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Neuroscience, Stanford News, Stroke, Surgery, Videos

Raising awareness of moyamoya disease

Raising awareness of moyamoya disease

Today isn’t just May 6, it’s also World Moyamoya Day. Well, not officially – but one patient is trying to change that.

Moyamoya, a rare cerebrovascular disease is often overlooked by neurologists, and its symptoms confused with those of chronic migraines. Tara MacInnes spent most of her childhood suffering from excruciatingly painful headaches and bouts of numbness and tingling in her hands, face and legs. Like many others with moyamoya disease, these episodes were overlooked by her pediatric neurologists. By age 16, when an especially bad episode led to an MRI and eventually a correct diagnosis, both sides of her brain had already suffered damage from strokes.

But MacInnes was lucky: She happened to live close to Stanford, where Gary Steinberg, MD, PhD, one of the world’s leading experts on moyamoya treatment, practiced. And like many patients, what MacInnes needed was more than just surgery – she needed a sense of belonging and the ability to interact with others who had gone through a similar experience.

Shortly after her surgery here MacInnes began volunteering at the Stanford Moyamoya Center, talking with patients and their families. The more she met with people, the quicker she realized it wasn’t just the general public that didn’t know much about the disease, but that many medical professionals had never heard of it. Now, 10 years after her successful surgery, MacInnes has become a devoted advocate and is determined to raise awareness about the disease; you can sign her petition to help spread the word and make World Moyamoya Day official.

Previously: How patients use social media to foster support systems, connect with physicians

Cardiovascular Medicine, In the News, Stanford News, Surgery

Looking at aortic valve replacement without open-heart surgery

SM heart imageSome patients with aortic stenosis undergo open-heart surgery to replace a constricted heart valve in an attempt to stave off heart failure. But others, such as elderly adults, aren’t candidates for this type of surgery. In 2011, the FDA approved a non-surgical alternative procedure called TAVR, or transcatheter aortic valve replacement, but the new method, as discussed in the New York Times earlier this month, also carries certain risks.

In the current issue of Stanford Medicine magazine, my colleague Tracie White digs into the surgery-or-TAVR debate and follows the story of one aortic stenosis patient who was treated by the newer method. Maryann Casey, at 62, is younger and healthier than the average TAVR candidate, but she had faced an increased risk for complications during open-heart surgery because of radiation treatment for breast cancer decades ago.

From the magazine piece:

Casey was lucky. Her Stanford oncologist, Frank Stockdale, MD, PhD, the Maureen Lyles D’Amrogio Professor of Medicine Emeritus, was well-informed about treatment options for aortic stenosis, a calcification of the heart valve. This new nonsurgical approach to valve replacement involves placing an artificial heart valve, made of cow tissue supported by a stainless steel mesh frame, inside the damaged valve. Referred to as “transcatheter aortic valve replacement” or TAVR, the procedure is designed for patients with severe, symptomatic aortic stenosis who have health conditions that make the preferred treatment, open-heart surgery, very high risk.

On Oct. 16, 2012, Casey became one of the more than 120 patients that year at Stanford to undergo the TAVR procedure. The first catheter-based aortic valve transplant was in 2002 in France. It has been approved for use for the past six years in 40 other countries including most of Europe, with a total of 45,000 procedures conducted worldwide.

In the United States, institutions such as Stanford, the Cleveland Clinic, Columbia University and the University of Pennsylvania have been leaders in introducing the new procedure and determining its effectiveness through the clinical trials.

Careful patient selection is key to the successful use of the procedure, says [D. Craig Miller, MD, the Doelger Professor of Cardiovascular Surgery], and that sometimes means not recommending TAVR for a patient who is too old or too sick with other illnesses to benefit from the device.

“That’s a very sobering point,” says surgeon Miller. For patients who are too old or ill, undergoing the procedure may not increase their quality of life or life expectancy; Miller says that the boundary line between TAVR “utility and futility” is still being defined.

Previously: Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questionsAsk Stanford Med: Answers to your questions about heart health and cardiovascular research and Major advancement for once inoperable ailing heart valves
Art, which originally appeared in Stanford Medicine, by Pixologicstudio

Research, Stanford News, Surgery

Stanford-developed device shown to reduce the size of existing scars in clinical trial

Stanford-developed device shown to reduce the size of existing scars in clinical trial

scar_2.10On the inside of my left hand is a thick oval scar – a result of a procedure performed more than a decade ago to remove a melanoma. I’m thankful that the skin cancer appeared on my palm, where the scar is largely concealed, rather than on a more exposed area. Many others are forced to face the public with far extensive scarring that can be unsightly and, in certain cases, make movements difficult or painful.

But a device invented by School of Medicine researchers has demonstrated in a small clinical trial that it can help decrease the size of existing scars when used after scar-revision surgery. In a story published today in Inside  Stanford Medicine, my colleague Christopher Vaughan explains the research, writing:

Currently, scar revision surgery does not work very well. Scars are cut out, the edges of the incision are closed, and surgeons work to make the new scar less obtrusive than the old one. But the revision surgery using current methods doesn’t work very well, [senior author of the study Michael Longaker, MD,] said. “Most of the time, after a year the patient feels that the scar is just as bad as it ever was,” he says.

In this clinical trial, surgeons cut out old scars on each of 10 patients and then placed the scar-reduction device over half of the incision; the other half they closed using traditional methods. After the study, patients were offered the chance to have the traditionally revised section of the scar closed using either of the two methods so that the two sides matched.

Six months after surgery, photos of the two halves of the scar were compared by four independent surgeons who did not know which sides of the scars had been treated with the device. Using a visual scoring system, the judges determined that the scar on the side treated with the scar-reduction device was significantly smaller. “It was pretty obvious,” Longaker said. “It was not even subtle.”

Previously: Stanford researchers reveal how mechanical forces contribute to scarring and In scar wars, a new hope
Photo by DrSam

Cancer, Research, Stanford News, Surgery

Chemistry technique improves cancer surgery

Chemistry technique improves cancer surgery

mass spectrometer

For many cancers of the stomach and intestinal tract, removing the tumor is the best way of treating a patient. The problem is that the cancerous cells don’t necessarily look any different from the normal cells. I wrote recently about a new technique to pick out those cancerous cells and help surgeons completely remove the tumor.

What’s fun about this story is that the idea started with a chemist, Livia Eberlin, PhD, who’s a post-doc in lab of chemistry professor Richard Zare, PhD. Zare is a member of Stanford’s Bio-X and from that has experience working with colleagues across campus. He suggested to Eberlin that she find a surgeon who would be willing to collaborate with her and test her approach to identifying the cancerous cells.

Eberlin knew that surgeons rely on pathologists during a surgery to help them figure out if they’ve removed the entire tumor, but the initial results aren’t always accurate. In some cases, pathologists find out days later, when results of a slower, more accurate test are complete, that the patient might need to come back for another surgery to remove more tissue.

Eberlin called up surgeon George Poultsides, MD, to see if he’d like to collaborate on her idea. As I wrote in my piece:

Eberlin’s expertise is in mass spectrometry, a tool not commonly used in a hospital setting. It takes a sample in one end, turns the molecules into charged particles, then detects how long it takes each charged molecule in that sample to migrate down a vacuum tube. The result is a jagged mountain range of tens of thousands of peaks, each representing a single chemical in the sample. The height of the peak indicates how much of that chemical the sample contained.

The idea was that maybe some of those peaks would be different in tissue samples that had cancerous cells versus those that didn’t. If it worked, this mass spectrometry approach might end up being more accurate than the approach being used now.

It took a team of statisticians, pathologists, surgeons and chemists to develop and test Eberlin’s idea. In the end, their approach seemed to be more accurate than what’s being used now. They are going to try their approach on a larger group of stomach cancers and in other cancers to see if it can help improve the odds of completely removing all cancerous cells during surgery.

Previously: Good-bye cancer, good-bye stomach: A survivor shares her tale
Photo – of Livia Eberlin, PhD, at a mass spectrometer used to identify cancerous cells in tissue samples – by L.A. Cicero

Applied Biotechnology, Microbiology, Patient Care, Research, Stanford News, Surgery

Staphylococcus aureus holes up in upper nasal cavity, study shows

Staphylococcus aureus holes up in upper nasal cavity, study shows

nostrilsA posse led by Stanford microbe sleuth and microbiologist David Relman, MD, has apprehended Staphylococcus aureus, one of the most notorious sources of serious infections, lurking in formerly unsuspected nasal hideaways. The discovery may explain why attempts to expunge S. aureus from the bodies of hospitalized patients being readied for surgery often meet with less than perfect results.

About one in three of us are persistent S. aureus carriers, and another third of us are occasional carriers. This bacterial shadow, which abounds on skin (especially the groin and armpits) and is quite at home in the nose, does us no harm most of the time. But if it gets into the bloodstream or internal organs, it can cause life-threatening problems such as sepsis, pneumonia and endocarditis (infection of heart valves). That makes S. aureus not such a good thing to be coated with if you’re about to have your skin punctured by a catheter or pierced by a scalpel.

This is exacerbated by the all-too-frequent presence, particularly in hospital settings, of S. aureus strains resistant to an entire family of antibiotics related to methicillin. In 2011, more than 80,000 severe methicillin-resistant S. aureus infections and more than 11,000 related deaths occurred in the U.S. alone, along with a much higher number of less-severe such infections.

In a study just published in Cell Host & Microbe, Relman – who pioneered the use of ultra-high-volume gene-sequencing techniques to sort out the thousands of species of microbes that communally inhabit our skin, orifices and innards – and his team used this method to show that mucosal sites way up high in our nose, where standard S. aureus-elimination techniques may not reach, can serve as reservoirs for S. aureus. That may, at least in part, explain why efforts to rid patients of this potentially nasty bug have so often fallen short of the mark, as I noted in my news release about the new findings:

Rigorous and somewhat tedious regimens for eliminating S. aureus residing on people’s skin or in their noses do exist, but it’s typically a matter of weeks or months before the bacteria repopulate those who are susceptible. The new study offers a possible reason why this is the case.

Previously: Cultivating the human microbiome, Anti-plaque bacteria: Coming soon to your toothpaste? and Eat a germ, fight an allergy
Photo by OakleyOriginals

Clinical Trials, Neuroscience, Research, Stanford News, Surgery, Technology

Stanford conducts first U.S. implantation of deep-brain-stimulation device that monitors, records brain activity

Stanford conducts first U.S. implantation of deep-brain-stimulation device that monitors, records brain activity

DBS team - 560

Mark down October 30 and November 20, 2013, as medical mileposts.

On Oct. 30, a Stanford surgical team led by neurosurgeon Jaimie Henderson, MD, implanted a next-generation deep-brain-stimulation (or DBS) device into a Parkinson’s disease patient’s brain. On the order of 100,000 nearly but not quite identical procedures have been performed worldwide in the past decade or so, to relieve symptoms of not only Parkinson’s but epilepsy, chronic pain and more. Making what took place just over a month ago unique wasn’t the surgery itself but, rather, the nature of the device that was implanted – the first time ever in the United States. (In August, a patient in Germany received such a next-generation DBS device, although for a different indication.)

With current DBS technology, a fine, insulated wire is threaded into the brain so that its lead, containing four electrodes, impinges on the relevant brain area. (In Parkinson’s, for instance, the targeted area would be key brain regions that participate in the generation of spontaneous involuntary tremors characteristic of that disease). In a second procedure, a pacemaker-like device called a neurostimulator is placed under the skin, typically near the collarbone. The neurotransmitter transmits signals – at frequencies, amplitudes and durations programmed by a neurologist – to the leads, which accordingly fire electrical impulses counteracting the aberrant brain signals producing the physical symptoms in question. Over time, the neurostimulator’s impulse-transmission pattern is optimized via a trial-and-error process involving extensive patient-neurologist interaction.

Stanford neurologist and Parkinson’s specialist Helen Bronte-Stewart, MD, routinely sees patients a few weeks after their DBS devices have been implanted. They come in having not taken their medications for a while, so she can observe their symptoms and watch how they respond to different DBS frequencies and intensities.

But the new device, manufactured by the same company (Medtronic, Inc.) that makes the existing one, has an additional capability. It can not only transmit signals to the brain but, in addition, monitor and record the brain region of interest’s electrical output.

This will let Bronte-Stewart remotely capture vast amounts of information about a particular patient’s brain-firing patterns to discern that patient’s “neural signature” – and ultimately, it is hoped, be able to develop algorithms for automating the device’s signaling program so that it changes in response to changes in brain activity. (The goal, in engineering vocabulary, is a “real-time negative-feedback loop.”)

On Nov. 20, after recovering from the surgery, the patient and Bronte-Stewart, a noted expert in movement disorders, embarked on the first of a series of groundbreaking sessions during which Bronte-Stewart will download data from the implanted device for thorough analysis. While brain-activity data has been downloaded from Parkinson’s patients while they’re lying still on the operating table after the initial electronic-lead implantation, the recorded data has by necessity reflected only activity in the brain while the patient is at rest. Now Bronte-Stewart will be able to identify the neural signatures of not only the resting state but also voluntary movement, task performance and the tremor itself, and to see how those neural signatures change in response to her manipulations of DBS frequency and voltage output.

Stanford has received 10 of the new “two-way” DBS devices from Medtronic, and is recruiting Parkinson’s patients who, while they may not benefit directly from the ongoing study, wish to make a difference in how this disease’s symptoms are treated.

Previously: Revealed: The likely role of Parkinson’s protein in the healthy brain, Mind-reading in real life: Study shows it can be done (but they’ll have to catch you first), Positive results for deep-brain stimulation trial for epilepsy and Stanford neurologist discusses advances in research on movement disorders
Photo courtesy of Jaimie Henderson

Medical Education, Stanford News, Surgery, Technology

SICKO web-based game helps surgeons practice decision making

SICKO web-based game helps surgeons practice decision making


Simulation in various forms has become an accepted form of medical education, especially for those techniques needed for surgical procedures. It’s obviously safer to practice on a mannequin than a real person. But one Stanford physician, surgeon James Lau, MD, was struck by a distinct absence of similar practice techniques for pre-surgical decision-making – those questions whose answers help a doctor decide whether to conduct a surgery. In fact, Lau knew, the only time a doctor is tested on those non-surgical skills is during the board certification process that takes places years into actual practice.

With the help of a grant designed to nurture innovative approaches to medical education, Lau collaborated with a Stanford medical student and a third-year Stanford surgical resident to build upon and expand the technology behind last year’s Stanford CME hit, Septris, a web-based game designed to teach doctors how to better identify and treat sepsis. The new game, SICKO (Surgical Improvement of Clinical Knowledge Ops), aims to duplicate what doctors face every day: the pressure of time and multiple patients.

But, to Lau’s goal of improving patient safety, none of SICKO’s patients are real – and practice might make perfect. I explain more in an Inside Stanford Medicine story today.

Previously: A conversation about digital literacy in medical educationThe data deluge: A report from Stanford Medicine magazine and Can battling sepsis in a game improve the odds for material world wins?
Image from Zak Akin

Cancer, Events, Stanford News, Surgery, Women's Health

Discussing trends in breast reconstruction choices

Discussing trends in breast reconstruction choices

Women are choosing silicone implants twice as often for breast reconstruction after mastectomy than using their own natural tissue for the reconstruction, a Stanford plastic surgeon says. Both methods have their advantages and drawbacks, Gordon Lee, MD, told an audience at a Stanford Health Library lecture last week.

Implant surgery is simpler, shorter and produces good results, but the implants “don’t last forever,” said Lee, an assistant professor and director of microsurgery in the Division of Plastic and Reconstruction Surgery. Tissue surgery takes longer and requires more recovery time, but it can provide natural-touch breasts that last long-term, with the “two-for-one” benefit of a tummy tuck for some women as well, he said.

Given the 1-in-8 chance that a woman in the U.S. will get breast cancer, reconstruction is an important topic to many

Given the 1-in-8 chance that a woman in the U.S. will get breast cancer, reconstruction is an important topic to many. “Patients should get a choice,” said Lee, who does both kinds of surgery.

Tissue surgery has been refined and improved for more than 30 years, with multiple options available to women now, Lee said. The most recent improvements enable surgeons to build new breasts using fat and skin tissue removed from the belly while leaving most or all of the belly muscles in place. Refined microsurgery techniques have also let surgeons connect arteries to the transplanted tissue with more precision, improving results.

Still, about two-thirds of U.S. women have decided to get implants in recent years, while one-third have had reconstruction using their own body tissues.

Many women choose implants because the procedure is simpler, they can recover in 1 to 2 weeks and get good-looking results sooner. Implants are made with a filler of either silicone or saline. About 95 percent of Lee’s patients who get implants choose silicone because they have a more natural feel and don’t flatten if the implant shell breaks.

Manufacturers estimate that implants last 10 years, on average, before rupturing, whether they are silicone or saline, Lee said. For any one woman, though, the rupture can occur much earlier or later – as soon one year or as long as 15 years after reconstruction, for example. Even if an implant shell ruptures, a woman may not notice it,  Lee said, because the silicone filler is likely to stay in place given that it is a cohesive material.

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Aging, Orthopedics, Stanford News, Stem Cells, Surgery

Stanford study shows protein bath may rev up sluggish bone-forming cells

Stanford study shows protein bath may rev up sluggish bone-forming cells

Fractures that are complex, pose a significant health risk, or don’t heal properly are repaired using bone grafts. The surgical process involves transplanting whole marrow, which is rich in stem cells that form bone, blood and the cells of the immune system, into a fracture site.

Although it’s preferable to use a patient’s own tissue to avoid rejection, elderly patients (whose older marrow forms bone less robustly), often require the use of donor bone marrow from younger people or the use of drugs to stimulate bone growth.

Now researchers at Stanford have identified a simple way to stimulate old marrow to form bone, which could allow the use a patient’s own cells without medications. My colleague explains the findings in a release:

In studies involving mice and rabbits, the researchers found that a quick dip in a bath of a signaling protein called Wnt3a can rev up sluggish bone-forming cells in older animals that would normally be unable to heal a fracture. If the simple treatment is eventually found to be effective in humans, it may significantly improve the success of bone grafts, which are performed more than 500,000 times every year in the United States.

“We’re very focused on designing a treatment that could be easily employed by orthopaedic surgeons in the normal course of bone grafting,” said professor of surgery Jill Helms, DDS, PhD. “We’ve shown that when we temporarily treat bone marrow from aged animals with Wnt before transplanting the cells into a fracture site, we see really robust bone formation.”

“Hip fractures in elderly people nearly triple the risk of dying within a year of the injury, and a rapidly aging population demands more effective treatments for this type of trauma,” said Helms.

Previously: Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure they’re making new knees and Biomarker can predict graft-versus-host disease in men after transplants from women donors

Aging, Imaging, Orthopedics, Research, Stanford News, Stem Cells, Surgery

Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure they’re making new knees

Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure they're making new knees

kneesAs a population ages, so do its knees. Americans undergo 700,000 knee-replacement operations annually – a number expected to quintuple within two decades.

Prosthetic implants, for the most part a godsend for those with knee problems, come with problems of their own. They can induce fractures in nearby bone. They can gradually loosen over time. Even in the absence of complications, they can wear out – their average lifetime is around 10 years – and a second surgery is technically tougher going than the first was.

In a fortunate development for the creaky-kneed among us, a study just published in Radiology and led by Stanford pediatric radiologist Heike Daldrup-Link, MD, PhD, promises to expedite clinical trials of  a class of “adult” stem cells with great potential for knee repair.

These cells, known as mesenchymal stem cells (which I’ll call MSCs), ordinarily reside in bone marrow. Unlike embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), MSCs can’t differentiate into all the 200-plus tissues in the physiological rainbow that is our body. That’s good: A major concern about using ESCs or iPSCs for regenerative medicine is their capacity to form tissues wildly inappropriate for the job at hand or even to spawn tumors.

MSCs pretty much generate only bone, cartilage, muscle or fat, in response to cues from their immediate environment. Plus, they can be easily extracted from bone marrow of patients who are going to undergo the knee-repair procedure.

The trouble is, just shooting MSCs into a knee-injury site doesn’t automatically mean they’ll generate the wanted tissues, in the wanted amounts, right where they’re wanted. They might migrate away. They might die, refuse to engraft or fail to replicate and differentiate. They might develop into, say, scar tissue instead of cartilage or bone.

But how would you know? One way to see how newly transplanted MSCs are behaving requires labeling them, by loading them up with iron in the laboratory, between their extraction and their injection into the knee.  This makes them visible via magnetic-resonance imaging (MRI), so they can be monitored afterwards.

But, as I wrote in my news release on the study:

Upon extraction, the delicate cells have to be given to lab personnel, incubated with contrast agents, spun in a centrifuge and washed and returned to the surgeons, who then transplant the cells into a patient.

Regulatory agencies and opinion leaders rightly look askance at the potential contamination that can be introduced when stem cells are manipulated in lab glassware. Besides, MSCs in a lab dish have scant appetite for iron particles.

Daldrup-Link’s team showed that – for whatever reason – the very MSCs that eschew iron in a dish munch it right up when they’re hanging out in the bone marrow. They gave rats an injected “snack” of  ferumoxytol, an FDA-approved supplement composed of iron-oxide nanoparticles. When they later harvested MSCs from those rats’ bone marrow and infused them into other rats’ injured knees, they could track the the iron-stuffed MSCs for weeks afterward because they gave off a powerful MRI signal.

Stanford orthopedic surgeon Jason Dragoo, MD, plans to conduct a clinical trial this fall using the new MSC-labeling method. MSCs extracted from feroxytol-supplemented knee-damaged patients’ bone marrow will be delivered to those same patients in a single procedure, eliminating the delay and greatly reducing the contamination risk associated with lab-based labeling.

Previously: Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later, FDA audit of Texas stem cell clinic revealed by Houston Chronicle and From college football player to team physician: A look at the career of Stanford’s Jason Dragoo
Photo by Jesse.Millan

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