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Older Age at Onset of Type 1 Diabetes Associated with Lower Brain Connectivity Later in Life

PITTSBURGH, July 14, 2015 – People diagnosed with type 1 diabetes in later childhood have weaker brain connectivity in midlife compared to those who were diagnosed at earlier ages according to a University of Pittsburgh Schools of the Health Sciences study.

The findings are reported in a special issue of Psychosomatic Medicine that is focused on diabetes, obesity and the brain. Sixty-six middle-aged adults (ages 32 to 58) who were diagnosed with type 1 diabetes as children participated in the study.

“Other studies have shown an association between earlier onset type 1 diabetes and cognitive difficulties, so we expected to find that people with earlier age of onset would have weaker connections between brain regions,” said John Ryan, Ph.D., assistant professor of psychiatry at Pitt. “But instead, we found that those who were diagnosed later in childhood had the weaker brain connections as they aged.”

All of the study participants had onset of type 1 diabetes before age 18 and were enrolled in the Pittsburgh Epidemiology of Diabetes Complications Study, which is an ongoing investigation led by Caterina Rosano, M.D., M.P.H., at Pitt’s Graduate School of Public Health  documenting long-term complications of type 1 diabetes among patients at Children’s Hospital of Pittsburgh of UPMC between 1950 and 1980.

The participant group is one of the few in the country in which people with childhood onset type 1 diabetes have been followed throughout their lifespan. “Due to advances in treatments, people with type 1 diabetes are living longer. But we don’t yet understand how diabetes and aging interact in the brain,” Dr. Ryan noted.

“The mechanisms underlying these associations are not yet clear,” he said.  “However, the relationships between age of diagnosis and connectivity was stronger in older participants, supporting a model of diabetes as accelerated aging.”

Additional researchers on this project include Howard J. Aizenstein, M.D., Ph.D., Trevor J. Orchard, M.B.B.Ch., M.Med.Sci., F.A.H.A., F.A.C.E., Christopher M. Ryan, Ph.D., Judith A. Saxton, Ph.D., David F. Fine, B.S., and Karen A. Nunley, Ph.D., all of Pitt Public Health.

Kids May Need More Vitamin D, Pitt/Children’s Study Finds

PITTSBURGH, July 9, 2015 – Currently recommended daily dietary allowances of vitamin D may be insufficient to prevent deficiency in children, according to researchers at Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine. In a report recently published in the Journal of Clinical Endocrinology and Metabolism, they noted that children with suboptimal vitamin D blood levels did not reach optimal levels after taking nearly twice the recommended amount of the nutrient daily for six months.

Vitamin D is important for calcium metabolism and bone health, said lead investigator and Children’s Hospital pediatrician Kumaravel Rajakumar, M.D., M.S., who also is an associate professor of pediatrics at Pitt’s School of Medicine. It is present in a few foods, milk is usually fortified with it and with enough exposure to sunlight the body naturally produces it.

“Vitamin D deficiency is common in the northeastern U.S., especially in black children whose darker skin complexions have higher amounts of melanin, preventing absorption of the ultraviolet light that’s needed to trigger vitamin D synthesis,” he explained.

Guidelines differ on adequate blood levels of vitamin D for bone health, highlighting the need for further research. Blood level of 25-hydroxyvitamin D is the best measure of vitamin D status. For example, a blood level of 20 or more nanograms per milliliter (ng/mL) of the vitamin is considered adequate for bone health by the Institute of Medicine, while the Endocrine Society recommends a level of 30 ng/mL for optimal bone health.

Between October and March of 2008 through 2011, the researchers randomly assigned 84 black and 73 white 8- to 14-year-old children from Pittsburgh and Kittanning, Pa., to take for six months either a daily pill of 1,000 international units (IU) of vitamin D3 or a placebo. They also performed periodic blood tests to assess their 25-hydroxyvitamin D levels and other markers of bone health.

The average vitamin D level at the initial assessment of all children, and particularly black children, was suboptimal (less than 20 ng/mL), and supplementation raised their average level to above 20 ng/mL but not as high as 30 ng/mL. After six months of vitamin D supplementation in children with initial vitamin D levels less than 20 ng/mL, 39 percent remained below 20 ng/mL and only 14 percent rose above 30 ng/mL. Biomarkers of bone turnover remained unchanged.

“Our findings suggest that currently recommended daily dietary allowances of vitamin D of 600 IU may be inadequate for preventing vitamin D deficiency in children,” Dr. Rajakumar said. “It may be important to revisit these recommendations, especially since the higher dose of vitamin D used in this study was safe and did not appear to lead to any side effects.”

The team included Charity G. Moore, Ph.D., M.S.P.H., Jonathan Yabes, Ph.D., Flora Olabopo, B.S., Mary Ann Haralam, M.S.N., Diane Comer, B.A., Susan Sereika, Ph.D., Jacqueline Dunbar-Jacob, Ph.D., and Susan L Greenspan, M.D., all of Pitt; Jaimee Bogusz, B.S., and Michael F. Holick, M.D., Ph.D., both of Boston University School of Medicine; and Anita Nucci, Ph.D., M.P.H., R.D., L.D., of Georgia State University.

The project was funded by National Institutes of Health grants HD052550, DK062895, AG024827, HL112985 and RR024153; and Children’s Hospital of Pittsburgh of UPMC.

Early HIV Treatment Improves Survival in Some Patients with Newly Diagnosed TB

PITTSBURGH, July 9, 2015 – Starting anti-HIV treatment within two weeks of the diagnosis of tuberculosis, or TB, improved survival among patients with both infections who had very low immune-cell counts, according to an analysis by researchers at the University of Pittsburgh Graduate School of Public Health. Those with strong immune systems, however, might benefit from waiting until after the end of the six-month TB treatment before initiating anti-HIV therapy, they found.

In a study published in the current issue of Annals of Internal Medicine, the team recommended updating physician guidelines to take the findings into account.

Infection with HIV can promote progression and re-infection to active TB after initial exposure to Mycobacterium tuberculosis, the organism that causes TB, explained senior author Jean B. Nachega, M.D., Ph.D., M.P.H., associate professor of infectious diseases and microbiology and of epidemiology, Pitt Public Health. Treating HIV and TB simultaneously is challenging for many reasons, including the requirement for patients to take multiple pills several times daily for each infection, drug-drug interactions and overlapping side effects.

“Current World Health Organization guidelines recommend starting TB treatment first, followed by HIV treatment as soon as possible within two to eight weeks for patients who have moderately to severely compromised immune systems, but there was not conclusive evidence to guide treatment in other levels of immune suppression,” Dr. Nachega said. “We aimed to investigate the optimal timing of HIV initiation in light of recent published randomized clinical trials on this topic.”

The team systematically reviewed data from more than 4,500 people participating in eight randomized clinical trials of early initiation of HIV anti-retroviral therapy (ART) conducted in Asia, Africa and the United States. They found that survival rates were better among patients who started ART within two weeks of the initiation of TB treatment and who also had very low CD4 T-cell counts of less than 0.050 x 109cells/liter, as measured by a blood test which reflects severe immune system suppression due to HIV infection. Of note, early initiation also was associated with a two-fold increase in the frequency of a complication called TB-Immune Reconstitution Inflammatory Syndrome, which can be fatal in rare occasions. There was no evidence to support or refute a survival benefit for patients with CD4 counts between 0.050 and 0.220 x 109cells/liter.

“Our findings support guidelines recommending early initiation of ART in patients with a high degree of immune system compromise,” Dr. Nachega said. “But delaying ART might be possible until the end of TB treatment with patients with CD4 counts greater than 0.220 x 109cells/liter, which could reduce the burden of taking two complex drug regimens at the same time.”

However, Dr. Nachega noted that there is other emerging evidence showing the clinical and public health benefits associated with early initiation of HIV treatment, other than survival. Indeed, early treatment may be beneficial by decreasing comorbidities due to ongoing inflammation caused by HIV and decreasing HIV sexual transmission.

“Clinicians will need to weigh these benefits against the burden of co-administration of TB and HIV treatment on a case-by-case basis, but the overarching goal is likely to be a move toward treating all HIV-positive people as early as possible,” said Dr. Nachega.

The team included researchers from the University of Pittsburgh; Warwick Medical School, United Kingdom; Liverpool School of Tropical Medicine, United Kingdom; Stellenbosch University, South Africa; South African Medical Research Council; University Medical Center Utrecht, The Netherlands; Johns Hopkins Bloomberg School of Public Health; and University College London, United Kingdom.

The research team was supported with funding from the Swedish Council for Working Life and Social Research; the National Institute for Allergy and Infectious Disease of the National Institutes of Health; the AIDS Clinical Trial Group; and Stellenbosch University Clinical Trial Unit; the Medical Education Partnership Initiative through the U.S. President Emergency Plan for AIDS Relief; the European Developing Countries Clinical Trial Partnership Senior Fellowship Award; the Wellcome Trust Southern Africa Consortium for Research Excellence; the European Commission Seventh Framework Programme (Rapid Identification of Respiratory Tract Infections Project); and the South African Medical Research Council.

Pitt Scientists Lead Consensus Guidelines for Thyroid Cancer Molecular Tests

PITTSBURGH, July 6, 2015 University of Pittsburgh Cancer Institute (UPCI) scientists recently led a panel of experts in revising national guidelines for thyroid cancer testing to reflect newly available tests that better incorporate personalized medicine into diagnosing the condition.

Their clinical explanation for when to use and how to interpret thyroid cancer tests is published in the July issue of the scientific journal Thyroid. The American Thyroid Association is revising its 2015 Guidelines for Thyroid Nodule and Thyroid Cancer Management to direct doctors to the scientific publication.

“Minimally invasive molecular testing for thyroid cancer has improved by leaps and bounds in the last several years,” said co-author Robert L. Ferris, M.D., Ph.D., professor and chief of the Division of Head and Neck Surgery in Pitt’s School of Medicine. “But different tests perform differently and, therefore, need to be interpreted carefully to make the best decisions regarding extent of surgery for patients with thyroid nodules. Our goal with this analysis is to give clinicians a clear understanding of what each type of test can tell them and when to use them to determine the best course of treatment.”

Cancer in the thyroid, which is located just below the “Adam’s apple” area of the neck, is the fifth most common cancer diagnosed in women. Thyroid cancer is one of the few cancers that continues to increase in incidence, although the five-year survival rate is 97 percent.

UPCI, partner with UPMC CancerCenter, has been a national leader in developing personalized genetic tests for thyroid cancer that have spared patients repeat or unnecessary surgeries. A low-cost test called ThyroSeq, developed by a team led by Yuri Nikiforov, M.D., Ph.D., director of Pitt’s Division of Molecular and Genomic Pathology, allows pathologists to simultaneously test for multiple genetic markers of thyroid cancer using just a few cells collected from the nodule.

This allows doctors to “rule-in” a specific cancer diagnosis with a high degree of certainty, without a biopsy to remove a large portion of the thyroid, which would then have to be followed with a second surgery if cancer is detected to remove the entire gland. As Dr. Nikiforov’s group added more genetic sequences to the ThyroSeq test to create a larger and more sensitive version of the test, it is now also performing as a “rule-out” test that can tell doctors with a high degree of certainty that a patient does not have cancer.

Other available tests use different technology to serve as accurate “rule-out” tools, but do not have the high sensitivity needed to also reliably “rule-in” cancer. And, in some cases, the accuracy of the “rule out” tests depends on the prevalence of cancer in the patients seen by each individual cancer institute. This is critical because clinicians must know this rate at their institution to correctly calculate the accuracy of “rule-out” test results for each patient.

In addition to Dr. Ferris and co-author Sally E. Carty, M.D., who is professor and chief of the Division of Endocrine Surgery in Pitt’s School of Medicine and co-director of the UPMC/UPCI Multidisciplinary Thyroid Center, the panel reviewing the tests was a multidisciplinary group from a dozen institutions in the U.S. and Canada.

“This was a very innovative and collegial initiative,” said Dr. Carty.  “Through an objective review of the existing tests and the scientific literature characterizing their performance, we are seeking to help clinicians make the best decisions for their patients.”

Dr. Ferris agrees, noting that “this is an exciting time in personalized medicine, and these tests give us the ability to not only better diagnose and treat thyroid cancer, but also significantly reduce surgeries for people who don’t have cancer.”

Additional authors on this publication are Zubair Baloch, M.D., Ph.D., University of Pennsylvania Medical Center; Victor Bernet, M.D., Mayo Clinic; Amy Chen, M.D., Emory University; Thomas J. Fahey III, M.D., New York Presbyterian Hospital; Ian Ganly, M.D., Ph.D., and Ashok Shaha, M.D., both of Memorial Sloan-Kettering Cancer Center; Steven P. Hodak, M.D., and Kepal N. Patel, M.D., both of New York University Medical Center; Electron Kebebew, M.D., National Cancer Institute; David L. Steward, M.D., University of Cincinnati Medical Center; Ralph P. Tufano, M.D., Johns Hopkins University; and Sam M. Wiseman, M.D., St. Paul’s Hospital & University of British Columbia.

Anti-Rejection Drug Can Prevent Pancreatic Inflammation Triggered by Common Procedure to Remove Gallstones

PrintPITTSBURGH, July 2, 2015 – Exposure to an X-ray dye during a common procedure to treat gallstones causes some patients to develop inflammation of the pancreas, according to researchers at the University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of UPMC. In a study published online in Gastroenterology, the team noted that a single dose of FK506, an anti-rejection drug typically used after organ transplantation, might be able to prevent the complication.

During the endoscopic retrograde cholangiopancreatography (ERCP) procedure, doctors insert a fiber-optic endoscope through the mouth, esophagus, stomach and duodenum to access the bile ducts, where a gallstone might be lodged. The X-ray dye, also known as radiocontrast, is infused through a catheter so doctors can visualize the bile ducts and anything obstructing them, explained senior author and principal investigator Sohail Z. Husain, M.D., associate professor of pediatrics at the Pitt School of Medicine and Children’s Hospital.

“Thousands of ERCP procedures are performed every year, particularly for the removal of gallstones,” Dr. Husain said. “But after the procedure, a fair number of patients develop acute pancreatitis, which is an exquisitely painful, life-threatening inflammation of the pancreas. Our findings provide the first explanation for why this complication occurs, namely through the signals that FK506 can block.”

The research team examined what happened to pancreatic cells in mice after they received infusions of two common radiocontrast agents. They found the agents elevated cellular calcium levels, in turn activating proteins, particularly calcineurin, involved in inflammatory pathways that cause tissue injury. Similar results were observed in experiments with human pancreatic cells. Also, mice that were genetically modified to lack calcineurin failed to develop pancreatitis after radiocontrast exposure.

Mice that were given the anti-rejection drug FK506, which is an inhibitor of calcineurin, before and after infusion of the X-ray dye also were protected from pancreatitis.

“In the future, we will test other radiocontrast agents to see if they, too, affect the same inflammatory pathways,” Dr. Husain said. “This study already sets the stage for a clinical trial to test whether calcineurin inhibitors alone or in combination with other drugs can prevent post-ERCP pancreatitis.”

The team included Shunqian Jin, Ph.D., Abrahim I. Orabi, B.S., Tianming Le, M.D., Tanveer A. Javed, B.S., Swati Sah, B.A., and John F. Eisses, M.D., Ph.D., all of the University of Pittsburgh; Rita Bottino, Ph.D., of Allegheny General Hospital; and Jeffery D. Molkentin, Ph.D., of the University of Cincinnati. The project was funded by National Institutes of Health grants DK083327, DK093491 and DK03002.

Mosquito-Borne Viruses Subject of $4M in Federal Grants to Scientists in Pitt’s Center for Vaccine Research

PITTSBURGH, July 2, 2015 – Scientists at the University of Pittsburgh Center for Vaccine Research (CVR) recently received nearly $4 million through five federal grants to study a group of related mosquito-borne viruses. The ultimate goal is to develop vaccines and therapies against the deadly diseases.

The research will be conducted in the Regional Biocontainment Laboratory (RBL) at Pitt, a unique, high-security facility that allows scientists to safely contain and examine potentially dangerous pathogens.

“This recent funding highlights the globally significant research being done right here in Pittsburgh to help develop ways to protect people against emerging diseases of growing concern,” said Ronald Montelaro, Ph.D., professor and co-director of Pitt’s CVR.

William Klimstra, Ph.D., associate professor at Pitt’s CVR, is principal investigator on three of the grants and about half the funding. Kate D. Ryman, Ph.D., also associate professor at Pitt’s CVR, is principal investigator on the other two grants.

“While the number of people who get these diseases is relatively small, the severity of disease and their potential emergence in larger populations or for use as bioweapons drive the necessity for development of countermeasures,” said Dr. Klimstra.

Two of Dr. Klimstra’s grants, both from the National Institutes of Health and totaling $847,000, focus on eastern equine encephalitis virus (EEEV), a rare disease that is found primarily in the Atlantic and Gulf states and kills about half of the people it infects. One of the grants will be used to examine a specific part of the genetic code of the virus that is largely responsible for the severity of human disease, while the other will go toward developing a novel, live-attenuated vaccine against the virus.Dr. Kilmstra

His other grant, which is a collaboration with colleagues at Washington University in St. Louis and Oregon Health and Sciences University, will provide $1.2 million to Dr. Klimstra and CVR colleagues from the U.S. Department of Defense (DOD). This will be used to develop a novel, inactivated vaccine against three strains of alphavirus, a group which comprises about 30 different viruses mainly transmitted by mosquitoes – including EEEV and Venezuelan (VEEV) and western (WEEV) equine encephalitis viruses, which cause periodic outbreaks in the Americas.

Dr. Ryman received $1 million from the DOD to study how these three encephalitic alphaviruses and another mosquito-borne virus, Rift Valley Fever virus (RVFV), enter the brain. The RVFV component is led by Amy Hartman, Ph.D., assistant professor at Pitt’s CVR. The goal is to develop ways to limit brain entry by the virus and identify biological markers of disease severity to use as a measure of the effects of the vaccines and therapeutics. This grant also involves studies with collaborators at the University of Wisconsin.

Dr. RymanFinally, Dr. Ryman received $725,000 from the DOD in collaboration with investigators at the Naval Medical Research Center to raise anti-VEEV antibodies by immunizing cows that have been genetically altered to produce human antibodies. These antibodies will then be assessed for their potential use in protection against alphavirus diseases, similar to convalescent sera, which is derived from the blood of people whose immune systems successfully fought off an infection.

Several of the grants have option periods that, given successful results in initial studies, will add an additional $3 million in funding.

“The technologies used in these studies and the systematic manner in which vaccines and therapeutics for the alphaviruses are being developed are novel and, given positive results, these approaches can be readily applied to other emerging infectious diseases,” said Dr. Ryman.

Some of the studies also involve Simon Watkins, Ph.D., of Pitt’s Center for Biological Imaging, and Douglas Reed, Ph.D., aerosol director for Pitt’s RBL.

Pitt Leads Trial to Reduce Antibiotic Overuse at Post-Acute and Long-Term Care Facilities

PITTSBURGH, June 30, 2015 – The University of Pittsburgh School of Medicine will be leading a $1.5 million national trial to examine methods to reduce unnecessary use of antibiotics in post-acute and long-term care (PA/LTC)facilities.

The three-year study, funded by the U.S. Department of Health and Human Services Agency for Healthcare Research and Quality (AHRQ), will investigate guidelines and tools to help PA/LTC facilities better manage urinary tract infections (UTIs), which are commonly misdiagnosed and incorrectly treated.

“Antimicrobial resistance is a hot button issue in health care nationally and internationally – and improper overutilization of antibiotics is the single largest culprit,” said David A. Nace, M.D., M.P.H., director of long-term care and flu programs in Pitt’s Division of Geriatric Medicine, and primary investigator on the AHRQ grant. “It is critically important that we find ways to cut unnecessary use of antibiotics.”

The World Health Organization and the White House, among others, recently made announcements declaring efforts to address antimicrobial resistance top priorities. JAMA Internal Medicine published an article today finding that antibiotic use is highly variable across nursing homes, exposing residents to an increased risk of antibiotic-related harms and indicating a need to improve antibiotic stewardship in PA/LTC facilities.

The leading reason for antibiotic use at PA/LTC facilities is to treat a suspected UTI. Antibiotics often are started before a correct diagnosis is made. However, as many as two-thirds of those suspected cases turn out not to be UTIs, and the patients don’t benefit from – and could be harmed by – the antibiotics.

When used incorrectly, antibiotics can kill good bacteria and allow harmful, drug-resistant bacteria to flourish. Antibiotics also can cause allergic reactions or side-effects and are the leading cause of adverse drug reactions in long-term care facilities.

Dr. Nace, also chief medical officer for UPMC Senior Communities, and his co-investigators at AMDA – The Society for Post-Acute and Long-Term Care Medicine and the University of Wisconsin are looking at existing guidance and research on UTIs to develop comprehensive guidelines and tools geared toward easy implementation at PA/LTC facilities. University of Wisconsin co-investigator Christopher Crnich, M.D., Ph.D., associate professor of medicine, is an expert in antimicrobial stewardship in long-term care facilities. AMDA has long been respected for improving care in nursing homes, and their reputation will be critical to disseminating the results of this project and improving care across the U.S.

Next year, the team will enroll 40 PA/LTC facilities from Pennsylvania, Texas, North Carolina and Wisconsin in their trial. Half will receive the guidelines, as well as on-going mentoring and education, while the other half will operate as normal.

For a year, the team will collect data on the number of UTIs before and after the trial, the rate of appropriate and inappropriate treatment, and adverse outcomes. Once the trial concludes, all the facilities will be given the guidelines, tools, mentoring and education.

“There’s a lot of pressure across both agriculture and medicine to rein in use of antibiotics,” said Dr. Nace. “We are very quickly running out of antibiotics to do the job for us, and the problem is only going to grow worse. New antibiotics are not being created and licensed fast enough to keep pace with bacterium’s ability to develop drug-resistance. Efforts like ours to become better stewards of existing antibiotics are among the few solutions left at our disposal.”

New Pitt Research Team Finds Different Immune Response in Severe Asthma; To Continue Such Studies

PITTSBURGH, June 29, 2015 – The immune response that occurs in patients with severe asthma is markedly different than what occurs in milder forms of the lung condition, according to researchers from the University of Pittsburgh School of Medicine. Those unique features could point the way to new treatments, they said in an article published online today in the Journal of Clinical Investigation (JCI).

People with severe asthma, in which the airways become inflamed and constrict to impair breathing, do not get better even with high doses of corticosteroids, the mainstay of treatment for typical asthma, explained Anuradha Ray, Ph.D., professor of medicine, Pitt School of Medicine.

“About 10 percent of asthma patients have a severe form of the disease, but they account for up to half of asthma costs in the U.S. and Europe,” Dr. Ray said. “That’s because these patients frequently need to go to the emergency room or be hospitalized when they have an acute asthma episode.”

For the study, conducted as part of the doctoral thesis of Mahesh Raundhal, a graduate student in the laboratory of Prabir Ray, Ph.D., Pitt professor of medicine and co-senior author, the research team examined lung cell samples obtained from patients also participating in the Severe Asthma Research Program (SARP), a National Heart, Lung, and Blood Institute of the National Institutes of Health-sponsored program to improve the understanding of severe asthma. Sally Wenzel, M.D., director of the University of Pittsburgh Asthma Institute of UPMC, serves as the Pitt SARP principal investigator.

Researchers observed that the immune cells, called CD4 T-cells, in the airways of severe asthmatics secreted different inflammatory proteins than those in mild disease, particularly interferon gamma. The analysis of human samples helped them to develop a mouse model of the disease by introducing an allergen and a bacterial product to induce an immune profile and airway hyper-reactivity that were poorly controlled by corticosteroids, comparable to human severe asthma patients.

When they subjected mice that lacked the interferon gamma gene to the severe asthma model, they found that the mice could not be induced to develop severe asthma. Using computer modeling to identify links between interferon gamma and asthma-associated genes, they learned that as interferon gamma levels rose, the levels of a protein called secretory leukocyte protease inhibitor (SLPI) dropped.

In follow-up experiments, the team found that boosting SLPI levels reduced airway hyper-reactivity in the animal model.

“We’d like to better understand why severe asthma occurs in most people right from the start,” Dr. Anuradha Ray said. “We also want to find agents that can raise SLPI levels for clinical use.”

In a new project that began this month, Drs. Anuradha Ray and Wenzel were recently awarded a five-year, $8 million grant from the National Institute of Allergy and Infectious Diseases (NIAID), also part of the National Institutes of Health (NIH), to continue studying the immune response and genetic roots of severe asthma in 120 patients and in animal models.

The research effort signifies a union of Pitt and UPMC scientists, immunologists and clinicians working under the NIAID grant to bring bench to bedside and bedside to bench, Dr. Wenzel said.

“It’s the unmet need of asthma,” Dr. Wenzel said. “This is one of the first true opportunities to integrate top-tier immunologists with translational clinical science. To find the many different mechanisms involved, you need a team effort such as this one.”

In addition to Drs. Wenzel and Anuradha Ray, the project leaders of this grant are core leaders Timothy B. Oriss, Ph.D., of the University of Pittsburgh, and Jay Kolls, M.D., of Children’s Hospital of Pittsburgh of UPMC, who also co-authored the JCI paper. Other members of the research team are Prabir Ray, Ph.D., and Fernando Holguin, M.D., Douglas Landsittel, Ph.D., and Donald DeFranco, Ph.D., all of Pitt.

The published project was funded by NIH grants HL113956, Al106684, AI048927, AI100012, HL69174, HL079142, and DK072506; as well as the Cystic Fibrosis Foundation Research Development Program.

Children’s Hospital of Pittsburgh of UPMC Named a Center of Excellence by Food Allergy Research & Education

PrintPITTSBURGH, June 29, 2015Children’s Hospital of Pittsburgh of UPMC has been named a center of excellence by Food Allergy Research & Education, which has established the FARE Clinical Network, an initiative that aims to accelerate the development of drugs for patients with food allergies as well as improve the quality of care for this serious illness. Children’s Hospital is one of 21 centers named as inaugural members.

FARE Clinical Network members will serve as sites for clinical trials for the development of new therapeutics and will develop best practices for the care of patients with food allergies. The Network will serve as a powerful driver of collaboration to advance the field of food allergy, with member centers contributing to the development of a national food allergy patient registry and biorepositories.

“We were honored to be invited to apply for membership with the FARE Clinical Network and to receive designation as a FARE Clinical Network Center of Excellence,” said Todd D. Green, M.D., Division of Pulmonary Medicine, Allergy and Immunology, Children’s Hospital. “This will be a great opportunity for food-allergic patients and their families in our region and will allow us to collaborate with other top food allergy centers on maximizing the quality of care these patients receive, as well as to participate in more multicenter research studies.”

Participation in the FARE Clinical Network will ensure that Children’s remains on the forefront of efforts to improve the quality of life for food-allergic individuals as they work toward development of potential new treatments.

“We need to push for the development of drugs and other therapies to prevent life-threatening food allergy reactions, while ensuring that children and adults with food allergy receive the best care possible,” said James R. Baker, Jr., M.D., C.E.O. and chief medical officer of FARE. “To that end, FARE will direct the Clinical Network centers of excellence across the country to a common goal of ensuring that patients with food allergies have access to state-of-the-art diagnosis, treatments and research. We will continue to expand the number of centers to provide access to more patients. This effort is fundamental to our mission — to improve the quality of life and the health of individuals with food allergies while providing them hope through the promise of new treatments.”

In addition to Children’s, the inaugural members of the FARE Clinical Network are:

  • Ann & Robert H. Lurie Children’s Hospital of Chicago
  • Arkansas Children’s Hospital Research Institute
  • Boston Children’s Hospital
  • Children’s Hospital Colorado
  • Children’s Mercy Kansas City
  • Children’s National Health System
  • Cincinnati Children’s Hospital Medical Center
  • Joe DiMaggio Children’s Hospital – a facility of Memorial Healthcare System
  • MassGeneral Hospital for Children
  • National Jewish Health (Denver)
  • Rady Children’s Hospital/University of California, San Diego
  • Riley Hospital for Children at IU Health
  • Sean N. Parker Center for Allergy Research at Stanford University
  • Texas Children’s Hospital Food Allergy Program, Baylor College of Medicine
  • The Children’s Hospital of Philadelphia
  • The Northwest Asthma and Allergy Center (Seattle)
  • The University of Chicago Medicine
  • UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill
  • University of Arizona College of Medicine – Tucson
  • UT Southwestern Medical Center and Children’s Medical Center Dallas

The centers of excellence selected as part of the FARE Clinical Network provide high-quality clinical and subspecialty food allergy expertise and services and are focused on applying new evidence-based knowledge to this important field. Additionally, these centers meet high standards for clinical care, teaching and clinical research.

Computer Simulation Predicts Development, Progress of Pressure Sores

PITTSBURGH, June 25, 2015 – Researchers at the University of Pittsburgh School of Medicine have devised a computational model that could enhance understanding, diagnosis and treatment of pressure ulcers related to spinal cord injury. In a report published online in PLOS Computational Biology, the team also described results of virtual clinical trials that showed that for effective treatment of the lesions, anti-inflammatory measures had to be applied well before the earliest clinical signs of ulcer formation.

Pressure ulcers affect more than 2.5 million Americans annually and patients who have spinal cord injuries that impair movement are more vulnerable to developing them, said senior investigator Yoram Vodovotz, Ph.D., professor of surgery and director of the Center for Inflammation and Regenerative Modeling at the Pitt School of Medicine.

“These lesions are thought to develop because immobility disrupts adequate oxygenation of tissues where the patient is lying down, followed by sudden resumption of blood flow when the patient is turned in bed to change positions,” Dr. Vodovotz said. “This is accompanied by an inflammatory response that sometimes leads to further tissue damage and breakdown of the skin.”

“Pressure ulcers are an unfortunately common complication after spinal cord injury and cause discomfort and functional limitations,” said co-author Gwendolyn A. Sowa, M.D., Ph.D., associate professor of physical medicine and rehabilitation, Pitt School of Medicine. “Improving the individual diagnosis and treatment of pressure ulcers has the potential to reduce the cost of care and improve quality of life for persons living with spinal cord injury.”

To address the complexity of the biologic pathways that create and respond to pressure sore development, the researchers designed a computational, or “in silico,” model of the process based on serial photographs of developing ulcers from spinal cord-injured patients enrolled in studies at Pitt’s Rehabilitation Engineering Research Center on Spinal Cord Injury. Photos were taken when the ulcer was initially diagnosed, three times per week in the acute stage and once a week as it resolved.

Then they validated the model, finding that if they started with a single small round area over a virtual bony protuberance and altered factors such as inflammatory mediators and tissue oxygenation, they could recreate a variety of irregularly shaped ulcers that mimic what is seen in reality.

They also conducted two virtual trials of potential interventions, finding that anti-inflammatory interventions could not prevent ulcers unless applied very early in their development.

In the future, perhaps a nurse or caregiver could simply send in a photo of a patient’s reddened skin to a doctor using the model to find out whether it was likely to develop into a pressure sore for quick and aggressive treatment to keep it from getting far worse, Dr. Vodovotz speculated.

“Computational models like this one might one day be able to predict the clinical course of a disease or injury, as well as make it possible to do less expensive testing of experimental drugs and interventions to see whether they are worth pursuing with human trials,” he said. “They hold great potential as a diagnostic and research tool.”

The team included co-senior author Gary An, M.D., of the University of Chicago; Cordelia Ziraldo, Ph.D., Alexey Solovyev, Ph.D., Ana Allegretti, Ph.D., Shilpa Krishnan, M.S., David Brienza, Ph.D., Qi Mi, Ph.D., all of Pitt; and M. Kristi Henzel, M.D., Ph.D., of the Louis Stokes Cleveland Veterans Affairs Medical Center.

The project was funded by the U.S. Department of Education; National Institutes of Health National Institute on Disability and Rehabilitation Research grant H133E070024; and an IBM Shared University Research Award.

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