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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

Clinical Trials, Ethics, Research, Stanford News

Should patients pay their way into clinical trials?

Should patients pay their way into clinical trials?

Photo of U.S. currency and a pharmaceutical capsuleIn a time of shrinking federal research budgets, here’s one idea for a solution: charge patients to participate in clinical trials.

Patients’ payment could fund studies that would not otherwise be conducted, said a group of medical ethicists led by Ezekiel J. Emanuel, MD, PhD, the former White House health-policy adviser who now chairs the Department of Medical Ethics and Health Policy at the University of Pennsylvania. Emanuel was asked by a group of academic investigators to review the legality and ethics of charging for enrollment in an early-phase clinical trial; he and his co-authors examine the pros and cons.

No laws or regulations prohibit pay-to-play, said the authors, and it has some upsides. By putting their money where their mouth is, patients could be demonstrating deep engagement with the research protocol, and affirming their informed consent. Their payment could be seen as a direct, Kickstarter-style version of a charitable contribution to medical research, or as an analogue to permissible payment for experimental treatments outside the confines of a clinical trial. Last but not least, there is a liberty argument, that “people should have the freedom to do whatever they want with their own money as long as they are not harming others or diminishing their rights and opportunities,” said the authors, whose perspective essay (subscription required) appears today in Science Translational Medicine.

But before going full libertarian, the authors put on the brakes. Let’s be honest, they said, this is less about a collaborative partnership than a potentially desperate need to save one’s own life; less about a charitable impulse than purchasing a service. It will skew research toward the health needs of the wealthy and could interfere with research integrity: A paying participant may be less willing to accept randomization to a control group or more reluctant to disclose symptoms and side effects. For their part, investigators might feel pressure to bend inclusion or removal criteria, or not to terminate a study. Ultimately, the authors conclude that pay-to-play is generally unethical, and warrants legislative and regulatory attention.

Co-author Govind Persad, JD, a Stanford graduate student in philosophy, told me he’s particularly concerned about participants feeling pressure to pay: “There is this real psychological pressure, if you or your kid are sick or in this desperate position, to do something that not only you wouldn’t have done, but that you see as having this direct, imminent benefit to yourself out of proportion to the benefit it’s likely to have.”

Persad hopes the essay will ignite an “educated debate” among researchers, policy makers, potential donors to medical research and people who stand to benefit from interventions to be studied in clinical trials. “An issue for people to think about going forward is: If we need more research into Condition X but pay-to-play is not the way, what would be some other good ways to try to expand the universe of trials?”

Related: A look at crowdfunding clinical trials, Can crowdfunding boost public support and financing for scientific research, Stanford forum on the future of health care in America posted online and When it comes to health-care spending, U.S. is “on a different planet”
Photo by David Goehring

Autoimmune Disease, Genetics, Immunology, Science, Stanford News, Technology

Women and men’s immune system genes operate differently, Stanford study shows

Women and men's immune system genes operate differently, Stanford study shows

A new technology for studying the human body’s vast system for toggling genes on and off reveals that genes connected with the immune system switch on and off more frequently than other genes, and those same genes operate differently in women and men. What’s more, the differences in gene activity are mostly not genetic.

A couple of years ago, geneticists Howard Chang, MD, PhD; Will Greenleaf, PhD, and others at Stanford invented a way to map the epigenome – essentially the real time on/off status of each of the 22,000 genes in our cells, along with the switches that control whether each gene is on or off.

Imagine a fancy office vending machine that can dispense 22,000 different drinks and other food items. Some selections are forever pumping out product; other choices are semi permanently unavailable. Still others dispense espresso, a double espresso or hot tea depending on which buttons you push. The activity of the 22,000 genes that make up our genomes are regulated in much the same way.

That’s a lot to keep track of. But Chang and Greenleaf’s technology, called ATAC-seq, makes it almost easy to map all that gene activity in living people as they go about their lives. Their latest study, published in Cell Systems, showed that the genes that switch on and off differently from person to person are more likely to be associated with autoimmune diseases, and also that men and women use different switches for many immune system genes. That sex-based difference in activity might explain the much higher incidence of autoimmune diseases in women — diseases like multiple sclerosis, lupus and rheumatoid arthritis.

The team took ordinary blood samples from 12 healthy volunteers and extracted immune cells called T cells. T cells are easy to isolate from a standard blood test and an important component of the immune system. With T cells in hand, the team looked at how certain genes are switched on and off, and how that pattern varied from individual to individual. Chang’s team also looked at how much change occurred from one blood draw to the next in each volunteer.

Chang told me, “We were interested in exploring the landscape of gene regulation directly from live people and look at differences. We asked, ‘How different or similar are people?’ This is different from asking if they have the same genes.”

Even in identical twins, he said, one twin could have an autoimmune disease and the other could be perfectly well. And, indeed, the team reported that over a third of the variation in gene activity was not connected to a genetic difference, suggesting a strong role for the environment. “I would say the majority of the difference is likely from a nongenetic source,” he said.

Previously: Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using
Photo by Baraka Office Support Services

Infectious Disease, Medical Education, Public Health, Research, Stanford News

A how-to guide on “galvanizing medical students” to administer flu vaccines

A how-to guide on "galvanizing medical students" to administer flu vaccines

image001Stanford’s Flu Crew, an initiative that gets medical students out into the campus and greater community administering flu vaccines, recently published a paper validating the importance of such initiatives for medical education and public health, and enumerating its best practices so other programs can follow in its footsteps.

Rachel Rizal and Rishi Mediratta were Flu Crew’s co-directors when we first wrote about their work in 2012. Rizal is now a fifth-year student and Mediratta a pediatrics resident at Stanford. They are lead authors on the article, “Galvanizing medical students in the administration of influenza vaccines: the Stanford Flu Crew,” which appears in the journal Advances in Medical Education and Practice.

I learned a lot about Flu Crew in an email exchange with Rizal, Mediratta, and a host of people they said were instrumental in this accomplishment. Catherine Zaw, a Stanford undergraduate who is a co-author on the recent paper, told me,”The Flu Crew concept has already spread to a couple of schools around the Bay Area, including UCSF, and I hope that with the publication of the paper, more medical schools will consider adopting it.”

The article is essentially a blueprint for replicating Flu Crew in other institutions. It describes Flu Crew’s innovative online-based curriculum, created by former Stanford medical student Kelsey Hills-Evans, MD (which she discussed in a post earlier this week). It lays out the planning needed to coordinate vaccination events, which in their case involves the medical school, undergraduate volunteers, the Vaden Student Health Center, Stanford’s Occupational Health Clinic, and community institutions like churches, libraries, and homeless shelters. And finally, it explains the impact on medical students’ attitudes to population health, as one of its main goals as a service-learning program is to provide students with experience in public health and patient interactions early on in their career.

Imee DuBose, MPH, who worked as operations manager at Occupational Health and was inspired by the “impressive professionalism” of Flu Crew’s student leadership to shift her career to student advising, told me: “As a public health professional, I see Flu Crew promoting community health through collaboration, and as a student affairs professional, I see student development and growth – this project combines the best of both worlds.”

Rizal and Mediratta’s successors for the two-year director position, Lauren Pischel and Michael Zhang, were also co-authors. Pischel explained that she thinks public health and preventative medicine are incredibly important in medical education.

“Campaigns like this link the individual you see sitting before you in clinic with the health of the population at large,” she said “I would like to see this paper be used to talk about how we can effectively integrate public health teaching and experience into medical school. There is quite a bit of room to grow in this direction.”

Previously: Stanford Medicine grads urged to break out of comfort zoneAn ounce of action is worth a ton of theory: Med student encourages community engagementFrenemies: Chronic cytomegalovirus infection boosts flu vaccination efficacyFlu Near You campaign aims to improve monitoring of flu outbreaks, vaccinations and Student “Flu Crew” brings no-cost flu vaccinations to the community
Related: The Flu Crew: Med students provide vaccinations to the community
Photo, of medical student Lichy Han administering a flu vaccine to Dean Lloyd Minor, MD, in 2012, courtesy of Imee Diego DuBose

Humor, Media, Medicine and Society, Neuroscience, Research, Stanford News

Did extraterrestrials chew up my news release, or does artificial intelligence still have a ways to go?

Did extraterrestrials chew up my news release, or does artificial intelligence still have a ways to go?

UFO

Almost two years ago, in a Scope blog entry titled “Can Joe Six-Pack compete with Sid Cyborg?” I posed the question: “Just how long will it be before we can no longer tell our computers from ourselves?”

I think it’s safe to say we’re not there yet. Either that, or extraterrestrials have been reading my news releases and finding them puzzling.

Last week we put out a news release I’d written about a dramatic discovery by Stanford radiologists Mike Zeineh, MD, PhD, Brian Rutt, PhD, and their colleagues. In brief, they’d analyzed postmortem slabs of brain tissue from people diagnosed with Alzheimer’s, compared them with equivalent brain-tissue slabs taken from people who’d died without any Alzheimer’s-like symptoms, and noticed some striking and intriguing differences. In a key brain region essential to memory formation, Zeineh and Rutt had spotted – only in Alzheimer’s brains, not normal ones – iron deposits engulfed by mobile inflammatory cells. This observation’s potentially big implications were plenty newsworthy.

It so happened that, on the day we issued the release, a high-powered five-day-long meeting on Alzheimer’s sponsored by the eponymous Alzheimer’s Association was in session in Washington, D.C. As a result, many of the brain-oriented science writers to whom my news release was targeted were preoccupied.

I was a little anxious about that. So, the other day, I turned to my favorite search engine to see if the release had managed to get some traction in the popular press. As I’d feared, the Washington conference had sucked up a lot of the oxygen in the earthly neuroscience arena.

But apparently, the release had done better in Outer Space. I saw that it had been picked up by, for example, Red Orbit (a website that I’ve always assumed, based on its name, emanates from Mars).

My eyes were next drawn to a link to an unfamiliar outfit called AZ News, which bills itself in a tagline as an “International Online News Site.” I clicked on the link, and saw a news report with the same title as my release. I started reading the text below.

The first words were: “In autopsy mind hankie from people not diagnosed with Alzheimer’s…” I don’t know what an “autopsy mind hankie” is, but I suspect it’s a mind-blower.

I checked our release. That’s not what I’d written at all. What I’d said was, “In postmortem brain tissue from people not diagnosed with Alzheimer’s…”

It seemed pretty clear that the release had been translated into some language – I had no idea which – and then, for some reason, reverse-translated back into English. I read on.

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Scope Announcements, Stanford News

Stanford Medicine is on Instagram

Stanford Medicine is on Instagram

Do you use Instagram? We do! Stanford Medicine recently launched a feed designed to capture the best of its places and people (the images above are among the ones posted this month), and we hope you’ll follow along.

Previously: Introducing the Scope magazine on Flipboard and 100,000 followers for @StanfordMed

Ask Stanford Med, Cancer, Genetics, Women's Health

Genetic testing and its role in women’s health and cancer screening

Genetic testing and its role in women's health and cancer screening

14342954637_3f8c3fde77_zYears ago, when I first learned that genetic testing could help screen for some cancers, such as breast, ovarian and bone, it seemed like a no-brainer to get this testing done. Now I know better; genetic testing is a helpful tool that can help you assess your risk for certain kinds of cancer, but it’s not recommended for everyone. Senior genetic counselor Kerry Kingham, a clinical assistant professor affiliated with the Cancer Genetics Clinic at Stanford, explains why this is the case in a recent Q&A with BeWell@Stanford.

Cancer can be “hereditary” or “sporadic” in nature, Kingham says. Hereditary cancers, such as the forms of breast cancer related to a mutation in the BRCA1 or BRCA2 genes, are associated with an inherited genetic mutation. In contrast, sporadic cancers arise independent of family history or other risk factors. Since genetics testing detects gene mutations, it can only be used to help screen for the mutations that may lead to forms of hereditary cancer.

Kingham elaborates on this point, when it makes sense to get genetic testing, and what the results may mean in the Q&A:

Twelve percent of women in the U.S. develop breast cancer; it is a common disease. Yet, only five to ten percent of these women will develop breast cancer because of a hereditary gene mutation.

The best step to take prior to deciding whether or not to proceed with genetic testing is to meet with a genetic counselor. Your doctor can provide a referral. The genetic counselor will take a three generation family history, discuss the testing that might be indicated for you or a family member, and explain the risks and benefits of the testing. They also discuss the potential outcomes of the testing: whether a mutation is found, a mutation is not found, or there are uncertain results. Even when a genetic test is negative, this may not mean that the individual or their family is not at risk for cancer.

At this point you may be wondering: Why bother with genetic testing if it’s only useful for hereditary cancers and a negative test result is no guarantee you’re risk-free? Kingham’s closing comment addresses this question nicely: “I would say that your genes don’t change – they are what they are, and knowing what is in our genes can often help us learn how to take better care of our health.”

Previously: Stanford researchers suss out cancer mutations in genome’s dark spotsAngelina Jolie Pitt’s New York Times essay praised by Stanford cancer expertNIH Director highlights Stanford research on breast cancer surgery choices and Researchers take a step towards understanding the genetics behind breast cancer
Photo by Paolo

Imaging, Microbiology, Research, Science, Stanford News, Technology

3-D structure of key signaling protein and receptor revealed

3-D structure of key signaling protein and receptor revealed

Using ultra-bright X-rays at SLAC National Accelerator Laboratory, a team of international researchers has captured the 3-D structure of a key signaling protein and its receptor for the first time.

The discovery provides new insight into the functioning of a common cell receptor called a G protein-coupled receptor or GPCR. Researchers estimate this protein, and its relatives, are the targets of about 40 percent of pharmaceuticals. From a SLAC release:

“This work has tremendous therapeutic implications,” said Jeffrey Benovic, PhD, a biochemist who was not involved with the study. “The study is a critical first step and provides key insight into the structural interactions in these protein complexes.”

Specifically, the researchers were able to illuminate the structure of the GPCR bonded with a signaling protein called arrestin. Arrestins and G proteins both dock with the GPCRs, however, researchers had previously only examined a bonded G protein. G proteins are generally the “on” switch, while arrestins usually signal the GPCR to turn off:

Many of the available drugs that activate or deactivate GPCRs block both G proteins and arrestins from docking.

“The new paradigm in drug discovery is that you want to find this selective pathway – how to activate either the arrestin pathway or the G-protein pathway but not both — for a better effect,” said Eric Xu, PhD, a scientist at the Van Andel Research Institute in Michigan who led the experiment. The study notes that a wide range of drugs would likely be more effective and have fewer side effects with this selective activation.

Previously: Why Stanford Nobel Prize winner Brian Kobilka is a “tour de force of science”, Funding basic science leads to clinical discoveries, eventually and Video of Brian Kobilka’s Nobel lecture
Video by SLAC National Accelerator Laboratory

Ethics, In the News, Medicine and Society, Science, Science Policy, Sports, Stanford News

Stanford expert celebrates decision stopping testosterone testing in women’s sports

Stanford expert celebrates decision stopping testosterone testing in women's sports

Female track and field athletes no longer need to have their natural testosterone levels below a certain threshold to compete in international events, the so-called “Supreme Court of sports”, the Court of Arbitration for Sport, ruled Monday.

Katrina Karkazis, PhD, a Stanford senior research scholar who was closely involved with the case, got the news on Friday, while she was in a San Francisco dog park. “What a day!” she said. “I was madly refreshing my email — I thought we were going to lose… I just started screaming and crying.”

Karkazis, who is an expert on ethics in sports and also gender, said she spent a year of her life working on the case.

She served as an advisor to 19-year-old sprinter Dutee Chand, who challenged the regulation that female athletes must have certain testosterone levels or undergo medical interventions to lower their testosterone to be allowed to compete against women in events governed by the International Association of Athletics Federations (IAAF), the international regulatory body of track and field.

The ruling suspends the IAAF’s testing regimen for two years, but Karkazis expects the decision will lead to permanent changes in women’s sports, including a reevalution by the International Olympic Committee.

“I’m thrilled,” Karkazis said. She said she was also surprised. “I didn’t think it was our time. I thought there were still too many entrenched ideas about testosterone being a ‘male hormone’ and it not belonging in women.”

Karkazis gained international attention after penning an op-ed in The New York Times in 2012 when the IAAF and the International Olympic Committee crafted a new policy banning women with naturally high levels of testosterone from competing.

“You can’t test for sex,” Karkazis said. “It’s impossible. There’s no one trait you can look at to classify people. There are many traits and there are always exceptions.”

She said that now women who have lived and competed their entire lives as women will be eligible to compete, a default policy she believes is sufficient to ensure a level playing field.

Previously: “Drastic, unnecessary and irreversible medical interventions” imposed upon some female athletes, Arguing against sex testing in athletes and Is the International Olympic Committee’s policy governing sex verification fair?
Photo by William Warby

Infectious Disease, Medical Education, Medicine and Society, Public Health, Stanford News, Videos

Online curriculum helps students and public learn about influenza

Online curriculum helps students and public learn about influenza

Stanford’s Flu Crew, which administers flu vaccines in and around the Stanford community, has had many successes over the last few years, which we’ll highlight in a post later this week. One achievement I thought deserved special attention is an innovative curriculum on influenza created by former medical student Kelsey Hills-Evans, MD, now an internal medicine resident at Harvard. Her online videos, such as the one above (which is the first in the series), are accessible not only to Flu Crew’s student participants but the public at large.

The videos were produced via a partnership with Khan Academy and built on the flipped classroom model championed by Charles Prober, MD, senior associate dean of medical education. They also received the Shenson Bedside Innovation Award in 2013. Rishi Desai, MD, a Stanford pediatric infectious disease physician and medical fellow at Khan Academy, supervised Hills-Evans’ efforts and told me in an email that Hills-Evans and the Flu Crew “put together some really amazing videos explaining everything from the basics of influenza to common misconceptions and fears that people have about the flu vaccine. They deserve all of the credit for the idea and execution of the project.”

Hills-Evans tried to keep each video under five minutes: “I wanted it to be a quick, high-yield snapshot of information that people could watch in one sitting and not easily forget.” She shared more details with me over email:

What did you aim to convey in these training videos? How did you imagine your audience? 

I wanted our student volunteers to come away from the training with enough general knowledge about influenza to answer nearly any question that patients might have. We equipped them with knowledge about its history, how it genetically changes over time, the clinical symptoms, the vaccine’s risks and benefits, specific patient populations, and even a section on flu shot myths. Our last video was meant for students to become public-health advocates equipped with facts and counter-arguments to some of the most common excuses people have for not protecting themselves with the flu vaccine.

For these general info videos, I was really aiming to be accessible to the general public. The topics are all applicable to the lay person, so I tried my best to stay away from clinical jargon. I wanted people to come away from the training with a better understanding of how dangerous influenza can be – many people shrug at the flu as a bit worse than a winter cold, but it kills tens of thousands of people every year. In addition, there are so many myths generated by popular media and the public about the illness itself (i.e., “I got a stomach flu” which is never actually an influenza virus) and especially about vaccines. It was important to me that we make these videos public so more individuals could be informed.

For the sections meant only for clinical personnel, our priority was to train the members of the Stanford Flu Crew, but I also wanted this component to be exportable to other medical programs. It was meant to teach students to deliver the best intramuscular (IM) injections possible. We’ve been told countless times that our method for IM injections yields extremely high patient satisfaction and nearly pain-free injections (some say “the best flu shot they’ve received”).

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