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Chronic Disease

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

Chronic Disease, Imaging, Pediatrics, Research, Stanford News

Why chronic disease harms kids’ bone development — and what to do about it

Why chronic disease harms kids' bone development — and what to do about it

osteoporosis“Someone once told me listening to me talk is like drinking from a fire hose,” Mary Leonard, MD, said to me at the end of our recent 45-minute interview. I had precisely the opposite reaction: After I left her office at Stanford Hospital, I was so parched from our conversation I walked across the street, bought a bottle of water and downed the whole thing.

Leonard, a professor of pediatrics and of medicine, has a sense of urgency for a reason: She’s trying to make sure children with chronic diseases build as much bone as possible before puberty ends. Once that window closes, she and other researchers believe, it’s too late to do much about it. And the likely consequence of emerging from adolescence with inadequate bone mass is early osteoporosis.

“Kids with kidney disease are, even as children, fracturing more than you would expect,” Leonard said. “Kids with arthritis are fracturing more than you would expect.” Ditto those with congenital heart disease, organ or bone marrow transplants, inflammatory bowel disease, cerebral palsy, muscular dystrophy or a history of cancer. The culprits: inflammation, immobility, malnutrition, stunted growth, steroid treatment or a combination thereof.

Leonard’s work fits in perfectly with the most recent issue of Stanford Medicine, which is all about how early experiences can have far-reaching consequences for our health. As she says in my story about her research program:

We believe that once you go through puberty, you’re not getting that bone back. I feel like we’ve described and described the problem, and now we need to do clinical trials to see what we can do to improve bone health in these patients. We just want to make sure they go into adulthood with the best, strongest skeleton possible — with bones to last a lifetime.

Leonard has several ideas about what would help — exercise interventions, medications, more aggressive treatment of the underlying condition at younger ages — and state-of-the-art imaging equipment with which to assess them. “We’re on the cusp,” she told me with excitement, “of transitioning from describing and describing to actually doing something.”

Previously: Stanford Medicine magazine tells why a healthy childhood matters, Pediatric nephrologist Mary Leonard discusses bone health in children with chronic diseases at Childx and Pediatrics group issues new recommendations for building strong bones in kids
Photo by Sebastian Kaulitzki/Shutterstock

Chronic Disease

Laughing through the pain: A comedy writer’s experience with chronic illness

Laughing through the pain: A comedy writer's experience with chronic illness

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, on a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; this month’s column comes from a Los Angeles woman with Ehlers-Danlos Syndrome.

woman laughing2When you fall down at least once a week, you learn to laugh it off. No matter how much it hurts, you laugh because you know it makes other people more comfortable with what’s going on. If they believe you’re all right, your story is a comedy rather than a tragedy. I’m quite sure that this lesson I learned as a child (and have called on hundreds of times since) had a big part in my decision to become a comedy writer and performer, a career I began a decade before I was finally diagnosed with Ehlers-Danlos Syndrome.

Everyone with my rare connective tissue disorder knows the routine of explaining our condition to others. I like to gauge at what point a healthy person’s eyes glaze over and they check out completely; it’s usually around when I get to my issues that are caused by EDS, like arthritis and gastroparesis. After my first few monotonous rundowns of what ails me failed to enthrall anyone, I began weaving elements of humor into my explanations: “I have hip dysplasia, so I can’t be in the Westminster dog show… My joints hyperextend, which is great for sex but terrible for JV soccer… I tore my hamstring in Greece, but it’s not like that’s the worst thing that ever happened there.” Once engaged, people are much more likely to find some aspect of my condition that interests them and ask about that. This type of light interaction is far more comfortable than feeling like I’m teaching an NIH seminar on some disease nobody cares about.

In my experience, the people who really appreciate someone with a sense of humor are those I rely on most: Doctors and nurses. Just after my diagnosis, I was so confused and in so much pain that I was relatively curt with medical professionals. I also thought that if I even smiled, they would think I was faking my illness. But once my symptoms started to improve a bit and I understood more about what was happening, I tried being open and jovial with those who were treating me. The result was great; it should not have come as a surprise that a doctor who likes his patient is more likely to pay attention to her. Regardless of how badly I feel or how much I think something devastating may be happening to my body, I now try my hardest to make whatever dumb jokes I can manage in the hospital or at the doctor’s office. The staff members, many of whom somehow make it through day after day of maudlin events and miserable people, respond quite positively to my Tommy Boy quotes and ridiculous metaphors about how the exam room smells like a robot dog’s pee. (In fact, I would like to think I get better treatment because of David Spade.)

The need to laugh off my issues has become so innate that it is now my first response when I go into shock. My old roommate loves to tell the story of when I stepped onto our back porch and it looked like a sniper hit me: I was down in an instant. She ran out to see what was wrong and found me laughing hysterically, screaming, “I’m fine! Everything’s fine!” When I saw her worried, maternal expression, it made me even more afraid; I knew I had to alleviate her concern for both of our sakes, so I kept up my laughing and made jokes even as the unbelievable pain set in. As it turns out, I had ruptured my Achilles tendon and torn my calf muscle so badly that the orthopedic surgeon said it looked “like pulled pork; like a zipper went down the whole thing from top to bottom.” Looking back, I laughed and joked to make my roommate think everything was fine – the way you would treat a toddler who fell down and looks to you to gauge the severity of his injuries – but really I was the toddler, and making myself laugh got me through it.

I do not know where my life would be without my love of comedy, nor how I would have made it through the ups and downs of Ehlers-Danlos Syndrome. When it comes to relating to people, passing time in the hospital, or just convincing ourselves that there’s a lighter side to almost every situation, the most important part of the human body is the funny bone.

Paula Dixon is a comedy writer and photographer based in Los Angeles. She is a graduate of the USC School of Cinematic Arts and the Spéos Institute of Photography in Paris. She will be returning soon with her humorous podcast The Chronic Life, which covers chronic illness as well as pop culture and personal revelations.

Photo by bruna camargo

Behavioral Science, Chronic Disease, Health and Fitness, Medical Apps, Technology

Can cute cat texts motivate patients to take their medication?

Can cute cat texts motivate patients to take their medication?

Sammie resizedThe right kind of motivation is key when you have a difficult or mundane task at hand. For example, when I wanted to learn Spanish, I tried several top-rated, online language tools to no avail because they felt like work to me. Then, half as a joke, my boyfriend suggested an app that associates Spanish phrases with images of cats acting out the meaning of the words. The app was so silly I used it often, and — to our amazement — it actually worked.

So when I saw this story on MedCity News about a company that plans to use cat photos to motivate people to take their medicine, I knew they were on to something. As the story explains, the texts are part of an online assistant that will pair irresistibly cute cat images with health prompts so the reminders are memorable and fun.

The company, called Memotext, plans to pilot test this tool on Type 2 diabetes patients (followed by patients with other chronic illnesses) to gain insights on the patients’ state of mind when they skip or forget to take a medication. They also hope to learn more about what can be done to change patients’ behavior so they’re able to follow their medication regimen better.

“We’re not only asking whether you did something, but why did you do it,” said Amos Adler, the company’s founder and president. Based on what I’ve learned about motivation so far, I think a cute cat text or two probably can’t hurt.

Previously: “Nudges” in health: Lessons from a fitness tracker on how to motivate patientsStudy offers clues on how to motivate Americans to change and Understanding the science and psychology of how habits work
Photo courtesy of Anna MacCormick

Chronic Disease, Palliative Care, Parenting, Pediatrics

Missing out on “normal”: Advice from an expert on how to help kids with serious illnesses

Missing out on "normal": Advice from an expert on how to help kids with serious illnesses

Erica Medina and mom Jan 2012 #2When I first met Erica Medina in 2012, she was already practiced at living in two worlds. Then 17, she loved the ordinary teenage realm of high school classes, basketball and volleyball games, and trips to the mall with her friends. But since her diagnosis with juvenile idiopathic arthritis at age 11, she had also spent a lot of time in the medical world, where she and her doctors struggled to manage the pain caused by a disease that has no cure.

The story I wrote about Erica explained how the two worlds sometimes collided:

Back pain made it taxing to sit through school lectures, go on field trips or walk through the mall with friends. It wasn’t just the pain that bothered her: “When I was younger I hated taking my meds,” Erica said, adding that it felt like “giving up” to take pain medicine.

Stephanie [Erica’s mom] was glad Erica’s doctors tackled this issue head-on. “They convinced her that treating pain has nothing to do with weakness,” she said.

Although juvenile idiopathic arthritis is fairly rare, Erica’s longing for normalcy is not. Children and teenagers with all kinds of chronic and serious conditions have the same desire, says pediatric psychologist Barbara Sourkes, PhD, who directs the palliative care program at Lucile Packard Children’s Hospital Stanford.

A big part of Sourkes’ role is to help children, teenagers and their families navigate the divide between living with a difficult diagnosis and simply being a kid. She’s summarized her insights about this in a thoughtful piece on the blog for Digging Deep, a publication designed to help kids facing health challenges. Young people like Erica “commute” between the normal and medical worlds, “an extraordinary challenge,” Sourkes says. From her piece, here is some of her advice for families and others on how to help:

Be aware and sensitive to the importance of feeling “normal” – as normal as possible – for all children and adolescents living with illness. While we typically focus more on adolescents’ desire to “fit in,” even very young children are sensitive to being “different.” Help them focus on and remember what aspects of their lives – and of themselves – are still the same despite the illness.

“Missing out on things” comes in two categories: (1) missing a specific, often special event or activity (e.g. a celebration, a trip) and (2) missing out on life in general (day-to-day daily life, in all its routine).

Adults tend to focus more on the first category, in part because these are events that stand out from the backdrop of daily life. Allow the child to express disappointment / anger / sadness at the prospect of missing the event – do not try to minimize these feelings. After the event, it is very important to let children know that people asked about them and that their presence was missed. It makes the “missing out on things” a little more shared and less one-sided. When realistically possible, promise the child that they will participate in a similar event at a future time.

The second category of “missing out on life in general” is more ongoing and subtle, and probably has more impact on adolescents than on young children. It is also harder to address, since it encompasses all the frustration and sadness of the impact of the illness. Most important is simply to listen to what the children say, without trying to distract them or “problem solve” or cheer them up. These are times that they may just want to be heard and to have their hardship acknowledged.

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Chronic Disease, Events, Medicine X, Sexual Health

A discussion of intimacy and illness at Medicine X: “Embrace yourself and embrace your normal”

A discussion of intimacy and illness at Medicine X: "Embrace yourself and embrace your normal"

21735972186_ef347da42d_zMedicine X is well known for shining a light on dark feelings and difficult-to-talk about topics, as well as being a safe place to hold such conversations within the health-care community. Last year, a key theme of the conference was addressing the relationship of mental and physical health. The discussion of treating the whole person, not just their disease or symptoms, was expanded this year to include sexual health.

In a Sunday session exploring intimacy and illness, Medicine X executive board member and well-known patient advocate Sarah Kucharski bravely spoke about her own relationship experiences as she led the discussion. “Illness completely changes one’s relationship with one’s body. It’s the idea of feeling broken. Of feeling you’re a burden. Of feeling not sexy,” she said.

Diagnosed at the age of 31 with intimal fibromuscular dysplasia, Kucharski has undergone multiple surgeries, resulting in permanent scarring of her body. She shared with the audience her anxiety over romantic partners seeing the scars for the first time during intimate moments and suddenly having to answer their questions. She said, “To expose that visual reminder of my health, maybe it’s too much. Maybe it’s forcing me to be who I really am instead of enjoying a certain escapism,” she said. “It takes away my opportunity to talk about my health.”

Many patients and caregivers can relate to Kucharski’s struggle with intimacy and illness. She conducted an informal online survey in preparation for the conversation. The biggest finding? There is no normal. But this reality often isn’t conveyed in doctor-patient conversations. For patients who undergo a medical procedure or women who give childbirth, physician advice is usually to wait for a certain period of time until they are physically healed and then resume sexual activity “when they feel ready.”

Matthew Dudley, MD, a hospitalist who works in Alaska, said one of the factors driving the lack of doctor-patient communication about sexual health is that “health care in this country is reactionary.” He added, “We end up dealing with this emergent actions, and so you don’t get time to sit down and talk about these issues.”

In addition, pointed out panelist Alexandra Drane, the medical education curriculum at many institutions doesn’t dedicate enough time to sexual health issues. Beyond expanding the training of future doctors, she advocated for “normalizing the conversation” about intimacy. “This is a topic that most people really, really want to talk about. There needs to be training [for doctors] on how to have these conversations and how to make someone feel safe and normal,” said Drane, co-founder of the Eliza Corporation.

But more training for medical students may not to be the silver bullet that resolves the problem, say some panelists. Dudely said he received a full two weeks of training on sexual health issues during medical school. “I thought at my school we did a good job,” he said, “But in the day to day it gets lost. We need patients to go to their doctors and say, ‘I want to know more about this.’ As our culture becomes more open about these issues, I think it will come to the forefront.”

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Addiction, Chronic Disease, Pain, Stanford News, Videos

“People are looking for better answers”: A conversation about chronic pain

"People are looking for better answers": A conversation about chronic pain

2048px-Low_back_painChronic pain limits the lives of an estimated 100 million people in one way or another and costs our country half a trillion dollars per year, according to Sean Mackey, MD, PhD, chief of the Division of Pain Medicine. To address the needs of the many people suffering from back pain, the most common kind of chronic pain, Mackey and other doctors and researchers in the division recently held a free Back Pain Education Day.

The event was popular enough that all seats were filled more than a week ahead of time, and a video stream of the day’s speakers was viewed by almost 1,500 people during the conference and in the week following. Recordings of the day’s talks can now be viewed on the Division of Pain’s YouTube channel.

We don’t have a cure for chronic pain. What we have are exceptional ways [to help] people get back their lives

During a recent conversation, Mackey told me the big turn-out reflects the keen interest people living with back pain have in finding solutions. “People are looking for better answers: why they have what they have and what they can do about it,” he said. “We wanted to provide them with real-world tools that they can use to control their pain.”

Speakers at the event covered varied ground, including physical therapy approaches to pain management, new research in using acupuncture to treat pain, self-management strategies, mindfulness-based pain reduction and the important role of sleep in pain. (Recent research has shown that poor sleep can intensify and prolong pain.) One over-riding theme was the role of the brain, Mackey said, not just in terms how people experience pain, but also how it can help turn down or turn up pain.

Mackey cautions that a quick fix often isn’t possible, so people living with chronic pain need to think about long-term management. “It’s a chronic disease, like diabetes. We don’t have cures for diabetes, and we don’t have a cure for chronic pain,” he said. “What we have are exceptional ways to control the disease and ways [to help] people get back their lives.” Speaker Beth Darnall, PhD, the event co-chair, emphasized that pain psychology techniques can empower people to lessen distress and pain, and begin moving toward meaningful life goals.

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Cardiovascular Medicine, Chronic Disease, Science, Stanford News, Stem Cells

Patching broken hearts: Stanford researchers regrow lost cells

Patching broken hearts: Stanford researchers regrow lost cells

Design 1_2Most heart attack survivors face a long and progressive course of heart failure due to damage done to the heart muscle. Now, in a study published in the journal Nature, researchers are reporting a method of delivering a missing protein to the lining of the damaged heart that regenerates heart muscle cells — cardiomyocytes — killed off during a heart attack.

The study, which was conducted in animal models, offers hope for future treatments in humans, according to the senior author of the study. “This finding opens the door to a completely revolutionary treatment,” Pilar Ruiz-Lozano, PhD, told me. “There is currently no effective [way] to reverse the scarring in the heart after heart attacks.”

The delivery system that researchers used in this study is a biodesigned tissue-like patch that gets stitched directly onto the damaged portion of the heart. The protein Fstl1 is mixed into the ingredients of the patch, and the patch, made of an acellular collagen, eventually gets absorbed into the heart leaving the protein behind. Our press release explains how the patch came to be:

The researchers discovered that a particular protein, Fstl1, plays a key role in regenerating cardiomyocytes. The protein is normally found in the epicardium — the outermost layer of cells surrounding the heart — but it disappears from there after a heart attack. They next asked what would happen if they were to add Fstl1 back to the heart. To do this, they sutured a collagen patch that mimicked the epicardium to the damaged muscle. When the patch was loaded with Fstl1, it caused new cardiomyocytes to regenerate in the damaged tissue.

In reading over the study, I was particularly interested in what an engineered tissue-like patch applied to a living heart looked like – and how exactly the patch got made. I called one of the study’s first authors and went to see him in his lab.

Vahid Serpooshan, PhD, a postdoctoral scholar in cardiology at Stanford, told me he can make a patch in about 20 minutes. It’s a bit like making Jell-O, he said; collagen and other ingredients get mixed together then poured into a mold. Serpooshan uses molds of various sizes depending on what kind of a heart the patch will be surgically stitched onto.

“The damaged heart tissue has no mechanical integrity,” Serpooshan said. “Adding the patch is like fixing a tire… Once the patch is stitched onto the heart tissue, the cardiac cells start migrating to the patch. They just love the patch area…”

Previously: Stanford physician provides insight on use of aspirin to help keep heart attacks and cancer away, Collagen patch speeds healing after heart attacks in mice and Big data approach identifies new stent drug that could help prevent heart attacks
Image, of a patch stitched to the right side of the heart, by Vahid Serpooshan

Chronic Disease, Health and Fitness, In the News, Nutrition, Obesity, Stanford News

A conversation about the diabetes epidemic

A conversation about the diabetes epidemic

On this morning’s KQED’s morning radio show, Forum, several doctors including Stanford’s Bryant Lin, MD, discussed how diabetes is affecting the health of millions of people globally.

A recent study in the Journal of the American Medical Association estimated that about half of all adults have diabetes (diagnosed or undiagnosed) or pre-diabetes. Lin and his fellow panelists talked about how changes in our diet and lifestyle have fueled the number of diabetic cases, as well as how genetics can tip the odds against certain patients. Lin mentioned that Asians have a higher rate of diabetes than whites, for example.

Like Lin, I have a family history of diabetes. (Like Lin, I’ve also struggled to maintain my weight). That history has made me keenly interested in staying abreast of recent findings about diabetes – and I surprised to hear that among young people, high rates of liquor consumption is influencing diabetes rates. It’s not just soda intake that we have to watch out for.

Another surprising finding that Lin described was that for pre-diabetics, taking Metformin, a drug that helps control diabetes and blood sugar, can help stave off full-blown diabetes. Eventually, it may become routine to prescribe this medication in certain populations, but Lin said that guidelines haven’t caught up with this aspect of diabetes care.

Other factors at play, Lin noted, include the role of the microbiome in promoting or protecting people from diabetes. And people who undergo bariatric surgery for weight management often find their diabetes is cured, but doctors don’t understand exactly why that’s the case.

Despite the staggering number of people affected, it’s clear that we still don’t understand all the complex factors that influence this disease.

Previously: Faulty fat cells may help explain how Type 2 diabetes beginsThe role of nutrition in diabetes prevention and managementThe importance of regular exercise in delaying and treating diabetes and Examining the role of exercise in managing and preventing diabetes

Cardiovascular Medicine, Chronic Disease, Women's Health

Surviving a betrayal of the heart

Surviving a betrayal of the heart

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; this month’s column comes from a patient with spontaneous coronary artery dissection (SCAD).

2259323415_ab113de5bc_zThis is a story about a betrayal of the heart — an actual heart. Girl has heart, girl treats heart well, heart gets torn up and girl figures out how to recover from this betrayal by her own body.

Last summer, I participated in my second sprint triathlon. The first part was a half-mile swim in a cold lake. I’d been swimming this distance for months and had done this same triathlon before. Yet, I couldn’t catch my breath, my chest hurt and swimming was appallingly hard for me. But I persevered and finished the biking and running events just fine.

Two weeks later, unnerved by my unsuccessful swim, I steeled myself for a similar swim across a lake in Idaho. Almost halfway through my swim, I started struggling to breathe and felt a band of pain and searing cold across my sternum. I felt weak and cold and couldn’t swim anymore.  Fortunately, my husband was on a paddleboard close by. I called him over, climbed on the board and hung onto his ankles for dear life (vomiting occasionally) as he paddled us to shore.

In retrospect, I had many of the typical symptoms women experience when having heart attack, but it took a while before it dawned on us that I was suffering from one. I don’t fit the profile: I was 53, nearly vegetarian, slim, fit with a mild addiction to kale smoothies. However, I had just gone through menopause and was on a low dose of HRT.

Fortunately, the ER doctor in Idaho did an EKG and figured out I was having a heart attack. The next day, an angiogram found a tear in the innermost wall of my coronary artery called a spontaneous coronary artery dissection (SCAD). This tear causes blood to flow between the layers of the arterial wall, blocking blood flow and causing a heart attack. SCADs are rare, yet, nearly 80-90 percent of SCAD patients are women in their early 40s with no additional risk factors.

It’s not yet known what causes SCADs. So, I am left with a lot of unanswered questions, and I’ve had to slowly rebuild trust in my own body and abilities, knowing my condition is rare and poorly understood.

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