A new approach to understanding the biology of wound healing

Press Release:

PHILADELPHIA – Our bodies frequently heal wounds, like a cut or a scrape, on their own. However patients with diabetes, vascular disease, and skin disorders, sometimes have difficulty healing. This can lead to chronic wounds, which can severely impact quality of life. The management of chronic wounds is a major cost to healthcare systems, with the U.S alone spending an estimated 10-20 billion dollars per year. Still, we know very little about why some wounds become chronic, making it hard to develop effective therapeutics to promote healing. New research from Jefferson describes a novel way to sample the cells found at wounds – using discarded wound dressings. This non-invasive approach opens a window into the cellular composition of wounds, and an opportunity to identify characteristics of wounds likely to heal versus those that become chronic, as well as inform the development of targeted therapies.

The study was published in Scientific Reports on September 15th.

“Studying wound healing in humans is very challenging, and we know very little about the process in humans,” says Andrew South, PhD, Associate Professor in the Department of Dermatology and Cutaneous Biology and one of the lead authors of the study. “What we do know is from animal studies, and animal skin and the way it heals is very different from human skin.”

Dr. South and his lab study a group of inherited skin diseases called epidermolysis bullosa (EB), where wound healing is severely impaired. Patients, often from birth, suffer from blisters and lesions that are slow to heal, and some become chronic. In a subset of patients, chronic wounds are at high risk of developing into aggressive skin cancer. At this time, it is very difficult to predict which wounds in a given patient will heal, and which won’t. Being able to sample the wounds is a key to understanding the mechanisms behind healing.

“Performing a biopsy to sample the cells in the wound would help us understand the differences between these wounds,” says Dr. South “But biopsy in these patients is extremely painful and could delay healing of the wound even further. On the other hand, collecting these bandages that are just going to be thrown away, it poses no harm to the patient, and can be applied to a variety of conditions where wounds don’t heal properly.”

The researchers, which included collaborators in Chile and Austria, collected and analyzed 133 discarded wound dressings from 51 EB patients. Both acute and chronic wounds were sampled, with acute defined as present for 21 days or less, and chronic as present for more than 3 months.

“Previous studies had used wound dressings or bandages to collect fluid and look at what proteins are in there,” says Dr. South. “But no one has actually looked at what cells are present. Applying the techniques our lab frequently uses, we were able to isolate viable or living cells from the dressings.”

The researchers recovered a large number of cells from the dressings, often in excess of a 100 million. The larger the wound, and the more time a dressing was on a wound, the more number of cells were recovered.

The researchers then characterized the cells to see what type of cells are present at the wound. They detected a variety of immune cells including lymphocytes, granulocytes or neutrophils, and monocytes or macrophages. When comparing dressings from acute and chronic wounds, they found a significantly higher number of neutrophils at chronic wound sites. Neutrophils are the first line of defense in our immune system, and when a wound starts to form, they’re the first ones to arrive at the scene.

“Previous findings from animal studies and protein analysis of human wound dressings had supported the idea that when neutrophils hang around longer than they should, that stalls the healing process and can lead to chronicity,” says Dr. South. “Our findings support that theory more definitively, by showing that chronic wounds are characterized by higher levels of neutrophils.”

These findings give more insight into wound healing, and could help develop therapies that promote the process; for instance, those that neutralize excess neutrophils, or recruit macrophages, the immune cells that begin the next stage in healing after neutrophils.

The researchers now plan to expand on their technique, by further analyzing the individual cells collected from the wound dressings, and the genetic material inside them. “Currently we’re working with colleagues in Santiago, Chile on collecting dressings from EB patients over a period of time,” says Dr. South. “This allows us to follow patients longitudinally, and observe a wound and how its cellular composition changes as it heals or doesn’t heal.”

The team hopes that this will reveal genetic markers that can predict healing or chronicity.

“This method of sampling could be an alternative to bothersome swabs or blood draws, which are especially hard to do in newborns,” says Dr. South. “Since we know EB can present at birth, this technique could give us really early insight into the how severe the disease might be.”

While the current study focuses on EB, Dr. South and his colleagues hope that this technique can be applied to a variety of other conditions, such as diabetic foot ulcers and vascular leg ulcers.

“The field of wound healing has been crying out for a better understanding of what drives a chronic wound,” says Dr. South. “This technique could be transformative, and eventually help patients live more comfortable and healthy lives.”

Walk a mile in their shoes

What are patients going through? What sorts of questions do they ask in social media? What do they think about what health professionals tell them about their conditions? Do you know?

Suggestion: on Facebook there are many groups for people with different health conditions. Join these groups for a while to see what they are talking about. Do not tout for business, use them an an opportunity to walk in their shoes to see what their issues are.

For example, there is this Facebook group on Freiberg’s disease and this one on Morton’s Neuroma.

Adult acquired flatfoot or posterior tibial tendon dysfunction or progressive collapsing foot deformity?

Which one is the correct name? There is a lot of discussion going on as to which is the more appropriate name. There are merits for each name.

A lot of it comes down to what is the primary pathology and if it is a primary problem of the posterior tibial tendon or is the driving factor and the primary structures that are involved are more than just that tendon, such as the spring ligament.

This topic has been ligated here.

Is ‘Overpronation’ a problem or not

This gets debated a lot. The views are mixed.

The issues are:

  • yes, pronation is a normal healthy motion
  • yes, there is no definition or consensus as to what is normal and what is overpronation
  • yes, plenty of people overpronate and get no problems
  • yes, other overpronate a small amount and gets lots of problem
  • yes, there are multiple causes of overpronation, so there is going to have to be multiple different treatments. One size is not going to fit all.
  • yes, there are too many who consider themselves experts in this when they have no idea what they are talking about.
  • yes, stick to what the consensus of the preponderance of the research says on the topic and not commentary in social media

Samaritan’s Feet Receives $5 Million Commitment From Sanford Health

Press release:

CHARLOTTE, N.C., Aug. 24, 2020 /PRNewswire/ — Sanford Health has committed to donating $5 million to Samaritan’s Feet as the non-profit organization launches a capital campaign to expand its global efforts. This gift from Sanford Health will allow Samaritan’s Feet to begin planning the core strategies of their growth initiatives: increase operational capacity in the United States, maximize efficiency in global delivery, expand experiential education, and ensure sustainability. Sanford Health’s donation will help address the global pandemic of the 1.5 billion people being infected with diseases that are transmitted through contaminated soil (World Health Organization, 2020).

“Samaritan’s Feet serves and inspires children by providing shoes across the world. Theirs is an inspiring mission that fits with the kind of impact Sanford Health strives to have in the world. Manny and his team have an ambitious plan for the future, and it’s a project we’re proud to support,” said Kelby Krabbenhoft, President and CEO, Sanford Health.

In addition to seed funding to expand Samaritan’s Feet’s capacity domestically and internationally, this partnership will foster further collaboration and engagement with Sanford Health and its associates and have the following impact on Samaritan’s Feet programs globally:

  • World Shoe Development: Lead necessary research of the World Shoe 2.0, a second-generation anti-microbial and biodegradable shoe for distribution in resource-constrained countries and vulnerable populations in the U.S.
  • Medical Advisory Champion: Serve on the Samaritan’s Feet Medical Advisory Committee, providing expertise in infectious diseases, podiatry, global health, and psychology.
  • International Programs: Provide shoes of hope in Ghana and Costa Rica, two strategic locations of the Sanford World Clinic, with their insight to determine in-country partners and distribution locations.
  • Domestic Programs: Develop Sanford Health Shoes for Seniors program to serve vulnerable senior citizens with fall-resistant shoes and foot-care information.
  • Shoezeum: Named recognition as the sponsor of Samaritan’s Feet’s Shoezeum, a mobile and permanent experiential learning center with opportunities for visitors to become immersed in cultures and conditions of those Samaritan’s Feet serves globally.

“Sanford Health’s generous gift and partnership play a crucial role in the expansion of Samaritan’s Feet’s programs. Together, we can provide more opportunities to give hope and healing to individuals around the world. We’re grateful for their support and share their commitment to improving the health and well-being of those we serve,” said Manny Ohonme, President and CEO, Samaritan’s Feet. “This donation allows us to kick-off our capital campaign to build our global headquarters in the Carolinas, housing our worldwide volunteer center and creating the Global Servant Leadership Institute.”

Sanford Health has supported Samaritan’s Feet through various fundraising events and shoe distributions in the U.S. and internationally. Through past financial gifts in excess of $1 million, Sanford Health has co-sponsored MLK Day of Service events and inspired barefoot coaches through their annual Barefoot Classic tournament. Additionally, Manny serves as Vice Chair of Sanford Health’s International Board. On Monday, August 24, executives from Samaritan’s Feet will be in Sioux Falls, S.D. meeting with leaders and doctors from Sanford Health.

“The work accomplished to date by Samaritan’s Feet is truly inspiring,” said Micah Aberson, Executive Vice President, Sanford Health. “Knowing what its efforts mean to kids and families across the world, makes this a natural fit for Sanford Health to support. To be part of an organization that can help Samaritan’s Feet take this next step is something all 50,000 Sanford Health employees can be proud to be part of.”

About Sanford Health

Sanford Health, one of the largest health systems in the United States, is dedicated to the integrated delivery of health care, genomic medicine, senior care and services, global clinics, research and affordable insurance. Headquartered in Sioux Falls, S.D., the organization includes 44 hospitals, 1,400 physicians and more than 200 Good Samaritan Society senior care locations in 26 states and nine countries. Nearly $1 billion in gifts from philanthropist Denny Sanford have transformed how Sanford Health improves the human condition. For information, visit sanfordhealth.org or Sanford Health News.

Study challenges widely held belief that gout is primarily caused by diet

Press release:

The widely held belief that gout is primarily caused by diet is not backed up by new evidence published in The BMJ today, which suggests that diet is substantially less important than genes in the development of high serum (blood) urate levels, that often precede gout.

Gout is a joint disease which causes extreme pain and swelling. It is most common in men aged 40 and older and is caused by excess uric acid in the blood (known as hyperuricaemia) which forms crystals that collect around the joints.

For centuries, diet has been seen as a risk factor for the development of gout. Recent studies suggest that certain foods (eg. meat, shellfish, alcohol and sugary soft drinks) are associated with a higher risk of gout, while others (eg. fruit, vegetables, low-fat dairy products and coffee) have a protective effect. Studies also show that genetic factors play an important role.

To better understand how both diet and genes might influence the development of gout, a team of researchers based in New Zealand analysed dietary survey data for 8,414 men and 8,346 women of European ancestry from five US cohort studies.

Participants were aged over 18 without kidney disease or gout, and were not taking urate-lowering or diuretic drugs.

Blood urate measurements and genetic profiles were recorded. Factors that could have affected the results, such as sex, age, body mass index, daily calorie intake, education, exercise levels, and smoking status, were also taken into account.

Dietary analysis revealed seven foods associated with raised urate levels (beer, liquor, wine, potato, poultry, soft drinks, and meat) and eight foods associated with reduced urate levels (eggs, peanuts, cold cereal, skimmed milk, cheese, brown bread, margarine, and non-citrus fruits).

However, each of these foods explained less than 1% of variation in urate levels.

Similarly, three diet scores, based on healthy diet guidelines, were also associated with lowered urate levels, while a fourth, based on a diet high in unhealthy foods, was associated with increased urate levels. Again, however, each of these diet scores explained very little (less than 0.3%) variance in urate levels.

In contrast, genetic analysis revealed that common genetic factors explained almost a quarter (23.9%) of variation in urate levels.

The researchers point to some limitations, such as the use of different food questionnaires between studies, and the fact that the study was limited to individuals of European ancestry without gout, so the findings may not be generalisable to other populations or to people with gout.

Nevertheless, they say their data “are important in showing the relative contributions of overall diet and inherited genetic factors to the population variance of serum urate levels.”

They conclude: “Our data challenge widely held community perceptions that hyperuricaemia is primarily caused by diet, showing for the first time that genetic variants have a much greater contribution to hyperuricaemia than dietary exposure.”

In a linked editorial, researchers at Keel University point out that people with gout often experience stigma from the misconception that it is a self-inflicted condition caused by unhealthy lifestyle habits and, as a result, are often reluctant to seek medical help.

This study, they say, “provides important evidence that much of patients’ preponderance to hyperuricaemia and gout is non-modifiable, countering these harmful but well-established views and practices and providing an opportunity to address these serious barriers to reducing the burden of this common and easily treatable condition.”