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Big data, Dermatology, Palliative Care, Patient Care, Precision health, Stanford News

Wounds too deep to heal: Study sheds light on which wounds may need special care

Wounds too deep to heal: Study sheds light on which wounds may need special care

WoundKids heal fast; old folks a lot more slowly. We all know that. But what happens when wounds take far longer to heal than is normal? Is it possible to predict which wounds need extra care?

Nigam Shah, MBBS, PhD, a Stanford associate professor of medicine, took another one of his deep dives into patient medical records to find out. The result is a creative proof-of-concept model that can predict which wounds need special care.

Earlier work has shown that even very simple models of wound healing can help caregivers pay attention to the wounds most likely to take 15 weeks or longer to heal, the definition of delayed healing.

For this work, Shah, an expert in biomedical informatics; first author Kenneth Jung, a research scientist at Stanford; and a national team of researchers turned to a dataset consisting of more than 150,000 wounds from more than 53,000 people. The team looked at hundreds of variables from patient records, including, for example the length, breadth, area, and depth of wounds, and how old patients were. The wounds in the study ranged from bed sores or diabetic ulcers to surgical or trauma wounds.

The researchers randomly assigned patients to one of two groups. One group constituted the raw data on which computers could learn which factors predicted slow wound healing in order to create a predictive model. The other group was the test that showed that the model worked on a new, and previously unseen, separate set of data.

They found that the best 100 predictors accounted for 95 percent of the influence on whether wounds were slow to heal. The single most important predictor of poor wound healing was whether a patient was receiving palliative care. Other good predictors of poor wound healing were the patient’s age, the size of the wound and how quickly it began healing in the first week.

The model’s strengths are that it works regardless of the kind of wound and it can be customized for different situations. However, as noted in the paper, the model was developed within the confines of a single company — a chain of specialty wound-care clinics called Healogics — so the model may not necessarily apply to wound healing at other institutions or for patients at home.

The paper, which made the front cover of the journal Wound Repair and Regeneration yesterday, is accessible for an academic paper — so if you’re interested in learning more about using patient records to create predictive health-care models, check it out.

Previously: Stanford researchers investigate source of scarring and To boldly go into a scar-free future: Stanford researchers tackle wound healing
Art — The Incredulity of Saint Thomas by Caravaggio — from Wikimedia

Dermatology, Education

The ups and downs in my path to dermatology

The ups and downs in my path to dermatology

country-road-809921_1920I went into medical school determined to be an ophthalmologist. A close family friend of mine is a great ophthalmologist and loves his job, which I found inspiring. A part of me also felt pressured to choose a field early on, because I worried that I couldn’t get into a competitive one unless I started doing research, volunteering, getting to know the faculty, etc. In retrospect, this is silly, because exploring different fields to find out what you like is probably the most important thing you can do as a medical student. But I thought I knew, and so I threw myself into my research on mouse retinas and time at the free eye clinic. I enjoyed working with my amazing mentor and PI, but fast forward to the end of third year, after I did two months of ophtho rotations, I realized that I didn’t love the clinical work.

Major uh-oh, as I was three months away from residency applications.

I did some quick and frantic soul searching and reached out to several mentors. One of my early mentors from undergrad suggested that I try a dermatology rotation. Crazy, I thought to myself at the time. I had been interested in dermatology as a first-year medical student, but after hearing about the insanely high board scores, the intense type-A pre-derm students who were at the top of their medical school classes, and the crazy number of publications you needed to get in, I was completely scared away from the field. My mentor told me to try anyways, and I listened.

At the end of my third year, I switched into a four-week dermatology rotation. I think I was actually half hoping that I wouldn’t fall in love with the field, so that I didn’t have to go through the grueling application process. But I completely fell head over heels.

Dermatology combined what I loved about internal medicine (the actual thinking about the medicine!) with super interesting visual diagnoses. I loved the mix of procedures and clinic, the continuity of care I got with patients, and the huge overlap between dermatology and other fields like rheumatology, cancer biology, immunology, etc. In short, I liked it more than any other clerkship I had done and I could really see myself in this field. So I decided to go for it.

It was two months before residency applications were due, and I didn’t know the faculty well and I had very little to show in terms of dermatology research. My board scores were nowhere near the quoted average needed to be a “successful applicant.” I emailed all the faculty to see if anyone had a short-term research project, and  I ended up working on and presenting a case report of graft vs. host disease with an amazing young attending named Bernice Kwong, MD, in the Stanford dermatology department. I also did a special rotation with Toby Maurer, MD, the chief of dermatology at SF General Hospital who is the leader in global health dermatology (another huge interest of mine).

Fast forward to that November. Everyone in my class had gotten interview invitations, but my inbox stayed quiet. Then… the floodgates opened, and not in a good way. I had applied to around 85 dermatology programs, and every day I got rejection after rejection after rejection. I remember getting twelve rejections in a day once, and then, the cherry on top, I got rejected from one of my top programs. I had just gotten off the Muni (public bus in San Francisco) and it was pouring rain, and I just stood there on the street holding my umbrella and broke into tears. I had never felt so insecure, so unsure of myself and my accomplishments, and I felt like I had no future in medicine.

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Cardiovascular Medicine, Chronic Disease, Dermatology, Research, Stanford News

Limb compression device reduces skin infections caused by lymphedema

Limb compression device reduces skin infections caused by lymphedema

Key among the nasty problems caused by lymphedema, a common cardiovascular disease that causes limb and trunk swelling, is the risk of skin infection. Lymphedema causes the skin to thicken and become inelastic, which open the doors for infection to enter more easily; according to Stanford’s Stanley Rockson, MD, about 25 percent of lymphedema patients experience recurring infections that can result in hospitalization.

Thus the results of a recent study published in JAMA Dermatology offers some exciting news, says Rockson, a world renowned expert in lymphedema.

The fact that we saw dramatic reductions in the incidence in rate of infections… is very noteworthy

In the study, an advanced model of a pneumatic compression device used to treat lymphedema was found to reduce skin infections from the disease by nearly 80 percent. Rates of cellulitis, the medical term for such skin infections, were lowered from 21 percent to 4.5 percent in the people with lymphedema due to cancer and from 28.8 percent to 7.3 percent in individuals whose lymphedema was not due to cancer.

Pneumatic compression devices, which have been in use for decades, are inflatable garments that when applied to the swollen area of the skin inflate and deflate in cycles to help drain lymph fluid build up. Most of these devices simply apply an increasing degree of pressure from the garment, but the model used in this study goes a step further. As Rockson, a co-author on the study, explains in a podcast accompanying the journal article:

This device works not just by adding pressure… It actually intends to simulate the intervention used by physical therapists when they do manual lymphatic massage. It places very low pressure stress on the skin increasing the filling of the lymphatic capillaries and thereby stimulating intrinsic contractility.

The idea is that the distribution of the pressure can be relegated and the treatment more targeted, he says.

“The fact that we saw dramatic reductions in both the incidence in rate of infections as well as the decreases in cost-related to care, ER visits, hospitalizations, intravenous antibiotics, is very noteworthy,” Rockson concludes.

The research was conducted at the University of Minnesota School of Public Health in collaboration with Vanderbilt University School of Nursing.

Previously: Home health care treatments for lymphedema patients cut costs and improve care; New Stanford registry to track lymphedema in breast cancer patients.

Dermatology, Genetics, Infectious Disease, Microbiology, Research, Stanford News

Inside job: Staphyloccus aureus gets critical assist from host-cell protein accomplice

Inside job: Staphyloccus aureus gets critical assist from host-cell protein accomplice

bank heistStaphylococcus aureus is a bacterium that colonizes the skin (and, often, the noses) of about one in three people, mostly just hanging out without causing symptoms. But when it breaches the skin barrier, it becomes a formidable pathogen.

S. aureus not only accounts for the majority of skin and soft-tissue infections in the U.S. and Europe, but can spread to deeper tissues leading to dangerous invasive infections in virtually every organ including the lungs, heart valves, and bones. These complications cause an estimated 11,000 deaths in the U.S. annually.

Making matters worse, antibiotic-resistant strains of S. aureus are becoming increasingly prevalent and even more difficult and costly to treat. All of which makes it crucial to understand the factors that control the bug’s virulence: What turns a common colonizer into a pathogen?

The answers that typically spring to mind involve molecules the pathogen produces that enable damage to cells of the host organism. Certainly S. aureus is no slouch in that arena. Prominent among the many virulence factors it produces, one called α-toxin aggregates on host cell surfaces to form pores that injure the cells’ outer membranes, often killing the cells.

But it turns out that forming pores appears not to be enough, by itself, for lethal host-cell injury. In a study published in Proceedings of the National Academy of Sciences, a team directed by Stanford microbe sleuths Manuel Amieva, MD, PhD, and Jan Carette, PhD, identified several hitherto-unsuspected molecules produced within host cells themselves that determine whether the cells live or die after α-toxin-induced pore formation.

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Chronic Disease, Dermatology, Immunology, Pain, Research, Science, Stanford News

Stanford researchers investigate source of scarring

Stanford researchers investigate source of scarring

2570500512_22e7fdcd48_zIf you’ve ever had a piercing that you’ve let grow closed, you’ll know that the healing process isn’t perfect. There’s almost always a little dimple to remind you of that perhaps questionable choice you may (or may not) have made during early adulthood.

Now former Stanford pediatric dermatologist Thomas Leung, MD, PhD, and developmental biologist Seung Kim, MD, PhD, have published some interesting research in Genes and Development regarding the healing and scarring process. Their findings may one day lead to advances in regenerative medicine.

As Leung, who is now an assistant professor at the University of Pennsylvania’s Perelman School of Medicine explained in an email to me:

One of the great mysteries in biology is how salamanders and worms regenerate lost body parts following trauma. In contrast to wound healing, tissue regeneration restores tissue to their original architecture and function, without a scar.  Although less dramatic, a few examples of mammalian tissue regeneration exist, including liver and digit tip regeneration.  These examples suggest that the underlying mechanisms driving tissue regeneration may still be intact in humans and perhaps we may use them for regenerative medicine.

The researchers studied how the ears of mice heal from a hole punched through the thin tissue (much like  ear piercing in humans). In many strains of mice, the holes partially fill but remain visible. In a few others, the holes heal with little perceptible scarring. Leung and Kim found that the strains of mice that heal well lack production of a protein that normally recruits white blood cells to the injury; blocking the ability of the protein, called Sdf1, to signal to the white blood cells resulted in enhanced tissue regeneration and less scarring in mice that would normally have been unable to close the hole.

Because the drug used to block Sdf1 signalling is already used clinically in humans for another purpose, Leung is hopeful that it can quickly be tested in humans struggling to heal  chronic or slow-healing wounds. He is currently designing a clinical trial to test the drug, called AMD3100.

The implications of improved wound healing with less scarring stand to benefit many more people than just those wishing away the physical evidence of a hasty cosmetic decision. Tens of millions of surgical incisions are made every year, and not all heal well. Scar tissue is less flexible than normal skin and can significantly interfere with function. In addition, people with certain medical conditions such as diabetes or poor circulation can face ongoing disability or amputation when wounds don’t heal. But the group that inspired Leung to conduct the research is especially poignant.

As Leung explained:

 The inspiration for this work was driven by our clinical experience.  At Stanford, I co-directed the Epidermolysis Bullosa (EB) clinic.  EB is a rare genetic skin disease (about eight babies are affected per million births in this country), where affected patients lack a protein that binds the skin together, resulting in fragile skin. Incidental trauma like rubbing of skin against clothing tears the skin and leaves a scar.  This endless cycle of trauma and scarring and fibrosis inevitably leads to decreased joint function and complete loss of hand function by teenage years.

My recent article for Stanford Medicine magazine and the accompanying video shed light on this devastating condition. Even a small improvement in the pain these children suffer would be a tremendous step forward. And, although Kim emphasizes that greater feats in regenerative medicine (limb regeneration, anyone?) are still years of research away, this finding shows that we’re making progress.

Previously: Limb regeneration mysteries revealed in Stanford studyTo boldly go into a scar-free future: Stanford researchers tackle wound healing and Life with epidermolysis bullosa: “Pain is my reality, pain is my normal”
Photo by The Guy with the Yellow Bike

Cancer, Chronic Disease, Dermatology, Stanford News, Surgery, Transplants

Rebuilding Cassie’s smile: A lung transplant patient’s struggle with skin cancer

lung patientWhen I first met Cassie Stockton, she was seated in an exam chair in Stanford’s dermatology clinic, getting cosmetic skin treatments. Lovely and young, just 21 years old, it seemed a bit silly. How could she possibly need injectable lip fillers or laser skin treatments?

I knew Stockton had a lung transplant at 15 and that the immunosuppressant drugs she was required to take to keep her body from rejecting the donated lungs had made her susceptible to skin cancer. But it wasn’t until I researched her story in depth that I truly understood how she ended up needing regular cosmetic treatments here.

As I explain in my recently published Stanford Medicine article, her story began at birth:

Born premature, [Cassie] was intubated the first two weeks of life, then sent home with her mother and an oxygen tank. She remained on oxygen 24 hours a day for the first two years of her life. Eventually, she was diagnosed with bronchopulmonary dysplasia, a chronic lung disorder …

Sixteen years later, the donated gift of new lungs saved her life – but it left scars, both emotional and physical:

The day Stockton woke up out of the anesthesia six years ago after a 13-hour surgery at the Transplant Center at Lucile Packard Children’s Hospital Stanford, she breathed in oxygen with newly transplanted lungs, and breathed out sobs. Tears streamed down her face. “At first, I thought she was in pain,” says her mother, Jennifer Scott, who stood by her side. But that wasn’t it. Stockton was overwhelmingly sad because she now knew her new lungs were the gift of a child. It was Dec. 6, 2009, just before Christmas. The death of someone else’s child had given her a whole new life.

And now:

Every four months, she and her fiancé make the four-hour drive from their home in Bakersfield, California, past the oil rigs and cattle farms to Stanford’s Redwood City-based dermatology clinic for her skin cancer screening. It’s been two years of treatments: freezings, laserings, a total of eight outpatient skin surgeries — the most significant resulting in the removal of the left half of her lower lip. The dermatologic surgeon removes the skin cancers, and then gets to work to repair the damage. “It’s heart-breaking to have to remove the lip of a 21-year-old woman,” says Tyler Hollmig, MD, clinical assistant professor of dermatology and director of the Stanford Laser and Aesthetic Dermatology Clinic, who leads Stockton’s treatment and keeps her looking like the young woman she is, restoring her skin, rebuilding her lip, making sure she keeps her smile.

Stockton doesn’t complain about any of the struggles she’s had post transplant. She knows she got a second chance at life. And, she tells me, it’s her job to take care of the lungs given to her by that child who died.

Previously: This summer’s Stanford Medicine magazine shows some skin
Photo by Max Aguilera-Hellweg

Dermatology, Public Health, Stanford News

It’s never too early to protect your skin from sun damage

It's never too early to protect your skin from sun damage

I’m not ashamed to admit that I dork out for Disneyland. I was there a few weeks ago, wearing a Minnie Mouse T-shirt and sprinting from one thrill ride to the next. But this trip was different in one respect: I made sure to apply a broad-spectrum sunscreen to my face and limbs before heading into the Magic Kingdom and then brought along the tube so that I could reapply it throughout the day.

Growing up, I was happy that my skin picked up a tan easily, with only occasional sunburn. As an adult, I watched the evidence pile up about the hazards of sun exposure and tried to remember to use sunscreen in the summer months when I was outside for long periods of time. But after speaking with several Stanford dermatologists for a story about skin protection for the recent issue of Stanford Medicine magazine, I resolved to be more vigilant year-round.

As my story notes, one in five Americans will develop skin cancer in their lifetime. One good way of warding off that threat is to use a broad-spectrum sunscreen, many of which are now much lighter and less greasy that the sunscreens of old.

“Your sunscreen should be considered your facial lotion,” dermatology professor Susan Swetter, MD, told me. “It works to moisturize the skin as well as to prevent photoaging and skin cancer.”

The story also includes tips for protecting your skin and for encouraging children to develop good skin-protection habits at an early age. Parents seem to be taking the message to heart: As I made my way through the crowded streets of Disneyland, one scent stood out among all of the others. The unmistakable smell of sunscreen.

Previously: This summer’s Stanford Medicine magazine shows some skinBeat the heat – and protect your skin from the sunWorking to protect athletes from sun dangers and The importance of sunscreen in preventing skin cancer
Illustration by Aleksandar Velasevic

Dermatology, Evolution, Pediatrics, Research, Science, Stanford News, Surgery

To boldly go into a scar-free future: Stanford researchers tackle wound healing

To boldly go into a scar-free future: Stanford researchers tackle wound healing

scarshipAs I’ve written about here before, Stanford scientists Michael Longaker, MD, and Irving Weissman, MD, are eager to find a way to minimize the scarring that arises after surgery or skin trauma. I profiled the work again in the latest issue of Stanford Medicine magazine, which focuses on all aspects of skin health.

My story, called “Scarship Enterprise,” discusses how scarring may have evolved to fulfill early humans’ need for speed in a cutthroat world:

“We are the only species that heals with a pathological scar, called a keloid, which can overgrow the site of the original wound,” says Longaker. “Humans are a tight-skinned species, and scarring is a late evolutionary event that probably arose in response to a need, as hunter-gatherers, to heal quickly to avoid infection or detection by predators. We’ve evolved for speedy repair.”

Check out the piece if you’re interested in reading more about this or learning how scarring happens, or why, prior to the third trimester, fetuses heal flawlessly after surgery. (Surprisingly, at least to me, many animals also heal without scarring!)

Previously: This summer’s Stanford Medicine magazine shows some skinWill scars become a thing of the past? Stanford scientists identify cellular culprit, New medicine? A look at advances in wound healing and Stanford-developed device shown to reduce the size of existing scars in clinical trial
Illustration by Matt Bandsuch

Dermatology, Research, Stanford News, Videos

Life with epidermolysis bullosa: “Pain is my reality, pain is my normal”

Life with epidermolysis bullosa: "Pain is my reality, pain is my normal"

“Pain is my life. It’s my reality. It’s my normal.” These are the words that haunted me for days after first watching this film about Paul Martinez, a 32-year-old Stanford patient with epidermolysis bullosa (EB). I’m used to being moved by films made by my colleague Mark Hanlon, but his latest effort, called “The Butterfly Effect,” is about as powerful (and tear-inducing) as anything I’ve seen during my time here.

EB, as Krista Conger described earlier this week, is “incurable, fatal, and nearly indescribably painful.” Dermatologist Paul Khavari, MD, PhD, says in the film that “it just breaks your heart” when talking to patients and their families about what they go through, and Martinez, who shared his daily life and opened his home to Hanlon, puts it this way:

The word ‘pain’ itself doesn’t even describe how bad EB is. Your body is constantly on fire – it burns from the wounds from raw flesh, and it keeps repeating over and over and over. The cycle is never ending.

Seeing what Martinez and his caretaker-mother endure every day (warning: it’s not easy to watch) makes you wonder, frankly, how they do it – and also illustrates just how desperately a cure for this terrible disease is needed. Luckily, as detailed both in the film and Conger’s accompanying Stanford Medicine magazine article, researchers here are working to combat the illness – and have been doing so for decades. And Khavari closes out the film with a hopeful tone, saying: “We can start to see on the horizon the potential to really make a difference for patients.”

Previously: The worst disease you’ve never heard of: Stanford researchers and patients battle EB and This summer’s Stanford Medicine magazine shows some skin

Cancer, Clinical Trials, Dermatology, Genetics, Pain, Pediatrics, Research, Stanford News

The worst disease you’ve never heard of: Stanford researchers and patients battle EB

The worst disease you've never heard of: Stanford researchers and patients battle EB

EB patient and docsI’m often humbled by my job. Well, not the job, exactly, but the physicians, researchers, and especially patients who take the time to speak with me about their goals and passions, their triumphs and fears. Their insight helps me as I struggle to interpret what goes on here at the Stanford University School of Medicine for others across the university and even around the world.

But every once in a while, an article comes along that brings me to my (emotional) knees. My article “The Butterfly Effect” in the latest issue of Stanford Medicine magazine describes the toll of a devastating skin disease called epidermoloysis bullosa on two young men and their families, as well as the determined efforts of a dedicated team of doctors and scientists to find a treatment. As a result, Stanford recently launched the world’s first stem-cell based trial aimed at correcting the faulty gene in the skin cells of patients with a severe form of the condition, which is often called EB.

I trace the path of one family as they learn, mere hours after his birth, that their son, Garrett Spaulding, has EB, which compromises the ability of the outer layers of the to stick together during friction or pressure. Patients develop large blisters and open wounds over much of their bodies. It’s incurable, fatal, and nearly indescribably painful. Paul Khavari, MD, PhD, now the chair of Stanford’s Department of Dermatology, was a young doctor at the time newborn Garrett was admitted to Lucile Packard Children’s Hospital Stanford in 1997.

“His whole body, his skin was blistered and falling off everywhere someone had touched him,” Khavari recalls in the article. “His parents were devastated, of course, at a time that was supposed to be one of the most joyful of their lives.”

Garrett’s now 18 years old, but the disease is taking its toll.

You’ll also meet Paul Martinez, one of the first participants in Stanford’s new clinical trial. He’s 32, which makes him an old man in the EB community. Unlike many EB patients, he has finished high school and completed a college degree in business marketing with a dogged determination that makes me ashamed of my petty complaints about my minor life trials. And he’s done it without relying on the pain medications essential for most EB patients. As he explains in the article:

We don’t know what it is like to not be in pain. It’s just normal for us. […] I have a very high tolerance, and don’t take any pain medication. I cherish my mind a lot. Rather than feel like a zombie, I prefer to feel the pain and feel alive.

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