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Clinical Trials, Immunology, Pain, Research, Stanford News, Surgery, Technology

Discovery may help predict how many days it will take for individual surgery patients to bounce back

Discovery may help predict how many days it will take for individual surgery patients to bounce back

pandaPost-surgery recovery rates, even from identical procedures, vary widely from patient to patient. Some feel better in a week. Others take a month to get back on their feet. And – until now, anyway – nobody has been able to accurately predict how quickly a given surgical patient will start feeling better. Docs don’t know what to tell the patient, and the patient doesn’t know what to tell loved ones or the boss.

Worldwide, hundreds of millions of surgeries are performed every year. Of those, tens of millions are major ones that trigger massive inflammatory reactions in patients’ bodies. As far as your immune system is concerned, there isn’t any difference between a surgical incision and a saber-tooth tiger attack.

In fact, that inflammatory response is a good thing whether the cut came from a surgical scalpel or a tiger’s tooth, because post-wound inflammation is an early component of the healing process. But when that inflammation hangs on for too long, it impedes rather than speeds healing. Timing is everything.

In a study just published in Science Translational Medicine, Stanford researchers under the direction of perioperative specialist Martin Angst, MD, and immunology techno-wizard Garry Nolan, PhD, have identified an “immune signature” common to all 32 patients they monitored before and after those patients had hip-replacement surgery. This may permit reasonable predictions of individual patients’ recovery rates.

In my news release on this study, I wrote:

The Stanford team observed what Angst called “a very well-orchestrated, cell-type- and time-specific pattern of immune response to surgery.” The pattern consisted of a sequence of coordinated rises and falls in numbers of diverse immune-cell types, along with various changes in activity within each cell type.

While this post-surgical signature showed up in every single patient, the magnitude of the various increases and decreases in cell numbers and activity varied from one patient to the next. One particular factor – changes, at one hour versus 24 hours post-surgery, in the activation states of key interacting proteins inside a small set of “first-responder” immune cells – accounted for 40-60 percent of the variation in the timing of these patients’ recovery.

That robust correlation dwarfs those observed in earlier studies of the immune-system/recovery connection – probably because such previous studies have tended to look at, for example, levels of one or another substance or cell type in a blood sample. The new method lets scientists simultaneously score dozens of identifying surface features and goings-on inside cells, one cell at a time.

The Stanford group is now hoping to identify a pre-operation immune signature that predicts the rate of recovery, according to Brice Gaudilierre, MD, PhD, the study’s lead author. That would let physicians and patients know who’d benefit from boosting their immune strength beforehand (there do appear to be some ways to do that), or from pre-surgery interventions such as physical therapy.

This discovery isn’t going to remain relevant only to planned operations. A better understanding, at the cellular and molecular level, of how immune response drives recovery from wounds may also help emergency clinicians tweak a victim’s immune system after an accident or a saber-tooth tiger attack.

Previously: Targeting stimulation of specific brain cells boosts stroke recovery in mice, A closer look at Stanford study on women and pain and New device identifies immune cells at an unprecedented level of detail, inside and out
Photo by yoppy

Events, Medicine and Society, Stanford News, Videos

How Stanford Medicine celebrated TEDMED

How Stanford Medicine celebrated TEDMED

Earlier this month, TEDMED, an annual global event dedicated to exploring the promise of technology and potential of human achievement in health and medicine, was held simultaneously in San Francisco and Washington D.C. Stanford Medicine served as a medical research institution partner for the event and hosted a reception to cap off Day Two of the three-day conference; the video above captures the evening’s activities and offers a taste of the future of biomedicine.

Previously: Abraham Verghese discusses stealing metaphors and the language of medicine at TEDMED and Stanford Medicine partners with TEDMED on “first-ever gathering on the West Coast”

Aging, In the News, Neuroscience, Stanford News

Exercise and your brain: Stanford research highlighted on NIH Director’s blog

Exercise and your brain: Stanford research highlighted on NIH Director’s blog

B0007367 Thigh muscle fibrilsThomas Rando, MD, PhD, who studies stem cells in muscle and longevity, and Tony Wyss-Coray, PhD, who studies the immune system’s impact on the brain, were awarded an NIH Director’s Transformative Research Award to study the slew of molecules that muscles release and how they help muscle cells communicate with other cells. (Rando and Wyss-Coray call this cellular communication network “the communicome.”) The onset of both depression and Alzheimer’s disease have been shown to be delayed with exercise, and Rando and Wyss-Coray theorize that molecules released by muscles during exercise may be the key to understanding how exercise can affect brain function so profoundly and so beneficially.

Today on the NIH Director’s blog, Francis Collins, MD, highlighted the Stanford duo’s research:

To study the communicome, Wyss-Coray and Rando will use a technique called parabiosis to couple the circulatory systems of physically active mice with mice that are less active. If the “couch potato” mice benefit from the blood of the active mice, then the team will analyze the blood to find the responsible factor(s).

This is definitely high-risk high-reward research. It won’t be easy, but finding molecules that mimic exercise’s brain-boosting effects may open the door to new ways of preventing or treating age-related cognitive declines and a wide range of other neurological conditions. This is especially important for people for whom it is difficult or even hazardous to exercise because of conditions such as arthritis, osteoporosis, and Alzheimer’s disease and other forms of dementia.

Earlier this year, Wyss-Coray published a study showing that older mice that received transfusions of younger mice’s blood improved their brain function. That study was based in part on Rando’s previous research showing that young mouse blood could activate old stem cells and rejuvenate older tissue. Their new collaboration may shed more light on the molecular mechanisms behind such observations.

Previously: Young mouse to old mouse: “It’s all in the blood, baby”, The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, “Alert” stem cells speed damage response, say Stanford researchers and Red light, green light: Simultaneous stop and go signals on stem cells’ genes may enable fast activation, provide “aging clock”
Photo, of thigh muscle fibrils, by David Gregory & Debbie Marshall, via Wellcome Images

Medical Education, Medical Schools, Stanford News

Free online Stanford course examines medical education in the new millennium

Free online Stanford course examines medical education in the new millennium

Prober_092314At this year’s Stanford Medicine X, executive director Larry Chu, MD, announced the launch of a new group of initiatives that would expand the conference and “quicken the pace of changing the culture of health care.” In addition to continuing to build community, the Medicine X Academy will aim to use technology, the principles of design thinking, and a model of inclusivity to redefine medical education.

“We’re moving from talking to doing,” said Chu. “We want to move the conversation earlier into the education system so students begin to think differently about health care and [so we can] improve medical education with the input of all stakeholders.”

As part of the academy, Chu, Kyle Harrison, MD, clinical assistant professor at the Palo Alto Veterans Affairs Hospital, and Nikita Joshi, MD, an academic fellow at Stanford, will begin teaching a massive open online course (MOOC) course titled “Medical Education in the New Millennium” this Thursday. Anyone can enroll in the class through Stanford OpenEdX. Additionally, it will be webcasted on the Medicine X website and live tweeted on the @StanfordMedX feed.

The eleven-week course will ask the fundamental question: What is the definition of medical education? Participants will explore a variety of topics including how to improve the educational experiences of today’s Millennial medical students and residents; how patients and caregivers can be active participants in their care teams; how MOOCs, social media, simulation and virtual reality change the face of medical education; and how to make learning continuous, engaging, and scalable in an age of increasing clinical demands and limited work hours.

Among the class guest lectures are Charles Prober, MD, senior associate dean for medical education at Stanford; Kirsten Ostherr, PhD, an English professor at Rice University and co-founder of the Medical Futures Lab; ePatient Britt Johnson; and medical and nursing students from Duke, Stanford and other universities.

As noted on the course website, the course is targeted not only towards medical students and educators but also patients, caregivers, and anyone who wants “to join a conversation about how to improve medical education.”

Previously: Medicine X aims to “fill the gaps” in medical educationRethinking the traditional four-year medical curriculum and A closer look at using the “flipped classroom” model at the School of Medicine
Photo of Charles Prober by EdTech Stanford University

Bioengineering, Imaging, Research, Stanford News, Videos

How CLARITY offers an unprecedented 3-D view of the brain’s neural structure

How CLARITY offers an unprecedented 3-D view of the brain's neural structure

Last year, Stanford bioengineer Karl Deisseroth, MD, PhD, and colleagues in his lab announced their development of CLARITY, a process that renders tissue transparent, sparking excitement among the scientific community. As explained in the above video, released yesterday by the National Science Foundation, researchers had been unable to directly study the human brain’s circuitry because much of the organ is covered in an opaque tissue. But using CLARITY researchers can “chemically dissolve the opaque tissue in a post-mortem brain, and in place of that tissue, they insert a transparent hydrogel that keeps the brain intact and provides a window into the brain’s neural structure and circuitry.” For this reason, the technique is “hailed as an important advance in whole-brain imaging.”

Previously: Process that creates transparent brain named one of year’s top scientific discoveries, An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”, Peering deeply – and quite literally – into the intact brain: A video fly-through and Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact

Genetics, Pediatrics, Stanford News, Surgery, Transplants

Double kidney transplants leave Hawaii siblings raring to go

Double kidney transplants leave Hawaii siblings raring to go

kidney patients

Two kids; two cases of a rare, often fatal disease; and now, thanks to the work of Lucile Packard Children’s Hospital doctors, two growing kids.

Both Julia Faisca, nearly 10, and Dominic Faisca, 8, suffer from cystinosis, a genetic disease that causes an amino acid — cystine — to build up in the kidney, eye and other places in the body.

The condition retarded the siblings’ growth, and damaged their kidneys. And by May 2013, Julia’s kidneys needed to be replaced. Fortunately, just three months later, she had a new kidney. And the Faisca family received the good news that a kidney was waiting for Dominic while they were flying to California from their home in Hawaii for a routine checkup for Julia.

“We’ve been busy — two kidney transplants in less than a year,” the kids’ mom, Natasha, said in a recent Inside Stanford Medicine story:

“Since their transplants, they aren’t picky eaters anymore,” Natasha said. “I joke with the doctors that the kids are eating me out of the house now. But it’s well worth it.”

Although they’ll always be on medication to protect their new kidneys and will need to return for twice-yearly checkups at Stanford, there’s finally a sparkle in their eyes, Natasha said.

“Dominic and Julia are growing like weeds and it’s really fun to watch them turn into regular kids,” said pediatric transplant specialist Paul Grimm, MD.

Both transplants were conducted by Waldo Concepcion, MD, a specialist in multi-organ transplantation.

Becky Bach is a science-writing intern with the Office of Communications and Public Affairs.

Previously: Baby born with rare, often-fatal kidney disease “doing well” at Packard Children’s Hospital, Contact sports OK for kids with one kidney, new study says and “Delivering hope” at Packard Children’s Hospital
Photo by Norbert von der Groeben

Clinical Trials, Ethics, Health Policy, Stanford News, Videos

Video explains why doctors don’t always know best

Video explains why doctors don’t always know best

“Over 85 percent of our major medical guideline recommendations are not based on high-quality evidence,” said Robert Califf, MD, director of the Duke Translational Medicine Institute, in an article I recently wrote for Inside Stanford Medicine.

This was the inconvenient truth that Stanford bioethicist David Magnus, PhD, had to explain to patients during focus groups, as he began developing policy recommendations for conducting ethical comparative-effectiveness research within physician practices.

“We had to dispel the myth that doctors always know which treatments are most effective for individual patients,” Magnus told me. “The truth is, in the absence of good evidence, these choices are often influenced by advertising, insurance coverage and local preferences.”

Gathering better treatment evidence is a key objective of the Affordable Care Act’s health-care reform mandate. It provides incentives for medical practices to continually evaluate the relative effectiveness of competing medical interventions as a way of delivering better, less costly care to more people. The widespread adoption of electronic medical records is enabling researchers to conduct these head-to-head comparisons in more automated ways, reducing the time and expense associated with the highly controlled clinical trials used to evaluate new drugs and devices.

A communications challenge with these new approaches, however, is how to explain the risks and rewards of participation to patients. In focus groups, Magnus found that no meaningful discussions could take place until his research team had educated patients on some fundamental concepts of medical research, such as standards-of-care, randomization and informed consent. To help with this process, his team produced three short, animated videos that would rapidly get everyone up to the same level of understanding. Magnus and his collaborators are making these videos available to all for educational purposes.

The first video, “Which Medication is Best?,” explores the influences and uncertainty associated with physicians’ prescribing preferences. “Research on Medical Practices” explains medical record reviews, study randomization and randomization of clinics and hospitals; and “Informing or Asking” describes ways to explain study participation to patients.

Magnus and his bioethicist collaborators from the Seattle Children’s Research Institute and University of Washington expect to publish their final ethics policy recommendations later this year.

Previously: Bioethicists say criticisms of preemie oxygen study could have “chilling effect” on clinical researchStanford biomedical ethicist discusses Choosing Wisely Initiative and Will new guidelines lead to massive statin use?
Videos by Booster Shot Media

Neuroscience, Research, Stanford News, Stem Cells

Cellular padding could help stem cells repair injuries

Cellular padding could help stem cells repair injuries

The idea of using stem cells to heal injuries seems so obvious. If you have a spinal cord injury, why not inject some new cells that can replace the ones that are lost?

Unfortunately, the very act of injecting those cells is rife with trouble. The scraping as they move through the needle damages the cells and can even kill them. Then, once in the site of the injury, the cells can easily ooze away into other tissue, or die from the onslaught of chemicals in the injury.

Material scientists Sarah Heilshorn, PhD, is trying to help these cells with a type of gel that can protect and support them, allowing them to live long enough to possibly repair the injury. A grant from Stanford Bio-X, the pioneering interdisciplinary life sciences institute, is now helping Heilshorn and her colleagues, neurosurgeon Giles Plant, PhD, and chemical engineer Andrew Spakowitz, PhD, get the project off the ground.

In a story I wrote about the work, Heilshorn equates the gel to ketchup:

It’s pretty thick, but when you bang on the bottle the sauce flows smoothly through the neck, then firms back up on the plate – a process she calls self-healing. “We want our polymers to self-heal better than ketchup,” she said. “It flows a bit across the plate.”

Her goal is to develop a polymer that supports the cells when they are loaded in a syringe, but then flows freely through the needle, padding and protecting the cells, then firming up quickly when it reaches the site of injury. “We don’t want the cells to flow away,” she says.

These Seed grants from Bio-X have been credited as part of what has made the institute so successful in bringing together people from diverse disciplines to solve biomedical problems. “The seed grants are the special Bio-X glue that brings teams of faculty from all over the university to tackle complex problems in human health using new approaches,” said Carla Shatz, PhD, who directs Bio-X.

We’ll be writing about a few of the most exciting projects being funded with the recently announced 2014 Bio-X Seed grants over the next few weeks.

Previously: They said “Yes”: The attitude that defines Stanford Bio-X

Applied Biotechnology, Bioengineering, Cancer, Research, Stanford News

New “decoy” protein blocks cancer from spreading

New "decoy" protein blocks cancer from spreading

14299-metastasis_news

Cancer becomes most deadly when it’s on the move – jumping from the breast to the brain or the pancreas to the liver and then onward.

But now, a team of Stanford researchers led by radiation biologist Amato Giaccia, PhD, and bioengineer Jennifer Cochran, PhD, have created a protein that may be able to thwart the metastasis.

They published their results this week in Nature Chemical Biology.

“This is a very promising therapy that appears to be effective and nontoxic in preclinical experiments,” Giaccia said in a Stanford release. ”It could open up a new approach to cancer treatment.”

The researchers created a protein that mimics Axl, a protein found on the surface of cancer cells. This decoy protein intercepts incoming messages – intended for the original Axl – cueing the cancer cells to find a new home.

The decoy Axl worked wonders in mice. Mice with breast cancer given the treatment had 78 percent fewer new tumors, and mice with ovarian cancer had 90 percent fewer new tumors than mice with cancer not given the treatment.

Becky Bach is a former park ranger who now spends her time writing about science or practicing yoga. She’s a science-writing intern in the Office of Communications and Public Affairs.

Previously: Studying the drivers of metastasis to combat cancer, A computer kit could lead to a better way to design synthetic molecules, Common drug class targets breast cancer stem cells, may benefit more patients, says study
Photo by Rod Searcey

Immunology, Infectious Disease, Pregnancy, Research, Women's Health

Study: Pregnancy causes surprising changes in how the immune system responds to the flu

Study: Pregnancy causes surprising changes in how the immune system responds to the flu

pregnant ladyWhen pregnant women get influenza, they tend to get really sick. Flu complications such as pneumonia are more common in pregnant women than other healthy young adults, and their risk of death from flu is higher, too.

Until now, doctors have ascribed the problem to the fact that the immune system is tamped down by pregnancy, a protective mechanism that keeps the woman’s body from rejecting her fetus. But a new Stanford study, the first ever to directly examine how a pregnant woman’s immune cells respond to flu viruses, found something unexpected: Instead of responding sluggishly, immune cells from pregnant women actually over-react to the flu. From our press release about the paper, which appears today in the Proceedings of the National Academy of Sciences:

“We were surprised by the overall finding,” said Catherine Blish, MD, PhD, assistant professor of infectious diseases and the study’s senior author. “We now understand that severe influenza in pregnancy is a hyperinflammatory disease rather than a state of immunodeficiency. This means that treatment of flu in pregnancy might have more to do with modulating the immune response than worrying about viral replication.”

In the lab, Blish’s team incubated immune cells obtained from pregnant and nonpregnant women’s blood samples with different strains of flu virus, including the H1N1 flu that caused the 2009 pandemic and also a less virulent strain of seasonal influenza. The responses they observed could help explain why flu, especially pandemic H1N1 flu, causes pneumonia in many pregnant patients:

Pregnancy enhanced the immune response to H1N1 of two types of white blood cells: natural killer and T cells. Compared with the same cells from nonpregnant women, H1N1 caused pregnant women’s NK and T cells to produce more cytokines and chemokines, molecules that help attract other immune cells to the site of an infection.

“If the chemokine levels are too high, that can bring in too many immune cells,” Blish said. “That’s a bad thing in a lung where you need air space.”

Why would influenza break the rules of how the immune system works in pregnancy? Blish thinks there’s a clue in the fact that the flu produces a fourfold increase in an expectant woman’s risk of delivering her baby prematurely. “I wonder if this is an inflammatory pathway that is normally activated later in pregnancy to prepare the body for birth, but that flu happens to overlap with the pathway and aberrantly activates it too early,” she said.

The research is a good reminder that flu season is just around the corner, and it’s time to start thinking about getting a flu shot, especially if you are pregnant or planning a pregnancy.

Previously: Text message reminders shown effective in boosting flu shot rates in pregnant women, Ask Stanford Med: Answers to your questions about seasonal influenza and Flu shots for moms may help prevent babies from being born too small
Photo by Meagan

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