Advancing the Science

Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.

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9 hours ago · Research breathes new air into donor lungs

Ex vivo lung perfusion technology is the process by which marginal donor lungs are treated with specialized solutions and gases that can reverse lung injury and remove excess fluids in the lung, making them clinically viable for transplant.

By Sara Nick

Four hundred: That’s the number of U.S. patients who die each year awaiting a lung transplant, or are removed from the wait list when they become too ill. Now, cutting-edge research underway on Mayo Clinic’s Florida campus aims to save as many of those lives as possible. “We’re hoping to wipe out the wait list and get that number as close to zero as possible,” says Mayo pulmonologist David Erasmus, M.B., Ch.B., M.D.

“Lungs are very delicate,” Mayo pulmonologist Jorge Mallea, M.D., says of the shortage. “Of all available organ donors, only about one in five can donate their lungs, which suffer greatly from the effects of brain death.” Additionally, he explains, it can be difficult for a medical team to predict whether a particular set of donor lungs can be successfully transplanted. “The goal of our research is to address these challenges. In doing so, we can increase the number of lungs available for donation,” he says.

Newly opened Discovery and Innovation Building on Mayo Clinic’s Jacksonville, Florida, campus.

At the center of this research is a recently developed technique called ex vivo lung perfusion. In this approach, a lung is removed from its donor, isolated, and placed in a specialized chamber where it is resuscitated and supported, making otherwise marginal donor lungs suitable for transplant. The process also allows experts to better predict whether donor lungs will be successful in transplant.

“Will donor lungs cared for in a
centralized system be just as good as — and ideally better than — those in the
traditional donor program? That’s the question our research is getting at,”
says Dr. Mallea.

The lung perfusion platform has already
been shown to be safe, so Mayo researchers are now looking at ways to maximize
its reach for the benefit of patients across the country. Currently, each
hospital that wants to use ex vivo lung perfusion for patients must have its
own equipment, staff, and space. “This is expensive and inefficient,” says Dr.
Mallea. Instead, they’re assessing whether a centralized system for lung
perfusion can better serve the needs of patients and hospitals. Under this
approach, donor lungs from any part of the country could be shipped to a
dedicated facility, cared for and evaluated by lung perfusion experts, and sent
back to recipient patients at any participating hospital.

Lung Bioengineering Center in the Discovery and Innovation Building in Jacksonville, Florida.

The scientists are collaborating with biotechnology company United Therapeutics. On August 22, Mayo and United Therapeutics celebrated the grand opening of a new lung bioengineering center on Mayo’s Florida campus.

Evaluating a centralized facility for ex vivo lung perfusion is just one aspect of the expansive lung transplant research scene on Mayo’s Florida campus. For example, Dr. Erasmus and colleagues are collaborating with a team from the University of Vienna to assess whether a new biomarker can be used to determine transplant recipients’ level of immunosuppression.

“If patients are overly immunosuppressed, they’re more susceptible to infection; if they’re under-suppressed, they’re more likely to reject the organ,” Dr. Erasmus explains. “This biomarker could help us adjust their medications accordingly, which is currently difficult to do.”

Additionally, in the field of regenerative medicine, Dr. Erasmus, Abba Zubair, M.D., Ph.D., and colleagues are working to determine whether bone-marrow derived mesenchymal stem cells can be administered to transplant recipients to prevent chronic organ rejection. The scientists also hope that stem cells could one day be applied during ex vivo lung perfusion can improve lungs’ suitability for transplant. “Mayo can offer patients everything from at-home pulmonary rehab exercises all the way through lung transplant,” says Dr. Mallea. “Stem cell therapy would allow Mayo to complete the whole gamut of treatment.”

“Mayo has always been at the forefront
of clinical medicine, and we’re in the midst of an incredible opportunity to
spearhead the area of lung transplant,” Dr. Erasmus adds. “This work can make a
significant difference for patients.”

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Related resources from Mayo Clinic:

5 days ago · Targeting therapy to each patient's unique cancer

Article by Sara Damore

Funda Meric-Bernstam, M.D.

As DNA sequencing technology helps bring genetic factors driving disease into focus, researchers have developed new cancer therapies to target a patient’s unique cancer, especially for those who do not respond to standard therapy.

Funda Meric-Bernstam, M.D., a physician-scientist at MD Anderson Cancer Center, will speak on Decision Support  for Precision Oncology – Evolving from Monotherapy to Combinations, highlighting innovative research efforts at this year’s Individualizing Medicine Conference: Precision Cancer Care through Immunotherapy and Genomics, hosted by Mayo Clinic Center for Individualized Medicine on Sept. 20-21, in Scottsdale, Arizona.

Alan Bryce, M.D.

“We’re excited to welcome Dr. Meric-Bernstam to this year’s conference. With her leadership, cancer research is bringing precision treatment options to thousands of patients,” says Alan Bryce, M.D., chair, Hematology and Oncology, and medical director of the Genomic Oncology Clinic at Mayo Clinic’s campus in Arizona.

Sharing expertise – using genomics to guide cancer care

Dr. Meric-Bernstam is one of many experts in precision oncology who will be sharing their expertise in genomics at this year’s conference. She is the chair of the Department of Investigational Cancer Therapeutics—the Phase I Program, and medical director, Institute for Personalized Cancer Therapy, at MD Anderson. Her basic and translational research programs focus on molecular therapeutics and identifying the mechanisms of action in targeted treatments in order to identify those patient populations who will benefit from these therapies.

In addition, she has an active basic, translational and clinical research program focused on breast cancer biology and novel breast cancer therapies.

Dr. Meric-Bernstam joined MD Anderson in 2001 after completing her research fellowship. She earned her medical degree from Yale University and completed her residency at University of Michigan and a postdoctoral fellowship at the National Institutes of Health.

Join us at the conference

As one of the conference directors, Dr. Bryce notes, “CIMCON19 is designed for practicing clinicians and researchers who want up to date information on the latest treatment strategies for cancer care.  Speakers will cover topics ranging from breast cancer genomics, to precision immunotherapy, CAR-T cell therapy, and serum tumor DNA analysis.”

Preconference sessions will provide an in-depth look at the science driving many advances in cancer care:

  • Drugs and Genes: Pharmacogenomics for the Modern Health Care Team
  • Basic Science of Immunotherapy
  • Advanced Molecular Oncology Testing: A Focus on Next Generation Sequencing Panels and Novel Genetic Technologies

For a complete schedule and list of speakers, visit the conference website.

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This article was originally published on the Mayo Clinic Center for Individualized Medicine blog.

6 days ago · Mayo fellow already an internationally recognized expert on celiac disease

Alberto Rubio Tapia poses in the Mayo  Plummer Library
Alberto Rubio Tapia, M.D.

Alberto Rubio Tapia, M.D., was a fellowship-trained gastroenterologist in Mexico. He came to Mayo Clinic in 2006 to gain research experience.

“My institution in Mexico City, National Institute of Medical Sciences and Nutrition (Salvador Zubiran), has a long tradition in clinical and research training collaboration with Mayo Clinic, so I was familiar with Mayo,” says Dr. Rubio Tapia. “I fully intended to return to Mexico to practice. However, I was offered a research staff position within my first year at Mayo and began to see what career opportunities in the U.S. could be like. So I stayed longer. Thirteen years later, I’m certain my career is in academic medicine in the U.S.”

It wasn’t as easy as it may sound. To practice in the U.S., Dr. Rubio Tapia, who was fully trained, had to complete another residency and fellowship. While completing those requirements, he continued his research and mentored his co-residents and co-fellows with their research, helping several of them get their first articles published and secure their first presentations at national meetings. Dr. Rubio Tapia describes this work as one of the Mayo Clinic opportunities he has enjoyed the most.

“My education and training have been extensive, but I’ve enjoyed every single step and love what I do,” says Dr. Rubio Tapia. “My residency and fellowship at Mayo were easy because I’d had strong training in Mexico at the best institution in the country for internal medicine and gastroenterology. My commitment to my profession and research is very high.”

When our best people, such as Dr. Rubio Tapia, finish training, the larger medical community benefits.”

Joseph Murray, M.D.

Dr. Rubio Tapia’s commitment has led him to become an internationally recognized authority on celiac disease. He has been lead author for celiac disease guidelines for the American College of Gastroenterology and has published 81 peer-reviewed manuscripts in all of the major journals of gastroenterology as well as 16 book chapters. His work has thousands of citations. Some of Dr. Rubio Tapia’s high-impact first-author studies include demonstration of an increased mortality in patients with undiagnosed celiac disease, the increasing prevalence of celiac disease in the U.S., the first description of olmesartan-induced celiac-like disease, and a new classification score for refractory celiac disease. For these and more efforts, Dr. Rubio Tapia received the Mayo Clinic Alumni Association Donald C. Balfour Award for Meritorious Research.

Laura Raffals, M.D., program director for the Mayo Clinic fellowship in gastroenterology and hepatology, says Dr. Rubio Tapia has more than earned his place as first author on the American College of Gastroenterology celiac disease guidelines. “For most of us, it takes a long time to achieve a milestone such as this. Dr. Rubio Tapia did it even before finishing his fellowship. He is routinely invited to moderate sessions and lecture on celiac disease at meetings of the leading societies in gastroenterology. We are fortunate in our division to train many fellows who go on to achieve international success in this field. We are not sure if we have ever had a better candidate for the Balfour Award.”

Joseph Murray, M.D

Despite the accolades, what Dr. Rubio Tapia is most proud of is being part of the Mayo Clinic family. “In particular, I’m very proud of the relationship I have with my mentor, Dr. Joseph Murray.

Dr. Murray says with Dr. Rubio Tapia on board, Mayo Clinic’s celiac disease research program has had its most productive years and Mayo has been cemented as a center of excellence for treatment of celiac disease. “His energy, enthusiasm, maturity, curiosity, insight, critical thinking, and ability to persevere despite challenges and limitations are part of the secret sauce of Dr. Rubio Tapia’s success. He developed a predictive tool for survival in refractory celiac disease and wrote the guidelines for celiac disease in Mexico. His work in the natural history of the disease is groundbreaking. There’s been a sea change around the world in regard to celiac in the last decade, and Dr. Rubio Tapia’s contributions have been central to that progress. We no longer think of celiac disease as rare. Today most physicians know it’s a common chronic disease they can test for.”

Bringing it all back home, Dr. Rubio Tapia says he’s especially proud of being inducted into the National Academy of Mexico in 2016. “This peer-review induction is the most important distinction for doctors in Mexico. Most people achieve that at the end of their careers. It’s very difficult to achieve before age 40. It feels good to be recognized for my hard work in research and the clinic by my home country.”

As Dr. Rubio Tapia prepares to complete his fellowship and continue his academic career, Dr. Murray reflects. “When our best people, such as Dr. Rubio Tapia, finish training, the larger medical community benefits. As a Mayo Clinic-trained clinician-investigator, he will expand the field of celiac disease across the nation and world. Dr. Rubio Tapia will continue to be a valued colleague and peer. His success is our success.”

Thu, Sep 5 6:00am · If it isn't broken, why fix it? Advancements in multiple myeloma diagnosis.

Dr. Murray points to something on a computer monitor. Dr. Dispenzieri looks on.
David Murray, M.D., Ph.D., worked with colleagues in the Division of Hematology including Angela Dispenzieri, M.D., to develop and introduce a new test to diagnose multiple myeloma.

The standard laboratory test to diagnose multiple myeloma dates back to the Eisenhower administration. Research at Mayo Clinic spearheaded by David Murray, M.D., Ph.D., and fueled by his experience as an industrial chemist has led to a new assay to screen and diagnose the disease.

Lacking in speed and specificity

Despite gargantuan leaps in medicine in the last 60 years, serum protein electrophoresis has remained the standard for finding a monoclonal antibody — often the first step in diagnosing multiple myeloma. This test, which is performed by hand, involves putting the patient’s serum on a gel, applying an electrical current to it, separating out the proteins, and looking for overexpressed immunoglobulins by immunoelectrophoresis or immunofixation. The process takes hours per patient sample, and the test isn’t particularly sensitive. The test may be negative when disease is still present in the patient as evidenced by bone marrow biopsy or other findings.

Angela Dispenzieri
Angela Dispenzieri, M.D.

“Physicians have known for quite a while that the standard test wasn’t sensitive enough to detect the disease in all cases,” says Angela Dispenzieri, M.D., a Mayo Clinic hematologist and the Serene M. and Frances C. Durling Professor. “Bone marrow biopsy is more sensitive, but it’s expensive, invasive and isn’t pleasant for the patient.”

Introducing industry expertise

Dr. Murray joined the Mayo Clinic staff in the Division of Clinical Biochemistry and Immunology in 2010 after completing a residency in pathology at Mayo Clinic School of Graduate Medical Education. Prior to medical school, he earned a Ph.D. in polymer chemistry and was an industrial chemist at Eastman Kodak for 10 years. He worked in material science, developing new plastics and materials for packaging and paint.

As a resident, he rotated through the Mayo Clinic Protein Immunology Laboratory and saw a knowledge gap and opportunity.

“I walked into the lab and thought, ‘They’re still running gel electrophoresis in this day and age?’” says Dr. Murray. “That’s an ancient technique. I spent a lot of time in a high-tech chemistry lab and know that mass spectrometry is much better. Most physicians don’t have that industry experience. I recognized a knowledge gap and saw that my talents could be used to develop a better test to help physicians and patients.

Dr. Kyle
Robert Kyle, M.D.

“I also saw unbelievable opportunity. Dr. Robert Kyle has a legendary database of serum samples of multiple myeloma patients dating back to 1960. For a researcher, that’s pure gold. It means we have access to unlimited samples to validate any new test on.”

Finding a bounty in serum database

Dr. Murray got to work on developing a new test with David Barnidge, Ph.D., a mass spectrometrist working in laboratory medicine at the time. They experimented with mass spectrometry, an analytical technique used to determine the molecular mass of specific molecules in a sample. The colleagues found that MALDI-TOF (matrix-assisted laser desorption/ ionization time of flight) mass spectrometry, which uses a rapid fire laser to ionize proteins into the gas phase, allowed them to rapidly analyze immunoglobulins.

After six years their team had developed a mass spectrometry testing method that was adaptable to the lab and was more sensitive than the standard gel technology used to diagnose multiple myeloma. Mass spectrometry identifies and quantifies monoclonal antibodies secreted in the patients’ serum. For two years the team performed clinical and analytical validation on 2,000 samples from Dr. Kyle’s database.

“We could never have done this at another institution without access to that serum database,” says Dr. Murray. “In the 1990s Dr. Kyle screened 77 percent of the Olmsted County population for MGUS (monoclonal gammopathy of undetermined significance), a condition in which a monoclonal or abnormal protein is present in the blood. MGUS causes no problems but can progress to multiple myeloma or related disorders. A group of those people who tested negative were diagnosed with MGUS more than a decade later. Dr. Kyle had preserved their negative-testing serum samples. Using our new testing method, we detected MGUS in the 1990s samples of half of that group. Had the more sensitive test existed then, those individuals could have been diagnosed much earlier.”

“I recognized a knowledge gap and saw that my talents could be used to develop a better test to help physicians and patients.”


David Murray, M.D., Ph.D

Launching a new test

Dr. Kyle stands talking with Dr Murray
David Murray, M.D., Ph.D. (right), collaborated with Robert Kyle, M.D., as he developed a new lab test to diagnose multiple myeloma. Dr. Murray describes Dr. Kyle’s legendary database of serum samples of multiple myeloma patients as pure gold.

The new test was introduced by Mayo Clinic Laboratories in July 2018. Mayo Clinic now uses the monoclonal gammopathy screening on all patients with or suspected to have a plasma cell disorder.

Mayo Clinic licensed the test technology to The Binding Site, a company that provides specialty diagnostic products to clinicians and laboratory professionals worldwide, to assist with obtaining Food and Drug Administration approval. Dr. Barnidge became laboratory director for The Binding Site, and the company built a research laboratory in Rochester to focus on this project.

Dr. Murray has been in high demand since the hematology community learned of this significant development at Mayo Clinic. At least once a week he’s invited to speak to groups about what his team has discovered about immunoglobulins.

“Long before multiple myeloma can be detected by conventional methods, mass spectrometry allows us to see the unique origins of the disease and possibly the disease mechanism,” says Dr. Murray. “New methods allow you to see things with new eyes. And new eyes were definitely needed to modernize the way we detect and diagnose this disease.”

Dr. Murray says Dr. Kyle, widely considered to be “the godfather of multiple myeloma,” is one of his biggest supporters. “Dr. Kyle said this is the greatest advance since the death of U-tube — U-tube electrophoresis, the predecessor to gel electrophoresis.

“If I’d done this work anywhere else, I’d have published a paper and no one would have paid attention to it. It’s gotten so much traction because Mayo Clinic is universally regarded as the home of multiple myeloma. The attitude in the myeloma community was, ‘If you guys can’t do it, no one can. We’ll wait for you to do it.’ The collaborative environment at Mayo allowed me to work closely with Dr. Kyle. It was a team effort from everyone in the lab and in the Myeloma, Amyloid and Dysproteinemia Group. Shared credit goes to John Mills, Ph.D., a former fellow who defined and is co-inventor of the MALDI-TOF assay; Surendra Dasari, Ph.D., who did the bioinformatics work and designed a software interface for the assay; and development technologist Mindy Kohlhagen, who spent countless hours optimizing and validating the assay. I couldn’t have done this work without them.”

Dr. Murray is working closely with Dr. Dispenzieri and her colleague S. Vincent Rajkumar, M.D., a Mayo Clinic hematologist and the Edward W. and Betty Knight Scripps Professor of Medicine in Honor of Edward C. Rosenow, III. Both serve on the International Myeloma Working Group, which develops guidelines for the diagnosis of multiple myeloma. The trio presented the new assay to the group in Stockholm, Sweden, in June 2018 for consideration in future guidelines.

The new test’s big debut was at the American Society of Hematology annual meeting in San Diego in December. Dr. Murray says the Mayo Clinic Laboratories booth had a steady stream of inquisitive clinicians and laboratorians interested in the role of the new test in detecting minimal residual disease and the possibility of eliminating gels from their labs.

“We’re letting the world know the test is available,” says Dr. Murray. “I’ve done grand rounds at other major cancer institutions, and there’s great excitement about it. Ultimately, the test needs to be offered by other institutions, not just Mayo Clinic Laboratories. A test can’t be the standard if you’re the only ones who offer it. We’re collaborating with The Binding Site to commercialize the assay. In the meantime, the test is available to Mayo Clinic patients and clients of Mayo Clinic Laboratories.”

“New methods allow you to see things with new eyes. And new eyes were definitely needed to modernize the way we detect and diagnose this disease.”

David Murray, M.D., Ph.D.

Reaping another benefit from the research

An unintended consequence of Dr. Murray’s work was the discovery that some patients have glycosylation on light chain immunoglobulins, which was shown to be a risk for AL amyloidosis, a rare bone marrow disorder in which plasma cells produce an abnormal antibody protein. AL amyloidosis may be undetectable by standard gel electrophoresis.

“A Mayo physician was trying to figure out if a symptomatic patient had AL amyloidosis,” says Dr. Murray. “Our new test indicated the patient had the indicative light chains, but the patient’s tissue biopsy didn’t show amyloid. Because the light chains indicated the patient was at high risk for the disease, I urged the physician to keep looking. A subsequent biopsy showed amyloid, and the diagnosis was established.

“AL amyloidosis is a terrible disease that can go years without diagnosis. This patient was able to be treated much sooner due to the definitive diagnosis. Without the new test for multiple myeloma, the diagnosis probably wouldn’t have been made until much later. It feels good to know I’m helping people.”

Dr. Murray and his team continue their work, looking for additional risk factors for AL amyloidosis and the light chain immunoglobulin that causes renal failure in multiple myeloma patients.

“Today multiple myeloma generally isn’t considered curable,” says Dr. Murray. “We’re getting glimpses into the mechanisms that cause the disease. And we’re strengthening the ability to know when the disease is still active. This advance could change how the disease is treated. For example, if we can tell more definitively when there’s still evidence of disease, we might keep treating it until there’s no evidence of disease.

“I’m humbled to have lent my chemistry skills honed in industry to this major milestone in the diagnosis and treatment of myeloma. My work stands on the shoulders of Dr. Kyle and everyone else who has worked in the group at Mayo that established Rochester, Minnesota, as the home of multiple myeloma research.”

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Wed, Sep 4 6:00am · Mayo experts provide insights into how genes affect medication response

The Mayo Clinic Center for Individualized Medicine team at this year’s Clinical Pharmacogenomics Symposium in Florida.

By Sharon Rosen

Pharmacogenomics – how a person’s genes affect medication response – is touching virtually every area of medical care.  Findings from the Mayo Clinic RIGHT study (Right Drug, Right Dose, Right Time–Using Genomic Data to Individualize Treatment) showed that 99% of participants had at least one genetic variant that may affect their response to medications.   

William Palmer, M.D.

But for many health care providers, understanding the rapidly advancing field of pharmacogenomics and how it applies to the patients they care for, can be a challenge. To help bridge this knowledge gap, Mayo Clinic Center for Individualized Medicine recently held a Clinical Pharmacogenomics Symposium on the Mayo Clinic campus in Florida. Providers and pharmacists from Mayo Clinic and other institutions gathered to learn firsthand how pharmacogenomics is already guiding clinical care.    

“As part of our mission, the Center for Individualized Medicine is committed to educate health care providers about how to translate genomics discoveries into patient care. This symposium was a perfect example of that effort, and we received glowing feedback from attendees and speakers for our case-based approach. This model offers physicians practical ways to incorporate pharmacogenomics into the selection of the best, individualized therapy for patients,” says William Palmer, M.D., a gastroenterologist at Mayo Clinic’s campus in Florida.

Richard Weinshilboum, M.D.

Mayo pharmacogenomics expert, Richard Weinshilboum, M.D., kicked off the symposium followed by Mayo pharmacist Michael Schuh, Pharm.D., R.Ph., who presented Pharmacogenomics 101 to introduce the underlying concepts of using genomics to guide treatment decisions.

Michael Schuh, Pharm.D., R.Ph.

“For many medications, pharmacogenomics may help predict whether a patient will benefit from the therapy or be at risk for suffering serious, sometimes life-threatening side effects,” says Dr. Schuh.

Highlights from the event showcase the pivotal role pharmacogenomics is already playing across many medical specialties.  


Breast cancer

Approximately 75% of breast cancers are estrogen receptor positive, meaning the cancer cells grow in response to the hormone estrogen. Many of these patients benefit from anti-estrogen therapies, such as tamoxifen and aromatase inhibitors, to reduce the risk of cancer recurrence after surgery.

Lauren Cornell, M.D.

However, some patients have variations in the CYP2D6 gene that may prevent them from processing these medications normally and benefitting from the treatment.

“Pharmacogenomics testing can help identify those patients who process these drugs too slowly or too rapidly. In these cases, physicians can consider whether to adjust the medication dose or select a different therapy,” explains Mayo Clinic internist Lauren Cornell, M.D.


Neurological diseases

William Freeman, M.D.

Pharmacogenomics testing can also play a key role in identifying those patients who take anti-seizure medications who may be at risk for developing serious side effects.

“Three of four commonly used anti-seizure medications carry a risk for life-threatening skin reactions,” says William Freeman, M.D., a neurologist at Mayo Clinic’s campus in Florida. “Patients with certain variants are at increased risk for developing Stevens-Johnson syndrome, a rare skin disorder that requires emergency treatment and hospitalization. In the future, I hope technology will help us identify these patients before treatment, so an alternative therapy can be used.”  

According to Dr. Freeman, pharmacogenomics can also play a key role in the treatment of patients who suffer from a ruptured aneurysm in the brain (aneurysmal subarachnoid hemorrhage), a life-threatening condition.

“Each year, 30,000 patients will suffer from a ruptured aneurysm. While the drug nimodipine can be an effective treatment, those patients with certain genetic variants may develop low blood pressure (hypotension) with this therapy. Pharmacogenomics testing can help us identify those patients at risk, so we can individualize dosing and ensure the best outcomes,” says Dr. Freeman.


Depression

Eric Matey, Pharm.D., R.Ph.

According to Mayo Clinic pharmacist Eric Matey, Pharm.D., R.Ph., 16.2 million adults in the U.S. had at least one major depressive episode and 50% of those individuals received medication therapy in 2016.

“Studies have shown that even for those patients who take commonly used medications, known as selective serotonin reuptake inhibitors, only approximately one third of them achieve remission from their symptoms,” says Dr. Matey.

He presented two cases where pharmacogenomics testing helped identify alternative therapies that enabled patients to finally find relief from depression.

“Often times, patients experience increasing side effects as they try multiple antidepressants, all the while still suffering from their depression symptoms. Pharmacogenomics testing can play a key role in helping physicians identify the right therapy the first time,” Dr. Matey says.


Reducing the risk of addiction

Sanjay Bagaria, M.D.

As the number of opioid overdose cases rise, physicians are exploring how pharmacogenomics testing can help guide the prescribing of these potentially addictive therapies.

“While we are working to reduce the quantity and duration of opioids being prescribed after surgery, pharmacogenomics can also provide critical information to improve recovery,” says Sanjay Bagaria, M.D., Mayo Clinic surgeon, and Cecilia and Dan Carmichael Family Associate Director for the Center for Individualized Medicine in Florida

“Some patients have genetic variants that cause them to process pain medications more slowly. If we have pharmacogenomics test results prior to surgery, it helps guide the selection of the most appropriate therapy for each patient and may reduce the risk for addiction.”

Read more about Mayo Clinic’s pharmacogenomics research

This article was originally published on the Mayo Clinic Center for Individualized Medicine blog.

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Wed, Aug 28 6:00am · Grant supplement opens doors for future cancer researchers in Native American communities

Mayo Clinic representatives and educators and leaders
from five tribal colleges meet in Shiprock, NM.

By Lydia Hansen, Public Affairs undergraduate intern

In the summer of 2014, Corinna Sabaque moved over 1,000
miles from her home in the Four Corners area in New Mexico to Rochester, Minn.
to complete a 10-week internship in breast cancer research at Mayo Clinic.

“Coming to Minnesota was hard,” Sabaque says. “I didn’t know
anybody. I didn’t even know whether I wanted to do cancer research.”

Despite those difficulties, Sabaque came back that fall for another internship. This time she spent seven months studying pancreatic cancer alongside Gloria Petersen, Ph.D., an epidemiologist and deputy director for Population Sciences at the Mayo Clinic Cancer Center.

A student from Diné College, a tribal college serving the
Navajo Nation, Sabaque was pursuing a four-year degree in community health. Now
she works at Mayo Clinic as a health sciences researcher, dividing her time
between pancreatic cancer research and health issues among Native populations.

Mayo Clinic’s 14-year partnership with Diné
College has opened up opportunities for students like Sabaque to gain
experience in fields like cancer where Native communities are often
underrepresented and underserved. In Sabaque’s case, those opportunities
launched a career in cancer research.

“Mayo opened a lot of doors for me to learn about cancer research, and that experience developed my interest,” Sabaque says.

Seizing opportunities

A $75,000 grant supplement from the National Cancer
Institute (NCI) is helping Mayo Clinic and Diné College offer more Native
students like Sabaque opportunities to learn about cancer research.

In April 2018, a group of Mayo representatives and educators
and leaders from five tribal colleges met in Shiprock, NM. For two days, they
shared ideas and discussed plans for a new cancer research curriculum at Diné
College. Part of Diné’s new four-year program in public health, the track will
promote diversity in cancer research.

The meeting at Shiprock facilitated exploration of cultural
perspectives and priorities in cancer research. These insights helped Mayo
experts develop materials for a Cancer 101 course.

“That meeting was critical,” Dr. Gloria Petersen says.  “It provided the time and space to develop
culturally sensitive approaches to attract and interest a new generation of
learners.”

Funding for the two-day workshop came from a supplement to Mayo
Clinic Cancer Center’s NCI Cancer Center Support Grant. These supplements were
offered to cancer centers that would promote cancer opportunities to
underserved minorities. Mayo applied for and received the supplement in 2017.

“This was an opportunity we were not going to miss,” Dr.
Gloria Petersen says of the supplement. “The Cancer Center really has something
to offer with our longstanding relationship with Native trips and our
combination of resources, experience, scientists and investigators who can
inspire young people and bring them along in a career in cancer research.”

What comes next?

With the support of researchers at Mayo, Diné
College is preparing an application for a second grant. The grant would support
implementation of a Cancer 101 curriculum based on existing models for cancer
education in Native American and Alaskan Native communities. Diné’s
curriculum will reach more than 50 students enrolled in advanced biology and public
health courses annually.

The current vision of the curriculum also includes five
10-week cancer research internships at Mayo Clinic for Diné students.
These are modeled after the opportunities Sabaque had as a student.

“Giving Native students the opportunity to come to Mayo
Clinic would open doors for hands-on learning experiences in laboratory and
clinical projects that they wouldn’t normally have,” Sabaque says. She credits
time spent in cancer research labs at Mayo for piquing her interest in the
field.

“This is really one step in a larger effort to help more Native students get involved in doing this kind of research,” says Christi Patten, Ph.D., a professor of psychology in the Behavioral Health Research Program. Dr. Patten was principal investigator on the first grant Mayo and Diné College partnered on 14 years ago.

“If we don’t have Native voices at the table, we’re missing
a whole dimension of cancer research,” Dr. Patten says. 

Only about four
percent
of Native American and Alaskan Native populations have the advanced
degrees necessary to be principal investigators in clinical research. Raising
that number could reduce health disparities and bring valuable insights to
cancer research.

“These students would be doing research that comes from their community and is sensitive to their specific needs in the health care system,” says Wesley Petersen, Ph.D., director of Native American Research Outreach at Mayo Clinic. “By addressing research questions that are important to those patients, we’re making steps toward improving their health.”

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Mon, Aug 26 6:00am · Hospice research aims to understand process of dying, help loved ones with end-of-life care

While death is inevitable, for patients at Mayo Clinic Health System in Mankato’s Hospice Program, the process of dying is becoming more bearable as a result of several research studies aimed at better understanding.


Death, ultimately, is inevitable. It happens to everyone. But for patients at Mayo Clinic Health System in Mankato’s Hospice Program, the process of dying is becoming more bearable for themselves and their families as a result of several research studies aimed at understanding more.

“We know Mayo Clinic is big on curing and healing patients by inventing new treatments and procedures, but the end of life is so important, and we cannot miss that,” says chaplain and principal investigator Jacek Soroka, Ph.D. “Because we will all die. We will all go through it, and we need to have the same quality of care at the end of life as we do with other aspects of care.”

The research studies, which focus on caregiver confidence, spiritual care, and end-of-life care involving the deactivation of a pacemaker, were conducted by Chaplain Soroka and Greg Kutcher, M.D., medical director of the hospice program in Mankato, as well as other members of the hospice team.

While each of the studies centers on a different aspect of hospice, they have a common goal.

“Even though it’s the end of life, it’s incredibly important for patients to have closure and resolution, and feel good about their life’s story and what they’re leaving with other people,” Dr. Kutcher says. “We need to better understand how to do that.”

Dr. Kutcher says studies show that if a loved one’s dying process is handled poorly, it can have a lasting effect on those left behind.

“If it’s handled well, it can be a positive thing in terms of creating a particular place in their heart for that person as they move forward,” he says. “And we should not leave that to chance.”

Absence of information prompts research

Even though hospice care has been available for many years, there is an opportunity to study the patient and caregiver experience more thoroughly, Dr. Soroka says.

The team’s research efforts grew out of a need for information to serve as guideposts on how to best direct end-of-life care.

Recently, the wife of a patient who’d gone through hospice summed up the fraught experience of many individuals who enter hospice programs.

“We knew as we were going through treatment that it wasn’t curable and eventually he would die, but this decline he was in, it was a black box,” she says. “We had no idea what was in this black box.”

That’s true for many people in end-of-life situations, Dr. Kutcher says. “They are experiencing things without any real understanding ahead of time,” he says. “This is a common experience. It’s not part of what we do in traditional medicine.”

We knew as we were going through treatment that it wasn’t curable and eventually he would die, but this decline he was in, it was a black box. We had no idea what was in this black box.

Wife of a hospice patient

Drs. Kutcher and Soroka hope to shed light on understudied aspects of care by focusing on areas with a pronounced dearth of data. The pacemaker study, for example, was born out of a lack of literature on pacemaker deactivation and resultant death.

“We went into the research to check what’s available and how we can be aided by the knowledge,” Dr. Soroka says. But published research had virtually nothing on what families could expect after their loved one’s pacemaker was deactivated.

“So we decided we needed to do the study and share that information with others,” he says.

In the case of the pacemaker study, it wasn’t only physicians who wanted to learn more — the affected family also championed the research.

“They were very intelligent and had done their own literature search and felt like the world needed to learn from this,” Dr. Kutcher says. “They offered themselves up to study the experience.”

As a result of studying the family’s experience, Drs. Soroka and Kutcher identified the needs of family members during this particular type of end-of-life experience, which had never been examined before. The research found that a lack of support from a patient’s medical team about the decision to deactivate a pacemaker can increase emotional and ethical stressors faced by family members. The study was recently published in the American Journal of Hospice and Palliative Medicine.

Although the pacemaker study was small and involved only one family, the other studies conducted at the Mankato Hospice Program have involved larger cohorts of patients.

A study surrounding the impact of spiritual support, which was conducted in 2017 and 2018, involved 200 patients. And 16 participants were involved in 2018 study focused on caregiver confidence.

Discoveries generate change

Just as Mayo Clinic is on the forefront of treatment discoveries, it should be a leader when it comes to the last phase of a patient’s treatment, says Dr. Soroka. Through the research, the team aims to better understand how to modify hospice practices with the goal of elevating care.

“We are dealing with people in the most vulnerable moment of their lives,” says Dr. Soroka. “It is so important to show that hospice is not just about providing care, but providing evidence-based excellent care in ways that can make a difference in people’s lives.”

One element of hospice care that’s proven to improve the process is spiritual involvement. The spirituality study examined why this offering was oftentimes bypassed by patients and families.

People who are getting spiritual care do better. It’s not a luxury. It’s really important.

Greg Kutcher, M.D.

“People who are getting spiritual care do better. It’s not a luxury. It’s really important,” Dr. Kutcher says. “And we found a significant number of patients are not availing themselves to spiritual care because they viewed it as religious care. They don’t understand the difference.”

For the spirituality study, participants were divided into two groups. The control group received traditional information about the availability of chaplain support and an offer of referral for these services. The other group received that same information, but also was informed about what chaplain services were and the evidence-based benefits of spiritual support during hospice.

Researchers found that between the groups, 64% of patients who received more education about the meaning of chaplain support asked for chaplain services. In the control group, only 52% of patients requested chaplain support.

As a result of the study — which was recently published in the Journal of Palliative Medicine — educational materials that explain spiritual care in hospice and its benefits were distributed to every hospice patient in Mankato.

Increased knowledge improves care

The next thing the team intends to study surrounds the caregiver experience with end-of-life delirium, which occurs in a high percentage of hospice patients, particularly cancer patients.

“We recently had several patients with delirium, and caregivers really struggle observing the signs of delirium,” Dr. Soroka says. “It’s so difficult and distressing for families and caregivers. The idea for this study comes from basically what we face in our daily practice.”

During the study, caregivers whose loved one experienced delirium will be invited to participate and be interviewed about their experiences.

“Talking to families and caregivers afterward brings a knowledge base of how people experience it, and then you can keep them in mind as you educate more patients and engage them in their care discussion,” Dr. Kutcher says.

By continuing to focus attention on overlooked aspects of the dying process, the researchers hope to increase knowledge and affect change on many levels.

“From a personal standpoint, what was profound to me was thinking that very few health care providers have the opportunity to spend 10 hours interviewing family to find out their perspective after the dust has settled,” Dr. Kutcher says. “To take time and learn about their experience has had a deep impact on how I think about these issues and frame them for families going through the process.”

Dr. Soroka says he hopes the research illuminates the critical role hospice plays in the lives of patients and the need for better understanding. The studies’ findings have not only been published in peer-reviewed journals, but team members have shared their research with global palliative care and hospice communities through presentations at the World Palliative Care Congress in 2016 and 2018, and the Minnesota Palliative Care Conference in April 2019.

“We want to lead the way so people know that hospice isn’t just some small department caring for dying people,” he says. “End-of-life care needs to be excellent.”

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Related resources:

Thu, Aug 22 6:00am · At Mayo Clinic, one Statistics and Data Management Center oversees hundreds of cancer clinical trials

By Lydia Hansen, undergraduate public affairs intern

The Mayo Clinic Cancer Center’s Statistics and Data
Management Center is one of the largest and most highly rated statistics and
data management centers working with cancer research in the world. The group has
an overall portfolio of 361 cancer-related clinical trials and information on
more than 185,000 patients in its database.

Housed within the Department of Health Sciences Research at Mayo Clinic, the Statistics and Data Management Center supports a range of cancer research. This includes clinical trials and associated projects funded through Mayo Clinic Cancer Center and its National Cancer Institute (NCI) Cancer Center Support Grant and Specialized Programs of Research Excellence. The center also supports research conducted through the Alliance for Clinical Trials in Oncology, Academic and Community Cancer Research United, the Cancer Prevention Network and several other large NCI and industry-sponsored cancer research programs. All data collected from the clinical trials funded by these networks passes through the center.

Sumithra Mandrekar, Ph.D.

“When a trial opens, we are responsible for every piece of data coming through that trial,” says Sumithra Mandrekar, Ph.D., group statistician for the Alliance for Clinical Trials in Oncology, and section head for Mayo Clinic Cancer Center Statistics. “It’s a very big machine,” she says.

The Statistics and Data Management Center’s primary focus is
to help Mayo Clinic Cancer Center and collaborating researchers design, conduct
and analyze data collected on clinical trials. Many of these trials involve
testing new drugs.

Statisticians and data managers from the Statistics and Data
Management Center get involved with each trial right from the beginning. Working
with study investigators, members of the center define the working hypotheses —
or research questions — of the trial. That information helps determine how the
trial should be conducted, what data should be collected, the number of
participants, and the definition of success for the drug or other treatment being
tested. The center then designs a database to house all of the data from the
trial.

After a trial has been approved and funded, project team
members from the Statistics and Data Management Center continue to monitor the
trial for patient safety and viability and perform regular cleaning and
querying of the data being collected. When the trial closes, the statistical
team helps investigators analyze the data collected and write manuscripts,
abstracts or presentations on any findings.

“We’re there the whole time, from the birth of a trial to
its completion,” Dr. Mandrekar says.

The Statistics and Data Management Center is a massive
repository of data collected from both Mayo Clinic-led trials as well as patient
data collected from other trials led by international organizations and
pharmaceutical companies. Investigators can use these databases to pose
additional questions about trials and the effectiveness of different treatments.

“We have the ability to pool data and look across multiple trials to ask questions that are not always possible to be answered using data from a single trial,” says Dr. Mandrekar.

Unlike other data centers, which often divide infrastructure and teams by funding source or research focus, Mayo Clinic’s Statistics and Data Management Center has a consolidated infrastructure. Teams organized by disease specialties oversee all cancer-related trials research. This practice of increased information-sharing is part of how the center keeps hundreds of clinical trials running smoothly and safely.

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