UPMC Physician Resources

UPMC Makes U.S. News & World Report’s Honor Roll of America’s ‘Best Hospitals’ for 17th Time

 UPMC is recognized on the national stage once again for its clinical expertise, earning 12th position on the annual US News & World Report Honor Roll of America’s “Best Hospitals,” moving up from 13th place in last year’s rankings.

“We are extremely pleased to be on the Honor Roll for the 17th year,” said Leslie C. Davis, senior vice president of UPMC, and executive vice president and chief operating officer of the Health Services Division. “What a fine testament year after year for our physicians, nurses and other clinical specialists and support teams who dedicate their work every day to providing this level of care for our patients and their families.”

US News & World Report analyzed approximately 5,000 hospitals nationwide based on a variety of factors, including hospital volume, patient safety, outcomes, and reputation for delivering high-quality care. The 2016-17 Honor Roll recognizes the 20 hospitals that earned the most points across 16 specialty areas included in the analysis. The Honor Roll is ranked from No. 1 to No. 20, based on earned points.

Nationally, UPMC is ranked for excellence in 15 of the 16 specialty areas, and is among the top 10 hospitals in four specialties: ear, nose and throat; gastroenterology and GI surgery; pulmonology; and rheumatology.

“In addition to our clinical excellence and patient care expertise across the board, we have a close affiliation with one of the best medical schools in the country, the University of Pittsburgh School of Medicine, to advance our scientific research that leads to clinical innovation in many specialties,” said Steven Shapiro, MD, executive vice president and chief medical and scientific officer at UPMC and president of the Health Services Division. “We are proud of that collaborative work.”

UPMC’s inclusion on the Honor Roll comes weeks after US News & World Report named its 2016 Honor
Roll of America’s Best Children’s Hospitals, recognizing Children’s Hospital of Pittsburgh of UPMC as No. 7 in the country, up from No. 8 last year. This is the 7th year that Children’s made the Honor Roll, ranking in 9 of 10 pediatrics specialty areas covered.

‘Starving’ Immune Cell Discovery Points to Cancer Immunotherapy-Boosting Strategies

The microenvironment that supports a cancerous tumor also starves the immune cells that the body sends in to destroy the cancer, University of Pittsburgh Cancer Institute (UPCI) scientists revealed in a discovery that holds the potential to significantly boost the performance of breakthrough immunotherapy drugs.

The UPCI team showed that when immune T cells enter the tumor microenvironment, their mitochondria—which act as mini-factories inside cells, making energy and crucial reagents a cell needs to survive—begin to shrink and disappear, indicating that the T cell is out of fuel and can’t do its tumor-destroying job. The finding, reported online today and scheduled for next week’s issue of the journal Immunity, opens the door to several potential clinical approaches that could help keep T cells functioning and boost the body’s ability to fight cancer.

“Immunotherapy to stimulate the body’s immune system has increasingly become the way we treat people with aggressive cancers. It’s effective for a subset of patients, but the truth is that only about 20 to 40 percent of patients will respond to the treatment, and it is still unclear why,” said senior author Greg M. Delgoffe, PhD, assistant professor of immunology and member of the Tumor Microenvironment Center at UPCI, partner with UPMC CancerCenter. “It’s a huge question in the cancer immunotherapy field, and we think we’ve found a big part of the answer.”

As tumors grow, they build a microenvironment, which develops its own blood supply and keeps the tumor thriving, protected and voraciously consuming all available nutrients.

When T cells enter the microenvironment, it’s as if they’re “automobiles that suddenly had the emergency brake applied; they can’t keep driving,” explained Dr. Delgoffe. Immunotherapies, like those that target negative regulators on the T cell surface, take these brakes off. “However, what we’re discovering in many cases is that even though the brakes have been taken off, there isn’t any fuel in the tank,” Dr. Delgoffe said. Or—in scientific terms—the lack of mitochondria in the tumor-infiltrating T cells keeps them from functioning.

“This is an exciting discovery because we already have various strategies to ‘fill the fuel tank’ and support T cell function in the tumor microenvironment,” said Dr. Delgoffe.

In laboratory experiments and tests with mice, Dr. Delgoffe and his team found that when they boosted the mitochondria in the T cells, they were better able to clear the tumor.

Dr. Delgoffe is partnering with other scientists to test various mitochondria-boosting strategies, including using drugs that already have proven safe in humans, such as those for type 2 diabetes, to stimulate T cell metabolism. He’s also working with existing immunotherapy studies to further modify the T cells so that their metabolism functions better in the tumor microenvironment.

Additional authors on this research are Nicole E. Scharping, BSc, Ashley V. Menk, BSc, Rebecca S. Moreci, BA, Ryan D. Whetstone, MS, PhD, Rebekah E. Dadey, BS, Simon C. Watkins, PhD, and Robert L. Ferris, MD, PhD, all of Pitt.

This work was supported in part by Sidney Kimmel Foundation for Cancer Research grant SKF-015-039 and National Institutes of Health grants 1S10OD016236-01, P50 CA097190 (UPCI Head and Neck Specialized Program of Research Excellence (SPORE)) and P50CA121973 (UPCI Skin Cancer SPORE).

Genetic Variant Newly Linked to Crohn’s Disease Also Associated with Altered Gut Microbiome Composition

An international team led by researchers at the University of Pittsburgh, Cedars-Sinai Medical Center and the University of California Los Angeles discovered that a genetic variation previously linked to obesity, cholesterol levels, blood pressure and schizophrenia also is associated with Crohn’s disease, a chronic inflammatory condition of the gastrointestinal tract that is estimated to cost the US $6 billion annually.
In addition, the genetic variant is associated with changes in the composition of the gut microbiome—which is made up of potentially billions of microbes that help people digest food, synthesize nutrients and perform myriad other essential functions—in healthy people, overweight people and people with Crohn’s disease. The findings are reported online and scheduled for the October issue of the journal Gastroenterology, and the research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and Helmsley Charitable Trust, among others.
“We knew from previous studies that there is reduced diversity of the gut microbiome in patients with Crohn’s disease,” said co-senior and corresponding author Richard Duerr, MD, a professor in Pitt’s School of Medicine, and co-director and scientific director of the UPMC Inflammatory Bowel Disease Center. “But that left us with a question: Does Crohn’s disease alter the composition of the gut microbiota, or do pre-existing changes in the gut microbiota confer risk for Crohn’s disease? Our study found that there is a reduction in the abundance of hundreds of minor species of gut bacteria in healthy, overweight and Crohn’s disease-affected people who carry this genetic variant, suggesting that the genetic variant may increase risk for disease by altering the gut habitat. This is an important step toward understanding how the disease works so we can develop therapies or a cure in the future.”
Under the leadership of Dr. Duerr and co-senior author Dermot McGovern, MD, PhD, FRCP (Lon), director of Translational Medicine in the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, the team focused their analysis on 10,523 blood samples from people with inflammatory bowel disease (half had been diagnosed with Crohn’s disease) and 5,726 samples from healthy people.  They discovered that a variation in the SLC39A8 gene is associated with Crohn’s disease.“This finding is another important example of how a particular genetic variant can have a role in the development and course of many diseases. Our study of this variant suggests that therapies effective in treating one disease also may benefit the treatment of some patients with other illnesses,” said Dr. McGovern, who also is director of Precision Medicine at Cedars-Sinai.

Taking it a step further, the team identified healthy people, overweight people and Crohn’s disease-affected people with the genetic variant and analyzed their gut microbiomes under the leadership of co-senior author Jonathan Braun, MD, PhD, chair and professor of pathology and laboratory medicine in the David Geffen School of Medicine at UCLA. That is how they discovered that the genetic variant is not just linked to Crohn’s and other conditions, but also to a reduction in hundreds of species of gut bacteria.
“Many of these species are believed to play roles in protecting the intestine against Crohn’s disease, and also in preserving a lean body physiology,” said Dr. Braun. “So, this may be an example where the gene increases risk for disease via its effect on types of bacteria we need to preserve our health.”

The findings have sparked additional questions and potential research avenues, but therapies are still quite a ways off, said Dr. Duerr, also a professor in the Pitt Graduate School of Public Health Department of Human Genetics. However, the recent establishment of the University of Pittsburgh Center for Medicine and the Microbiome will help accelerate this research and bring potential therapies—which may involve the center’s clinical fecal transplantation program—to patients.

“This study illustrates the remarkable interaction between our proper genome and our symbiome—the organisms and environment inside and outside of us that influence our well-being—in the setting of inflammatory bowel disease,” said Mark T. Gladwin, MD, chair of medicine and Dr. Jack D. Myers Professor of Internal Medicine at Pitt. “Insights from this study are likely to guide the development of microbiome modulating therapies that hold the promise to alleviate patient suffering.”

Additional institutions with researchers who participated in this study are Cleveland Clinic; Yale University; Karolinska Institutet and Örebro University, both in Sweden; Biocruces Health Research Institute in Spain; University Hospital Munich-Grosshadern, University of Ulm, Krankenhaus Waldfriede and Ludwig-Maximilians-University, all in Germany; QIMR Berghofer Medical Research Institute, Royal Brisbane and Women’s Hospital and University of Queensland, all in Australia; Inselspital Bern and University Hospital Basel, both in Switzerland; Emory University; University of Chicago; Harvard University; Université de Montréal, Hôpital Maisonneuve-Rosemont, University of Toronto and Montreal Heart Institute, all in Canada; Icahn School of Medicine at Mount Sinai; University of California Riverside; The Children’s Hospital of Philadelphia; Massachusetts Institute of Technology; and Johns Hopkins University.

Additional support for this research was provided by numerous grants to the individual researchers, as listed in the Gastroenterology research publication.

Pitt Researchers Solve Mystery on How Regenerative Medicine Works

A study from the University of Pittsburgh School of Medicine and the McGowan Institute for Regenerative Medicine identifies a mechanism by which bioscaffolds used in regenerative medicine influence cellular behavior, a question that has remained unanswered since the technology was first developed several decades ago. The findings were recently published online in Science Advances.

Bioscaffolds composed of extracellular matrix (ECM) derived from pig tissue promote tissue repair and reconstruction. Currently, these bioscaffolds are used to treat a wide variety of illnesses such hernias and esophageal cancer, as well as to regrow muscle tissue lost in battlefield wounds and other serious injuries.

“Bioscaffolds fulfill an unmet medical need, and have already changed the lives of millions of people,” said lead study investigator Stephen Badylak, DVM, MD, PhD, professor of surgery at Pitt and deputy director of the McGowan Institute, a joint effort of Pitt and UPMC.

Researchers know that ECM is able to instruct the human body to replace injured or missing tissue, but exactly how the ECM material influences cells to cause functional tissue regrowth has remained a fundamental unanswered question in the field of regenerative medicine.

In the new study, Dr. Badylak and his team showed that cellular communication occurs using nanovesicles, extremely tiny fluid-filled sacs that bud off from a cell’s outer surface and allow cells to communicate by transferring proteins, DNA and other “cargo” from one cell to another.

Exosomes are present in biological fluids such as blood, saliva and urine, where they influence a variety of cellular behaviors, but researchers had yet to identify them in solid body tissues.

“We always thought exosomes are free floating, but recently wondered if they are also present in the solid ECM and might facilitate the cellular communication that is critical to regenerative processes,” Dr. Badylak said.

To explore this possibility, researchers used specialized proteins to break up the ECM, similar to the process that occurs when a bioscaffold becomes incorporated into the recipient’s tissue.

The research team then exposed two different cell types – immune cells and neuronal stem cells – to isolated matrix bound vesicles, finding that they caused both cell types to mimic their normal regrowth behaviors.

“Sure enough, we found that vesicles are embedded within the ECM. In fact, these bioscaffolds are loaded with these vesicles,” Dr. Badylak said. “This study showed us that the matrix bound vesicles are clearly active, can influence cellular behavior and are possibly the primary mechanism by which bioscaffolds cause tissue regrowth in the body.”

Researchers also found that vesicles isolated from different source tissues have distinct molecular signatures, and they are now focused on harnessing this new information for both therapeutic and diagnostic purposes.

Additional coauthors of the study include Luai Huleihel, PhD, George Hussey, PhD, Juan Diego Naranjo, MD, Li Zhang, MD, MS, Jenna Dziki, BS, Neill Turner, PhD, and Donna Stolz, PhD, all of Pitt.

Pitt Receives $62.3 Million, Five-Year NIH Award to Speed Up Translational Scientific Research into Implementable Solutions

The University of Pittsburgh Clinical and Translational Science Institute (CTSI) will receive nearly $62.3 million over five years from the National Institutes of Health (NIH) to broaden its mission of speeding translation of scientific research into realistic treatments for the people who need them.

In 2006, CTSI was among the first 12 recipients of NIH’s Clinical and Translational Science Awards (CTSA). Since then, Pitt’s CTSA funding has totaled more than $221 million. Including the recently announced funding for Pitt’s participation in NIH’s Precision Medicine Initiative Cohort Program, CTSI-supported programs have been awarded approximately $108 million in research funding over the next five years.

“This award is emblematic of the significant contribution that University of Pittsburgh researchers and physicians are continuing to make to advance our understanding of biomedical science and improve clinical care,” said Arthur S. Levine, MD, Pitt’s senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine.

Over the past 10 years, CTSI has built an infrastructure of programming to support all avenues of scientific investigation, from guidance in regulatory requirements and study design to career/workforce development, education and training, community engagement, biomedical informatics, pilot funding of early-stage research, and innovation. It has trained 850 investigators and supported more than 2,000 investigators who have conducted more than 4,000 research studies.

“Among our most important goals for the next five years is engaging a broader range of people and communities in research,” said CTSI Director Steven E. Reis, M.D., who also is associate vice chancellor for clinical research, health sciences, and a professor of medicine at the Pitt School of Medicine. “We also will expand CTSI’s reach by launching several new programs, including a focus on entrepreneurship in research and in translating discoveries to practice.”

New initiatives during the upcoming grant period include:

• Innovation as a Discipline
• Biomedical Modeling
• Integrating Special Populations
• Clinical Trial Recruitment and Efficiency
• Clinical Trial Innovation
• Multidisciplinary Team Science

Funding is being provided through NIH’s National Center for Advancing Translational Sciences.

NIH-Funded Pitt Research Study to Evaluate New Voice Therapy Technique

A voice therapy program that was refined by experts at the UPMC Voice Center and successfully piloted on a small group of patients with voice disorders, will be reaching more patients due to a $300,000 National Institutes of Health (NIH) grant recently awarded to the University of Pittsburgh School of Medicine.

The new voice therapy approach, Conversation Training Therapy (CTT), concentrates on voice training in spontaneous, conversational speech for patients with voice impairment.

“With this approach, we focus on patients becoming aware and efficient in conversation, instead of in voice exercises. Results from our initial trial showed that patients met their voice therapy goals in just three sessions, substantially below the number of sessions typically required in traditional voice therapy programs, which can take up to 12 or even 24 sessions. Patients also reported that they noticed marked improvement in their voice impairment,” said lead researcher Amanda Gillespie, PhD,  assistant professor, Department of Otolaryngology, Pitt School of Medicine, and director of Clinical Research, UPMC Voice Center.

Treatment aimed at modifying behaviors that cause or contribute to voice disorders is the standard of care for many people experiencing voice issues. Although voice therapy is effective at treating voice disorders, substantial limitations exist with traditional treatment models. These limitations cause a protracted length of time in required treatment, as well as drop out and voice problem relapse rates approaching 70 percent, which contribute to the high costs associated with treating voice disorders.

CTT was developed by a team of expert voice-specialized speech-language pathologists at voice centers around the U.S. The goal of this study is to determine the effectiveness of CTT in the rehabilitation of patients with two common voice disorders—benign vocal fold lesions and muscle tension dysphonia. Once that is determined, the long term goal is to conduct multi-center trials comparing CTT to traditional voice therapy programs in people with voice disorders.

Pitt’s research study is the first to look at a voice therapy program based in theories of motor learning and neuroplasticity, developed with input from patients with voice disorders and expert, clinical, speech-language pathologists.

“Results of the current research have the potential to dramatically change how voice therapy is delivered, including the necessary time spent in treatment, resulting in a potential savings of health care funds and improved quality of life for people with voice disorders,” said Jackie L. Gartner-Schmidt, PhD,  co-investigator on the study, co-director of the UPMC Voice Center, and director of Speech-Language Pathology-Voice Division, Pitt School of Medicine.

Researchers will recruit 60 participants to undergo four weeks of treatment with a CTT-trained voice therapist. Each will be evaluated prior to starting CTT, before each treatment session, and at one-week and three-month intervals after the last CTT session. Outcome measures will include participant-perceived voice handicap, acoustic, aerodynamic and audio-perceptual voice analyses, and will be compared to matched past patients who previously underwent traditional voice therapy. Participants are compensated for their time.

The three-year grant (R03 DC015305) was awarded by the National Institute on Deafness and other Communication Disorders.

Other co-investigators at the University of Pittsburgh are Clark Rosen, MD, and Jonathan Yabes, PhD.

For more information, call 412-647-SING (7464) or email Tina Harrison, study coordinator, at harrisonta@upmc.edu.

Study Shows Overlooked Benefit of Successful Healthy Lifestyle Programs: Improved Quality of Life

The value of a healthy lifestyle isn’t reflected only in the numbers on the scale or the blood pressure cuff. University of Pittsburgh Graduate School of Public Health researchers demonstrated that it also can be measured through improved “health-related quality of life.”

In an analysis published in the August issue of the journal Quality of Life Research, the scientists showed that participation in a community-based behavioral lifestyle intervention program to improve health not only helped people lose weight, increase their physical activity levels, and reduce their risk of diabetes and heart disease, but also increased their health-related quality of life by an average of nearly 10 percent. The research was funded by the National Institutes of Health (NIH).

“These community-based lifestyle intervention programs have additional valuable benefits, beyond the improvement of risk factors for type 2 diabetes and heart disease,” said lead author Yvonne L. Eaglehouse, PhD, a postdoctoral researcher at Pitt Public Health. “Our study demonstrates that these programs, delivered in diverse community settings such as senior centers and worksites, simultaneously and significantly improved the quality of life of the participants.”

Dr. Eaglehouse and her colleagues investigated the impact of the Group Lifestyle Balance program, modified from the lifestyle intervention program used in the highly successful US Diabetes Prevention Program (DPP). The DPP was a national study demonstrating that people at risk for diabetes who lost a modest amount of weight and increased their physical activity levels sharply reduced their chances of developing diabetes and metabolic syndrome and outperformed people who took a diabetes drug instead.

Group Lifestyle Balance is a 22-session program administered over a one-year period aimed at helping people make lifestyle changes to improve their risk for diabetes and heart disease. The goals of the program are to help participants reduce their weight by 7 percent and increase their moderate-intensity physical activity (such as brisk walking) to 150 minutes per week.

As part of the Pitt community intervention effort, a total of 223 participants were enrolled to test the effectiveness of the Group Lifestyle Balance program at a worksite and three community centers in the Pittsburgh area. The participants averaged 58 years of age and had pre-diabetes or metabolic syndrome or both.

Before beginning the program, each participant ranked his or her current health on a scale from 0 “worst imaginable health state” to 100 “best imaginable health state.” The US average is 79.2, whereas the participants averaged 71.5 at baseline.

After completing the year-long Group Lifestyle Balance program, the participants increased their average health-related quality-of-life score to 78.2. When looking at only those with baseline health-related quality of life below the U.S. average, there was an even greater magnitude of improvement, from 61.8 at baseline to 74 at the end of the program. Once scores were adjusted for meeting weight loss and physical activity goals, participants who met the program goals were found to have increased their health-related quality-of-life score by nine more points compared to those participants who met neither program goal.

“It is exciting that we were able to document an improvement in health-related quality of life in addition to improvement in risk factors for diabetes and cardiovascular disease,” said senior author Andrea Kriska, PhD, professor in Pitt Public Health’s Department of Epidemiology and principal investigator of the NIH study. “This important benefit was most evident in those who started the intervention program having a relatively lower quality of life—in other words, those who needed to improve the most.”

Additional authors on this research are M. Kaye Kramer, DrPH, RN, Vincent C. Arena, PhD, and Rachel G. Miller, MS, all of Pitt; and Gerald L. Shafer, PhD, of Carroll College in Helena, Montana.

This study was funded by NIH National Institute of Diabetes and Digestive and Kidney Diseases grant R18 DK081323-04.

UPMC Comprehensive Pulmonary Hypertension Program Earns National Distinction

The Comprehensive Pulmonary Hypertension Program at UPMC has been added to the short list of programs nationwide to earn accreditation by the Pulmonary Hypertension Association (PHA) as a Center of Comprehensive Care. UPMC is one of 39 medical centers nationally to receive the distinction for the quality of its pulmonary hypertension program.

“The accreditation is an important component in recognizing the exceptional care that we offer our patients,” said Stephen Y. Chan, MD, PhD, associate professor of medicine, University of Pittsburgh School of Medicine, and director, UPMC Center for Pulmonary Vascular Biology and Medicine at the Vascular Medicine Institute at the University of Pittsburgh. “With the significant resources and expertise that we are focusing on pulmonary hypertension, this accreditation and our already sterling reputation as a first-class research center in pulmonary hypertension make us one of the top programs in the world for both research and clinical care.”

Pulmonary hypertension is high blood pressure that occurs in the arteries in the lungs, making it difficult for blood to flow from the heart to the lungs. Symptoms of the disease, which can lead to heart failure, include shortness of breath, fatigue and chest pain, and in its early stages might not be noticeable for months or even years. A rare and life-threatening condition, it becomes progressively worse, making early and accurate diagnosis important to allow treatment methods to extend and improve the quality of life for many patients.

Featuring one of the largest multidisciplinary teams in the country, the UPMC Comprehensive Pulmonary Hypertension Program is a joint program of the UPMC Heart and Vascular Institute and the Pitt Division of Pulmonary, Allergy and Critical Care Medicine. It offers state-of-the-art diagnostics and a full range of therapy, as well as opportunity for patients to participate in cutting-edge clinical research aimed at improving diagnosis and treatment methods.

“Many centers have one or two people focused on pulmonary hypertension, but here at UPMC we have more than 60 people—researchers, physicians, nurses, pharmacists and clinical practitioners—all committed to fighting this disease,” Dr. Chan said. “We are pushing discovery forward, and getting closer to the point of creating new therapies that won’t just make our patients feel better, but rather will help reverse, prevent and hopefully cure pulmonary hypertension.”

The accreditation process began two years ago and is based on criteria established by the PHA that includes the program’s overall commitment to patients with the disease, scope of services offered and expertise of the care team. Programs that receive the distinction also agree to contribute to the PHA Registry, a new patient registry used to evaluate outcomes for people living with pulmonary hypertension to help researchers learn more about the disease.

Children’s Hospital of Pittsburgh of UPMC Part of New Pennsylvania Program to Improve Behavioral Health for Kids

PrintChildren’s Hospital of Pittsburgh of UPMC’s primary care network, Children’s Community Pediatrics (CCP), has been selected by the HealthChoices managed care organizations to take part in a new program to improve behavioral health treatment for children in the state.

Ted Dallas, secretary of the Department of Human Services in Pennsylvania, announced the selection of organizations to administer behavioral health treatment through the new Telephonic Psychiatric Consultation Service Program (TiPS). The announcement was made today at Children’s Hospital, with Dallas joining Christopher Gessner, president of Children’s Hospital, and Abigail Schlesinger, MD, medical director, Community Based Services, Behavioral Science Division of Children’s Hospital.

TiPS is a new program designed to provide real-time resources to physicians seeking consultation and advice for pediatric patients with behavioral health concerns who are served by Medicaid. A physician who uses the TiPS service will have access to a child and adolescent psychiatrist to discuss treatment options and get help linking the child to appropriate treatment if services outside of primary care are deemed necessary.

CCP, through its award-winning behavioral health program, will be manning the hotline to provide telephone consultation to any physician who is prescribing behavioral health medications to kids.

“It is critical that all children, regardless of where they live, have access to quality health care services,” said Dallas. “Access to child psychiatry has been a significant problem nationwide for years. Today’s announcement means that more of our kids will have the services they need, and not just another prescription.”

“Being able to provide behavioral health services in the primary care setting was a vision of ours and something that we’ve been doing for 8 years now,” said Dr. Schlesinger. “We’re excited to partner with the state of Pennsylvania to further enhance families’ ability to access behavioral health services in our region.”

CCP will serve the 26 counties in both the Southwest and Northwest zones. The Children’s Hospital of Philadelphia will serve the Southeast zone and Penn State Children’s Hospital will serve the Northeast and Lehigh/Capital zones.

For more information, visit www.childrenspeds.com.

Regenerative Medicine Improves Strength and Function in Severe Muscle Injuries

Results of a study conducted by researchers at the University of Pittsburgh School of Medicine and the McGowan Institute for Regenerative Medicine showed significant improvement in strength and range of motion, as well as evidence for skeletal muscle regeneration, in 13 patients who were surgically implanted with bioscaffolds derived from pig tissue to treat muscle injuries. The patients had failed to respond to conventional treatment before use of the extracellular matrix (ECM). The findings were published online today in npj Regenerative Medicine.

“Previously, there was no effective treatment for these patients, but this approach holds significant promise,” said senior investigator Stephen F. Badylak, DVM, PhD, MD, professor of surgery at Pitt and deputy director of the McGowan Institute, a joint effort of Pitt and UPMC. “This approach could be a game changer and not just an incremental advance.”

For the Muscle Tendon Tissue Unit Repair and Reinforcement Reconstructive Surgery Research Study, which was sponsored by the US Department of Defense, 11 men and two women who had lost at least 25 percent of leg or arm muscle volume and function first underwent a customized regimen of physical therapy for four to 16 weeks.

Lead study surgeon J. Peter Rubin, MD, UPMC Professor and Chair of Plastic Surgery, Pitt School of Medicine, then surgically implanted a “quilt” of compressed ECM sheets designed to fill in their injury sites. Within 48 hours of the operation, the participants resumed physical therapy for up to 24 additional weeks.

By six months after implantation, patients showed an average improvement of 37.3 percent in strength and 27.1 percent in range of motion tasks compared with pre-operative performance numbers. CT or MRI imaging also showed an increase in post-operative soft tissue formation in all 13 patients.

“For well-selected patients with this type of loss, we now have a treatment available to help improve their function,” Dr. Rubin said.

The new data builds upon a previous Pitt study that showed damaged leg muscles grew stronger and showed signs of regeneration in three out of five men whose old injuries were surgically implanted with ECM derived from pig bladder. Those patients also underwent similar pre- and post-operative physical therapy.

The recent results included more patients with varying limb injuries; used three different types of pig tissues for ECM bioscaffolds; investigated neurogenic cells as a component of the functional remodeling process; and included CT and MRI imaging to evaluate the remodeled muscle tissue.

“The three different types of matrix materials used all worked the same, which is significant because it means this is a generic property of these materials and gives the surgeons a choice for using whichever tissue they like,” Dr. Badylak said. “Prior to the surgery, each patient went through physical therapy focused on getting them to the point where they couldn’t get any better. We then started active rehab 24 hours after surgery, which proved to be critically important for these patients.”

The research team included lead authors Jenna Dziki, Dr. Badylak, Dr. Rubin, and others from Pitt and McGowan. The project was supported by a research grant from the US Department of the Interior, grant D11AC00006.

The US Department of Defense’s Limb Salvage and Regenerative Medicine Initiative and the Muscle Tendon Tissue Unit Repair and Reinforcement Reconstructive Surgery Research Study are collaboratively managed by the Office of the Secretary of Defense. The initiative is focused on rapidly and safely transitioning advanced medical technology in commercially viable capabilities to provide wounded warriors the safest and most advanced care possible today.

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