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Experimental Baby Formula Doesn’t Prevent Development of Antibodies Associated with Type I Diabetes in Early Childhood

First Large Trial of Type I Diabetes Prevention Approach Still Underway

PITTSBURGH, June 10, 2014 – Early findings from the first large international trial to try to prevent type I diabetes show that infants at risk for the disease who were fed a special baby formula that lacks complex cow milk proteins still made antibodies against the insulin-producing cells of the pancreas by the time the youngest children studied were six years old. Previous studies suggested the experimental formula might prevent the development of the auto-antibodies, which represent inflammatory changes in the organ.

But that doesn’t mean the children will definitely develop type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM), as they get older, caution researchers at Children’s Hospital of Pittsburgh of UPMC, which is the coordinating center for the American arm of the study. The findings were published today in the Journal of the American Medical Association.

In type I diabetes, the body’s immune system attacks its own pancreatic beta cells, which make insulin to regulate blood sugar levels. That autoimmune process is thought to start very early in life, explained U.S. principal investigator Dorothy Becker, MBBCh, professor of pediatrics at Children’s Hospital and the University of Pittsburgh School of Medicine. Some smaller studies and animal experiments have shown that exposure during infancy to complex foreign proteins, such as the cow milk proteins in conventional baby formula, is associated with the presence of these autoimmune antibodies in children who have a parent or sibling with the condition and other indications of genetic risk.

“This has been a controversial issue, in part because different natural history studies have come to different conclusions,” Dr. Becker said. “We hope that when our intervention trial concludes in February 2017, which is when all the participating children will be at least 10 years old, we should have enough evidence to say whether or not this experimental formula can prevent them from getting Type I diabetes.”

From 2002 to 2007 at 78 study sites in 15 countries, the “Trial to Reduce IDDM in the Genetically at Risk,” or TRIGR, research group randomly assigned 1,078 high-risk infants to be weaned to a “hydrolyzed” formula made almost completely with smaller, less complex casein proteins and 1,081 to get conventional formula, which is made with 80 percent cow milk proteins and 20 percent of the hydrolyzed casein protein. The two formulas were similar in taste and smell so that neither the parents nor researchers could tell the difference between them. Each baby’s parents made their own decisions about breastfeeding and age of weaning to formula.

Blood samples from the umbilical cord and at three, six, nine, 12, 18 and 24 months of age, and yearly after that to age 10, were tested for antibody levels. After an average of seven years of follow-up — the youngest participants are now six — the researchers found no differences in antibody levels between the two groups.

“This tells us that the kind of formula the baby drinks doesn’t affect the inflammatory changes going on in the pancreas,” Dr. Becker said. “But it doesn’t tell us yet whether they will develop diabetes. In one animal study, mice that were fed the experimental formula had the inflammatory markers, but diabetes was almost totally prevented using the same experimental formula. That could be the case with these children, too.”

The TRIGR study group includes the Data Management Unit and researchers from six centers in the U.S., centers in Scandinavia led by the University of Helsinki, and centers throughout Canada, Australia and Europe.

The project was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Special Statutory Funding Program for Type 1 Diabetes Research and Digestive and Kidney Diseases, both part of the National Institutes of Health (grant numbers HD040364, HD042444 and 338 HD051997); the Canadian Institutes of Health Research; the Juvenile Diabetes Research Foundation International; and the Commission of the European Communities.

Children’s Hospital of Pittsburgh of UPMC Named One of America’s Top 10 Children’s Hospitals

PITTSBURGH, June 10, 2014 – Children’s Hospital of Pittsburgh of UPMC has been named one of America’s Best Children’s Hospitals by U.S. News & World Report.

Children’s Hospital ranks ninth on the magazine’s 2014-15 Honor Roll of America’s Best Children’s Hospitals, which was released today. Children’s also ranks in each of the 10 pediatrics specialties ranked by U.S. News. This is the fifth consecutive year Children’s has been named to U.S. News’ Honor Roll.

The Best Children’s Hospitals rankings highlight the top 50 U.S. pediatric hospitals in each of 10 specialties: cancer; cardiology and heart surgery; diabetes and endocrinology; gastroenterology and GI surgery; neonatology; nephrology; neurology and neurosurgery; orthopaedics; pulmonology; and urology.

Children’s ranked in the top 25 of all 10 specialties, including fifth in diabetes and endocrinology; sixth in gastroenterology and GI surgery; sixth in pulmonology; eighth in neonatology; and ninth in neurology and neurosurgery.

“Our inclusion on the honor roll and our rankings in each of the 10 specialties speaks to the breadth and depth of our clinical programs,” said Christopher Gessner, Children’s president. “It speaks to the expertise and commitment of our physicians, nurses and other staff who make Children’s Hospital a global leader in pediatric health care.”

The 2014-15 Best Children’s Hospitals rankings will be released online today and also will be published in the U.S. News Best Hospitals 2015 guidebook, available in August.

In addition to Children’s Hospital of Pittsburgh of UPMC, the other hospitals named to U.S. News’ Honor Roll of Best Children’s Hospitals for 2014-15 are:

  • Boston Children’s Hospital
  • Children’s Hospital of Philadelphia
  • Cincinnati Children’s Hospital Medical Center
  • Texas Children’s Hospital, Houston
  • Children’s Hospital Los Angeles
  • Children’s Hospital Colorado, Aurora
  • Nationwide Children’s Hospital, Columbus, Ohio
  • Ann and Robert H. Lurie Children’s Hospital of Chicago
  • Johns Hopkins Children’s Center, Baltimore

UPMC Expands Reach in Italy with Outpatient Diagnostic Center

PITTSBURGH, June 6, 2014 – Adding to its successful transplant and cancer treatment facilities in Italy, UPMC announced today that it is expanding its Italian operations to include outpatient diagnostic services for liver and digestive disorders in the Region of Tuscany.

UPMC is managing and operating the new center, the UPMC Institute for Health, at the Terme di Chianciano Spa in Chianciano Terme. Located near Siena, between Florence and Rome, the facility will build on the traditional attraction of the spa’s thermal water therapies and is expected to attract patients from throughout Italy and beyond when it opens on June 9, 2014.

The new center will offer diagnostic screenings, imaging and procedures for liver and digestive disorders, cardiovascular diseases, diabetes and other illnesses. Patients also will be educated about personal risk factors, healthy lifestyle and diet. Those who need more advanced care may be referred to local hospitals or to other UPMC facilities in Italy, namely the ISMETT transplant hospital in Palermo and the UPMC San Pietro Cancer Center in Rome.

“Building on our long reputation for clinical excellence in Italy, we are proud to expand our high-quality services into a new region of the country,” said Charles Bogosta, president of UPMC’s International and Commercial Services Division. “This popular destination for patients will now have the only facility in the area that can offer a complete digestive check-up in a place that already draws thousands of people every year to its healing waters.”

UPMC is partnering with Terme di Chianciano, a company that operates and manages historical thermal premises in the region, as well as with the municipality and the local health care authority. UPMC is leasing and renovating the spa’s existing medical center.

“With UPMC’s clinical, scientific and management know-how and the well-established treatments of Chianciano Spa, this partnership will deliver a higher level of services to patients in one convenient location,” said Bruno Gridelli, M.D., medical and scientific director of UPMC’s International and Commercial Services Division and chief executive officer of ISMETT.

UPMC’s international footprint already includes operations or services in Italy, Ireland, India, Canada, China, Singapore, Japan and Kazakhstan. Through its international growth and commercialization efforts with industry partners, UPMC is diversifying its revenue base, fueling economic development in its communities, and strengthening its ability to recruit and retain the best and brightest clinicians who are working together to improve health care outcomes globally.

Dad’s Alcohol Consumption Could Influence Sons’ Drinking, Pitt Mouse Study Finds

PITTSBURGH, June 4, 2014 – Even before conception, a son’s vulnerability for alcohol use disorders could be shaped by a father who chronically drinks to excess, according to a new animal study from the University of Pittsburgh School of Medicine. The findings, published online Wednesday in PLOS ONE, show male mice that were chronically exposed to alcohol before breeding had male offspring that were less likely to consume alcohol and were more sensitive to its effects, providing new insight into inheritance and development of drinking behaviors.

Previous human studies indicate that alcoholism can run in families, particularly father to son, but to date only a few gene variants have been associated with Alcohol Use Disorder and they account for only a small fraction of the risk of inheriting the problem, said senior investigator Gregg E. Homanics, Ph.D., professor of anesthesiology and pharmacology & chemical biology, Pitt School of Medicine.

“We examined whether a father’s exposure to alcohol could alter expression of the genes he passed down to his children,” Dr. Homanics said. “Rather than mutation of the genetic sequence, environmental factors might lead to changes that modify the activity of a gene, which is called epigenetics. Our mouse study shows that it is possible for alcohol to modify the dad’s otherwise normal genes and influence consumption in his sons, but surprisingly not his daughters.”

In the study, he and lead author Andrey Finegersh, M.D./Ph.D. student in the Department of Pharmacology & Chemical Biology graduate program, chronically exposed male mice over five weeks to intermittent ethanol vapor, leading to blood alcohol levels slightly higher than the legal limit for human drivers. Then, they mated them to females who had not been exposed to alcohol.

Compared to those of ethanol-free sires, adult male offspring of ethanol-exposed mice consumed less alcohol when it was made available and were less likely to choose to drink it over water. Also, they were more susceptible to alcohol effects on motor control and reduction of anxiety.

“We suspected that the offspring of alcohol exposed sires would have an enhanced taste for alcohol, which seems to be the pattern for humans,” Mr. Finegersh said. “Whether the unexpected reduction in alcohol drinking that was observed is due to differences between species or the specific drinking model that was tested is unclear.”

The researchers plan to examine other drinking models such as binge drinking, identify how alcohol modifies the genes, and explore why female offspring appear unaffected.

The project was funded by grants AA10422 and AA021632 from the National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health.

Children’s Hospital of Pittsburgh Foundation Receives $2.5 Million Gift from the Mario Lemieux Foundation to Establish New Lymphoma Center

PITTSBURGH, June 4, 2014Children’s Hospital of Pittsburgh Foundation announced today that it has received a $2.5 million gift from the Mario Lemieux Foundation to establish a new center for rare and hard-to-treat lymphomas that is expected to benefit children and young adults from around the world.

UPMC will provide matching funds to support the creation of the Mario Lemieux Lymphoma Center for Children and Young Adults at Children’s Hospital of Pittsburgh of UPMC.

The center will focus on clinical care as well as laboratory and clinical research surrounding difficult-to-treat childhood lymphomas. It will be led by Linda McAllister-Lucas, M.D., Ph.D., chief of the Division of Pediatric Hematology/Oncology at Children’s Hospital. She is an internationally recognized expert in lymphoma whose laboratory research has provided new insights into the molecular basis of these types of diseases.

Representatives from the Mario Lemieux Foundation, including Mario Lemieux, joined leaders from Children’s Hospital and its Foundation for today’s announcement. The Mario Lemieux Foundation will donate $2.5 million over seven years, with $2.5 million in matching support from UPMC.

“We are grateful to Mario and Nathalie Lemieux and to the Mario Lemieux Foundation for sharing our vision of a center that capitalizes on our unique expertise to offer hope to a group of patients with a devastating diagnosis,” said Greg Barrett, president, Children’s Hospital of Pittsburgh Foundation.

Lymphoma is the third most common type of childhood cancer, and in the United States, more than 1,500 children are diagnosed per year with some form of the disease, according to the American Cancer Society. While standardized treatment protocols are used for the majority of pediatric lymphoma cases, currently there is no effective treatment for up to 20 percent of patients.

“I was fortunate to have a type of lymphoma that has proven treatments with good outcomes,” Mario Lemieux said. “I want to create a place of hope for kids and young adults and their families who are diagnosed with lymphomas that have no known cures.”

In addition to the research of Dr. McAllister-Lucas, who has studied rare lymphomas with her husband, Peter Lucas, M.D., Ph.D., since 1999, Ed Prochownik, M.D., Ph.D., and J. Anthony Graves, M.D., Ph.D., both physician scientists within pediatric oncology at Children’s, direct research laboratories investigating the mechanisms that underlie the development of lymphoma. The Lemieux gift will now allow Children’s to also recruit an expert clinical researcher who can coordinate clinical trials of cutting-edge treatments for lymphomas, improving research that can have a global impact on care. In addition, the gift will foster the growth of the hospital’s Survivorship Program to support our patients who survive childhood cancer, the majority of whom have had leukemia and lymphoma.

“Children’s and Pittsburgh already had a strong infrastructure in place to provide treatment for lymphomas and other childhood cancers, including a renowned bone marrow transplant program, a cancer program dedicated to adolescents and young adults, and a close collaboration with the University of Pittsburgh Cancer Institute,” said Dr. McAllister-Lucas, who joined Children’s and the University of Pittsburgh School of Medicine in 2012 from the University of Michigan. “The support of the Mario Lemieux Foundation gives us the ability to enhance our basic and clinical research in a way that could lead to improved and potentially new treatments for patients from around the world who currently have very limited options.”

The Mario Lemieux Foundation has been an important supporter of Children’s for many years. The Foundation endowed a fund for pediatric cancer research, has helped to build beautiful spaces within the hospital that help all our patients, including an Austin’s Playroom that is open to all inpatients and offers extended hours, and the Lemieux Sibling Center for young brothers and sisters of patients who have to accompany the family to the hospital, as well as partnered with local Microsoft employees to outfit over 100 inpatient rooms with Xboxes to help distract kids during long hospital stays.

Pitt Public Health Names First Katherine M. Detre Chair in Population Health Science

PITTSBURGH, June 2, 2014 Anne B. Newman, M.D., M.P.H., has been selected as the first Katherine M. Detre Endowed Chair of Population Health Science at the University of Pittsburgh Graduate School of Public Health.

The purpose of this chair is to recruit clinical specialists who are familiar with the methodology of large scale clinical trials to study new therapeutics or novel diagnostic technologies and whether they provide greater value than existing ones.

“An appointment to a named chair is among the highest honors a university can bestow upon a member of its faculty,” said Donald S. Burke, M.D., Pitt Public Health dean and UPMC-Jonas Salk Chair of Global Health. “This appointment recognizes and rewards the quality and impact of Dr. Newman’s work to date, which has earned deep and widespread respect. It also is an expression of our confidence that in the years ahead, she will continue her important contributions to the field of epidemiology, to the University and to the broader society.”

This chair was named after the late Katherine M. Detre, M.D., Dr.P.H., one of the nation’s foremost epidemiologists, particularly noted for her leadership of large-scale clinical studies investigating cardiovascular disease. Dr. Detre was a distinguished professor of epidemiology and founded Pitt Public Health’s Epidemiology Data Center.

“I am so honored to serve the department in Katherine Detre’s name,” said Dr. Newman, who is chair of Pitt Public Health’s Department of Epidemiology and director of the school’s Center for Aging and Population Health. “She was a mentor and a role model for me and for many young faculty in our department. Dr. Detre was an insightful and creative scientist, and she thoroughly enjoyed her work.”

Internationally known as an expert in aging and public health, Dr. Newman has been a professor of epidemiology at Pitt Public Health since 2005. Through research and clinical practice, she has shown people how to remain productive, active and healthy as they age.

Dr. Newman is principal investigator of numerous epidemiologic studies and clinical trials exploring differing aspects of aging, including the Health, Aging, and Body Composition Study, the Long Life Family Study, the Cardiovascular Health Study All Stars, the Lifestyle Interventions for Independence in the Elderly study, and the Aspirin to Reduce Events in the Elderly study.

Potential Breast Cancer Drug Performs Well in Early Clinical Trials

CHICAGO, June 1, 2014 – A drug previously studied to improve chemotherapy may be effective in treating patients with cancers related to the BRCA 1 or 2 genetic mutations, as well as patients with BRCA-like breast cancers, according to a University of Pittsburgh Cancer Institute (UPCI) clinical trial.

The results of the phase I study were presented today at the 50th annual American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The drug, veliparib (ABT-888), is a PARP inhibitor, which means it lowers the resistance of cancer cells to treatment by targeting the polymerase (PARP) family of enzymes responsible for a wide variety of cellular processes in cancer cells, particularly DNA repair.

“Cancer cells have increased levels of PARP, which we believe may, in part, lead to resistance to chemotherapies and other cancer treatments,” said Shannon Puhalla, M.D., assistant professor of medicine, University of Pittsburgh School of Medicine, and breast oncologist with UPMC CancerCenter at Magee-Womens Hospital of UPMC. “Tumor cells in patients with BRCA mutations are particularly sensitive to the effects of PARP inhibitors due to underlying DNA repair abnormalities caused by the BRCA mutation. Veliparib can act as personalized medicine for patients with tumors caused by an inherited BRCA mutation, due to this particular sensitivity.”

The study enrolled 60 patients with a BRCA genetic mutation and 28 patients without a mutation. The objectives of the trial included determining how veliparib affected cancer cells and observing how patients responded to the drug.

“We found that veliparib is well-tolerated by patients, with fewer side effects than what can be seen with chemotherapies. In addition, anti-tumor activity was detected in both our BRCA-positive and our BRCA-negative patients,” said Dr. Puhalla.

Dr. Puhalla and a research team at UPCI have been investigating ABT-888 for five years. Their research began in the laboratory and progressed to human clinical trials. Dr. Puhalla currently is leading a phase II clinical trial with ABT-888.

“Many cancer patients with BRCA mutations end up exhausting their treatment options. Veliparib may give them another option.” Dr. Puhalla said.

The study was funded in part by an ASCO career development award Dr. Puhalla received in 2010 and an ASCO translational research professorship received by the late Merrill Egorin, M.D., who co-directed the Molecular Therapeutics and Drug Discovery program at UPCI. This study also is supported by the Pittsburgh-based Frieda G. and Saul F. Shapira BRCA Cancer Research Program and Cancer Fighting Princess.

Three UPMC Experts Named Among Top Sports Knee Surgeons in North America

PITTSBURGH, May 30, 2014 – Three orthopaedic surgeons from UPMC were named in the Top 28 North American Sports Knee Surgeons of 2014 in Orthopedics This Week. Freddie H. Fu, MD, Christopher D. Harner, MD, and Robin V. West, MD were among those selected through a survey of their colleagues throughout North America.

Dr. Fu is David Silver Professor and chairman of the Department of Orthopaedic Surgery, and director of sports medicine at UPMC. He also serves as the head team physician for the University of Pittsburgh Department of Athletics.

Dr. Harner, professor of orthopaedic surgery at the University of Pittsburgh School of Medicine, is the medical director of the UPMC Center for Sports Medicine, where he also directs the fellowship program.

Dr. West is an associate professor of orthopaedic surgery at the UPMC Center for Sports Medicine and a team physician for the Pittsburgh Steelers.

For the more information, please view the complete listing of surgeons.

Gastroenterology Experts Present at 2014 Digestive Disease Week

The Division of Gastroenterology, Hepatology, and Nutrition was well represented in Chicago at the recent Digestive Disease Week annual meeting, DDW 2014. Division research was featured in both oral and poster presentation throughout the week.

There were more than 50 faculty presentations highlighting topics such as pediatric IBD; nausea and vomiting; pancreatic genetics, physiology, and cell biology; and colon cancer screening. Presenters from the division included:

For more information on the presentations at DDW 2014, please visit the conference page.

  • Nijole Pollock

UPMC, Pitt Honors and Presentations Among Highlights at ATS Annual Meeting

PITTSBURGH, May 29, 2014 – Several UPMC and University of Pittsburgh School of Medicine experts were honored at the recent American Thoracic Society (ATS) annual meeting in San Diego. For the second year in a row, a study involving UPMC has been published by the New England Journal of Medicine (NEJM) in conjunction with a presentation at ATS.

Research on chronic obstructive pulmonary disease (COPD), which included work by Frank Sciurba, MD, Division of Pulmonology, Allergy and Critical Care Medicine (PACCM), was featured in NEJM and the study’s findings were highlighted during a late-breaking abstracts session at ATS. Under a grant from the National Heart, Blood and Lung Institute (NHLBI), researchers from the United States and Canada found that a therapy of cholesterol-lowering statins fails to improve the health of patients with COPD or acute respiratory distress syndrome (ARDS).

A second study was published in NEJM and discussed at an ATS news conference. Derek Angus, MD, MPH, Department of Critical Care Medicine, was one of five authors on the study, which found sepsis contributes to as many as half of all U.S. hospital deaths.

During ATS, Recognition Awards for Scientific Accomplishment were presented to Rama Mallampalli, MD, professor of medicine and director, Acute Lung Injury Center at the University of Pittsburgh, and Juan Celedón, MD, chief,  Division of Pediatric Pulmonology, Allergy and Immunology at Children’s Hospital of Pittsburgh of UPMC. Dr. Mallampalli was recognized by ATS for his “groundbreaking discoveries in pulmonary cell and molecular biology” and Dr. Celedón for “research on childhood asthma and health disparities in asthma.”

Several other UPMC physicians and researchers served as facilitators, moderators, presenters, or panelists at ATS, including:

For more information about this year’s presentations and awards, visit the ATS conference page.

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