Arthritis

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Interdisciplinary guidelines to optimise the treatment of childhood arthritis at global level

Acute flaccid myelitis

Interdisciplinary guidelines to optimise the treatment of childhood arthritis at global level

So far, there no uniform guidelines have existed for the treatment of arthritis of the jaw, a potentially debilitating consequence of juvenile arthritis.

Doctors around the world lack insight into how best to treat arthritis of the jaw, which is a frequent and serious consequence of juvenile arthritis.

Now, a team of researchers from Aarhus University, in collaboration with experts from a wide range of international professional groups, have developed a set of interdisciplinary guidelines to optimise the treatment of patients with the disease.

The guidelines have a special focus on early diagnosis and screening, and they can benefit children all over the world, according to Peter Stoustrup, associate professor at Department of Dentistry and Oral Health at Aarhus University.

“A more timely initiation of treatment will result in a better treatment outcome. Untreated, arthritis of the jaw can cause major problems in adulthood, but treatment of the condition has lagged considerably due to uncertainty among health professionals and health systems, so this study is important for all children with jaw arthritis,” he says.

Complicated joint – complicated treatment

Around 1,500 children in Denmark have a diagnosis of juvenile arthritis, which often results in inflammation of the jaw joint. This leads to pain, reduced joint function, and growth disruption in the face, which in severe cases may give rise to sleep apnoea and a need for surgical treatment of the patient’s jaw.

Up until now, it has proved difficult to find an effective treatment for arthritis of the jaw, as it is a complicated joint, and optimal treatment requires the involvement of many different groups of medical professionals, including radiologists, paediatric rheumatologists, physiotherapists, maxillofacial surgeons and orthodontists.

But now, a group of experts from these disciplines has come together to produce common recommendations and guidelines for interdisciplinary collaborative treatment in connection with arthritis of the jaw.

“Health systems are organised in different ways around the world, and the treatments offered have therefore been a bit random. Now, guidelines have been drawn up for optimal collaboration in treating this condition, which can guide the treatment of the individual patient, but also help the health systems to organise themselves in such a way that this interdisciplinary approach to treatment is possible,” explains Peter Stoustrup.

The new recommendations and guidelines are based on the knowledge and evidence available in the area.

The study on which the guidelines are based provides a basis for follow-up research and information work, and the guidelines will be revised as new knowledge becomes available.

Of great value in countries without health insurance

In Aarhus, the interdisciplinary approach to treatment has been normal practice for several years, and researchers from Aarhus University have therefore been the driving force behind the development of the guidelines in the area.

With the recommendations in hand, Peter Bangsgaard Stoustrup says it will be easier to establish centres that practise multidisciplinary treatment for children and young people with arthritis of the jaw.

This will be particularly valuable for patients in countries without public health insurance – for example USA.

“We have on board centres like Boston Children’s Hospital and hospitals in Atlanta and Calgary, who are rolling out the organisational and interdisciplinary approach to this treatment that we are proposing. It is our hope that this can provide inspiration for other centres,” says Peter Bangsgaard Stoustrup.

Posted on Arthritis

Stiff, achy knees? Lab-made cartilage gel outperforms the real thing

Hydrogel-based implant could relieve pain in damaged joints.


Duke researchers have developed a gel-based cartilage substitute to relieve achy knees that’s even stronger and more durable than the real thing. Clinical trials to start next year. Credit: Canva#

Over-the-counter pain relievers, physical therapy, steroid injections — some people have tried it all and are still dealing with knee pain.

Often knee pain comes from the progressive wear and tear of cartilage known as osteoarthritis, which affects nearly one in six adults — 867 million people — worldwide. For those who want to avoid replacing the entire knee joint, there may soon be another option that could help patients get back on their feet fast, pain-free, and stay that way.

Writing in the journal Advanced Functional Materials, a Duke University-led team says they have created the first gel-based cartilage substitute that is even stronger and more durable than the real thing.

Mechanical testing reveals that the Duke team’s hydrogel — a material made of water-absorbing polymers — can be pressed and pulled with more force than natural cartilage, and is three times more resistant to wear and tear.

Implants made of the material are currently being developed by Sparta Biomedical and tested in sheep. Researchers are gearing up to begin clinical trials in humans next year.

“If everything goes according to plan, the clinical trial should start as soon as April 2023,” said Duke chemistry professor Benjamin Wiley, who led the research along with Duke mechanical engineering and materials science professor Ken Gall.

To make this material, the Duke team took thin sheets of cellulose fibers and infused them with a polymer called polyvinyl alcohol — a viscous goo consisting of stringy chains of repeating molecules — to form a gel.

The cellulose fibers act like the collagen fibers in natural cartilage, Wiley said — they give the gel strength when stretched. The polyvinyl alcohol helps it return to its original shape. The result is a Jello-like material, 60% water, which is supple yet surprisingly strong.

Natural cartilage can withstand a whopping 5,800 to 8,500 pounds per inch of tugging and squishing, respectively, before reaching its breaking point. Their lab-made version is the first hydrogel that can handle even more. It is 26% stronger than natural cartilage in tension, something like suspending seven grand pianos from a key ring, and 66% stronger in compression — which would be like parking a car on a postage stamp.

“It’s really off the charts in terms of hydrogel strength,” Wiley said.

The team has already made hydrogels with remarkable properties. In 2020, they reported that they had created the first hydrogel strong enough for knees, which feel the force of two to three times body weight with each step.

Putting the gel to practical use as a cartilage replacement, however, presented additional design challenges. One was achieving the upper limits of cartilage’s strength. Activities like hopping, lunging, or climbing stairs put some 10 Megapascals of pressure on the cartilage in the knee, or about 1,400 pounds per square inch. But the tissue can take up to four times that before it breaks.

“We knew there was room for improvement,” Wiley said.

In the past, researchers attempting to create stronger hydrogels used a freeze-thaw process to produce crystals within the gel, which drive out water and help hold the polymer chains together. In the new study, instead of freezing and thawing the hydrogel, the researchers used a heat treatment called annealing to coax even more crystals to form within the polymer network.

By increasing the crystal content, the researchers were able to produce a gel that can withstand five times as much stress from pulling and nearly twice as much squeezing relative to freeze-thaw methods.

The improved strength of the annealed gel also helped solve a second design challenge: securing it to the joint and getting it to stay put.

Cartilage forms a thin layer that covers the ends of bones so they don’t grind against one another. Previous studies haven’t been able to attach hydrogels directly to bone or cartilage with sufficient strength to keep them from breaking loose or sliding off. So the Duke team came up with a different approach.

Their method of attachment involves cementing and clamping the hydrogel to a titanium base. This is then pressed and anchored into a hole where the damaged cartilage used to be. Tests show the design stays fastened 68% more firmly than natural cartilage on bone.

“Another concern for knee implants is wear over time, both of the implant itself and the opposing cartilage,” Wiley said.

Other researchers have tried replacing damaged cartilage with knee implants made of metal or polyethylene, but because these materials are stiffer than cartilage they can chafe against other parts of the knee.

In wear tests, the researchers took artificial cartilage and natural cartilage and spun them against each other a million times, with a pressure similar to what the knee experiences during walking. Using a high-resolution X-ray scanning technique called micro-computed tomography (micro-CT), the scientists found that the surface of their lab-made version held up three times better than the real thing. Yet because the hydrogel mimics the smooth, slippery, cushiony nature of real cartilage, it protects other joint surfaces from friction as they slide against the implant.

Natural cartilage is remarkably durable stuff. But once damaged, it has limited ability to heal because it doesn’t have any blood vessels, Wiley said.

In the United States, osteoarthritis is twice as common today than it was a century ago. Surgery is an option when conservative treatments fail. Over the decades surgeons have developed a number of minimally invasive approaches, such as removing loose cartilage, or making holes to stimulate new growth, or transplanting healthy cartilage from a donor. But all of these methods require months of rehab, and some percentage of them fail over time.

Generally considered a last resort, total knee replacement is a proven way to relieve pain. But artificial joints don’t last forever, either. Particularly for younger patients who want to avoid major surgery for a device that will only need to be replaced again down the line, Wiley said, “there’s just not very good options out there.”

“I think this will be a dramatic change in treatment for people at this stage,” Wiley said.

Posted on Arthritis, Pain Management

Turmeric – Does It Work For Arthritis And Joint Pain?

Turmeric - Does It Work For Arthritis And Joint Pain? - YouTube

DO NOT TAKE TURMERIC IF YOU ARE ON BLOOD THINNERS. AS ALWAYS, CHECK WITH YOUR HEALTH CARE PROVIDER BEFORE TAKING ANY NEW MEDICATION OR SUPPLEMENT. The surgeons discuss the use of a common spice named turmeric for the treatment of inflammation.

Posted on Arthritis

Why Moringa Superfood Helped Reduce My Rheumatoid Arthritis Joint Pain and Inflammation

Why Moringa Superfood Helped Reduce My Rheumatoid Arthritis Joint Pain and Inflammation - YouTube


In this video, I talk about a superfood that has helped to reduce rheumatoid arthritis joint pain and inflammation in my body. I know there are a ton of superfood trends out there, but this is the real deal with scientific evidence to back it up.



Posted on Arthritis

How one inflammatory disorder exacerbates another

With interactions in the bone marrow, inflammatory disorders exacerbate one another


Inflammation in the gums can increase susceptibility to other forms of inflammation, such as arthritis, through changes to immune cell precursors in the bone marrow, according to new research led by Penn scientists and collaborators. CREDIT Katie Vicari

The immune system remembers. Often this memory, primed by past encounters with threats like bacteria or viruses, is an asset. But when that memory is sparked by internal drivers, like chronic inflammation, it can prove detrimental, perpetuating a misguided immune response.

In a new paper in Cell, researchers from the School of Dental Medicine, together with an international team including colleagues at the Technical University of Dresden, lay out the mechanism by which innate immune memory can cause one type of inflammatory condition—in this example, gum disease—to increase susceptibility to another—here, arthritis—through alterations to immune cell precursors in the bone marrow. In a mouse model, the team demonstrated that recipients of a bone marrow transplant were predisposed to more severe arthritis if their donor had inflammatory gum disease.

“Although we use periodontitis and arthritis as our model, our findings go above and beyond these examples,” says George Hajishengallis, a professor in Penn Dental Medicine and a corresponding author on the work. “This is in fact a central mechanism, a unifying principle underlying the association between a variety of comorbidities.”

The researchers note that this mechanism may also prompt a reconsideration of how bone marrow donors are selected, as donors with certain types of immune memory caused by underlying inflammatory conditions might put bone marrow transplant recipients at a higher risk of inflammatory disorders.

Basis in the bone marrow

In previous work, Hajishengallis had partnered with co-corresponding author Triantafyllos Chavakis of Technical University of Dresden and collaborators to explore the role of innate immune memory. Their findings showed that, just like the adaptive immune system’s T cells and B cells, the innate immune system’s myeloid cells, such as neutrophils and macrophages, could “remember” past encounters, becoming more responsive when exposed to a new threat. The work also pinpointed how this memory was encoded, tracing it to the bone marrow, and showed that this “trained immunity” could be transferred from one organism to another through a bone marrow transplant, protecting recipients from cancer through an innate immune response. 

While that is good news, Hajishengallis and Chavakis also believed that trained immunity could be detrimental in the right contexts. While attending a meeting on innate immunity in Greece in 2019, the two scientists brainstormed over dinner at an outdoor tavern, jotting down their thoughts on a napkin. They later formalized some of their hypotheses about this potential “dark side” of trained immune in a publication in Nature Reviews Immunology in 2021.

“The thoughts went like this: We knew the gum disease periodontitis increased the risk of comorbidities like cardiovascular disease,” says Hajishengallis. “And the reverse is also true: People with the inflammatory disease colitis, for example, have an increased prevalence of periodontal disease. Different mechanisms have been proposed, but no one unifying mechanism could explain this bidirectionality.” 

“We started thinking about a possible unifying mechanism that could underlie the association between several distinct comorbidities,” says Chavakis. 

Building on their earlier discovery related to “trained” precursors in the bone marrow, the scientists set out to see whether they could trace the source of the association between comorbidities to the innate immune training they already knew was happening in the bone marrow.

Setting out to test this hypothesis, the team first showed that, within a week of inducing a mouse to have periodontal disease, the animal’s myeloid cells and their progenitor cells expanded in the bone marrow. Examining these cells weeks later, after periodontitis was intentionally resolved, the researchers did not notice significant changes in how the cells looked or behaved. 

However, these progenitor cells appeared to have memorized the inflammation they were exposed to, as they harbored important epigenetic changes: alterations in molecular markers that affect the ways genes are turned on and off but do not alter the actual DNA sequence. The researchers found that these alterations, triggered by inflammation, could alter the manner in which the genes would be expressed after a future challenge. The overall pattern of epigenetic changes, the researchers noted, was associated with known signatures of the inflammatory response.

Mice with induced periodontal disease also had more severe responses to a later immune system challenge, evidence of trained immunity.

To put the whole picture together regarding the link between inflammatory conditions, the “critical experiment,” as Hajishengallis explains, was a bone marrow transplant. Mice that had periodontitis, a severe form of gum disease, served as donors, as did a group of healthy mice serving as controls. Two hundred stem cells from their bone marrow were transplanted into mice that had never had gum disease and which had had their own bone marrow irradiated. A few months later, these mice were exposed to collagen antibodies, which trigger arthritis. 

“Mice that received the transplant from mice with periodontitis developed more severe arthritis than mice that received a donation of stem cells from periodontally healthy mice,” says Hajishengallis. 

“And higher joint inflammation in recipient mice was due to inflammatory cells deriving from the periodontitis-trained stem cells,” says Chavakis. 

Further experiments suggested that the signaling pathway governed by a receptor for the molecule IL-1 played a vital role in contributing to this inflammatory memory. Mice that lacked IL-1 receptor signaling could not generate the immune memory that made the recipient mice more susceptible to comorbidities, the researchers found. 

The work has implications for bone marrow transplants in humans, a common course of therapy in addressing blood cancers. 

“Of course, it’s a great thing if you find a matching donor for bone marrow transplantation,” says Hajishengallis. “But our findings suggest that it’s important for clinicians to keep in mind how the medical history of the donor is going to affect the health of the recipient.” 

The work also underscores that blocking IL-1 receptor signaling could be an effective approach to mitigate against these knock-on effects of trained immunity.

“We’ve seen anti-IL-1 antibodies used in clinical trials for atherosclerosis with excellent results,” Hajishengallis says. “It could be that it was in part because it was blocking this maladaptive trained immunity.”

Follow-up projects are examining how other inflammatory conditions, may be linked with periodontal disease, a sign, the researchers say, of how crucial oral health is to overall health.

“I’m proud for the field of dentistry that this work, with significance to a wide range of medical conditions, began by investigating oral health,” Hajishengallis says.