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Imaging, Research, Stanford News, Stroke, Technology

Image-interpretation software could open window of treatment for stroke

Image-interpretation software could open window of treatment for stroke

open windowRestoring blood flow to the brain quickly after a stroke is key to damage control as well as to optimal recovery. But restoring blood flow to brain tissue that is already dead can cause problems, like swelling and hemorrhage.

That makes the treatment of choice – an intravenous dose of a substance called tPA, which dissolves clots – a double-edged sword. The consensus in the medical community is that tPA is not a good idea once 4-1/2 hours have elapsed since a patient has suffered a stroke.

But the consensus is based on averages, derived from numerous studies. Clinicians have tended to treat that 4-1/2 hour time-point as analogous to a window slamming shut. Yet every stroke, and every patient who experiences one, is unique.

A new study published in the New England Journal of Medicine joins three earlier ones that show improved results when tPA administration is combined with the insertion of a device – a so-called stent retriever – that can mechanically break up clots in the brain.

Even more exciting, two of the four studies, including the new one, employed software called RAPID – designed and developed at Stanford at the instigation of Stanford neurologist Greg Albers, MD – that quickly interprets brain scans of patients and helps clinicians decide which patients will benefit from supplementing the standard intravenous tPA infusion with the stent retrieval procedure. In both of these two studies, substantial majorities of patients selected as good candidates for the combination had extremely high rates of solid recovery as measured three months after their stroke – the best results ever obtained in stroke studies.

Albers, who is also one of the co-authors of the new NEJM study, hopes to move stroke care away from the clock on the wall and instead focus on a biological clock – what the brain image shows to be going on inside this patient’s brain, now – so that each patient’s care can be individualized and optimized. It could turn out that for some patients, 4-1/2 hours after a stroke is already too late for aggressive clot-busting treatment, while for others the window remains wide open for 6, 7, 8 hours or longer.

Previously: Targeted stimulation of specific brain cells boosts stroke recovery in mice, Calling all pharmacologists: Stroke-recovery mechanism found, small molecule needed and Stanford neuroscientists uncover potential drug treatment for stroke
Photo by glasseyes view

Research, Science, Stanford News, Surgery

Will scars become a thing of the past? Stanford scientists identify cellular culprit

Will scars become a thing of the past? Stanford scientists identify cellular culprit

346801775_c5a1e37a6d_zI have a scar on my chin from a fall I took while rollerskating when I was about 12. One minute I was blithely zooming along to Bob Seger’s hit Against the Wind (earworm alert!), reveling in my new ability to skillfully cross one foot in front of the other and thinking about that cute boy by the snack counter, and the next I was chin down skidding across the flat, grey and (I then realized) very hard floor to come to rest against the wooden wall in an ignominious heap.

Although the experience left an impression on my psyche, as well as my skin, I can’t claim any long-lasting problem from the thin line on my chin. After all, nearly all of us have something similar. But scars can also be debilitating and even dangerous.

Now plastic and reconstructive surgeon Michael Longaker, MD, and pathologist and stem cell expert Irving Weissman, MD, have identified the cell type in mice that is responsible for much of the development of a scar. They’ve shown that blocking this cell’s activity with a small molecule can reduce the degree of scarring. Because a similar drug molecule is already approved for use in humans to treat Type 2 diabetes, the researchers are hopeful that they can begin clinical trials in humans soon. The research was published today in Science.

As Longaker explained in our release on the study:

The biomedical burden of scarring is enormous. About 80 million incisions a year in this country heal with a scar, and that’s just on the skin alone. Internal scarring is responsible for many medical conditions, including liver cirrhosis, pulmonary fibrosis, intestinal adhesions and even the damage left behind after a heart attack.

Longaker and his colleagues found that a subset of a skin cell called a fibroblast is responsible for much of the collagen deposition that leads to scarring. Inhibiting the activity of a protein on the surface of the cells significantly reduced the amount of scarring during wound healing in laboratory mice – from about 30 percent of the original wound area down to about 5 percent -the researchers found. Furthermore, they showed the cells are also involved in the thickening and darkening of skin exposed to radiation therapy for cancer, as well as the spread of melanoma cancer cells in the animals.

Longaker’s been interested in how the skin heals for decades–ever since he learned as a student that, prior to the third trimester, human fetuses heal from trauma or surgery without any scarring. Now he’s excited to learn whether there’s a way to recapture that long-lost ability as adults and at least reduce the degree of scarring during skin repair.

“I’ve been obsessed with scarring for 25 years,” Longaker told me. “Now we’re bringing together the fields of wound healing and tumor development in remarkable new ways. It’s incredibly exciting.”

Longaker and Weissman are both also members of the Stanford Cancer Institute.

Previously: New medicine? A look at advances in wound healing, Stanford-developed device shown to reduce the size of existing scars in clinical trial and Mast cells not required for wound healing, according to Stanford study
Photo by Paulo Alegria

Biomed Bites, Immunology, Research, Science, Technology, Videos

Not immune from the charms of the immune system

Not immune from the charms of the immune system

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers.

Once upon a time, a researcher named Holden Maecker, PhD, met flow cytometry, a technique used to examine cells by suspending them in fluid and then passing them by an electronic detector.

A match that could only be made in a science lab, Maecker was hooked. Maecker tells the tale in the video above:

Flow cytometry is a great technique for looking at the immune system and it’s also a little bit of an art, which also attracted me. It’s something that not everybody can do perfectly well and I got a little bit good at it and decided it was a fun thing to do and a good way to look at the immune system.

Maecker and flow cytometry haven’t parted, yet he’s broadened his mastery of a variety of other techniques to study the immune system as the director of Stanford’s Human Immune Monitoring Center.

“It’s a very interesting position because it allows me to collaberate with a lot of different peopel doing projects that have to do wiht human immune responses — everything from sleep apnea and wound healing to flu vaccines and HIV infections,” Maecker said. “It’s amazing the breadth we have here [at Stanford].”

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail, Immunology meets infotech and Stanford Medicine magazine traverses the immune system

Research, Sports, Stanford News

Stanford bioengineers and clinicians team up to shed light on how concussions affect the brain

Stanford bioengineers and clinicians team up to shed light on how concussions affect the brain

9764280602_4d132cd012_zIn an effort to better understand and prevent concussions, bioengineers and clinicians at Stanford have turned athletic fields into laboratories to tackle fundamental questions about brain injuries. A story recently published in Stanford Magazine offers a detailed look at the ongoing research involving high-tech, data-gathering mouth guards worn by players during games to record the impact of hits and advanced imaging studies to measure subtle changes on athletes’ brain scans.

Kristin Sainani writes:

Unfortunately, after years of inattention, the science of concussions remains in its infancy. “We don’t even know what a concussion is at a basic, biological level,” says Mona Hicks, who oversaw traumatic brain injury research at the National Institutes of Health for nine years and is now chief scientific officer at One Mind, a nonprofit focused on brain disease. This scientific void creates uncertainty when it comes to addressing such controversies as how long to hold concussed athletes out of play, whether to ban heading in youth soccer and how much to change the game of football.

David Camarillo, assistant professor of bioengineering and a former football player at Princeton University, is studying the physics of such hits. His lab has outfitted most of Shaw’s team with high-tech, data-gathering mouth guards that the players wear during games. Seattle-based X2Biosystems had developed prototypes for a commercial product; Camarillo’s group customized the design for research use. The devices measure how violently a player’s head gets tossed around during collisions, falls and other impacts.

“My long-term goal is to prevent concussions,” Camarillo says. “The first step is to understand what causes them.”

Previously: Forces at work in concussions more complicated than previously thought, new Stanford study reveals, Stanford undergrad studies cellular effects of concussions, Developing a computer model to better diagnose brain damage, concussions and Stanford researchers working to combat concussions in football
Photo by West Point – The U.S. Military Academy

In the News, Neuroscience, Research, Sleep, Stanford News

Stanford researcher’s work, which clarifies role of brain activity during sleep, featured on NPR

Stanford researcher's work, which clarifies role of brain activity during sleep, featured on NPR

ParviziMuch to my delight, I heard the voice of Josef Parvizi, MD, PhD, on NPR yesterday afternoon. He was discussing the results of his latest study, which showed that the brain’s activity during sleep is far from random.

“There is something that’s going on in a very structured manner during rest and during sleep,” Parvizi told NPR. “And that will, of course, require energy consumption.”

A Shots blog entry accompanying the segment describes the findings:

The team saw activity in two widely separated brain areas known to be involved in episodic memories. And the activity was highly coordinated — suggesting the different brain regions were working together to answer the questions…

“What we found,” he says, “was that the same nerve cells that were activated to retrieve memories… have a very coordinated pattern of noise.”

This explains, in part, why the brain consumes 20 percent of the body’s energy, although it constitutes only 2 percent of its weight. There are more details on the study in our press release.

Previously: New findings on exactly why our “idle” brains burn so much fuel, The brain whisperer: Stanford neurologist talks about his work, shares tips with aspiring doctors and How epilepsy patients are teaching Stanford scientists more about the brain

Evolution, In the News, Research, Science

Chins make us human; new study examines why

Chins make us human; new study examines why

il-150226-ts-08When we think of what makes us human, it’s common to think of something like language or tool-making. Something that likely doesn’t pop into mind is the chin – but humans are the only species to have one! The bony prominence is missing from the skulls of Neanderthals, archaic humans, primates, and indeed all other animals. (In the photo, the skull on the left is human, and the one on the right is Neanderthal).

Scientists have puzzled for more than a century over why chins developed, and the dominant theory has been that they resulted from mechanical forces like chewing. Bones under pressure sustain tiny tears that then enable new bone to grow, much like weight lifting does to muscles. But a new study conducted by University of Iowa researchers suggests that mechanical forces have nothing to do with it: It’s more likely that chins resulted from shifting social dynamics.

The study, published in the Journal of Anatomy, capitalized on the fact that children don’t have chins either – the bone underneath their lower lip is smooth, and the prominence develops with age. The study examined nearly 40 people ranging from 3-20 years old, correlating their chin development with various forces exerted by their cranio-facial anatomy (during chewing, for example), and concluded that mechanical forces don’t play a role in chin development. In fact, those with the most mechanical force had the smallest chins.

Nathan Colton, PhD, professor of orthodontics at the UI College of Dentistry and lead author of the study, is quoted in a UI press release:

In short, we do not find any evidence that chins are tied to mechanical function and in some cases we find that chins are worse at resisting mechanical forces as we grow. Overall, this suggests that chins are unlikely related to the need to dissipate stresses and strains and that other explanations are more likely to be correct.

Instead, the researchers think that the chin results from the facial structure being rearranged as faces got smaller – human faces are 15 percent smaller than those of Neanderthals. This reduction resulted from a decrease in testosterone levels, which happened as males of the species benefitted more from interacting socially with other groups rather than fighting other males.

Robert Franciscus, PhD, professor of anthropology at UI and a contributing author on the study, also comments:

What we’re arguing is that modern humans had an advantage at some point to have a well-connected social network, they can exchange information, and mates, more readily, there’s innovation. And for that to happen, males have to tolerate each other. There had to be more curiosity and inquisitiveness than aggression, and the evidence of that lies in facial architecture.

Previously: Humans share history – and a fair amount of genetic material – with Neanderthals
Photo by Tim Schoon, University of Iowa

Behavioral Science, Cardiovascular Medicine, Patient Care, Research, Stanford News

A little help from pharmacists helps a-fib patients adhere to prescriptions

A little help from pharmacists helps a-fib patients adhere to prescriptions

TurakhiaIt’s not always easy to take drugs as prescribed — life often gets in the way of taking a pill at the same time each day. And it’s relatively easy to ignore the tiny printing on a medication container, to rationalize why that doesn’t apply to you, or how a few exceptions certainly wouldn’t hurt.

Except sometimes precise prescription adherence is important. And that’s the case for a new class of blood thinners such as dabigatran that are used to treat atrial fibrillation.

With these twice-daily oral drugs, “even missing a few doses can lead to acute events such as stroke,” said Mintu Turakhia, MD. Along with other researchers, Turakhia was puzzled when he learned that patients weren’t adhering very well to these drugs. It seemed surprising because the drugs didn’t require frequent blood tests like warfarin, the traditional blood thinner used to treat atrial fibrillation.

Digging into the data, Turakhia and his team found that adherence varied by treatment site, not by individual patient. How odd, they thought. To figure out what was going on, “we rolled up our sleeves and looked at what each site was doing,” Turakhia said.

My colleague explained the result of the researchers’ work, which appears today in the Journal of the American Medical Association, in a release:

At the sites with the highest patient adherence, there was usually a pharmacist actively educating patients on medication adherence, reviewing any possible drug interactions, and following up to make sure patients were taking the medication when they were supposed to and that prescriptions were being refilled on time…

“We’re suggesting that greater structured management of these patients, beyond the doctor just prescribing medications for them, is a good idea,” Turakhia said. “Extra support, like that provided in the VA anticoagulation clinics with supportive pharmacist care, greatly improves medication adherence.”

Previously: One label fits all? A universal schedule for prescription drugs, Raising awareness about the importance of taking medications properly and Study highlights increased risk of death among patients with atrial fibrillation who take digoxin
Photo of Turakhia by Norbert von der Groeben

Big data, Clinical Trials, Ethics, Public Health, Research, Stanford News

The public wants easier ways to participate in medical research, study shows

The public wants easier ways to participate in medical research, study shows

Informed consent, the time-consuming process for obtaining permission to conduct health-care research on a person, was developed long before computers, the Internet and smartphones. Last year, when government regulators proposed to add an even greater burden of paper, red tape and so-called patient protections to this process, a team of bioethicists cried foul. And they took the issue to the public via a cross-sectional survey study that was published today in the Annals of Internal Medicine.

What the survey respondents said surprised them: Keep the permissions simple, but always ask permission, even when the research only involves anonymized medical records.

“The good news was that most people said that they would accept simpler approaches to granting permission, even verbal permissions, if requiring written agreements would hinder this type of comparative-effectiveness research,” study author Mildred Cho, PhD, associate director of the Stanford Center for Biomedical Ethics, said in our press release.

Bioethicists from Stanford and the University of Washington are on the leading edge of addressing the ethical challenges of evolving research methods, where researchers will increasingly use data from wearable devices, electronic medical records, genomic databases and other sources to help improve our population’s health.

In an editorial accompanying Cho’s article, John Lantos, MD, from Children’s Mercy Hospitals and Clinics, summarized the importance of the study:

Cho and colleagues challenge us to think of a better way. Autonomy should mean participatory engagement. Respect for persons should mean empowering them to develop the rules. It is time to ask whether a system in which the fundamental principle is ‘respect for persons,’ can continue to ignore the preferences of many of the persons it claims to respect.

As a next step, the bioethicists will be developing media-rich tools to explain the risks and benefits of research that uses electronic medical records and stored biological samples. For example, the video above was developed to explain the concept of informed consent to survey respondents unfamiliar with research terminology.

Previously: Build it (an easy way to join research studies) and the volunteers will comeHarnessing mobile health technologies to transform human health and Video explains why doctors don’t always know best
Video by Booster Shot Media

In the News, Mental Health, Research, Sleep

The importance of screening soldiers for sleep problems to combat mental-health conditions

The importance of screening soldiers for sleep problems to combat mental-health conditions

Watching over

A new report from the RAND Corporation suggests that treating military members’ sleep disturbances early on may be an important step in preventing serious mental-health conditions, including post-traumatic stress disorder, depression, and traumatic brain injury.

The two-year multi-method study examined sleep-related policies and programs across the U.S. Department of Defense and surveyed almost 2,000 veterans from various branches of the military to evaluate their sleep habits. The findings emphasized the negative effects of poor sleep on soldiers’ mental health, daytime impairment and perceived operational readiness; and it outlined interventions for helping identify and prevent sleep problems for service members.

The Huffington Post reports:

The researchers recommended that the military improve screening for sleep disturbance, and develop guidelines for doctors on how to identify and treat sleep disorders in the military. Apps on mobile phones might be one new way to identify and monitor sleep problems so they do not become chronic and debilitating, the researchers said.

Although the new report focused on activity-duty troops, studies show that sleep problems are often missed in veterans as well, [Wendy Troxel, PhD, co-author of the report] said, so there is also a need to develop guidelines for treating this population. In a previous survey of 3,000 veterans, 74 percent had symptoms of insomnia, but only 28 percent had talked with their doctor about it, Troxel said.

The researchers also recommended improving policies and programs to educate military personnel about the importance of sleep, and provide guidance on how to help military members get better sleep.

Previously: Study shows benefits of breathing meditation among veterans with PTSD, The promise of yoga-based treatments to help veterans with PTSD and Using mindfulness therapies to treat veterans’ PTSD
Photo by DVIDSHUB

Biomed Bites, Imaging, Neuroscience, Research, Technology, Videos

Peering under the hood – of the brain

Peering under the hood - of the brain

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers.

Fixing a broken brain is much like fixing a malfunctioning car, misbehaving computer or most anything else that isn’t working as it should.

“Whenever we’re trying to fix something that’s broken, it can be very helpful indeed to understand how that thing works,” says Stephen Smith, PhD, in the video above. “I believe the brain does not pose an exception to this rule.”

That’s why Smith, a professor of molecular and cellular biology, emeritus, has spent his career developing better ways to understand — and see — the brain.

Currently, he’s most excited about a technique called array tomography that allows researchers to observe the brain’s wiring, the linkages between neurons, and gain a better understanding of how it functions.

That technique, as well as others, offers real hope for fixing brains broken by autism, Alzheimer’s disease or other brain disorders. Here’s Smith:

I think the progress we’re making today in understanding basic brain mechanisms is likely to help us greatly as we develop new drugs that can help lessen or reverse the wide array of neurodegenerative or neurodevelopmental or injury-related disorders of the brain.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Visualizing the brain as a Universe of synapses, Examining the potential of creating new synapses in old or damaged brains and Fantastic voyage: Stanford researcher offers a virtual flight through the brain

Stanford Medicine Resources: