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Tiny Heart, Big Promise
Understanding how cells become coronary vessels may lead to advances in repairing heart damage




veins that remove deoxygenated blood. This system of vessels nourishes the heart, enabling it to pump blood to all the other organs and tissues of the body. Yet despite their critical importance, the process and molecules required for coronary vessel development have not been fully determined.

Studying zebrafish, investigators at The Saban Research Institute and the Heart Institute of Children’s Hospital Los Angeles discovered a new source for cells that can develop into coronary vessels and have identified the signaling protein, a chemokine called CXCL12, which guides this process. Results of the study will be published online May 26 by the journal Developmental Cell. 

Zebrafish have emerged as an important vertebrate model for cardiovascular research for a number of reasons, including the ability to regenerate its heart if damaged, and because the transparency of the embryos allows easy observation of internal processes like blood vessel development. Using confocal and time-lapse imaging, the investigators were able to visualize coronary vessels developing from the endocardium, or the inner lining of the heart – specifically from the atrioventricular canal, the structure that divides the heart into compartments. 

“This furthers our efforts into heart regeneration to repair human hearts,” said Ching-Ling (Ellen) Lien, PhD, principal investigator at The Saban Research Institute of CHLA and senior author on the paper. “We have now found a novel source of cells that can differentiate into coronary vessels and have identified the factors required.”

Lien and her team observed that zebrafish with a mutation at the CXCR4 receptor survive, but are not able to form coronary vessels or undergo heart regeneration following injury. Since fish without this mutation are able to do both, the investigators concluded that an interaction between CXCR4 receptors on endothelial cells and the CXCL12b protein expressed by the myocardium regulate the process. In addition to providing basic information about the developing heart, this finding may also have clinical relevance. 

“Children or young adults may not be aware of having abnormal coronary vessels because their circulation is adequate until the heart is stressed by increased demands, for instance when participating in strenuous sports,” explains Lien, who is also an assistant professor at the Keck School of Medicine and an investigator at the Cardiovascular Thoracic Institute, both at the University of Southern California. “Then suddenly, an apparently healthy, young person dies. Alternatively, a person with abnormal coronary vessels might have higher risk of experiencing heart attacks later on in life. Our findings will guide future study toward understanding these devastating conditions in order to be better able to diagnose them and develop interventional strategies.”

The first author, Dr. Michael R.M. Harrison is a CIRM scholar and Saban RCDF fellow. Additional contributors include Ying Huang and Arthela Osorio, The Saban Research Institute of CHLA; Jeroen Bussmann and Arndt F. Siekmann, Max Planck Institute for Molecular Biomedicine, Muenster, Germany; Long Zhao, C. Geoffrey Burns and Caroline E. Burns, Harvard Medical School; and Henry M. Sucov, Broad Center for Regenerative Medicine and Stem Cell Research at USC. 

The study was supported in part by the National Heart, Lung and Blood Institute R01HL096121, The Saban Research Institute Career Development Award, and a California Institute for Regenerative Medicine (CIRM) postdoctoral fellowship TG2-01168.

About Children’s Hospital Los Angeles: Children's Hospital Los Angeles has been named the best children’s hospital on the West Coast and among the top five in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll. Children’s Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States. Children’s Hospital is also one of America's premier teaching hospitals through its affiliation since 1932 with the Keck School of Medicine of the University of Southern California.

For more information, visit CHLA.org. Follow us on our blog http://researchlablog.org/. 
The heart has its own dedicated blood supply, with coronary arteries that supply oxygen-rich blood to the heart and cardiac
Deficiency of specific protein in brain’s blood vessels increases risk for Alzheimer’s disease 
New study finds that PICALM protein regulates removal of toxic plaques from brain




target for the treatment of Alzheimer’s disease.

In a study that appears in the May 25 edition of the scientific journal Nature Neuroscience, researchers identify this new role for PICALM, which is a known genetic risk factor for Alzheimer’s disease.

Alzheimer’s is the most common type of dementia, characterized by the loss of memory and other mental abilities linked to an accumulation of amyloid-beta and other toxic compounds in the brain. The study found that a deficiency in PICALM in cerebral blood vessels and in PICALM-related gene variants associated with increased risk for Alzheimer’s, disable amyloid-beta from being cleared out of the brain across a region known as the blood-brain barrier.

“There have been many new genes discovered to be associated with Alzheimer’s disease, but the biology of these genes are poorly understood,” said the study’s principal investigator Berislav Zlokovic, M.D., Ph.D., director of the Zilkha Neurogenetic Institute and holder of the Mary Hayley and Selim Zilkha chair for Alzheimer’s Disease research at the Keck School of Medicine of USC. “Our new study shows that a deficiency in PICALM in blood vessels and its variants associated with increased risk for the disease inactivate amyloid-beta clearance from the brain, leading to its accumulation and cognitive impairment. This new study provides fundamental new information about PICALM and brings to light novel potential therapeutic targets for increasing amyloid-beta clearance in Alzheimer’s disease.”

Autopsies from Alzheimer’s disease patients and recent research in experimental models have shown the importance of brain blood vessels in the disease’s initiation and progression. For more than two decades, Zlokovic and his research team have studied the cellular and molecular mechanisms of brain blood vessels that maintain normal cognition with hopes of developing new treatments for Alzheimer’s and other neurodegenerative diseases. One focus of their lab at the Zilkha Neurogenetic Institute is on PICALM, or phosphatidylinositol binding clathrin assembly protein, which in humans is encoded by the PICALM gene.

By performing a neuropathological study in humans with Alzheimer’s and using transgenic animals to model the disease, the group found that low levels of PICALM in brain endothelial cells lead to amyloid-beta accumulation in the brain. Genetic variants associated with the PICALM gene have been shown to increase the risk of Alzheimer’s disease. The researchers also generated human endothelial cells from induced pluripotent stem cells to examine the consequences of a known PICALM variant associated with increased risk for Alzheimer’s; they found that this genetic alteration disrupted amyloid-beta clearance by cerebral blood vessels.

These new findings have prompted Zlokovic to address new questions about the role of PICALM in Alzheimer’s disease. Future studies will explore how genetic flaws in the PICALM gene influence its expression levels and clearance function at the blood-brain barrier and the general health of cerebral blood vessels. The team also will work on developing therapeutic strategies, including gene therapy, and screening for new drugs to overcome PICALM deficiency.

Co-authors on the study from USC include Zhen Zhao, Abhay Sagare, Qingyi Ma, Matthew Halliday, Pan Kong, Kassandra Kisler, Ethan Winkler, Anita Ramanathan, Nelly Chuqui Owens, Sanket Rege, Gabriel Si, Ashim Ahuja, Carol Miller, Tohru Sugawara and Justin Ichida.

The study was funded in part by the National Institutes of Health (R37NS34467, R37AG23084, R01AG039452, R01AG035355 , R01AG027924, R00NS07743), Cure for Alzheimer Fund, American Cancer Society (RSG–13–379–01–LIB), Rainwater Charitable Foundation, Donald E. and Delia B. Baxter Foundation, and Daiichi Sankyo Foundation of Life Science. This study used sample ND10689 from the NINDS Cell Line Repository, as well as clinical data.

Article cited:
Zhao, Z., Sagare, A. P., Ma, Q., Halliday, M. R., Kong, P., Kisler, K., … & Zlokovic, B. V. (2015). Central role for PICALM in amyloid–β blood–brain barrier transcytosis and clearance. Nature Neuroscience. Published online May 25, 2015; doi: 10.1038/nn.4025

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology (No. 9), and among the Top 25 hospitals in the United States for urology (No. 20) and cancer care (No. 23).

For more information, go to www.keckmedicine.org/beyond
Scientists at the Keck School of Medicine of the University of Southern California (USC) have discovered that a protein known as PICALM regulates removal of toxic plaques from the brain, which could be a potential therapeutic
Has Brazil found the way to better health care?





Under Brazil’s family health program, when a woman learns that she is pregnant, she contacts her local community health agent, who often is a neighbor.

Typically, the agent visits her home to arrange an appointment with the neighborhood’s family health team, and the woman visits the health center for an assessment by a nurse assistant and a physician. During the pregnancy, if she misses a prenatal care appointment, the agent checks in on her at home and helps her reschedule her visit. Any prenatal medications she needs are provided free of charge.

Brazil — home to the world’s fifth-largest population and seventh-largest economy — has made rapid progress toward universal health care coverage through its national health system, the Sistema Único de Saúde, since it emerged from a dictatorship in 1985. In 1994, the health system launched an ambitious community-based, primary care approach called the Family Health Strategy, which is markedly different from systems in the U.S. and other nations.

A study led by UCLA professor James Macinko finds that Brazil’s primary care approach appears to be working quite well. The research is published in the current online edition of the New England Journal of Medicine.

“This cost-effective way of delivering health care costs about $50 per person per year and has led to dramatic reductions in infant mortality rates, decreased hospitalizations due to complications of chronic conditions, and reduced deaths from stroke and heart disease, among a host of other benefits,” said Macinko, a professor of health policy and management and of community health sciences at the UCLA Fielding School of Public Health.

“And all of this took place in less than 20 years. It is a truly remarkable achievement,” he said.

Macinko, who studies how different ways of organizing and delivering health care impact the health of populations around the world, found Brazil’s system to be particularly intriguing. Collaborating with co-author Matthew Harris of New York University and Imperial College London’s School of Public Health, Macinko worked with the Brazilian government and local researchers to conduct more than a dozen studies of the nation’s health system, including research aimed at understanding how pregnant women and people with chronic conditions like heart disease would fare in the system.

As opposed to the U.S.’s Affordable Care Act, which is based on expanding health insurance, the Family Health Strategy, or FHS, is designed to meet the government’s constitutional obligation to provide health care to all citizens. It is funded primarily through taxes, and all health services — from routine checkups to heart transplants — are available to everyone free of charge at the point of service. 

Other national health coverage systems, such as the United Kingdom’s, are organized in a similar fashion, but the Brazilian system is unusual because of its emphasis on community-based primary care. At the nucleus of each FHS team are a physician, nurse, nurse’s assistant, and four to six full-time community health agents. Family health teams are organized geographically, covering populations of about 1,000 households each. Each FHS team member has defined roles and responsibilities, and the team’s responses to most health problems typically follow national guidelines.

It’s a unique way to provide health care, said Macinko. “Even in high-income countries there are few examples of health systems that provide universal coverage for their citizens via such a community-based primary care approach.”

The community health agents are the heart of the FHS; each is assigned to approximately 150 households, usually in the same neighborhood where the agent lives. The agents visit each household within their area at least once per month, regardless of demand, and record updated information about each individual and each household. During each visit, they may ask household members why they missed a doctor’s appointment (and help schedule a new one), check whether prescriptions have been filled and whether patients have been taking their medications regularly, inquire about changes to the household, and identify potential warning signs of violence, neglect, truancy or drug use, among other problems. They also actively look for signs of smoking and other health risks, and for symptoms of common chronic disease such as hypertension and diabetes. The agents are salaried members of a health care team, and they are supervised by trained health professionals, including a physician.

Macinko said the community health agents help bridge the divide between primary care and public health efforts, and their ranks have grown rapidly. In 1998, there were roughly 2,000 teams, including 60,000 community health agents, providing services to 7 million people — or about 4 percent of the population. In 2014, there were 39,000 teams, with more than 265,000 community health agents, in addition to 30,000 teams of dentists and dental technicians, which combined served 120 million people — roughly 62 percent of the population. 

That rate of expansion is projected to continue, Macinko said.

The study notes that the FHS is not without its problems. For one, although the national health system is public, the Brazilian government probably spends too little on it, compared with national health systems in wealthier European countries. For another, the rapid expansion has created a shortage of physicians and variations in quality of care. In addition, the program has focused on delivering care to poorer populations, and although the approach has improved health care equity, it hasn’t yet reached most of the nation’s wealthier citizens, who may prefer to seek services from private-sector providers. Finally, limitations in technology have slowed the introduction of electronic medical records and advanced diagnostic instruments at primary care clinics.

Still, said Macinko, the nation’s approach to universal health care merits consideration. “Brazil’s community-based primary care approach is worth emulating — or, at the very least, learning from — in countries both rich and poor.”
Has Brazil found the way to better health care?

The world’s fifth largest nation has made rapid progress toward universal coverage, notes UCLA researcher
USC Receives $25 Million Gift to Name USC Tina and Rick Caruso Department of Otolaryngology
Head and Neck Surgery and USC Caruso Family Center for Childhood Communication


 

largest and most highly ranked for research and treatment of diseases of the ear, nose and throat.

The Carusos’ exceptionally generous gift also names and endows the department’s affiliated treatment center for young children with severe hearing loss. This funding for the USC Caruso Family Center for Childhood Communication will enable the center to expand its leadership as the region’s top resource for testing and therapies that enable children to hear.

The USC Caruso Department serves patients facing a range of conditions affecting the head and neck, such as cancer, thyroid disease, facial paralysis, chronic sinusitis and tumors of the cranial base. As a key program within the Department, the Caruso Family Center’s life-changing technologies and services allow children to experience sounds—from their parents’ voices to music, laughter and nature—often for the very first time.

For the Caruso family, these advances carry great personal significance. With a daughter impacted by hearing loss at birth, the Carusos have experienced first-hand the challenges of early-onset hearing loss. Inspired by their experiences, the family has steadfastly supported pioneering research, health care and education. With this gift, Rick and Tina Caruso build on that legacy of support, and align this specific philanthropic focus with the research and treatment advances taking place at USC.

“This gift reflects the Caruso family’s far-reaching and passionate commitment to USC,” said USC President C. L. Max Nikias. “As benefactors, Rick and Tina Caruso inspire so many throughout Los Angeles and our nation, and we should all warmly applaud their philanthropic vision, their dedication to medical discovery, and the profound breadth of their generosity.”

Rick Caruso, a highly respected business and community leader, is the founder and chief executive officer of one of the nation’s largest, privately held real estate companies, Caruso Affiliated. The company’s holdings include The Grove, The Americana at Brand, The Commons at Calabasas, The Promenade at Westlake, Waterside at Marina del Rey and 8500 Burton Way, among others. He graduated with a bachelor’s degree with honors from the USC Marshall School of Business and joined the USC Board of Trustees in 2007. He serves in several leadership positions with the USC board, including chairing the board’s personnel committee, and serves on the executive, development and campus planning committees. He also serves on the board of councilors for the USC Sol Price School of Public Policy.

The Carusos' teenage daughter, Gianna, was born with mild to moderate hearing loss, and doctors and therapists have worked closely with her ever since. Although Gianna could hear some sounds with assistance, she relied on reading lips to ensure she understood what was being said. This presented challenges in daily life, including in the classroom.  This all changed as Gianna experienced a miracle last year, Caruso said, when she saw the team of USC doctors who provided her with a new highly sensitive hearing device that was inserted into her ear canal.

“The minute the hearing device went in, there was a huge difference. Gianna immediately started crying—all of us started crying,” Caruso said. “It was a life changer.”

“It is so profound how hearing loss affects everything in your life,” Caruso said. “I still can’t fully appreciate all of the challenges, even though I saw Gianna live with it every day. And it also was what she was missing—she had never heard a bird chirping before receiving this device.

“There have been some profound moments for our family, like a few months ago, when it rained in L.A., we were sitting at home watching a movie and she said, ‘Dad and Mom, I hear rain outside.’ I said, ‘Yeah, it’s raining.’

“She said, ‘No, Dad. I hear the rain.’”

That’s the promise and the potential to impact lives, Caruso says.

Caruso said he believes that with the endowment, USC has the potential to help thousands of children, perhaps millions of people who have suffered hearing loss to hear for the first time, or to ultimately cure hearing loss altogether. Gianna plans to work with kids at the Center as well.

“We’ve been very fortunate in our lives,” Caruso said. “This is obviously a very personal mission for us. It has affected Gianna in so many difficult ways, but it also has been a blessing in many ways. It’s made our family sensitive to so many needs of others, and we have been inspired by Gianna’s courage and successes.”

“This gift is going to help kids that wouldn’t otherwise have the ability to afford these technologies or have access to this level of health care,” he said.

The Caruso name is already well known in USC life. The couple’s latest gift builds on a broad legacy of support to USC that spans nearly four decades and includes more than $35 million in philanthropic gifts. Their previous naming gift established the USC Caruso Catholic Center, and was the lead gift to build the Center and Our Savior Parish Church, which provide spiritual support for many USC students.

Through the Caruso Family Foundation, the family has focused on education and healthcare causes that improve the lives of children.

About the USC Caruso Department

The USC Tina and Rick Caruso Department of Otolaryngology – Head and Neck Surgery ranks among the top 10 nationwide in federal research funding. Its research, training and patient care focus on the wide range of conditions affecting the head and neck.

The department is led by John K. Niparko, the holder of the Leon J. Tiber and David S. Alpert Chair in Medicine at the Keck School of Medicine of USC. He is an internationally renowned otoneurologic surgeon and researcher recruited to USC in 2012 from The Johns Hopkins University. A national expert on hearing technologies, Niparko has built USC’s otolaryngology group into one of the nation’s finest, recruiting 44 outstanding researchers from around the country and spearheading a long-running national clinical trial of treatments for children with hearing loss.

The Carusos’ endowment support will bolster the depth of the department’s research and help expand treatment options for hearing loss—the third most-common diagnosis affecting mankind, behind arthritis and hypertension. About 30 million Americans suffer hearing loss of varying severity.

With regional and national recruits, Niparko founded and directs the newly named USC Caruso Family Center for Childhood Communication. The center assists more than 5,000 children and their families who are coping with hearing conditions and disease. Profound hearing loss affects one in every 1,000 children at birth, and one in 500 by age five.

”Early intervention is critical to ensure that children with hearing loss develop their speech and language skills,” Niparko explained. “There is an early window of opportunity when sound exposure empowers a child to learn to comprehend and connect information from speech and the environment.  Tina and Rick Caruso have a profound understanding of these concerns and are compassionate believers in the importance of this work. Generations of children will bear the imprint of their generosity.”

“Hearing loss is a shared disability. And one thing that we have learned from the Caruso family is that digital hearing devices are responsive and nimble devices that restore tonal hearing. But when paired with the awareness and support of family and friends, the results can be extraordinary,” Niparko said.

Niparko and Rick A. Friedman, a leader in treatment of acoustic neuromas and one of the nation’s top ear surgeons, oversee patient care at the USC Caruso Family Center.

The Carusos’ gift will help expand the center’s services through the establishment of satellite clinics, expanded educational programs, professional training opportunities and an effort to raise public awareness of hearing-related disease and conditions.

Much like the Caruso Family Foundation, which supports organizations that improve the lives of children while advancing health care and education, the USC Caruso Department and Center operate in tandem to assist families from the region and around the world, regardless of financial circumstances.

USC Caruso Center experts offer novel interventions to help children use their restored hearing to further develop their language and literacy skills. The center’s audiologists, educators and speech and language therapists provide children and their families with training and educational outreach that take hearing technologies to their fullest potential. Those services include expertise in pediatric cochlear implants, bimodal fittings, and the effects of multilingualism on speech and language development of children who have cochlear implants.

Although the cochlear implantation has become the standard of care for deafness and advanced levels of hearing loss, Niparko notes that researchers are looking beyond that technology for advances in areas such as stem cell therapies. He and others believe there may be a way to prompt, through a biologic treatment utilizing stem cells, the regeneration of hair cells within the inner ear that are critical for sensitive hearing.

“We are on a path of triggering reprogrammed cells to undergo a metamorphosis—a sort of caterpillar to butterfly change that can resupply the ear with the cellular machinery needed to recover hearing,” Niparko said.

Achieving a biological breakthrough for treatment of hearing loss would rank among the greatest and most enduring legacies of the Caruso family’s gift.

The Carusos’ generous gift further advances The Campaign for the University of Southern California, a multiyear effort that seeks to raise $6 billion or more in private philanthropy to advance USC’s academic priorities and expand its positive impact on the community and world. Just four and a half years after its launch, the campaign has raised more than $4.2 billion.
Business leader and USC Trustee Rick J. Caruso and his wife, Tina, have donated $25 million to endow and name the USC Tina and Rick Caruso Department of Otolaryngology – Head and Neck Surgery, one of the nation’s
Vitreomacular adhesion patients report improved vision with non-surgical treatment in USC Eye Institute-led clinical studies
Common condition of aging eyes could lead to blindness if left untreated




symptomatic vitreomacular adhesion (VMA), a condition related to the aging eye that could cause permanent vision loss if left untreated.

“These are the first large studies that document patient-reported visual improvement after injection of ocriplasmin for symptomatic VMA,” said Rohit Varma, M.D., M.P.H., director of the USC Eye Institute and lead author of the study. “These improvements were achieved without surgery, consequently avoiding the risks, recovery time, possible complications and costs associated with surgery. This is an important finding in our search for safer and more effective treatments to prevent blindness.”

As the eye ages, it is normal for the vitreous — the thick clear gel that fills the center of the eye — to liquefy and separate from the back of the eye, called the retina. In some cases, parts of the vitreous remain attached to and may pull on the retina, causing vision distortion, vision loss and even blindness. Previous studies have estimated that 1.5 percent of the population suffers from eye diseases associated with or caused by VMA. The standard of care for VMA patients at high risk for vision loss is a vitrectomy, or surgical removal of the vitreous.

In the two randomized and masked Phase 3 clinical trials, researchers at the USC Eye Institute in Los Angeles, Wills Eye Hospital in Philadelphia and Cole Eye Institute in Cleveland studied 652 patients with symptomatic VMA who opted for treatment with ocriplasmin at clinic-based centers in the United States and Europe. Across the two studies, 464 patients received the drug and 188 received a placebo. The study investigators performed complete eye examinations at regular intervals before and up to six months after injection, with the option to recommend and perform surgery if vision deteriorated.

As described in the June 11, 2015, issue of the peer-reviewed journal JAMA Ophthalmology, the patients treated with the ocriplasmin injection reported greater improvements in vision-related activities and visual function and were less likely to have experienced worse vision at six months when compared to patients who received the placebo.

Ocriplasmin, marketed as Jetrea by the biopharmaceutical company ThromboGenics, was approved by the Food and Drug Administration in 2012 and commercially launched in 2013. The clinical studies and analyses were funded by ThromboGenics. Varma serves as a consultant for Aerie, Allergan, AqueSys, Bausch and Lomb, and Genentech.

Article cited:
Varma, R., Haller, J. A., & Kaiser, P. K. (2015). Improvement in patient-reported visual function after ocriplasmin for vitreomacular adhesion: Results of the microplasmin for intravitreous injection-traction release without surgical treatment (MIVI-TRUST) trials. JAMA Ophthalmology. Published online June 11, 2015; doi:10.1001/jamaophthalmol.2015.1746

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology and among the Top 25 hospitals in the United States for urology and cancer care.

For more information, go to www.keckmedicine.org/beyond
In two ancillary studies of two multi-center international clinical trials led by the University of Southern California (USC) Eye Institute, the injectable drug ocriplasmin appears to improve vision among patients suffering from
USC physicians ask Southern Californians to take online brain tests to help find cures for Alzheimer’s, Parkinson’s and other brain disorders
Brain Health Registry promises new treatments through faster, better clinical trials




disorders such as Alzheimer’s, Parkinson’s and depression.

Launched in San Francisco in April 2014 by the University of California, San Francisco, the Brain Health Registry promises to significantly cut the time and cost of conducting clinical trials for brain diseases. USC is the registry’s first targeted expansion outside of Northern California.

To join, individuals 18 years or older sign up for the registry online, provide a brief personal history and periodically take online neuropsychological tests in game format. By completing these online tests, participants provide snapshots of their brain function, allowing researchers to better understand the human brain as it ages and changes – quicker and at less cost. For most people, participation takes less than three hours per year.

“Recruiting participants for a clinical trial comprises a large expense, which drives up the cost of developing new drugs,” said Lon S. Schneider, M.D., USC’s principal investigator for the registry and professor of psychiatry, neurology and gerontology at the Keck School of Medicine of USC and USC Davis School of Gerontology. “The registry is a safe and easy way for physician scientists to track changes in brain function of thousands of people over time and increase the pool of pre-qualified clinical trial participants. We hope this will lead to faster cures for Alzheimer’s disease, depression and other brain disorders.”

Schneider is clinical core director of USC’s Alzheimer’s Disease Research Center, a network of centers across the country supported by the National Institute on Aging to translate research into therapies for people with the debilitating disease. The center is part of Keck Medicine of USC’s Memory and Aging Center, which provides diagnostic services and treatment for age-related diseases, including Alzheimer’s, the most common form of dementia.

Brain Health Registry organizers hope to recruit 100,000 people by the end of 2017. More than 25,000 volunteers, primarily from the San Francisco Bay Area, have joined the registry so far.

A select number of volunteers will be asked by researchers to do more than take online brain tests, such as providing saliva or blood samples, or participating in clinical trials to test potential cures. Volunteers can participate as little or as much as they like. All information will be gathered in accordance with federal privacy laws under the Health Insurance Portability and Accountability Act (HIPAA), as well as the highest standards of medical ethics.

Leading funders for the project include the Rosenberg Alzheimer’s Project, the Ray and Dagmar Dolby Family Fund, Kevin and Connie Shanahan, General Electric and The Drew Foundation. Lumosity, the San Francisco-based brain training company, and Cogstate, a global leader in computerized cognitive assessment tools, have also partnered with the Brain Health Registry and provided online neuropsychological tests.

For more information, go to http://neuro.keckmedicine.org/brain-health-registry.

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology and among the Top 25 hospitals in the United States for urology and cancer care. For more information, go to www.keckmedicine.org/beyond
Doctors at the Keck School of Medicine of the University of Southern California (USC) are calling on Southern Californians to join the Brain Health Registry, an Internet-based health registry, and help find cures for neurological
Keck School of Medicine of USC research finds air pollution may affect the way the brain ages and functions
Effects on brain’s white matter seen in older women who lived in locations with high levels of small particles in ambient air




that it may also have a negative impact on how the brain’s white matter  ages.

The research indicates that older women who lived in geographic locations with higher levels of fine particulate matter in ambient air had significantly smaller white matter volumes across a wide range of brain areas.

Fine particulate matter is smaller than 2.5 micrometers and is known as PM2.5, a form of pollution that easily enters the lungs and possibly the bloodstream.  White matter connects brain regions and determines how information is processed in the brain.

“Investigating the impact of air pollution on the human brain is a new area of environmental neurosciences,” said Jiu-Chiuan Chen, M.D., M.P.H., Sc.D., associate professor of preventive medicine at the Keck School of Medicine and lead author of the research. “Our study provides convincing evidence that several parts of the aging brain, especially the white matter, are an important target of neurotoxic effects induced by long-term exposure to fine particles in the air.”

The study found that older women ages 71 - 89 who had lived in places with greater PM2.5 exposures had significantly smaller volumes of white matter, and that this could not be explained by the geographic region where they lived, their race or ethnic background, socioeconomic status, lifestyle, or medical conditions that may also influence brain volumes.

The researchers performed brain magnetic resonance imaging (MRI) scans of 1,403 women who are part of the Women’s Health Initiative Memory Study (WHIMS), a nationwide study based at Wake Forest Baptist Medical Center in Winston-Salem, N.C. The researchers also used residential histories and air monitoring data to estimate the participants’ exposure to air pollution in the previous six to seven years.

This is the first study to differentiate between white and gray matter while examining the neurotoxic effects of PM2.5 on brain volumes of older people, The USC-led research may be the largest neuroimaging study conducted in community-dwelling elderly persons to examine the association between long-term PM2.5 exposures and volumes of gray matter and white matter in the brain.

White matter contains nerve fibers and connects brain regions with each other by traveling deep within and passing nerve signals throughout the brain. Gray matter is primarily composed of neuronal cell bodies, dendrites, glial cells, and capillaries. The study did not find impacts from exposure to air pollution in participants’ gray matter.

The WHIMS study began in 1996 at Wake Forest Baptist Medical Center for the purpose of studying how postmenopausal hormone treatment affects cognitive impairment and brain aging.

The research appears in the June 15, 2015 issue of the Annals of Neurology. Co-authors include Xinhui Wang, M.S., and Helena Chui, M.D. of the Keck School of Medicine of USC; John McArdle, Ph.D. of the USC Dornsife College of Letters, Arts and Sciences; Gregory Wellenius, Sc.D. of Brown University; Mark Serre, Ph.D. of the University of North Carolina; Ira Driscoll, Ph.D. of the University of Wisconsin; Ramon Casanova, Ph.D. and Mark Espeland, Ph.D. of Wake Forest Baptist Medical Center; and JoAnn Manson, M.D., Dr. P.H. of Harvard Medical School.

The collaborative study was funded in part by the National Institutes of Health grant R01AG033078 and by the Rosenblith Award from the Health Effects Institute, an organization jointly funded by the United States Environmental Protection Agency and certain auto and engine manufacturers. The work was also supported by the Southern California Environmental Health Sciences Center (5P30ES007048). The research was also supported by the National Heart, Lung, and Blood Institute, National Institute on Aging, National Institutes of Health, U.S. Department of Health and Human Services through contracts and by Wyeth Pharmaceuticals, Inc, St. Davids, Pa., and Wake Forest Baptist Medical Center, which funds the Women’s Health Initiative Program and its memory study.

Article cited:
Chen, J.C., Wang, X., Wellenius. G.A., Serre, M.L., Driscoll, I., Casanova, R. McArdle, J.J., Manson, J.E., Chui, H.C., Espeland, M.A.. Ambient Air Pollution and Neurotoxicity on Brain Structure: Evidence from Women's Health Initiative Memory Study. Annals of Neurology June 15, 2015. doi: 10.1002/ana.24460. [Epub ahead of print]. PMID: 26075655

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology and among the Top 25 hospitals in the United States for urology and cancer care.

For more information, go to www.keckmedicine.org/beyond
Exposure to air pollution has been known to affect respiratory diseases, lung function and cardiac health, but a new study led by Keck School of Medicine of the University of Southern California (USC) researchers shows for the first time
Brain scan can predict who responds best to certain treatment for obsessive-compulsive disorder
UCLA study may lead to more precise treatments for OCD




by recurrent, intrusive, and disturbing thoughts (obsessions), and/or stereotyped recurrent behaviors (compulsions). Left untreated, OCD can be profoundly distressing to the patient and can adversely affect their ability to succeed in school, hold a job or function in society.

One of the most common and effective treatments is cognitive-behavioral therapy, which aims to help patients understand the thoughts and feelings that influence their behaviors and then work toward eliminating them. But not all OCD sufferers benefit over the long term: In an estimated 20 percent of patients, symptoms eventually return after the therapy is complete.

A new study by researchers at the Semel Institute for Neuroscience and Human Behavior at UCLA suggests that a certain detail from patients’ brain scans could help clinicians identify which people are more likely to relapse after cognitive-behavioral therapy — and why.

“The efficiency of brain network connectivity before treatment predicts the worsening of symptoms after treatment,” said Jamie Feusner, a UCLA associate professor of psychiatry and director of the Semel Institute’s Adult OCD Program.

Feusner and Joseph O’Neill, a UCLA associate professor of child psychiatry and a research scientist at the Semel Institute, were the study’s co-principal investigators. The research was published in the open-access journal Frontiers in Psychiatry.

The researchers used functional magnetic resonance imaging, or fMRI, to study the brains of 17 people, aged 21 to 50 years old, with OCD. Scans were taken both before and immediately after the patients completed an intensive four-week course of cognitive-behavioral therapy, and the doctors monitored the patients’ clinical symptoms over the next 12 months.

“We found that cognitive-behavioral therapy itself results in more densely connected local brain networks, which likely reflects more efficient brain activity,” Feusner said.

However, the researchers also found that people who had more efficient brain connectivity before they began treatment actually did worse in the follow-up period. Surprisingly, neither the severity of symptoms before treatment nor the amount that symptoms improvement during treatment were accurate predictors of the patients’ post-treatment success.

The researchers say that knowing more about which patients might not fare well long-term could potentially help doctors and patients choose the best course of treatment.

“Cognitive-behavioral therapy is in many cases very effective, at least in the short term. But it is costly, time-consuming, difficult for patients and, in many areas, not available,” Feusner said. “Thus, if someone will end up having their symptoms return, it would be useful to know before they get treatment.”

He added that the findings don’t mean that some people with OCD cannot be helped — just that four weeks of intensive cognitive-behavioral therapy might not be the most effective long-term approach. OCD can also be treated with medication or through cognitive-behavioral therapy that lasts longer than the four-week period evaluated in the study.

The UCLA study was the first to use brain connectivity to help predict a post-treatment clinical course, and the first to test the effects of cognitive-behavioral therapy on brain network connectivity. Feusner and his colleagues are conducting several other studies to understand the effects of the treatment on the brain in people with OCD and with other OCD-related disorders, including body dysmorphic disorder and anorexia nervosa.

“We are now starting to translate knowledge of the brain into useful information that in the future could be used by doctors and patients to make clinical decisions,” Feusner said. “Although a brain scan may seem expensive, these scans only took about 15 minutes and thus the cost is not exceptionally high, particularly in comparison to medication or cognitive-behavioral therapy treatments, which over time can cost many thousands of dollars.”

Feusner, O’Neill and their colleagues plan to conduct another study in a larger number of patients in an attempt to validate the findings; they also will assess additional measures of brain function and structure that they hope will offer more clues to determining the long-term course of symptoms in people being treated for OCD.

The research was funded by a grant from the National Institute of Mental Health (R01MH085900).
Tens of millions of Americans — an estimated 1 to 2 percent of the population — will suffer at some point in their lifetimes from obsessive-compulsive disorder, a disorder characterized
UCLA studies identify predictors of depression and PTSD among African-Americans and Latinos
Researchers develop screening tool that may help deliver more targeted care




Disease Control and Prevention. Two new studies by the UCLA Center for Culture, Trauma and Mental Health Disparities shed light on the causes and impacts of this disparity.

The first study, published online by the journal Psychological Trauma, analyzed certain types of negative experiences that may affect low-income African-Americans and Latinos. It found five specific environmental factors, which the researchers call “domains,” that can predict adult depression, anxiety and post-traumatic stress disorder.

In the second study, published online by the journal Psychological Assessment, researchers used the same five domains to develop a new screening tool for use in clinical settings. The UCLA Life Adversities Screener, or LADS, is a brief questionnaire that can help providers offer more accurate treatment for stress and trauma.

The five domains identified in the first study are:

·        Experiences of discrimination due to racial, ethnic, gender or sexual orientation
·        A history of sexual abuse
·        A history of violence in the family or from an intimate partner
·        A history of violence in an individuals’ community
·        A chronic fear of being killed or seriously injured

The researchers said the effects of these experiences are cumulative and their impact accrues over a person’s lifetime.

“The costs to society of these life experiences are substantial,” said Hector Myers, a former UCLA psychology professor and first author of the Psychological Trauma study. (Myers is now a professor at Vanderbilt University.) “We know there is a poorer overall quality of life, a loss of productivity, greater social dependency, disability, health and mental health care costs, and early mortality as a result of repeated experiences of stress and trauma.”

In the first study, researchers asked 500 low-income African American and Hispanic men and women to self-report various measures of stress and mental health, including experiences of discrimination, childhood violence, poverty and trauma. Using structural equation modeling — statistical methods designed to test a concept or theory — they found a correlation between the cumulative burden of these adversities and the likelihood the subjects would later experience psychological distress. They also found that the greater people’s overall burden of these experiences over their lifetime, the greater the likelihood that they would experience more severe symptoms of depression, anxiety and PTSD.

“Unfortunately, much of the psychological distress stemming from chronic life stress and trauma remains undetected and untreated,” said Gail Wyatt, a professor of psychiatry at the UCLA Semel Institute for Neuroscience and Human Behavior and a senior author of both studies.

“Only a small proportion of individuals with psychological distress are identified in health care settings, and a smaller fraction of those ever receive appropriate treatment, especially for the experiences of discrimination,” said Wyatt, who also is director of UCLA’s Center for Culture, Trauma and Mental Health Disparities. “We talk about being discriminated against, but people don’t learn how to cope with it effectively throughout their lives. If they don’t manage it well enough, the consequences can be long-lasting and life-threatening.”

The second study was led by first author Honghu Liu, a professor in the UCLA School of Dentistry. Working with the five domains, the researchers used regression modeling — a statistical process for estimating relationships among variables — to develop the LADS, a set of questions health care providers can use to screen patients for the effects of adversity and trauma.

“Given the utility and ease of use, LADS could be effective as a screening tool to identify ethnic and racial minority individuals in primary care settings who have a high trauma burden, and who need more extensive evaluation,” said Liu, who is an expert in the design of research studies, data analysis and statistical modeling. “We feel it will capture experiences that could be missed with current screening approaches. This could optimize affordable care as it strives to improve prevention of mental health problems.”

The Congressional Budget Office estimates that 16 million people have gained health insurance under the Patient Protection and Affordable Care Act. “The ACA provides a unique opportunity to identify those who have not been assessed for the adversities and trauma that can affect mental health needs. This research could provide the tools to make that assessment,” Wyatt said.

“The next step is to offer individuals tools to more effectively cope with the adversities and trauma that they endure. One of the advantages of affordable primary care is that we will have the opportunity to offer skills for people who have not had mental health care for those experiences, one day soon. They will no longer have to manage on their own.”

Funding for both studies was provided by grants from the National Institutes of Health (NCT01641146) and National Institute of Mental Health (5P50MH073453 and 1 R34 MH077550).
Chronic disease and mental health issues disproportionately affect low-income African-Americans, Latinos and Hispanics, according to the Centers for 
Providence Little Company of Mary Torrance named among nation’s 100 Great Community Hospitals





Providence Little Company of Mary Torrance was one of just six California hospitals named today to the prestigious list, which includes hospitals of no more than 550 beds and with minimal teaching programs.

The Becker's Hospital Review editorial team selected hospitals for inclusion based on various rankings and awards, including those from iVantage Health Analytics, Truven Health Analytics, Healthgrades and CareChex. Providence Little Company of Mary has been honored for the past four years by Truven as one of America’s Top 100 Hospitals and has earned Healthgrades’ Distinguished Hospitals for Clinical Excellence for the past two years.

“I’m so grateful to our care teams for the compassion, excellence and innovation they combine to provide the best possible care for each and every patient,” said Liz Dunne, chief executive, South Bay community. “Our hospital has consistently been ranked among the nation’s best, and the credit goes to our physicians, nurses and all the caregivers who treat each patients as they would family.”

The "100 Great Community Hospitals" The full list can be read here: http://bit.ly/1IQZdXR

About Providence Health & Services: Providence Health & Services, Southern California, is a Catholic not-for-profit, mission-driven healthcare system. Providence Southern California operates six award-winning hospitals and a comprehensive, fully-integrated network of primary care clinics, urgent care centers, home care, TrinityCare and TrinityKids Care hospice as well as Providence High School. Providence is anchored locally by Providence Holy Cross Medical Center in Mission Hills, Providence Saint Joseph Medical Center in Burbank, Providence Saint John’s Health Center in Santa Monica, Providence Tarzana Medical Center and Providence Little Company of Mary Medical Centers in Torrance and San Pedro. With more than 3,400 physicians, Providence provides coordinated primary and specialty care through an array of physician groups and individual providers including Providence Medical Institute and physician groups in the South Bay, the West Valley and Santa Clarita. Providence affiliate, Facey Medical Group, provides primary and specialized care in the San Fernando, Santa Clarita and San Gabriel valleys. For more information, visit California.providence.org<http://California.providence.org>.
For the third straight year, Becker’s Hospital Review included Providence Little Company of Mary Medical Center Torrance on its list of 100 Great Community Hospitals across the nation.
Despite ban, online searches for flavored cigarettes are smoking, Keck School of Medicine of USC researchers find




cigarettes are still available for purchase over the Internet and are popular search targets.

The researchers found heightened online interest in flavored cigarettes by doing a case study on Djarum, a manufacturer of flavored cigarettes and cigars, the latter of which are legal. By monitoring the search terms “Djarum cigarettes” and “Djarum cigars” in Google, the scientists discovered in the first 50 search results for “Djarum cigarettes” that 72 percent of websites promoted and 34 sold the illegal cigarettes. In addition, there were 291 percent more searches for the flavored cigarette line than the replacement cigar line five years after the ban.

“We weren’t surprised that the web is being used to circumvent tobacco regulations,” said Jon-Patrick Allem, Ph.D., a postdoctoral fellow with the USC Tobacco Center of Regulatory Science (TCORS) and corresponding author on the study. “Most surprising was the constant rate of interest in the illegal products (the cigarettes) versus the legal products (cigars).”

The study is among the first to examine the reactions of consumers and the tobacco industry to flavored cigarette bans, which are also in force in the European Union and other countries.

The researchers suggest beefed-up enforcement, fines and shutting down websites where possible, though tobacco vendor websites can be hosted outside of the country that has enacted a ban.

In 2013, the Keck School of Medicine of USC Department of Preventive Medicine became one of 14 academic institutions to establish an NIH-funded TCORS, intended to help create the scientific base for decision-making by the FDA on tobacco products.

“Using data from the web to inform regulatory science is one of the goals for us here at USC moving forward,” Allem said.

The paper, “When a ban really is not a ban: Internet loopholes and Djarum flavoured cigarettes in the USA,” was published June 17, 2015, in the peer-reviewed journal Tobacco Control. The research team included John Ayers, San Diego State University; Ben Althouse, The Santa Fe Institute; and Rebecca Williams, University of North Carolina at Chapel Hill.

The research was funded by National Cancer Institute (grants 5R01CA169189-02 and T32CA009492).

Article cited:
Allem, J. P., Ayers, J. W., Althouse, B. M., & Williams, R. (2015). When a ban really is not a ban: Internet loopholes and Djarum flavoured cigarettes in the USA. Tobacco Control. Published online June 17, 2015; doi:10.1136/tobaccocontrol-2015-052309

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology and among the Top 25 hospitals in the United States for urology and cancer care.

For more information, go to www.keckmedicine.org/beyond
Think clove cigarettes are so six years ago? A new study from Keck School of Medicine of the University of Southern California (USC) researchers finds that despite a federal Food and Drug Administration (FDA) ban in 2009, flavored
Keck School of Medicine of USC establishes USC Alzheimer’s Therapeutic Research Institute



located in San Diego, CA. Distinguished Alzheimer’s disease scientist, Paul Aisen, M.D., has been appointed founding director of USC ATRI, effective June 21, 2015 and is being proposed as professor of neurology at the Keck School of Medicine of USC.

Aisen will lead the institute in pursuit of its mission to accelerate the development of effective treatments for Alzheimer’s disease through innovative, collaborative, multicenter clinical trials.

“Dr. Aisen has been a leading figure in Alzheimer’s disease research for more than two decades, having developed novel methodologies as well as designed and directed many large therapeutic trials,” said Carmen A. Puliafito, M.D., MBA, dean of the Keck School of Medicine of USC. “We are proud to have him join USC, where his expertise and leadership will help the Keck School and USC create a leading hub of basic, translational and clinical research in neuroscience and neurological diseases.”

To accomplish this ambitious goal, USC is actively recruiting transformative faculty researchers to focus on the human brain and its role in numerous medical conditions including Alzheimer’s disease and multiple sclerosis. These efforts align closely with President Obama’s BRAIN Initiative, announced in April 2013.

The establishment of the USC ATRI with Aisen as director adds a strong clinical research program to complement USC’s existing strengths in Alzheimer’s disease research.

“Keck School of Medicine of USC provides an optimal environment for this research program,” said Aisen. “Close collaboration with Keck investigators, including Drs. Arthur Toga and Paul Thompson at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Dr. Helena Chui at the Alzheimer’s Disease Research Center, and Dr. Berislav Zlokovic at the Zilkha Neurogenetic Institute, will facilitate rapid progress in data sharing and analytical methods central to the drug development process. USC ATRI will be the clinical outlet for testing of new treatments.”

Aisen received his B.A. in biochemistry and molecular biology from Harvard and his medical degree from Columbia. He completed his residency at Case Western Reserve University in Cleveland and Mount Sinai Medical Center in New York, and then fellowship training in rheumatology at New York University. After serving as chief medical resident at Mount Sinai, he began a solo practice in internal medicine and rheumatology in New York. Aisen joined the faculty of Mount Sinai in 1994 and was recruited to Georgetown University in 1999 as a professor of neurology and medicine. That year, he founded the Memory Disorders Program, a clinical and research program for Alzheimer's disease and related disorders. He continued basic research studies on therapeutic targets and biomarkers and designed and directed multicenter therapeutic trials. He became vice chair of the Department of Neurology at Georgetown in 2004. From 2007 through 2015, he was professor in the Department of Neurosciences at the University of California, San Diego and director of the Alzheimer’s Disease Cooperative Study.

Alzheimer’s disease is the sixth leading cause of death in the United States, and the only disease among the top 10 in America that cannot be prevented, cured, or slowed, according to the Alzheimer’s Association.

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology and among the Top 25 hospitals in the United States for urology and cancer care.

For more information, go to www.keckmedicine.org/beyond
The Keck School of Medicine of the University of Southern California (USC) has established the USC Alzheimer’s Therapeutic Research Institute (USC ATRI),
Simply Observing Men with Very Low- and Low-Risk Prostate Cancer Very Effective and Underused, UCLA Researchers Find
As Many as 40 Percent of Patients May be Overtreated




with localized tumors and could spare them the debilitating side effects of aggressive treatments that are too often unnecessarily used in this patient population, a UCLA review of common practices in prostate cancer has found.

Since the initiation of PSA screening tests, most men with prostate cancer are now diagnosed with localized, low-risk prostate tumors that are unlikely to kill them. However, nearly all of these men undergo surgery or radiation, putting them at risk for ongoing side effects such as erectile dysfunction and impaired urinary function. As many as 40 percent of patients may currently be overtreated, said review senior author Dr. Mark Litwin, professor and chair of UCLA Urology.

“This study is the most up-to-date and comprehensive review of expectant management of prostate cancer patients worldwide. This represents an important resource for patients and providers considering surveillance for prostate cancer,” Litwin said. “Active surveillance and other observational strategies have produced excellent, long-term disease-specific survival and minimal morbidity for men with prostate cancer. Despite this, expectant management remains underused for men with localized prostate cancer.”

The study appears in the July/August 2015 issue of the peer-reviewed journal CA: A Cancer Journal for Clinicians.

The review clearly lays out a number of aspects of expectant management for men with low-risk prostate cancer. First, the UCLA team clarified the definitions of types of surveillance, making it easier for physicians and their patients to decide which is best for them. Active surveillance uses repeated PSA testing and prostate biopsies to monitor for development of more aggressive disease in younger, healthier patients who might benefit from delaying treatment. Watchful waiting avoids aggressive testing and watches for any physical symptoms of progressive disease. It is generally reserved for avoiding treatment altogether for older, sicker patients who will most likely die from something else.

The review describes the current surveillance protocols, and reviews the outcomes for each of these strategies in terms of cancer survival and quality of life. Additionally the review addresses the novel technologies such as prostate MRI and fusion biopsies that may prove beneficial for surveillance patients.

“Considerable questions remain regarding both the identification of optimal candidates for surveillance, as well as understanding the ideal monitoring strategy after the initiation
of observational protocols,” said Dr. Leonard Marks, study co-author and a professor of urology. “Using strict inclusion criteria for very low-risk or low-risk prostates cancer can select a group of prostate cancer patients for active surveillance who would avoid the side effects of therapy while experiencing comparable survival and quality of life.”

Going forward, Marks said, more work is required to optimize the delivery of these expectant management strategies for patients treated in certain settings that may not have incorporated active surveillance into their treatment repertoire. Despite increased adoption of expectant management, active surveillance still remains broadly underused and more data will be needed to clarify the factors contributing to this finding at a population level.

Prostate cancer is the most frequently diagnosed cancer in men aside from skin cancer. An estimated 233,000 new cases of prostate cancer will occur in the United States in 2015. Of those, nearly 30,000 men will die. It’s estimated that more than two million prostate cancer survivors are living in the United States today.

“Ultimately, the decision-making process surrounding treatment for a man with localized prostate cancer must take an individualized approach. The risks and benefits of expectant management vis-a-vis  active treatment should be reviewed with the patient in light of existing knowledge, potentially  with the use of decision aids to help enable a truly shared decision-making process,” the review states. “Active surveillance is a viable approach for most men with low-risk prostate cancer, and its broader adoption has the potential to stop the overtreatment of men with indolent lesions and redirect resources to men with more serious cancers.”

The study was funded in part by the American Cancer Society.

For more than 50 years, the urology specialists at UCLA have continued to break new ground and set the standards of care for patients suffering from urological conditions. In collaboration with research scientists, UCLA’s internationally renowned physicians are pioneering new, less invasive methods of delivering care that are more effective and less costly. UCLA’s is one of only a handful of urology programs in the country that offer kidney and pancreas transplantation. In July of 2014, UCLA Urology was once again ranked fourth in the nation by U.S. News & World Report, a ranking it has held for the last 16 years. For more information, visit http://urology.ucla.edu/
Monitoring men with very low- and low-risk prostate cancers using watchful waiting or active surveillance, called expectant management, is a useful approach for a large number of men