UPMC Physician Resources

Pitt Study Links Biomarkers to Long-term Kidney Damage and Death in Critically Ill Patients

PITTSBURGH, Jan. 14, 2015High levels of two novel urinary biomarkers early in critical illness are associated with adverse long-term outcomes in patients with acute kidney injury (AKI), according to an international, multi-center study led by University of Pittsburgh School of Medicine Researchers. AKI is a condition that often affects those in intensive care and can occur hours to days after serious infections, surgery or taking certain medications.

The results, available online in the Journal of the American Society of Nephrology, show that the combination of tissue inhibitor metalloproteinase-2 (TIMP-2) and IGF-binding protein-7 (IGFBP7) can identify patients with AKI who are at increased risk for death or requiring renal replacement therapy, such as dialysis or kidney transplant, over the next nine months. The two biomarkers are indicators of cell stress and injury, key components in the development of AKI.

AKI is largely asymptomatic, lacking warning signs such as pain, shortness of breath or other clinical symptoms, particularly in the early stages when intervention is most beneficial. The incidence of AKI is high among critically ill patients, with up to 50 percent developing some degree of AKI during their illness, increasing the risk of death due to kidney failure.

“We found that not only do these biomarkers predict the development of AKI but, at high levels, they also tell us about long-term prognosis,” said senior investigator John Kellum, M.D., a critical care physician at UPMC and director of the Center for Critical Care Nephrology at the University of Pittsburgh. “This should greatly aid clinicians and researchers attempting to address this too-common complication.”

Investigators enrolled 692 critically ill patients at 35 medical centers in North America and Europe. The primary analysis assessed the outcomes of patients using an FDA-approved biomarker test, known as NephroCheck®, within the first day of arrival into the intensive care unit. The team found strong associations between the biomarker combination and the risk of renal replacement therapy or death.

Co-authors of the study include Jay L. Koyner, M.D, of the University of Chicago; Andrew D. Shaw, M.B., B.S. of Vanderbilt University; Lakhmir S. Chawla, M.D., and Eric A.J. Hoste of Washington, D.C.,Veterans Affairs Medical Center; Azra Bihorac, M.D., of the University of Florida; Kianoush Kashani, M.D., of Mayo Clinic; Michael Haase, M.D., of Otto von Guericke University; and Jing Shi, Ph.D., M.D., M.S., of Walker Biosciences.

The study was sponsored by Astute Medical Inc. Dr. Kellum has received grant support and consulting fees from Astute Medical.

Charles F. Reynolds III, MD, Named Future Editor-in-Chief of the AJGP

PITTSBURGH, Jan. 12, 2015 – The American Association for Geriatric Psychiatry (AAGP) has named the next editor-in-chief of its flagship journal, the American Journal of Geriatric Psychiatry (AJGP). The AAGP Board of Directors selected Charles F. Reynolds III, MD, UPMC Endowed Professor in Geriatric Psychiatry, and professor of Behavioral and Community Health Sciences at the University of Pittsburgh Graduate School of Public Health.

Dr. Reynolds, who also serves as director of the Aging Institute of UPMC and the University of Pittsburgh, and director of the John A. Hartford Center of Excellence in Geriatric Psychiatry, has been an associate editor of the AJGP since 2001, and he has published more than 650 peer-reviewed papers. He served as a past president of the AAGP, and is also a candidate for presidency of the American Psychiatric Association (APA).

Dr. Reynolds will succeed Dilip V. Jeste, MD, associate dean for Healthy Aging and Senior Care at the University of California, San Diego, who will complete his 15-year tenure as AJGP editor-in-chief on Dec. 31, 2015. Dr. Reynolds’ tenure will begin Jan. 1, 2016, following a transitional period set to start in January 2015.

For more information on the American Journal of Geriatric Psychiatry, please visit AJGPOnline.org.

Landmark Trial Shows Early Blood Glucose Control Extends Lifespan in People with Type 1 Diabetes

PITTSBURGH, Jan. 6, 2015 – People with type 1 diabetes who intensively control their blood glucose soon after diagnosis are likely to live longer than those who do not, a recent report led by a University of Pittsburgh Graduate School of Public Health investigator revealed.

Data from a long-running trial and follow-up observational study funded by the National Institutes of Health (NIH), with participants from 27 academic medical centers in the U.S. and Canada, showed a 33 percent reduction in deaths over the past several decades among participants who had early, good control of their blood glucose. The findings are detailed in the current issue of the Journal of the American Medical Association (JAMA).

“We can now confidently tell doctors and patients that good, early control of blood glucose greatly reduces any risk for early mortality in people with type 1 diabetes, usually diagnosed in children and young adults,” said lead author Trevor Orchard, M.D., professor of epidemiology at Pitt Public Health. “These results also remove any lingering concern that intensive therapy may lead to increased mortality.”

The Diabetes Control and Complications Trial (DCCT) and the subsequent Epidemiology of Diabetes Control and Complications (EDIC) observational study have significantly changed treatment protocols for type 1 diabetes and improved the outlook for people with the condition over the past several decades, explained Griffin P. Rodgers, M.D., director of NIH’s National Institute of Diabetes and Digestive Kidney Diseases (NIDDK).

“Thanks to the findings over the years from the landmark DCCT/EDIC study, millions of people with diabetes may prevent or delay debilitating and often fatal complications from the disease,” said Dr. Rodgers. “NIH’s mission is to help improve lives through biomedical research. These kinds of results provide hard evidence that what we do helps people live longer, healthier lives.”

Type 1 diabetes happens when the body does not produce insulin, a hormone that is needed to convert sugar into energy. By regularly monitoring their blood glucose levels and adjusting doses of insulin accordingly, patients can work to keep their blood glucose in a normal range.

Beginning in 1983, the DCCT enrolled 1,441 volunteers between ages 13 and 39 with recent-onset type 1 diabetes. Half were randomly assigned to intensive efforts to keep blood glucose – also known as blood sugar – as close to normal levels as possible. The other half were assigned to the conventional treatment at the time, which simply sought to keep blood glucose levels from getting so high or low that patients would show symptoms, such as blurred vision or shortness of breath.

The trial ended in 1993 when the intensive group was found to have less eye, nerve and kidney disease. All participants were then taught the intensive blood glucose control techniques and early, good control of blood glucose was recommended for all people with type 1 diabetes. The EDIC study was then launched to continue tracking the health of all the participants.

Since 1983, 107 trial participants have died, with 64 in the group that originally received standard treatment, compared with 43 in the intensive treatment group.

The most common causes of death were cardiovascular disease at 22 percent, cancer at 20 percent and acute diabetes complications at 18 percent, all of which were more common in the group that originally received conventional treatment. Accidents or suicide were the fourth most common cause of death at 17 percent, with nominally more deaths in the people assigned to the early intensive treatment.

Higher average glucose levels and increased protein in the urine – a marker of diabetic kidney disease – were the major risk factors for death.

“These results build on earlier studies that suggested that increased protein in the urine largely accounts for shorter lifespans for people with type 1 diabetes,” said Dr. Orchard. “Our findings further emphasize the importance of good, early glucose control, as this reduces the risk for increased protein in the urine in general, as well as for diabetic kidney disease itself.”

While this study found an association between intensive blood glucose control and decreased mortality in people with type 1 diabetes, Dr. Orchard and his colleagues noted that the results cannot be extended to people with type 2 diabetes. Previous, unrelated studies have shown conflicting results for type 2 diabetes.

Additional authors on the JAMA publication are senior author John M. Lachin, Sc.D., of The George Washington University; co-authors Patricia Cleary, M.S., and Jye-Yu C. Backlund, M.P.H., also both of George Washington; David M. Nathan, M.D., Harvard Medical School; Bernard Zinman, University of Toronto; and David Brillon, M.D., Cornell University Medical Center.

This research was funded by NIH, with primary funding from the NIDDK, most recently under grant numbers U01 DK094176 and U01 DK094157. Additional NIH support for DCCT/EDIC was provided by the National Eye Institute, National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program and Clinical Translational Science Center Program.

Experts Present at American Academy of Addiction Psychiatry Annual Meeting

PITTSBURGH, Jan. 6, 2015 – Western Psychiatric Institute and Clinic of UPMC (WPIC) and the University of Pittsburgh Department of Psychiatry were well-represented at the recent American Academy of Addiction Psychiatry (AAAP) 25th Annual Meeting and Symposium in Aventura, Fla. Experts from WPIC and the department presented several abstracts, including topics such as:

Kenneth C. Nash, MD, Chief of Clinical Services at Western Psychiatric Institute and Clinic of UPMC and Vice Chair for Clinical affairs in the Department of Psychiatry and the Department of Psychiatry, also hosted an alumni and friends cocktail reception on behalf of WPIC and the department.

For more information about the AAAP Annual Meeting and Symposium, please visit AAAP.org/Annual-Meeting.

Save the Date: ‘Care Across the Continuum’ BCI Conference

PITTSBURGH, Jan. 5, 2015 – The Brain Care Institute (BCI) of Children’s Hospital of Pittsburgh of UPMC will host a one-day conference on Aug. 1, 2015, in the Mary Jo Howard Dively Auditorium at the John G. Rangos Sr. Research Center at Children’s Hospital. Entitled “Care Across the Continuum,” the meeting is designed to provide local pediatricians and pediatric specialists with information regarding the multidisciplinary experts and services available to them via the BCI.

The topics will highlight the advantages of collaboration between the BCI and area pediatricians in the diagnosis and development of treatment plans for patients. The speakers are all BCI experts in their respective fields and include:

Please save the date, and check back soon for more information and registration details.

Coupling Head and Neck Cancer Screening and Lung Cancer Scans Could Improve Early Detection, Survival

PITTSBURGH, January 5, 2015 – Adding head and neck cancer screenings to recommended lung cancer screenings would likely improve early detection and survival, according to a multidisciplinary team led by scientists affiliated with the University of Pittsburgh Cancer Institute (UPCI), a partner with UPMC CancerCenter.

In an analysis published in the journal Cancer and funded by the National Institutes of Health (NIH), the team provides a rationale for a national clinical trial to assess the effectiveness of adding examination of the head and neck to lung cancer screening programs. People most at risk for lung cancer are also those most at risk for head and neck cancer.

“When caught early, the five-year survival rate for head and neck cancer is over 83 percent,” said senior author Brenda Diergaarde, Ph.D., assistant professor of epidemiology at Pitt’s Graduate School of Public Health and member of the UPCI. “However, the majority of cases are diagnosed later when survival rates generally shrink below 50 percent. There is a strong need to develop strategies that will result in identification of the cancer when it can still be successfully treated.”

Head and neck cancer is the world’s sixth-most common type of cancer. Worldwide every year, 600,000 people are diagnosed with it and about 350,000 die. Tobacco use and alcohol consumption are the major risk factors for developing the cancer.

The early symptoms are typically a lump or sore in the mouth or throat, trouble swallowing or a voice change, which are often brushed off as a cold or something that will heal. Treatment, particularly in later stages, can be disfiguring and can change the way a person talks or eats.

Dr. Diergaarde and her team analyzed the records of 3,587 people enrolled in the Pittsburgh Lung Screening Study (PLuSS), which consists of current and ex-smokers aged 50 and older, to see if they had a higher chance of developing head and neck cancer.

In the general U.S. population, fewer than 43 per 100,000 people would be expected to develop head and neck cancer annually among those 50 and older. Among the PLuSS participants, the rate was 71.4 cases annually per 100,000 people.

Recently, the U.S. Preventive Services Task Force, as well as the American Cancer Society and several other organizations, recommended annual screening for lung cancer with low-dose computed tomography in people 55 to 74 years old with a smoking history averaging at least a pack a day for a total of 30 years. The recommendation came after a national clinical trial showed that such screening reduces lung cancer mortality.

“Head and neck cancer is relatively rare, and screening the general population would be impractical,” said co-author David O. Wilson, M.D., M.P.H., associate director of UPMC’s Lung Cancer Center. “However, the patients at risk for lung cancer whom we would refer for the newly recommended annual screening are the same patients that our study shows also likely would benefit from regular head and neck cancer screenings. If such screening reduces mortality in these at-risk patients, that would be a convenient way to increase early detection and save lives.”

Dr. Diergaarde’s team is collaborating with otolaryngologists to design a national trial that would determine if regular head and neck cancer screenings for people referred for lung cancer screenings would indeed reduce mortality.

Additional researchers on this study are Ronak Dixit, Joel L. Weissfeld, M.D., M.P.H., Paula Balogh, D.N.P., F.N.P., Pamela Sufka and Jennifer R. Grandis, M.D., F.A.C.S., all of Pitt; and Jill M. Siegfried, Ph.D., of the University of Minnesota.

This research was funded by NIH grants P50 CA097190, P50 CA090440 and P30 CA047904.

Newly-Identified Genetic Mutations Could Help Explain Early Menopause, Infertility

Pittsburgh, Dec. 31, 2014 –Two newly-identified genetic mutations could increase our understanding of the causes behind premature ovarian failure, which is one cause of infertility, and potentially guide options for treating women with the condition, according to research from Magee-Womens Research Institute (MWRI) recently published online in the Journal of Clinical Investigation and the American Journal of Human Genetics.

The mutations, which occurred in women with premature ovarian failure, a condition that causes a woman’s ovaries to stop working prior to 40 years of age, were found in genes that repair damaged DNA in the cells of the ovary that eventually become egg cells. In the U.S., premature ovarian failure affects about one percent of women during their reproductive years, some as early as their teenage years. Apart from compromising fertility, the condition also puts women at high risk for osteoporosis and heart disease.

Researchers from MWRI, in collaboration with international colleagues, performed genome sequencing on blood and skin samples from three families. Each family had at least one woman with premature ovarian failure.

“Most women with premature ovarian failure don’t know why they can’t reproduce, and it can be devastating for them,” said the senior author of the studies, Aleksandar Rajkovic, M.D., Ph.D., a researcher with MWRI and the Marcus Allen Hogge chair in reproductive sciences at the University of Pittsburgh. “Our findings indicate that genetics may play a strong role in this condition and raise the prospect of one day developing therapies to delay the early onset of menopause.”

According to Dr. Rajkovic, this research shows the power of whole genome sequencing. “Now that we understand some of the contributors to premature ovarian failure, we can work toward correcting the condition,” he said.

Radiation Dose Benchmarks During Cardiac Catheterization

Division of Pediatric Cardiology faculty member, Sara Trucco, MD, was part of a team that recently published results of a study that aimed to define age-stratified, procedure-specific benchmark radiation dose levels during interventional catheterization for congenital heart disease. The study found that radiation exposure was lowest in patent ductus arteriosus closure and highest in transcatheter pulmonary valve placement. The full article is available here.

Welcoming New Faculty to Children’s Hospital of Pittsburgh of UPMC

Children’s Hospital of Pittsburgh of UPMC is pleased to welcome three new faculty members.

Marcus Malek, MD, has joined the Division of Pediatric General and Thoracic Surgery as the director of pediatric surgical oncology. He has completed dual-fellowships in pediatric surgery (at Children’s Hospital of Pittsburgh) and pediatric surgical oncology at the Memorial Sloan-Kettering Cancer Center in New York City. Dr. Malek is one of the few dual-fellowship trained pediatric surgical oncologists in the Pennsylvania tri-state area.

Gary Mason, MD, has joined the division as a pediatric neuro-oncologist. He completed his fellowship in the Division of Neuro-Oncology at the Children’s National Medical Center in Washington DC. Dr. Mason will work closely with Ian Pollack, MD, in neurosurgery and will be leading several clinical trials in brain and CNS cancers.

Craig Byersdorfer, MD, PhD, is new to the Division of Pediatric Blood and Marrow Transplantation and Cellular Therapies. He completed his fellowship in pediatric hematology/oncology at the C.S. Mott Children’s Hospital in Ann Arbor, Michigan.

Leaders in Kidney Development Research

Pediatric Division of Nephrology faculty, Carlton Bates, MD, and Jacqueline Ho, MD, have recently been recognized for their work on kidney development research. One of the key missions of the Division of Pediatric Nephrology is to extend the knowledge of pathophysiology of renal disease through basic laboratory and clinical research.

Dr. Bates was elected to the American Society for Clinical Investigation; the medical honor society recognizes physicians who have accomplished meritorious original, creative, and independent investigations in the clinical or allied sciences of medicine. Dr. Bates studies genetic mouse models of kidney and lower urinary tract development. By suppressing or altering the activity of certain genes, he and his team are able to breed mice with structural kidney disease akin to what is seen in affected children, leading to new insights into the causes of congenital kidney and bladder diseases, which are leading causes of pediatric chronic kidney disease.

Dr. Ho was recently awarded a prestigious RO1 research grant by the NIH. She also has received numerous research awards, including the 2014 March of Dimes Basil O’Connor Starter Scholar Research Award and the 2013 International Pediatric Nephrology Association Renée Habib Young Investigator Award.

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