Paul Aisen, the founding director of USC’s Alzheimer’s Therapeutic Research Institute and a professor of neurology at the Keck School of Medicine of USC, was honored Friday as the inaugural recipient of the Epstein Alzheimer’s Disease Director’s Chair.

Aisen’s receipt of the honor — the highest academic honor at the Keck School — was the capstone moment of an extraordinary effort by USC Trustee Daniel J. Epstein and his family to accelerate the search for Alzheimer’s treatment and a cure. Colleagues, university leaders, family and friends crowded the San Diego event to share their appreciation for Aisen’s work in pushing the limits of what is known about the disease.

Defeating this disease is really one of the most daunting moonshots in medicine today.

Carol L. Folt, USC president

“Defeating this disease is really one of the most daunting moonshots in medicine today,” said USC President Carol L. Folt, characterizing Aisen and Epstein as ambitious problem-solvers dedicated to making a difference in the health and well-being of others. “But [Epstein’s] optimism and dedication have always enabled the best to do cutting-edge research, and this record of success continues with this new chair and with the work that all of you do.”

Aisen echoed Folt’s recognition of the role of teamwork: “Everybody in this room has a common mission of accelerating the development of effective treatments. What allows us to accomplish what we’ve accomplished is having everybody here together in an academic environment, supported by a fabulous university, working on innovation, collaboration, data sharing and moving the field forward.”

An unusual gift

Galvanized by a family loss — Epstein’s twin brother lived for 15 years with Alzheimer’s disease — the Epstein Family Foundation announced a $50 million joint gift to USC and the University of California, San Diego, in January 2022. The family made the unusual stipulation that the donation, split evenly, foster collaboration between the two institutions.

The family also established the USC Epstein Breakthrough Alzheimer’s Research Fund, which funds innovative, interdisciplinary research projects across USC that advance the development of new therapies and preventive measures for Alzheimer’s disease.

Our family’s support for Alzheimer’s research is intended to inspire others and generate real impact.

Daniel J. Epstein, USC trustee

“Our family’s support for Alzheimer’s research is intended to inspire others and generate real impact,” Epstein said. “We hope our commitments resonate with those who have the means to contribute to the cause — we urge them to look at their resources and say, ‘I want to help, too.’ Funding can accelerate promising research. Above all, it can shorten the time until we see more effective treatments and therapeutics, which we’re on the verge of, right now.”

Epstein, who earned his bachelor’s degree in engineering from the USC Viterbi School of Engineering in 1962, has served as a USC trustee for two decades. He is the founder of the San Diego-based ConAm group of companies. A longtime champion of USC initiatives, he traces his success to his USC education.

In 2021, Epstein and his wife, Phyllis, contributed $14 million to his namesake department at USC Viterbi in industrial and systems engineering. The gift was part of $25 million in total support that he has contributed to advance industrial and systems engineering research, teaching and learning.

Linked by loss

Like the Epsteins, Aisen has a personal tie to Alzheimer’s: His maternal grandmother died from the disease.

His clinical interest in the disease goes back to his time at Mount Sinai Medical Center in New York, where he served as chief medical resident. It was there, in the late 1980s, that some of the first attempts at treating memory loss took place.

In 1999, Aisen founded the Memory Disorders Program at Georgetown University, a clinical and research program for Alzheimer’s disease and related disorders. After many years of basic research studies, he became founding director of USC’s Alzheimer’s Therapeutic Research Institute in 2015. His work deepened scientific understanding of the crucial early years before symptoms manifest, which could offer an important window for potential treatments.

Under Aisen’s leadership, ATRI organizes and conducts rigorous trials investigating potential treatment avenues for Alzheimer’s disease — supported by millions of dollars in federal funding as well as contracts with private industry. On Friday, an FDA advisory panel unanimously endorsed the clinical benefits of the Alzheimer’s drug lecanemab, moving it forward for consideration for full FDA approval. ATRI played a pivotal role in advancing the treatment, with Aisen as the senior investigator for the clinical trial.

At least 6 million people in the United States are living with this debilitating and ultimately fatal brain disorder, and the situation is likely to worsen. As the U.S. population ages, the number of Americans suffering from Alzheimer’s could reach 14 million by 2060, according to the Centers for Disease Control and Prevention.

Aisen’s efforts unite Alzheimer’s researchers across the country. ATRI oversees the Alzheimer’s Clinical Trials Consortium, which centralizes resources and facilitates the sharing of expertise to accelerate the development of effective interventions.

Aisen and his team also are key partners in running a comprehensive training program (IMPACT-AD) to educate and diversify the next generations of clinical trial professionals.

Folt noted that Aisen’s favorite hobby is astrophotography — taking pictures of the night sky or objects in space.

“It’s really the perfect hobby: The glimmer of stars are much like the pulsing neurons of the human brain,” Folt said. “And I know you have made it your life’s work to assure that these constellations of light that power our emotions and thoughts never dim with the onset of Alzheimer’s.”

When Professor Yan Liu was growing up in Changchun, China, her father wanted her to become a doctor like him. When she chose computer science, “I was a tiny bit disappointed,” Xiwen Liu, a retired anesthesiologist, acknowledges.

But their worlds collided in 2011, when the elder Liu was diagnosed with prostate cancer. It was a surprise. At 67, he was relatively young, had a healthy lifestyle and had no symptoms. Like many of the 1.2 million men diagnosed with prostate cancer each year, he had surgery to remove tumors in his prostate, but he suffered from incontinence, bleeding and infections for years after the surgery.

Nearly 6,000 miles away, at the USC Viterbi School of Engineering, Yan Liu felt helpless.

Even with access to the best doctors and hospitals, he experienced pain, slow recovery and long-term side effects.

Yan Liu

“The complications involved with prostate cancer surgery brought my dad significant personal challenges,” says Liu, a professor of computer science, electrical and computer engineering and biomedical sciences. “Even with access to the best doctors and hospitals, he experienced pain, slow recovery and long-term side effects.”

Liu resolved to use her skills to help others like her father. Working on research at the intersection of artificial intelligence and health care for more than a decade, she teamed up in 2016 with Dr. Andrew Hung, a urologist at Keck Medicine of USC, to create AI tools that measure and help improve surgeons’ technical skills during the radical prostatectomy procedure — the removal of the entire prostate gland.

By harnessing deep learning algorithms, their system learns from past movements to identify specific areas where a surgeon can improve during a robotic surgery. Together, Hung and Liu have since published more than 17 peer-reviewed papers in this field and recently received a $3 million award from the National Institutes of Health to advance their research.

They are working on developing an AI-based system to deliver real-time feedback during a procedure and even alert surgeons if they are at risk of erring. Their aim? To shorten the learning curve for surgeons, maximize patient safety and reduce postoperative complications.

“AI comes into play to assess the skill of the surgeon — to see what parts of the operation they are good at, and what needs to be improved,” says Liu, director of the USC Melady Lab, which focuses on machine learning with real-world applications. “It also comes into play during the simulation and learning stage for training new surgeons.

“Ultimately, what we want to do is provide real-time assistance to surgeons as they operate,” she says.

The Learning Curve

Removing the prostate gland through surgery is an option for men whose cancer has not spread. Today, robotically assisted radical prostatectomy constitutes about 85% of the 90,000 such operations performed every year in the United States.

Robotically assisted radical prostatectomy constitutes about 85% of the 90,000 such operations performed every year in the United States.

To operate using a robotic system, the surgeon makes tiny incisions and manipulates miniaturized instruments from a nearby console, making detailed work less invasive. As with any surgery, however, risk is involved: The surgeon must avoid damaging adjacent tissues and organs. Despite advances in medical technology, up to 40% of patients experience incontinence after the procedure.

Decades of research suggests that some hospitals and surgeons have significantly better outcomes than others. Indeed, the procedure has a steep learning curve: Studies say surgeons must perform about 100 radical prostatectomies to start reaching optimal outcomes. Yet surgeons often do not get a good sense of how they are performing.

“As surgeons in the operating room, we don’t get much immediate feedback in terms of the things we do,” says Hung, a leader in innovative surgical simulation technology and the director of the Center for Robotic Simulation and Education at Keck School of Medicine of USC. “Short of a major complication, some of the outcomes after prostate surgery are not apparent until weeks, months or years later.”

While surgical performance assessment is a critical need, it’s not always available, Hung says. “It’s simply not scalable to have a perfect surgeon evaluator look at every surgeon’s operation and give feedback.”

How AI Can Help

During robotic surgery, every snip, clamp and stitch generates massive amounts video data and kinematic data tracing the surgeon’s movements. AI can analyze this data to give surgeons feedback on instrument moving speed, distances traveled and wrist angulations during the robotic surgery. Using data and expertise from Hung and his group, Liu and her team have developed algorithms that teach the computer to learn as it is fed thousands of these data points.

Liu’s team uses this data to train the classifier to “understand what it sees,” she said. Once training is complete, deep learning models can provide objective evaluations based on learned representations of ideal versus non-ideal technical skills. To test the accuracy of the system, the machine’s ratings are compared with the surgeons’ ratings of the same surgeries.

“Based on this, we can predict whether the patient will have complications after the surgery and the expertise of each participant,” Liu says.

Using the raw data, Liu and her team determined that machine learning algorithms could predict each participant’s level of expertise with 87% accuracy. Eventually, she hopes the system will alert surgeons to potential problems, such as risk of injury to vital organs that could result in long-term complications.

“When we move toward the grand challenge goal of AI-assisted surgery, then we need to look at specific segments of the operation,” Liu says. “Then we can use this information to predict, based on the current stage of the operation, if there will be any risk factors for the next step so we can provide a timely warning.”

‘A Needle in a Haystack’

The process has allowed the researchers to identify the parts of the operation that seem most closely tied to outcomes. “It’s like a needle in a haystack,” Hung says. “How can you find the one needle that drives the outcomes, and what do you focus on in a procedure that’s between two and four hours long? AI brings objectivity and also scalability.”

AI brings objectivity and also scalability.

Andrew Hung

In a recent study focused on predicting urinary control outcomes, researchers found that algorithms home in on a critical step in the radical prostatectomy: when the clinician must suture a gap between the bladder and the urethra after the prostate is removed.

Done properly, this step prevents internal leakage of urine during and after the procedure. If it is incorrectly done, the patient can suffer such complications as incontinence and damage to the bladder.

Using AI, researchers found almost all the metrics that predict continence recovery were related to suturing, possibly because, Hung says, “measuring surgeon performance is nicely captured by the suturing task, and it lends itself well to evaluation.”

But while machine learning can help find the needle in the haystack, it doesn’t offer explanations — that’s still in the hands of the human experts.

Robots in the OR

When Hung and Liu started working together, they were looking at metrics that summarized an entire operation. Now they can analyze performance at the level of individual stitches, narrowing the focus to different levels of suturing. This would allow the system to give surgeons specific, actionable feedback. Their recent research results showed a 20% to 30% improvement in assessing surgical skills when using AI-assisted assessment compared with human graders.

Research results showed a 20% to 30% improvement in assessing surgical skills when using AI-assisted assessment compared with human graders.

“When you’re measuring technical skills and you provide that kind of feedback, it’s actually meaningful to surgeons,” Hung says. “As opposed to telling a surgeon, ‘You’re just not moving your hands fast enough,’ you’re actually telling them, ‘The way you’re holding the needles in this specific suture is incorrect.’”

The research is at the investigational stage, meaning the systems are not yet used in any high-stakes evaluations. But how do surgeons feel about a future of AI-assisted robots in the operating room?

“When I present this idea to my peers, I definitely get folks in both camps: those who embrace the idea and those who feel threatened,” Hung says. “In some cases, surgeons can be resistant to the concept at first. No one really likes being evaluated, least of all by a machine. But once they see the opportunity for evolving their skills and helping their patients, they become curious and open up to the idea.”

Although their exploration in understanding the “perfect stitch” has focused on urology, it could also be applied to other procedures, including hysterectomies and hernia repairs.

“We want to find out how surgeons can evolve more quickly,” says Hung. “[Improving] how we teach and train surgeons to do surgery will not cure disease magically, but it can certainly enhance how we anticipate patient outcomes and take better care of our patients.”

The final step is to prove that such feedback can improve outcomes and use it to train new surgeons. “Our goal is to use AI to help surgeons by detecting potential issues and [offering] warnings and possible suggestions in terms of what type of action the surgeon should take,” Liu says.

For Liu, the team’s progress brings hope that they can improve the lives of people like her father and the approximately 644,000 people who undergo some robotic surgery each year in the United States alone.

“In terms of translating AI into practice, I think this project has one of the shortest runways,” Liu says. “A very realistic goal that could happen in the next five to 10 years is this AI-assisted robotic surgery, which could improve post-surgery outcomes and recovery.”

As a patient, father and former clinician, Xiwen Liu welcomes that news.

“On nights when a patient would pass away during a surgery, I felt awful, always asking the what-if questions,” he says. “Improving health delivery means [everything] to patients, but it could even improve doctors’ psychological health, as well.

“Somehow, after all these years, our paths of medicine and computer science have crossed. Maybe [my daughter] found the best way to help people and save lives after all.”

During a routine medical appointment in Pasadena, Bridget Graves — a 57-year-old management consultant who identifies as transgender — realized that her physician knew very little about the standard of care for transgender patients. Graves’ after-visit notes confirmed her suspicions. Her physician had included “transgender” under the list of maladies Graves was seen for. Graves immediately called back to request a correction but never received a response.

Graves explained that these microaggressions — including medical staff who misgender patients and physicians who resist using preferred names on medical records — keep transgender and nonbinary patients from seeking health care.

Today, the mother of five, competitive cyclist and longtime yoga teacher is a patient at Keck Medicine of USC’s innovative Gender-Affirming Care Program, a multidisciplinary collaborative providing comprehensive health care to transgender and nonbinary people while affirming their gender identity.

Graves’ sentiments on her experience before coming to Keck Medicine reflect the struggles of many in the transgender and nonbinary community to find inclusive, continuous health care.

Gender-affirming care in a medical context means supporting and respecting someone in their gender identity, however they identify in their lifetime.

Laura Taylor

“Gender-affirming care in a medical context means supporting and respecting someone in their gender identity, however they identify in their lifetime,” says Keck Medicine primary care physician Laura Taylor, the program’s medical director.

For many people, this care boils down to hormone therapies and surgical interventions. But Taylor emphasizes that at Keck Medicine, it means individualizing all of a patient’s health needs based on their personal goals. These goals can include hormones to induce different physical characteristics or surgery to change somebody’s chest or genitals, but also routine care such as preventative medicine and specialized mental health care.

Keck Medicine was already providing gender-affirming care before the program began, but the process was decentralized and patients had to seek out individual specialists, says Felipe Osorno, Keck Medicine Chief Performance and Transformation Officer. Through the Gender Affirming Care Program, Keck Medicine patients can now access a centralized model where providers holistically monitor every aspect of health, including primary care, mental health, endocrinology, gynecology, urology, physical and occupational therapy, voice training and surgery.

Discussions about starting a centralized program began in 2019, brought about by a deeper awareness of diversity, equity and inclusion across the country. Later, the pandemic and the murder of George Floyd spurred the need for action around health equity and inclusion for populations traditionally excluded from the health care system apparent.

A New Approach

Before Graves became a patient with Keck Medicine, she, like many transgender and nonbinary patients, struggled to find a medical facility where she felt safe and understood.

“Historically, the transgender and nonbinary community have experienced — and still experience — a lot of discriminatory practices in health care, substandard care and so many barriers to health care,” Taylor said. “Unfortunately, these communities often have a harder time getting insurance due to a higher risk of issues with employment and insurance companies that may not cover gender-related services.”

Other barriers to care include transportation, financial constraints, family support and — especially in conservative states — the criminalization of gender-affirming treatments.

Finding Keck Medicine of USC after an extended internet search was a breath of fresh air for Graves. “It was like night and day,” she said. “This physician asked all the right questions and was open to keeping the continuity of my medications, my hormones and what had already been working for me.” This led to her eventually working with Taylor, whose trans flag on her ID badge put Graves at immediate ease.

Having someone willing to help, who knew how to work with me and made me feel comfortable, was amazing.

Bridget Graves

During her initial intake, Graves communicated that there were certain physical exams that typically made her uncomfortable. Taylor offered to personally perform those physical exams, so that Graves wouldn’t have to worry about them in subsequent visits with other providers. Taylor also offered to do more research on an experimental therapy Graves was interested in during an upcoming medical convention for transgender health care.

“The fact that she was already scheduled to go [to a transgender convention] meant a lot to me,” Graves said. “Having someone willing to help, who knew how to work with me and made me feel comfortable, was amazing.”

The program encourages patients to establish a long-term relationship with a primary care physician to foster this kind of continuity of care. The goal is to manage preventative and routine health care alongside gender-specific therapies without patients having to explain themselves repeatedly or see multiple physicians and specialists where the environment may be less supportive.

Starting De Novo

Taylor points out that while other places have historically offered gender-affirming care in Los Angeles — including LQBTQ+-friendly clinics, nonprofits and other academic health systems — a high need remains. “There are not enough doctors and health care providers who are adequately trained to do this care, and it hasn’t been a part of medical education,” Taylor says. “This is particularly harmful to the [transgender and nonbinary] community because often people have to educate their health care team.”

Assistant Professor of Clinical Surgery Roberto Travieso, the surgical director for the program, says one of their goals is for transgender or nonbinary patients to receive care that is supportive and respectful of their gender identity — regardless of whether their needs are complex (surgery) or routine (treating high blood pressure).

“Transgender and nonbinary people have the same health care concerns that others have outside of specifically gender-affirming surgeries and therapies,” Travieso says. While the program is adding services that were not available before — such as newly available surgeries and the consolidation of specifically gender-affirming care such as hormone therapy and primary care — Travieso stresses that the program is sparking institutional change: “We’re also making sure that this training and emphasis goes throughout the entire health enterprise to involve every facet of health care available through Keck.”

To accomplish this, Travieso, Taylor and Osorno — along with Process Architect Lindsey Morrison — regularly brainstorm with a large group of Keck Medicine colleagues. They discuss issues such as the wording on clinical intake forms, the appearance of medical record systems and where to place pronouns on documents so they’re clearly visible.

“Because we’re starting something de novo, we have the potential to avoid mistakes that have been made elsewhere, where patients don’t feel welcome,” Travieso says. Early on, he and the team realized that the key to the program’s success would be including the community during the planning stage.

Allied Collaboration

In March 2022, Keck Medicine of USC announced a strategic collaboration with The TransLatin@ Coalition — one of the largest trans-led nonprofit organizations in the country that advocates for the medical, social and economic needs of transgender, gender nonconforming and intersex immigrants. The collaboration underscores the health system’s commitment to working with the transgender and greater LGBTQ+ community with the goal of greater health equity for all.

It’s important to have this type of partnership between large institutions and community-led organizations; our collective work is great.

Bamby Salcedo

“We’re very appreciative and grateful for our partnership with Keck Medicine,” says activist Bamby Salcedo, president and CEO of The TransLatin@ Coalition. “It’s important to have this type of partnership between large institutions and community-led organizations; our collective work is great. We’re looking forward to ensuring that together, we continue to support and provide optimal health care to the local trans, gender nonconforming and intersex (TGI) community of Los Angeles.”

As a gay man who identifies as Latinx, Osorno is proud of Keck Medicine’s approach to the collaboration. “It was very meaningful for USC to both welcome the transgender community into our campus and have a celebration with our CEO and their leadership. The symbolism of that is very important because it’s saying, ‘We see you, we hear you, we’re here with you and we recognize you.’”

Keck Medicine leadership promoted mutual listening within the collaboration by hosting bilingual focus groups at USC facilities and at the coalition’s headquarters in Koreatown to ensure that transgender and nonbinary community members had a say in crystalizing the program’s vision.

Keck Medicine physicians heard heartbreaking stories of constant misgendering and individuals going to dangerous lengths — including self-administering hormones — to access the gender-affirming therapies they needed.

Based on that feedback, Morrison spearheaded the training of thousands of Keck Medicine staff — from nurses to admitting staff to those who interact with patients on the phone.  — because one negative or harmful interaction could be enough to turn away a patient in need.

The partnership also produced a peer navigation model: hiring a part-time social worker from the trans community to be the point of contact for patients and to help navigate the program.

According to Travieso, the program’s creation pairs well with Keck Medicine’s overall mission of making health care more accessible to everyone. “It’s not just us physicians who are working day to day; it comes from the top leadership and administration who have expressed significant support for the program and made it one of the core goals of the health care system.”

The program leaders urge people to donate to the continued evolution of the program as the state anticipates an increase in what is being called medical refugees — individuals forced by anti-transgender policies in other states to travel to California to receive the gender-affirming care they deserve.

“Our vision long-term is to provide gender-affirming care to anyone, regardless of their ability to pay,” Osorno said. “With this intentional philosophy, we really hope to become the preeminent gender-affirming care program on the West Coast.”

Keck Medicine of USC is phasing out one of the most commonly used — and environmentally toxic — anesthetics for its surgeries, desflurane.

The discontinuation of desflurane is part of a universitywide effort to re-examine both USC’s and Keck Medicine of USC’s impact on climate change and to implement healthier, sustainable solutions whenever possible.

The operating room is one of the biggest — if not the biggest — waste generators in any hospital, says Arash Motamed, medical director for Keck Main Perioperative Operations and Keck Medicine of USC Sustainability.

“They’re very resistant to degradation; they stay in that environment for many years,” says Motamed, an associate professor and vice chair of clinical operations for the department of anesthesiology at the Keck School of Medicine of USC.

In June, the Association of Anesthetists noted the inconvenient truth about anesthetics.

It cited research showing that anesthetics are responsible for 0.1% of the world’s carbon emissions. At the hospital level, inhaled anesthetics make up more than 5% of acute hospital carbon emissions and 50% of perioperative emissions.

Anesthetics in the atmosphere

During a surgery with anesthetics, a patient breathes in an anesthetic gas, which circulates through the body and keeps the person unconscious. After the operation, the anesthetics are turned off, the concentration in the body decreases and the patient regains consciousness.

Keck’s operating rooms have three primary anesthetics, Motamed says. Each achieves similar effects but has different drawbacks.

Desflurane is very quick to come on and very quick to come off — that’s why people love it. But it’s expensive and horrible for the environment.

Aren Nercisian, anesthesiologist at Keck Medicine of USC

“Desflurane is very quick to come on and very quick to come off — that’s why people love it,” says Aren Nercisian, an anesthesiologist at Keck Medicine of USC. “But it’s expensive and horrible for the environment.”

Desflurane is the most commonly used. Yet, studies show desflurane is so harmful to the environment that an eight-hour surgery causes as much damage to the atmosphere as driving a car from Los Angeles to Maine.

“The contribution to emissions is huge,” said Howard Hu, holder of the Flora L. Thornton Chair in Preventive Medicine and chair and professor of population and public health sciences at the Keck School of Medicine of USC. “That insight became a clarion call for us to do something about it.”

In its own call to action on pollution reduction, the California Society of Anesthesiologists noted that desflurane lingers the longest of any anesthetic — 14 years — in the atmosphere’s lowest layer, the troposphere, just above the Earth’s surface. On the other hand, sevoflurane remains in the troposphere for just over a year while isoflurane lingers for 3.2 years.

Helping the environment, cutting costs

Global warming potential (GWP) is a way to quantify the amount that an agent contributes to global warming over a period of time. Nercisian, who leads sustainability efforts for the anesthesiology department at Keck Medicine of USC, explains that GWP measures how much energy the emission of 1 ton of a gas will absorb over a given period, relative to the emissions of 1 ton of carbon dioxide.” The larger the GWP, the more it warms the Earth compared to carbon dioxide. The GWP of carbon dioxide is 1.

Desflurane has a 20 times higher global warming potential than sevoflurane, Nercisian says.

Desflurane has the highest global warming potential — 2,540 — compared with sevoflurane, which has a GWP of 130.

The triple aim of a health system should be improving patient experience, improving the health of the population and reducing the cost of health care … sustainable delivery of care should be the fourth aim.

Arash Motamed

The three also differ in cost. Desflurane tends to be the most expensive. And so far, no studies have indicated whether one is worse for patients than the others.

“There’s never been a study to prove that you have better outcomes with sevoflurane vs. desflurane vs. isoflurane,” Nercisian says. “Though some agents have specific advantages.”

Keck Medicine of USC has not ordered more desflurane in the past year.

“According to the Institute for Healthcare Improvement, the triple aim of a health system should be improving patient experience, improving the health of the population and reducing the cost of health care,” Motamed says. “Howard Hu, chair of Population and Public Health Sciences at USC, says that sustainable delivery of care should be the fourth aim. I couldn’t agree more.”