2021 Donor Impact Report: Research That Moves People: Advancing Bone and Joint Care at Rush

2021 Donor Impact Report

Research That Moves People Advancing Bone and Joint Care at Rush

Thank You for Your Partnership When it comes to eliminating pain and restoring mobility, only a select few institutions in the world match Rush University Medical Center’s 50-year track record of innovation. Our concentrated expertise in orthopedics has fueled some of the most influential discoveries in the field, from safer and longer-lasting joint replacements to minimally invasive and preventive treatments. With our vast data, technology and knowledge, we continue to elevate bone and joint care — for our patients and those far beyond Rush who benefit from our discoveries.

Rush’s history of leadership in orthopedic care and research is only possible because of a rich legacy of philanthropic partnerships.

Investments from our generous donor community — people who recognize the life-altering impact of musculoskeletal disease and the need for new solutions — are critical to our work. Your gifts accelerate leading-edge studies, help us gather preliminary data needed to secure federal grant funding and fuel the kind of unique research collaborations that define medical progress today. Thank you for your loyal partnership and faith in our work.

Our Year in Numbers

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1

Top-ranked orthopedics program in Illinois

by U.S. News & World Report

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6

Rush orthopedic program’s national ranking by U.S. News & World Report, our ninth straight year in the top 10

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81

10k+

Professional sports teams and collegiate athletic programs that turn to Rush specialists as their preferred orthopedic providers, including the Chicago White Sox and Chicago Bulls

Attending physicians and research faculty in the Department of Orthopedic Surgery at Rush — one of the most productive departments in the nation

The number of times scientific colleagues cite Rush bone and joint researchers each year, positioning our team as one of the most influential in the field

Advancing Research Shoulder to Shoulder

Surgeons and Laboratory Scientists at Rush Team Up to Improve Shoulder Replacements Total shoulder replacements are the fastest-growing implant surgery in the U.S. The vast majority of these surgeries result in successful, long-lasting implants.

However, even a very small failure rate affects thousands of patients. Physician Grant Garrigues, MD, and scientist Robin Pourzal, PhD, discuss how orthopedic surgeons and laboratory researchers at Rush are building on a decades-long track record of collaborative research to understand why some shoulder replacements fail and how to make them last even longer.

Garrigues: Shoulder replacement surgeries have been around longer than total hip replacements. Even though they’re less common, they’re generally fantastically successful, and surgeons are performing more each year. For patients, it’s a life-changing operation. However, we want to maximize longevity. Let’s say a patient comes to Rush when their original implant fails — we’ll reconstruct their shoulder with a new implant and then send the device that comes out to the Rush Implant Tribology Lab. Robin, what led you to specialize and collaborate in this area of research?

Pourzal: I’m a mechanical engineer by training with a focus on material science. I’ve been studying implant materials for a long time, especially the metals and polyethylene used in total hip and knee replacements. Those happen to be, for the most part, the exact same materials used in the shoulder. We are at a point now where it’s really important to start looking

Grant Garrigues, MD

Robin Pourzal, PhD

Associate Professor, Department of Orthopedic Surgery Director of Upper Extremity Research

Associate Professor, Department of Orthopedic Surgery Director of Implant Materials Analysis

at how those shoulder implants wear down. Any bearing has, by design, wear and tear in which foreign particles are released into the joint. That debris can impact patients. When you joined Rush — not only as an extremely experienced revision surgeon for total shoulders but also one with a great research resume — it was frankly the perfect match. We’ve collected more than 100 implant devices from patients over the last three years and currently have the country’s largest registry of shoulder devices and donated tissues.

Garrigues: You mentioned speaking the same language — I did a med school research program that was a Harvard- and MIT-combined program. It was basically medical school for engineers. So this has been a passion of mine going way back, and Rush’s expertise in this area is what drew me here. You and the entire basic science group have an incredible track record of doing this kind of research in the hip and knee arena.

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While the problems in hips and knees are a little different than those in the shoulder, there are a lot of similarities. That led to our collaborative work to look at the factors affecting whether an implant will last five years or the rest of a patient’s life. Obviously that is a huge difference. Companies will design implant devices, and then the FDA looks at a couple of years of data. No one ever looks at them again unless someone like you and me team up.

Pourzal: And for the most part, this work is retroactive.

Patients first have to use these implants. Ideally they won’t fail at all, but some obviously do. When that happens, patients from around the country find you, your team retrieves them in the operating room, patients generously consent to share them with our lab and we learn from them.

Over time, the human body interacts with these devices in ways we can’t always anticipate. The development of better implants takes many years of research. It’s not something that just happens immediately.

Garrigues: I agree. I routinely work with companies to help design new implant systems. We’re constantly asking, “What’s the clinical problem, and how can we make this better?” We’re trying to more precisely pinpoint these problems by studying how the implants hold up over time in people. We’ve gotten to the point where we’re going to find some design features that were not good ideas and could lead to premature failure. We currently retrieve a couple of failed implants each week — it’s on us to make these problems known and get those implants out of circulation.

What else would you say will come from the analysis of the implants we’re gathering?

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Pourzal: You need to study both the implant and the surrounding tissue to get the full story. You need to see the cellular response to debris in the tissue and what types of different cells could be associated with inflammation.

We’re already beginning to make some very interesting findings in this regard, but it’s important we don’t overreach and make big claims without additional study and a larger sample size. As we’ve proven in our work with hip and knee implants over the years, this is research that will never really end. Our goal now is to get an NIH-funded grant, which will provide us with the funding needed to keep us going independently and further strengthen the credibility of our findings. Donor support has positioned us really well for this by funding preliminary studies, high-tech equipment we use in the lab, and its continued maintenance, student stipends, and salaries for postdoctoral researchers.

Garrigues: You said it perfectly. What resonates with me the most is that this research is never done, and donor support keeps us going. We might identify a problem that will impact how implants are designed going forward, but we don’t know that those changes will solve the problem without creating a new one. These implants work well, but they’re not perfect. It’s coming back full circle — we want patients to have a shoulder that is pain-free, has full motion and allows them to do all the things they want to do throughout their lifetime. Even if there’s only a low failure rate, it becomes significant if it happens to you or your loved one. That’s why it’s important we make them better. I’m confident we can do that thanks to Rush’s scientific legacy in the field of joint replacement.

Moving the Science of Bone and Joint Care Forward

Notes From Our Research Labs Safer, Cheaper, Easier

Breaking Ground to Implement Ultrasound in Orthopedics Compared to X-rays, MRI scans and other tools used in the diagnosis and treatment of orthopedic issues, ultrasound has a lot of advantages. Ultrasound technology is inexpensive, portable and doesn’t expose patients to radiation. Its application in orthopedics is limited, although researchers at Rush are leading the way in maximizing its potential.

Partnering with colleagues in radiology and basic scientists in Rush’s Biomechanics Lab, surgeons Jorge Chahla, MD, PhD, and Brian Cole, MD, MBA, are testing how ultrasound can be used to diagnose problems with the knee’s meniscus.

Shane Nho, MD, MS, is also collaborating with the lab to study how ultrasound could serve as an alternative to X-ray in the operating room when placing the instrumentation portals for arthroscopic hip surgery.

A Major Finding With microRNA

Mouse Model of Arthritis Could Shape Alzheimer’s Disease Breakthroughs

Arthritis and Alzheimer’s disease are both incurable, age-related diseases affecting hundreds of millions of adults worldwide.

As Rush researchers have found, our scientific approach to understanding these diseases could have a lot in common, too.

Animal models are essential in uncovering new knowledge about disease, and orthopedic scientist Jian Huang, PhD, has spent years working to develop a mouse model of accelerated aging to study arthritis. In Huang’s recent experiments, his lab created a mouse model with two deleted microRNA genes that triggered several aging-related changes, including brain deficits consistent with Alzheimer’s disease. Their exciting finding earned a grant from the National Institutes of Health, or NIH, to further explore the role of these microRNA genes, which may yield new information to develop and test potential therapies.

The Best of the Best at Preparing Bone and Joint Scientists

Three Rush Postdoctoral Trainees Recognized Among Thousands Each year more than 3,000 researchers submit their work to the Orthopedic Research Society, or ORS, one of the field’s leading professional societies that recognizes the best of the best at its annual meeting. Among thousands of early-career scientists who apply for the New Investigator Recognition Awards, 40 finalists are selected to present their work to a committee of leaders in the field. Three Rush researchers were selected as finalists in 2021: John Hamilton, MD, PhD; Steven Mell, PhD; and Simona Radice, PhD. Mell and Radice advanced to the top 10 as awardees for their leading-edge studies related to knee replacement and implant materials.

This recognition from the ORS speaks to the merit of our trainees’ research findings and Rush’s dedicated efforts to train aspiring bone and joint scientists. Our internationally recognized research faculty in joint health have mentored hundreds of early-career researchers over the years and currently lead a prestigious T32 grant from the NIH to train even more.

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A Joint Discovery

How a Study in the Orthopedic Labs Shaped a Major Finding in COVID-19 As legend has it, Sir Alexander Fleming’s breakthrough discovery of the antibiotic penicillin in 1928 came about by accident.

Returning to his messy lab from a two-week vacation, Fleming found bacteria-resistant mold in a contaminated petri dish — an observation that ultimately altered the course of medicine.

The origin story of penicillin is ingrained in scientists everywhere and serves as a lesson to explore unexpected observations, which could lead to groundbreaking findings. Over the past year, a collaborative team of researchers at Rush has been doing just that — with a basic science study from our orthopedic labs resulting in a discovery that could have implications in managing patients with COVID-19.

‘The only thing that changed was the anesthesia’ With the support of donors, bone and joint scientists at Rush have spent years tackling the problem of periprosthetic joint infection — a rare but serious complication from joint replacement surgery. In a recent study in mice, the team examined how various agents could activate immune cells in the knee to fight off infection.

“Our experiments weren’t working any longer,” recalls Markus Wimmer, PhD, professor in the Department of Orthopedic Surgery and vice chair of research. “The only thing that changed was the anesthesia we were using to sedate the mice.”

The researchers, led by John Hamilton, MD, PhD, a postdoctoral scientist and instructor in the department, found the new anesthetic agent used in their studies, xylazine, seemed to prevent immune cells called neutrophils from migrating to the knees of the mice in response to injection with immune activating agents.

Neutrophils are white blood cells that are highly effective at fighting certain types of infections. But they can also become overreactive and cause damage to healthy tissues. From the early part of the COVID-19 pandemic, the infiltration of neutrophils in the lungs of severely ill COVID patients quickly became viewed as a significant driver of organ damage and respiratory failure.

After using a new anesthetic agent to treat mice with knee infections, the researchers noticed that immune cells called neutrophils were no longer preventing severe inflammation — depicted in the above histology slide from their studies. Given the role of neutrophils in severe COVID-19 illness, the team explored these findings further with experts in pulmonary and critical care medicine.

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As Hamilton worked from home after the animal labs were temporarily closed due to the state-mandated lockdown, he began searching literature related to the anesthetic agent that caused the setback in the mouse study. He then realized this drug could play a role in the management of COVID.

Forming a unique partnership with physician-researchers at the front line of COVID

A reduction in COVID-19 mortality of more than 50%

“We wondered if the unexpected findings we found in regard to modulating the immune system could help reduce disease severity in COVID-19,” says Hamilton. “We contacted the critical care physicians on the front line of managing patients with COVID-19 and determined that dexmedetomidine, an agent highly similar to the one in our mouse study, was a sedative option already being used at Rush for patients in the ICU and on ventilators — including patients with COVID-19.”

Hamilton and Wimmer, along with Balk, Vashi and colleagues from the Rush Research Informatics Core, designed a retrospective study — controlling for multiple variables — to determine if severely ill patients with COVID-19 who were sedated with dexmedetomidine had a better chance of survival. Their findings, recently published in the journal Frontiers in Medicine, indicate that they did — a much better chance.

When mechanical ventilation becomes necessary to help a patient breathe, anesthesia is used to intubate the patient.

Anesthesia with dexmedetomidine is not typically the first choice, but Rush physicians utilized it more frequently during the early part of the pandemic when there was a national shortage of sedation medications.

“We found that dexmedetomidine use was associated with a greater than 50% reduction in mortality in critically ill patients with COVID-19,” says Hamilton.

Partnering with Robert Balk, MD, director of pulmonary and critical care medicine, and pulmonologist Mona Vashi, MD, the researchers sought to conduct a retrospective analysis of COVID-19 patients at Rush who required mechanical ventilation. There were a lot of patients to analyze: Rush treated thousands of the region’s most severely ill COVID-19 patients and is now recognized among the top 10 medical centers in the country at preventing mortality from the disease.

The team’s findings, which may guide care for COVID-19 and related respiratory diseases going forward, exemplify the commitment to collaborative science at Rush.

“It is certainly unique that we translated findings from an orthopedic mouse study to a clinical COVID-19 study,” says Hamilton. “The integration of physicians, researchers and research infrastructure at Rush made these research endeavors and findings possible.”

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It Started With a Spark

Grant-Funded Research Fueled by Donor Support Grants from the National Institutes of Health, or NIH, are awarded through a rigorous peer-review process and considered the “gold standard” in medical research. Fierce competition for limited resources means an American researcher’s chance of receiving an NIH grant today stands at less than 10% — the lowest in the agency’s history. And despite the burden of bone and joint diseases on public health and our economy, just 2% of the NIH’s research budget is directed to orthopedic research.

Donor gifts are more critical than ever in helping Rush researchers get over the NIH finish line. By providing scientists with the seed funding they need to gather preliminary data in support of their hypotheses, philanthropy strengthens investigators’ grant applications and nurtures self-sustaining research programs. Rush’s rich history of donor support in bone and joint is a key reason we’re leading more NIH-funded research in orthopedics than almost anyone else in the nation.

In 2021 — thanks to you — we built upon that track record in a big way.

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Only Possible at Rush

Data and Technology Meet to Help Cure Implant Failure

The vast majority of hip replacement surgeries result in complication-free, long-lasting implants. In a new collaborative research program, propelled by donors and now supported by a significant grant award from the NIH, Rush scientists are joining forces to better explain the rare instances when hip implants fail.

Scientists in the Robbins and Jacobs Family Biocompatibility and Implant Pathology Lab, directed by Robin Pourzal, PhD, and Deborah J. Hall, BS, have spent years collecting and analyzing failed implants — in addition to well-functioning implants from generous donors. Now, Hannah Lundberg, PhD, director of the Computational Biomechanics Laboratory, is leveraging data from the thousands of hip implants her colleagues have analyzed to run advanced computer models. These simulations are helping determine how various factors — implant design attributes, surgical assembly technique and patient activities — put stress on the implant and contribute to failure. With continued study, this leading-edge science offers hope that we can pinpoint the factors causing implant failure and further minimize the chance of it happening to patients.

Characterizing Cartilage

First NIH Grant Awarded to Rush Sports Medicine Surgeon

For more than 15 years, the physician-scientists in the Cartilage Restoration Center at Rush have pioneered procedures related to cartilage transplantation. In the first-ever grant awarded to a clinician-scientist from the Division of Sports Medicine, Adam Yanke, MD, PhD, (pictured to the left) assistant director of the center, along with co-investigator Nozomu Inoue, MD, PhD, are pushing the field forward even further.

Osteochondral allograft transplantation is a form of cartilage restoration where tissue from a deceased donor is used to replace the damaged cartilage that lines the ends of bones in the knee joint in a patient — helping to reduce pain and improve mobility. Successful cartilage transplantation relies on ensuring proper matching between the donor tissue and the recipient. Through this grant, Yanke and Inoue are studying techniques — including innovative 3D scanning technology using handheld devices in the operating room — to improve tissue matching and the surgical transplantation technique overall.

Making Pain Research Painless in Chicago

An Unprecedented P30 Award Everyone understands pain. But when it comes to the biological causes of joint pain, scientists understand less than you might expect. Scientific failures to uncover the mechanisms of joint pain to date (and therefore develop better treatments) have resulted in serious consequences: an unquantifiable loss of productivity, costly surgeries that don’t always eliminate pain, and alcohol and substance misuse resulting from chronic pain — including an opioid crisis that has devastated countless families and gripped the nation.

Steered by leading rheumatology research Anne-Marie Malfait, MD, PhD, Rush was awarded its first-ever P30 grant from the NIH to establish the Chicago Center on Musculoskeletal Pain. P30 awards, multi-year grants representing millions of dollars in support, provide for shared resources and facilities for use by multiple investigators with a shared research goal.

The primary goal of this new center — a collaborative hub for scientists not just at Rush but across the Midwest — is to bridge the gap between orthopedics researchers and neuroscientists who often study pain from different perspectives.

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Advancing Orthopedic Practice

Highlights From Our Physician-Scientists Testing the Tech

Examining Outcomes After Robot-Assisted Knee Replacement Surgery

Robotic-assisted technologies have existed in health care and beyond for some time, but now this innovative tech is beginning to carve out a name for itself in orthopedics. In knee replacement surgery, the robotic assistance aims to ensure precise implant placement for optimal performance. Reconstructive surgeons, led by Denis Nam, MD, MSc, and Vasili Karas, MD, MS, (pictured above) have recently introduced these tools at Rush.

Now, Karas is partnering with researchers to gather evidence that will help further elucidate how robotic-assisted surgery improves patient outcomes. Karas, along with Markus Wimmer, PhD; Christopher Knowlton, PhD; and Steven Mell, PhD, are conducting various tests with patients who received surgery with robotic assistance in the Joan and Paul Rubschlager Motion Analysis Laboratory and comparing them to patients who received conventional surgery.

Rush’s Cutting-Edge Motion Analysis Lab Gets Even Sharper, Thanks to a Grateful Patient of Richard Berger, MD Barbara Bowman was so happy with both of her joint replacements from Richard A. Berger, MD, that she wanted to show her gratitude by donating new state-of-the-art cameras to Rush’s Motion Analysis Lab. This innovative camera system will vastly expand researchers’ ability to measure larger and full body movements, high speed movements like those used in sports, and patient populations for whom a lengthy setup is not possible. It will also enable the team to mobilize our lab and conduct studies off-site. Bowman’s gift to enhance the Motion Analysis Lab strengthens a resource used by many scientists at Rush beyond orthopedics, including rheumatology, Alzheimer’s disease, neurology and preventive medicine research teams.

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5-Year Study Pays Off

Results of Landmark Biologics Study Could Transform Rotator Cuff Surgery Over the past five years, Brian Cole, MD, MBA, and his colleagues have rigorously studied how bone marrow aspirate concentrate, or BMAC, a biologic therapy using the patient’s own cells at the surgical site, could help improve recovery from rotator cuff surgery. Even with minimally invasive arthroscopic surgery techniques — including those pioneered by Cole — recovery from rotator cuff surgery can be lengthy, and many patients do not heal sufficiently.

The team enrolled 82 patients into a randomized, controlled research trial — the superior study design for evaluating experimental treatments — with patients randomly assigned to BMAC or placebo therapy. They were followed at multiple points in their recovery for two years. In 2021 the researchers finally became “unblinded” and analyzed the vast data, including MRI images taken from patients one year after surgery. They found surgical augmentation with BMAC was associated with faster and more complete healing of the tendon, a finding that will shape rotator cuff surgery going forward.

An FYI to the Field About LVI

Improving Methods to Identify Aggressive Bone Cancers

A team of specialists at Rush are leaders in the Midwest in treating osteosarcoma, a type of bone tumor that is one of the most common cancer diagnoses in children and young adults. They’re also at the forefront of research into the condition to ensure more patients achieve remission while preserving their limbs. Orthopedic oncology experts Steven Gitelis, MD; Alan Blank, MD, MS; and Matthew Colman, MD, collaborating with pathologist Ira Miller, MD, PhD, recently advanced this tradition with a major publication in the Journal of Surgical Oncology.

The researchers published on their findings related to lymphovascular invasion, or LVI, which occurs when cancerous cells from the bone tumor penetrate nearby blood vessels or lymphatic system tissues. Studying pathology records from osteosarcoma patients treated at Rush over 10 years, they found patients with LVI had 5-year survival rates lowered by more than 50% when compared to those without LVI. Historically LVI has not been a major factor in determining a patient’s prognosis or treatment plan — something the Rush team hopes to change with these important findings.

Can Vitamin D Improve Knee Replacement Outcomes?

Vitamin D plays an important role in many bodily processes, but it’s of particular interest in orthopedics because of the role it plays in maintaining calcium levels and in bone mineralization. Reconstructive surgeons Craig Della Valle, MD, and Denis Nam, MD, MSc, are leading a placebo-controlled research study to evaluate if a significant dose of vitamin D the morning of knee replacement surgery will improve measurable measures of knee function as well as outcomes patients report at various milestones after surgery.

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In Gratitude In the earliest days of the pandemic, it was understandable when some patients postponed an orthopedic procedure or visit with a specialist. Now, almost two years later, it’s understandable that our clinics are busier than ever.

Life during the past two years has reminded everyone of the importance of mobility. Taking walks, riding bikes, playing golf and many other physical activities have become a part of our rituals like never before. Yet, for many individuals with bone and joint pain, it’s been a challenging time.

As highlighted in this report, every aspect of our work at Rush — from providing world-class care and advancing orthopedics through research to training future experts in bone and joint disease — centers on eliminating pain and restoring mobility. Across all of these areas, our donors are helping us deliver on that goal. More people are leading active lives, free of pain, as a result.

It is a privilege to thank you for your partnership. Your faith in Rush’s bone and joint programs inspires our team, and your gifts inspire new solutions in our laboratories and clinics every day. Our work helps get people moving, and we’re continuously moved by your generous support.

Joshua J. Jacobs, MD The William A. Hark – Susanne G. Swift Professor of Orthopedic Surgery Chairperson, Department of Orthopedic Surgery

To support bone and joint research at Rush, or to learn more about the topics covered in this report, please contact: Derek Lambert Senior Director of Development (312) 942-6289 derek_lambert@rush.edu

Colleen Madden Assistant Director of Development (312) 942-6871 colleen_m_madden@rush.edu