Discoveries Winter 2020

Cedars-Sinai • Winter 2020

SPECIAL REPORT

Misunderstood & Misdiagnosed MEDICINE HAS FAILED WOMEN FOR CENTURIES. THE SCIENCE ON SEX DIFFERENCES IS FINALLY CATCHING UP.

Cedars-Sinai

EXECUTIVE VICE PRESIDENT AND DEAN OF MEDICAL FACULTY Shlomo Melmed, MB, ChB SENIOR VICE PRESIDENT AND CHIEF ADVANCEMENT OFFICER Arthur J. Ochoa, JD VICE PRESIDENT, MARKETING AND COMMUNICATIONS Pattie Cuen EXECUTIVE DIRECTOR, BRAND STRATEGY Jennifer Fagen EDITOR IN CHIEF Laura Grunberger SENIOR EDITOR Sarah Spivack LaRosa MANAGING EDITOR Susan L. Wampler ASSOCIATE EDITOR Cassie Tomlin DESIGN B&G Design Studios, bgdesignstudios.com CEDARS-SINAI DISCOVERIES

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ABOUT CEDARS-SINAI

CEDARS-SINAI MAINTAINS THE

Cedars-Sinai is a national leader in providing high-quality, 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, Cedars-Sinai 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. Cedars-Sinai demonstrates a longstanding commitment to strengthening the Los Angeles community through wide-ranging programs that improve the health of its most vulnerable residents.

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 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 about this policy, contact the public civil rights coordinator, at 310-423-7972.

WINTER 2020

Contents

In This Issue

40 A Disease Ignites

Max Gerber

The usually harmless sexually transmitted human papillomavirus (HPV) is triggering a surge in throat cancer incidence among older men like Bill Reid.

Now cancer-free, he and his wife, Ruth, are vocal advocates for increasing the HPV vaccination rate.

There’s more to discover online…

For more stories about the latest medical advances and scientific breakthroughs, and the patients who benefit from them, visit cedars-sinai.org/discoveries

Also: web exclusives and videos that you can share in a click!

Contents Departments 5 NEWS & NOTES Responding to public health crises; protecting young kidney-transplant recipients; how cancer cells reshape their surrounding environment; new guidelines for urinary tract infections; solving medical mysteries; genes tied to increased ovarian cancer risk; using improv to help women recover from breast cancer; and more

20 MEET MAKING BIRTH BETTER Kimberly Gregory, MD, MPH, is on a mission to make childbirth safer and more fulfilling—not just for her own patients, but for all women. She aims to convince hospitals to pay more attention to the type of maternity care women prefer.

22 LEARN MATTERS OF THE HEART Smidt Heart Institute experts weigh in on cardiology gamechangers and—because the heart is associated with all things pitter-patter—their favorite love stories as well.

24 THINK CANCER-FIGHTING ‘AHA’ MOMENTS Jane Figueiredo, PhD, heads the nation’s largest study on prevention and treatment of colorectal cancer in Latino people.

Here, she shares revelations that drive her commitment to fighting disparities in underserved populations.

45 FACULTY NEWS Partnership prepares young healthcare professionals to master the health system’s complexities to improve patient experience; awards and grants

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Cover Story 26 The Unfair Sex Kim Baily, 50, (on the cover) is one of eight women profiled in this special report on gender bias in healthcare. Baily suffered from chest pains and heart attacks that went undiagnosed by doctors because her condition doesn’t present the way heart disease does in men. After three years of unanswered questions, she found the Barbra Streisand Women’s Heart Center, where she was diagnosed with and treated for microvascular disease.

“I was walking two miles a day, fit and in my 40s. I didn’t look like a typical heart patient to some doctors,” she says. “Keep looking until you find the doctor who listens.”

48 MEET THE KIDS In a new series, children of Cedars-Sinai staff share their best guesses on what their parents do.

This special report examines why women’s symptoms have been dismissed for centuries, and how today’s female clinicians and investigators are leading the charge to understand and solve women’s health challenges.

For more of Baily’s and other patients’ stories, visit https://ceda.rs/unfairsex.

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COVER Rachael Porter

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From the Dean

In Celebration of Diversity

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[Our leading] doctors provide a beacon for women long misunderstood by a medical system that still has much to learn about female bodies.

t Cedars-Sinai, our devotion to quality healthcare and medical knowledge is epitomized by a commitment to two of our most significant founding values: diversity and inclusion.

In 1902, we opened as Kaspare Cohn Hospital with a promise to treat anyone who sought our help, no matter how poor or unwell. Through the years, we have embraced this legacy as we have grown into one of the largest academic medical centers in one of the most diverse regions in the country.

We celebrate diversity in its many forms. Patients from all creeds pray together with chaplains from our Spiritual Care department. Patients received care in more than 60 languages last year, and our physicians represent an expansive tapestry of nationalities. This year, Cedars-Sinai was awarded status as a “Leader in LGBTQ Healthcare Equality” by the Healthcare Equality Index—a national benchmarking tool—for our inclusive policies and practices.

Just as we treat our patients with respect and meet their culturally specific needs, we maintain a safe and welcoming environment for our trainees, residents, doctors, nurses and administrative employees.

This issue of Discoveries focuses on one area of diversity vital to the future of medicine: gender parity. The clinicians and investigators who founded our Center for Research in Women’s Health and Sex Differences further CedarsSinai’s quest to make healthcare equitable for all. With their leadership and compassion, these doctors provide a beacon for women long misunderstood by a medical system that still has much to learn about female bodies. Along with the leaders showcased in this story, we have recently recruited female department chairs in Neurology, Cardiac Surgery, Cardiology, and Obstetrics and Gynecology. These experts were sought out and selected not for their gender but because these women were the most highly qualified candidates.

We continuously seek to expand our medical staff to reflect all walks of life.

This year, we welcomed Nicole Mitchell, Cedars-Sinai’s first director of Diversity and Inclusion, who participates in all faculty search committees and provides education on implicit bias. She is a crucial partner in recruiting top talent to our medical staff.

Our leadership is invested in training the next generation of diverse leaders: The Cedars-Sinai Biomedical Education Pipeline Initiative offers paid, 10-week internships for undergraduate students from diverse and underrepresented backgrounds who plan to pursue graduate or medical school.

Our community becomes stronger as we add to our bold mosaic of many histories and cultures. These efforts serve the broad potential of diversity and inclusion: new, unique perspectives and innovations from dedicated and engaged physicians, medical staff and employees.

Shlomo Melmed, MD

EXECUTIVE VICE PRESIDENT, ACADEMIC AFFAIRS DEAN OF THE MEDICAL FACULTY HELENE A. AND PHILIP E. HIXON DISTINGUISHED CHAIR IN INVESTIGATIVE MEDICINE

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News & Notes Winter 2020

6 GOOD TO KNOW | 8 THIS VS. THAT | 10 TECH CORNER | 16 WHO’S WHO | 17 WORD

Oli Winwood

Recipe for Disaster Medical disaster movies can be exciting to watch, but for Jonathan Grein, MD, director of Hospital Epidemiology, they are often frustrating. “So many fascinating things could be shown, but they don’t emphasize those,” he says.

As head of the Special Pathogen Response Team, Grein has firsthand experience simulating public health crises.

His team is one of only 10 groups selected nationwide to treat highly infectious diseases, like Ebola and MERS, that carry severe consequences. The team conducts drills year-round so they are prepared to contain real-life harm should a worst-case scenario occur.

To achieve (occasionally icky) realism, the team has used oatmeal to mimic vomit and Gatorade for urine. A cafeteria tray serves as a toilet cover, and an invisible fluorescent dye called Glo Germ stands in for blood. “You can rub it on all sorts of surfaces, like bed rails,” Grein says. “Afterward, we bring in the black light so staff can see where they contaminated themselves on their protective suits.”

But the most difficult reality to mimic is the adrenalized, emotional state of a true emergency situation.

“One of the hardest scenarios was when we had a healthcare worker down … and you basically have to execute a rescue,” says Sylvia Cumplido, RN, MSN, a nurse-epidemiologist, describing a drill in which a staff member mimicked passing out in a patient’s room.

“You want to move fast but, if we slow down and go methodically, we don’t make mistakes,” Grein adds.

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N & N GOOD TO KNOW: KIDS’ KIDNEYS

Kidney School Care team helps protect donor organs by making sure teens do one simple thing: stay on their meds.

and her team created the Pediatric to Adult Transition research project. Their multidisciplinary approach helps adolescents transition to the adult phase of care through education on diet, psychosocial implications and medications. Patients learn about their drugs, why they’re crucial, what the side effects are, how to get refills and how to tell if they no longer work.

The pediatric transplant team also has offered surgery to more than 20 children considered too difficult to transplant

STATS : KIDNEY CARE FOR THE YOUNGEST PATIENTS Just as it takes a village to raise a child, communities of caregivers must safely steer children through the challenges of kidney transplants. At Cedars-Sinai, a team of 11 clinicians, including surgeons and social workers, helps young patients prepare for transplant, cope with the necessary postsurgical immunosuppressive drugs—and get healthy so they can go back to just being kids.

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by other centers. These patients are highly sensitized, meaning they have an overabundance of antibodies primed to attack a donor organ. An innovative procedure offered by the Cedars-Sinai Kidney and Pancreas Transplant Center—intravenous immunoglobin therapy coupled with other medications—helps desensitize such patients, giving new hope to both children and adults with kidney failure. Some 40% of all patients who come to Cedars-Sinai for a kidney transplant are highly sensitized.

4 177 HOURS

length of a typical pediatric kidney transplant surgery

pediatric kidney transplants completed to date

Richard Mia

For children facing kidney failure, a transplant can provide 20 years of function before another donor organ must be found—or until medical advances can provide a lifelong solution. Pediatric patients ages 14–16 who receive a kidney transplant have a 42% chance of losing their new organ within a decade, according to the American Medical Association.

The reason for this troubling statistic?

Noncompliance. “Simply put, the patient is not taking his or her medications,” says Dechu Puliyanda, MD, director of the Cedars-Sinai Pediatric Nephrology and Transplantation Program. Most transplant recipients need five to 15 medications daily to prevent organ rejection.

“You get a chance to get a kidney just once, maybe twice in your lifetime,” Puliyanda says. “If you don’t take care of it, you can lose it, and lose it very quickly.”

To address this problem, Puliyanda

N&N

Heartfelt Hobby A physician combines her knowledge of anatomy with a love of needlework.

Rachael Porter

Dr. Dechu Puliyanda crafts needlework art, a hobby passed down from her grandmother.

Dechu Puliyanda, MD, has dedicated her life to two practices: medicine and cross-stitching—not to be confused with the surgical closing of wounds. The pediatric nephrologist picked up her first tapestry needle when she was in second grade, learning from her mother—who, in turn, learned from her mother. While in medical school, Puliyanda used cross-stitching to relieve the stress of intense studying.

Over the years, she’s created a pattern of starting every morning with a cup of coffee and at least 15 minutes of needlework.

“In general, I am quite wired and am on the go,” Puliyanda says. “Stitching calms me down.

It’s an extremely zen thing that I can do anywhere.”

The director of the Cedars-Sinai Pediatric Nephrology Program has become so advanced in the art that several of her friends and her mother regularly ask for stitching advice.

Most of Puliyanda’s embroidered pieces are of cheerful birds, fluttering butterflies or, her favorite, colorful poppies.

Recently, she’s been pursuing a project that reflects her profession—cross-stitching patterns of major organs: lung, kidney, heart and liver.

Each piece takes up to six months to complete.

“I love how the otherwise bland and nerdy organs can be made so whimsical yet so uplifting and happy, with all the colors and elements used.”

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youngest kidney transplant recipient, in 2002

Cedars-Sinai’s first pediatric kidney transplant performed

YEARS

expected life span of a transplanted kidney

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N & N THIS VS. THAT

Tumors vs. Plants Cancer cells can reshape their surroundings—just like invasive plants crowd out native flora. Discoveries asked a handful of cancer and plant experts to extend the metaphor.

“Cancer cells only have one mission: live, grow, proliferate. If the environment they create can be readjusted in favor of destruction of the cancer cells, that gives us an advantage in helping patients.”

TUMOR MICROENVIRONMENT

INVASIVE PLANT ENVIRONMENT

THE BASICS

A tumor microenvironment includes cancer cells that surround healthy cells and “rogue” cells that have been recruited by cancer cells. Interactions among these cells create the microenvironment.

A species is defined as invasive when it outcompetes native plants for resources. This can change how local birds and animals eat, nest and interact with their environment.

GRABBING LIQUID RESOURCES

Tumor cells in the microenvironment send out signals to recruit blood vessels to grow into the area to feed the tumor.

Saltcedar, an invasive shrub, grows a long taproot deep into the soil, starving surrounding plants of adequate water. It can soak up more than 30 gallons of water daily.

POISONING THE COMPETITION

Healthy cells produce collagens the body needs to function normally. Cancer changes the types of collagens that healthy cells produce to help the cancer cells grow and spread.

Saltcedar exudes a toxin that prevents other plants from growing.

HIDING OUT

Fibroblasts, cells usually found in connective tissue, seem to play a role in hiding cancer cells from the immune system.

English ivy, originally planted as a ground cover, climbs up trees and hides plants below from the sun.

HOT SPOTS

Larger tumors increase glucose metabolism, creating a kind of “hot spot” in the body.

Some invasive plants—like red river gum, a kind of eucalyptus— burn hotter even than California’s native chaparral, increasing the risk of wildfires.

FIGHTING BACK

Samuel Oschin Comprehensive Cancer Institute investigators are looking for ways to reclaim the microenvironment—not by directly attacking cancer cells but by weakening their defenses and making them more susceptible to immunotherapy and targeted therapies.

Changing growing conditions can discourage an invasive weed from further choking off other plants.

Sources: Robert Figlin, MD; Sandra Orsulic, PhD, professor of Obstetrics and Gynecology; David Bare, director of horticulture at Descanso Gardens in La Cañada Flintridge, California; Frank McDonough, botanist at Los Angeles County Arboretum and Botanic Garden

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LJ Davids

—Robert Figlin, MD, director, Division of Hematology/Oncology, and the Steven Spielberg Family Chair in Hematology-Oncology, Samuel Oschin Comprehensive Cancer Institute

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UTIs Gotta Go Investigator spearheads new guidelines for a common condition.

Egle Plytnikaite

More than half of women will develop a urinary tract infection (UTI) in their lifetimes, and many suffer recurring infections. But frequent use of medications can lead to antibiotic resistance.

New guidelines from the American Urological Association (AUA) aim to give women lasting relief by helping physicians better manage recurrent UTIs while reducing antibiotic overuse. Jennifer Anger, MD, associate director of Urological Research at Cedars-Sinai, chaired the AUA’s guideline development panel.

“Classically, a woman with a UTI would get a prescription for antibiotics,” Anger says. “The problem is that women suffer ‘collateral damage’ from too many antibiotics—side effects like risk of further infection or even musculoskeletal soreness.”

Based on rigorous analysis of decades of scientific literature, the guidelines call for physicians to perform a urine culture before giving antibiotics.

By allowing the culture to incubate for a few days in a lab for any bacteria to grow, physicians can be better informed about which drug will work best, or rule out infection entirely.

Designed for women who are otherwise healthy and not pregnant, the new guidelines also encourage more attention to preventive measures. For those with persistent UTIs, low-dose antibiotics at the time of sexual activity are recommended. For women in or past menopause, low-dose vaginal estrogen creams, tablets and pills can deter infection by helping regulate pH balance. Over-thecounter cranberry supplements are unproven but harmless. Physicians may eventually identify the right formulation of supplements to help patients.

“Patients don’t want to be overtreated with antibiotics; they’re afraid of the consequences, too,” she says. “When you offer them alternatives to the standard treatment, they appreciate that.”

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Medical Mysteries Experts strive to diagnose the previously undiagnosable.

Mysteries in real life are seldom as fun as those in fiction—especially when rare or chronic health conditions leave physicians baffled and patients in pain.

Cedars-Sinai’s new Center for the Undiagnosed Patient teams up diagnostic sleuths to solve such conundrums so patients can get answers and, hopefully, relief.

The center includes cardiologists, geneticists, neurologists, endocrinologists, gastroenterologists and infectious-disease experts—all dedicated to bringing patients’ “diagnostic odysseys” to a healthy destination. Led by Medical Director Leon Fine, MD, and Associate Director Michael Lewis, MD, these multidisciplinary specialists collaborate to create personalized treatment plans for patients of all ages.

Often, investigating difficult-to-diagnose conditions leads doctors to discover new diseases or new variations on a disease—dramatically pushing forward the medical frontier.

The center is supported by CedarsSinai Precision Health.

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N & N TECH CORNER

Laser Tag

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The laboratory of Pramod Butte, PhD, is chockablock with bins of computer innards, pumps, dials, “useless random fasteners,” capacitors and chunky buttons begging to be pushed. From such seemingly arcane items, he forges innovative methods to help surgeons distinguish cancerous cells from healthy ones.

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PROBLEM:

DISTINGUISHING TUMORS FROM HEALTHY TISSUE

“The problem with brain surgery has been that we don’t know where the boundary is between tumor and normal tissue,” says Butte, a research scientist in the Maxine Dunitz Neurosurgical Institute. Traditionally, neurosurgeons use MRI brain scans, but those are imprecise.

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SOLUTION:

LIGHT THEM UP

Butte is helping surgeons “see” tumors using fluorescence, like “what happens with black light at the bowling alley,” he explains.

When hit with ultraviolet (UV) light, tissue absorbs the radiation and rapidly spits back its own signal. Butte hypothesized that cancerous and healthy cells would emit different signals, and he thought fluorescence could help surgeons pinpoint tumors in the operating room.

The UV laser Butte developed flashes for 350 picoseconds. A picosecond is one trillionth of a second. “It’s a very, very fast laser,” he adds.

Butte and his team worked on designing and refining the laser for more than a decade. They also devised a machine to detect the fluorescent signal as well as software to analyze it. A 2016 clinical trial tested whether the system could distinguish between tumors and normal tissue.

Not only was his system accurate, but the trial demonstrated its potential to help direct surgeons toward which areas to cut—and which not to—in real time. With the brain tumor results as proof of concept, Butte’s lab is conducting a similar clinical trial with breast cancer patients.

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Tools of the Trade

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Discoveries raided the Butte Laboratory and absconded with an assortment of tools used to craft visualization technolgies.

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Rachael Porter

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1. High-speed steel twist drills 2. Inductors 3. Push-to-connect union tee to split compressed air 4. Dial indicating mechanical motion to 1/1000th of an inch 5. Metal bellows placed over laser beams to protect the eyes 6. Crimp contacts used to build custom cable connectors 7. Voltage regulators 8. Arcade buttons 9. SMA patch chord 10. Mint box amplifier used to amplify music or more scientific signals 11. Solder 12. FiberPort collimator to straighten diverging light beams 13. Machining coolant hose on magnetic base 14. Digitizer connector block 15. Rubber bellows 16. FiberPort coupler 17. Variable RF attenuator to reduce the strength of radio frequency signals 18. Momentary electrical button 19. PCB terminal blocks 20. CNC tool holder with twist drill 21. CNC tool holder with fly cutter 22. Solder 23. Industrial start button 24. RF amplifier 25. Miniature speaker 26. Brass components used to route compressed air to blow chips of material off finished parts: (from left) quick connect coupling (female); tubing adapter; quick connect coupling (male) 27. Momentary push buttons 28. Soldering wick 29. Vinyl electrical tape 30. Superglue

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N&N

Form and Function

Pfeffer is a national leader in procedures to correct foot and ankle deformities, including those caused by CharcotMarie-Tooth disease, one of the most common inherited neurological disorders.

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Joseph Escamilla

“I started working with bonsai trees when I was still in medical school. Both bonsai and orthopaedic foot and ankle surgery combine science and art. You start with twisted limbs and use wires, screws and plates to turn them into something beautiful and highly functional.” — Glenn Pfeffer, MD, director, Foot and Ankle Center, co-director, Cedars-Sinai/USC Glorya Kaufman Dance Medicine Center.

N&N

Stroke of Insight

Ovarian Cancer Culprits

Adria Fruitos

Scientists pinpoint genes tied to increased ovarian cancer risk.

Ovarian cancer has a survival rate of more than 90%—but only if caught early. It remains challenging to detect due to its vague symptoms and the lack of noninvasive screening options. Most cases are diagnosed only after the cancer has grown or spread, when the chances of survival drop precipitously to 29%.

Now, a multisite study led by Cedars-Sinai investigators Simon Gayther, PhD, and Kate Lawrenson, PhD, has identified 34 genes related to increased risk of the disease. Their findings may not only help warn women in jeopardy of ovarian cancer but also pave the way for therapies targeting the guilty genes.

The team’s work builds on previous research by the Ovarian Cancer Association Consortium comparing the genetic profiles of nearly 25,000 ovarian cancer patients to 45,000 healthy women.

They found more than 30 regions in the genome associated with the disease.

To pinpoint exact genetic culprits in these regions, the study elucidated the significance of risk factors and abnormal expression of genes in ovarian and other tissues. This process was complicated by the fact that thousands of possible gene targets exist that can be affected by numerous mechanisms.

“Putting the pieces together is a huge computational and statistical effort,” notes Gayther, co-director of the Applied Genomics, Computation and Translational Core and the Barth Family Chair in Cancer Genetics in honor of Beth Y. Karlan, MD. “This study also shows how critical it is to study specific cells from which ovarian cancers arise,” says Lawrenson, assistant professor of Obstetrics and Gynecology.

Researchers hope the findings will eventually help identify ways to prevent ovarian cancer from progressing to late, lethal stages.

A stroke-causing blood clot is treated by either dissolving it or surgically removing it. While both methods help patients heal, studies in mouse and rat models suggest that certain therapies may help protect the brain during these treatments and improve patient recovery.

To assess the effectiveness of such treatments, the National Institutes of Health (NIH) has named Cedars-Sinai the coordinating center in the Stroke Preclinical Assessment Network (SPAN)—a consortium of seven major academic centers from New England to California. Under the leadership of Patrick Lyden, MD, the Carmen and Louis Warschaw Chair in Neurology at Cedars-Sinai, SPAN investigators will also study whether some surgical procedures or medications approved by the Food and Drug Administration for other diseases, such as cancer and multiple sclerosis, can be repurposed to treat stroke patients.

“This program will look beyond the standard of care to see if we can find new ways to help patients get back to normal after a stroke,” says Nancy Sicotte, chair of the Cedars-Sinai Department of Neurology and the Women’s Guild Distinguished Chair in Neurology.

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N&N

Step It Up Clinicians routinely monitor heart rate, blood pressure and other vital statistics to track a patient’s progress after major surgery. Cedars-Sinai scientists recently demonstrated the benefits of also logging a patient’s steps.

A new study led by prostate cancer surgeon Timothy Daskivich, MD, and Brennan Spiegel, MD, director of the Center for Outcomes Research and Education, found that each 100 steps a patient takes reduces the length of their hospital stay by 4%. (No further benefit was seen after the first 1,000 steps.) To help encourage movement, the team created a smartphone app that takes patients on a museum-style tour of the medical center’s art collection, while a Fitbit tallies their steps. Four art tours were created for each surgical unit, enabling patients to choose shorter or longer walks.

“We’re operationalizing this popular tech device for a real clinical purpose, and using rigorous science to guide the process,” says Daskivich, who is also director of Health Services Research for the Department of Surgery. “We think it’s exciting, and patients are responding to it.”

No-Fun Fungus Crohn’s disease inflames the digestive tract, causing abdominal pain, diarrhea, fever, nausea and other unpleasant symptoms. While the chronic disease can be managed, its causes remain a mystery. But Cedars-Sinai investigators may have found a clue.

David Underhill, PhD, and his team found that many patients with Crohn’s also had high concentrations of a fungus called Malassezia in their digestive tracts. Malassezia is omnipresent on human skin and can cause dandruff but is harmless for most people.

“This suggests that there’s something going on both from a microbiome and a genetics point of view,” says

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Underhill, the Janis and William Wetsman Family Chair in Inflammatory Bowel Disease.

The team now wants to learn whether Malassezia gut overgrowth might make Crohn’s symptoms worse.

But the fungus might not be all bad.

Underhill says we still have much to learn about its purpose in our bodies: Does it protect us from other conditions? Does it truly make Crohn’s worse?

The investigators hope to develop clinical trials to remove Malassezia from the body to answer these questions.

And maybe even reduce dandruff.

Daria Kirpach

Dandruff is linked to Crohn’s disease.

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Take My Cancer, Please

Guilio Bonasera

Improvisation has taken center stage in helping women recover from breast cancer, thanks to a Cedars-Sinai clinical trial. Arash Asher, MD, director of Cancer Rehabilitation and Survivorship, helped create an improv comedy class and is evaluating its benefits to patients.

As anyone who has ever taken an acting course knows, improv involves performing without a script. But instead of being concerned with participants’ perfect timing, Asher is exploring the therapeutic advantages of mindfulness.

“They can be present in the moment, connect authentically with other people and do away with

Finer Fracture Care

self-judgment,” he says.

That isn’t to say that there aren’t laughs to be had. Course leaders include comedian and Emmynominated writer Shelly Gossman, a Second City alum whose credits include Saturday Night Live.

She has also faced cancer and beaten it—twice.

“You don’t lose your sense of humanity and wonder and laughter when you are sick,” Gossman told NBC News, which produced a story about the program.

So far, Asher is optimistic about the outcomes for participants. “Improv has made a big impact on depression, on anxiety, on wellbeing,” he says.

Hip fractures can be serious for seniors: After a fall, about a third die within a year of related complications. Another third will never regain mobility.

Cedars-Sinai’s new Geriatric Fracture Program is spearheaded by Kathy Breda, MSN, lead nurse practitioner in the Department of Orthopaedics, in collaboration with geriatricians and physicians specializing in hospitalized patients. It aims to improve outcomes for patients 65 and over.

The program’s specialized training includes techniques for preventing muscle decay, tailoring medication to reduce opioid use and monitoring patients for delirium, which occurs in half of patients with hip fractures. The condition can be caused by pain, dehydration, infection, or drug and alcohol withdrawal, and results in longer hospital stays, more complications and increased risk of death.

Nurse-scientists will analyze patient data to help providers better understand patient readiness for surgery, pain management, and how to decrease opioid use and reduce length of hospital stays.

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N & N WHO’S WHO

Meet the Rosens When Sonja Rosen, MD, was a student at Fairfax High School in Los Angeles, she served as a teen volunteer at Cedars-Sinai. Now it’s her daughter’s turn. Fourteen-yearold Clarissa joined the Teen Volunteers Program last fall. Here, the mother-daughter duo discuss their shared passion for singing, literature and savory snacks.

Sonja Rosen, MD, medical director and chief, Section of Geriatric Medicine, Department of Medicine Clarissa Rosen, ninthgrader, Marlborough School in Los Angeles

PERSONAL MISSION SR: I went into geriatrics because I love helping older people live well. As a child, I spent summers with my grandparents in Finland, where I was born. I probably related better to older people than to my peers.

CR: I love helping people, too. That’s why I’m so excited about becoming a Cedars-Sinai volunteer. I’m learning about the medical world, and I get to talk to patients and make sure they have what they need.

HARMONIOUS PASSIONS SR: I love Agatha Christie mysteries and books by Bruce Cook, my late stepfather. For music, I listen to a range—from Chopin to Luther Vandross Jr. My favorite film is Casablanca.

CR: My passions include water polo, swimming, reading—especially books

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by my late grandfather, Bruce Cook, and Jane Austen—and films like Franco Zeffirelli’s Romeo and Juliet.

INSPIRING ANCESTORS SR: Both of my parents are concert violinists. My American grandfather was Victor Aller, music supervisor for Warner Bros. in the 1940s, and a Capitol recording artist and concert pianist who performed with the Hollywood String Quartet.

My Finnish grandfather was Veikko Talvi, a soldier in the Winter War [a 1939–1940 conflict between the Soviet Union and Finland] and a well-known historian in Finland. He lived to be 100.

CR: My grandmother, Judith Aller, is a concert violinist who studied with Jascha Heifetz. She’s passionate and driven, and she’s the most generous and intellectual person I know. And my grandfather, IIkka Talvi, is a violinist who served as concertmaster of the Seattle Symphony for many years.

MAKING MUSIC SR: I love to sing R&B and soul, and Sinatra songs

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like “Just the Way You Are.” As a cellist, I enjoy playing Bach’s suites.

CR: I also love to sing— especially with my choir at Marlborough and music from the 1950s like “Tonight You Belong to Me” by Patience and Prudence. My favorite piano piece to play is Beethoven’s “Moonlight Sonata.”

MOST EXCITING PROJECT SR: I’m thrilled to be co-investigator on a research project called Leveraging Exercise to Age in Place (LEAP). It’s funded by the AARP Foundation to help combat social isolation and prevent falls.

Cedars-Sinai is at the forefront of a national effort to develop evidence-based programs

to fight social isolation.

This is so important— loneliness can have the same negative impact on a senior’s health as smoking 15 cigarettes a day.

CR: For my final project in history last year, I wrote an essay about Charlemagne, king of the Franks and the Lombards and ruler of the Holy Roman Empire. I was blown away by how much one illiterate king was able to impact religion, literature and literacy.

FUTURE GOAL SR: I’d like to write a book someday—maybe something that spreads the beauty of knowing older people and learning about life from them.

CR: I want to be a geriatrician just like my mom.

WORDS TO LIVE BY SR: “Be kind, for everyone you meet is fighting a great battle.”—Philo Judaeus CR: I can’t argue with that!

HIGH NOTE SR: Marrying my wonderful husband, Richard Rosen, on June 16, 2002, at Temple Israel in Hollywood CR: Studying English literature and creative writing at the University of Oxford in England for two weeks last July

OFFBEAT SR: My favorite candy is salmiakki, salty black licorice from Finland.

CR: I love Flamin’ Hot Cheetos.

Vanessa Dell

OFFICIALLY KNOWN AS

N&N

Gateway to the Brain Scientists recreate a blood-brain barrier defect outside the body.

While building a brain capable of powering Frankenstein’s monster remains out of reach, Cedars-Sinai scientists have recreated a critical component—the blood-brain barrier.

The blood-brain barrier acts as a gatekeeper by blocking toxins and other foreign substances in the bloodstream from entering brain tissue and damaging it. But it can also prevent potential therapeutic drugs for neurological and other disorders from reaching the brain.

The study, published in Cell Stem Cell,

used induced pluripotent stem cells— which can produce any type of cell—to generate the neurons, blood-vessel linings and support cells that constitute the blood-brain barrier. The living cells were placed in Organ-Chips, which are about the size of AA batteries and replicate the body’s microenvironment. The cells soon coalesced into a functioning replica of the blood-brain barrier.

Even more significantly, these cells also copied the neurological diseases of the patients from whom they were derived.

This achievement provides a new way to make discoveries about brain disorders and, potentially, predict which drugs will work best for an individual patient.

The research combined innovative stem cell science from the Cedars-Sinai Board of Governors Regenerative Medicine Institute with the advanced Organs-on-Chips technology of Emulate Inc. in Boston.

Disclosure: Cedars-Sinai owns a minority stock interest in Emulate Inc. An officer of Cedars-Sinai serves on Emulate’s board of directors. Emulate provided no financial support for this research. Six of the study’s authors are employees and shareholders of Emulate.

Word

CREPITUS

[kreh-puh-tuss] Definition:

Jeff Hinchee

The crackling, crunching, grinding or grating noise that accompanies flexing a joint Even though “crepitus” comes from the Latin word for “creak” and has the same root as “decrepitude,” its snap, crackle and pop sounds do not necessarily signify advanced age. The sound arises from air or other gases in tissue under the skin. For example, crack your knuckles and the microscopic nitrogen bubbles inside pop to attention. But since it takes a while for the gas to build back up, you have to be patient before doing it again for your own delight—or the annoyance of those around you. And while crepitus can be a sign of arthritis, no evidence exists that popping your joints causes the condition. Crepitus may indicate cartilage wear or an injured joint, and the grimace-inducing noise also may be heard when fractured bone fragments move against one another.

WINTER 2020 | DISCOVERIES |

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Meet

Q A &

Making Birth Better: Kimberly Gregory, MD, MPH

By Katie Sweeney

Kimberly Gregory, MD, MPH, is on a professional mission to make childbirth a safer and more fulfilling experience—not just for her own patients, but for all women. One of her tactics aims to convince hospitals to pay more attention to the type of maternity care women prefer.

The vice chair of Women’s Healthcare Quality and Performance Improvement in Obstetrics and Gynecology at Cedars-Sinai, Gregory recently led the Childbirth Experience Survey, which asked 2,700 expectant mothers what kind of support they desired during childbirth, and then followed up to see if they received it.

Based on the findings, Gregory and her team developed a patient satisfaction model, now being studied in nine California hospitals. Here, she tells Discoveries about what pregnant women want, the future of labor and delivery care—and how her own childbirth experience made her a better doctor.

Did you always know you wanted to be a doctor?

Pretty much. The story my family always tells is that I wanted to be a nurse, and my father told me I was too bossy and should be a doctor! That was around age 5. I’ve wanted to be a doctor ever since. I just sort of felt it as a calling. There was a moment when I thought I might want to be a teacher but, as it turns out, I’m a doctor who teaches because I’m on the full-time faculty, training residents.

What inspired your latest research?

The groundswell of women interested in home birth is a reflection that they’re not getting what they want in a hospital. Childbirth is the No. 1 reason for hospitalization globally, and yet medical centers usually do not ask questions about patient satisfaction specific to childbirth. That was a glaring need. We also want to make sure birth is safe. A big national effort is underway to standardize maternity care because of the frightening rise in maternal mortality in the U.S. This country has the highest rate in the developed world—more than 700 women die each year from pregnancy or childbirth-related causes. Significant racial disparities persist, with African-American women nearly four times more likely to die during childbirth than white women.

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What do women want when they’re having a baby?

They want respect, and they want to feel safe.

Communication is big. The more I talk to women, the less I am convinced that we do a good job of explaining what’s happening and why during the birth process. One of our findings was that, although women are the ones in labor, how their partners are treated is super important to them.

Another issue is breastfeeding. Nationally, hospitals are trying to get to 85% of patients exclusively breastfeeding at discharge. Breastfeeding provides significant health benefits to the baby, but some patients—particularly educated, affluent, professional women—have decided not to breastfeed and sometimes feel harassed. If she says no, she means no!

How was your own childbirth experience? Did any of it …

Weigh on me? I definitely think it made me a better doctor. You tend to give pat answers to certain patient complaints because that’s what you were trained to say. When you experience those issues yourself, you’re like, wow, that is some real pain!

But I had a labor nurse who was really supportive.

We watched TV and played cards, and she offered to give me a foot massage. I did not have an epidural. I’m a big proponent of physiologic labor, so I had to put my money where my mouth is. All my residents bet I wouldn’t make it, but I did.

What is the biggest challenge in improving the quality of maternity care?

People are afraid of change. For example, there’s still a tendency to think that a caesarean delivery is safer, without taking into consideration that it is major surgery with risks to the mom. European studies show that going through the birth canal is protective for the baby in terms of their immune system and the subsequent development of a normal microbiome for their gut. In the U.S., the C-section rate for first-time, low-risk mothers is around 32%. The Centers for Disease Control and Prevention has set a national goal to reduce that to below 24%. At Cedars-Sinai we’re just slightly above that. So we’re getting there.

KIMBERLY GREGORY, MD, MPH Vice chair of Women’s Healthcare Quality and Performance Improvement, Department of Obstetrics and Gynecology, director and fellowship director of the Division of Maternal-Fetal Medicine, and The Helping Hand of Los Angeles–Miriam Jacobs Chair in MaternalFetal Medicine

BORN AND RAISED

Born in Gary, Indiana, and raised in Los Angeles from the age of 5, she is the first doctor in her family. Her father was an aeronautical engineer, and her mother was a special education teacher.

THE FAMILY WAY

Married to Richard Casey, MD, an ophthalmologist at UCLA. Daughter Kendra, 21, is interested in pursuing medicine but as yet undecided on her career path.

RECHARGE TIME

Al Cuizon

Beyond caring for your patients, what motivates you?

I have ideas, and I feel a need to share them because they could make a difference. I’m fortunate to work with an extremely talented research team that can help me execute these ideas in a very scientific and rigorous way. My team has this saying: “Let’s just keep putting one foot in front of the other.” We believe in what we’re doing, and this kind of patient experience research is starting to become more accepted and valued. I think we’re on the right track.

What does the future of childbirth look like?

The opportunity to have a home-like birth in a safe hospital environment—that is the future. I think there will be a broader use of midwifery, and more hospitals may start having affiliated birth centers; that model works in a lot of European countries.

Also, I would like to see more one-on-one time with the nurse or midwife. Bonding with this person who knows what you’re going through is priceless.”

“I get my hair done religiously; that’s my treat!

We go to church, and we love live music. We’ll do Hollywood Bowl, Staples Center, Microsoft Theater— any kind of live music.”

BEST-EVER CONCERT

“Prince. Hands down. I don’t think I ever missed a Prince concert in any city I’ve ever been in. He once played every day for a week at the L.A. Forum, and I went five out of seven days.”

This interview has been edited and condensed.

WINTER 2020 | DISCOVERIES |

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Learn

Matters of the Heart

By CARRIE ST. MICHEL The heart busily beats about 115,000 times per day, while shuttling the 2,000 gallons or so of oxygenated blood that keeps the body’s other vital organs in business.

Plenty can go wrong with this four-chambered pump, as evidenced by the fact that heart disease is the leading cause of death worldwide. Fortunately, physicians like the 100-plus cardiovascular specialists at the Smidt Heart Institute have dedicated their careers to revolutionizing cardiovascular care.

Here, five Smidt Heart Institute experts weigh in on cardiology game-changers and— because nonexperts tend to associate the heart with this anatomically inaccurate emoji and all things pitter-patter—their favorite love stories as well.

ALFREDO TRENTO, MD

Senior Heart Surgeon Estelle, Abe and Marjorie Sanders Chair in Cardiac Surgery EXPERTISE: Alfredo Trento, MD, performed the first heart transplant at Cedars-Sinai in 1988. Since then, he’s performed more than 10,000 cardiac surgeries—including heart transplants, coronary artery bypass grafts, valve repairs and complex multivalve surgeries.

GAME-CHANGER: Robotic-assisted surgery. Since 2005, Trento has used a robotic-surgical system that’s improved patient outcomes for a host of procedures, from coronary artery bypass to mitral valve repair and replacement.

NEXT BREAKTHROUGH: Aortic heart-valve replacements made of polymers. Defective valves currently are replaced with mechanical or animaltissue-based valves that either wear out or require a lifetime of taking blood thinners. Polymer valves being tested for safety are free of these downsides and the surgery is minimally invasive.

FAVORITE LOVE STORY: Nine years ago, a 35-year-old married father of twin 3-year-old boys suddenly developed heart failure. Nine months later, Trento

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performed a successful transplant.

“Seeing the couple in the ICU simultaneously sobbing and hugging, you could feel the love,” Trento recalls.

ALI AZIZZADEH, MD

Director of Vascular Surgery EXPERTISE: While Ali Azizzadeh, MD, humbly describes himself as “a plumber for the body,” he’s widely recognized for his expertise in repairing trauma to the aorta and for pioneering minimally invasive techniques to treat vascular disease.

GAME-CHANGER: In 2018, Azizzadeh became the first vascular surgeon to use a minimally invasive device to repair potentially life-threatening aortic aneurysms.

NEXT BREAKTHROUGH: Azizzadeh’s sights are set on the aortic arch, which transports blood to the head, neck and arms. He’s testing a device to treat aneurysms and tears without making chest incisions.

FAVORITE LOVE STORY: At the tender age of 10, Azizzadeh saw Love Story, starring Ali MacGraw and Ryan O’Neal.

“That was my first introduction to an adult romantic relationship,” Azizzadeh says. He felt “profoundly sad” when

MacGraw’s character dies of cancer. “I became a doctor because I love science and people, but maybe this movie influenced me on a subconscious level.”

JIGNESH PATEL, MD, PHD

Medical Director, Heart Transplant Program Director, Cardiac Amyloidosis Program EXPERTISE: Jignesh Patel, MD, PhD, specializes in advanced heart failure.

“Being able to take care of very sick patients and get them better and back to their families is extremely fulfilling,” he says.

GAME-CHANGER: Demand for heart transplants consistently outpaces supply.

“What’s helping fill this void are ventricular assist devices,” Patel explains. These implanted devices buy time for those awaiting transplants and, in some instances, can restore heart function.

NEXT BREAKTHROUGH: Patel just completed a pilot study testing the investigational use of a drug to treat certain blood disorders. “We’re the first medical center worldwide to use this medication to prevent organ rejection, and we’re very pleased with the results.”

FAVORITE LOVE STORY: Patel managed the care of a woman who had a heart transplant. Soon after the operation, her boyfriend proposed to her, fully aware she would face lifelong medical challenges.

He became a professional athlete, and later an actor, but always made taking care of her his top priority. In the end, cancer took her life. “He was a man of his word and always by her side. Seeing that was very touching,” Patel says.

Pep Montserrat

JANET WEI, MD

NEXT BREAKTHROUGH: “Cardiovascu-

Cardiologist, Barbra Streisand Women’s Heart Center, Smidt Heart Institute Associate Program Director, Cedars-Sinai Cardiology Fellowship Training Program Assistant Medical Director, Biomedical Imaging Research Institute

lar disease is the leading cause of death among pregnant women and those post-pregnancy. We’ve recognized that pregnancy is really a woman’s first official stress test in life,” Wei says.

FAVORITE LOVE STORY: Jane Austen’s novel Pride and Prejudice warms Wei’s heart “because it’s not a traditional love story. Mr. Darcy and Elizabeth Bennet’s journey to build a relationship results in each becoming a better person.”

EXPERTISE: When Janet Wei, MD, was a resident, she diagnosed coronary microvascular dysfunction—a condition more common in women than men—in a woman with chronic angina that other doctors concluded was in the patient’s imagination. “She was so relieved her pain was caused by a real disease,” Wei recalls.

GAME-CHANGER: Wei says studies demonstrate that men are often brought to the cath lab for emergency treatment of acute heart attacks more quickly than women, and that women have higher heart attack morality rates. “We’ve conducted research showing that if the same protocol is followed for men and women, these gender differences disappear,” she says.

EVAN ZAHN, MD

Director, Guerin Family Congenital Heart Program, Smidt Heart Institute Director, Division of Pediatric Cardiology EXPERTISE: Evan Zahn, MD, is among the world’s preeminent interventional cardiologists. His revolutionary, lifesaving methods treat congenital heart defects and structural problems with minimally invasive procedures. He heads a nationwide clinical trial testing a procedure he’s pioneered to noninvasively mend holes in

the hearts of premature infants.

GAME-CHANGER: “One very meaningful advance is the dramatically increased survival rates for infant heart surgeries.

Another is our ability to treat all four valves of the heart without requiring open-heart surgery,” Zahn says.

NEXT BREAKTHROUGH: Zahn calls a stent he’s developing with biomedical engineers “the Holy Grail.” “The goal is to create a stent that could be inserted into a tiny baby’s narrowed pulmonary artery; it would then remain there throughout adulthood,” he explains.

FAVORITE LOVE STORY: Zahn’s parents.

After returning from World War II to his Brooklyn home, his father spotted a young woman sitting on a stoop. It was mutual love at first sight. “My dad died many years ago, and Mom consistently says, ‘I married the man of my dreams; there will never be anyone else.’”

LEARN MORE

For more stories from our heart experts, visit cedars-sinai.org/discoveries

WINTER 2019 | DISCOVERIES |

21

Think

10 Cancer-Fighting

‘Aha’ Moments AS TOLD TO SHERRY ANGEL

we’re hoping to answer through the Hispanic Colorectal Cancer Study—the largest of its kind, with nearly 2,000 patients.

“Aha” moments in cancer research are like earthquakes— the Big One could happen any time. But ideas and revelations on the lower end of the seismic scale can also have a major impact. Jane Figueiredo, PhD, heads the nation’s largest study on prevention and treatment of colorectal cancer in Latino people. Here, she shares revelations—some small, some earth-shattering—that drive her commitment to fighting colorectal cancer and cancer disparities in underserved populations.

We should not look at the U.S. Latino population as a single entity.

Most people still group Latinos together, but we can’t fully understand the cancer care needs of this underserved group without seeing how diverse it is. Research must encompass different cultural and socioeconomic perspectives as well as the genetics of colorectal cancer among Latino subgroups, with varying degrees of indigenous American, European and African ancestry.

1

Latinos are dangerously underrepresented in research investigating colorectal cancer. It’s astonishing that we have so little data about the disease in the largest ethnic minority group in the United States. Cancer is the leading cause of death among U.S. Latinos, and colorectal cancer is the second most common and fatal cancer in this population. Latinos tend to get colorectal cancer at a younger age and have more advanced disease when they are diagnosed. It’s particularly alarming that they’re experiencing a slower decline in mortality rates compared to non-Hispanic whites. Yet most of the research on this cancer focuses on non-Hispanic whites. Fortunately, this is beginning to change.

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2

Colorectal cancer is highly preventable. We have incredible opportunities to intervene—with screening tools such as the colonoscopy— and improve outcomes. Physicians and investigators have a responsibility to develop culturally sensitive education and prevention strategies that enable underserved populations to better protect their health.

3

Latinos have a lower rate of colorectal cancer screening than nonHispanic whites. What keeps Latinos from getting screened? Is this why they tend to be sicker when they get diagnosed? Or are they at higher risk genetically for more aggressive cancer?

These are very important questions that

4 5

Underlying causes are complicated.

Sorting this out to reduce cancer disparities requires scientists to adopt a multilevel framework for assessing disease risk—and do a lot of teamwork. As researchers, we need to engage the community, including policymakers, faith-based leaders and others in examining everything from the environment in which people live to their lifestyle choices, socioeconomic conditions and genetics.

6

Cultural influences count. As Latino populations assimilate into the U.S. lifestyle, they may acquire additional risk factors related to diet and lack of exercise that make them more susceptible to colorectal cancer. Across all major cancers, Latinos born in the U.S. have higher incidence and lower survival rates than those who are foreign-born.

7

Progress in cancer risk research may have unintended consequences. As we develop genetic models that can tell individuals whether they are at low, moderate or high risk for colorectal cancer, we also need to study their response to this information. For example, we don’t want those at low risk to stop taking preventive steps. We also need to understand risk differences across ethnic and racial populations and develop culturally tailored education. Everyone should make healthy choices—regardless of their level of risk.

8

Genetics and diet can mean double trouble. Burgers, hot dogs and cured meats shouldn’t be staples in anyone’s diet. But we now know that avoiding these foods is even more critical for the 1 in 3 people who have inherited a certain genetic variant that, combined with red or processed meat, substantially increases the risk of colorectal cancer. The good news: What we are learning about how genes and diet interact increases our ability to prevent cancer.

9

Davide Bonazzi

Vitamin supplements may do more harm than good. Complementary health practices are common among Latinos who have survived colorectal cancer. One study showed that 35% use herbal products and dietary supplements, but most don’t talk about this with their doctor. It’s important to share this information because these are biologically active agents that can interact with medication—and seriously increase health risks.

10

Colorectal cancer and heart disease share risk factors such as obesity, poor diet and lack of exercise. In collaboration with the Smidt Heart Institute and the Biomedical Imaging Research Institute, we’re beginning to study the risk of cardiovascular problems in colorectal cancer survivors so we can help prevent another potentially life-threatening health crisis.

Investigator: Jane Figueiredo, PhD Director of Community and Population Health Research, Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute Associate Director, Cedars-Sinai Center for Integrated Research in Cancer and Lifestyle Faculty Member, Cedars-Sinai Research Center for Health Equity

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SPECIAL REPORT

unfair Sex The

Gender inequality permeates healthcare. Medical studies excluded female patients for decades, while women’s symptoms have been dismissed for centuries. In this special report, we feature real women who have overcome a biased system, and shine light on the female clinicians and investigators leading the charge to understand and solve women’s health challenges.

By CASSIE TOMLIN AND NICOLE LEVINE Photography by RACHAEL PORTER

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“I dug my heels into the carpet and said ‘I won’t leave this office until you find out what’s wrong with me.’”

Patti Lavine AGE 62 SYMPTOMS Stabbing pain between shoulder blades, sweating, pressure and tingling in her arms and chest, severe fatigue, family history of fatal heart disease DOCTORS SAID For months she sought answers from doctors, even providing death certificates as proof of her risk for heart disease. One doctor suggested she see a psychiatrist, confirming her fears she wasn’t being taken seriously.

EVENTUAL DIAGNOSIS At her insistence, the doctor finally ordered an angiogram, which revealed two of her arteries were more than 90% blocked.

TODAY Loving her work with a dog rescue for Brittany spaniels

p

SPECIAL REPORT

ain gripped Victoria Ventura’s chest so fiercely she couldn’t climb stairs, eat—or even take a deep breath.

It throbbed down her arm and into her jaw, common symptoms of heart disease, but the first doctors she saw dismissed cardiac trouble as the source. The next nine years were a crucible of misdiagnosis.

Stress, a benign brain tumor and uterine bleeding were all blamed and treated—but the ache in her chest remained. At age 47, Ventura saw a cardiologist who found an abnormality in her electrocardiogram.

Still, he told her, “Young lady, I’ve been doing this for over 30 years, and this has nothing to do with your heart.”

“I felt dismissed because I am a woman,” Ventura says.

After nearly a decade of pain, she sought help from C. Noel Bairey Merz, MD, a world leader in identifying how heart disease manifests in women. From Bairey Merz, director of the Barbra Streisand Women’s Heart Center at the Smidt Heart Institute, Ventura learned that she has coronary microvascular disease—a heart condition that mostly affects women and doesn’t always appear the way heart disease does in men.

Her story is all too common. Women and girls are chronically misdiagnosed, underdiagnosed and mistreated—and not just for heart disease. They suffer, unrecognized, from autoimmune diseases, post-traumatic stress disorder and attention deficit hyperactivity disorder (ADHD).

Sex and gender bias is baked into the healthcare system.

Since females have been historically underrepresented in clinical trials and basic science studies, drugs are developed for male bodies and physicians often look for men’s symptoms.

“It’s not necessarily willful, but people study the things they identify with and are interested in,” says Nancy Sicotte, MD, chair of the Department of Neurology. “Plus, female hormones are a complicating factor, so there’s been a feeling that it’s easier to study medicine from a male perspective.”

Correcting Course

Often, the male perspective has confined the study of women to their breasts and reproductive organs, limiting understanding of less explicit, but impactful, sex differences in other systems of the body.

“Women’s health is often still treated as ‘bikini medicine,’ but more women still die of lung cancer than breast cancer and from colon cancer than ovarian cancer,” Bairey Merz says.

“We can do better.”

In some cases, doing better comes in the form of renewed

A Force for Change Cedars-Sinai launched the Center for Research in Women’s Health and Sex Differences (CREWHS) to address the pervasive gender bias in healthcare research and medical practice. The goal of the women-led center is to support Cedars-Sinai

investigators “so they can discover and implement knowledge that will change the course of women’s lives,” says CREWHS co-founder Sarah J. Kilpatrick, MD, PhD. Discoveries interviewed each of these faculty leaders for this special report.

CREWHS Steering Committee Susan Cheng, MD, MMSc, MPH Director, Cardiovascular Population Sciences, Barbra Streisand Women’s Heart Center, Smidt Heart Institute Director, Public Health Research, Smidt Heart Institute Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science

26

Roberta A. Gottlieb, MD Director, Molecular Cardiobiology Director, Metabolism, Mitochondria and Mouse Cardiac Phenotyping Core Vice Chair, Translational Medicine, Department of Biomedical Sciences Dorothy and E. Phillip Lyon Chair in Molecular Cardiology in honor of Clarence M. Agress, MD

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Sarah J. Kilpatrick, MD, PhD Chair, Center for Research in Women’s Health and Sex Differences Steering Committee Chair, Department of Obstetrics and Gynecology Associate Dean, Faculty Development and Diversity Helping Hand of Los Angeles Endowed Chair in Obstetrics and Gynecology

C. Noel Bairey Merz, MD Director, Barbra Streisand Women’s Heart Center, Smidt Heart Institute Director, Linda Joy Pollin Women’s Heart Health Program Director, Erika J. Glazer Women’s Heart Research Initiative Director, Preventive and Rehabilitative Cardiac Center Irwin and Sheila Allen Chair in Women’s Heart Research

Nancy L. Sicotte, MD Chair, Department of Neurology Director, Multiple Sclerosis and Neuroimmunology Program Women’s Guild Distinguished Chair in Neurology

Jennifer Van Eyk, PhD Director, Advanced Clinical Biosystems Institute, Department of Biomedical Sciences Director, Basic Science Research, Barbra Streisand Women’s Heart Center, Smidt Heart Institute Erika J. Glazer Chair in Women’s Heart Health

“I felt dismissed because I am a woman.”

Victoria Ventura AGE 49 SYMPTOMS Seven years of severe chest pain and difficulty breathing DOCTORS SAID Her nerves, her uterus, her brain and stress were at fault.

A cardiologist said it wasn’t her heart, even after she had abnormal test results.

EVENTUAL DIAGNOSIS Microvascular disease NOW Hasn’t had chest pain in over a year

Truzane Styles AGE 64 SYMPTOMS Multiple heart attacks with loss of consciousness, pain, shortness of breath, difficulty walking for nearly a year INCONCLUSIVE TESTS She passed out during a stress test, but none of the tests registered a problem.

EVENTUAL DIAGNOSIS Microvascular disease. “Dr. Bairey Merz said I did have a heart attack. The other doctors just missed it.”

TODAY “I can go up a flight of stairs with no fear of having another heart attack.”

“They kept telling me I don’t fit the classic symptoms of what a heart attack looks like, and I found that frustrating. You start to wonder why you think you don’t feel good.”

SPECIAL REPORT

guidelines from national regulatory bodies. In 1992, the sleeping pill Ambien flooded the market, quickly becoming the nation’s most prescribed drug. In 2013, after studies showed that women wake up with more of the drug in their bodies because they metabolize it differently, the Food and Drug Administration cut the dosage guidelines for women by half. For 21 years, women had been overmedicated by nearly twice the safe amount.

“Unfortunately, that’s hardly an isolated incident,” says Sarah Kilpatrick, MD, PhD, chair of the Cedars-Sinai Department of Obstetrics and Gynecology. “Some 80% of drugs withdrawn by the Food and Drug Administration between 1997 and 2000 were removed at least in part because they posed a risk to women. The pharmaceutical industry and medical practitioners treat women as if they are just smaller men. They are not.”

Now, new rules from the National Institutes of Health (NIH), the country’s largest biomedical research funding agency, aim to circumvent such instances of ignorance-induced harm. Traditionally, animal research studies have focused almost exclusively on males, reasoning that varying estrogen levels in female animals could muddy the results.

That means female models of disease have rarely been used, making it difficult to devise clinical studies that could lead to useful discoveries about women.

In 2016, the NIH announced it would require investigators to include female animals in all studies, and collect, analyze and report how they differ from male animals—noting that female animals’ estrogen fluctuations are among the many reasons that scientists need to study them.

The NIH rolled out a similar policy in 1986, demanding women be represented in human subject studies, but only in the last 10 years have women become close to half of U.S. clinical trial participants.

“Males should not be considered the default, with females an inferior or lesser research subject,” says Chyren Hunter, PhD, associate director of Basic and Translational Research in the NIH Office of Research on Women’s Health. “These policies are going to benefit women and men as we begin to

develop more personalized care for sex and gender across many disease states and treatments.”

Roberta Gottlieb, MD, director of Molecular Cardiobiology at Cedars-Sinai, says this research rule could help create a framework for organizing sex differences.

“Our failure to understand sex differences in how disease manifests and how treatments work means that we’ve been mistreating half the population,” Gottlieb says.

A New Horizon

Ventura’s arduous health journey ultimately led her to enroll in a Cedars-Sinai clinical trial for an investigational stem cell treatment for microvascular disease. Her pain has ebbed and she is happily running the printing and graphics business she owns with her husband in Lancaster, California.

“I never realized before how sometimes we settle for less,” she says, reflecting on how long she she hid her pain and exhaustion from friends and colleagues. “We say ‘OK,’ and we let it be. And we shouldn’t have to settle like that.”

At Cedars-Sinai, medical pioneers are tackling sex and gender bias on multiple fronts. Research is uncovering sex differences that impact what health looks like, whether medications work, and how and when disease is most likely to strike. Investigators are advocating for major changes to every facet of healthcare—how we train doctors, how we treat patients, how we conduct medical research and how we invest in the science that reveals our differences.

It’s a challenge, even for female researchers.

“As women, we want to think we’re not that different from men,” says Susan Cheng, MD, MPH, MMSc, director of Public Health Research in the Smidt Heart Institute. “We’re subject to the same exposures and environment, so we think we should be treated equally, which has led us to shoot ourselves in the foot, because it causes us to be analyzed and studied as a variant of male. The more carefully we look at the data, the more we realize we’re not just another line on the same axis.”

VIDEO

To see these women tell their stories of overcoming gender bias in medicine, visit cedars-sinai.org/https://ceda.rs/unfairsex

RESEARCH LOWLIGHTS

Women are up to 25% more likely to be sent home from the emergency room while having a stroke.

Women are twice as likely as men to develop PTSD, but they suffer symptoms for four years before a diagnosis, while men go untreated for one year.

In a nationwide survey from 2016, 63% of medical students said they believe their curriculum is mostly related to males.

In the same survey, only about 13% of medical students reported being taught that dosing guidelines for Ambien differ for men and women.

From 1977–1993, the FDA recommended excluding women of “childbearing potential” from joining clinical trials for new drugs.

From 1909–2009, only 15% of medical research studies included both male and female animal models.

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Everybody Hurts How a toxic cocktail of ignorance and bias fueled decades of underdiagnosis for women in pain.

“The diagnosis just got missed for so long—women’s symptoms he medical field has a long history of dismissing women’s pain, despite actual differences were minimized by doctors who thought that women didn’t get between how the sexes interpret it. In women, this disease and that their back pain came from having a baby,” says pain is more intense than in men. In many Mariko Ishimori, MD, interim director of the Division of Rheumatology. cases, even with the same disease, studies show Ishimori says women need to take their own pain seriously and that women and men experience pain in different be open and detailed in discussing it. More importantly, she says, body parts and to different degrees. The roots of doctors need to listen carefully. these sex differences likely lie in the complexities of “As physicians, we should be detectives,” Ishimori says. “When hormonal functions, gene expression and neurobiola patient doesn’t mention back pain because she doesn’t want to ogy—and the connections aren’t fully understood. be seen as a complainer, that means we’re missing the complete Perhaps this is why women seeking help from their picture. It’s the job of physicians to draw those facts out by asking doctors are frequently dismissed as “hysterical, emotional, not pointed questions. You have to be open to every possibility when wanting to get better, malingerers and fabricating the pain, as if it you meet somebody.” is all in her head,” according to a 2018 literature review on gender bias in healthcare.

Doctors must first and foremost recognize pain and tailor an Pain is, by definition, a physical and emotional experience that individualized search for the source of the problem, says Howard should be managed patient by patient, according to Cedars-Sinai Rosner, MD, director of the Cedars-Sinai Pain Center.

Pain Center expert Mary Alice Vijjeswarapu, MD, assistant profes“No matter who is sitting in front of us, we’ve got to believe what sor of Anesthesiology. they’re telling us,” Rosner says. “They should never be minimalized “The idea that women are more emotional about their pain needs or trivialized. We also have to understand that physiological and a deeper dive,” she says. “We know pain has a psyanatomic dissimilarities can make a difference, and chological impact regardless of gender, and that can we’re still learning a lot about that.”

RESEARCH present in different ways for different patients. WomRevelations about variations in AS point to a LOWLIGHT en are just traditionally written off more.” need for greater study of a range of inflammatory Recent research suggests that, for one painful auconditions, Ishimori says, especially since 80% of Although, nationtoimmune condition, the tendency to dismiss womautoimmune patients are women. Rheumatoid wide, more men en, coupled with a lack of research into sex-based arthritis, Sjogren’s syndrome and lupus—diseases than women die of differences, may be to blame for decades of underdiin which the immune system attacks healthy tissue opioid overdoses, agnosis. and organs—are chronic and debilitating. New drug fatalities are rising in middleAnkylosing spondylitis (AS), a rheumatologic confunding to study their causes and symptoms will aged women. This help investigators consider their various manifesdition that inflames the spinal joints, was long may be due to the tations across the sexes. thought to be overwhelmingly a man’s disease. We fact that women are Cedars-Sinai researchers are investigating connow know that women make up at least a third of twice as likely to be nections between lupus and heart disease, if stem AS patients, if not half. The disease has long been prescribed opioids.

In addition, a defined by its most common symptoms: lower back cell infusions could benefit lupus patients and growing collection of pain and stiffness. New findings show that women whether certain drugs can prevent the condition studies indicates with AS also experience neck, hip and joint pain, in women who are at risk for developing it. The that women develop which means they may suffer more complications resulting knowledge will help physicians more addiction more and a worse quality of life while waiting for the corquickly and accurately alleviate pain—in all kinds quickly than men. rect diagnosis. of patients. –CT

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“Finally a doctor just said ‘I don’t know what to do.’

I’m glad that doctor acknowledged he couldn’t help me.”

Hinna Parwaiz AGE 30 SYMPTOMS Weakness and exhaustion so severe she couldn’t turn a doorknob or hold a cup of tea DOCTORS SAID After inconclusive blood tests and on-and-off hospitalization, doctors accused her of drinking, smoking or overdosing on Tylenol. “I’m Muslim and, in our religion, we don’t do those things. There was no point for me to lie because they were doing so many tests.”

EVENTUAL DIAGNOSIS She was referred to Vinay Sundaram, MD, director of Hepatology Outcomes Research, who diagnosed her with autoimmune hepatitis, a rare condition more common in women—and more severe in women in their 20s and 30s NOW School social worker who appreciates little things like enjoying meals with her family

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Lisa Hoffman AGE 63 SYMPTOMS Months of abdominal pain, cramping, diarrhea and acid reflux EVENTUAL DIAGNOSIS Irritable bowel syndome.

Mark Pimentel, MD, director of the Medically Associated Science and Technology Program at Cedars-Sinai, helped her identify what foods trigger her symptoms. She also takes medications that help her manage them.

TODAY She cooks foods she enjoys. She doesn’t shy away from long car trips or feel like she has to be close to a bathroom at all times.

“Dr. Pimentel changed my life.”

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“My previous doctor didn’t take me as seriously as I would have liked. He kept saying, ‘Everyone has some form of indigestion’ and ‘Just learn to live with it.’”

SPECIAL REPORT

Hearts and Minds

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Two Cedars-Sinai leaders discuss how to make healthcare more equitable for all.

hen there’s “a need for big changes, people always say, ‘That’s really hard to do!’ But then they do it,” says Nancy Sicotte, MD, chair of the Department of Neurology.

Changes necessary to improve healthcare for women will require rethinking how we train doctors and researchers, adds C. Noel Bairey Merz, MD, director of the Barbra Streisand Women’s Heart Center. Among Sicotte and Bairey Merz’s goals: Increase the number of women in science and medicine, and better educate all doctors to be aware of sex and gender differences.

On the Importance of Visibility SICOTTE: When my daughter was 7 or 8, she came running home from school one day, burst through the door and said: “Mom! Guess what! Men can be doctors, too!” I just laughed. It was such a revelation to her. So at least the younger generations understand. Now she’s finishing up her first year of medical school. These changes don’t have to take long.

We see versions of this all the time. We noticed a female bias among folks applying to our residency program here. Turns out the most influential factor for someone picking a residency is the program director. Women are more likely to want to train in programs with a woman director. That really made me step back and consider how I’m a role model for both men and women.

The Building Blocks of Precision Medicine BAIREY MERZ: We talk about genomics, proteomics, artificial intelligence, machine learning—but what if we just started with when the patient walks through the door. Are they male or female?

SICOTTE: The way I see it, we have two levels at work here.

There’s the implicit level, just having female role models and physicians on the ground who are going to be addressing gender differences in many ways, like clinical presentations and managing illnesses. Then the explicit level, and that’s the curriculum, where we still have work to do. We have to inspire this next group of trainees to ask these most fundamental questions if we’re going to move toward medicine that’s truly targeted toward individuals.

BAIREY MERZ: It’s just sharpening the sword. We keep working

at it. –NL

If They Teach to the Test, Change the Test BAIREY MERZ: If you want doctors to understand sex differences, you have to put it on the medical board test. Then it gets into the curriculum. A coalition did some work on this almost 20 years ago in cardiology and other disciplines, starting with the board exams that physicians must take to be licensed. I was eventually asked to serve on a question-writing committee.

SICOTTE: So that is the quickest, easiest way to inculcate medical students with new information. Get it on the test. But you have to have a seat at the table when the tests are being made. I don’t think sexism and racism occur necessarily because people have bad intent. It’s often because it doesn’t represent their experience. That’s the power of diversity.

Dr. Nancy Sicotte and Dr. C. Noel Bairey Merz aim to increase equity and awareness of gender differences.

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Misconceptions

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Studying pregnant women carries risks—but so does excluding them from research.

the body. The program provides cardiovascular assessment and hat we don’t know about the effect treatment if needed, as well as heart health education and of medications on pregnancy could fill a followup for women who had preeclampsia, gestational large medical textbook. More than 90% of hypertension, gestational diabetes or other adverse pregnancy prescriptions haven’t been tested on outcome. expectant mothers, leading to a lot of uncertainty.

“Few studies have been done on pregnancy with underlying A Push to Better Understand Pregnancy medical diseases or medications,” says Sarah Kilpatrick, MD, Faculty leaders across Cedars-Sinai formalized their efforts to chair of the Department of Obstetrics and Gynecology. “We just address the pressing need to study women’s health by launching don’t have good information. Is it hard to study? Yes. But it the Center for Research in Women’s Health and Sex Differences. doesn’t matter if it’s hard. Women deserve better.”

The center awarded its first-ever grant in spring 2019.

Pregnancy has been difficult to study for a host of medical and “I was blown away by the quality of the science and the ideas ethical reasons, largely driven by a desire to protect women and put forward,” Kilpatrick says. their developing babies. While arguing that it might be better to That first study, led by Cedars-Sinai gastroenterologist be safe than sorry, not studying pregnant women ultimately Nirupama Bonthala, MD, will investigate pregnancy and affects their health and safety. The Centers for Disease Control inflammatory bowel disease (IBD), a group of conditions, and Prevention found that about 90% of pregnant women take including Crohn’s disease and ulcerative colitis, in which the at least one medicine—including over-the-counter drugs—durdigestive tract is constantly swollen, causing diarrhea, abdomiing pregnancy, and 70% take prescription medication. nal pain, bleeding, fatigue and weight loss.

High blood pressure, diabetes, asthma, mental Bonthala aims to correct a major misconcephealth conditions, autoimmune disorders, cancers tion about IBD, a condition shared by 3 million RESEARCH and other conditions require ongoing treatment.

Americans. “I find a lot of women with IBD think LOWLIGHT But few medications are approved for use during they cannot get pregnant and cannot have a pregnancy, and most drugs come with little data to family, when for the vast majority of them it is Infertility is just as often the culprit of a guide doctors’ and patients’ decisions. safe,” she says. man’s physiology as Until 2019, federal policies listed pregnant With Kilpatrick, Bonthala runs one of the a woman’s—and the women, along with children and people with nation’s only clinics specifically designed for problem is more mental health disabilities, as “vulnerable to pregnant women with IBD. Bonthala serves as common than coercion or undue influence,” largely barring them their GI specialist and Kilpatrick as the maternal people think, says Jessica Chan, MD, from participating in clinical trials. Changing this fetal medicine specialist—and patients see both assistant professor policy marks a small step toward finding ways to doctors on the same day. of Obstetrics and safely include mothers-to-be in clinical trials. The While most of them have healthy pregnancies, Gynecology. About National Institutes of Health is now awarding some women seem more prone to IBD flare-ups 1 in every 8 couples more grants to study pregnancy itself as well as during pregnancy, which can lead to preterm seeking to have children face funding research into what gestation can tell us birth, low birth weight and miscarriage. Bonthala infertility. “It’s a about a woman’s future health. and her team will study tissue samples from secret diagnosis that Cedars-Sinai doctors and scientists are commitmothers with IBD, seeking a common biomarker a lot of people ted to leading this new trend, pursuing studies on to help predict which women are at highest risk struggle with and preeclampsia—one of the most common and of pregnancy complications. there may still be a stigma surrounding serious pregnancy complications—and enrolling “If we knew which women were at risk, we treatment,” she says. women in the Postpartum Heart Health Program, could change their treatment and potentially recognizing that pregnancy is like a stress test for improve outcomes,” Bonthala says. –NL

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“It’s common for women to think we have to grin and bear it.”

Melanie McComb AGE 27 SYMPTOMS More than a decade of severe abdominal pain before being diagnosed WHAT SHE THOUGHT At first she thought she had “excitement pains” caused by kissing her boyfriend. Later, she described them as excitement pains coupled with “bad periods.”

DOCTORS SAID “It was psychosomatic from guilt because I was kissing boys.”

EVENTUAL DIAGNOSIS Endometriosis NOW Living pain-free with her fiancé and pursuing a writing career

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“I don’t think any woman should die because she’s been ignored by her doctors.”

Maria Robles Garcia AGE 54 SYMPTOMS Nearly a year of vomiting, diarrhea, abdominal pain, weight loss with a swelling abdomen, hair loss, hard lumps in her belly, heavy periods, chronic body pain, severe back and pelvic pain DOCTORS SAID She had irritable bowel syndrome and suggested she lose weight. She begged for a CT scan three times to no avail.

EVENTUAL DIAGNOSIS Stage 2 ovarian cancer. After going to the Cedars-Sinai Ruth and Harry Roman Emergency Department, doctors found and removed a 25-pound tumor on one ovary and a 5-pound tumor on the other.

ADVICE “Never be afraid to advocate for yourself. No one, not even doctors, knows your body better than you do.”

TK Credit Here

NOW Enough energy to mow the lawn and participate in Cedars-Sinai’s cancer survivorship program

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The Age Gap In older age, why are women prone to more severe illness?

t’s a paradox that science is only now seeking to understand: Women live longer and appear to age better than men—but when they do develop disease, they suffer worse outcomes.

“The idea that women are healthier and live longer is an oversimplification of what’s going on with us as we age,” says Susan Cheng, MD, MPH, MMsc, director of Public Health Research in the Smidt Heart Institute. “It’s not a phenomenon that is widely recognized, but when women develop disease, we tend to carry a heavier burden.”

Cheng’s lab is interrogating a trove of existing population health data—decades of blood work, physical measurements, cognitive tests, lifestyle information and disease outcomes collected from tens of thousands of people—in hopes of

illuminating intricate biological pathways that lead to disease across the sexes. She hopes that better clarity will fuel the development of more personalized, sex-specific guidelines on how to diagnose and treat disease. The ultimate goal is better care for both women and men.

Among the questions Cheng seeks to answer: In older age, why are women more predisposed to certain types of heart failure than men? Why do women in the earliest stages of Alzheimer’s disease suffer worse cognitive decline? When women develop impairment in kidney function, why are they prone to worse cardiovascular outcomes?

“We need to reorient ourselves, drop the assumptions we’ve made about male/female differences and start with a blank slate,” Cheng says. “Then we can begin to make more progress in terms of better understanding how women and men really are different in health as well as in disease.” –CT

Progress, Molecule by Molecule Microscopic diagnostic clues could bridge a healthcare gender gap.

b

iomarkers—measurable traces of molecules in blood or tissue—can provide clues for diagnosing and treating diseases. They indicate distinctions in age, lifestyle and chronic conditions—and they also promise to reveal crucial differences in how disease acts in women and men.

“The fundamental biology between men and women is often different,” says Jennifer Van Eyk, PhD, director of Basic Science Research in the Barbra Streisand Women’s Heart Center. “That means diseases and their underlying mechanisms can affect us differently.”

One clear example: Heart attacks traditionally have been diagnosed with a test measuring the level of troponins in the blood. These proteins play a role in contractions of the cardiac muscle, and more of them appear in the bloodstream following heart injury. However, even though data shows that women in cardiac crisis have lower levels of troponins than men, the tests remain one size fits all, resulting in women’s heart attacks often going undiscovered.

Now, a study that only includes women, Van Eyk’s team is identifying biomarkers that she predicts will allow for early and nearly continuous monitor-

ing of patients with atherosclerosis. Her team also seeks to use biomarkers to identify patients with rheumatoid arthritis (RA) who are at particularly high risk of developing heart disease. RA is a condition that primarily affects women.

Other paths of biomarker exploration include traumatic brain injury, chronic kidney disease and urinary pain syndrome.

Although the Van Eyk Laboratory focuses on heart disease, sex differences have been documented in many health conditions, including cancer, Alzheimer’s disease and prediabetes. –NL

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Menopause Matters More than a third of women are in or past menopause. Yet medical understanding of the process and how it should be treated remain cloudy.

The menopause symptoms hot flashes and night sweats strike about 80% of women—and can last more than a decade.

Additionally, nearly half of the 50 million menopausal women in the United States suffer from vaginal dryness and changes that can lead to sexual discomfort and increase the risk of getting urinary tract infections. Though both hormonal and nonhormonal therapies can safely and effectively improve vaginal health, one study found only about 11% of women who sought help from physicians found it.

But menopause is more complicated than its wretched side

effects: The dramatic decline in estrogen, which happens to most women around age 51, changes the body in ways that are still not fully understood—by women or doctors.

We know that menopause coincides with a rise in a woman’s blood pressure and bad cholesterol, which increases heart disease risk. We know that during the first year of menopause bone density dips drastically, putting women at risk for osteoporosis. But only recently have we begun to understand the connections between menopause and depression, dementia, Alzheimer’s disease and sexual health.

Hormonal Fluctuations Hormone replacement therapy (HRT)’s reputation has undergone dramatic ups and downs on the way to becoming the standard treatment for menopause symptoms and related conditions of aging. Here, a brief history of the fraught, ever-changing knowledge about HRT.

1942 UPTREND

The Food and Drug Administration (FDA) approves estrogen hormone therapy to treat hot flashes and night sweats.

1950 Studies show that women’s heart disease spikes at around menopause, leading to the accepted hypothesis that low estrogen is to blame for heart disease.

1966 Feminine Forever, by Robert Wilson, MD, claims that menopause is a “totally preventable” estrogen-deficiency, spurring a rash of estrogen prescriptions so women will be “much more pleasant to live with” and “not become dull and unattractive.”

DOWNTREND

1975 The long-term Coronary Drug Project clinical trial on the effects on men (and only men) who previously suffered heart attacks is stopped early, noting that men taking estrogen have more heart attacks and blood clots.

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2002 The Women’s Health Initiative publishes its results, causing panic about HRT. The trial is stopped three years early because women who began taking hormones 10 years after menopause suffered increased risk of breast cancer, heart attack and blood clots.

SPECIAL REPORT

“Often we think of menopause as simply the end of a woman’s periods, but it’s really a systemic and global change throughout the whole body,” says Jessica Chan, MD, assistant professor of Obstetrics and Gynecology, who specializes in reproductive endocrinology.

“We know menopause impacts patients’ quality of life, but we don’t know to what extent we could be helping them get through it,” she adds. “We need more dedicated research so we can take care of women as they transition—not just ease their symptoms, but improve their long-term health.”

Chrisandra Shufelt, MD, director of the Women’s Hormone and Menopause Program, a specialized clinic in the Barbra

1975 Two studies in the New England Journal of Medicine find that estrogen alone increases endometrial cancer risk. FDA recommends estrogen plus progestin for women who still have a uterus.

Streisand Women’s Heart Center at the Smidt Heart Institute, says our collective understanding of menopause is still recovering from the confusion that arose over the course of a decade about the risks of menopause hormone therapy. Physicians are beginning to recognize that women deserve individualized treatment for their concerns, “to treat the right symptoms at the right time,” she says.

“Menopause is not just about the reproductive system,” she says. “The symptoms can be different in every woman, and they’re vast and impact probably every area of our bodies. It’s not terribly surprising that if doctors are confused about menopause, patients are going to be confused about menopause.” –CT

1993 1990s Several observational studies show that women taking estrogen suffer fewer deaths from heart attack and blood clots. HRT becomes the country’s most prescribed category of drug.

2017

The National Institutes of Health launches the Women’s Health Initiative, the first clinical trial aiming to determine if HRT prevents chronic conditions, including heart disease, in postmenopausal women.

The North American Menopause Society publishes an updated position statement calling HRT the most effective treatment for hot flashes and vaginal symptoms when prescribed in healthy women at the onset of menopause.

2007 Prescriptions for HRT plummet by 80%. Women’s Health Initiative investigators re-analyze their finding to conclude that women who start HRT within 10 years of the onset of menopause did not have increased risk of coronary artery disease.

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A Disease

Ignites:

When HPV Leads to Throat Cancer

THE USUALLY HARMLESS SEXUALLY TRANSMITTED HUMAN PAPILLOMAVIRUS (HPV) IS TRIGGERING A SURGE OF THROAT CANCER AMONG BABY BOOMERS. THE SEXUAL REVOLUTION THAT LIBERATED A GENERATION ALSO ESCALATED THEIR EXPOSURE TO THE VIRUS. TWO CEDARS-SINAI INVESTIGATORS ARE WORKING TO EASE THE BURDEN OF TREATMENT ON THE POPULATION MOST AT RISK: OLDER MEN.

By SHERRY ANGEL Illustration by YUKO SHIMIZU

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“W

here did it come from?” Bill Reid asked.

“It makes no difference,” his wife, Ruth, replied.

His question wasn’t about his newly diagnosed throat cancer. It was about what caused it: the sexually transmitted human papillomavirus (HPV).

At age 76, Reid had been feeling fine, except for some discomfort from what he thought was postnasal drip. Then, in early 2016, a routine check-up led to the throat cancer diagnosis. He was still absorbing the news when he asked about HPV. His doctors at Cedars-Sinai explained that 70% of throat cancers are caused by HPV, and the virus is so prevalent that no one can trace its origin.

HPV is like the common cold: easy to catch and usually harmless and fleeting. But high-risk strains can linger undetected for many years and then trigger a potentially life-threatening health crisis. HPV-related throat cancer is increasingly prevalent among men like Reid. His care team at Cedars-Sinai was led by two clinical scientists who share a deep concern about the growing impact of HPV-related throat cancer on his generation.

Allen Ho, MD, director of the Head and Neck Cancer Program in Cedars-Sinai’s Samuel Oschin Comprehensive Cancer Institute, and Zachary Zumsteg, MD, assistant professor of Radiation Oncology, were among the first to document a sharp increase in HPV-positive oropharyngeal squamous cell cancer—which affects the back of the throat, base of the tongue and tonsils—among persons over age 65, predominantly white men. Scientists predict that incidence of the disease will continue to rise dramatically in this group for at least the next decade.

As baby boomers age, this cancer could take a heavy toll on quality of life at a time when patients may already be grappling with multiple health issues.

Love and Biology

O

n July 4, 1989, Reid, then a California resident traveling on business, looked up from a Robert Ludlam novel in an airport boarding area and saw a woman who was “very attractive in a non-flashy sort of way.” Their eyes met. After they landed in Florida, he approached her. Their first date was that night. Eight months later, after a whirlwind long-distance courtship, they were married and began their life together in Florida.

Like most couples, they had no specific idea what “in sickness and in health” might mean for them. But they never doubted they would be there for each other in a crisis.

After his diagnosis, Reid’s wife, a retired surgical nurse, reassured him: “Whatever caused this cancer makes no difference. It’s not like you can put a mask on and avoid HPV.” When Ho gives a diagnosis related to HPV, he offers information that he hopes will spare patients and their partners from going down a rabbit hole of questions related to sexual history. “The virus is pretty much everywhere—80% of people who are sexually active get the infection at some point in their life,” he says.

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Nearly 80 million Americans currently have one of the many types of HPV, according to the Centers for Disease Control and Prevention (CDC). In 9 out of 10 cases, the immune system fights it off within a couple of years with no symptoms. But high-risk HPV causes the majority of cancers of the cervix, vagina, vulva, penis, anus and throat. While Pap smear tests help identify women at risk for cervical cancer early, no screening test is available for any of the other HPV-related cancers. Throat cancer has surpassed cervical cancer as the most common HPV-related cancer in the United States, according to the National Cancer Institute.

Ho and Zumsteg assure patients there’s no way to know how they got HPV or how long they’ve had it. “We do a lot of destigmatizing,” Ho says. “This is something patients have no control over. It just happens.”

The rate of HPV-related throat cancer is significantly higher among men than women. The same is true for the rate of oral HPV infection. At any given time, 10% of men have oral HPV versus 3.6% of women, according to the CDC. Women may have a stronger immune response to the virus than men.

“It could be biological or behavioral. We don’t know,” Ho says.

“But we do know that certain sexual practices increase the risk.”

Changing Sexual Mores

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umsteg co-authored a paper published in June 2019 in the Journal of Clinical Oncology that showed the sharp increase in HPV-related throat cancer among this population reflected a growing risk to those born between 1940 and 1960.

The study suggested that this was likely due to changes in sexual behaviors during the 1960s and beyond, as practices that increase exposure to HPV—including multiple partners, earlier sexual activity and oral sex—became more prevalent.

The HPV virus can be transmitted through any sexual, skin-toskin contact, including deep kissing, notes Bobbie J. Rimel, MD, assistant professor of Obstetrics and Gynecology at Cedars-Sinai.

She explains that the virus is passed between mucous membranes like the common cold. Just as some people get pneumonia from a cold, some develop cancer from HPV. Smoking and alcohol can increase the risk that HPV will cause cancer, according to the CDC. Scientists have provided an effective solution—the HPV vaccine.

But only about 49% of teens are up to date on the vaccine. Rimel believes a realistic view of sexual behavior in today’s world is needed to increase the vaccination rate.

“We’ve moved on from the preconceived notions of sex that our grandparents had,” she says. “Part of the sexual revolution was a sexual evolution, and we have to go with that in science, too. Thank God we have scientists who developed a vaccine that can protect our children and grandchildren from HPV-related cancers.”

The Reids set aside the topic of HPV to focus on “getting rid of cancer,” but they knew they would come back to it later—not to discuss the past but to advocate that boys and girls get the HPV vaccine, along with adults up to age 45. As wine ambassadors at

Ruth Reid lands a kiss on husband Bill at Europa Village winery in Temecula, where they are wine ambassadors. Bill can no longer taste his favorite varietal since receiving treatment for throat cancer, but the devoted couple is thrilled he is cancer-free.

a vineyard near their home in Temecula, California, the couple is as likely to recommend the vaccine as they are to sing the praises of local wines.

“We’re very open about the cause of Bill’s cancer, and we tell people if he’d had the opportunity to have the vaccine, this probably wouldn’t have happened to him,” Ruth Reid says.

‘You Can Do It’

I

t was not unusual that Reid’s cancer had progressed so dangerously without notice, as throat cancer is hard to detect in early stages. One of its most common signs is a lump in the throat men find while shaving.

Reid faced a grueling regimen of chemotherapy and radiation five days a week for seven weeks. He lost 50 pounds at an alarming rate. “My throat hurt so bad, even with all the pain medication, that I could barely swallow,” he says. “I had no taste even for the liquids I lived on for three weeks. I had absolutely no energy.”

During the final two weeks of treatment, Reid was so weak that he trailed behind his wife as they headed to radiation oncology.

“I traveled a lot for years and I used to zoom through airports.

Ruth would say, ‘Slow down. Let me catch up with you.’ Now she had to slow down for me,” he explains. “I was pretty low.”

Zumsteg says side effects tend to build up during radiation treatment “and then gradually get better in a mirror-image fashion.” However, some patients have long-term difficulties with dry mouth, swallowing, sense of taste and smell, and overall energy.

Reid is no longer able to enjoy a good Syrah or even smell a skunk, but he looks robust after regaining 30 pounds and is back to the activities he took up after retiring from a long career as a cartographer—including exercising several days a week and tending his vegetable garden. Most important, he says, is that he remains cancer free. He still comes to Cedars-Sinai for checkups and receives physical therapy for lymphedema—swelling in the neck that can be a side effect of radiation.

Ho and Zumsteg are working to determine whether less is more in treating HPV-related throat cancer. Ho has been reevaluating how the stage of the disease is determined to help ensure that each patient receives the right level of treatment. And Zumsteg is designing a clinical trial to explore whether radiation treatments can be “de-intensified” to reduce side effects.

“We have to figure out how to treat older patients in the best way possible because we’re seeing more and more of them,” Zumsteg says. “Patients over 70 have either been excluded from clinical trials or enrolled in very small numbers. These are the most challenging people to treat, yet we have virtually no data to tell us whether the things we do for a 50-year-old with this cancer are also beneficial for someone 75 or 80.”

Both Ho and Zumsteg are optimistic about reducing the burden of care because HPV-related throat cancer is more responsive to treatment than the now less common type caused by smoking.

While both doctors look toward the future, Reid savors each moment and jumps at opportunities to encourage other patients with the words that helped him most: “You can do it.”

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WHAT TYPE ARE YOU? O-

O+

A-

A+

B-

OLD AB-

B+

AB+

Be the giving type. Donate blood today.

Schedule an appointment now at cedars-sinai.org/donateblood or call 310-423-5346.

Faculty News Winter 2020

Heal the System A Cedars-Sinai partnership empowers young healthcare professionals to improve experiences for both patients and providers. By CASSIE TOMLIN

Rachael Porter

Dr. Ish Bhalla studies how to effectively and efficiently treat mental health patients in the Cedars-Sinai Ruth and Harry Roman Emergency Department.

How can clinicians improve access to healthcare?

Can a policy change help address unmet health needs? New physicians and nurses are seeking solutions to the frustrating problems that can arise from well-intentioned layers of bureaucracy.

For the past three years, Cedars-Sinai has partnered with UCLA on the National Clinician Scholars Program, a consortium at six institutions.

The program trains doctors and PhD nurses to navigate, evaluate and sometimes redesign the

healthcare system to better serve clinicians and patients. That includes recognizing systemic shortcomings as well as proposing and evaluating solutions to influence public health policy.

Teryl Nuckols, MD, vice chair of Clinical Research, who oversees the program, says, “Fellows have the opportunity to devise answers to big questions, such as, ‘What does it cost to improve quality of care?’” (continued on page 43)

Christine M. Albert, MD, MPH, has been appointed founding chair of the new Department of Cardiology in the Smidt Heart Institute. A pioneer and leading expert in the epidemiology of heart rhythm disorder, Albert will lead the strategic direction of clinical, operational, academic and research programs in the newly established department. Previously, she was director of the Center for Arrhythmia Prevention at Brigham and Women’s Hospital in Boston and professor of Medicine at Harvard Medical School.

Joanna Chikwe, MD, has been named founding chair of the new Department of Cardiac Surgery in the Smidt Heart Institute. A recognized leader in the field of mitral valve repair and coronary revascularization, she comes to Cedars-Sinai from the Mount Sinai Health System in New York, where she was founding chair of the Department of Cardiovascular Surgery at Mount Sinai St. Luke’s, chief of the Division of Cardiothoracic Surgery and director of the Heart Institute at the State University of New York at Stony Brook.

James S. Forrester, MD, is the 2019 recipient of the Cedars-Sinai Lifetime Achievement

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Faculty News

Award. Former director of the Division of Cardiology and former Burns and Allen Chair in Cardiology Research, he received the honor at the 2019 Commencement of the CedarsSinai Graduate School of Biomedical Sciences.

Mark O. Goodarzi, MD, PhD, director of Endocrinology, Diabetes and Metabolism, and the Eris M. Field Chair in Diabetes Research, was selected for the Josiah Brown Memorial Visiting Professor Lectureship at UCLA, an honor for individuals who have made an impact in diabetes or metabolism research.

James D. Grant, MD, MBA, has joined Cedars-Sinai as chair of the Department of Anesthesiology and physician-executive in Perioperative Services.

He will direct all aspects of the department, including advanced pain medicine, and will oversee residency and fellowship programs. He was chair of Anesthesiology at Oakland University William Beaumont School of Medicine in Michigan. In 2018, Grant was elected 100th president of the American Society of Anesthesiologists.

Jayoung Kim, PhD, associate professor of Surgery and Biomedical Science, has been selected to serve a two-year term as

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president of the Los Angeles chapter of KWiSE, a nonprofit that seeks to establish and strengthen the network of Korean American women scientists and engineers.

Shouri Lahiri, MD, assistant professor of Neurology, Neurosurgery and Biomedical Sciences, and interim director of the Neurocritical Care Program, received a career development award from the American Academy of Neurology. The $450,000 award is presented each year to one young investigator of great promise. Lahiri’s research focuses on the physiological mechanisms of neurological injury that arise in the context of elevated right atrial pressure.

Kate Lawrenson, PhD, assistant professor of Obstetrics and Gynecology, received the 2019 Liz Tilberis Early Career Award from the Ovarian Cancer Research Alliance. The award recognizes a junior faculty member with a strong commitment to an investigative career in ovarian cancer research.

Patrick D. Lyden, MD, the Carmen and Louis Warschaw Chair in Neurology, received the American Stroke Association’s William M. Feinberg Award for Excellence in Clinical

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Stroke to recognize his significant contributions to the investigation and management of clinical research in stroke.

Heather L. McArthur, MD, MPH, medical director of Breast Oncology, was awarded the Stand Up To Cancer Laura Ziskin Prize in Translational Research.

The one-year, $250,000 prize is shared by two scientists at different institutions to collaborate on high-risk, high-reward breast cancer research focused on quickly getting new treatments to patients.

Shlomo Melmed, MB, ChB, MACP, executive vice president of Academic Affairs, dean of the medical faculty, and the Helene A. and Philip E. Hixon Distinguished Chair in Investigative Medicine, received the Frontiers in Science Award from the American Association of Clinical Endocrinologists.

The award recognizes exemplary contributions to the individual’s profession or area of expertise.

Rekha Murthy, MD, vice president of Medical Affairs, has been elected to a three-year term on the board of trustees for the Society for Healthcare Epidemiology of America, which represents physicians and other healthcare professionals globally who have expertise in healthcare epidemiol-

ogy, infection prevention and antimicrobial stewardship.

Paul W. Noble, MD, chair of the Department of Medicine, director of the Women’s Guild Lung Institute, and the Vera and Paul Guerin Family Distinguished Chair in Pulmonary Medicine, received the 2019 Prize for Research in Scientific Medicine (PRISM), an annual award that recognizes a scientific breakthrough or critical medical insight made within the past five years by a Cedars-Sinai faculty member. Noble’s work has significantly expanded understanding of the molecular mechanisms of lung injury and repair, and he has uncovered new mechanisms that regulate lung regeneration and progressive pulmonary fibrosis.

Steven S. Shin, MD, has been appointed vice chair of the Department of Orthopaedics and clinical affairs director of the Orthopaedic Center.

He has been co-director of the Hand Surgery program since 2018 and was previously a hand surgeon at the Cedars-Sinai KerlanJobe Institute. He serves as a hand consultant for the Los Angeles Rams, Dodgers and Kings, and other local sports teams.

Chrisandra L. Shufelt, MD, associate director of the Barbra Streisand Women’s Heart Center

in the Smidt Heart Institute and director of its Women’s Hormone and Menopause Program, was elected to a two-year term on the North American Menopause Society’s board of trustees.

Nancy L. Sicotte, MD, chair of the Department of Neurology, has been named the inaugural Women’s Guild Distinguished Chair in Neurology. She is also director of the Multiple Sclerosis Program and the Neurology Residency Program.

Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer and the PHASE ONE Foundation Distinguished Chair in Oncology, has been elected a member of the Association of American Physicians, an honor society of leading physician-scientists.

Jennifer Van Eyk, PhD, director of the Advanced Clinical Biosystems Institute in the Department of Biomedical Sciences and Basic Science Research in the Women’s Heart Center, and the Erika J. Glazer Chair in Women’s Heart Health, received the 2019 Donald F. Hunt Distinguished Achievement in Proteomics Award from the Human Proteome Organization for achievements in the field of proteomics.

(continued from page 45) MEET THE FELLOWS CARL BERDAHL, MD, Emergency Medicine

THE PROBLEM: Even though paperwork is now mostly digital, primary care physicians almost universally express frustration with its increased burden. One study found that 70% of physicians report IT-related stress. Increasingly stringent requirements to document visit details and update electronic health records squeeze them for time—often at the expense of patients.

THE STUDY: Recent rules from the Centers for Medicare & Medicaid Services (CMS) aim to incentivize physicians to focus on quality care but require even more documentation. Berdahl studied physician reactions to one “pay for performance” policy implemented by CMS in 2015.

THE OUTCOME: Most physicians agreed the policy’s crushing administrative burdens cost them time with patients, for a net negative effect. Berdahl says his work demonstrates that CMS should simplify requirements and provide more technical assistance to doctors who struggle to find enough time in their workdays for administrative demands.

THE TAKEAWAY: “What we want and what patients want is to be face to face addressing each other, but a lot of things need to go on behind the scenes to ensure we’re doing our jobs well,” he says.

“However, it’s hard to make meaningful change when you’re spending so much time in front of a computer screen.”

PARALLEL PROJECT: Berdahl also spent a month in Washington, D.C., analyzing health policies at the U.S. Department of Health and Human Services during the transition between presidential administrations.

“Despite varying political beliefs, a lot of federal employees are trying to do great things on the inside,” he says.

ISH BHALLA, MD, Psychiatry

THE PROBLEM: Patients suffering from mental illness are often admitted to emergency departments (EDs) in hospitals that don’t have inpatient psychiatric departments. In Los Angeles County, about 57 times a day a patient is transferred out of an ED to a more appropriate facility.

THE STUDY: Bhalla, who subspecializes in forensic psychiatry, evaluated a pilot program implemented by L.A. County at 10 EDs—including the Cedars-Sinai Ruth and Harry Roman Emergency Department—designed to streamline the transfer process. The program allowed physicians to facilitate transfers immediately, instead of waiting hours or days for county-designated representatives.

THE OUTCOME: “This change had ripple effects throughout the entire array of services—from outpatient to the ED to inpatient,” says Bhalla, who also found that the program helped avoid treatment delays and alleviate backups in EDs. “Patients who come into the ED are in crisis—they may have used drugs or are suicidal or thinking about becoming violent,” he says. “This change has helped them more quickly get to the inpatient hospital so they don’t have to sit in the ED, which is a loud and busy place. You can’t heal in that environment.”

THE TAKEAWAY: “It’s not just what medications we put them on when they’re here,” he says. “When they’re released, how do they get their prescriptions filled by a pharmacy? How does the patient manage to actually put pills in their mouth? What about housing, employment, transportation and therapy?”

PARALLEL PROJECT: Bhalla also studies how the criminal justice system handles mental health services, how inmates are evaluated to stand trial and how they receive services behind bars.

MOLLY EASTERLIN, MD, Pediatrics

THE PROBLEM: Pediatricians are trained to recognize when family stress affects a child’s health, Easterlin says, but they often struggle to find opportunities to intervene.

THE STUDY: In a 2019 study published in JAMA Pediatrics, Easterlin found that among children who experienced neglect, abuse, divorce, parental incarceration or other hardships, those playing team sports in adolescence were less likely to be diagnosed with anxiety or depression during young adulthood.

THE OUTCOME: Easterlin says her findings indicate that pediatricians should consider recommending team sports to foster resiliency, and also that public health policies should expand access to team sports in lower-socioeconomic schools and neighborhoods.

“Families often have to pay thousands of dollars for children to participate,” she says. “Sports programs should be accessible to everyone.”

THE TAKEAWAY: “We need to find ways that the healthcare profession can support families,” she says. “There’s not always a medicine for these things.”

PARALLEL PROJECT: After graduating from the National Clinician Scholars Program, Easterlin began a fellowship at the neonatal intensive care units at Los Angeles County+USC Medical Center and Children’s Hospital Los Angeles. With Cedars-Sinai researchers, she is also studying whether virtual reality can alleviate stress and anxiety for children with chronic diseases.

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47

Meet the Kids

When your mom is a pediatric cardiologist In a new series, children of Cedars-Sinai staff give us the inside scoop on living with a healthcare provider, and share their best guesses about what their parents do. gram. Then, sometimes, when she’s about to go home, she gets a patient with a heart problem. Usually, it’s a baby that is sensitive and their chest is hurting.

Q: What do you think your mom does at work all day?

Arjun: A healer of some sort with smart glasses or a visor. But not a helmet. The glasses would be like an X-ray, and give her super vision so she can zoom in. She

Arjun: She eats a snack, looks at her computer and maybe an echocardio-

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Q: What do you know about the human heart?

Arjun: I know it has a left ventricle, right ventricle, right atrium, left atrium and two cords, one from each side, but I don’t know what those are called.

Q: Do you think your mom works a lot?

Arjun: Yeah, she’s always stressed out.

And when she comes home early, she has to do more work. And she leaves the house at 6 a.m. every day and she’s usually at work for 12 hours.

Q: If your mom were a superhero, what kind would she be?

would use them to look inside a person to see what is wrong with them so she can fix them. Maybe like in Black Panther, when T’Challa puts on his necklace, it creates his outfit. When my mom would put on the glasses, it would create her superhero outfit.

Q: What does she do that embarrasses you?

Arjun: When we’re out and someone asks her if she has any kids, she right away calls my brother and me over. It makes me feel uncomfortable because people say, “Look at his eyes!”

Q: Do you know if your mom is afraid of anything?

Arjun: I don’t know. Everyone is afraid of something. I don’t like sharks.

Q: What do you want to be when you grow up?

Arjun: Some sort of doctor—maybe a brain surgeon. But it depends on how I do in college.

Rachael Porter

Arjun McIntosh, an active fifth-grader who has a passion for snowboarding, is an avid basketball player and enjoys a good game of hide-and-seek.

When the 10-year-old is not playing sports, his mother says you can find him rocking out on his electric guitar or captivated by video games.

Arjun’s mother is Ruchira Garg, MD, director of Congenital Noninvasive Cardiology and associate director of the Smidt Heart Institute’s Guerin Family Congenital Heart Program. Garg specializes in diagnosing and managing cardiac birth defects, such as “a hole in the heart,” in fetuses, babies, children and adults.

We sat down with Arjun to learn about his life as the son of a pediatric cardiologist and how he dislikes people fawning over his stunning seagreen eyes.

“I am grateful for the

compassionate team at Cedars-Sinai who saw me through my second heart transplant…

They gave me another chance at life and the opportunity to pursue my dream: Go back to school to complete a degree in psychology and become a child psychologist.”

— Joelle Earle, Grateful Patient & Donor

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In This Issue 26 The Unfair Sex

20 Making Birth Better

16 Meet the Rosens

24 Cancer-Fighting ‘Aha’ Moments

Medical studies largely excluded female patients for decades, while women’s symptoms have been dismissed for centuries. Now, female clinicians and investigators are leading the charge to understand and solve women’s health challenges.

Mother-daughter duo Sonja Rosen, MD, medical director and chief of Geriatric Medicine, and Clarissa Rosen have both served as Cedars-Sinai teen volunteers. They discuss their shared passion for music, literature and savory snacks.

Kimberly Gregory, MD, MPH, director of the Division of Maternal Fetal Medicine, is on a mission to make childbirth a safer and more fulfilling experience. She aims to convince hospitals to pay more attention to the type of maternity care women prefer.

Jane Figueiredo, PhD, heads the nation’s largest study on prevention and treatment of colorectal cancer in Latino people. She shares revelations that drive her commitment to fighting disparities in underserved populations.

40 An Epidemic Ignites

The usually harmless sexually transmitted human papillomavirus (HPV) is triggering a surge of throat cancer among baby boomers. Two Cedars-Sinai investigators are working to ease the burden of treatment on those most at risk: older men.

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