UPMC Physician Resources

Blacks with Atrial Fibrillation at Greater Risk for Adverse Outcomes

Blacks with atrial fibrillation (AFib) have nearly double the risk than their white counterparts of stroke, heart failure, coronary heart disease (CHD) and mortality from all causes, according to a study published today in JAMA Cardiology.

The study, funded by a grant from the Doris Duke Foundation and led by Jared Magnani, MD, associate professor of medicine, Division of Cardiology, University of Pittsburgh School of Medicine, and cardiologist at the UPMC Heart and Vascular Institute, analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study to examine racial differences in adverse outcomes associated with AFib.

AFib is the most common heart rhythm problem in the US It affects approximately 1 percent of the adult population and more than 5 percent of those 65 years old and older. It also is known to be strongly associated with increased risks of stroke, heart failure and mortality.

“We knew blacks were likely to have an increased risk of stroke, but the findings for heart failure, CHD and mortality are novel and important,” Dr. Magnani said. “This should put the focus on improving prevention efforts for adverse outcomes in blacks with atrial fibrillation, and drive further studies into the reasons behind why this is happening.”

The ARIC Study, sponsored by the National Heart, Lung, and Blood Institute, recruited 15,792 men and women, 45 to 64 years old, from four communities in the United States—Forsyth County, North Carolina; Jackson, Mississippi; the northwest suburbs of Minneapolis, Minnesota; and Washington County, Maryland. The community-based cohort was designed to investigate causes of atherosclerosis and cardiovascular disease, and included baseline examinations in 1986 and more than 20 years follow up.

“ARIC provided an opportunity to examine racial differences in outcomes related to atrial fibrillation. In general, most large studies of individuals with atrial fibrillation are predominantly of white participants,” Dr. Magnani said. “We know that atrial fibrillation is associated with adverse outcomes, but these data provided important insights into differences by race.”

After exclusions, 15,080 participants (8,290 women and 3,831 blacks) were included in the new analysis. Noteworthy racial differences at baseline examination included a body mass index of 27 percent for whites and 29.6 percent for blacks. Black participants also had a higher prevalence of hypertension and diabetes.

During analysis of the 20-year follow-up, 2,348 cases of AFib were identified—1,914 in whites with an incidence rate of 8.1 per 1,000 person-years, and 434 in blacks, with an incidence rate of 5.8 per 1,000 person-years. Researchers found that adverse outcomes in black participants were almost double that for whites.

The incidence rate of strokes in black participants was 21.4 compared to 10.2 in their white counterparts. For heart failure and CHD, the rate difference was almost two-fold higher in blacks than whites. Blacks also had a rate difference of 106 for mortality compared to 55.9 in whites.

Researchers also believe the results are enough to warrant an addition to the current guidelines for the management of patients with AFib developed by the American College of Cardiology, American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society to include the significant difference in adverse outcomes between blacks and whites with AFib.

Limitations of the study noted by researchers included that ARIC participants were from only four geographic regions and that the study is biracial. The researchers are careful to note that generalizability to other geographic regions or to other races and ethnicities may be limited.

“There needs to be further investigation,” said Dr. Magnani, who completed his research while at Boston University School of Medicine. “It’s going to be important to dissect the mechanisms behind why blacks with atrial fibrillation are highly more likely to have adverse outcomes than whites.”

The mission of the Doris Duke Charitable Foundation is to improve the quality of people’s lives through grants supporting the performing arts, environmental conservation, medical research and child well-being, and through preservation of the cultural and environmental legacy of Doris Duke’s properties.

Children’s Hospital of Pittsburgh of UPMC Ranked in National Top 10 Seven Years in a Row

PrintChildren’s Hospital of Pittsburgh of UPMC, for the seventh consecutive year, has been named to the US News & World Report Honor Roll of America’s Best Children’s Hospitals.

The hospital is ranked seventh on the 2016-17 Honor Roll of America’s Best Children’s Hospitals, which was released today. The Best Children’s Hospitals rankings highlight the top 50 US pediatric hospitals in each of 10 specialties: cancer; cardiology and heart surgery; diabetes and endocrinology; gastroenterology and GI surgery; neonatology; nephrology; neurology and neurosurgery; orthopedics; pulmonology; and urology.

“We’re very proud to once again be recognized as one of the top children’s hospitals in the country,” said Christopher Gessner, president, Children’s Hospital. “Patients and families with complex medical conditions and needs increasingly are choosing our hospital because our physicians, nurses, and staff, who are among the leaders in their fields, are committed to providing the highest quality pediatric healthcare in the world every single day.”

The 2016-17 Best Children’s Hospitals rankings will be released online today and also will be published in the U.S. News “Best Hospitals 2017” guidebook, available in September.

US News introduced the Best Children’s Hospitals rankings in 2007 to help families of children with rare or life-threatening illnesses find the best medical care available. The rankings open the door to an array of detailed information about each hospital’s performance.

Children’s tied with one other hospital for seventh place. The 11 hospitals named to US News’ Honor Roll of Best Children’s Hospitals for 2016-17 are:
1. Boston Children’s Hospital
2. Children’s Hospital of Philadelphia
3. Cincinnati Children’s Hospital Medical Center
4. Texas Children’s Hospital, Houston
5. Seattle Children’s Hospital
6. Ann and Robert H. Lurie Children’s Hospital of Chicago
7. Children’s Hospital of Pittsburgh of UPMC
7. Children’s Hospital Los Angeles
9. Children’s Hospital Colorado, Aurora
10. Lucile Packard Children’s Hospital at Stanford, Palo Alto, California
10. Nationwide Children’s Hospital, Columbus, Ohio

University of Pittsburgh’s Rocky Tuan, PhD, Receives Research Award to Conduct Studies on International Space Station

Rocky S. Tuan, PhD, has received a research grant from the Center for the Advancement of Science in Space (CASIS) to continue his work on a 3D microphysiological system (MPS) to be conducted on board the International Space Station (ISS) to evaluate the accelerated aging and degeneration process of bones that occurs in space.

“Studying such rapid progression of the disease offers great advantages to developing treatments for osteoporosis faster and more effectively, in ways that are not possible on Earth,” said Dr. Tuan. “Our research will benefit not only the health of astronauts for long stays in space on the ISS or a future journey to Mars, but also will help people on Earth, providing capabilities for the screening of drug therapies, enhancing personalized medicine, and developing  bioreactor technologies for tissue engineering.”

The award is part of the 3D Microphysical Systems for Organs-On-Chips Grand Challenge by CASIS, which was chosen by NASA in 2011 to be the sole manager of the ISS U.S. National Laboratory. Monday’s announcement was made at the White House Organ Summit.

Dr. Tuan is director of the Cellular and Molecular Engineering Lab and Distinguished Professor in the Department of Orthopaedic Surgery at the University of Pittsburgh School of Medicine. He is internationally known for his research in stem cell biology, musculoskeletal tissue engineering, regenerative medicine, and for his innovative leadership role in biomedical education. He also is associate director of Pitt’s McGowan Institute for Regenerative Medicine and director of the Center for Military Medicine Research.

“We are particularly appreciative of the research award from CASIS as recognition of our work on developing veritable models for skeletal tissues that may be used to understand the mechanisms of disease and to expedite drug screening for degenerative conditions such as osteoporosis and osteoarthritis,” Dr. Tuan said.

The award was accepted by Peter Alexander, PhD, and Riccardo Gottardi, PhD, on behalf of Dr. Tuan and the University of Pittsburgh research team.

Under Dr. Tuan, Pitt’s Center for Cellular and Molecular Engineering focuses on the science of treating injuries and diseases of the musculoskeletal system, utilizing nanotechnology and mechanobiological principles in combination with bioreactor and biomaterials technologies, including 3-dimensional printing, for functional skeletal tissue engineering and regeneration.

The MPS project has been partially funded by the Ri.MED Foundation, a collaboration between Italy’s government, the University of Pittsburgh, and UPMC. The foundation, based in Palermo, Italy, promotes, supports and leads biomedical and biotechnological research projects, with emphasis on the translation of innovative results into clinical practice.

Leading International Expert in Metabolic Liver Disease to Direct Hepatology Program at Children’s Hospital of Pittsburgh of UPMC

PrintPatrick McKiernan, MD, a leading expert in metabolic liver disease, has been appointed director of the Pediatric Hepatology Program at Children’s Hospital of Pittsburgh of UPMC, part of the Division of Pediatric Gastroenterology, Hepatology, and Nutrition. Dr. McKiernan will also join the staff of the hospital’s Center for Rare Disease Therapy.

Dr. McKiernan specializes in treating children with inherited metabolic disease and has an interest in developing less invasive therapies to help patients avoid or delay the need for liver transplantation. His research focus covers the clinical aspects of inherited metabolic liver disease, portal hypertension, novel endoscopic techniques, non-invasive markers of hepatic fibrosis, and immunosuppression following liver transplantation. He is actively involved in research on stem cell therapy for metabolic liver diseases and recently was the UK principle investigator on a stem cell study involving children with urea cycle disorders and Crigler-Najjar syndrome.

“Dr. McKiernan is among the world’s leading physician-scientists with expertise in pediatric hepatology, specifically inherited metabolic disease,” said Mark Lowe, MD, PhD, chief of the Division of Pediatric Gastroenterology, Hepatology and Nutrition at Children’s Hospital. “His appointment enhances Children’s ability to provide care for children from around the world with complex metabolic conditions in need of the highest level of care.”

Dr. McKiernan also has a special interest is tyrosinemia, an inherited disorder caused by an enzyme deficiency that can lead to life-threatening liver and kidney failure. In a study published in 2014, Dr. McKiernan and his colleagues found that children whose tyrosinemia was identified at birth through newborn screening and started on the drug nitisinone developed normally and showed no signs of liver or kidney disease.

Dr. McKiernan comes to Children’s from Birmingham Children’s Hospital in the United Kingdom, where he was a hepatologist in the liver unit since 1994. He trained in medicine and pediatrics at Queen’s University in Belfast.

Dr. McKiernan is a member of the British Medical Association, British Society of Pediatric Gastroenterology, Hepatology and Nutrition, British Association for the Study of the Liver, and American Association for the Study of Liver Diseases. He also is an associate professor at the University of Pittsburgh School of Medicine.
As an international expert in metabolic disease, Dr. McKiernan is part of the Center for Rare Disease Therapy at Children’s, an integrated team of experts who have developed innovative therapies to treat a multitude of rare diseases.

Children’s has performed more than 330 liver transplants for patients with metabolic disease, which is more than any other center, including adult facilities. In addition, Children’s is a leading center for liver transplantation as a therapeutic option for children with maple syrup urine disease (MSUD). Children’s developed the first liver transplant protocol for MSUD in 2004 and since then has successfully performed more liver transplants in patients with MSUD than any other center in the world with 100 percent patient and graft survival.

For more information on Dr. McKiernan and the Pediatric Hepatology Program at Children’s Hospital of Pittsburgh of UPMC, please visit www.chp.edu/hepatology.

Pitt-Developed Test Holds Potential to Diagnose Myriad Conditions with Drop of Blood

Researchers at the University of Pittsburgh have developed a unique method for detecting antibodies in the blood of patients in a proof-of-principle study that opens the door to development of simple diagnostic tests for diseases for which no microbial cause is known, including auto-immune diseases, cancers and other conditions.

The results, reported in the Journal of Immunological Methods and funded by the Bill & Melinda Gates Foundation, are the first evidence that it is possible to develop blood tests for any infectious disease by screening random libraries of non-biological molecular shapes.

“This ‘needle-in-a-molecular haystack’ approach is a new way to develop diagnostic assays,” said senior author Donald S. Burke, MD, Pitt Graduate School of Public Health dean and director of Pitt’s Center for Vaccine Research. “The method does not rely on starting with known viral components. This is important because there are conditions for which there isn’t a known antigen, such as newly emerged epidemics, autoimmune diseases or even responses to traumatic injury.”

When a person’s immune system is faced with an antigen or foreign invader, such as an infectious disease, or even an injury with tissue damage, it responds by producing antibodies. Like puzzle pieces, specific parts of the surface of these antibodies fit to the shape of the molecules on the invader or the damaged tissue.

The Pitt researchers used a technique pioneered by co-author Thomas Kodadek, PhD, of the Scripps Research Institute, that synthesizes random molecular shapes called “peptoids” hooked onto microscopic plastic beads. The technique can produce millions of molecular shapes. The peptoids are not organic, but if they match to the corresponding shape on an antibody, that antibody will connect to them, allowing the scientist to pull out that bead and examine that peptoid and its corresponding antibody.

Using this technique, Dr. Burke’s team chemically generated a huge library of random molecular shapes. Then, using blood from HIV-infected patients and from non-infected people, the researchers screened a million of these random molecular shapes to find the ones that bound only to antibodies present in the blood of HIV-infected patients, but not the healthy controls. No HIV proteins or structures were used to construct or select the peptoids, but the approach, nonetheless, successfully led to selection of the best molecular shapes to use in screening for HIV antibodies.

The team then resynthesized that HIV-antibody-targeting peptoid in mass and tested it by screening hundreds of samples from the Multicenter AIDS Cohort Study (MACS), a confidential research study of the natural history of treated and untreated HIV/AIDS in men who have sex with men (supported by the National Institutes of Health). Study co-author Charles Rinaldo, PhD, chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology and director of the Pittsburgh arm of the MACS, selected the samples, but blinded the testers to which samples were HIV-positive or -negative.  The test distinguished between the samples of HIV-positive blood and HIV-negative blood with a high degree of accuracy.

“This technology means that we may be able to take a single drop of blood from a patient and detect antibodies to all manner of infections, cancers or other conditions they may be carrying or been exposed to. We hope that this is the first step toward development of an ‘Epi-chip’ that can be used to reconstruct a person’s entire exposure history,” said Dr. Burke, who also holds the UPMC-Jonas Salk Chair of Global Health at Pitt.

Additional co-authors on this study are Tricia L. Gearhart, PhD, Ronald C. Montelaro, PhD, Mark E. Schurdak, PhD, Yongseok Park, PhD, Kazi Islam, Raymond Yurko and Ernesto T.A. Marques Jr., MD, PhD, all of Pitt; and Chris D. Pilcher, MD, of the University of California, San Francisco.

This work was funded by Bill & Melinda Gates Foundation grant OPP1068374. In addition to the MACS, the Consortium for the Evaluation and Performance of HIV Incidence Assays also provided blood samples.

Pitt Researchers Find Key to Parkinson’s Disease Neurodegeneration

Researchers at the University of Pittsburgh School of Medicine have uncovered a major reason why the Parkinson’s-related protein alpha-synuclein, a major constituent of the Lewy bodies that are the pathological hallmark of Parkinson’s disease (PD), is toxic to neurons in the brain. The finding has the potential to lead to new therapies that could slow or stop progression of the devastating illness. The new research appears online today in Science Translational Medicine.

PD is a degenerative neurological disease characterized by tremor, slowness, and gait and balance difficulties that affects about 1 million people in the United States. The symptoms are caused by the degeneration and loss of neurons in the brain, particularly those crucial for the initiation and coordination of movement.

“It’s really exciting that we have found a mechanism we can target to create new treatments for this devastating disease,” said lead investigator J. Timothy Greenamyre, MD, PhD, Love Family  Professor of Neurology in Pitt’s School of Medicine and director of the Pittsburgh Institute for Neurodegenerative Diseases (PIND).

PIND’s goal is an integrated, interdisciplinary approach to the study of neurodegenerative diseases and their mechanisms, with the aim of transforming cutting-edge science into novel therapies and diagnostics that directly benefit individuals affected by neurodegenerative diseases.

“With four different PIND investigators working together, the new study highlights the power of this collaborative approach,” Dr. Greenamyre added.

Current treatments for PD can reduce symptoms, but they do not slow the inevitable worsening of the disease. To slow or halt illness progression, scientists must first determine why and how the neurons are dying.

Degenerating neurons contain large clumps of a protein called alpha-synuclein. People whose cells make too much alpha-synuclein or make a mutated form of the protein are at high risk of developing PD because of the protein’s toxicity, researchers found. Scientists also demonstrated that the accumulation of alpha-synuclein in PD is toxic because it disrupts the normal functioning of mitochondria—the tiny powerhouses responsible for generating a cell’s energy.

In the new study, Dr. Greenamyre and his team—led by coauthors Roberto Di Maio, PhD, and Paul Barrett, PhD, both of PIND—used a well-established rodent model of PD to show exactly how alpha-synuclein disrupts mitochondrial function. They found that by attaching to a mitochondrial protein called TOM20, alpha-synuclein prevented the mitochondria from functioning optimally, which resulted in the production of less energy and more damaging cellular waste.

Ultimately, this interaction between alpha-synuclein and TOM20 leads to neurodegeneration, Dr. Greenamyre explained.

The researchers then confirmed their animal findings in brain tissue from people with PD.

“The effects of alpha-synuclein on mitochondria are like making a perfectly good coal-fueled power plant extremely inefficient, so it not only fails to make enough electricity, but also creates too much toxic pollution,” said Dr. Greenamyre.

Using cell cultures, the research team also found two ways to prevent the toxicity caused by alpha-synuclein: gene therapy that forced the neurons to make more TOM20 protein protected them from the alpha-synuclein; and a protein that was able to prevent alpha-synuclein from sticking to TOM20 prevented alpha-synuclein’s harmful effects on mitochondria.

While more research is needed to determine whether these approaches could help PD patients, Dr. Greenamyre is optimistic that one or both may ultimately make it into human clinical trials in an effort to slow or halt the otherwise inevitable progression of PD.

Coauthors of the study are Charleen Chu, MD, PhD, Edward Burton, MD, PhD, Teresa Hastings, PhD, Eric Hoffman, PhD, Caitlyn Barrett, PhD, Alevtina Zharikov, PhD, Anupom Borah, PhD, Xiaoping Hu, BS, and Jennifer McCoy, BS, all of PIND.

This work was supported by research grants from the DSF Charitable Foundation, the Ri.MED Foundation, the Consolidated Anti-Aging Foundation, the National Institutes of Health (grants NS095387, NS059806, ES022644, ES020718, ES020327, NS065789, AG026389 and P50AG005133), the United States Department of Veterans’ Affairs (grant 1I01BX000548), the Blechman Foundation, the American Parkinson Disease Association and the Department of Biotechnology, Government of India.

Pitt Awards Dickson Prize to Jennifer Doudna, PhD

A researcher known for breakthrough discoveries in genetics that have allowed scientists to efficiently and precisely modify DNA sequences and correct genetic defects in any cell will receive the University of Pittsburgh’s 2016 Dickson Prize in Medicine.

Jennifer A. Doudna, PhD, will accept the University of Pittsburgh School of Medicine’s most prestigious honor during Science 2016—Game Changers, a showcase of the region’s latest research in science, engineering, medicine and computation that will be held from Oct. 19 to 21 on Pitt’s campus. Dr. Doudna holds the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences at the University of California, Berkeley, where she is a professor of molecular and cell biology and a Howard Hughes Medical Institute investigator.

“Dr. Doudna’s discoveries have helped start the gene-editing revolution, and by elucidating the DNA-editing mechanisms of the CRISPR-Cas9 system, have given scientists the tools to add or delete genes in any type of cell,” said Arthur S. Levine, MD, Pitt’s senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine. “In the near future, this technology might be used to eliminate mutated genes that cause conditions like sickle cell and a host of other diseases. It also could enable the genetic engineering of crops that resist disease and insect pests that fail to reproduce.”

Dr. Doudna and her colleagues investigated clustered regularly interspaced short palindromic repeats (CRISPR)—repeating sequences seen in many bacterial genomes. CRISPRs represent an adaptive immune system capable of inserting new snippets of viral DNA into a bacterial genome, which is then passed on to ensuing generations to protect them from the same virus.

In a June 2012 issue of the journal Science, Dr. Doudna and her colleagues demonstrated that the CRISPR-associated protein Cas9 could be used with prepared sequences of guide RNA to cut DNA at virtually any spot on the genome. Using the system, researchers have successfully corrected genetic defects in animals and altered DNA sequences in embryonic cells. The Doudna Lab, which explores molecular mechanisms of RNA-mediated gene regulation, currently is working toward delivering Cas9 protein-RNA complexes into specific tissues and on uncovering the mechanisms of target search and binding in live cells.

During Science 2016—Game Changers, Dr. Doudna will deliver the Dickson Prize in Medicine lecture. Her talk is titled “CRISPR Systems and the Future of Genome Engineering.”

Dr. Doudna’s honors include the 2016 Heineken Prize, 2016 Canada Gairdner Award, the 2016 L’Oréal-UNESCO for Women in Science Award, the Breakthrough Prize in Life Sciences, the Gruber Genetics Prize, the Lurie Prize in Biomedical Sciences, and many others. In 2015, she was named one of Time magazine’s 100 most influential people. She is a fellow of the American Society for Microbiology and a member of the National Academy of Inventors, the National Academy of Medicine, the American Academy of Arts and Sciences, and the National Academy of Sciences.

In addition to Dr. Doudna, three other renowned researchers will deliver plenary lectures at Science 2016. The Mellon Lecture will be given by Howard Y. Chang, MD, PhD, a pioneering dermatologist and geneticist from Stanford University; the Hofmann Lecture will be given by Lasker Prize-winning neurologist and leading Parkinson’s disease researcher Mahlon DeLong, MD, of Emory University; and the Provost Lecture will be given by Jo Handelsman, PhD, associate director for science at the White House Office of Science and Technology Policy, who is widely recognized for her work on microbiology and metagenomics, science education, and women and minorities in science.

Adults at Risk for Diabetes Double Activity Levels through Healthy Lifestyle Program

Adults at risk for type 2 diabetes or heart disease or both can substantially increase their physical activity levels through participating in a lifestyle intervention program developed at the University of Pittsburgh Graduate School of Public Health for use in community-settings, such as senior centers or worksites.

Previous studies have demonstrated that such programs decrease weight and reduce diabetes risk, but this National Institutes of Health (NIH)-funded evaluation is one of the first to document that these programs also result in significant increases in the participants’ physical activity levels. The results are reported in this month’s issue of the Translational Journal of the American College of Sports Medicine, coinciding with the organization’s 62nd annual meeting in Boston, the largest sports medicine and exercise meeting in the world.

The analysis also confirmed that season matters, with participants getting more physical activity in the summer, versus winter, months. “This may seem like an obvious finding, but this evidence that season influences the physical activity levels of participants in community-based lifestyle interventions will allow us to adjust these programs accordingly and offer extra encouragement and strategies to continue striving to meet physical activity goals during the winter,” said lead author Yvonne L. Eaglehouse, PhD, a postdoctoral researcher at Pitt Public Health.

Dr. Eaglehouse and her colleagues investigated the impact of the Group Lifestyle Balance program, modified from the lifestyle intervention program used in the highly successful U.S. Diabetes Prevention Program (DPP). The DPP was a national study which demonstrated that people at risk for diabetes who lost a modest amount of weight and sharply increased their physical activity levels reduced their chances of developing diabetes or metabolic syndrome, and outperformed people who took a diabetes drug instead.

Group Lifestyle Balance is a 22-session program administered over a one-year period aimed at helping people make lifestyle changes to lower their risk for diabetes and heart disease. The goals of the program are to help participants reduce their weight by 7 percent and increase their moderate intensity physical activity (such as brisk walking) to a minimum of 150 minutes per week.

As part of the Pitt community intervention effort, a total of 223 participants were enrolled to test the effectiveness of the Group Lifestyle Balance program at a worksite and three diverse community centers in the Pittsburgh area. The participants averaged 58 years of age and had pre-diabetes or metabolic syndrome or both.

Participants were surveyed to determine the amount of leisure physical activity they achieved each week. As a result of participating in the program, participants added an average of 45 to 52 minutes of moderate intensity activity similar to a brisk walk to their weekly routine, which was maintained after the program ended at one year.

“This is one of the few programs of its kind to report on physical activity-related outcomes in a large group and the only known diabetes prevention healthy lifestyle program to examine the effect of season and weather on changes in physical activity levels,” said senior author Andrea Kriska, PhD, professor in Pitt Public Health’s Department of Epidemiology and principal investigator of the NIH study. “Since increased physical activity is one of the primary targets of these programs, it is critical to know if it is working and what can be done to improve the chances that participants reach their goals.”

Additional authors on this research are Bonny J. Rockette-Wagner, PhD, Mary Kaye Kramer, DrPH, RN, Vincent C. Arena, PhD, Rachel G. Miller, MS, and Karl K. Vanderwood, PhD, MPH, all of Pitt.

This study was funded by NIH National Institute of Diabetes and Digestive and Kidney Diseases grant R18 DK081323-04.

Early Detection, Smaller Cancer Among Benefits of Skin Cancer Screening at Primary Care Visits

Skin cancer screenings performed by primary care physicians (PCPs) during routine office visits improve the detection of potentially deadly melanomas and find them in earlier stages, according to new research from the University of Pittsburgh School of Medicine.

The results will be presented today at the 52nd annual American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

“Our findings suggest that PCP screening is an effective way to improve early detection of melanoma, which could potentially save lives,” said lead author Laura Ferris, MD, PhD, associate professor, Department of Dermatology, Pitt School of Medicine and member of the Melanoma Program, University of Pittsburgh Cancer Institute.

Rates of melanoma, the most dangerous form of skin cancer, are on the rise, and skin cancer screenings are one of the most important steps for early detection and treatment, said Dr. Ferris. Typically, patients receive skin checks by setting up an appointment with a dermatologist.

The goal of the new UPMC screening initiative, which was modeled after a promising German program, was to improve the detection of melanomas by making it easier for patients to get screened during routine office visits with their PCPs, explained Dr. Ferris.

PCPs completed training on how to recognize melanomas and were asked to offer annual screening during office visits to all patients aged 35 and older. In 2014, during the first year of the program, 15 percent of the 333,788 eligible UPMC patients were screened in this fashion.

On average, the melanomas detected in the group who received a screening at a primary care visit were nearly twice as thin as those detected in the group that was not screened by a PCP. Thinner melanomas have a better prognosis than thicker ones that are more advanced, so the new findings suggest PCP screening is able to find melanomas at an earlier, more treatable stage, said Dr. Ferris.

In addition, only 5 percent of people in the screening group had especially worrisome melanomas that were thicker than 1 millimeter—which are more likely to metastasize and require a biopsy of a nearby lymph node—while 20 percent of the unscreened group did.

“The PCP screenings prevented a lot of people from needing more aggressive therapy. Additionally, we did not see a high rate of false positive biopsies, in which no skin cancer was present, nor did we see a high rate of unnecessary dermatology referrals or skin surgeries, all of which suggest that the program did not simply drive up health care costs needlessly,” Dr. Ferris said.

Another important finding was that nearly half of the screened patients were men, who are more likely to get and die from melanoma than women but have been underrepresented in other skin cancer screenings published to date. “It’s exciting that our approach improves detection in this especially vulnerable population,” said Dr. Ferris.

Funding for this study was provided by a National Cancer Institute Specialized Program of Research Excellence (SPORE) grant in skin cancer (5P50CA121973-08).

Additional members of the research team included Melissa Saul, MS, Francis Solano, MD, Erica Neuren, BA, Jian-Min Yuan, MD, PhD, and John Kirkwood, MD, all of UPMC; Martin Weinstock, MD, PhD, of Brown University; and Allan Geller, MPH, RN, of Harvard University.

Immunotherapy Improves Survival, Quality of Life in Rapidly Progressing Head and Neck Cancer

Immunotherapy doubles overall survival and improves quality of life, with fewer side effects, in a treatment-resistant and rapidly progressing form of head and neck carcinoma, reports a large, randomized international trial co-led by investigators at the University of Pittsburgh Cancer Institute (UPCI). The new trial was considered so successful that it was stopped early to allow patients in the comparison group to receive the new drug.

Findings from the international CheckMate-141 phase III clinical trial were presented today at the 52nd annual American Society of Clinical Oncology (ASCO) meeting in Chicago. A subset of the results were previously presented at the American Association for Cancer Research meeting in April of this year.

“These exciting results indicate that there is a new standard of care option for a population of head and neck cancer patients with no other treatment options,” said the trial’s international co-chair Robert Ferris, MD, PhD, UPMC Endowed Professor, and chief of the Division of Head and Neck Surgery and co-leader of the Cancer Immunology Program at UPCI.

The new drug, nivolumab, which belongs to a class of drugs known as immunotherapeutics, enables the body’s immune system to destroy cancer cells. It currently is approved to treat certain types of cancers, including melanoma and lung cancer.

The trial enrolled 361 patients with recurrent or metastatic head and neck squamous cell carcinoma who had not responded to platinum-based chemotherapy, a rapidly progressing form of the disease with an especially poor prognosis, said Dr. Ferris. Patients were randomized to receive either nivolumab or a single type of standard chemotherapy until tumor progression was observed.

The nivolumab group achieved better outcomes than the standard chemotherapy group by all accounts. After 12 months, 36 percent of the nivolumab group was alive, compared to just 17 percent of the standard chemotherapy group.

Nivolumab treatment also doubled the number of patients whose tumors shrunk, and the number whose disease had not progressed after six months of treatment. Importantly, these benefits were achieved with just one-third the rate of serious adverse events reported in the standard chemotherapy group.

In addition, on average, patients receiving nivolumab reported that their quality of life remained stable or improved throughout the study, while those in the chemotherapy group reported a decline.

While nivolumab improved survival rates in the overall study population, it appeared to be most successful in patients whose tumors were positive for the human papillomavirus (HPV). This is important because the fraction of head and neck cancers attributable to HPV infection has increased by 250 percent over the past several decades, Dr. Ferris explained.

“Unfortunately, most patients in this trial still experienced a progression of their cancer, demonstrating that we still have a lot of work to do. But, the future appears brighter than ever before because there is a new class of agents, immunotherapies, which we now know can prolong survival and improve quality of life, with few side effects, in head and neck cancer,” said Dr. Ferris.

The research team currently is working to identify new biomarkers that will allow them to develop a better understanding of how drug resistance develops, and how to best design effective combinations of medications that may improve patient responses.

The trial’s other co-chair is Maura Gillison, MD, PhD, from Ohio State University. Additional U.S. institutions that participated in the trial include University of Texas MD Anderson Cancer Center, Stanford Cancer Institute, University of Chicago, University of Michigan, and Dana-Farber Cancer Institute. International collaborators are located at Centre Leon Berard, Centre Antoine Lacassagne, and Institut Gustave Roussy, all in France; Fondazione IRCCS Istituto Nazionale Tumori, in Italy; The Institute of Cancer Research, in the United Kingdom; University Hospital Essen, in Germany; and National Cancer Center Hospital East and Kobe University Hospital, both in Japan.

The trial was funded by the drug manufacturer, Bristol-Myers Squibb, who is now seeking FDA approval for the use of nivolumab in head and neck carcinoma.

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