On the Cover:
Illustration by Chris Buzelli
“I remain an AI healthcare evangelist because I see the potential,” says Dr. Tiffani Bright (above), co-director of the Center for Artificial Intelligence Research and Education at CedarsSinai (see page 28).
Powerful promise hangs in the balance with potential peril as hospital systems integrate artificial intelligence into research and patient care. Physicians and investigators endeavor to collect exhaustive data—and scrub it clean of bias—to feed clinic-focused machine-learning tools. AI’s big boom comes with big responsibility to develop fair, accurate algorithms. Can scientists harness the revolutionary power of AI while maintaining humanity in healthcare?
A first-of-its-kind stem cell therapy for ALS passes a critical safety benchmark while investigators grow patient-derived stem cells to model the disease. Can the cure to this degenerative condition lie in the endlessly regenerative power of stem cells? By
Cassie TomlinExecutive Vice President of Academic Affairs and Dean of Medical Faculty
SHLOMO MELMED, MB, CHB
Director of Burns and Allen Research Institute and Vice Dean for Research and Graduate Education
JEFFREY A. GOLDEN, MD
Vice President of Marketing and Communications and Chief Marketing Officer
BETH M c DONNELL
Chief Communications Officer and Executive Director of Communications
DUKE HELFAND
Editor in Chief
LAURA GRUNBERGER
Senior Editor
SARAH SPIVACK LAROSA
Associate Editors
CASSIE TOMLIN
NICOLE LEVINE
Project Manager
KAREN LINK
Creative Director
ROBERT F. PARSONS / SEVEN ELM
SEVENELM.COM
Staff Writers
VICTORIA PELHAM
ROSANNA TURNER
Contributing Writers
JASMINE AIMAQ
KATIE BRIND’AMOUR
JEREMY DEUTCHMAN
LISA FIELDS
AMY PATUREL
SUSIE WAMPLER
KOREN WETMORE
Image Specialist
STEPHEN BEDNAREK
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Cedars-Sinai investigators are deeply engaged in two synergistic, revolutionary sciences that are both dramatically changing medicine: regenerative medicine and artificial intelligence.
BY SHLOMO MELMED, MB CHBRegenerative medicine is reaching a pivotal peak in its ongoing professional ascent: Now, after many years of perseverance, we are in clinical trials and seeing the promise of stem cells to ameliorate debilitating disease. This science is proving cautiously hopeful in addressing degenerative conditions like amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Alzheimer’s disease and retinitis pigmentosa—deteriorative diagnoses that have long confounded medical science.
Cedars-Sinai is at the forefront of the latest techniques in cell revitalization and transplantation to restore diseased or aged tissue. In this issue of Discoveries, we outline the pioneering work of Board of Governors Regenerative Medicine Institute and ALS Clinic investigators to study and treat ALS with stem cells. Culminating decades of study, investigators recently completed a Phase I trial that demonstrated the safety of the implantation of novel human stem cells engineered to secrete a growth factor to protect neurons. A similar ongoing study aims to test the safety of cells engineered to protect against blindness when administered to patients with retinitis pigmentosa.
Although progress is quite preliminary and much work remains before such experimental approaches are converted into therapies to benefit patients at large, completion of the safety trial is a promising step. Now, investigators proceed to the next phase, in which they will test the cell therapy’s efficacy in slowing disease progression. This research is so significant and hope-engendering to ALS patients and their families, who so desperately seek to control the disease and so selflessly join the cause as clinical trial participants.
This issue also focuses on a less tangible, equally fascinating emerging science. At Cedars-Sinai, we are building the most robust information technology platforms to
improve research and patient care. Our artificial intelligence (AI) tools integrate massive amounts of data—some of it subcellular—to assist physicians and scientists in diagnosing and treating patients and in understanding population health paradigms. The brilliant and principled physicians, scientists and administrators who comprise Cedars-Sinai’s AI Council aim to make us a leader in the design, development and responsible use of AI. We are helping to steer an AI healthcare revolution in delivery of care.
You will also read about CedarsSinai’s newly developed children’s health program, Guerin Children’s. As our experts build this world-class pediatrics enterprise, they rely on our longstanding commitment to cutting-edge science. Investigators are leveraging AI to elucidate mechanisms underlying developmental disorders in children and are exploring the power of regenerative medicine to help children who require therapeutic cellular repair of genetic deficits.
At Cedars-Sinai, our programs and institutes are consistently ranked among the best in the country by U.S. News & World Report. Our interconnectedness—our readiness to collaborate across disciplines to learn from and lean on each other—is what makes us the #2 hospital in the nation and the #1 hospital in California, according to U.S. News’ “Best Hospitals 2022-2023” rankings. When we put our minds together, we are truly excellent.
As we remain dedicated to compassionate care and leadingedge research, we continue to warmly appreciate your continued confidence and support.
“Our interconnectedness—our readiness to collaborate across disciplines to learn from and lean on each other—is what makes us the #2 hospital in the nation and the #1 hospital in California.”
Dr. Harris’ bicultural upbringing led her to appreciate both the magic of diversity and the commonalities that tie people together. Today, as vice president and chief health equity officer at CedarsSinai, she works to overcome health disparities and promote equity. She graduated from Harvard Medical School and completed her internship and residency in internal medicine at New YorkPresbyterian/Weill Cornell Medical Center.
Buzelli graduated from Rhode Island School of Design and began his illustration career in New York City. His conceptual illustrations are published in newspapers, magazines, books and advertising campaigns. Among his numerous clients are
The New York Times, The Washington Post, Rolling Stone, ESPN, Tropenmuseum in Amsterdam and the USPS. Buzelli also exhibits his original artwork in galleries worldwide.
Dr. Manning’s path to the history of medicine began with the study of philosophy, took a turn at the history of science and reached its destination with a research year spent in medical school. Today, as director of the History of Medicine Program in the Department of Biomedical Sciences, he studies the evolution of medical theory, practice and institutions; conceptions of life, health and experimentation; and measures of medical success.
More than 31,000 people in the U.S. have amyotrophic lateral sclerosis (ALS). Clinical trials offer key insights into this lethal disease, yet patient enrollment is low. See story, page 36.
90% of patients have no known family or genetic history.
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Cedars-Sinai is a national leader in providing highquality, patient-centered healthcare encompassing primary care as well as specialized medicine and conducting research that leads to lifesaving discoveries and innovations.
Since its beginning in 1902, Cedars-Sinai has evolved to meet the healthcare needs of one of the most diverse regions in the nation, continually setting new standards in quality and innovation in patient care, research, teaching and community service. Today, CedarsSinai is widely known for its national leadership in transforming healthcare for the benefit of patients. Cedars-Sinai impacts the future of healthcare
globally by developing new approaches to treatment and educating tomorrow’s physicians and other health professionals. CedarsSinai demonstrates a longstanding commitment to strengthening the Los Angeles community through wide-ranging programs that improve the health of its most vulnerable residents.
Cedars-Sinai maintains the following goals for biomedical research: Sustain a program of outstanding biomedical research, healthcare services and nursing research by fostering basic and clinical investigation in the prevention and causes of medical illnesses, their pathologic mechanisms and diagnoses, and
10% of ALS patients are enrolled in a clinical trial.
Up to 44% of patients are ineligible for clinical trials at time of diagnosis.
the development of cures for the ailments that afflict our society. Translate research discoveries appropriately to a clinical setting. Provide research training opportunities for graduate students and professional teaching programs. Foster the transition of biomedical discoveries to the realms of product development, patient care application and marketing. Provide cross-fertilization and interdependent synergy between the medical center and the biotechnology industry. Protect the rights of human and animal subjects.
Cedars-Sinai is fully accredited by the Association for the Accreditation of Human Research
Protection Programs Inc. (AAHRPP) for assuring protection for human subjects during research. Cedars-Sinai was the first institution in California to receive this designation. AAHRPP is a Washington, D.C.-based nonprofit organization that uses a voluntary, peer-driven educational model to accredit institutions engaged in research involving human subjects.
Cedars-Sinai does not discriminate against any person on the basis of race, color, national origin, disability, age or sex in admission, treatment or participation in its programs, services and activities, or in employment. For further information, please call 310-423-7972.
At Cedars-Sinai, representation matters. We want our faculty and staff to reflect the communities we care for—because the only thing better than a provider who listens is a provider who can relate.
Dr. Dellapiana is one of many helping us in this effort. We believe it’s important to recruit diverse trainees into our programs so patients can feel reassured, safe and heard.
Learn more at cedars-sinai.org
The majority of people infected with the Omicron variant of SARS-CoV-2 didn’t realize they had the virus.
Most people infected with the Omicron variant of SARS-CoV-2 didn’t realize they had the virus, according to a Cedars-Sinai study. Investigators learned that 56% of those surveyed were unaware of their infection and, of that percentage, only 10% reported having any symptoms—which they attributed to a cold or other type of infection. ¶ “We hope people will read these findings and think, ‘I was just at a gathering where someone tested positive,’ or, ‘I just started to feel a little under the weather. Maybe I should get a quick test.’ The better we understand our own risks, the better we will be at protecting the health of the public as well as ourselves,” says Susan Cheng, MD, MPH, MMSc, director of the Institute for Research on Healthy Aging in the Department of Cardiology at the Smidt Heart Institute at Cedars-Sinai and corresponding author of the study. Dr. Cheng is also the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science. ¶ The team is now studying patterns and predictors of reinfections and their potential to offer long-lasting immunity to SARS-CoV-2. In addition to raising awareness, this information could help individuals enhance management of their long-term risk.
This year, Cedars-Sinai welcomed its most diverse class of residents ever.
BY JEREMY DEUTCHMAN
Advancing the boundaries of medicine is not a singular, specific event; rather, it unfolds over time. So, too, efforts around diversity, equity and inclusion (DEI) at Cedars-Sinai: We are making important strides even as we recognize that there is work yet to be done.
This year, Cedars-Sinai welcomed our most diverse class of residents ever, and we have innovated with the launch of new initiatives like the DEI Ambassadors program, which engages residents from underrepresented groups through mentorship, outreach and education.
“Our institution is committed to recruiting a more diverse class of residents and also to making sure those residents feel a sense of belonging once they get here,” says Mark Noah, MD, associate dean of Medical Education in Academic Affairs and the Melvin Brody, MD, Chair in Medical Education. “Right now, approximately 14% of students who match in our residency programs come from communities that are historically underrepresented in the field of medicine. We’re focused on pushing that number forward every year.”
HOMETOWN: VEREENIGING, SOUTH AFRICA
“I chose Cedars-Sinai because it’s an amazing, world-renowned hospital and because L.A. is a great, diverse place to live. My program has been extremely supportive of its minority participants. I’ve been connected with several surgeons of color who have become my mentors. As a DEI ambassador, I’ve had opportunities to help boost recruitment of historically underrepresented minorities in the Department of Surgery and to engage with diverse middle and high school students, introducing them to career paths in medicine they might not think are open to them.”
Nicole Mitchell, MBA CHIEF DIVERSITY AND INCLUSION OFFICER
“Our residents are the future of medicine, and in one of the most diverse cities in the world, we believe that future should reflect what our patients look like. We want patients to feel seen at Cedars-Sinai, no matter their background. When your doctor walks into the exam room and looks like you or speaks your language, it may encourage you to open up about your health-related concerns. That’s at the heart of our efforts around DEI: removing barriers and meeting patients where they are.”
Stephen Avila, MD NEUROLOGY RESIDENT
HOMETOWN: MODESTO, CALIFORNIA
“I am a first-generation physician from a Mexican American family. From my standpoint as a resident of color and DEI ambassador, this is one of the rare places I have worked where I don’t feel like a minority. Cedars-Sinai’s commitment to diversity is very evident in our resident, attending and administrative population. The patients we serve deserve to be understood and cared for with excellence, and I believe our emphasis on DEI throughout the years is something that has allowed us to reach these goals.”
Black and Latina patients are less likely to undergo minimally invasive procedures for uterine fibroids.
Black and Latina women are much less likely than white women to undergo minimally invasive procedures for uterine fibroids, Cedars-Sinai research finds. Published in the Journal of Minimally Invasive Gynecology, the retrospective cohort study examined the records of 1,311 women who were treated between 2015 and 2020.
Previous examinations of racial disparities in gynecologic surgery have focused on hysterectomies. But this new study addressed surgery for uterine fibroids, including myomectomy, which removes fibroids but keeps the uterus intact, as well as hysterectomy.
The findings are important “because we know that Black women are disproportionately affected by fibroids,” notes Matthew Siedhoff, MD, MSCR, vice chair of Gynecology at Cedars-Sinai and the study’s principal investigator.
“Educating both practicing gynecologists and patients in the community about the value and availability of minimally invasive procedures is an important step we can take now to address these racial disparities,” says Cedars-Sinai gynecologist Rebecca Schneyer, MD, lead author of the study.
Pioneering research may lead to an accurate predictor of heart failure risk in women.
Processes leading to heart failure differ by gender, according to research conducted by Cedars-Sinai investigators. The disparity stems from cellular-level differences in the heart muscle and surrounding tissue caused by fibrosis, according to cardiologist Alan Kwan, MD, lead author of the study, which was published in the journal Heart. ¶ “We have known for some time that, with aging, women’s hearts tend to have a thicker wall, shrink more in size, and pump faster and harder than men's hearts,” Dr. Kwan says. “While these structural differences
can be seen with the naked eye, it requires more sensitive and detailed imaging to understand how these changes lead to, or result in, heart failure.”
The discovery was made possible by an innovative cardiacimaging technique devised by study senior author Susan Cheng, MD, MPH, MMSc, director of the Institute for Research on Healthy Aging at the Smidt Heart Institute. The method measures high-spectrum signal-intensity coefficient in cardiac ultrasound images to detect microstructural changes that would otherwise remain invisible.
Using this novel technique, researchers extracted unprecedented levels of data from the ultrasound images of 2,511 adult hearts. The images used were from the National Institutes of Health’s Framingham Offspring Study. “We evaluated whether a measurement of cardiac microstructure could predict heart failure,” says Dr. Cheng, who holds the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science.
These microstructural changes, likely the result of greater amounts of fibrosis, predicted future diagnosis of heart failure, especially in women. Dr. Kwan notes that this process may be a key reason why women, as they age, are more likely than men to develop heart failure with preserved ejection fraction (HFpEF).
The team now plans to expand their cardiac-imaging capacity to further elucidate personalized risks of heart disease. Their goal is to develop better diagnostic tools and more precise treatments for HFpEF and other cardiac conditions.
Women have long reported higher stress levels than men. This may be due in part to psychological and biological gender differences in the stress response. The resulting higher cortisol levels in women may lead to anxiety-related weight gain and cause obesity-associated metabolic disturbances.
But what causes these higher cortisol levels in women? And what does the human sense of smell have to do with it? These are two of the questions that Celine Riera, PhD, research scientist at
Cedars-Sinai’s Board of Governors Regenerative Medicine Institute, hopes to answer with her project, “Influence of Olfactory Stressors on Female Metabolic Health,” which received a grant from Cedars-Sinai’s Center for Research in Women’s Health and Sex Differences.
Dr. Riera’s research attempts to identify molecular components responsible for generating elevated stress in women. The project evaluates the role of sex-based differences in pathways associated with
stress perception in metabolic health, specifically examining the roles of the olfactory senses and the hypothalamus, a brain region that controls hormones.
“We know that the predator odors engage neurons to adjust physiological responses in order to survive,” Dr. Riera says. “However, once animals realize that they cannot evade this stress, their metabolism becomes lower and, quite remarkably, females’ metabolisms become much lower than males’. This hypometabolic response is associated with potential higher weight gain in females.”
By better understanding the connection between olfactory sensing, elevated cortisol and how it’s regulated in the brain, Dr. Riera aims to address an understudied aspect of women’s health.
“Women deal with all kinds of stressrelated health problems,” Dr. Riera says. “It’s amazing to see how much higher stress can be in women compared to men. Research on women’s specific stress and adaptation to chronic stress has been overlooked, and we need to generate proper models to solve these questions.”
ROSANNA TURNERWhile women and men are at equal risk of sudden cardiac arrest, women are less likely to be resuscitated. Cedars-Sinai researchers are investigating whether a simple change to CPR training—adding breasts to CPR mannequins—will help. “CPR has only been taught on ‘male’ mannequins, leading to a host of trainees who, unfortunately, are only taught how to recognize physical landmarks and to perform compressions on someone who is flat-chested,” says Tara Cohen, PhD, director of Surgical Safety and Human Factors Research. The investigators commissioned female mannequins with moderately sized breasts and added them to healthcare providers’ CPR training courses. The team is observing physicians’ techniques with these new mannequins and their flat-chested counterparts to identify any sex-related differences that affect treatment. “Think of this as our opportunity to save lives,” says researcher Pooja Nawathe, MD, associate director of the Congenital Cardiac Intensive Care Unit. “To ensure we move toward healthcare equity, understanding any sex-related difference that exists in CPR treatment is crucial and has important implications for future training for all healthcare professionals.”
LISA FIELDS
Mass spectrometry instruments uncover new cellular insights.
BY CASSIE TOMLINDisease originates within a single cell—an infinitesimal universe of possibility. At Cedars-Sinai’s Board of Governors Innovation Center (BOGIC), experts are helping develop cutting-edge mass spectrometry instruments and other approaches that analyze cell behaviors—and the tens of thousands of proteins that underlie them. Investigators are exploiting rapid advances in technology to uncover new insights, including the earliest indications of cellular dysfunction.
“This is a huge breakthrough—the concordance of faster, more automated technology and our understanding of study design,” says Jennifer Van Eyk, PhD, director of the Advanced Clinical Biosystems Institute and the Erika J. Glazer Chair in Women’s Heart Health. “We’re learning really fast.”
IsoPlexis
This single-cell proteomics device scores the functional status of live, individual immune cells by measuring their cytokine secretion. A BOGIC group is using the IsoPlexis to support chimeric antigen receptor (CAR) T-cell therapy.
Echo Liquid Handler
Access Laboratory
Workstation
This robotic system uses acoustic supersonic sound to dispense the smallest droplets of liquid for analysis by the mass spectrometer. It creates accurate samples at only half a microliter—a volume
Dr. Michelle Kittleson’s new book provides a how-to for practicing medicine in a way that centers patients.
BY AMY PATURELWith Mastering the Art of Patient Care, Michelle Kittleson, MD, PhD, wrote the book she wishes she’d had when she embarked on her medical career. Dr. Kittleson starts by tackling the most difficult questions in the field.
How do we help trainees develop the competency to make decisions under duress and act as compassionate caregivers? How can we mentor young physicians on processing grief, overcoming the sting of mistakes and setting boundaries to preserve their wellbeing? How do we make space for family life and a medical career?
undetectable to the eye—without sacrificing any of a cell’s proteins. The machine also allows BOGIC investigators to scale up throughput to thousands of cells a day, particularly useful for drug screenings.
timsTOF SCP
The most sensitive mass spectrometry machine available measures thousands of proteins in a single cell, elucidating their pathways and disease processes. A BOGIC team is studying proteins expressed by cardiac cells to uncover mechanisms associated with heart disease.
“None of my academic accomplishments prepared me for mastering the art of patient care,” Dr. Kittleson writes. With this book, she provides a road map for physicians at every stage of their career—from surviving medical school to mentoring the generation of physicians that come after them. And by recounting her trials and triumphs, she gives readers an unexpected gift: an in-depth view of the human side of a career in medicine.
“Medical training is all-consuming and at times demoralizing,” she writes. “This handbook is my contribution toward making it better … my system of surviving and thriving in medicine.”
The book evolved from the pearls of wisdom Dr. Kittleson amassed during her years in medicine
Mastering the Art of Patient Care
By Michelle Kittleson, MD, PhD, director of Postgraduate Medical Education in Heart Failure and Transplantation at the Smidt Heart Institute Springer, 2022 209 pages“None of my academic accomplishments prepared me for mastering the art of patient care.”
DR. MICHELLE KITTLESON
A hypothesis developed by Cedars-Sinai scientists and published in Frontiers in Immunology may illuminate why some people’s COVID-19 symptoms persist long after their initial infection. According to the researchers, the spike proteins that enable SARSCoV-2 to latch onto cells may contain neurotoxin motifs able to cross the blood-brain barrier and damage brain cells. This could explain brain fog and other neurological symptoms associated with COVID-19 and long COVID in children and adults.
According to other studies by Cedars-Sinai investigators, people with long COVID may carry fragments of the virus in their gut or other parts of their bodies months after initial infection. Continuous exposure to motifs that lodge themselves in different parts of the body and have superantigen-like properties may cause autoimmune symptoms in people with long COVID and multisystem inflammatory syndrome.
and dispensed to students and colleagues alike. In April 2019, Dr. Kittleson took to Twitter with #kittlesonrules, a compendium of her thoughts on how to improve patient care, such as the nuts-andbolts of heart failure management, optimizing communication with patients and colleagues, and learning from mistakes.
Mastering the Art of Patient Care reminds readers that while diseases may become routine with experi-
ence, patients must not. The book pushes physicians to look beyond blood levels, test results and vital signs, to know the person behind the numbers so they can provide the best care.
Ultimately, Dr. Kittleson’s book makes the case that practicing medicine is about relationship building.
“Trust and confidence are the cornerstones of the patient-physician relationship,” she writes. “This relationship is not science; it is an art.”
Hypertension more than doubles the risk of Omicron-related hospitalization, even in people who are fully vaccinated and boosted, according to research led by Smidt Heart Institute investigators. The study, published in Hypertension, also notes that obesity and diabetes are less strongly associated with hospitalization during the Omicron surge, despite being identified as risk factors early in the COVID-19 pandemic. The authors note that the biological processes that trigger more severe COVID-19 in people with hypertension require elucidation in order to reduce such risk.
Sex may be an important factor in antibiotic therapy.
Antibiotics have sex-specific effects on the gut microbiome of male and female laboratory animals, according t o Cedars-Sinai research. The findings, published in Frontiers in Microbiology, have implications for how such drugs are used in humans to treat or prevent bacterial infections.
“Interestingly, male and female rats respond differently to antibiotics during treatment, and their microbiome also showed different patterns of recovery after treatment,” says endocrinologist Ruchi Mathur, MD, the study’s principal author.
Investigators from CedarsSinai’s Medically Associated Science and Technology (MAST) Program compared the gut microbiome composition of male and female rats before, during and after treatment with broad-spectrum antibiotics.
“These results show that sex is a variable that might be an important consideration when prescribing antibiotic therapy,” explains MAST Director Mark Pimentel, MD, co-author of the study.
Neurons are stimulated to study epilepsy.
Cedars-Sinai scientists have created biorealistic, multimodal and data-driven computer models of human brain cells to form a complete picture of the electrical, genetic and biological changes brought about by epilepsy. Such models can be used to test hypotheses that would otherwise require dozens of experiments. “These artificial intelligence models capture a repertoire of what we know about neurons, including their shape and the timing and speed of the electrical signals that neurons fire to communicate with each other, which is considered the basis of brain function,” says Costas Anastassiou, PhD, research scientist in the departments of Neurology and Neurosurgery and the Board of Governors Regenerative Medicine Institute and senior author of the research, which was published in Cell Reports. The team employs high-performance computing and artificial intelligence to study brain cell function and disease.
Recent research co-led by CedarsSinai scientists has identified an intestinal component that plays a critical role in repairing damaged tissue. The investigators found that endothelial cells in the lymphatic vessels produce molecules essential for maintaining and regulating intestinal stem cells and tissue.
Lymphatic molecules express several factors, including the gene RSPO3, which supports stem cell function. To determine the gene’s role in intestinal stem cell regulation, researchers deleted the gene in mice. Using single-cell sequencing, they observed that the lack of RSPO3 hindered recovery by
reducing the number of stem cells and progenitor cells.
“This discovery showed us that lymphatic endothelial cells are a key component of the intestinal niche and essential for intestinal repair after cases of damage, such as from chemotherapy,” says Ophir Klein, MD, PhD, executive director of Cedars-Sinai Guerin Children’s, the David and Meredith Kaplan Distinguished Chair in Children’s Health, and senior author of the study, which was published in the journal Cell Stem Cell. “Deciphering the mechanisms that explain how the ecosystem that supports stem cells works will help lay the foundation for future discoveries that could one day lead to therapeutic strategies to repair damaged tissue.”
says Dr. Ophir Klein, senior author of the study and executive director of Cedars-Sinai Guerin
“It’s important for us to understand niches and how lymphatics communicate with stem cells as part of the niche,”
Children’s.Cedars-Sinai investigators have created biorealistic and complex computer models of individual brain cells—in unparalleled quantity.
Learning the history of medicine can point the way to a better future.
BY SARAH SPIVACK LAROSA
Even if the letters “PhD” or “MD” follow your name, your training in science or medicine may not be complete. Not only is the history of medicine fascinating in its own right, but it also can uproot assumptions, disrupt bias and point the way to a better future, says medical historian Gideon Manning, PhD, director of the History of Medicine Program in the Department of Biomedical Sciences. ¶ Cedars-Sinai houses the only substantive history of medicine program embedded within an independent academic medical center. The research group has become a scholarly destination welcoming speakers and researchers from around the world. ¶ Here, Dr. Manning makes a strong case for casting your gaze back to earlier days of science and medicine.
How can clinicians and investigators benefit from understanding the history of medicine?
Dr. Gideon Manning: We take many things for granted today concerning the organization of medical knowledge, the benefits of technology, who should be a physician and even who qualifies as being ill. These and similar assumptions inform the practice of
medicine and biomedical research, as well as patient experiences, and each of these assumptions has a history. When you look carefully at the emergence of a scientific medical culture, you see that it is a human creation that took shape over a long period of time.
Let me give you an analogy. Medicine is like a building that has taken generations to complete, like one of Europe’s Gothic cathedrals. If you have the right training and look carefully at such a building, you will find evidence of the builders’ hesitation or incompetence, and you’ll notice some of the parts don’t quite fit together because
there were different builders over time with different priorities and interests who even used different building techniques.
All to say, studying the history of the building can help us understand and explain why the building looks as it does and why the floors sometimes creak and the ceiling occasionally leaks. In medicine, history can illumi -
nate why some things don’t work so well today and what might be changed in the future because it needn’t be the way it is.
Take the case of sickle cell anemia: We effectively knew all the genetic information we needed to know about the disease even before the Human Genome Project was complete. But research into the condition wasn’t actively pursued because it predominantly affects people of recent African descent, and they haven’t had a sizable access to clinical trials. We need more diversity and inclusion in medical research to fix the problem.
There are also long-standing disparities in heart health between men and women, an issue that CedarsSinai has been working hard to correct. Information about whose voice matters, who gets sick with what disease, or simply who becomes a scientist or a physician are at the root of many such disparities.
The history of medicine is, in part, about bringing attention to the contexts in which these assumptions have taken hold, and, in so doing, directing us to those places where the floors creak and the roof leaks in modern medicine. Historians of medicine, like the rest of us, are out to fix these disparities. We just carry slightly different tools in our toolbox when compared to clinicians and other investigators.
Reclaiming the Joy of Medicine: Finding Purpose, Fulfillment and Happiness in Today’s Medical Industry
By Alen Voskanian, MD, MBA, Medical Director, Cedars-Sinai Medical GroupNew Degree Press, 2022
190 pages
Physician burnout is at an all-time high because of widespread fatigue and work-related distress caused by the COVID-19 pandemic.
As many physicians nationwide are questioning their longterm commitment to medicine, Alen Voskanian, MD, MBA, shares a hopeful perspective, explaining how he found purpose and meaning as a physician after experiencing work-related burnout 20 years ago.
After Dr. Voskanian chose to leave a grueling position that required him to see patients every 10 minutes and handle an avalanche of bureaucratic tasks, his passion for medicine reignited. Now at Cedars-Sinai, he’s taken on an administrative role to help other physicians rediscover their love of medicine, hoping to change policies that “conflict with some of the core principles of being a physician—namely the autonomy and flexibility to choose the best care for our patients.”
Dr. Alen Voskanian experienced physician burnout 20 years ago. In his new book, he explores reasons for burnout and suggests ways to conquer the problem.
Dr. Voskanian shares his personal journey, plus stories from other physicians who have overcome burnout. Instead of suggesting that his colleagues strive to become more resilient, he advocates for widespread change from healthcare organizations, which should “focus on removing the unnecessary tasks that lead to death by 1,000 paper cuts.”
He suggests that physicians may benefit from remembering why they entered their field, choosing positions that align with their values and “realizing what is and what is not in our control— and not worrying about the latter.” It may not be the first time doctors have heard such advice, but it’s well worth reiterating, whatever field you’re in.
Dr. Alen Voskanian’s new book aims to help physicians reclaim their passion for medicine.
“History of medicine is one of many areas in the humanities and the arts that promotes the wellbeing of someone at work, but also more generally.”
DR. GIDEON MANNING
Counting lymph nodes provides a reliable predictor of patient tumor progress.
Counting metastatic lymph nodes provides a reliable predictor of patient outcomes for nearly all solid cancers, according to research at CedarsSinai Cancer. “We found that this simple process is much more effective for determining solid tumor prognoses than all other factors used today,” says radiation oncologist Zachary S. Zumsteg, MD, who led the study. “It should be the backbone of nodal staging because it is the best predictor of mortality, irrespective of the disease site.”
The research, published in the Journal of the National Cancer Institute, analyzed data from the National Cancer Database and the Surveillance, Epidemiology and End Results registry. The team examined outcomes for more than 3 million patients. Focused solely on survival, the findings were validated across 16 of the most common solid cancers in the United States.
In addition to accuracy, the method has the advantage of being easily adopted. “Lymph node counting is possible in virtually all medical settings, including resource-poor countries,” notes radiation oncologist and study co-author Anthony T. Nguyen, MD, PhD.
Recent studies of bladder cancer led by Cedars-Sinai investigators have revealed predictive biomarkers for therapeutic effectiveness in addition to addressing gender and racial disparities in patient outcomes.
Research published in the Journal of the National Cancer Institute identified genetic signatures that could be used to predict how bladder tumors and other cancers will respond to immunotherapy. Led by Director of Cedars-Sinai Cancer Dan Theodorescu, MD, PhD, the PHASE ONE Foundation Distinguished Chair and director at the Samuel Oschin Comprehensive Cancer Institute, the project identified four unique gene signatures modulated by genes called discoidin domain receptor tyrosine kinase 1 and 2 that were closely associated with tumor response to immunotherapy.
Co-authors Keith Syson Chan, PhD, and Sungyong You, PhD, examined these genetic signatures across multiple cancer types using data from The Cancer Genome Atlas. “The next step is to validate the predictive abilities of these signatures on additional samples from prospective clinical trials,” Dr. Theodorescu notes.
Another study, published in Science Immunology, may explain why men carry a higher risk of bladder cancer than women.
Xue Li, PhD, and colleagues discovered that androgens induce CD8+ T-cell exhaustion, making them less effective in eliminating tumor cells. Using a bladder cancer mouse model, the investigators found that androgen deprivation therapy reduced bladder tumor size
in male mice and improved the efficacy of immunotherapy.
“These findings suggest that male patients may benefit more from immunotherapy when combined with androgen deprivation therapy,” Dr. Li says.
Additional research headed by Dr. Theodorescu and Dr. You found that gene expression differs by race in patients with high-risk non-muscleinvasive bladder cancer. The discovery, published in Urologic Oncology, arose from studies profiling the gene expression of 14 African American and European American patients.
The team’s analysis found a molecular subtype of bladder cancer to be most common among African Americans and white patients, which has been
previously associated with more adverse clinical outcomes.
The researchers identified 10 genes with higher expression in tumors from African American patients compared to tumors in white patients in two independent cohorts. In these genes, the team saw an overexpression of the protein EFEMP1, which has previously been found to be overexpressed in patients with muscle-invasive bladder cancer.
“Findings suggest a stepwise progression with increased EFEMP1 expression as a plausible mechanism contributing to risk of muscle invasion in African American patients,” Dr. You says, adding that “this mechanism can potentially lead to a new novel therapeutic target.”
Although notochordal cells have long been thought to disappear in childhood, Cedars-Sinai investigators recently found them in a 70-year-old. The research, published in iScience, used single-cell RNA-sequencing technology to identify the cells, which serve as precursors of the intervertebral disc and can therefore be used as novel markers to identify different cell subtypes. This paves the way for developing therapies that target these cells to rejuvenate the intervertebral disc and relieve severe back pain with a minimally invasive procedure. This, in turn, could help patients avoid major surgery and potentially addictive drugs.
Understanding the cellular landscape and the heterogenicity of the intervertebral disc and development processes can help lead to the development of more targeted therapeutics for lower back pain.
“These findings suggest a stepwise progression with increased EFEMP1 expression as a plausible mechanism contributing to risk of muscle invasion in African American patients. This mechanism can potentially lead to a new novel therapeutic target.”
DR. SUNGYONG YOU
Health equity requires that physicians start seeing patients differently.
BY CHRISTINA HARRIS, MD, Cedars-Sinai Vice President and Chief Health Equity Officeratient-centered care” is one of the most commonly used phrases in medicine. It’s what physicians believe in and what we promise to deliver. Yet we cannot provide patient-centered care unless we grapple with one of the most urgent challenges in healthcare today: health equity. As society becomes more cognizant of the many dimensions of diversity—especially in a highly dynamic region like Southern California—and as we begin to grasp the sheer scope of inequity affecting millions of our neighbors and patients, healthcare providers can help shift the culture. Only if we make changes to our practice and our mindset can we claim to deliver truly patient-centered care. ¶ Race, ethnicity, gender identity, sexual orientation, socioeconomic status and differences in ability are among the traits long
associated with barriers to quality care and poor outcomes. This can manifest as inadequate treatment for serious illnesses, higher risk of chronic disease and shorter lifespans.
But the consequences go beyond medical problems. While illness and injury don’t always prevent people from achieving their goals, good health can help facilitate educational and professional progress. Conversely, poor health can exacerbate challenges in every area of life, including school, training and gainful employment. The risks are especially egregious in a society where quality healthcare isn’t afforded to everyone. Inequity in healthcare perpetuates and amplifies inequality.
To be sure, achieving equity in healthcare lies beyond the power of the individual clinician. Historical forces have given rise to systemic barriers that no single doctor can overcome. But every patient and every visit offer an opportunity to advance health equity through the care we deliver.
To make a difference, physicians must start by practicing self-awareness. Perhaps it sounds paradoxical, but being patient-centered means looking closely at ourselves, because that’s how we uncover our assumptions and biases— the way we fill in the gaps of someone else’s story. These shortcuts are magnified in the clinic setting under the time pressures of modern medicine. As patients speak, our minds are already searching for patterns and clues that will help us determine the next step. The questions we ask—and how we hear the answers—are based on associations that have been cultivated throughout our lives. Some are based on our experience and training, but others are born of false narratives acquired by living in a country built upon inequities and uneven playing fields. We must learn to tell the difference. I recall a patient who presented as a highly organized and capable individual with impressive health literacy. One day, he admitted to being so far behind on his rent that he was close to being evicted, and I realized I had made assumptions that could have impacted the care I delivered. None of us are immune to bias. I find it helpful to recall the following guidelines.
First, there are no patterns to be found in the person, only in the illness. People cannot be understood on the basis of characteristics like skin color, age, sexual orientation or differences in abilities. Unlike the medical conditions we
encounter, an individual does not have a limited, knowable number of trajectories. Our patients are infinitely variable, which means we must remain infinitely curious.
Second, remember the double meaning of the phrases seeing patients and practicing medicine. Seeing someone means clearing your mind of what’s assumed to make room for what’s true. Likewise, a medical practice is where we work, but practicing also means to do something repeatedly to improve. Every appointment is a chance to practice self-awareness: What did I assume about the patient because they used a wheelchair/spoke with an accent/didn’t fit a gender archetype/acknowledged drug use/were my grandfather’s age?
At the same time, self-awareness isn’t enough. Our industry’s definition of healthcare is biased, too, targeting medical conditions with medical solutions. As important as that is, equity means going beyond the medical and understanding the factors that set people up for health challenges— including social determinants like housing, food security, income, transportation and safety. These factors can only be addressed by multidisciplinary teams, including community groups.
Health equity is about giving people the opportunity to achieve optimal health regardless of their social standing. As a society, we have failed too many for too long. But if we commit to making changes, I believe we can finally move that needle. We have much talent and skill to draw upon. In the words of the first youth poet laureate in L.A. and the nation, Amanda Gorman, “we are not broken but simply unfinished.”
“ Inequity in healthcare perpetuates and amplifies inequality throughout society.”
Guerin Children’s experts offer insights into research and treatment that seek to serve patients from gestation to graduation.
BY NICOLE LEVINE
Discoveries in pediatric diseases could hold answers to some of the biggest questions in medicine. ¶ Experts at Cedars-Sinai Guerin Children’s are committed to reshaping the understanding and treatment of a spectrum of diseases. Supported by a $100 million gift from the Shapell Guerin Family Foundation, Guerin Children’s has an ambitious vision for children’s healthcare. It will couple a scientific mission with seamless and innovative clinical care that serves patients from their first breath to their first steps into adulthood. ¶ Guerin Children’s physicians share their hopes for the program and their vision for the next wave of breakthroughs in pediatric medicine.
PEDIATRIC NEPHROLOGIST
EXPERTISE: KIDNEY TRANSPLANTATION
Sometimes, pediatrics can get buried in the big adult world. Being at a medical center with adult and pediatric patients turned out to be a great advantage because of the collaborations that are possible. For example, I was covering transplants in adults on weekends, and I saw that they were doing a test to predict early detection of rejection—which we’ve never had for children. It wasn’t approved by the Food and Drug Administration yet for pediatrics, which often happens with drugs, testing and other advances. We developed a memorandum of understanding with the company that makes the test, and they gave us 150 testing kits. We enrolled 67 patients in our study and found that this test for donorderived, cell-free DNA is an excellent predictor of organ rejection in children.
CHAIR OF PEDIATRICS
EXPERTISE: INFLAMMATORY BOWEL DISEASE (IBD)
In our field, we get excited about the success of new medications, but if you look in detail, most of these successes are in the 30% to 40% range. That’s not good enough. We need to reach more patients, get them into remission and achieve that deep healing of their tissues, so they’re not at risk of long-term complications. That’s why it’s so important to match the right patient at the right time with the right treatment. It’s one of the reasons it’s important to study children diagnosed with IBD before age six. They’re a unique cohort with a genetically driven disease that can be more severe. Our collaboration with our Board of Governors Regenerative Medicine Institute is seeking novel ways to study these patients and better understand how to effectively treat IBD. We work with teams in regenerative medicine, genomics, proteomics, and microbiome in treatment and research. Our doctors, nurses, dietitians and social workers consider every aspect of what our patients are eating, how they are feeling and their mental health alongside medical interventions.
Andrew Freedman, MDWALTER AND SHIRLEY WANG CHAIR
IN PEDIATRIC SURGERY
EXPERTISE: PEDIATRIC UROLOGY
When we do research in pediatrics, there are several factors to consider, and we often must study the impact to the entire family. We feel strongly that we need uniquely pediatric research.
We say all the time that kids are not just little adults, and so the science must be specific to them. Guerin Children’s is wellpositioned because we have access to all the core resources of Cedars-Sinai: We have a Board of Governors Regenerative Medicine Institute, Department of Computational Biomedicine, biostatistical support, biobanks and genomic support—all the advanced, high-level tools we need and an opportunity to use them to focus on the needs of kids.
We’re building on the Cedars-Sinai model of care, and that is premised on excellence, innovation and research.
Tyler Pierson, MD, PhDPEDIATRIC NEUROLOGIST
EXPERTISE: PEDIATRIC NEUROLOGY, REGENERATIVE MEDICINE/STEM CELLS
CENTER FOR THE UNDIAGNOSED PATIENT
Studying rare diseases doesn’t just help those who are directly affected by them. In fact, the study of a rare disease led to the development of statins, which revolutionized how we treat heart disease, the No. 1 cause of adult death in the world.
Most rare diseases are genetic, and most people with these conditions are children. Guerin Children’s has the expertise across many disciplines to facilitate important discoveries and potentially find solutions for problems that affect patients of all ages.
An example of this is the work we’re doing with GATAD2B-associated neurodevelopmental disorder, or GAND. When I first started working with patients with GAND, there had only been about four cases of it in history, and now we’ve identified about 250. I’ve worked with Helping Hands for GAND, a family research group, to help them identify and register other patients so we can better study the condition. In the laboratory, we’re working with multiple models to better understand how the brain organizes itself and how GAND affects that. We’re using patient-derived induced pluripotent stem cells to create cerebral organoids, and we can compare those to what we see in a mouse cortex to identify which genes the GATAD2B protein is affecting. These new technologies allow for better disease-modeling tools that could make a big difference for understanding and treating rare diseases.
Eugene Kim, MDDIRECTOR, DIVISION OF PEDIATRIC SURGERY
EXPERTISE: SURGICAL ONCOLOGY
One of the game-changers for children with cancer is immunotherapy. We’re looking at drugs as well as methods to turn on the immune system to fight the cancer within the body, like monoclonal antibody treatments and reprogramming immune cells. We’re seeing novel results, and there’s still a lot to discover.
I treat neuroblastomas—these massive tumors that can grow inside children and spread to organs and bone. Removing them can take 10 to 16 hours in surgery. Often, we find we can clear cancer from the abdomen, but it comes back to the bone marrow and other areas we cannot control. We’re working to develop treatments to prevent that spread, seeking new pathways and new drugs that will prevent cancer recurrence. As surgeons, we try to leverage surgical techniques to create models that will really mimic the human condition.
“Sometimes, pediatrics can get buried in the big adult world. Being at a medical center with adult and pediatric patients turned out to be one of our greatest advantages because of the collaborations that are possible.”
DR. DECHU PULIYANDA
“We’re going to be able to expand into areas that require multidisciplinary teams, and that’s exciting for me. We’re building on the CedarsSinai model of care, and that is premised on excellence, innovation and research.”
DR. ANDREW FREEDMAN
Dr. Francesco Boin, director of the Scleroderma Program and member of the Kao Autoimmunity Institute, shares his vision for the future.
BY CASSIE TOMLINFrancesco Boin, MD, is driven by the tangled intricacies of his work in scleroderma, a chronic autoimmune condition that can cause debilitating scarring of skin and internal organs. The multisystem disease is complex and difficult to study, says Dr. Boin, director of the Division of Rheumatology, director of the Scleroderma Program at the Kao Autoimmunity Institute, and the Cedars-Sinai Chair in Rheumatology. But faced with a lack of treatments and high patient mortality, Dr. Boin and his colleagues can make enormous progress through creative scholarship and lifelong bonds with patients. ¶ “Our work is the epitome of internal medicine,” Dr. Boin says. “This disease exalts the power of clinical observation—it requires a thorough and investigative clinical approach.” ¶ Here, Dr. Boin shares his most pressing research questions and how he and his team are poised to answer them.
Why is it so important, at our clinical centers of excellence, to integrate patient care and autoimmunity research? We do our best work by creating a clinical environment that allows us to learn about diseases directly from patients and immediately generate important research questions for the scientific team. The Kao Autoimmunity Institute is recruiting the most talented scientists to tackle difficult research questions and unravel the disease mechanisms underpinning rheumatic diseases. I’m humbled and excited by how our patients support our efforts: 99% participate
in research. Having this kind of partnership with patients helps us define high-priority areas of research.
In our model, people at the laboratory bench constantly interact with people at the bedside; there is mutual enrichment. This is what defines us and guides us as we recruit new leading medical scholars. The integration of research and care offers the greatest promise to deliver a cure for these diseases.
Which of your research questions are generated from directly observing patients? In clinic, I’ve learned that every patient is unique.
For example, not everyone with scleroderma will develop severe lung damage, but we don’t have good predictors of disease progression and outcomes. This motivated us to ask: How can we determine who is at risk for the most dire complications—what are the early hints that disease
may be progressing? We identified a unique subset of immune cells that appear more frequently in patients who develop damage and loss of lung and heart function. Our U.S. Department of Defense-funded study, in collaboration with scientists at Harvard University, examines the characteristics of these cells and whether we can recognize them when the disease is still in early its stages.
We’re also trying to unravel the deeply intertwined relationship between a genetic predisposition for scleroderma and the body’s response to environmental cues like infection and pollution, so we can identify who is most vulnerable.
How can we best improve the lives of patients with scleroderma? We need to diagnose the disease early before the damage is irreparable and design more personalized treatment plans that are respectful of each unique patient. This science is critical—often, we use medications that have a broad effect, with side effects that can be worse than the disease itself. It’s like trying to kill a fly with a cannonball. Wouldn’t it be better if it were more like laser tag—if we could direct the weapon only at the cells we know are responsible for the disease?
And we need to address the burden of this chronic, incurable disease on patients’ quality of life. So many of the devastating implications are on a personal, social level. When you look in aggregate at the factors that determine how a person experiences their illness, physicians are an integral part of that journey. We must really listen to understand and address what is most challenging for the individual and their loved ones.
“ The integration of research and care offers the greatest promise to deliver a cure to these diseases.”
Powerful promise hangs in the balance with potential peril as hospital systems integrate artificial intelligence into research and patient care. Physicians and investigators endeavor to collect exhaustive data—and scrub it clean of bias—to feed clinic-focused machine-learning tools. AI’s big boom comes with big responsibility to develop fair, accurate algorithms that do no harm. Can scientists harness the revolutionary power of AI while maintaining humanity in healthcare?
It’s
By NICOLE LEVINE Illustration by KIRSTEN ULVEARTIFICIAL INTELLIGENCE HELPS schedule hospital staff, assign beds, guide robotic surgery, and analyze genetic and imaging tests—while reshaping scientific discovery. Since the 1950s, when an artificial intelligence-driven computer successfully played a game of checkers, AI has hibernated through winters of little progress and boomed through scientific summers of advances. Now, the endless summer of AI has arrived—for healthcare as well as virtually every other industry. Poised at a crossroads where AI could push care in a direction that is patient-driven—or could perhaps generate distrust—it’s the human factor that matters most.
“In this endless summer, the ques-
tion is how can we harness the power of AI so that it can make the care of our patients better, more accurate and more efficient?” says Sumeet Chugh, MD, director of Cedars-Sinai’s Division of Artificial Intelligence in Medicine. “To answer that question, we need doctors and researchers dedicated to keeping patients at the center of AI development. So much AI has come from big technology and has not been conceived and born in a health system.”
AI has powerful potential to assist scientists in making groundbreaking medical breakthroughs and free up doctors to spend more time focusing on patients. To unlock that potential requires partnerships that span medical and technological disciplines, and a commitment to leverage only unbiased, comprehensive data. Health systems must invest resources to move to the front lines of these innovations—to help shape the tools of healing and discovery, Dr. Chugh says.
Creating an AI algorithm with the potential for deep learning—wherein it continues to learn and evolve as it digests more data—is complex. Using one is not. From a technical standpoint, such tools are ready to proliferate to the average clinical computer workstation as readily as similar technologies have permeated our smartphones.
“We already have the technology to make AI accessible to anybody who wants it,” says Jason Moore, PhD, chair of Computational Biomedicine at Cedars-Sinai. Dr. Moore has spent close to a decade developing tools to make AI accessible and effective for clinicians. “The real challenge is creating trustworthy models that are sound enough to assist in making clinical decisions (see page 30).”
Dr. Moore and his team have already created software that acts as an easy-to-use data science assistant (see sidebar, right). It’s a snap to learn, and Dr. Moore notes that similar tools are also available commercially.
“The struggles with putting AI into clinical practice are not technological,” Dr. Moore says. “It’s the broader questions—like how to make sure you’re addressing the bias in the data and that the AI is giving high-quality, clean results.”
Dr. Chugh’s division focuses on deploying AI tools in research and care that are calibrated to patient needs. His group includes clinicians, researchers and machine-learning engineers.
“Because we’re clinicians and scientists who are embedded in healthcare, we can identify where we have gaps in medical knowledge. We use large amounts of data—which
not enough for algorithms to be accurate. They must be trustworthy, explainable and unbiased.
are ethically vetted and secured with appropriate safeguards—to drill down on very specific questions,” says Dr. Chugh, who is also medical director of the Smidt Heart Institute’s Heart Rhythm Center and holds the Pauline and Harold Price Chair in Cardiac Electrophysiology Research. Enhancing diagnostic assessments, improving imaging and predicting sudden cardiac arrest are among the important AI interventions Dr. Chugh’s team is developing (see page 29).
“It’s time to challenge some assumptions and dogma about how we predict and prevent disease, because without doing a more effective job of matching treatments to those who will benefit from them, our healthcare model isn’t sustainable,” Dr. Chugh says. “It’s up to the medical community to drive that. Health systems have an opportunity to pose the right questions and develop AI that keeps patients at the center.”
The one question AI is not very good at answering is a crucial one: Why?
AI has a black box problem, says Dr. Moore. We know the questions being posed and the data fed to the algorithm. We know the predictions and answers the AI tool generates. But in a deep-learning scenario, it can be impossible to determine how it arrived at its answers.
“A clinician must always be able to ask why, and the answer needs to be understood clearly by the providers and by their patients,” Dr. Moore says. “Right now, that’s a major limitation of AI. It’s not good at the ‘why’ question.”
Explainability requires extra effort by an AI tool’s creators to track the algorithm as it iterates and to be able to present the path it took to arrive at an answer.
“If the algorithm is so complex that even the developer cannot understand how it works, it’s not going to be a good candidate for use in healthcare,” Dr. Moore says. “That’s why our teams develop transparent AI systems that encourage the sound and ethical use of the technology.”
In this same critical moment when AI is filtering into wider use, clinicians and scientists are locked in a quest to achieve health equity. Scientists recognize and are addressing the significant role discrimination based on race, sex, sexuality, gender, poverty and other factors plays in health outcome disparities. An algo-
AI tools are part of everyday operations at CedarsSinai, assisting in the lab and the clinic so their human counterparts can work more effectively.
Imagine if every clinician had a data science assistant. With Aliro, they can, says Dr. Moore. Aliro allows clinicians and researchers with no machine-learning or coding expertise to run analysis through a sleek web interface. Anyone who can find their way around a spreadsheet or load a data set into a web browser can master this tool. Aliro learns from experience and remembers every analysis it’s ever completed, allowing it to improve over time.
ALEx is a powerful AI tool aiding Cedars-Sinai professionals in capacities that span many disciplines and departments—from helping with the logistics of placing patients to assisting with research and even finding savings on surgical supplies. Matching resources to ever-fluctuating demands is a daily challenge for medical centers, and ALEx has proved a reliable partner for several years. The AI assistant is used daily in the Capacity Command Center to synthesize thousands of forecasts into useful patterns to aid in determining staffing needs, placing patients, discharge planning and other patient flow operations. During the COVID-19 pandemic, ALEx used public health data to assist with bed planning, staffing, serviceline planning and supply chain needs. ALEx also helped generate models to assist in the transition when the medical center reopened for elective surgeries. ALEx has a role in research, such as predicting which patients are likely to require C-section deliveries (see page 33).
rithm based on data with inherent bias could amplify and magnify those disparities.
“We must always keep the clinician in mind as we develop and evaluate AI tools,” Dr. Moore says. “We need to think first about what’s good for all patients and how we earn the trust of those charged with their health and wellbeing. Our teams are dedicated to capturing the benefits of innovation and applying them equitably.” (See page 28 for insights about optimizing AI for health equity.)
Building AI that will seamlessly blend into the complex workflows of a busy medical center, laboratory or physician’s office and improve the patient experience is key to its adoption, says Michael Thompson, vice president of Enterprise Data Intelligence. That means building programs that span medical and academic disciplines, administration, and technology departments.
“Often, artificial intelligence stops at publishing a paper,” Thompson says. “Many programs are created in universities rather than a hospital setting, causing a massive gap between the mathematical AI models and the people and systems that need to use them.”
One AI tool spanning research and logistical functions at Cedars-Sinai is ALEx, named for “automated learning by example.” ALEx is a helpful colleague, developed to assist in research and fulfill functions that free up nurses and doctors to spend more time with patients. That ALEx was created by and for medical professionals made a difference, Thompson says.
“As we help move AI into a clinical workflow and into a patient setting, our goal always is to make sure that it can add value to patient outcomes. We make sure that the clinician who is using the results of AI knows how to use it appropriately,” he says. “We created a comprehensive strategy and approach to using AI across the board—in patient treatment, in research, in testing and in hospital operations and with our values driving that strategy.”
Managing the human element of AI is essential to deploying it effectively and applying it equitably in healthcare.
“We believe in innovation, in discovery and in moving the needle so the patient benefits,” Dr. Chugh says. “AI is a tool that can do that if— and only if—we keep the core questions we’re asking of it close to the patient.”
Dr. Tiffani Bright believes in AI’s power in medicine, and she believes developers should wield this technology to support health equity.
By NICOLE LEVINE Photograph by BEN ROLLINSTIFFANI BRIGHT, PHD, is a self-described AI champion and skeptic. She works at the nexus of two essential healthcare issues: the profound potential of advancing technology and the importance of health equity.
“I’m a researcher foremost,” says Dr. Bright, a research scientist and co-director of the Center for Artificial Intelligence Research and Education (CAIRE) at CedarsSinai. “You must start there. You must come to the present reality knowing where we are and why patients and doctors can be
distrustful of the guidance AI provides. I remain an AI healthcare evangelist because I see the potential—and I get that hope from a few recent developments.”
One of the key questions doctors and AI experts raise is, “What about the Obermeyer study?” Tell us about that study. In 2019, Ziad Obermeyer was the lead author of a paper published in Science that served as a siren to the entire healthcare informatics community. His study found that a widely used population health algorithm was exhibiting racial bias. By using healthcare costs as a proxy for complex health needs, the algorithm concluded falsely that Black patients are healthier than equally sick white patients and diverted resources from Black patients, exacerbating existing health disparities. We learned a lot from that study, and new best practices emerged.
What are the developments in AI that give you hope that it can enable more people to access equitable healthcare? The American Medical Association has issued guiding principles for developing healthcare AI. First, it must enhance the patient experience of care and outcomes. Next, it must improve population health. It must reduce overall costs for healthcare systems while increasing value. Lastly, it must support the professional satisfaction of healthcare workers. That’s our beacon of hope: AI enabling ethics, evidence and quality.
What human factors must researchers consider when optimizing AI for health equity? I’ve worked in academic settings and also been in industry, where you can get up close with the technology and the developers. It’s very different to be working with innovators who are hungry to push the technology forward but are guided by patients to get it right. AI is being developed everywhere, but in healthcare, the motives, the mission and finding the right team to move forward make all the difference. It also matters that we have diversity among those who are developing AI. We need racial diversity, neurodiversity, ethnic diversity and gender diversity. When you’re evaluating an algorithm, you need a team that understands the cultural and social norms of the populations it will be serving. When we develop these tools, are we aware of our teams? Are our teams looking like society? This is a critical element.
AI SYSTEMS ARE most robust when they are built on broad data sets drawn from a diverse array of patients. A Cedars-Sinai team published a study in the European Journal of Nuclear Medicine and Molecular Imaging that describes how to train an AI system to perform well in all applicable populations—not just the specific population the system was built on.
Some AI systems are trained using high-risk patients, which can cause overestimation of disease probability. To ensure that the AI model works accurately for all patients and to reduce bias, Piotr Slomka, PhD, and his team trained their AI system using simulated variations of patients to scan images to predict heart disease.
The team found that models trained with a balanced mix of cases more accurately predicted the prob-
ability of coronary artery disease in women and low-risk patients, which can potentially lead to less invasive testing and more accurate diagnosis.
The models also led to fewer false positives, suggesting that the system may reduce the number of tests the patient undergoes to rule out the disease.
“The results suggest that enhancing training data is critical to ensuring that AI predictions more closely reflect the population that they will be applied to in the future,” says Dr. Slomka, director of Innovation in Imaging at Cedars-Sinai and a research scientist in the Division of Artificial intelligence in Medicine and the Smidt Heart Institute.
Predicting and diagnosing heart conditions can be greatly improved by applying artificial intelligence tools, according to rigorous Cedars-Sinai studies.
In the first blinded randomized clinical trial of artificial intelligence in cardiology, Smidt Heart Institute and Artificial Intelligence in Medicine researchers led by cardiologist David Ouyang, MD, found that AI is more successful in assessing cardiac function than echocardiogram assessments made by sonographers.
Investigators led by Damini Dey, PhD,
professor of Biomedical Sciences, developed an AI-based tool that measures plaque buildup in the coronary arteries from a standard CT test. They also matched results with images taken by two invasive tests considered to be highly accurate in assessing coronary artery plaque and narrowing: intravascular ultrasound and catheter-based coronary angiography. The investigators discovered that measurements made by the AI algorithm from CTA images accurately predicted heart attack risk within five years.
Sumeet Chugh, MD,
has spent much of his career studying the most lethal of heart disease problems: sudden cardiac arrest. Dr. Chugh—director of the Center for Cardiac Arrest Prevention, the Pauline and Harold Price Chair in Cardiac Electrophysiology Research, and director of Artificial Intelligence in Medicine—and his team working in the community for more than two decades discovered a novel scoring system that sums up a person’s risk of ventricular fibrillation. They have now embarked on the Observational Study of Cardiac Arrest Risk, or OSCAR, that will study
nearly 400,000 Los Angeles County residents. These large collections of clinical data are being analyzed with AI tools to validate and improve the ability to predict who is at risk of a fatal cardiac arrest.
“By the time someone collapses from cardiac arrest and 911 has been dialed, it is too late for 90% of people,” Dr. Chugh says. “The way we predict and prevent cardiac arrest now is not sustainable. AI can help us build a better prediction model that will quickly get interventions to the people who really need them and save lives.”
Graciela Gonzalez-Hernandez, PhD, vice chair of Research and Education in the Department of Computational Biomedicine.
One way to achieve clean, widely applicable data, according to Dr. Gonzalez-Hernandez: Train AI programs with natural-language processing, which mines meaning from large sets of fluid text. Instead of keyword matching—rigid scouring for specific terms— natural-language processing analyzes large sets of sentences or phrases (on social media, in health records or from literature) to uncover more nuanced insights.
Analyzing unstructured data is costly and time consuming, whereas pulling codes is, in theory, less ambiguous and less prone to error. But the more egregious error in studying, for example, a set of people diagnosed with heart disease lies in ignoring variables only found in unstructured notes. Without accessing such text, researchers ignore people with heart disease who went undiagnosed and can also miss valuable insights into how symptoms differ across gender, race or age.
The Division of Artificial Intelligence in Medicine at Cedars-Sinai is using AI to help close gaps in understanding and treatment of major human disease conditions.
The Chugh Laboratory at the Smidt Heart Institute focuses on arrhythmia research. The team investigates mechanisms of ventricular arrhythmias with a view to improve prediction, prevention and management of sudden cardiac arrest.
The Dey Laboratory, affiliated with the Biomedical Imaging Research Institute and the Department of Biomedical Sciences, focuses on automated derivation of imaging measures from noninvasive cardiac image data and clinical implementation of novel automated computerprocessing algorithms.
ONLY 12% OF HEALTHCARE ORGANIZATIONS operate mature artificial intelligence (AI) programs. The AI gold standard integrates algorithms into a health system’s framework that are consistently vetted for bias and methodically monitored for compliance. The lack of trustworthy AI tools that translate between institutions can breed imbalanced, incomplete and skewed data.
Clean, AI-derived data is hard to come by. Less than half of 1% of studies that mine information from electronic health records (EHRs) harvest anything other than structured data fields, such as dates or diagnostic codes. This narrow approach excludes valuable context found in unstructured clinical notes and risks study results that don’t reflect actual population health.
“When data is not analyzed correctly, and the wrong conclusions are reached and the wrong actions are taken, that defeats the purpose of research and renders it harmful,” says
Natural-language processing can make all the difference in establishing a real understanding of the actual landscape of disease. Dr. Gonzalez-Hernandez points to a 2016 paper published in Diabetes Research and Clinical Practice comparing big-data strategies in the study of how often Type 2 diabetes patients experienced hypoglycemia. Researchers at Optum Epidemiology and Merck & Co. found that AI that utilized natural-language processing methods to read EHRs, combined with standard approaches, revealed a much higher prevalence of hypoglycemia than standard AI approaches alone.
A 2009 federal mandate requires physicians to use EHRs to report clinical data and quality measures. The rule was intended to standardize the capture of such information, facilitate its exchange, and improve research and care. But the effort has fallen far short, in part, because large-scale population health studies ignore unstructured EHR data, Dr. Gonzalez-Hernandez says.
“We’ve just begun to tap into this promise of using many records together to take advantage of cumulative knowledge to uncover patterns and come up with better ways to treat people,” she says. “After all these years, we’re still barely using EHRs, even though the data is all there.”
The Ouyang Laboratory in the Smidt Heart Institute focuses on cardiology and cardiovascular imaging, working on applications of deep learning, computer vision and the statistical analysis of large data sets. The team applies deep learning for precision phenotyping in cardiac ultrasound and researches the deployment of AI models.
The Slomka Laboratory focuses on developing innovative methods for fully automated analysis of cardiac imaging data using novel algorithms and machine-learning techniques and on developing integrated motion-corrected analysis of PET/CT and CT angiography imaging.
The Zhang Laboratory develops automated deep-learning methods to accommodate rapid biotechnology development. These models help elucidate causal effects of genetic variations in epigenetics, transcription, post-transcriptional regulation, genome editing and various diseases.
Clinicians should always maintain liability for their tools, intelligent or not.
By CASSIE TOMLIN Illustration by CHRIS BUZELLIIN MEDICINE, every clinical decision at each juncture in a patient’s medical journey carries consequence— for everyone involved. And the consequences can be colossal when
life and health are in play. When physicians enlist the help of artificial intelligence (AI) to identify patients for clinical trials, flag emergent imaging scans and select medications based on a person’s individual profile, the stakes are high. But the burden of getting it right belongs solely to the people who create and use AI algorithms, says Virginia Bartlett, PhD, assistant director of the Center for Healthcare Ethics at Cedars-Sinai.
“AI is a tool—it is not its own entity,” she says. “Both the way it is made and used are still human responsibilities.”
As healthcare systems integrate AI into workflows and decision-making, providers are ethically bound to uphold transparency, fairness, harmlessness, responsibility and privacy, according to a global survey of attitudes published in Nature Machine Intelligence.
First and foremost, Dr. Bartlett says, developers should scrutinize systems to ensure they don’t perpetuate biases introduced in their creation. When consulting AI in formulating treatments, physicians should pay most attention to the patients in front of them, in the flesh. Finally, researchers, clinicians and patients alike should seize the opportunity to voice their worries and questions about AI— which often reflect entrenched fears about technology and the ways we interact with illness and healing.
When a physician is tasked with determining, for example, a course of cancer treatment based on an individual’s condition and genetics, AI can offer informed risk-stratification guidance. But a treatment plan formulated by an algorithmic calculation alone may stoke fears about access and discrimination.
Physicians must continue to learn and prioritize their patients’ values, goals and preferences, Dr. Bartlett says. AI only works in balance with a physician’s knowledge of existing literature, as well as consultation with their clinical colleagues.
“The physician has to judge how accurate the prediction is,” she says. “No matter how fine-grained AI manages to get, we won’t be making decisions in a vacuum. For one person with cancer, a 15% chance of a drug working may be totally worth it, but for somebody else, considering side effects, the burden might not be worth the benefit.”
As Cedars-Sinai develops its own AI applications, the organization’s AI Council of clinical, operational and research leaders helps ensure that the technology is built with strong, deliberate strategies and with bias mitigation in mind. Physicians are responsible for ensuring the AI algorithms they employ are accurate and appropriate, and they should engage in critical dialogue with developers, Dr. Bartlett says. The AI Council will facilitate and encourage such collaboration.
The skillful construction of AI tools and the way physicians leverage them to help answer their questions are the most critical variables in the technology’s success. AI’s utility to process enormous sets of information in search of patterns and trends depends on the careful attention and integrity of its human creators.
“AI’s intelligence is derived from human intelligence, and its design is based on the ways we make sense of the world,” Dr. Bartlett says. “If we start to see problems in the AI programs, it’s a chance to reflect inward. It gives us two opportunities: change the AI, and change our practices that reflect it.”
MORE THAN 10,000 babies are born in the United States every day, but how they’re born isn’t always predictable. Cedars-Sinai investigators developed a machine-learning model that can predict whether a woman will deliver vaginally or by cesarean section.
“This can help us set expectations with our patients early on in their labor,” says Melissa Wong, MD, MHDS, assistant professor of Obstetrics and Gynecology and first author of the study in the American Journal of Perinatology. “We can prevent a C-section from being performed if a vaginal delivery is likely, or we can prevent a patient from laboring for a long time if the model predicts that a C-section is probable.”
Significant disparities in outcomes based on race and ethnicity
were part of the reason Dr. Wong wanted to develop this tool and hopefully curb unnecessary C-sections, which account for about a third of births in the U.S.—with rates even higher among people of color. While a C-section can be required for a pregnant patient or their baby in many circumstances, it is a serious surgery that carries risks for both.
These disparities posed a challenge in creating an algorithm that would make accurate predictions without building in inherent biases that cause outcome gaps.
Part of the solution was building into the prediction tool the ability to understand how the AI came to its conclusions. For example, if a patient’s likelihood of a vaginal delivery drops from 80% to 60%, clinicians can click on the prediction to see that it’s because the patient’s membranes have been ruptured for a long time and she has developed a fever.
“You need to be able to ask questions of the model, just as you would a colleague,” Dr. Wong says. “The last thing anybody wants is to feel like we’re strictly making decisions from gut instinct, even the instinct of an algorithm.”
“AI is a tool—it is not its own entity. Both the way it is made and used are still human responsibilities.”
Dr. Virginia Bartlett
CUIZON
Scientists began laying the groundwork for artificial intelligence in the early 1950s and were exploring multiple AI medical applications by the 1970s. In the years since, the empowering technology has proliferated.
1950
In Computers and Intelligence, Alan Turing describes the “Turing test,” designed to uncover whether computers are capable of human intelligence.
1966
“Shakey,” the first robot capable of interpreting instructions, is unveiled by Stanford Research Institute.
1956
John McCarthy coins the term “artificial intelligence” as the science and engineering of building intelligent machines.
1986
University of Massachusetts releases DXplain, using inputted symptoms to generate diagnoses for 500 diseases—now expanded to more than 2,600 conditions.
1971
Scientists create INTERNIST-1, which uses a powerful ranking algorithm to reach diagnoses.
1975
The National Institutes of Health sponsor the first AI in Medicine workshop at Rutgers University.
1978
Rutgers University develops the causal-associational network model, which couples statistical pattern recognition and AI for glaucoma consultations.
1989
Cedars-Sinai cardiologists debut CorSage, a clinical tool that combines AI and statistical techniques to help physicians identify heart patients who are most likely to suffer another coronary event.
1991
The Pathology Expert Interpretative Reporting System generates pathology reports with nearly 95% diagnostic accuracy.
2021
Established under the leadership of Jason H. Moore, PhD, the Department of Computational Biomedicine bolsters Cedars-Sinai’s researchcomputing infrastructure.
2022
The FDA authorizes 91 AI-powered devices. One, the EchoGo Heart Failure tool, detects heart failure from a single echocardiogram.
2003
1976
“Backward chaining” AI system MYCIN delivers suggested antibiotic treatments for potential bacterial pathogens. The Present Illness Program is introduced to help evaluate edema.
2007
IBM creates the open-domain questionanswering system Watson. In 2011, Watson wins first place on Jeopardy and, in 2017, neurologists use it to identify RNA-binding proteins altered in ALS.
The Human Genome Project provides a wealth of data on the genetic basis of disease.
2020
Google DeepMind uses AI to predict a protein’s 3D structure from its aminoacid sequence, solving one of biology’s greatest challenges.
2019
The FDA approves the first AI-powered device for cancer diagnosis as well as a deep-learning algorithm for interpretation of brain MRIs.
2015
Pharmabot assists in medication education for pediatric patients and caregivers.
2017 Arterys earns Food and Drug Administration (FDA) approval for a product that analyzes heart MRIs in seconds.
2017
Deep-learning applications screen for diseases ranging from diabetic retinopathy to skin cancer with astonishing accuracy. The FDA approves the first AIpowered device for operating-room use.
2019
Cedars-Sinai establishes the Division of Artificial Intelligence in Medicine, led by Sumeet Chugh, MD, the Pauline and Harold Price Chair in Cardiac Electrophysiology Research, who relies on AI and population-wide data to demystify risk of cardiac arrest.
Machine-learning algorithms benefit neurofibromatosis patients.
By KATIE BRIND’AMOUR Photograph by BILL POLLARD
mors as well as benign tumors capable of malignant transformation. When combined with machine-learning algorithms informed by both retrospective and prospective scans, investigators believe the technique could revolutionize proactive management and preventive interventions for cancer predisposition syndromes.
“Not all cancer predisposition syndromes can easily obtain insurance authorization for whole-body MRI scans. This study provides a screening MRI for patients, interpreted by a radiologist, that can be followed up with standard clinical imaging if any masses are found,” says Nicole Baca, MD, the pediatric hematologist/ oncologist who led the project.
CHILDREN WITH A CANCER PREDISposition syndrome called neurofibromatosis are benefiting from artificial intelligence in a collaboration between Cedars-Sinai Cancer and the Biomedical Imaging Research Institute at Cedars-Sinai.
A pilot study is using MRI scans of pediatric patients to screen for markers that predict cancerous tu-
Cedars-Sinai investigators have made exciting progress in machinelearning algorithms to predict postsurgical pain, medication dependency, readmission rates and other key outcomes in spine surgery. In time, this tool—which uses thousands of variables— could give patients personalized predictions of their long-term pain levels and func-
tion before they decide on surgery.
The surgeons are collaborating with Jason Moore, PhD, chair of the Department of Computational Biomedicine, and other experts. Together, they aim to preserve the ultimate goal of medicine—do no harm— while enhancing clinical practice. Thus, the goal is to identify those who may require support
weaning off of opioids, as well as facilitating more intensive interventions to patients at greatest risk of suboptimal outcomes.
Applying this knowledge to proactively provide support services—rather than deny surgery to at-risk individuals—is at the heart of the collaboration’s mission.
“When patients come here, they’re
getting the best in technology as well as the highest level of accurate decisionmaking,” says Corey Walker, MD, assistant professor of Neurosurgery at Cedars-Sinai. “They’re getting a care team that thinks about these things, examines the data and applies knowledge from these studies to carry the field forward.”
KATIE BRIND’AMOUR
A FIRST-OF-ITS-KIND STEM CELL THERAPY FOR ALS PASSES A CRITICAL SAFETY BENCHMARK, ADVANCING THE SEARCH TO SLOW DOWN, REVERSE AND PREVENT THE DISEASE. CAN THE CURE TO THIS DEGENERATIVE CONDITION LIE IN THE ENDLESSLY REGENERATIVE POWER OF STEM CELLS?
By Cassie TomlinIllustration by Brian Stauffer
Photographs by Rachael Porter
FIRST, HER HANDS STIFFENED. THEN SHE DEVELOPED a limp. Ashley Fisher was 48 when she was diagnosed with amyotrophic lateral sclerosis (ALS). During the following three years, as the unstoppable disease took hold of her body, she lost the ability to work, hike by the beach or shop swap meets on Saturday mornings. So, she sought out what she could do with the time she had left: She enrolled in a clinical trial. • Even after paralysis stole her speech, Ashley consented to a fivehour spine operation, took immunosuppressive drugs
for a year and underwent extensive testing at Cedars-Sinai’s ALS Clinic, where a team monitored the impact of the procedure on her body—specifically, one of her legs. Their goal: to test the safety of a combination stem cell/gene therapy to treat the rare neurodegenerative disease, caused by the unexplained, unstoppable death of motor neurons in the brain and spinal cord.
Moments after her death, in May 2021 at a hospital in Oregon, Ashley’s daughter, Courtney Fisher Olsen, relayed to a nurse the urgent instructions impressed upon her in the previous months: Call Cedars-Sinai and ask them to collect Ashley’s spinal tissue.
“She made this research a priority, and she was really proud of it,” Courtney says. “She would do anything to be part of finding answers.”
Ashley, along with the 17 others in the study, gave investigators their only opportunity to make a critical advance: The trial proved, for the first time, the safety of the implantation into the lumbar spinal cord of specialized stem
cells—neural progenitors—engineered to express a powerful growth factor known to protect neurons. The findings, published in September 2022 in Nature Medicine, cleared investigators to study the therapy’s efficacy and continue refining the approach they hope that, ultimately, will slow or stop the disease.
“These patients are the heroes of this research,” says Richard Lewis, MD, director of the Electromyography Lab and principal investigator of the study at the ALS Clinic. “They knew we weren’t going to cure their disease, only pursue whether the cells and this surgical approach were safe. We are encouraged enough with the results to proceed to more patients and attempt to slow disease progression.”
Until now, ALS has frustrated researchers with a notoriously impenetrable monolith. Only 5% to 10% of patients carry genes known to cause the disease. Without the ability to biopsy brain and spinal tissue, little is understood about its mechanisms. In the ab-
sence of biomarkers, physicians can only diagnose ALS after it has already taken hold, and the three treatments approved by the Food and Drug Administration (FDA) do little to slow its progression. The highly specialized, resourceful clinicians at Cedars-Sinai’s ALS Clinic, an ALS Association Certified Treatment Center of Excellence, can only leverage tools and technologies to support their chief goal: to preserve quality of life as patients become paralyzed and die.
Buoyed by breakthroughs in the study of stem cells, CedarsSinai investigators are challenging assumptions and evolving their questions about ALS. Because fresh progress in the disease is fueled by the body’s cells at their most naive state, the ALS Clinic team have embarked on a new clinical trial to test the safety of stem cell implantation directly into the cerebral cortices of ALS patients. They are growing cells from ALS patients in petri dishes to model the disease. Having built the largest library of hyperspecific
disease data, they’re reconsidering whether ALS is not one disease but a collection of conditions. They aim to differentiate between genetic and sporadic forms of ALS and scour the models for the earliest signs of cellular decline. Every approach takes square aim at the ultimate questions: Why do patients develop ALS, and how can we stop the suffering?
For nearly 20 years, Clive Svendsen, PhD, executive director of the Board of Governors Regenerative Medicine Institute and the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine, has cultivated a multipronged sneak attack against neurodegenerative disease. The approach aims to replace diseased astrocytes, star-shaped cells that support motor neurons. In ALS, diseased astrocytes play a role in motor neuron death, which causes paralysis. Glial cell line-derived neurotrophic factor (GDNF) is a potent growth factor that can protect motor neurons, but delivering it to patients is difficult since GDNF is too large to cross the blood-brain barrier. So, years ago, Dr. Svendsen generated a line of human neural progenitors that can become astrocytes and genetically engineered them to release GDNF.
In 2007, he and colleagues at the University of Wisconsin published a paper in PLOS One demonstrating that, when implanted into the lumbar spinal cords of rat models of ALS, the neural progenitors became astrocytes and released GDNF. After Dr. Svendsen joined Cedars-Sinai, further success showing the function and safety of the cells in animal studies earned his group an $8 million grant from the California Institute for Regenerative Med-
icine (CIRM). The team also was granted FDA approval, in 2016, to begin the 18-patient trial in which Ashley Fisher participated.
“Proving the safety and getting the cells to survive was a huge lift,” Dr. Svendsen says. “Drug development can stop at any point, so to have 18 patients and no safety issues—we’re very excited to move forward.”
The Phase I/IIa study was overseen by Pablo Avalos, MD, associate director of Translational Medicine at the Board of Governors Regenerative Medicine Institute. A neurosurgical team, led by J. Patrick Johnson, MD, comedical director of the CedarsSinai Spine Center and vice chair of the Department of Neurosurgery, injected the cells into the exact part of the spinal cord that controls movement in either the right or left leg. The procedure was found to be safe for all patients. Investigators also observed, as a secondary measure, that the cells slowed disease progression in the treated leg in some patients, though this did not reach overall statistical significance. ALS typically causes decline in both sides of the body at the same rate. Since patients received cells in only one side of the spinal cord, their own untreated leg acted as an “internal control” for comparison.
Postmortem spinal tissue revealed that the stem cells were still alive and producing GDNF in the treated side of the spine for up to three-and-a-half years after transplantation. Investigators continue to study postmortem spinal cord and brain tissue, searching for differences in dysfunction between lower motor neurons located in the spinal cord and upper motor neurons found in the motor cortex of the brain. While clinicians can detect ALS with electromy-
“THESE PATIENTS ARE THE HEROES OF THIS RESEARCH. THEY KNEW WE WEREN’T GOING TO CURE THEIR DISEASE, ONLY PURSUE WHETHER THE CELLS AND THIS SURGICAL APPROACH WERE SAFE. WE ARE ENCOURAGED ENOUGH BY THIS APPROACH TO PROCEED IN AN ATTEMPT TO SLOW DISEASE PROGRESSION.”
Dr. Richard LewisClive Svendsen, PhD, remembers the patient who inspired his work.
I had worked on Parkinson’s disease for years, but in 2002, in Wisconsin, I met Jeff Kaufman, a young patient with ALS. I was astounded at the horror of this disease—he had been an athletic man, a wonderful lawyer in his 30s with a lovely wife and four beautiful kids, when he was diagnosed. When I met him, he could only use his eyes to communicate through a computer. His first words to me were, “Can stem cells help me?”
At the time, I was founder and co-director of the Stem Cell and Regenerative Medicine Center at the University of Wisconsin. After encountering Jeff, I dove into the literature and started asking questions. I realized that the approach we’d been studying in other neurodegenerative diseases—using astrocytes and GDNF as a protective strategy—could also protect motor neurons that die in ALS. So I switched my focus and applied for funding from the ALS Association, and it’s all cumulated into the work we do now.
When I met Jeff, he had been fighting the disease for 10 years. He died at 54 in March 2010, and I’ve now been fighting for 20 years. While we don’t have the knockout blow yet, we have landed some punches, and I’m not going to stop.
ography and strength assessments that indicate lower motor neuron function, they have no measurable disease markers for upper motor neuron changes.
Frank Diaz, MD, PhD, a neuromuscular medicine specialist and assistant professor of Neurology who diagnoses and treats patients in the ALS Clinic, is employing novel MRI techniques to identify markers of upper motor neuron dysfunction in postmortem brains and in living patients. He hopes to detect signal abnormalities in upper motor neurons. When paired with corresponding clinical data, this could support the development of more specific diagnostic tools, he says.
“Some patients do not have obvious clinical evidence of upper motor neuron dysfunction early on, which leads to delays in diagnosis and treatment and even precludes their participation in clinical trials,” Dr. Diaz says. “Identifying markers of dysfunction will help us tremendously in understanding how the disease starts in the first place.”
In tandem with clinical trials, Cedars-Sinai investigators are leveraging patient-derived stem cells to model the disease in the lab and in animals.
Ritchie Ho, PhD, assistant professor of Neurology and Biomedical Sciences, who runs a lab at the Cedars-Sinai Board of Governors Regenerative Medicine Institute, is investigating motor neurons made from induced pluripotent stem cells (iPSCs) of ALS patients to identify the earliest signatures of disease and elucidate how disease pathways differ among patients based on their genes.
Dr. Ho’s research trajectory syncs with the groundbreaking
discovery, in 2006, of iPSC technology. His PhD thesis focused on the mechanisms of stem cell reprogramming: the complex process of turning blood or skin cells back into a blank slate, so they can be coaxed, by the addition of specific protein growth factors, to become any type of cell in the body.
In a 2021 paper published in Cell Systems, Dr. Ho uncovered molecular differences between iPSC models of patients with sporadic and familial ALS. Though sporadic and familial disease lead to the same outcome, for the 90% of ALS patients without an identified gene associated with the disease, there is no explanation for its development.
“The hope is that, for those patients, we can use their own stem cells to analyze their genetic background,” Dr. Ho says. “Maybe the cause of their disease is genetic—there could be an undiscovered constellation of gene mutations. Maybe it’s not just one gene that causes ALS, but a series of unfortunate events, a critical mass gone wrong.”
This leads to questions about whether investigators can stratify ALS and its pathological processes to segment the disease more specifically based on whether the cells experience problems clearing proteins, processing energy or conducting other activities.
“ALS is potentially an umbrella disease—we don’t know, out of 1,000 patients, if there could be 100 different groups,” Dr. Ho says. “We’re coming to the point where the spheres of medicine and basic research are at a conjunction. We solve these unknowns through integrating patients’ genetics with how their cells behave in the petri dish and which RNA and proteins they express. Then we can connect these data patterns back to
what’s going on in patients’ bodies as observed in the ALS Clinic and eventually develop truly personalized medicine. We hope to predict how a person will develop ALS and treat their cells before they degenerate.”
At the Cedars-Sinai Biomanufacturing Center, Dr. Svendsen’s group, in collaboration with Dhruv Sareen, PhD, the center’s executive director, is building the largest-ever collection of iPSCs from ALS patients as part of the nationwide Answer ALS initiative. The stem cell lines are paired with an open-source repository of corresponding clinical, genetic, molecular and biochemical information, amounting to the most comprehensive collection of ALS data in history.
The project is groundbreaking in scale and specificity, and intended to encourage and enable researchers everywhere to leverage the data to develop deeper questions—and pursue answers. Earlier this year, Dr. Svendsen’s group and collaborators published a paper in Nature Neuroscience utilizing Answer ALS data to uncover disease subtypes.
Though stem cells have vastly expanded our insights into ALS, the grim reality of the disease and the lack of treatments are never far from mind for devoted investigators. “This is how depressing it is— we started collecting the lines four years ago, and 700 of those 1,000 patients have died,” Dr. Svendsen says. “That’s why we’re determined to do these big projects to understand more. We’re just starting to crack the surface in uncovering clusters of patients with certain characteristics, and we’ve started breaking down questions about what causes it. You can’t
design a drug treatment for a disease if you don’t know its cause.”
Challenges in finding a cause remain: No model of any disease is perfect. What might get lost or introduced into iPSCs during “reprogramming” to make them less reliable imitators of disease behavior? Investigators hope to address this open question to improve the best tools we have.
Last year, with an additional $12 million from CIRM, CedarsSinai investigators launched another first-ever, 16-patient safety trial, transplanting the GDNFproducing stem cells into the brain in a region of the motor cortex that controls hand movement. The research team hopes the operation will leave patients with nothing worse than a scar under their hairline and that they’ll see a positive effect on hand use, which the team will monitor in the ALS Clinic.
Clinical trials proceed slowly, and participant selection is a frustrating paradox: Patients must show early stages of paralysis to qualify, by which time they likely cannot regain long-term function of their bodies. But investigators hope that the process of proving safety will ultimately lead to an efficacy trial combining delivery to both the spinal cord and motor cortex.
“This is a protective strategy, and it’s definitely about timing,” Dr. Svendsen says. “If all the motor neurons are dead, no matter how much progenitor cells and GDNF we deliver, they’ve got nothing to act on. In the future, we can intervene earlier in the disease, and that’s when we might start slowing the progression.”
Cell-based regenerative medicine isn’t the only approach that
Descriptions of major disorders like cancer, lung disease and heart disease date to at least 1500 B.C.—but ALS wasn’t identified until 1869, and it wasn’t widely known until 1939, when baseball player Lou Gehrig was diagnosed.
Because ALS typically presents between the ages of 55 and 75, perhaps a shift in life expectancy—from under 40 in premodern times to a turn-of-the-20th-century increase— could explain why the neurodegenerative disease was undocumented before the modern era. But if ALS is a consequence of our expanded longevity, what explains why it strikes in old age? What are the hazards in aging?
After discovering, as outlined in a 2016 Nature Neuroscience study, that motor neurons derived from iPSCs of ALS patients more closely resemble fetal cells than adult cells, Ritchie Ho, PhD, is attempting to “age” them in the lab to more faithfully model late-onset disease. He hopes to accelerate iPSC maturation—to synthesize a lifespan—and search for signs of preprogrammed cellular “events” that instigate the onset of ALS.
“If we can activate the aging program, we can start to see the neurons become diseased and die, and how,” Dr. Ho says. “We’re trying to look at the very early origins of ALS, assuming there’s something in the neuron that sets it up to die, and trying to understand what that is in order to intervene before it manifests in paralysis.”
To try to trick time, Dr. Ho is measuring gene expressions of iPSC-built motor neurons against gene expressions in tissue from ALS patients and healthy patients. He’s attempting to adjust the manufactured cells to better mimic adult cells by adding small molecules known to switch genes on and off.
In theory, the artificial, expedited aging of iPSCs can help identify what triggers disease onset, Dr. Ho says. “If we can see the full cycle of ALS from start to finish—how the cellularenergy expenditure is different, how proteins accumulate and, at the last stage, how cells are dying—we can pick it apart and see where along a lifespan the disease processes happen.”
offers hope. Scientists at Houston Methodist are focused on immunotherapy: A 2022 study published in Neurology proved the safety of the intravenous application of T-cells meant to slow ALS progression. Another trial, completed at six sites including Cedars-Sinai, met safety benchmarks for the infusion of ALS patients’ own bone marrow stem cells into their spinal fluid; but a Phase III study, published in a
2022 Muscle Nerve paper, did not meet its efficacy endpoint.
Dr. Lewis remains focused on stem cells’ potential for progress and hopes that continued clinical trials will validate the approach.
“We are not going to be able to convert this into a therapy for people who currently have the disease,” he says. “But the scientific question is an important one, and the fact that the stem cells survive is crucial—it’s a start.”
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Dr. Sicotte honored by National Multiple Sclerosis Society.
Early in the pandemic, patients with multiple sclerosis (MS), an autoimmune disease, were thought to possibly be at higher-than-average risk for COVID-19. It turns out they are not more vulnerable, but it was a confusing time.
Nancy Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai,
has been lauded for her work at the nexus of COVID-19 and MS. The National Multiple Sclerosis Society presented her with its 2022 Inspiration Award, which honors individuals for their passion and dedication to the MS community. Dr. Sicotte chaired the society’s National Medical Advisory Committee task force on COVID-19. She led initiatives offering guidance, education and support to people with MS and their healthcare providers during the pandemic.
“It was a very intense period,” Dr. Sicotte says. “We were working in real time to provide information to people with MS about all things COVID-19—especially vaccines.” The resources she oversaw included a dynamic and extensive website for patients and practitioners.
“I’m grateful to the National Multiple Sclerosis Society for its incredible dedication to helping us provide the most up-to-date and accurate information possible to people living with MS,” Dr. Sicotte says.
“We were working in real time to provide information to people with MS about all things COVID-19—especially vaccines,” Dr. Nancy Sicotte says.
When Ali Rezaie, MD, arrived at Cedars-Sinai as the first GI motility fellow in 2012, few such fellowships were available in North America. Today, as medical director of GI Motility Medicine, Dr. Rezaie strives to increase training opportunities in his field.
“Up to 35 million people in the United States suffer from at least one GI motility disorder, but we have far fewer specialists than needed to serve these patients,” he says. “Cedars-Sinai
houses one of the largest GI motility centers in the country, serving more than 7,000 patients per year.” The volume and diversity of patients—some of whom seek out Cedars-Sinai from other countries—along with the breadth of the faculty’s expertise, makes the training program a unique opportunity for one funded fellow each year.
“We treat diseases that involve the movement of the gut from ‘gum to bum,’” Dr. Rezaie says. “Cedars-Sinai is exceptional because we provide services for the foregut, midgut and hindgut, while most programs focus narrowly on one area.”
Dr. Rezaie notes that fellows benefit from exposure to research methodology and clinical care. Such training isn’t widely available in part because GI motility is a relatively new field requiring advanced technology for disease detection.
“There is no shortage of large medical centers,” Dr. Rezaie says, “but the forward-thinking culture at Cedars-Sinai and the willingness to invest in technology are why our gastroenterology programs are so strong.”
Moshe Arditi, MD, executive vice chair for research in the Department of Pediatrics at Cedars-Sinai Guerin Children's and the GUESS?/Fashion Industries Guild Chair in Community Child Health, received the 2022 Prize for Research in Scientific Medicine (PRISM) award, the highest honor bestowed by Cedars-Sinai. Dr. Arditi was recognized for seminal discoveries about postCOVID-19 development of multisystem inflammatory syndrome in children (MIS-C).
C. Noel Bairey Merz, MD, professor of Cardiology and Biomedical
Sciences, director of the Barbra Streisand Women’s Heart Center, and the Irwin and Sheila Allen Chair in Women’s Heart Research, received the Gold Medal Award from the International Society for Heart Research, North American Section, for her outstanding contributions to women’s heart health and research.
Linda Burnes Bolton, DrPH, RN, Cedars-Sinai chief nursing officer emeritus, received the 2022 Lifetime Legacy Award from the American Academy of Nursing in recognition of her 50-year career of leadership and contributions to improve
patient care, advance health equity and promote the nursing profession.
Mitchell Kamrava, MD, director of the CedarsSinai Radiation Oncology Residency Program, has been named president of the Association for Directors of Radiation Oncology Programs, which advances the quality of radiation oncology education and residency training. Dr. Kamrava, director of Brachytherapy Services at Cedars-Sinai, is also gynecologic editor for the journal Brachytherapy and an oral examiner for the American Board of Radiology.
Eduardo Marbán, MD, PhD, the Mark Siegel Family Foundation Distinguished Chair and executive director of the Smidt Heart Institute, was selected for the President’s Distinguished Lecture Award by the International Society for Heart Research, North American Section, in recognition of his leadership in cardiovascular research.
Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs, dean of the Medical Faculty and Distinguished Professor of Medicine, was named as the inaugural recipient of the Transatlantic Alliance Award
As of January 2023, Cedars-Sinai scientists were running 738 active clinical trials. This important work has the power to change the way medicine is practiced and create new possibilities for patients. Researchers are investigating new procedures, medications and technologies across dozens of medical disciplines. Here’s how they break down.
from the European Society of Endocrinology and the Endocrine Society. Dr. Melmed, who is also the Helene A. and Philip E. Hixon Distinguished Chair in Investigative Medicine at Cedars-Sinai, was recognized for his pioneering research in pituitary medicine and endocrine tumors.
Janette Moreno, DNP, RN, director of Nursing Education in the Geri and Richard Brawerman Nursing Institute, was elected to the Association of California Nurse Leaders’ Board of Directors. On the board, which includes some of the state’s most influential nursing leaders,
• Cancer: 396
• Heart: 117
• Medicine: 79
• Neurology/ Neurosurgery: 44
• Gastroenterology/ Colorectal Surgery: 32
Moreno will represent the association’s southern region.
Cedars-Sinai urology resident Aurash NaserTavakolian, MD, and radiation oncology resident Anthony Nguyen, MD, PhD, received the 2022 Cedars-Sinai Rubenstein Award for Excellence in Resident Research for their cancer studies. The annual award—which honors Paul Rubenstein, MD, Cedars-Sinai’s first director of Medical Education—fosters clinical and translational research, enriches knowledge and encourages development of residents as investi-
• Surgery/Urology/ Anesthesiology: 23
• Orthopaedics: 15
• Pediatrics/ Neonatology: 12
• Other: 20
gators across CedarsSinai. Dr. NaserTavakolian was recognized for a study finding that physician biases can affect decision-making for prostate cancer patients, while Dr. Nguyen was selected for his research on the use of lymph nodes for determining a prognosis for cancer patients.
Pooja Nawathe, MD, associate professor of Pediatrics and Cardiology, was selected as the president-elect of the Southern California Chapter of the Society of Critical Care Medicine, which advances critical care, education and research.
Patients with digestive tract cancers often experience severe abdominal pain that drastically affects their health and quality of life. In this study, patients explore lifelike, relaxing 3D worlds using VR goggles. The study aims to assess the efficacy of VR to treat pain and potentially reduce use of opioid medications. The study, which is currently underway and recruiting patients, will compare the use of skills-based VR and distraction-based VR with a control group.
A clinical trial is testing the safety and tolerability of a monoclonal antibody known as PRA023 in patients with moderate to severe ulcerative colitis. In addition, investigators aimed to determine the added value of a companion biomarker developed at Cedars-Sinai. Preliminary trial results showed a significant difference between the antibody and placebo after 12 weeks, with 26.5% of patients taking PRA023 achieving clinical remission compared to 1.5% who received a placebo. The study suggested that participants who are positive for the genetic biomarker may be even more likely to achieve therapeutic benefits, though this finding warrants further research.
Visit clinicaltrials.cedars-sinai.edu to find information about active clinical trials.
Howard Sandler, MD, chair of the Department of Radiation Oncology at Cedars-Sinai Cancer and the Ronald H. Bloom Family Chair in Cancer Therapeutics, has been elected president of the American Society for Radiation Oncology (ASTRO). The new position adds to Dr. Sandler’s history of service to the society, which includes serving on its Board of Directors and chairing its Government Relations Council. He also has been an instrumental part of ASTRO’s Prostate/GU Resource Panel.
Rita Shane, PharmD, professor of Medicine and chief pharmacy
officer; and clinical pharmacist Thanh Tu, PharmD, received an Honorable Mention in the 2022 Innovative Pharmacy Practice Awards from the California Society of Health-System Pharmacists. They were recognized for the Grandparents Project, a pilot program that taught high school students how to ensure that their parents and grandparents are taking medications correctly.
Alexis N. Simpkins, MD, PhD, director of Vascular Neurology Research and the Stroke RNA, Imaging and Protein Predictors for Patient
Tailored Treatments (SkRIPT) Program, recently graduated from the American Academy of Neurology’s Women Leading in Neurology program, which tackles gender disparities and seeks to advance participants to the top levels of leadership in their subspecialties.
Brennan Spiegel, MD, MSHS, professor of Medicine and Biomedical Sciences and director of Health Services Research, was elected as governor of Southern California for the American College of Gastroenterology (ACG), a three-year, competitive position selected by ACG’s membership.
She never wanted to be a surgeon. Then, in medical school, she discovered that she belonged in the operating arena: the teamwork, the challenge, the problem-solving and helping patients all thrilled her. Today, Cristina R. Ferrone, MD, is an accomplished surgical oncologist and chair of the CedarsSinai Department of Surgery. A specialist in the care of patients with complex hepatopancreaticobiliary disease, she has pioneered novel minimally invasive surgical techniques and developed immunotherapeutic strategies for treating cancers of the pancreas, liver and biliary system. Here, she shares what she envisions for the future of surgery at Cedars-Sinai.
Why did you choose to specialize in treating pancreatic and hepatobiliary cancers? That really comes down to four things: the influence of amazing mentors, the technical challenge of the surgeries, an interest in the biology of the cancers and the knowledge that not many treatment options were available for patients with these malignancies.
What research have you been pursuing, and why is it so vital? I spend most of my time thinking about and working on treatment options for pancreatic, bile duct and liver cancers—exploring the biology of the diseases and studying the immunologic responses and gene-expression patterns of these diseases. This helps us understand what mutations occur and how to manipulate the immune
A diverse pool of investigators is laying the foundation for the newly minted Division of Population Sciences Research in the Department of Biomedical Sciences. Along with population sciences initiatives across Cedars-Sinai Cancer, the new division aims to develop a deeper understanding of human disease. “In addition to studying animal models and cell lines, we focus on human beings as the source of our inspiration and the subjects we study,” says Robert Haile, DrPH, the division’s new director and the Cedars-Sinai Chair in Cancer Population Health Sciences.
At the heart of population sciences is translating research into actionable information that closes healthcare gaps. In cancer, for example, researchers might analyze whether genetic factors drive tumors differently by race and ethnicity.
According to David Underhill, PhD, Biomedical Sciences Department chair and the Janis and William Wetsman Family Chair in Inflammatory Bowel Disease, “Cedars-Sinai’s diverse community, rich repository of patient data and highly skilled team positions us to become an international leader in the field of population sciences.”
system to target them. These treatments not only allow us to help patients live longer and feel better but also enable us to operate on more people. A deeper understanding of the biology allows us to downstage locally advanced patients. With targeted therapy, tumors shrink in size and move away from critical blood vessels, so we can remove the cancer.
What role does collaboration play in improving patient outcomes? It’s the central tenet. It allows us to attack cancer in a multidimensional way that takes advantage of everyone’s knowledge and expertise. That means whoever is involved—surgeons, medical oncologists, radiation oncologists—we are seeing patients together and having conversations when reviewing patient charts. Patient care improves because communication between the providers improves.
What new techniques and technologies may transform surgery in the near future? Advancements in surgical techniques and instrumentation and the use of 3D imaging for preoperative planning will improve surgical safety.
Looking forward 10 years, what do you envision for the surgical program at Cedars-Sinai? CedarsSinai has an amazing surgical faculty. My goal, in collaboration with the other department and hospital leaders, is to further build our academic productivity and mission. I’d like to provide the infrastructure to run more clinical trials that utilize the large, diverse, local and regional patient population we serve. It’s really doing research bedside to bench back to bedside.
Nestor Gonzalez, MD, professor of Neurosurgery and director of the Neurovascular Laboratory, was selected as the 2022 Stroke Council Award Lecturer for this year’s American Heart Association (AHA) Scientific Sessions. The lectureships are awarded to leading clinicians and researchers from each of the AHA councils. Dr. Gonzalez is the first surgeon to receive the Stroke Council honor.
genetics and genomics, drug discovery, and adult and pediatric care to improve treatments for IBD.
Nunzio Bottini, MD, PhD, has joined Cedars-Sinai as inaugural director of the Kao Autoimmunity Institute. Dr. Bottini has been continuously funded by the National Institutes of Health (NIH) since 2006 for research that includes rheumatoid arthritis and scleroderma. Most recently, he was section chief in the Division of Rheumatology, Allergy and Immunology and professor of Rheumatology at the University of California, San Diego. The Kao Autoimmunity Institute was launched in 2019 to advance research and treatment of rheumatologic diseases.
Bernice Coleman, PhD, director of Nursing Research, has been appointed to the Food and Drug Administration’s Immunology Devices Panel. The panel is one of 18 that comprise the Medical
Devices Advisory Committee, which reviews and evaluates data and makes recommendations about the safety and effectiveness of devices for clinical use in the fields of oncology, immunology and allergy.
Damini Dey, PhD, professor of Biomedical Sciences, director of the Quantitative Image Analysis Program and co-associate director of the Biomedical Imaging Research Institute, recently served as co-chair of the first workshop for artificial intelligence (AI) in cardiovascular imaging at the National Heart, Lung and Blood Institute. The workshop focused on how the NIH and other stakeholders can support research and development to move AI from promising proofs of concept to robust, generalizable, equitable, scalable and implementable tools.
Martha Gulati, MD, MS, has joined the Smidt Heart Institute as director of Preventive Cardiology, associate director of the Preventive and Rehabilitative Cardiac Center, and associate director of the Barbra Streisand Women’s Heart Center. Dr. Gulati, who also holds the Anita Dann Friedman Chair in Women’s Cardiovascular Medicine and Research, was previously professor of Medicine and chief of the Division of Cardiology at the University of Arizona College of Medicine—Phoenix. She also is president of the American Society for Preventive Cardiology.
Stephan Targan, MD, the Feintech Family Chair in Inflammatory Bowel Disease, has been appointed director of the new F. Widjaja Inflammatory Bowel Disease (IBD) Institute at CedarsSinai. A gift from the F. Widjaja Foundation established the institute, which encompasses basic science,
Cedars-Sinai Cancer Director Dan Theodorescu, MD, PhD, the PHASE ONE Foundation Distinguished Chair and director at the Samuel Oschin Comprehensive Cancer Institute, heads a new, federally funded program aimed at accelerating oncology breakthroughs by training emerging scientists. The Convergent Science Virtual Cancer Center was created through a multiyear grant from the U.S. Department of Defense that totals more than $12 million.
James Turkson, PhD, professor of Medicine in the Division of Medical Oncology, has been named director for Diversity, Inclusion and Strategy at Cedars-Sinai Cancer. He previously served as an ambassador on the CedarsSinai Diversity, Equity and Inclusion Council and on the academic diversity task force.
Yuan Yuan, MD, PhD, a breast medical oncologist and physician-scientist who specializes in triplenegative breast cancer and breast cancer immunotherapy, has joined CedarsSinai Cancer as director of Breast Oncology. Before joining Cedars-Sinai, she was medical director of breast cancer immunotherapy at City of Hope.
Dr. Marcel Maya muses on the talismans that remind him to go outside.
Marcel
nosis and treatment of cerebrospinal fluid (CSF) leak, an uncommon condition caused by a tear in the lining of the spinal cord or by direct communication between the spinal fluid space and veins. In a study published in JAMA Neurology, Dr. Maya and colleagues found that minimally invasive MRI technologies are
just as accurate in detecting CSF leak as the standard test, a CT scan.
The Objects: These miniature die-cast Tour de France cyclists are a souvenir from a winter trip to Paris that Dr. Maya and his wife took nearly 20 years ago.
Why They’re Important: Dr. Maya is a cycling afficionado who used to take long weekend rides
through the scenic hills of Benedict Canyon. He’s since hung up his bike helmet for a tennis racket, but the little riders remain on his desk as a moving memento, a symbol of freedom and a reminder to embrace the thrill of adventure. “It’s a nice reminder to go outside and be hopeful, to be active and challenge myself,” Dr. Maya says.
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