Poor sleep is likely to make you feel grumpy and unfocused, but more importantly it puts you at risk for serious medical conditions such as obesity, type 2 diabetes and heart disease — and it shortens your lifespan.
A new study shows that sleep loss also increases your risk of cardiovascular disease by changing how your body metabolizes cholesterol.
Recently reported in Scientific Reports, University of Helsinki’s sleep team studied the cholesterol metabolism of sleep-deprived people, measuring their gene expression and the levels of blood lipoprotein, a molecule that transports cholesterol through the blood. They assessed these factors for a small group of volunteers who only slept four hours per night for five days. The team also looked at longer-term effects on cholesterol metabolism using data from two large population studies with 2739 participants.
The study found that people getting insufficient sleep have fewer high-density lipoproteins (HDL) — the “good” proteins that act as cholesterol scavengers to decrease accumulation of atherosclerosis within the walls of arteries — than people who get enough sleep.
“It is particularly interesting that these factors contributing to the onset of atherosclerosis, that is to say, inflammatory reactions and changes to cholesterol metabolism, were found in the experimental study and in the epidemiological data,” said Vilmo Aho, a graduate student at the University of Helsinki, in a recent news release.
The bad news is they showed that even a week of sleep deprivation had a significant impact. Aho explained in the release:
The experimental study proved that just one week of insufficient sleep begins to change the body’s immune response and metabolism. Our next goal is to determine how minor the sleep deficiency can be while still causing such changes.
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
New research shows that familial hypercholesterolemia — a genetic condition that leads to high LDL cholesterol — is commonly diagnosed late and patients often don’t get adequate treatment. FH can cause aggressive and premature heart disease, including heart attacks, strokes, narrowing heart valves and sudden cardiac death.
Joshua Knowles, MD, PhD, assistant professor of cardiovascular medicine and chief medical advisor for the FH Foundation, is senior author of a new study that characterizes adult FH patients in the United States using data from the new CASCADE FH Registry™. As reported in Circulation: Cardiovascular Genetics, the study found many flaws in the current treatment of patients with FH. I spoke with Knowles about this silent and deadly disease:
What is Familial Hypercholesterolemia?
Familial Hypercholesterolemia is the medical term given to very high cholesterol that runs in families. We say, ‘We never find an individual with FH. We only find families with FH.’
It’s caused by genetic mutations that control the body’s ability to recycle LDL cholesterol. Your liver makes cholesterol and sends it through the bloodstream. Your body takes what it needs and then sends excess LDL cholesterol back to the liver for recycling.
In FH patients, the liver cannot recycle LDL cholesterol because there are defects in some receptors that pull the cholesterol from the blood. Therefore, the LDL levels remains very high in the blood, which is toxic to the blood vessels over time. If you have FH, your LDL cholesterol levels are two to three times higher than normal and that puts you at a much, much higher risk of early onset coronary disease such as heart attacks.
How is FH diagnosed?
There are over a million people in the US with this disorder, but less than ten percent have been diagnosed. In the US, genetic testing hasn’t become standard of care yet, largely due to the cost. So usually FH is diagnosed with a clinical point system based primarily on your personal and family medical history.
If you’re not diagnosed and treated, your risk of a heart attack is extremely high. However, if you are diagnosed, you can be treated and live a long and healthy life. So it’s a poster child for preventative and personalized medicine.
How is FH treated?
Lifestyle changes — like improving your diet or exercising — are almost never enough for FH patients. FH patients need to be treated with medications that lower their LDL cholesterol. For most people with high cholesterol, one drug is sufficient. However, many FH patients require more than one drug.
The most common and important medications for FH are statins, which work by tricking the body into activating the LDL recycling program. Normally for every gene, you have one copy from Mom and one copy from Dad. In the most common form of FH, you’ve inherited the mutation from one parent. So you have one receptor in the liver that works well and one that doesn’t work at all. The statin drug tricks the body into increasing the levels of the good receptors to compensate for the bad ones — basically putting the good receptors in overdrive to activate the LDL recycling program.
What do you recommend for patients with a family history of early heart disease?
Really the biggest and best thing is to get your cholesterol tested when you’re young, when nothing but the genetic condition causes high cholesterol. If you wait until your 60 years old, it can get trickier to figure out and may be too late. Guidelines from the American Academy of Pediatrics recommend cholesterol screening for children as young as ten years old for the general population and as young as two years old for families with a history of FH. Current research shows that intervening early has a big impact.
What is the CASCADE FH Registry and why is it important?
To advocate for change, it’s really important to have some numbers to back up what we’re saying. When we publish on the data, it raises the profile of the condition. We also need a baseline to compare to in the future. The beauty of the new CASCADE FH Registry is that we’ll be able to follow patients over time to see if what we are doing is making a difference.
It’s not just important for the individual to know whether they have FH. It’s also important for the family to know. When you identify one person with FH, the real potential benefit comes with screening the rest of the family so you can identify ticking time bombs before they have problems. This is called cascade screening – hence the name of the registry. We want to prevent people with FH from becoming patients with FH. We want to prevent those heart attacks.
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
Despite careful patient selection, only about 75 percent of heart recipients survive three years after the transplant surgery. Identifying the patients most in need of additional care has always been tricky, but now Stanford researchers have found a better way to predict which heart transplant recipients have a higher risk of dying or needing another heart transplant, as reported in Circulation today.
One key reason transplant patients die is cardiac allograft vasculopathy, an accelerated and aggressive form of coronary artery disease.
William Fearon, MD, professor of cardiovascular medicine and senior author, explained the significance of their results in a recent email:
Identifying patients at higher risk of dying from cardiac allograft vasculopathy is helpful, because it allows the transplant physicians to be more aggressive with medical therapy and monitoring than they might otherwise be, in order to hopefully prevent adverse events.
The researchers conducted a clinical trial involving seventy-four heart transplant recipients, whose heart physiology was invasively assessed within eight weeks and one year after transplantation. They found that two particular diagnostic procedures were able to successfully identify high-risk recipients — fractional flow reserve and index of microcirculatory resistance.
Fractional flow reserve is a procedure that measures the blood pressure and flow through a specific part of the coronary artery. It is often used to determine whether blood flow is significantly obstructed by a blockage or lesion, guiding a cardiologist’s decision of whether to stent the blockage.
Fearon’s team determined that a low fractional flow reserve measured soon after the transplant independently predicted the heart transplant recipients’ risk of death or retransplantation.
Index of microcirculatory resistance measures the functionality of the tiny vessels that supply blood to the heart, such as capillaries, arterioles and venules. Fearon found that a higher than normal reading measured one year after the heart transplant was also an independent predictor of the recipients’ event-free survival.
The Stanford researchers hope that more emphasis will be placed on these two invasive assessments of cardiac physiology in heart transplant recipients, so their medical regimen can be adjusted to improve the odds of their survival.
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
Just about everyone I know feels overwhelmed with an endless ‘to do’ list of work assignments, chores, errands and appointments. By the end of the day, we often don’t feel up to hitting the gym or going out. We just want to go home to collapse and recharge.
Our busy lives can make it hard to spend much quality time with friends and family. However, research suggests that we need to make this a priority, because social connections impact our health and wellness.
Many studies show that there are distinct, positive physical and emotional benefits from having supportive social connections. Research suggests that illness rates are lower, as is premature death, for those who are socially connected. What seems eminently clear is that positive, supportive connections help people manage the stress of daily living better than people who do not have the outlet of someone who will listen and empathize with their experience.
Gomperts recommends several ways to expand your social connections, such as joining a book club or knitting club, taking a class or volunteering. The key is to find something that works for you. She explained:
For some people, getting out can be really hard — whether due to depression, social anxiety or a lack of time due to pressures in life. However, finding a way to connect is incredibly important, and there are Internet options that can be very useful.
Some people can also benefit from sharing their sense of isolation, loneliness or desire to have more social connections with a counselor or support group — such as those offered at the Faculty Staff Help Center.
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
One of the oldest scientific debates is “nature versus nurture” — do inherited traits or environmental factors shape who we are, and what we do?
So far it’s a draw.
For instance, a massive meta-study, reported in Nature Genetics, quantified the heritability of human traits by analyzing more than 50 years of data on almost 18 thousand traits measured in over 14.5 million pairs of twins. They determined that heritability accounted for 49 percent of all traits and environmental influences for 51 percent.
They essentially found that genes and the environment play an equal role in human development. But that isn’t the end of the debate.
The researchers used PET imaging to measure the glucose — or energy — metabolism throughout the brain. The authors explained their motivation in the JNM article:
“The patterns of glucose metabolism in the brain appear to be influenced by various factors, including genetic and environmental factors. However, the magnitude and proportion of these influences remain unknown.”
The researchers studied 40 identical twin pairs and 18 fraternal twin pairs. Any differences between identical twins is expected to be due to environmental factors since they are genetically identical, whereas fraternal twins only share half the same genes on average.
The researchers compared imaging results between the two types of twins to estimate the extent of genetic and environmental influences. When a genetic influence is dominant, the identical twins would have more trait similarity than fraternal twins. When an environmental influence is dominant, the trait similarity would be the same for identical and fraternal twins.
The researchers found that both genetic and environmental factors influenced glucose metabolism in the brain, but they predominantly affected different areas. Genetic influences played a major role in the left and right parietal lobes and the left temporal lobe, whereas environmental influences were dominant in other regions of the brain.
The brain’s parietal lobes process sensory information such as taste, temperature and touch, and the temporal lobes process sounds and speech comprehension. More research is needed to understand why these areas of the brain where influenced more by genetics.
In addition to adding new information to the “nature verses nurture” debate, these results could be applied to other research areas, such as using imaging to better understand the underlying cause of Alzheimer’s disease or psychiatric disorders. Identifying which regions of the brain are more influenced by genetics or the environment may add critical information to help better understand and treat diseases.
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
Stanford chemists have now developed a highly sensitive and specific tool to screen cancer and HIV — 1000 times more sensitive than current clinical tests. More precise screening could allow for much earlier detection and treatment, as well as help avoid false positive results and their resulting unnecessary procedures and stress.
Developed in the lab of chemist Carolyn Bertozzi, PhD, this new ultrasensitive screening technique has already been tested as a biomarker for thyroid cancer in clinical trials. The study results were recently reported in ACS Central Science.
Many standard clinical blood tests are based on immunoassays, which use highly specific antibodies to detect specific molecules known to be associated with the target disease. Bertozzi’s new screening test adds the power of DNA detection to this standard procedure. Rather than marking, or “flagging”, disease-related antibodies using customary chemical compounds, the team flagged the antibodies using DNA.
The researchers tested their technique, with its signature DNA flag, against four commercially available, FDA-approved tests for a biomarker for thyroid cancer. It outperformed the sensitivity of all of them, by at least 800 times, and as much as 10,000 times. By detecting the biomarkers of disease at lower concentrations, physicians could theoretically catch diseases far earlier in their progression.
Bertozzi is currently testing their ultrasensitive screening method in clinical trials for other diseases, including HIV. If its effectiveness is proven, the researchers expect it to be readily adopted in clinics. Cheng-ting “Jason” Tsai, co-author and graduate student in Bertozzi’s group, said in the news release:
Many of our collaborators are excited that the test can be readily deployed in their lab. In contrast to many new diagnostic techniques, this test is performed on pre-existing machines that most clinical labs are already familiar with.
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
Most of us suffer through at least minor acne as a teenager, but many battle severe acne into adulthood. It affects up to 50 million people annually and can cause permanent scarring, poor self-image, depression and anxiety.
The American Academy of Dermatology recently published new guidelines for acne treatment in the Journal of the American Academy of Dermatology. The new guidelines recommend using several therapies at once. I spoke about them with Justin Ko, MD, MBA, clinical assistant professor of dermatology.
What is your advise for people that suffer from mild to severe acne?
There are great treatments out there! Find a physician with whom you feel comfortable; someone who is willing to talk through the reasons behind acne and formulates with you a personalized treatment approach based on your type of acne, skin type, other health issues, preferences, etc. A therapeutic partnership between a provider and patient is essential. I think that being able to treat acne successfully and effectively is the mark of a good dermatologist. It is and remains immensely satisfying for me to go through this journey with my patients and see them come out the other side with a newfound comfort in their skin.
What do you think of the new American Academy of Dermatology guidelines?
The AAD’s acne treatment recommendations represent the current standard of care. Our core treatment arsenal is comprised of topical treatments, oral antibiotics, hormonally-based treatments and isotrenoin (accutane), as well as other less-commonly used treatments that can have their place for the appropriate patent or situation. I agree with the guidelines that it is especially important for a topical regimen to form the foundation of any approach to acne treatment and not to rely on a single modality.
How has acne treatment changed in the past two decades?
We now have an appreciation for the fact that different types of acne require different approaches. I myself am using oral antibiotics less and more hormonally-based treatments and isotrenoin (accutane) when I think a patient will benefit. Here at Stanford, we also see acne-like eruptions in different forms due to underlying medical conditions and treatments, including new targeted-cancer treatments.
How do laser treatments and photodynamic light therapy work?
In the right settings these treatments can be good, as a companion to “traditional” treatments or situations when a patient is unable to use “traditional” treatments. They work in a couple ways. Some light-based treatments take advantage of a property of selected wavelengths of light that reduce the skin’s immune activity. Acne is fundamentally inflammation around hair follicles, so these light-based treatments can help.
Photodynamic therapy and intensive treatment protocols for PDT actually aim to shrink the oil glands, which play a role in acne formation in unlucky people. This intensive treatment can be quite painful, but it can be effective.
As with any of this, it’s essential to find a provider who is trained in the appropriate, safe and effective use of laser therapy.
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
Imagine you visit a doctor in a far-off land with a different language. Although you have an interpreter, the doctor barely looks at you — instead relaying all information through the interpreter. You feel extra, ignored. If anything, you are building a relationship with the interpreter, not the doctor.
And that’s not good, VJ Periyakoil, MD, clinical associate professor of medicine, points out in the video above.
Our goal is to talk with the patient, through the interpreter, not talkaboutthe patient,tothe interpreter.
The video is part of the Stanford Cross Cultural Medicine Microlecture Series, a series of very short talks (about one to five minutes) that aims to bridge the growing communication gap between doctors and their patients as the U.S. population becomes older and more diverse. There are already11 millionAmericans that are nonliterate in English and 25 million with only limited English proficiency.
Are doctors prepared?
These talks highlight key issues in cross-cultural encounters, including a range of practice tips for health professionals provided by experienced medical interpreters and from Periyakoil. The videos typically end with a take-home message listing the problem and solution — making it easy to quickly learn the concept. Periyakoil and her colleagues hope that health professionals will use the series as a tool to reflect on their own practice.
Microlecture 4emphasizes the importance of talking directly to the patient even when working with a medical interpreter. Patients with limited English proficiency have the right to complete healthcare information, as well as the right to the therapeutic bond between every doctor and patient.
There are currently 16 microlectures posted on thewebsite, but many more are on their way. A total of 44 microlectures have been made and two new ones are being released each week. The lectures also build off recommendations developed in a paper on ethnogeriatrics by the American Geriatrics Society.
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
Approximately 22,280 women will be diagnosed with ovarian cancer, and an estimated 14,240 will die from the disease in the United States this year. Ovarian cancer is deadly in part because the early warning signs are limited and nonspecific — such as abdominal bloating, pelvic pain, a frequent need to urinate and quickly feeling full when eating — so the symptoms are often blamed on other more common conditions. And pap smears don’t detect it, so only 15 percent of ovarian cancer cases are detected before the disease has spread to other tissues.
In 2009, the Department of Defense Ovarian Cancer Research Program created a unique, interactive virtual academy for early-career ovarian cancer researchers, called the OCRP Ovarian Cancer Academy. I recently spoke with a new member of the academy, Erinn Rankin, PhD, assistant professor of obstetrics and gynecology and radiation oncology, about the program and her research
What is unique about the Ovarian Cancer Academy?
The program is a really special funding mechanism that pairs early-career investigators with a local university mentor and a secondary mentor from another university. It provides early-investigators access to the ovarian cancer community, mentorship from established researchers and networking opportunities. Once a year, all members meet together in person. We also have monthly webinars that cover topics for early career development, such as introducing us to patient advocacy groups. And we discuss our individual research and try to identify areas where we can collaborate.
It’s a great grant that will support my research for five years with a total of about one million dollars. But really the access to all the mentors, investigators and networking is more important to my career than the money. I’m very honored and privileged to be part of it. I have a really supportive mentor, Jonathan Berek, MD, who is chair of obstetrics and gynecology here at Stanford. He’s fostered my career in ovarian cancer research. He’s also provided me with the opportunity to collaborate with other great researchers, like Oliver Dorigo, MD, PhD.
What are the major challenges of ovarian cancer diagnosis and treatment?
Ovarian cancer is a highly metastatic and deadly disease. Most patients are diagnosed with advanced metastatic disease. The standard of care for these patients is quite striking. They go through a surgical debulking and then they are treated with conventional chemotherapy. Unfortunately, most of them become resistant to the chemotherapy after multiple cycles, so they end up succumbing to their disease.
It’s such a devastating cancer. If we can make an impact for these patients, it would be wonderful. Since we don’t have good mechanisms to detect the disease earlier, a good way to improve overall survival is to develop new therapies that can effectively treat resistant metastatic disease and prevent recurrence.
What is the specific focus of your ovarian cancer research?
I study how the microenvironment of a tumor influences metastatic progression. In particular, I focus on how hypoxia, or low oxygen supply, drives ovarian cancer metastasis and its resistance to therapy. Virtually every solid tumor has areas of hypoxia. And hypoxia in these tumors is often associated with poor response to therapy, further metastatic progression and poor patient survival. This is the case in ovarian cancer.
We’ve identified a new, really exciting cancer therapy target — a cell receptor enzyme called axl that has a molecular link to hypoxia. Axl is highly expressed in ovarian cancer metastatic lesions in comparison to normal ovary tissue. We identified axl as a key factor regulating ovarian cancer metastasis through genetic means. We then collaborated with Amato Giaccia, PhD, in the radiation oncology department and Jennifer Cochran, PhD, in the bioengineering department to develop a novel therapeutic agent to target axl for metastatic therapy.
Our research now focuses on how our anti-axl therapy works to treat advanced metastatic ovarian cancer. We’re testing it in combination with the standard of care, which is chemotherapy, in two preclinical mouse models of ovarian cancer. We’re really excited. Our anti-axl therapy appears to be a highly potent and safe hypoxia inhibitor. Once we generate more preclinical data, we plan to take this agent into clinical trials. I hope our therapy will make a difference for these patients.
This is a reposting of my Scope medical blog story, courtesy of Stanford School of Medicine.
Dr. Marcus Maydew, radiologist from Creighton University, reviews an x-ray (Offutt Air Force Base).
As a Hodgkin’s lymphoma survivor, I’ve had plenty of CT scans, mammograms, chest X-rays and MRIs during my diagnosis, therapy and 20 years of follow-up care. So I’ve interacted with radiologists at many Bay Area clinics, including Stanford where I was treated — that is, if you count getting summary reports in the mail as “interactions.”
This type of interaction may be changing with the growing movement toward patient-centered care, which is a critical component of the new American College of Radiology’s Imaging 3.0 initiative. Some radiologists are now going beyond image interpretation by discussing test results directly with their patients.
“Many interventional radiologists are now creating their own clinics, seeing patients and following them like any other surgeon,” Sandip Biswal, MD, a Stanford associate professor of radiology, told me. “Patient interactions are also quite heavy in mammography, particularly if the radiologist sees something suspicious.”
As radiologists come out of their reading rooms, many need to improve their communication skills, and a new training program at UMass Memorial Medical Center, called “Coming Out of the Dark,” teaches first and fourth-year radiology residents effective communication skills through role-playing. The program is led by Carolynn DeBenedectis, MD, an assistant professor of radiology there.
The participants practice six scenarios, such as delivering bad news from breast imaging tests, with trained actors performing as the patients. They are evaluated by both the patient actors and attending radiologists with prior communication skills training. The sessions are also videotaped and reviewed with the residents. The same participants return two weeks later to role-play six similar scenarios in order to evaluate their improvement.
At the Radiological Society of North America 2015 meeting, DeBenedectis reported on last year’s pilot program results. Participants were graded using a standard communications assessment scale and their scores on average improved about 5 percent between the two sessions — from 74 percent to 79 percent for first-year residents. More importantly, participants found the training useful, as reported in a recent online story.
We could probably all benefit from improved communication skills. However, there is some controversy over whether diagnostic radiologists should discuss imaging results directly with their patients after their scans. Biswal explained to me:
In the patient’s best interest, we really need to take a team approach. The primary care physician or referring specialist has the best understanding of what the patient is going through, so they can better convey the news. For radiologists to sit down with a patient and give them imaging results without knowing their full story can be potentially dangerous. There is an art to conveying this type of information that takes years of practice. I think of it like this: if it was my mother, how would I want her to be treated?
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
Scientists Talk Funny 
