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AI meets offers real-world benefits to healthcare

In contrast to the science fiction portrayal of evil computers plotting to overthrow humankind, artificial intelligence (AI) in fact seems poised to help improve human health in a multitude of ways, including flagging suspicious moles for dermatologist follow-up, monitoring blood volume in military field personnel and tracking flu outbreaks via Twitter.

The Colorado Clinical and Translational Science Institute (CCTSI) recently held the 7th annual CU-CSU Summit on the topic of “AI and Machine Learning in Biomedical Research”, with over 150 researchers, clinicians and student attendees from all three CU campuses and CSU.

Ronald Sokol, MD, CCTSI director, said, “The purpose of the CCTSI is to accelerate and catalyze translating discoveries into better patient care and population health by bringing together expertise from all our partners.” Rather than individual campuses operating in silos, the annual Summit brings together clinicians, basic and clinical researchers, post-doctoral fellows, mathematicians and others to highlight ongoing research excellence, establish collaborations and increase interconnectivity of the four campuses.

This year’s conference on AI hit capacity for registration, including attendance by more mathematicians and with more poster submissions than the preceding six events. “The topic of AI in research is everywhere. No one knows exactly what is going to happen,” Sokol said, referencing the many privacy and ethics concerns about AI use in research. “I’m here to learn too – I’m not sure I understand it all.”

Living up to the ‘hype’

Lawrence Hunter, director of the Computational Bioscience program at CU Anschutz, framed AI as having the potential to change the way people practice medicine. “There’s a lot of hype, so we need to be careful how we talk about it,” Hunter said.

What, specifically, is AI doing for biomedical research in Colorado? Michael Paul, PhD, assistant professor of Information Science from CU Boulder, uses social monitoring through sites like Twitter and Google to track and predict public health, including yearly flu rates and Zika virus outbreaks. The Centers for Disease Control (CDC) is typically considered the gold standard for public health information, but Paul points out that CDC data is always at least two weeks behind. In contrast, Google Trends provides a daily population snapshot: as a fictional example, ‘1 million people in Colorado searched for ‘flu symptoms on September 15, 2019’.

Steven Lakin of CSU
Steven Lakin, a CSU veterinary medicine student, displays his supercomputing research project at the CU-CSU Summit.

Social media sources like Twitter can be mined for tweets containing terms like ‘flu’ within a specific geographic area or demographic group of interest. Using Twitter, researchers can distinguish between “I have the flu” vs. “I hope I don’t get the flu”, whereas Google data cannot make this distinction.

Steve Moulton, MD, trauma surgeon, director of Trauma and Burn Services at Children’s Hospital Colorado and CU School of Medicine and co-founder of Flashback Technologies, Inc, used a machine learning system originally designed to help robots navigate unfamiliar terrain in outdoor, unstructured environments to create a new patented handheld medical device called the CipherOx, which was granted FDA clearance in 2018.

The CipherOx, developed in partnership with the Defense Advanced Research Projects Agency (DARPA) from the United States Department of Defense, monitors heart rate and oxygen saturation and estimates blood volume through a new AI-calculated number called the compensatory reserve index (CRI), which indicates how close a patient is to going into shock due to blood loss or dehydration. While designed to be used in military field operations, the CipherOx can also be used to monitor patients en route to the hospital and postpartum women. Of note, Moulton’s pilot studies were funded by the CCTSI.

AI basics

AI use in machine learning can be broken into three broad categories: supervised, unsupervised and reinforcement learning. In supervised learning, AI systems learn by being trained to make decisions. For example, in 2016 Google developed an AI-based tool to help ophthalmologists identify patients at risk for a diabetes complication known as diabetic retinopathy that can result in blindness. The Google algorithm learned from a set of images diagnosed by board-certified ophthalmologists and built a set of criteria for making yes vs. no decisions.

In unsupervised learning, AI relies on probabilities to evaluate complex datasets; predictive text on your cellphone is an example of this. In biomedical research, an example of unsupervised learning is using AI to analyze drug labels to find common safety concerns among drugs that treat similar conditions.

Finally, reinforcement learning, like Google’s AlphaZero, the world’s best machine chess player, allows AI to try a lot of options to maximize reward while minimizing a penalty. In reinforcement learning, an AI program can fully explore a hypothetical space without causing trouble. Reinforcement learning in biomedical research can be useful when AI is given a narrow range of choices, for example, predicting best patient response within a narrow range of possible drug doses.

Human mistakes vs. AI mistakes

According to Lawrence Hunter from CU Anschutz, a major problem with AI in healthcare is not proving how good AI is, but paying attention to where it fails. “With 92% correct AI, that gives us confidence that the system is accurate, but we have to be really careful about the other 8% because the kinds of errors AI makes are different (and can be more severe) than the kinds of errors humans make,” he said.

Matt DeCamp, associate professor with the Center for Bioethics and Humanities from CU Anschutz, gave an example of this phenomenon: when AI was used to classify pictures, a picture of a dragonfly was alternatively identified as a skunk, sea lion, banana and mitten. “Some mistakes are easily detected (dragonfly doesn’t equal sea lion),” DeCamp said, “but other mistakes closer to the realm of reasonable may challenge how risks are evaluated by Institutional Review Boards (IRB),” the panels of scientists and clinicians responsible for evaluating patient risks in clinical trials.

THE AI LANDSCAPE

Matt DeCamp, associate professor with the Center for Bioethics and Humanities from CU Anschutz, framed the AI landscape:

  • Up to $6 billion anticipated for AI investment into biomedical research by 2021
  • At least 14 recent AI-related FDA approvals in past two years, mostly in imaging, ophthalmology and pathology
  • 55 active or pending clinical trials using the term “deep learning”
  • 141 startup biotech companies using AI
  • Insurance companies actively using AI to review records and optimize care for chronic conditions

In examples like Google’s system for helping ophthalmologists catch patients at risk of blindness, AI has been heralded as increasing patient access, particularly in rural areas and for patients with limited mobility, and decreasing costs for providers and hospitals. While potential for using AI to improve human health is high, DeCamp echoed Hunter’s comments and cautioned against automatic acceptance of AI superiority. “It’s possible that an AI system could be better on average, but remember that being better on average can obscure systematic biases for different subpopulations. And that is an issue of justice.”

Challenges and concerns

Some issues relative to AI use in biomedical research involve patient privacy. For example, a lawsuit made headlines this summer when a patient at the University of Chicago claimed that his privacy was violated in breach of contract and consumer protection law as a result of data sharing between the university and Google. Michael Paul from CU Boulder said that recent studies regarding use of recreational drug brings up obvious concerns about how to balance public health research with privacy, since Twitter exists in a public space.

Truly informed consent is also an ethical concern, given the ‘black box’ nature of AI algorithms. DeCamp from CU Anschutz clarified, “Black box, meaning that the algorithmic workings are not only unknown, but may be in principle unknowable.”

Just because we can, should we?

Matt DeCamp said that as an ethicist, AI raises big questions. “What is an appropriate use of AI in the first place? Just because we can, does that mean we should? For example, there’s interest in developing robot caregivers. Should we? Would computer-generated poetry be ‘real’ poetry?” Patients may fear further de-personalization of health care in a system that can already seem impersonal at times.

Long-lasting effects of AI are even more uncertain. Will AI change the way we think or act toward each other? DeCamp highlighted research from sociologist Sherry Turkle, PhD, from the Massachusetts Institute of Technology that validates this possibility. In summary of Turkle’s research, DeCamp said, “Computers don’t just change what we do, but also what we think.”

Guest contributor: Shawna Matthews, a CU Anschutz postdoc

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Scientists use advanced imaging to map uncharted area of genome

Using advanced imaging techniques, researchers at the University of Colorado Anschutz Medical Campus have mapped a previously uncharted region of the human genome that gives rise to a variety of disease, setting the stage to potentially test for the conditions in the future.

The study, published Sept. 3 in the journal Genome Research, was conducted by scientists at CU Anschutz led by Tamim Shaikh, PhD, the University of California San Francisco (UCSF) led by Pui-Yan Kwok MD, PhD and KU Leuven in Belgium led by Joris Vermeesch, PhD.

Dr. Tamim Shaikh, PhD, professor of pediatrics in the section of Genetics and Metabolism at CU School of Medicine.
Dr. Tamim Shaikh, PhD, professor of pediatrics in the section of Genetics and Metabolism at CU School of Medicine.

The research upends the view of many that the human genome was fully mapped in 2001 with the completion of the Human Genome Project.

“We have realized over time that this is not entirely true, as there are numerous gaps that remain in the reference human genome sequence,” said Shaikh, one of the senior authors of the study.  Shaikh is a professor of pediatrics in the section of Genetics and Metabolism at University of Colorado School of Medicine. “These gaps are present in regions that are unmappable and often `invisible’ to past and most current sequencing technologies.”

The researchers focused on a region on Chromosome 22, known as 22q11. There were numerous gaps in the sequence of this chromosome due to unmappable genetic sequences known as low copy repeats or LCRs.

LCRs are a significant source of genetic instability and can break chromosomes. That leads to a loss or gain of large pieces of DNA which can cause serious diseases. The loss of DNA in 22q11 leads to the 22q11 deletion syndrome resulting in symptoms which may include intellectual disability, dysmorphic features, heart defects, seizures, Autism spectrum disorders and schizophrenia.

Using two state-of-the-art genome mapping technologies known as fiber FISH and Bionano optical mapping, the researchers were able to see long DNA molecules and discover an unprecedented and extreme level of variability between individuals and populations. These differences can be hundreds of thousands to over two million base pairs of DNA.

“The large differences between people cannot be assessed without the mapping technologies deployed in this study,” said Dr. Pui-Yan Kwok, Henry Bachrach Distinguished Professor at UCSF, a collaborator of Dr. Shaikh who co-authored the paper. “Our approach brings clarity to the organization of the highly complex region studied.”

Shaikh agreed.

“You are mapping these chromosomal fragments back to the genome to see what is different,” Shaikh said. “We looked at over 150 apparently healthy people. We found the region in question was drastically different in each person.”

Some people carried far less and some far more DNA in this part of the genome.

Children with the 22q11 deletion syndrome and their parents were also tested to determine if their 22q11 LCRs were different.

“Now we can start asking questions like, `Is someone with more or  less DNA more disposed to have a child with disease?’” Shaikh asked. “If so, then it might be possible to genetically test parents before they have children.”

Shaikh said this region of the genome is constantly evolving.

“If you look from one generation to the next you may see changes within the same family,” he said. “That is pretty incredible.”

The study was funded multiple sources including a grant from the National Institutes of Health to Shaikh and Kwok.

 

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Research shows positive effects of CBD in Parkinson’s patients

Parkinson’s disease is a neurodegenerative disease that affects 15,000 Coloradans. From feeling fatigued, depressed and anxious, to experiencing uncontrollable muscle spasms and tremors, symptoms can interrupt every aspect of daily life. Maureen Leehey, MD, has worked with Parkinson’s patients for over 30 years and is looking to the booming world of cannabis for a potential treatment.

‘Let’s do the research’

Leehey, a neurology professor and director of the Movement Disorders Division in the CU School of Medicine, believes cannbidiol, most commonly known as CBD, may provide some relief for patients. CBD is a chemical component of cannabis that has anti-inflammatory properties and does not produce the high associated with marijuana.

“There is a lot of literature that suggests CBD might slow down Parkinson’s disease,” she explained. “This research is in basic science and in animal studies. We really wanted to look at how it could potentially benefit our patients. So we thought let’s do the research.”

‘Jumping through regulatory hoops’

Maureen Leehey
Maureen Leehey, MD, director of the Movement Disorders Division in the CU School of Medicine.

Studying cannabis in a rigorous, scientific manner is incredibly difficult. Due to its schedule I rating from the Drug Enforcement Administration (DEA), a prospective researcher must navigate a complicated regulatory pathway to administer it to study participants. However, this didn’t stop Leehey.

“Once marijuana became legalized recreationally in Colorado, our patients started asking about how it could help them,” she said. “There was a lot of interest, and we wanted to look at how we could help our patients make informed decisions about it.”

After almost two years of attaining compliance to a seemingly endless amount of governing bodies, Leehey’s tenacity paid off.

“We were fortunate in that CU Anschutz provided us with the resources we needed to overcome obstacles and really make this study possible,” she said. A special ventilated room was created for the study participants to consume the marijuana-type study drugs on site, and a storage site for these products was bolted to the ground under the protection of a dual-key lock.

Following regulatory approval, Leehey then received the funds from a grant from the Colorado Department of Public Health and Environment (CDPHE) to start her study.

‘Less irritability and improved nighttime sleep’

Leehey was finally set to administer and monitor the effects of a CBD pharmaceutical on Parkinson’s patients. Thirteen patients entered the study and each was given approximately 400 mg of CBD to start; dosing was increased as appropriate.

Overall, the participants reported they felt less irritable and that they were sleeping better, Leehey said. They even saw that some of their motor symptoms, including stiffness and slowness, improved.

Although the participants experienced some mild side effects, the benefits were clear. These results, along with more anecdotal evidence from her patients outside of the study, encouraged Leehey to run another study. This time, she wants to look at the potential benefits of a small amount of THC combined with CBD in patients with Parkinson’s. She is actively recruiting for this study.

‘Support for other researchers interested in cannabis’

Leehey wants other researchers at CU Anschutz who are interested in cannabis to have support in their endeavors.

“CDPHE gave out a few grants for cannabis research,” she said. “We came together and navigated this research path.”

The awardees have since created a group called the Colorado Cannabis Research Consortium, the C2RC.

“Anyone who is really into cannabis research can be a part of this group,” said Leehey. “A lot of researchers get started and then run into problems. We have been there. We want to use this experience to mentor others and really get this research going.”

If you are interested in participating in Leehey’s study, please contact Ying Liu at 303-724-8288 or ying.3.liu@CUAnschutz.edu.

If you are interested in joining the Colorado Cannabis Research Consortium (C2RC), please contact Kirk Hohsfield at kirk.hohsfield@CUAnschutz.edu.

Guest contributor: Blair Ilsley

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Puzzling case of lung cancer leads to breakthrough discovery

Cancer patient Emily Daniels

Getting ready to catch a morning flight to Chicago in February 2018, Emily Daniels felt a strange tightness in her chest. She noticed a shortness of breath. Taking her mother’s advice, she called her obstetrician who said she should go to the ER.

She remembers thinking, “Emergency room … is that really necessary?” Nonetheless, Emily went to an ER near her home in Lakewood and re-booked for a 5 p.m. flight, thinking she’d still make her business trip. After an initial test, doctors advised a CT scan, which revealed two blood clots in Emily’s lungs and a mass in the bottom of her right lung.

“Cancer didn’t even register in my mind,” she said. “What could that (mass) be? I’m young, healthy, no history of disease, never smoked.”

The doctor said it could be lymphoma, a virus or lung cancer and said she should remain in the hospital. Adding to the urgency: Emily was 33 weeks pregnant with her second child.

‘Fight for our kids’

A subsequent biopsy confirmed the mass was cancerous and additional scans showed cancer in Emily’s bones and right adrenal gland. Stage IV lung cancer.

“Initially, it was shocking, devastating,” she said. “But we (along with her husband Brian) also knew we couldn’t wallow in our sadness. We had a 3 ½-year-old girl (Paige) and a baby on the way, so we were going to fight for our kids.”

Emily stayed in the hospital and delivered her baby, Brady, but her diagnosis precluded the new-mother things, like nursing and a quick release from the hospital, she enjoyed with Paige. What should have been a celebratory time felt overshadowed by a startling and grim diagnosis.

She remembers the trip home from the hospital with Brian – Paige was at home with Emily’s parents – where “we pulled over on the side of the road and broke down.”

Pivotal decision for personalized care

Brian Daniels, a former football standout at the University of Colorado, consulted a handful orthopedic doctors he knew from his playing days. Their advice: Get an appointment with Ross Camidge, MD, PhD, professor and director of thoracic oncology, at the CU Anschutz Medical Campus. “He’s one of the best in the world with this targeted therapy,” Emily said. “It was a no-brainer … this is where I needed to do my treatment.”

Ross Camidge
Dr. Ross Camidge

The decision has proven to be pivotal, as Camidge, in collaboration with Robert Doebele, MD, PhD, associate professor of medicine, CU School of Medicine, eventually devised a completely novel and personalized treatment that has, for more than eight months, stopped the spread of Emily’s cancer.

However, before making this major discovery, which will be presented at next week’s World Conference on Lung Cancer in Barcelona, Emily’s medical team worked through their clinical bag of tricks in a very short time. In the ensuing battle, it was readily apparent that Emily’s cancer did not play by the normal rules.

Targeted therapies

In basic terms, the cancer battle comes down to exposure and attack: identifying the genetic pathways that enable cancer to grow, and developing therapies that inhibit those pathways.

BREAKTHROUGH ON WORLD STAGE

Camidge and Doebele are co-authors on the report about the living-cell line that gave doctors insight into Emily Daniels’ cancer and resulted in her novel, personalized treatment regimen that will be presented at the World Conference on Lung Cancer in early September.

Soon after Emily was first seen in the lung cancer multi-disciplinary clinic at the CU Cancer Center Camidge quickly discovered that she had ALK-positive non-small cell lung cancer. Over a decade ago, Camidge was on the clinical-trial forefront that developed the first treatment for lung cancers driven by acquired changes in the anaplastic lymphoma kinase (ALK) gene, causing the cells to grow abnormally fast and aggressively.

A few years later, the initial drug was replaced by more effective ones; Camidge co-led an international trial in 2017 that established alectinib as the initial go-to therapy for this sub-type of lung cancer.

In late-February 2018, Emily started on alectinib and initially responded well to the four pills taken in the morning and four more in the evening. But in just a couple months, her cancer was progressing again.

Another biopsy, tested with the CU Colorado Molecular Correlates Laboratory’s cutting-edge assays, did not show any identifiable reason for the cancer’s resistance. Camidge tried another ALK inhibitor, brigatinib – a drug he also helped develop and one that showed great promise for longer-duration disease control.

Dr. Robert Doebele
Dr. Robert Doebele

However, within a month, Emily’s cancer was progressing again.

Living cells are key to breakthrough

In June 2018, the addition of a specific chemotherapy regimen, identified by Camidge in 2011 as being particularly effective in ALK-positive lung cancer, helped stop her cancer – but only for 3 ½ months. The team then applied another CU-developed treatment strategy: weeding the garden – or radiotherapy treatment of “oligo-progression” as Camidge’s team coined it – whereby they kept Emily on her drug treatments while treating individual spots of cancer with highly focused radiation.

However, nothing completely slowed the cancer. “My colleague Dr. Bob Doebele had this idea that not everything driving resistance in a cancer cell can be found just by looking with the already-established tests,” Camidge said.

Doebele knew there were only a certain number of interrogations that could be done on the kind of preserved pieces of tissue from biopsies like the one sent to the Colorado Molecular Correlates lab. So when the biopsy of Emily’s cancer was taken, as part of a CU research protocol, some of her cancer was sent directly to Doebele’s lab to see if live cancer cells could be grown from it.

“When Bob grows it and it’s living, he can poke it and see which signaling pathways go up and down,” Camidge said. “He was able to deduce that Emily’s cancer had become dependent on another signaling pathway, separate from the ALK side of things.”

That pathway is called MET, and it essentially acts as a second driver of Emily’s cancer.

‘Responded like a dream’

Importantly, all of the known ways of activating MET, the methods doctors test for it in preserved cancer tissue, showed normal results. The key difference were the living cells.

living cancer cells
This is a photo of Emily Daniels’ living cancer cells studied in Dr. Robert Doebele’s lab on the CU Anschutz Medical Campus.

“Entirely because Dr. Doebele was able to grow the cells in a lab, we were able to say for the first time to a patient, ‘Look, your cancer cells have tons of MET signaling going on,’” Camidge said. “In the living cell lines, if we put on a MET inhibitor as well as an ALK inhibitor, they get really unhappy.

“Emily is technically the only patient I know of that has this exact mechanism resistance,” he said.

‘I just have to have hope and believe that the doctors are going to keep coming up with new things.’ – Emily Daniels

Based on Doebele’s data, which will be highlighted at the Barcelona conference, Camidge added crizotinib, a licensed drug designed for other purposes but which can function as a MET inhibitor, to Emily’s treatment.

What has been her response to this targeted-therapy regimen — one that’s been applied to a handful of patients, if that, in the world? Emily started the regimen last December and “she has responded like a dream,” Camidge said.

Patient advocate

Emily, 33, is enjoying every day with her children, watching Paige head off to kindergarten and hearing Brady utter his first words. In August, she and Brian took a long-planned trip to the French Alps and coastal Italy. Every chance Emily gets, she logs a several-mile run, does yoga or lifts weights.

She has also become an advocate for other people battling the disease. She and Brian organized a golf tournament – Links for Lungs – which tees off again on Sept. 11. Last year’s debut tournament raised over $130,000 for the Lung Cancer of Colorado Fund.

“It’s important for me to be an advocate for research and be the face of lung cancer,” she said. “This can happen to anyone – it’s not just smokers and older people.”

‘Truly cutting edge’

Emily said she need not look beyond the CU Anschutz Medical Campus and UCHealth University Hospital for her care. “The research is truly cutting edge,” she said. “They’re doing things at the hospital that they’re not doing at other places. The research that Dr. Doebele and Dr. Camidge are doing truly saved my life and gives me unique treatment options.”

‘Here we are at the cutting edge again. Our whole team lives there and we’re comfortable with it.’ – Dr. Ross Camidge

Camidge is impressed by the way Emily has turned her disease into a positive as she reaches out to other lung cancer patients. “Even though she’s hit many bumps in the road, her attitude is kind of like, ‘Yeah, it’s just another one,’” he said. “So she’s actually much more inspiring to them – not necessarily because things have gone well, but because she’s dug in there… It’s like, she can really say to other lung cancer patients, ‘We’ve been through it, and I know what you’re going through.’”

Emily knows she’ll never be completely cancer free; she has to stay on treatment to control the disease. The important thing is to keep moving forward. “I just have to have hope and believe that the doctors are going to keep coming up with new things,” she said. “I want see Paige go to kindergarten, and Brady grow up and play football and do all the things a parent wants to do with their kids.”

Camidge said all indications show that the combination therapy is working in Emily’s case, but they must remain vigilant.

What’s next?

The next move is to develop a clinical trial with a MET inhibitor that is better at getting into the brain than crizotinib. “The brain is known to be a problem area for crizotinib to reach,” he said. “So we are not waiting to react; we are working on developing the next generation of MET-ALK combinations for Emily and anyone else who needs them.”

The research into cancer’s vulnerabilities, to ideally overcome the disease, grows ever stronger, thanks to the fundraising efforts of people like the Daniels and the novel clinical trials taking place at academic medical centers such as CU Anschutz.

“Here we are at the cutting edge again,” Camidge said. “But that’s OK. Our whole team lives there and we’re comfortable with it.”

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Health care workers unprepared for magnitude of climate change

An epidemic of chronic kidney disease that has killed tens of thousands of agricultural workers worldwide, is just one of many ailments poised to strike as a result of climate change, according to researchers at the University of Colorado Anschutz Medical Campus.

“Chronic kidney disease is a sentinel disease in the era of climate change,” said

Dr. Cecilia Sorensen
Dr. Cecilia Sorensen, lead author of the article in the New England Journal of Medicine.

Cecilia Sorensen, MD, of the Colorado School of Public Health and the University of Colorado School of Medicine. “But we can learn from this epidemic and choose a wiser path forward.”

The article was published today in the New England Journal of Medicine.

Lead author Sorensen and her colleague, Ramon Garcia-Trabanino, MD, said chronic kidney disease of unknown origin or CKDu is now the second leading cause of death in Nicaragua and El Salvador. The death toll from the disease rose 83% in Guatemala over the past decade.

The exact cause of the disease, which hits agricultural workers in hot climates especially hard, remains unknown. It doesn’t align with typical chronic kidney disease which is usually associated with diabetes and hypertension.

“What we do know for certain is that CKDu is related to heat exposure and dehydration,” Sorensen said, adding that exposure to pesticides, heavy metals, infectious agents and poverty may also play a role.

Sugar cane workers in Central America, who often toil in 104-degree heat in heavy clothing, are often victims of the illness.  Sorensen said there is evidence that constant exposure to high temperatures can result in chronic kidney damage.

“They can’t say it’s too hot, they don’t want to go work in the fields,” she said. “If they don’t work, they don’t eat that night.”

The disease is also showing up in the U.S. in places like Florida, California and Colorado’s San Luis Valley.

And the hotter it gets, Sorensen said, the more likely it will increase along with other diseases.

“When it gets hotter, we see more people in emergency rooms with cardiovascular disease,” said Sorensen, who is an emergency department physician at CU Anschutz and a member of the CU Consortium for Climate Change & Health. “We are seeing average global temperatures gradually creep up but one of the biggest risks are heat waves.”

She said U.S. public health officials are not prepared for the kinds of heat waves seen in Europe in 2003 that killed over 70,000 people.

“We are way behind the curve on this compared to Europe,” she said. “We are also seeing Lyme disease in places we never saw it before because the winters are no longer cold enough to kill off the ticks that carry it.”

She said the mosquitos that carry diseases like Zika, dengue fever and Chikungunya are now showing up in the U.S.

“If we are to address both the CKDu and other climate-related diseases, we will have to integrate environmental information into clinical and public health practice and build robust early-warning systems focused on vulnerable communities and climate-sensitive diseases…so we can respond rapidly,” she said. “We believe physicians have the opportunity to change the course of the future.”

 

 

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Researchers discover why intense light can protect cardiovascular health

Researchers at the University of Colorado Anschutz Medical Campus have found that intense light amplifies a specific gene that bolsters blood vessels and offers protection against heart attacks.

“We already knew that intense light can protect against heart attacks, but now we have found the mechanism behind it,” said the study’s senior author Tobias Eckle, MD, PhD, professor of anesthesiology at the University of Colorado School of Medicine.

The study was published today in the journal Cell Reports.

Tobias Eckle, MD, PhD, professor of anesthesiology
Tobias Eckle, MD, PhD, professor of anesthesiology

The scientists discovered that housing mice under intense light conditions for one week `robustly enhances cardio protection’, which resulted in a dramatic reduction of cardiac tissue damage after a heart attack. They also found that humans could potentially benefit from a similar light exposure strategy.

In an effort to find out why, they developed a strategy to protect the heart using intense light to target and manipulate the function of the PER2 gene which is expressed in a circadian pattern in the part of the brain that controls circadian rhythms.

By amplifying this gene through light, they found that it protected cardiovascular tissues against low oxygen conditions like myocardial ischemia, caused by reduced oxygen flow to the heart.

They also discovered that the light increased cardiac adenosine, a chemical that plays a role in blood flow regulation.

Mice that were blind, however, enjoyed no cardio protection indicating a need for visual light perception.

Next, they investigated whether intense light had similar effects on healthy human volunteers. The subjects were exposed to 30 minutes of intense light measured in lumens. In this case, volunteers were exposed to 10,000 LUX, or lumens, on five consecutive days. Researchers also did serial blood draws.

The light therapy increased PER2 levels as it did in mice. Plasma triglycerides, a surrogate for insulin sensitivity and carbohydrate metabolism, significantly decreased. Overall, the therapy improved metabolism.

Eckle has long known that light plays a critical role in cardiovascular health and regulating biological processes. He pointed out that past studies have shown an increase in myocardial infarctions during darker winter months in all U.S. states, including sunnier places like Arizona, Hawaii and California. The duration of the light isn’t as important as the intensity, he said.

“The most dramatic event in the history of earth was the arrival of sunlight,” Eckle said. “Sunlight caused the great oxygen event. With sunlight, trillions of algae could now make oxygen, transforming the entire planet.”

Eckle said the study shows, on a molecular level, that intensive light therapy offers a promising strategy in treating or preventing low oxygen conditions like myocardial ischemia.

He said if the therapy is given before high risk cardiac and non-cardiac surgery it could offer protection against injury to the heart muscle which can be fatal.

“Giving patients light therapy for a week before surgery could increase cardio protection,” he said. “Drugs could also be developed that offer similar protections based on these findings. However, future studies in humans will be necessary to understand the impact of intense light therapy and its potential for cardio protection.”

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CU Movement Disorders Center named a Center of Excellence

The University of Colorado Movement Disorders Center is now one of now 48 International Centers of Excellence designated by the Parkinson’s Foundation.

CU Motion Disorders Center group photo.
Faculty and staff of the University of Colorado Motion Disorders Center. Center co-directors are Dr. Maureen Leehey, bottom row, far left, and Dr. Lauren Seeberger, bottom row, center.

Designations this year were focused on medical centers that focus on underserved populations. “Other criteria included the ability to provide the highest level of evidence-based patient-centered care, conduct relevant clinical research that serves patient priorities, demonstrate leadership in professional training and conduct impactful patient education and community outreach.”

Here is a link to the Parkinson’s Foundation news release.

The Center of Excellence network is an important part of the Parkinson’s Foundation goal to ensure everyone living with Parkinson’s has access to expert care so they can live better lives. Every center must recertify after five years to ensure the required standards of care.

The center is located within the CU School of Medicine. Dr. Lauren Seeberger and Dr. Maureen Leehey will serve as co-directors of the CU Movement Disorder Center.

Guest contributor: Nicole Leith, Movement Disorders Center Coordinator and Marketing Specialist.

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Bus revs up innovative access to sun safety

Neil Box and Sun Bus

Strolling across the manicured lawn of the Denver Polo Club under a bluebird Colorado sky, Neil Box, PhD, walks his sun-safety talk. He wears a wide-brimmed Wallaroo hat, dark sunglasses and EltaMD sunscreen, while greeting the many attendees of the recent “Mallets for Melanoma,” an annual fundraising event for the Colorado Melanoma Foundation (CMF).

Box, associate professor of Dermatology in the CU School of Medicine, is an expert on UV exposure and the measures to prevent the sun’s damaging effects, especially here in Colorado, where the rate of skin cancer diagnosis well exceeds the national average.

“I like to say to people, ‘You only have one skin, and once you’ve ruined it, it’s ruined,’” he says. “Everybody’s got a skin on them, and everybody’s getting sun damage.”

Making Coloradans sun smart

Box shows a guest a Colorado health creation – the Sun Bus – which in just a few months has rolled to the fore of the CMF’s community education efforts. A fixture at many of the state’s biggest summer festivals, the Sun Bus offers free skin cancer screenings and education, sun-safety products such as hats, shirts and sunscreen, as well as cutting-edge technology that measures hidden sun damage and shows exactly how sunscreen is covering – or not – your body.

Polo match at Mallets for Melanoma
Attendees of the “Mallets for Melanoma” fundraiser enjoyed watching polo matches on the grounds of the Denver Polo Club.

The well-equipped 40-foot-by-10-foot vehicle casts an impressive shadow – as well it should.

“That’s the beauty of it,” Box says of the bright-yellow bus. “It’s a big presence – highly visible. It gets people’s attention, and that’s what you need to do. We need to get people’s attention on this subject and get them thinking about skin health.”

Reveal imager on Sun Bus
“Mallets for Melanoma” attendees get their faces photographed at the Sun Bus’s reveal imager. Using polarized wavelengths of light, the imager reveals hidden sun damage in the skin.

The Sun Bus is playing a key role in the CMF’s awareness building, including in July, which is UV Safety Awareness Month. “Our bus is a driving billboard – a massive billboard for our project. Our partners, who have their logos on the bus, help steer money toward a cause that we know is important to our community,” Box says. “There’s a huge interest in having free screenings available.”

Big numbers

Since debuting at Denver’s Cinco de Mayo festival, the Sun Bus has been at events with a total of over 600,000 people. Also:

  • It has provided over 550 free skin screenings;
  • It has referred over 70 people with lesions to specialty care, with the on-bus clinicians noting that at least three of those cases were likely to be melanomas.
  • It has hosted over 12,000 significant engagements where people interacted with the technology, information and products available on the bus.

“These are big numbers,” says Box, CMF president. “The bus is having an impact.”

And that’s a good thing, he adds, because skin-cancer prevention efforts in the United States haven’t kept up with how treatment options have significantly “launched forward” in the last eight years. “In the screening and prevention space, we need to keep up with the progress the oncologists have made.”

Researching susceptibility to skin cancer

The Sun Bus has a research component as well. Along with researchers in the CU Cancer Center, and assisted by interns from the Gates Summer Internship Program (through the Gates Center for Regenerative Medicine), and CU medical students and staff, Box is looking for genetic factors that make some people more susceptible to skin cancer.

Why Colorado is a burner

Colorado gets some of the highest UV exposure levels in the nation because of its altitude and average of 300 sunny days per year. Box said there are more UVA and UVB rays present in Colorado because of the state’s altitude.

Both UVA and UVB rays can cause mutations in the DNA and other kinds of skin damage, he said. “The nature of the problem here is that sun damage is higher than a lot of other places because the exposure you’re getting is that much more potent.”

At Denver’s altitude of 5,280 feet, people are exposed to 26 percent more UV in the visible light than at the same latitude at sea level, he said. At 10,000 feet, they are exposed to 50 percent more UV in the visible light, and climbing a 14,000-foot-peak they are exposed to 70 percent more UV.

Key measures to prevent sun damage are: limit your time in the sun; wear a hat, sunglasses, sun sleeves and/or a sun shirt; and use at least 30 SPF broad-spectrum sunscreen on exposed skin and reapply every two hours. For more information on sunscreens, follow the American Academy of Dermatology’s recommendations on sunscreen.

Researchers are age-, sex- and genotype-matching subjects from the Cancer Center’s cutaneous oncology clinic with non-melanoma subjects from the general community, he says, “and seeing if we can find better ways to capture the results of environmental exposures in relation to melanoma epidemiology and skin cancer epidemiology.”

Box notes there are more skin cancers than any other cancer type. In the United States, about 3 million non-melanoma skin cancers – such as basal- and squamous-cell carcinoma – are diagnosed each year. Melanoma, the deadliest type of skin cancer, is the most frequently diagnosed cancer in women in their 20s and 30s. In Colorado, 1,800 new melanomas will be diagnosed this year and about 140 of those patients will die.

“We’re above the national average for sure,” Box says. “We’re in the highest levels of UV exposure but states like Washington and Oregon get higher per-capital rates of melanoma than Colorado.”

Steering toward alignments

Box hails from Australia, which has mounted successful public awareness campaigns about sun safety, resulting in significant improvements in skin cancer rates, and he’d like to see similar efforts occur in the States. Unlike other nations where governmental programs lead the way in raising awareness, “in the U.S. it has to happen through corporate money and finding alignments where (the campaign) fits the business partners’ strategy.”

The Sun Bus concept is the brainchild of Karen Nern, MD, a CMF board member and the Market Medical Director for Epiphany Dermatology’s Vail, Aspen, Breckenridge and Glenwood Dermatology clinics. The Sun Bus is sponsored by EltaMD skincare, the Cancer League of Colorado, Vail Health and other local stakeholders.

It’s gratifying to see people of all ages stroll up to the Sun Bus and learn habits that can lead to a much healthier future, especially here in outdoors-oriented Colorado.

“We need to get creative in how we bring these types of services to people. It’s about creating reasonable healthcare access,” Box says. “And it’s very appropriate that we are trialing a program like the Sun Bus right here in Colorado because of the sun exposure we get. It would be great to see similar programs emerge in the Southern states as well.”

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Greater prevalence of congenital heart defects in areas with high intensity of oil and gas well activity

Mothers living near more intense oil and gas development activity have a 40-70% higher chance of having children with congenital heart defects (CHDs) compared to those living in areas of less intense activity, according to a new study from researchers at the Colorado School of Public Health.

“We observed more children were being born with a congenital heart defect in areas with the highest intensity of oil and gas well activity,” said the study’s senior author Lisa McKenzie, PhD, MPH, of the Colorado School of Public Health at the University of Colorado Anschutz Medical Campus.  At least 17 million people in the U.S. and 6% of Colorado’s population live within one mile of an active oil and gas well site.

Dr. Lisa McKenzie
Lisa McKenzie, PhD, MPH, of the Colorado School of Public Health

The study was published today in the peer-reviewed journal Environment International.

The researchers studied 3,324 infants born in Colorado from 2005-2011. They looked at infants with several specific types of CHDs.

Researchers estimated the monthly intensity oil and gas well activity at mother’s residence from three months prior to conception through the second month of pregnancy.  This intensity measure accounted for the phase of development (drilling, well completion, or production), size of well sites, and production volumes.

They found mothers living in areas with the most intense levels of oil and gas well activity were about 40-70% more likely to have children with CHDs. This is the most common birth defect in the country and a leading cause of death among infants with birth defects. Infants with a CHD are less likely to thrive, more likely to have developmental problems and more vulnerable to brain injury.

Animal models show that CHDs can happen with a single environmental exposure during early pregnancy. Some of the most common hazardous air pollutants emitted from well sites are suspected teratogens – agents that can cause birth defects – known to cross the placenta.

The study builds on a previous one that looked at 124,842 births in rural Colorado between1996-2009 and found that CHDs increased with increasing density of oil and gas wells around the maternal residence. Another study in Oklahoma that looked at 476,000 births found positive but imprecise associations between proximity to oil and gas wells and several types of CHDs.

Those studies had several limitations including not being able to distinguish between well development and production phases at sites, and they did not confirm specific CHDs by reviewing medical records.

The limitations were addressed in this latest study. Researchers were able to confirm where the mothers lived in the first months of their pregnancy, estimate the intensity of well activity and account for the presence of other air pollution sources. The CHDs were also confirmed by a medical record review and did not include those with a known genetic origin.

“We observed positive associations between odds of a birth with a CHD and maternal exposure to oil and gas activities…in the second gestational month,” the study researchers said.

The study data showed higher levels of CHDs in rural areas with high intensities of oil and gas activity as opposed to those in more urban areas. McKenzie said it is likely that other sources of air pollution in urban areas obscured those associations.

Exactly how chemicals lead to CHDs is not entirely understood. Some evidence suggests that they may affect the formation of the heart in the second month of pregnancy. That could lead to birth defects.

McKenzie said the findings suggested but did not prove a causal relationship between oil and gas exploration and congenital heart defects and that more research needs to be done.

“This study provides further evidence of a positive association between maternal proximity to oil and gas well site activities and several types of CHDs,” she said. “Taken together, our results and expanding development of oil and gas well sites underscore the importance of continuing to conduct comprehensive and rigorous research on health consequences of early life exposure to oil and gas activities.”

The study co-authors include William Allshouse, PhD, BSPH and Stephen Daniels, MD, PhD, both of the University of Colorado Anschutz Medical Campus.  The study was funded by a grant from the American Heart Association.

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The importance of the mental side of healing

Bruce Gordon

Bruce Gordon has always been an athlete. Climbing mountains, endurance swimming and biking came naturally to him.

But he also had a lingering concern that had always weighed on him: a family history of heart attacks. And in November 2017, that genetic propensity caught up to him. While he was at the airport heading for his departure gate, Gordon suffered a major heart attack that required multiple resuscitations and triple bypass surgery at UCHealth University of Colorado Hospital to save his life.

After surgery and the physical recovery that followed, Gordon entered unfamiliar territory. He struggled with anxiety and a feeling of fragility, and he was ultimately afraid he was going to have another heart attack. It became clear that he needed to seek mental health support.

“The anxiety was paralyzing,” he says. “I remember my daughter coming up to me and touching me on the shoulder, and I jumped. I couldn’t believe it. It was like I was having PTSD.”

What many people don’t realize, says C. Neill Epperson, MD, chair of the Department of Psychiatry at the University of Colorado School of Medicine, is that “Having a severe or life-threatening medical problem like a heart attack can have a direct, negative effect on brain health – from functionality, to how you feel, to how you think about your health moving forward.

“When you’ve experienced a traumatic event or a life threatening health condition, you can feel terrified and helpless in the moment, and that feeling of extreme fear doesn’t automatically go away just because the event is over,” Epperson explains. “Memories of the event are indelibly encoded in the brain. However, things we may have seen, smelled, heard or thought during the event can also become linked to it in such a manner that they provoke a similar terror when re-experienced, even in a safe context. We can become anxious, irritable and jumpy. As Mr. Gordon discovered during his recovery, trauma-informed, cognitive behavioral therapies change the brain so that these memories – potential triggers for anxiety and worry – are no longer as powerful.”

“You have to address the mental side of healing,” says Gordon, who worked with a sports psychologist to help him navigate this essential aspect of his recovery. “Even if you reach a point when you’re feeling good physically, if you’re pushing down the pain or the trauma of the mental side, it’s going to manifest itself in a negative way. You can’t be afraid to face it – to let your emotion come out, to cry. Talking to someone professionally is super important.”

Learn more about Dr. Epperson’s insights into the relationship between mental health and physical health in the video below.

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