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Cancer, Genetics, Pediatrics, Research

California collaboration focuses on analyzing pediatric cancers

California collaboration focuses on analyzing pediatric cancers

Breakthroughs in medical research can take a frustratingly long time to reach doctors and the patients they treat. But a newly funded collaboration between computational biologists at UC Santa Cruz and researchers conducting pediatric cancer clinical trials at three California institutions, including one led by Stanford’s Alejandro Sweet-Cordero, MD, may set the stage to bring the power of cancer genomic research into the hands of clinicians and their patients.

The California Initiative to Advance Precision Medicine is funding the UC Santa Cruz Genomics Institute’s California Kids Cancer Comparison project. The project will develop technology to use a cancer’s genetic mutations, its DNA signature, to match it to similar cancers regardless of the tissues the cancers originated from. So, if a lung cancer’s DNA signature more closely resembles a certain kind of brain cancer’s signature, then doctors may pursue treatments that have proven effective against that brain cancer. This technique is especially beneficial for pediatric cancers, which are rarer than adult cancers and less likely to have been included in clinical drug trials.

The project builds on the UC Santa Cruz Genomic Institute’s Treehouse Childhood Cancer Project, led by bioinformatics researcher and UCSC postdoctoral scholar Olena Morozova, PhD, which showed how the academic investigations could have real world consequences.

“Treehouse was started as a research project – we weren’t thinking we could go clinical with it,” Morozova told me. That changed when she and colleagues analyzed the genes of an aggressive sarcoma from an 8-year-old boy enrolled in a cancer genomic clinical trial six months ago.

The child’s cancer had originated in his brain and had gone into remission after a standard treatment of chemotherapy, radiation and a bone marrow transplant. But two years later doctors found tumor growths in his lungs.

Morozova and her colleagues found that genes turned on in the boy’s cancer cells matched those turned on in a rare neuron tumor called a neuroblastoma that is found almost exclusively in children.

Neuroblastomas happened to be the cancer Morozova researched for her PhD, and she knew of a molecular signaling pathway that could be active in the boy’s cancer. Two drugs that target this pathway had been shown to be effective in clinical trials and had received Food and Drug Administration approval for adult patients. The UCSC researcher’s passed on their data supporting that the pathway was active in the tumor to the boy’s physician, who chose to administrate the drugs.

By partnering with researchers like Sweet-Cordero, who’s conducting a trial on difficult-to-treat cancers in children and young adults, the California Kids Cancer Comparison project will be able to compare the cancer DNA sequences to a collected database of both adult and pediatric cancers. And they hope to automate parts of the analysis to make this technology accessible to doctors without degrees in bioinformatics.

“If it is successful, we hope to offer it to every child with cancer in California and elsewhere,” said Morozova.

Kim Smuga-Otto is a student in UC Santa Cruz’s science communication program and a former writing intern in the medical school’s Office of Communication and Public Affairs. 

Previously: Gene-sequencing rare tumors – and what it means for cancer research and treatment

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

Pediatrics, Podcasts, Public Safety, Women's Health

Jimmy Carter: The final campaign

Jimmy Carter:  The final campaign

People Jimmy CarterShortly after leaving the White House in 1980, Jimmy and Rosalynn established the Carter Center. It is from there that their efforts at “waging peace, fighting disease and building hope” – the center’s mission – have been launched.

Along with his global travels to advance democracies around the world, his projects in global health, and his time building for Habitat for Humanity, Jimmy Carter is also a prolific writer. He’s written twenty-eight books. One of his most recent – A Call to Action, Women, Religion, Violence, and Powerdetails the discrimination that women and girls face worldwide. Widely recognized for his Christian beliefs and noted as a Sunday school teacher for more than 70 years – Carter challenges those who use religious texts to deny women equality. In a Call to Action, he writes, “Women and girls have been discriminated against too long in a twisted interpretation of the word of God.”

For the latest Stanford Medicine, a special on issue on pediatric research and care, I spoke with Carter about girls and women’s equality – an issue that he said would receive his highest priority in his final years. But this summer brought disturbing health news, and a different priority has entered his life: treating metastatic cancer that has spread to his brain.

I worked in the Carter White House. Like many others who served there, I wasn’t prepared for this news – we viewed Jimmy Carter to be indestructible. Even the word “cancer” in regards to Carter seems oxymoronic when you know firsthand his indomitable spirit and boundless energy.

I spoke with him for this 1:2:1 podcast and Q&A before his diagnosis. Later in the summer, I followed up with an email wishing him well and a speedy recovery, and he responded: “Thanks, Paul. I am at ease, and grateful. Jimmy”

And then late last month, just two days before Carter’s 91st birthday, Habitat for Humanity announced that his medical team approved his traveling to Nepal in November to build a home there. (Note from editor: Habitat for Humanity has cancelled the trip due to safety concerns.) Talk about an indomitable spirit and boundless energy.

Previously: Stanford Medicine magazine tells why a healthy childhood matters and Lobbying Congress on bill to stop violence against women
Illustration by Gérard DuBois

Cardiovascular Medicine, Pediatrics, Pregnancy, Research

Higher blood sugar in pregnancy tied to heart defects in baby, even if mom isn’t diabetic

Higher blood sugar in pregnancy tied to heart defects in baby, even if mom isn't diabetic

five-heartsFor many years, doctors have known that women who had diabetes during pregnancy faced an increased risk of giving birth to a baby with a congenital heart defect. But now, for the first time, researchers have shown that the risk isn’t limited to women with diabetes. A new Stanford study, publishing today in JAMA Pediatrics, found that women who were carrying a fetus with tetralogy of Fallot, the most common cause of blue baby syndrome, had higher blood sugar levels on average than women carrying healthy fetuses, even if the mothers were not diabetic.

From our press release about the research:

“Diabetes is the tail end of a spectrum of metabolic abnormalities,” said James Priest, MD, the study’s lead author and a postdoctoral scholar in pediatric cardiology. “We already knew that women with diabetes are at significantly increased risk for having children with congenital heart disease. What we now know, thanks to this new research, is that women who have elevated glucose values during pregnancy that don’t meet our diagnostic criteria for diabetes also face an increased risk.”

The Children’s Heart Center at Lucile Packard Children’s Hospital Stanford (where Priest, who is also a pediatric cardiology fellow, sees patients) is already a world leader in treating children born with tetralogy of Fallot. Pediatric cardiothoracic surgeon Frank Hanley, MD, has developed a surgical technique called unifocalization that allows him to repair the defect in a single, long operation – which is safer than the alternative of putting babies and children through several open-heart surgeries. Many families come long distances so their children can receive the lifesaving surgery.

Although the Heart Center team is glad to be able to offer state-of-the-art treatment for kids who already have heart defects, they would be even happier to know how to prevent such defects from happening in the first place. Genetics plays into some heart defects, but in most cases, the cause is a mystery.

So this new study, though relatively small with 277 subjects, gives a clue that the Stanford team is eager to follow with other investigations:

“I’m excited by this research because it opens up a lot of questions about how physiologic processes in the mother may be related to congenital heart disease,” Priest said. “Most of the time we don’t have any idea what causes a baby’s heart defect. I aim to change that.”

The study’s senior author, Gary Shaw, DrPH, professor of pediatrics in neonatal and developmental medicine, added, “There are several other kinds of structural birth defects, in addition to heart defects, that have been linked with overt diabetes. This new work will motivate us to ask if underlying associations with moderately increased glucose levels may be similarly implicated in risks of some of these other birth defects.”

I also chatted with pediatric cardiologist and Heart Center director Stephen Roth, MD, who pointed out a practical advantage of the new finding that hadn’t occurred to me: We already know how to address elevated blood sugar with strategies such as dietary change, exercise and medications. If today’s discovery is replicated in larger studies, it wouldn’t be hard to translate it into action.

“It’s always wonderful to discover new information about the cause of a disease or class of diseases,” Roth told me. “And it’s particularly encouraging when we have the possibility of modifying the cause with existing therapies to reduce the likelihood that the disease occurs.”

Previously: Patient is “living to live instead of living to survive” thanks to heart repair surgery, Little hearts, big tools and When ten days = a lifetime: Rapid whole-genome sequencing helps critically ill newborn
Photo by emdot

Global Health, Pediatrics, Stanford News

Stanford Medicine magazine tells why a healthy childhood matters

Stanford Medicine magazine tells why a healthy childhood matters

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I’ve forgotten most of my childhood experiences – which is perfectly normal. But apparently my body remembers many of those experiences – and I learned while editing the new Stanford Medicine magazine that’s normal too. The fall issue’s special report, “Childhood: The road ahead,” is full of stories of researchers realizing the impact early experiences can have on adult health. Some of their discoveries are surprising.

“Some people think kids are protected by virtue of being kids. In fact, the opposite is true,” pediatric psychiatrist Victor Carrion, MD, told writer Erin Digitale, PhD, when she interviewed him for her story on the long-term effects of childhood trauma. Other writers found the same goes for other types of early damage: Kids are resilient but they also carry hidden scars.

The report also includes a Q&A with former President Jimmy Carter on discrimination against women and girls, which he considers the most serious human rights problem on Earth. The online version of the magazine includes audio of the Carter conversation.

Other highlights of the magazine’s special report include:

  • Go to bed“: An article on the devastating toll inadequate sleep takes on teens, with an update on efforts, including a Stanford project, to fix the problem.
  • When I grow up“: A report on the growing need for support of chronically ill children making the jump to adult care, and on the progress that’s being made.
  • Beyond behavior“: A story about a high school student’s return to health after an assault, and the new type of therapy that helped her.
  • Rocket men“: A feature about three rocket-combustion experts teaming up with a pediatrician to analyze the breath of critically ill children at warp speed.
  • Warm welcomes“: An article on blending Western medicine into traditional culture to reduce newborn mortality in the developing world.
  • Bad for the bone“: A quick look at a new way to study the toll of childhood disease on bones.

The issue also has an article on a surprising role for viruses in human embryos, as well as a report from India on how vision, investment and medical know-how has brought about an ambulance system — now 10 years old and one of the most important advances in global health today. The online version includes a video showing the ambulance system in action.

Many thanks to Lucile Packard Children’s Hospital Stanford, which helped support this issue.

Previously: This summer’s Stanford Medicine magazine shows some skin, Stanford Medicine magazine reports on time’s intersection with health and Stanford Medicine magazine traverses the immune system
Illustration from the cover of Stanford Medicine magazine’s fall 2015 issue by Christopher Silas Neal

Pediatrics, Public Safety, Stanford News

A reminder to parents to be careful of open windows

A reminder to parents to be careful of open windows

7867279958_6d74bdf4f7_z croppedPreventing falls from windows may not be something that’s on the mind of every parent – especially this time of year. But as the Indian summer continues here in the Bay Area and elsewhere, windows in homes may be left open, leaving kids vulnerable to accidents.

Over on the Healthier, Happier Lives Blog yesterday, Daniel Imler, MD, assistant professor of pediatric emergency medicine, talked about injuries caused by falls, noting that the most common kinds are extremity fractures, traumatic brain injuries, and damage to the cervical spine. After saying that “window screens only offer minimal help,” he also outlined some preventive tips for parents:

Move furniture away from windows and prevent children from climbing over. Locking all closed doors and windows is a great preventative measure as well. If you do open a window safety locks can help keep the window open only 4 inches for safety. Some families choose to install windows that open from the top down on floors above the ground level.

Previously: A young child, a falling cabinet, and a Life Flight rescueCarseats save lives, but only if kids are buckled in and Rattled by one child’s injury, a whole family becomes accident-prone
Photo by Kalexander2010

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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Neuroscience, Pediatrics, Research

Tutoring changes the brain in kids with math learning disabilities

Tutoring changes the brain in kids with math learning disabilities

One-on-one tutoringA new Stanford study, publishing today in Nature Communications, sheds light on how to help children with math learning disabilities. One-on-one cognitive tutoring improves math performance in these children and also normalizes brain activity in several regions important for numerical problem solving, the research found.

The findings are important because math learning disabilities often fall off educators’ and parents’ radar. (Everyone has heard of dyslexia, but its numerical equivalent, dyscalculia? Not so much.) Yet math learning disabilities can hamper a child’s ability to gain basic life skills such as managing time and money, and can prevent children from growing up to pursue math- and science-related careers.

The new study is similar to another recent experiment that demonstrated alleviation of math anxiety with tutoring. Both studies are the work of the Stanford MathBrain Project, directed by Vinod Menon, PhD. Teresa Iuculano, PhD, a postdoctoral scholar working with Menon, is the new study’s lead author.

In the new research, 30 children in third grade received eight weeks of one-on-one tutoring in basic arithmetic skills; half of the kids had math learning disabilities and half did not. The instructors adjusted the sessions’ pace and emphasis individually for each child, helping students past bottlenecks in their learning without making them feel like they might be falling behind their peers. All of the children got MRI brain scans before and after tutoring.

Before tutoring began, the kids with math learning disabilities had abnormal function in a network of brain areas involved in solving numerical problems, including the parietal, prefrontal and ventral temporal-occipital areas. Kids without math learning disabilities did not show these problems. After tutoring, the differences between the two groups’ brain scans disappeared. The children’s math performance also improved, in sync with the brain changes.

These findings suggest that tutoring actually fixes the brain issues at the root of math learning disabilities, rather than providing children with a work-around that circumvents the real problem.

“We demonstrate that, in parallel with performance normalization, 1:1 tutoring elicits extensive functional brain changes in children with math learning disabilities, normalizing their brain activity to the level of neurotypical peers,” the researchers wrote in their paper.

The scientists want to conduct follow-up studies to find out how long the effects of tutoring last. Their new discoveries also lay a framework for studying how to intervene in other forms of learning disabilities.

Previously: Stanford team shows that one-on-one tutoring relieves math anxiety in children, Stanford team uses brain scans to forecast development of kids’ math skills and New research tracks “math anxiety” in the brain
Photo by U.S. Department of Education

FDA, Health Policy, Nutrition, Pediatrics, Public Health, Research, Stanford News

How much Bisphenol A is okay?

How much Bisphenol A is okay?


A new study came out this week that happened to remind me of one of my pet peeves about certain biomedical studies — choosing an “outcome” measure that doesn’t tell you what you really want to know. The study, which was led by Stanford postdoctoral fellow Jennifer Hartle, DrPH, and estimated the amount of BPA a child is exposed to in the course of a normal school day, was great. But her description of EPA safety tests on the plastics component Bisphenol A, or BPA — done back in the 1980s — made me think back to earlier work by University of California, Berkeley biologist Tyrone Hayes, PhD.

In the 1990s, the agricultural herbicide atrazine was safety tested by exposing frogs to low doses of atrazine as they developed from eggs to tadpoles to frogs. The adult frogs didn’t die or show obvious deformities such as extra legs, so the pesticide was deemed safe. But Hayes took a closer look and, in 2002, found that even at very low levels of atrazine exposure, male frogs were producing eggs instead of sperm.

So no gross deformities if you just looked at the frogs for 30 seconds. But in fact the animals had experienced a dramatic change in their health and biology. The lesson is that, in biology, sometimes the right outcome measure is something you have to really look for. There is a lot more to the Hayes-atrazine story.

But back to the current study: Hartle and her colleagues turned their attention to national school breakfast and lunch programs, which provide nutritious meals to 30 million kids every year but also deliver small amounts of BPA, an estrogen mimic that messes with hormones. Children’s meals are disproportionately packaged in tiny one-meal containers. Those tiny packages of apple sauce and juice have a greater BPA-emitting surface area than a big carton or can for the amount of food. And school kids often eat meals off plastic trays with plastic forks and spoons. For children who eat a lot of meals at school, it can add up.

According to Hartle’s paper, appearing today in the Journal of Exposure Science and Environmental Epidemiology, the question isn’t whether the kids are getting BPA in their meals — they are — but whether any of them are getting doses of BPA that could affect their long-term health. Based on those 1980s studies, the EPA estimates that BPA is safe at chronic exposure levels below 50 μg per kilogram of body weight per day. Happily, Hartle and her colleagues found that children are getting far less than that — as little as 0.0021 μg for a low-BPA breakfast to 0.17 μg for a high-BPA lunch. Everything should be hunky-dory, right?

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Clinical Trials, Mental Health, Parenting, Pediatrics, Research, Stanford News

Parents can help their teens recover from bulimia, say Stanford researchers

Parents can help their teens recover from bulimia, say Stanford researchers

Mom&teenTeenagers with bulimia nervosa benefit from their parents’ help in stopping their eating disorder. In fact, a therapy that involves parents works better for teens than one that does not, according to the first large head-to-head comparison in adolescents of two well-known bulimia treatments.

The findings are described in a study of 130 young people with bulimia that was published last week in the Journal of the American Academy of Child and Adolescent Psychiatry.

The research, which was jointly led by Stanford’s James Lock, MD, PhD, and a longtime collaborator, Daniel Le Grange, PhD, compared an approach tailored to teens with one commonly used in adults. In family-based therapy, the bulimia patient and a parent work together to stop the disordered eating behavior. In contrast, in cognitive behavioral therapy, which is widely recognized as the best approach for bulimic adults, there is more focus on changing abnormal thoughts about food and less emphasis on behavior change.

At the end of six months of treatment, 39 percent of patients in family-based therapy had abstained from the binge-and-purge cycle of bulimia for at least four weeks. Only 20 percent of those in the cognitive behavioral therapy group had done the same. The gap persisted six months after treatment ended, though it seemed to have closed by a year after the end of treatment.

Lock, who directs the Comprehensive Eating Disorders Program at Lucile Packard Children’s Hospital Stanford, said the findings are not surprising, given that teens are at a different stage of the illness and have different cognitive capabilities than adults with bulimia. But they are very important, since they suggest that the family-based approach is a faster way for young patients to recover from bulimia. From our press release about the study:

“The strategy for cognitive behavioral therapy requires a fair amount of abstract reasoning, motivation and persistence that often has not reached full capacity in teens,” [Lock] said, adding that doctors may need to decide on a case-by-case basis whether a teen would benefit from one treatment versus the other. “The cognitive and developmental context is very different for teens than for adult patients,” he said.

And it’s normal for teenagers to need their parents’ assistance in navigating difficult situations, he added. “The big take-home message is that families can really help their kids with bulimia nervosa.”

Previously: Family therapy an effective way to treat anorexic teens, Incorporating the family to help teens overcome eating disorders and Families can help their teens recover from anorexia, new study shows
Photo by J.K. Califf

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