analgesics may interfere with their other existing medications. This is just one example of why we need to update clinical guidelines to support our health professionals.”

Co-author Dr Katie de Luca, from CQUniversity, said if the right action is not taken, low back pain can become a precursor to chronic health conditions such as diabetes, cardiovascular disease and mental health conditions, invasive medical procedures, and significant disability.

“Low back pain continues to be the greatest cause of disability burden worldwide. There are substantial socio-economic consequences of this condition, and the physical and personal impact directly threatens healthy ageing.”

-ENDS-

Declaration: The authors declare no conflicts of interest.

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May 22, 2023

Tag: Pain

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