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Pitt Shares in $17 Million Federal Grant to Improve Traumatic Brain Injury Clinical Trials

PITTSBURGH, Sept. 30, 2014 – University of Pittsburgh researchers are key players in a national “dream team” that seeks to identify the best biological and imaging markers of traumatic brain injury (TBI) to improve the ability of clinical trials to find effective treatments for the condition, which annually affects 2.5 million people in the U.S., including athletes and soldiers.

The $17 million initiative, called the TBI Endpoints Development (TED) Award, is funded by the U.S. Department of Defense (DOD) and includes many universities, the U.S. Food and Drug Administration (FDA), companies and philanthropies. It is overseen by the University of California, San Francisco.

“This project is going to redefine how we measure the outcomes for traumatic brain injury studies,” said TED investigator Stephen Wisniewski, Ph.D., senior associate dean and co-director of the Epidemiology Data Center at the University of Pittsburgh Graduate School of Public Health. “We need a more robust, detailed way to determine what challenges a person faces when he suffers a traumatic brain injury, and that is what we’re setting out to accomplish with this ambitious study.”

Under Dr. Wisniewski’s leadership, Pitt Public Health will run the data analysis for the project, meaning the school will compile data from previous studies and analyze it to see what existing methods for measuring traumatic brain injuries prove most promising. That information will be used as a launch point for clinical evaluation in real-life situations.

David Okonkwo, M.D., Ph.D., associate professor of neurological surgery and clinical director of the Brain Trauma Research Center at Pitt’s School of Medicine, is co-leading the second branch of the project to test those findings through the previously announced $18.8 million National Institutes of Health (NIH) project called Transforming Research and Clinical Knowledge in TBI, or TRACK-TBI.

“In the clinical component of the TED project, we will take the insights Dr. Wisniewski and his team gather from their systematic review of previous research and apply that to real-world TBI cases,” said Dr. Okonkwo. “If we can more accurately identify and quantify these injuries, we will be better able to select appropriate patients for clinical trials and to evaluate the success or failure of our therapies.”

TED will examine data from thousands of patients to identify effective measures of brain injury and recovery, using biomarkers from blood, new imaging equipment and software, and other tools. The research collaborators will be collecting a broad range of long-term data from existing studies and databases, and integrating these into a dataset that can be interrogated for TBI associations and causes in a way that has never before been possible.

The project is specifically designed to overcome the difficulty in demonstrating the effectiveness of TBI drugs and medical devices by actively involving the FDA in clinical-trial design from the outset. It also fosters collaboration between the DOD, the NIH, foundation-funded research networks, industry co-sponsors such as General Electric, and patient advocacy groups to try to develop procedures, outcomes measures and standards for interpreting clinical data.

Each year, more than 2.5 million people in the U.S. seek medical care for traumatic brain injuries that arise when blows to the body or nearby explosions cause the brain to collide with the inside of the skull. According to the U.S. Centers for Disease Control and Prevention, an estimated 2 percent of the U.S. population now lives with TBI-caused disabilities, at an annual cost of about $77 billion. No TBI treatment has proved to be effective.

“TBI is really a multifaceted condition, not a single event,” said UCSF neurosurgeon Geoffrey T. Manley, M.D., Ph.D., principal investigator for the new award and chief of neurosurgery at San Francisco General Hospital and Trauma Center, a UCSF partner hospital. “TBI lags 40 to 50 years behind heart disease and cancer in terms of progress and understanding of the actual disease process and its potential aftermath. More than 30 clinical trials of potential TBI treatments have failed, and not a single drug has been approved.”

UPMC Residency Programs Rank Nationally

Physician network Doximity, along with U.S. News & World Report, announced the first comprehensive national evaluation of residency programs. In these results, 11 UPMC programs ranked in the top 10.

To determine the rankings, 3,691 residency training programs were evaluated by combining over 50,000 peer nominations from board-certified US physicians. U.S. News & World Report, nationally known for their education and health care rankings, consulted on the methodology.

Here is a listing of UPMC programs in the top 10:

  • Anesthesiology: No. 10
  • Obstetrics and gynecology: No. 3
  • Plastic surgery (integrated): No. 3
  • Otolaryngology: No. 4
  • Emergency medicine: No. 7
  • Physical medicine and rehabilitation: No. 7
  • Psychiatry: No. 7
  • Orthopaedic surgery: No. 8
  • Pediatrics: No. 8
  • Neurological surgery: No. 9
  • Surgery: No. 10

The results are used in a free tool from Doximity called Residency Navigator. The tool is designed for third- and fourth-year medical students.

Save the Date: Stroke Update 2014

PITTSBURGH, July 7, 2014 – Stroke Update 2014 will be held at the Wyndham Grand Pittsburgh Downtown in Pittsburgh, Pa., on Friday, September 5, 2014.

This conference will cover the identification, management, and treatment of stroke in young adults, intracerebral hemorrhage, subarachnoid hemorrhage, and intracerebral swelling. Clinical applications for telemedicine and the benefits of telestroke also will be discussed.

Who Should Attend
This conference is designed for neurologists, neurosurgeons, interventionalists, emergency medicine physicians, family practitioners, internists, nurses, nurse practitioners, pre-hospital personnel, and hospital administrators.

Location
Wyndham Grand Pittsburgh Downtown
600 Commonwealth Place
Pittsburgh, PA, 15222

Course Directors
Tudor G. Jovin, MD
Associate Professor of Neurology and Neurosurgery
Director, UPMC Stroke Institute
Department of Neurology

Lori M. Massaro, MDN, CRNP
Clinical Supervisor
UPMC Stroke Institute
Department of Neurology

Ashutosh P. Jadhav, MD, PhD
Assistant Professor of Neurology
UPMC Stroke Institute
Department of Neurology

To view the full course brochure, or to register online, please visit the Upcoming Events page at the Center for Continuing Education in the Health Sciences and click the ‘Stroke Update 2014′ link.

Continuing Education Credit
The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The University of Pittsburgh School of Medicine designates this live activity for a maximum of 6.5 AMA PRA Category 1 Credits™. Each physician should claim only credit commensurate with the extent of their participation in the activity. Other health care professionals are awarded 0.6 continuing education units (CEUs) which are equal to 6.5 contact hours.

Nursing: The University of Pittsburgh Medical Center (UPMC) is an approved provider of continuing nursing education by PA State Nurses Association, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation. This program is awarded 6.5 contact hours. Participants must attend the entire day and complete an evaluation form to be awarded a certificate and 6.5 contact hours.

Pitt Study Shows for First Time How Huntington’s Disease Protein Could Cause Death of Neurons

PITTSBURGH, May 18, 2014 – Scientists at the University of Pittsburgh School of Medicine have identified for the first time a key molecular mechanism by which the abnormal protein found in Huntington’s disease can cause brain cell death. The results of these studies, published today in Nature Neuroscience, could one day lead to ways to prevent the progressive neurological deterioration that characterizes the condition.

Huntington’s disease patients inherit from a parent a gene that contains too many repeats of a certain DNA sequence, which results in the production of an abnormal form of a protein called huntingtin (HTT), explained senior investigator Robert Friedlander, M.D., UPMC Professor of Neurosurgery and Neurobiology and chair, Department of Neurological Surgery, Pitt School of Medicine. But until now, studies have not suggested how HTT could cause disease.

“This study connects the dots for the first time and shows how huntingtin can cause problems for the mitochondria that lead to the death of neurons,” Dr. Friedlander said. “If we can disrupt the pathway, we may be able to identify new treatments for this devastating disease.”

Examination of brain tissue samples from both mice and human patients affected by Huntington’s disease showed that mutant HTT collects in the mitochondria, which are the energy suppliers of the cell. Using several biochemical approaches in follow-up mouse studies, the research team identified the mitochondrial proteins that bind to mutant HTT, noting its particular affinity for TIM23, a protein complex that transports other proteins from the rest of the cell into the mitochondria.

Further investigation revealed that mutant HTT inhibited TIM23’s ability to transport proteins across the mitochondrial membrane, slowing metabolic activity and ultimately triggering cell-suicide pathways. The team also found that mutant HTT-induced mitochondrial dysfunction occurred more often near the synapses, or junctions, of neurons, likely impairing the neuron’s ability to communicate or signal its neighbors.

To verify the findings, the researchers showed that producing more TIM23 could overcome the protein transport deficiency and prevent cell death.

“We learned also that these events occur very early in the disease process, not as the result of some other mutant HTT-induced changes,” Dr. Friedlander said. “This means that if we can find ways to intervene at this point, we may be able to prevent neurological damage.”

The team’s next steps include identifying exact binding sites and agents that can influence the interactions of HTT and TIM23.

Co-authors of the paper include other scientists from the University of Pittsburgh School of Medicine and Washington University School of Medicine.

The project was funded by National Institutes of Health grants NS039324, NS077748 and AG033724; the Brain & Behavior Research Foundation; the DSF Charitable Foundation; and the Huntington’s Disease Society of America.

Second Annual Update on the Multidisciplinary Management of Pituitary Tumors

PITTSBURGH, Feb. 27, 2014 – The Second Annual Update on the Multidisciplinary Management of Pituitary Tumors will be held at UPMC Shadyside in Pittsburgh, Pa., on Friday, April 4, 2014.

This conference will cover the most recent advances in the diagnosis and treatment of pituitary tumors, including functioning and nonfunctioning tumors, hypopituitarism, and pituitary adenomas. The role of and advances in surgical and medical therapies for pituitary tumors, and perioperative management of pituitary tumors will also be discussed.

Who Should Attend
This conference is designed for physicians, physicians’ assistants, nurses, and other health care professionals practicing in the areas of Endocrinology and Metabolism, Family Medicine, General Internal Medicine, and Neurosurgery.

Location
UPMC Shadyside, West Wing Auditorium – First Floor, 5230 Centre Avenue, Pittsburgh, PA, 15232

Course Directors
Paul A. Gardner, MD
Associate Professor of Medicine
University of Pittsburgh School of Medicine
Co-Director, Center for Cranial Base Surgery, UPMC

Sue M. Challinor, MD
Associate Professor of Medicine
Division of Endocrinology and Metabolism
University of Pittsburgh School of Medicine

For more information, or to register online, please visit the Center for Continuing Education in the Health Sciences page.

Continuing Medical Education
The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The University of Pittsburgh School of Medicine designates this live activity for a maximum of 6.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other health care professionals are awarded 0.6 continuing education units (CEUs) which are equal to 6.2 contact hours.

UPMC Physicians Offer Lectures Throughout the Region

UPMC has assembled a group of physician leaders from UPMC Passavant who will be available to make informal, informational presentations to small groups as well as larger audiences in western Pennsylvania, northern West Virginia, and eastern Ohio. These physicians represent a wide range of specialties and will discuss topics related to their specific clinical interests.

Physician presenters can discuss topics such as brain surgery, cardiac surgery, cardiology, colon and rectal surgery, orthopaedics, plastic and reconstructive surgery, spine surgery, surgical oncology, and vascular surgery.

The featured speakers include:

For more information about this new lecture series and specific topics, or to schedule a presentation, in western Pennsylvania, northern West Virginia, or eastern Ohio email OPRoutreach@upmc.edu.

Chief of Pediatric Neurosurgery Named Chairman of Scholarly Journal

Ian F. Pollack, MD, chief of the Division of Pediatric Neurosurgery at Children’s Hospital of Pittsburgh of UPMC, was recently named chairman of the editorial board of the Journal of Neurosurgery: Pediatrics. Dr. Pollack has served on the editorial board since 2003.

The Journal of Neurosurgery publications are scholarly journals of the American Association of Neurosurgeons. The Journal of Neurosurgery: Pediatrics was originally a quarterly supplemental, but has been published monthly since 2005.

Dr. Pollack is the Walter Dandy Professor of Neurological Surgery at the University of Pittsburgh School of Medicine and co-director of the Brain Tumor Center of the University of Pittsburgh Cancer Institute. His primary research interests focus on identifying and evaluating innovative strategies for treating malignant brain tumors, improving the treatment of children with brain tumors, and optimizing the management of childhood craniofacial disorders.

Children’s Hospital of Pittsburgh of UPMC & Pitt Public Health Researchers Receive NIH Grant to Study Pediatric Traumatic Brain Injuries

PITTSBURGH, July 25, 2013 Children’s Hospital of Pittsburgh of UPMC and University of Pittsburgh Graduate School of Public Health researchers have been selected by the National Institutes of Health (NIH) to lead a $16.5 million international study to evaluate treatments for pediatric traumatic brain injuries (TBI).
This effort is being led by Michael J. Bell, M.D., director, Pediatric Neurocritical Care and Neurotrauma at Children’s Hospital and Stephen Wisniewski, Ph.D., senior associate dean and co-director of the Epidemiology Data Center at Pitt Public Health. Dr. Bell will coordinate patient enrollment and clinical activities within the project and Dr. Wisniewski will coordinate data collection and the statistical analysis for this project.
The five-year study aims to provide compelling evidence to change clinical practices and provide recommendations for guidelines that could immediately improve outcomes for injured children.
The researchers plan to enroll 1,000 children up to 18 years old from over 36 locations in the United States and abroad to compare the effectiveness of immediate treatments of the injury, including strategies to lower intracranial pressure, strategies to treat secondary injuries and the delivery of nutrients in a study that is called the Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial.
“Incremental improvement in outcomes of traumatic brain injury could make enormous differences for the health of children, but such advances have remained elusive,” said Dr. Bell, also associate professor, Critical Care Medicine and Neurological Surgery at the University of Pittsburgh School of Medicine. “No mitigating treatments have been translated into clinical practice, so we hope this study helps us gain a better understanding of contemporary therapies.”
“Traumatic brain injury is the leading cause of death in children in the U.S. with the CDC estimating more than 7,000 children dying each year from TBI,” said Dr. Wisniewski, also professor of Epidemiology at Pitt Public Health. “Given the incidence of the condition and the outcomes from previously reported clinical studies, we estimate that up to 1.3 million life-years are at risk each year from severe TBI. Any benefits that can be gained by improving clinical practice can have enormous consequences for children right now, and for clinical trials in the future.”
The study, which is expected to more than double existing evidence-based treatment recommendations for traumatic brain injuries in children, will provide volumes of data for improved TBI research protocols that would limit variability in treatments. Such variability has led to the failure of previous randomized controlled trials. The study also will evaluate the effectiveness of six therapies encompassing three specific aims – intracranial hypertension therapies, secondary insult prevention, and metabolism.
Children with severe traumatic brain injuries where an intracranial pressure monitor is placed will be enrolled in the study. The children will receive the standard of care offered by their hospital in the United States and Europe and extensive data on their cases will be collected over the week following the injury. Outcomes will be tested at 6 months and 1 year after injury for all children.
Dr. Wisniewski plans to use statistical methods to evaluate the impact of treatments on outcomes up to one year after the injury. This will allow the researchers to determine what approach works best.
“Completion of this study will provide compelling evidence to change clinical practices, provide evidence for new recommendations for future guidelines and lead to improved research protocols that would limit inconsistencies in traumatic brain injury treatments – helping children immediately through better clinical practices and ultimately through more effective investigation,” Dr. Bell said.
“Beyond the large impact that these recommendations will have on the field of pediatric traumatic brain injury, we expect our study to lead to the development of feasible randomized controlled trials,” Dr. Wisniewski said. “Such trials are the best way to provide assurances that a recommended treatment truly has the greatest odds of healing an injured child.”
“This novel study, which includes many dedicated international physicians and scientists, has the potential to accelerate our knowledge of how to treat children who sustain severe traumatic brain injuries,” said Ramona Hicks, Ph.D., a program director at the NIH National Institute of Neurological Disorders and Stroke (NINDS), which is providing the grant support for the study. “NINDS looks forward to rapid results that will inform clinical practice within the next few years.”
Other key investigators on the project include an international group of TBI experts: Patrick M. Kochanek, M.D. and Sue Beers, Ph.D., University of Pittsburgh; P. David Adelson, M.D., Barrow’s Neurological Institute Phoenix Children’s Hospital; Jamie Hutchison, M.D., The Hospital for Sick Children in Toronto; Robert Tasker, M.D., Boston Children’s Hospital; and Monica Vavilala, M.D., University of Washington. Statisticians and epidemiologists include Tony Fabio, Ph.D., M.P.H. and Sheryl Kelsey, Ph.D., Pitt Public Health; and Joel Greenhouse, Ph.D., M.P.H., Carnegie Mellon University.  Collaborators from the NIH include Deborah Hirtz, M.D., and Ramona Hicks, Ph.D.

UPMC Again Earns Top-10 Spot on U.S. News & World Report Honor Roll of America’s Best Hospitals

PITTSBURGH, July 16, 2013UPMC clinches the 10th place in U.S. News & World Report’s annual Honor Roll of America’s Best Hospitals for the second year in a row – again making it the highest-ranked medical center in Pennsylvania.
 
“This prestigious recognition speaks to the skill and commitment of UPMC physicians, nurses and staff as they continue to provide exceptional care to our community. UPMC is dedicated to making a difference in the lives of our patients, and we are honored when our excellence in health care is recognized,” said Elizabeth Concordia, executive vice president of UPMC and president of the Hospital and Community Services Division. “We are proud that patients continue to choose us to deliver world-class care right here in western Pennsylvania.”
 
Nationally, UPMC is ranked for excellence in 15 of the 16 specialty areas, and is among the top 10 hospitals in eight specialties: Ear, Nose & Throat; Gastroenterology; Geriatrics; Gynecology; Neurology and Neurosurgery; Psychiatry; Pulmonology and Rheumatology.
 
Last month, U.S. News named its 2013 Honor Roll of America’s Best Children’s Hospitals, on which Children’s Hospital of Pittsburgh of UPMC ranked 10th. This year marks UPMC’s 14th appearance on the Honor Roll.
 
“UPMC’s national ranking highlights our unique combination of superb medical care, a leading health insurance plan and close ties to one of the nation’s best medical schools at the University of Pittsburgh,” added Steven Shapiro, M.D., executive vice president and chief medical and scientific officer, UPMC.  “We are proud to be a leader on the U.S. News Honor Roll — but, most importantly, to be leading the way in developing new and better ways of taking care of patients.”

Brain Abnormalities Found in Concussion Patients Similar to those in Alzheimer’s Patients, Pitt Study Finds

PITTSBURGH, June 18, 2013 – The distribution of white matter brain abnormalities in some patients after mild traumatic brain injury (mTBI) closely resembles that found in early Alzheimer’s, according to a new study published in this month’s Radiology by University of Pittsburgh School of Medicine investigators.
White matter in the brain is made up of long, finger-like fibers projecting from nerve cells and is covered by a whitish fatty material. While gray matter, the part of our brain without the fatty covering, holds our knowledge, white matter is what connects different regions of gray matter, allowing different parts of the brain to communicate with one another.
The study suggests that the initial traumatic event that causes mTBI, or concussion, acts as a trigger for a sequence of degenerative changes in the brain, which result in patient symptoms and are very similar to the degenerative changes seen in early Alzheimer’s. Saeed Fakhran, M.D., assistant professor of radiology at Pitt, and his research team wanted to see if there was a relationship between white matter injury patterns and severity of post-concussion symptoms in mTBI patients with normal findings on conventional magnetic resonance imaging (MRI) exams. The researchers studied data from imaging exams performed on 64 mTBI patients and 15 control patients utilizing an advanced MRI technique called diffusion tensor imaging (DTI), which identifies microscopic changes in the brain’s white matter.
“In the past, we believed that patients with mTBI have symptoms because of abnormalities secondary to the initial injury,” said Dr. Fakhran. “Our preliminary findings suggest that the initial event causing the concussion is like lighting a fuse, acting as a trigger for a sequence of degenerative changes resulting in patient symptoms that could potentially be prevented.”
According to Dr. Fakhran, sleep-wake disturbances (SWD) are among the most debilitating post-concussive symptoms, affecting patients’ quality of life and productivity and magnifying post-concussion memory and social dysfunction. Such disturbances are among the earliest symptoms in Alzheimer’s patients, and also are seen in many mTBI patients. In addition, many mTBI patients have difficulty filtering out white noise and concentrating on important sounds, making it difficult for them to understand the world around them. Hearing problems are an independent risk factor for developing Alzheimer’s disease, and the same type of problem in mTBI patients has predicted which patients with memory problems will eventually develop Alzheimer’s disease.
“For this study, we looked back, analyzing images of injuries. In further research, we hope to recruit patients immediately after their injury and watch brain changes as they occur over time. The first step in developing a treatment for any disease is understanding what causes it, and if we can prove a link, or even a common pathway, between mTBI and Alzheimer’s it could potentially lead to effective treatment strategies for both diseases,” said Dr. Fakhran.
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