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Research, Stanford News, Surgery

Immune cell linked to surgery recovery time, Stanford scientists find

Immune cell linked to surgery recovery time, Stanford scientists find

surgery shotWe don’t think about doctors getting sick, or about them feeling just as lousy and miserable as the rest of us when they’re recovering. But it happens.

“In medical school I had a chest surgery and had a horrible recovery — in the hospital 10 days, and exhausted for about two months,” recalled Dan Sessler, MD, professor and chair of the Department of Outcomes Research at the Cleveland Clinic, when I spoke with him recently. “I was so tired I couldn’t pick up a remote and turn on the television.”

Sessler did recover — his was a successful surgery — but going into the operation neither he nor his doctor had any inkling that Sessler wouldn’t experience the normal two-week recovery.

Now, research published online in the journal Anesthesiology could lead to an “immune stress test” where blood taken from a patient prior to surgery could help predict when the patients would be back on their feet. The investigators, including co-senior authors/Stanford physicians Garry Nolan, PhD, and Martin Angst, MD, collected blood from 25 hip replacement patients and exposed the blood to chemicals to mimic how the immune system would respond to a traumatic event like surgery. They found the behavior of a white blood cell called a monocyte was related to how quickly patients recovered.

The researchers are working to replicate the findings in a larger study of 80 patients, and they plan to adapt their findings into a test that can run on standard hospital lab machines. As I wrote in our press release about the practical benefits of such a test:

Knowing the likely recuperation times will help patients plan better for their return to work and other post-surgery commitments. For patients at risk for longer recovery times, doctors could schedule additional physical therapy or special care, or the surgery could be postponed while exercise, dietary changes and stress-release techniques are implemented.

As for Sessler, who was not involved in this study, he said he sees great value in adapting the paper’s results into a test. Predicting a patient’s recovery is “clinically important, and we don’t do a good job” of it, he said.

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: Discovery may help predict how many days it will take for individual surgery patients to bounce back, New device identifies immune cells at an unprecedented level of detail, inside and out and The importance of human connection as part of the patient experience
Photo by ChaNaWiT

Ethics, Research, Science, Stanford News

Clues could help identify fraudulent research before publication

Clues could help identify fraudulent research before publication

4443921690_d3b8c60e91_zLiars leave behind evidence, researchers have found, whether they’re bluffing at poker or fabricating financial reports. Now, a study published in the Journal of Language and Social Psychology has identified clues left by researchers who falsify their work.

The study’s authors examined 253 primarily biomedical papers that were retracted from journals for fraud and compared them to papers from the same journals, time periods and publication topics. They developed a “obfuscation index,” which included abstract language, jargon, positive emotional terms, casual language and a reading difficulty score. Fraudulent papers had higher scores than accurate papers, the team found.

A Stanford Report article explains:

“We believe the underlying idea behind obfuscation is to muddle the truth,” said graduate student David Markowitz, the lead author on the paper. “Scientists faking data know that they are committing a misconduct and do not want to get caught. Therefore, one strategy to evade this may be to obscure parts of the paper. We suggest that language can be one of many variables to differentiate between fraudulent and genuine science.”

The results showed that fraudulent retracted papers scored significantly higher on the obfuscation index than papers retracted for other reasons. For example, fraudulent papers contained approximately 1.5 percent more jargon than unretracted papers.

“Fradulent papers had about 60 more jargon-like words per paper compared to unretracted papers,” Markowitz said in the article. “This is a non-trivial amount.”

Previously: New Stanford Medicine magazine explores bioethics, Using social media in clinical research: Case studies address ethical gray areas and “U.S. effect” leads to publication of biased research, says Stanford’s John Ioannidis
Photo by Alan Cleaver

Big data, Medical Apps, Patient Care, Precision health, Research, Stanford News, Technology

Precision health in practice: Using HealthKit to monitor patients’ blood-sugar levels

Precision health in practice: Using HealthKit to monitor patients' blood-sugar levels

Rajiv Kumar and patient - 560

Imagine having to keep track of your diabetic son’s constantly changing blood sugar levels by typing each individual reading into an email. Then, once in the doctor’s office, having to spend a chunk of your precious time with your clinician waiting for her to download that data.

That was the plight of Lori Atkins, whose son has Type 1 diabetes, until this March, when the Atkins joined a pilot project involving Apple’s HealthKit. Pediatric endocrinologist Rajiv Kumar, MD, is using HealthKit – a new technology that can securely share health data with third-party applications – to more easily monitor the blood-sugar levels of 10 patients.

A recent Inside Stanford Medicine article describes the project:

Patients like Blake wear a continuous glucose monitor that sends 288 blood-sugar readings a day to an Apple mobile device through Bluetooth. The data is securely transmitted via HealthKit into the patient’s electronic medical record at Stanford Children’s Health through the MyChart app.

The system also improves clinical outcomes, Kumar said: “Our endocrinologists are now able to easily assess large volumes of blood-sugar data between clinic visits — and quickly identify trends that could benefit from insulin dosing regimen changes.”

Kumar is planning to expand the use of the app to more of his patients.

Previously: A look at the MyHeart Counts app and the potential of mobile technologies to improve human health, Harnessing mobile health technologies to transform human health and A picture is worth a thousand words: Researchers use photos to see how Type 1 diabetes affects kids
Photo by Norbert von der Groeben

Infectious Disease, Medicine and Society, Parenting, Public Health, Research, Stanford News

California’s vaccination exemptions cluster in white, affluent communities

California's vaccination exemptions cluster in white, affluent communities


California’s measles epidemic was no fluke; between 2007 and 2013 the percentage of kindergarteners using a “personal belief” exemption to enroll in school without vaccinations doubled.

In that year, 3 percent of kindergarteners entered school unvaccinated. In some schools, the percentage of vaccinated children was so low that it threatened herd immunity, or the ability for a population to keep a pathogen at bay, according to Stanford health-policy researcher Michelle Mello, PhD, JD.

To understand the rapid increase, Mello worked with a team led by Tony Yang, ScD, with George Mason University. Their research is published today in the American Journal of Public Health.

They found the highest resistance to vaccinations among white, affluent communities. In contrast to previous studies, however, they did not find a correlation between higher levels of education and vaccine exemptions.

“Beliefs about vaccination risk tend to be more entrenched among certain communities of mothers,” Mello said. The study didn’t investigate reasons for seeking exemption, but other studies suggest some mothers in affluent communities may believe they can adequately protect their children through “intensive parenting techniques” such as an organic diet and restricting contact with sick children, Mello said.

Although California eliminated the personal belief exemption this summer in a broad-reaching law that requires all medically eligible school students to be vaccinated, the study speaks to how other states might approach the problem of vaccine exemptions, Mello said.

Similar clusters of vaccine resistance exist elsewhere and the findings could help public health agencies refine outreach methods, she said. For example, by specifically targeting local groups and reaching out to community leaders, officials may have more success providing education about vaccine risks and benefits, Mello said.

The results are particularly striking given the history of vaccination efforts, she said. In the first half of the twentieth century, public health officials struggled to ensure vaccines reached disadvantaged communities. Now, as fear of the targeted diseases has paled, parents may be more fearful of vaccines, leaving the entire population vulnerable.

Previously: Infectious disease expert discusses concerns about undervaccination and California’s measles outbreak, Stanford researchers analyze California’s new vaccine law and The earlier the better: Study makes vaccination recommendations for next flu pandemic
Photo by woodleywonderworks

Bioengineering, Events, Mental Health, Research, Stanford News, Videos

Stanford’s Karl Deisseroth talks about the work he was “destined to do”

Stanford's Karl Deisseroth talks about the work he was "destined to do"

Earlier this week we announced the exciting news that Stanford bioengineer Karl Deisseroth, MD, PhD, had won a $3 million 2016 Breakthrough Prize in Life Sciences. Before he took the stage to accept his award during a star-studded Academy Awards-like ceremony Sunday evening, the video above was shown to highlight the significance of his work. One of Deissoroth’s quotes:

There are deep questions about the brain that may never be answered, but we’re making headway with optogenetics… We’re headed down a path that gets us to understanding [questions like] why does one person feel the way they do and why does it create a disease when they do a particular way, and what can be done to correct it?

Noting that the suffering of people with psychiatric disease “is a very, very serious and pervasive matter,” he also says “the nature of the illnesses – their complexity, the amount of suffering and the mystery – has made this what I was destined to do.”

Previously: Stanford bioengineer Karl Deisseroth wins 2016 Breakthrough Prize in Life SciencesInside the brain of optogenetics pioneer Karl DeisserothLightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact and An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”
Video courtesy of National Geographic Channel

Clinical Trials, Pain, Research, Stanford News

Pain-in-the-neck, begone! Better way to relieve chronic neck and shoulder pain?

Pain-in-the-neck, begone! Better way to relieve chronic neck and shoulder pain?

shoulderHundreds of millions of people worldwide (115 million in the United States alone) suffer from chronic pain. Stanford diagnostic radiologist Sandip Biswal, MD, calls this group “one of the largest populations in the world for medical need of any kind.” But current treatments either aren’t all that great or – in the case of opioids, which are highly effective – put patients at risk for addiction.

A pair of randomized, double-blinded clinical trials, described in a study co-authored by Biswal, former Stanford visiting scholar Charlie Koo, PhD, and several colleagues and published in Nature Scientific Reports, may point to a potential path toward more pain-free lives. In the trials, patients with chronic neck or shoulder pain were treated with three to six 90-minute sessions of either standard physical therapy – so-called transcutaneous electrical nerve stimulation,  or TENS, along with exercise and both manual and heat treatments – or a protocol designed by Koo, who now runs a facility called the Pain Cure Center in Palo Alto, California.

The new method, which Koo calls Noxipoint therapy, also employs electrical stimulation of painful areas, but in a carefully defined way: electrodes are placed precisely at both of the two attachment points for each muscle in pain, and the electrical-current jolt is brief and just enough to cause local soreness and dull, but not sharp, pain. Patients receiving the novel therapy are also told to take it easy for several days after each treatment.

In both trials, Noxipoint therapy proved superior to conventional physical therapy using TENS by close to an order of magnitude. Four weeks after their last treatment, patients given Noxipoint therapy reported substantial pain reduction, restoration of function (for example, regained range of motion) and improved quality of life, without significant side effects. Those given standard treatment reported no significant lasting improvement.

These trials are preliminary and call for confirmation in larger studies, Biswal told me. Given the pressing need for safe, lasting relief from chronic pain and the apparent success of this new method, it would be nice to see those expanded trials take place.

Previously: “People are looking for better answers”: A conversation about chronic painNational survey reveals extent of Americans living with pain and Stanford researchers address the complexities of chronic pain
Photo by Jason Trbovich

Cancer, Imaging, Research

Researchers develop molecular target for brain cancer

Researchers develop molecular target for brain cancer

cai CD146 cancer detection_labels_560x270

About 23,000 new cases of brain and central nervous system tumors are diagnosed annually, and more than 15,000 patients are expected to die of brain cancer this year in the United States, according to the American Cancer Society. Glioblastoma multiforme is the most common brain malignancy, but it remains incurable with only 5 percent of patients surviving at least 5 years after diagnosis. This bleak scenario has motivated the search for a better molecular target for glioblastoma multiforme diagnosis and therapy.

Weibo Cai, PhD, an associate professor of radiology and medical physics, and his research team at the University of Wisconsin-Madison searched the Cancer Genome Atlas database and identified an effective biomarker for the deadly glioblastoma multiforme: the CD146 gene, which is highly active in glioblastoma.

CD146 genes place unique CD146 proteins on the surface of cells. Cai’s team developed an antibody that selectively latches onto the CD146 proteins concentrated on the glioblastoma tumors. They also tagged the antibody with a radioactive copper isotope, so the tumors could be easily identified and localized with a positron emission tomograph (PET), an imaging scanner commonly used to detect cancer.

Cai tested their antibody by implanting animal models with human glioblastoma tumors, injecting them with the antibody and imaging them with a small animal PET scanner. The copper-labeled antibody preferentially accumulated in the tumors, allowing PET imaging to accurately identify tumors as small as 2 mm. Their study results were recently reported in the Proceedings of the National Academy of Sciences.

As Cai explained in a university news release:

We’ve created a tag that – at least in our mouse model – is highly specific for this aggressive brain cancer. If the technique proves out in further tests, it could be used to diagnose some strains of aggressive glioblastoma, and also to evaluate treatment progress or even to test potential drugs.

The researchers also found high activity of CD146 in ovarian, liver, and lung tumors so their antibody could have a wide range of applications. However, there is a lot of research to be done before the technique could be used in the clinic. Cai said in the news release, “This targets tumors with the worst survival, but I want to emphasize that human trials are some years in the future.”

Jennifer Huber, PhD, is a science writer with extensive technical communications experience as an academic research scientist, freelance science journalist, and writing instructor.

Previously: You know it when you see it: a precision health approach to diagnosing brain cancerA Stanford neurosurgeon discusses advances in treating brain tumors, and A century of brain imaging
Images by Weibo Cai/Department of Radiology, University of Wisconsin-Madison. On the left, the antibody is linked to a label that shows up in a PET scanner, and the aggressive cancer shines brightly. On the right, a similar cancer without the molecular marker is less obvious.

Chronic Disease, Infectious Disease, Microbiology, Research, Science, Stanford News

Bad actors: Viruses, pathogenic bacteria co-star in health-horrific biofilms

Bad actors: Viruses, pathogenic bacteria co-star in health-horrific biofilms

biofilmA group under the direction of Stanford infectious disease investigator Paul Bollyky, MD, PhD, has uncovered a criminal conspiracy between two microbial lowlifes that explains how some of medicine’s most recalcitrant bacterial infections resist being expunged.

In a study published today in Cell Host & Microbe, Bollyky and his associates reveal that bacterial pathogens responsible for a big chunk of chronic infections can team up with a type of virus that bacteria ordinarily consider their worst enemies to form biofilms, which, our news release on the study explains, are “slimy, antiobiotic-defying aggregates of bacteria and organic substances that stick to walls and inner linings of infected organs and to chronic wounds, making infections excruciatingly hard to eradicate.” More from that release:

Biofilms factor into 75 to 80 percent of hospital-acquired infections, such as those of the urinary tract, heart valves and knee-replacement prostheses, Bollyky said. “A familiar example of a biofilm is the plaque that forms on our teeth,” he said. “You can brush twice a day, but once that plaque’s in place you’re never going to get rid of it.”

The study first focused on Pseudamonas aeruginosa, which accounts for one in ten hospital-acquired infections, many chronic pneumonia cases and much of the air-passage obstruction afflicting cystic-fibrosis patients.

Cystic fibrosis is deadly mainly because of biofilms formed by P. aeruginosa, Bollyky told me. “These biofilms fill up all the air spaces, and antibiotics can’t seem to penetrate them,” he said.

But he and his colleagues found that P. aeruginosa forms biofilms only when it’s been infected itself.

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Medical Education, Mental Health, Research, Surgery, Women's Health

Stereotype perception linked to psychological health in female surgeons

Stereotype perception linked to psychological health in female surgeons

8116089104_be12619731_oFemale surgeons who believe there’s a stereotype that men are better doctors are more likely to suffer from psychological distress, according to a recent study led by a former Stanford resident.

First author Arghavan Salles, MD, PhD, looked at the correlation between the perception of a stereotype — whether individuals think others believe certain groups are superior physicians — and the overall mental well-being of residents.

The team surveyed 382 residents from 14 medical specialties. To examine views on stereotypes, participants were asked: “Do you think residents in your program expect men or women to generally be better [doctors]?” They were also given standard psychological assessments.

Female surgeons were the only group where stereotype perception was correlated with psychological health. Surgery has traditionally been dominated by men and remains a specialty chosen by about twice as many men as women, leading to the persistence of gender stereotypes.

“As a surgical resident, I was aware of the stereotype that men are better surgeons than women. Although I found the stereotype upsetting, I didn’t think about it too much,” Salles told me. Then, after studying stereotype perception while pursuing a doctorate in education, Salles decided to combine her two specialties to determine whether residents experience stereotype threat; a question that no one had asked before.

The link she found has implications for physician productivity and patient care, Salles said.

“I think it’s important to realize that in the world of medicine, although the ratio of males to females is changing, some of these old stereotypes still have an impact on the practitioners,” said co-senior author Claudia Mueller, MD, PhD.

The belief that others think women aren’t good enough adds an unnecessary stressor to the female residents’ already harried lives, Mueller said. It could also contribute to the high attrition rate of females in surgical disciplines, the study states.

Mueller said the study, which appears in the Journal of the American College of Surgeonsis noteworthy for its rare integration of two quite disparate fields, surgery and psychology.

The authors suggest that simply increasing the number of female surgeons may help dissipate the stereotype. Sharing information about the stereotype may also help, as could investigating any practices that may have a differential effect on men and women, the researchers write.

Salles is now querying residents, faculty members and members of the public to see how prevalent stereotypes about gender-based differences in ability actually are.

Previously: How two women from different worlds are changing the face of surgery, Keeping an even keel: Stanford surgery residents learn to balance work and life and Stanford Medicine magazine opens up the world of surgery
Photo by Phalinn Ooi

Cancer, Pediatrics, Research, Stanford News

A family’s story changes the science of a rare tumor

A family's story changes the science of a rare tumor

Super-DylanWhen Danah Jewett’s 5-year-old son, Dylan, was dying from a brain tumor in 2008, she wanted to know if there was anything her family could do to help other children who might someday face the same terrible diagnosis. Yes, said Dylan’s doctor, Michelle Monje, MD, PhD: Would you be willing to donate his tumor for cancer research after his death?

Danah and Dylan’s dad, John, didn’t hesitate. If it will help, they said, we’ll do it.

Monje explained that scientists needed a way to study Dylan’s rare tumor, diffuse intrinsic pontine glioma, in the lab. The tumor grows tangled into a part of the brain stem that is risky to biopsy in living patients, and decades of chemotherapy trials had not budged the disease’s five-year fatality rate of 99 percent. But having DIPG tumor cells in a dish would open a new world of research options for understanding the biology of the tumor and – Monje hoped – developing new treatments.

After Dylan’s death in early 2009, Monje’s team succeeded in transforming his tumor cells into the world’s first DIPG tissue culture. A few months later, I wrote a feature story for Stanford Medicine magazine about the Jewetts’ donation and its impact. In the intervening years, as I’ve continued to report on Monje’s DIPG research, she has also kept me abreast of the effect of Dylan’s story. It’s pretty remarkable: So far, 21 other families have donated DIPG tissue from their deceased children, many after reading the Stanford Medicine story. And DIPG families have also raised more than $1 million to help fund Monje’s work. Their generosity is enabling new understanding of how the tumor functions, and has helped Monje’s team identify an existing drug that slows DIPG in mice.

I recently interviewed Danah for a short follow-up piece for Stanford Medicine about the impact of Dylan’s story. I asked her to reflect on why she felt able to share the story, given that many families wouldn’t want to open a window for the world into such a heartbreaking part of their lives.

“It’s a hard one,” Danah told me. “I do know a lot of families stay private, but it didn’t dawn on me at the time. I knew then that I just didn’t want to let his memory die. By sharing the story, it helped Dylan to be living on – in my heart and other people’s.”

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