Scientists at the world’s top universities have collaborated to develop a device that, by sifting tiny particles from blood samples, could be a boon to both scientific research and medical applications by allowing researchers to study hard-to-reach tissues — such as the human placenta — through a blood sample.
Combining acoustic and microfluidic technologies, the scientists from the Magee-Womens Research Institute (MWRI) at the University of Pittsburgh, Duke University, Massachusetts Institute of Technology (MIT), Carnegie Mellon University (CMU) and Nanyang Technological University in Singapore, developed the prototype, which is designed to be used at the patient point-of-care.
It sifts blood nanoparticles, called exosomes, which are released from every cell type in the body and which are thought to play a large role in cell-to-cell communication and disease transmission. Exosomes have been researched since their discovery three decades ago, and because they contain biomolecules that reflect their tissue of origin, they open the door to sophisticated diagnostic testing of tissues previously out of reach.
In a paper published in the Proceedings of the National Academy of Sciences USA, the researchers demonstrated a better method based on acoustofluidics — the fusion of acoustics and microfluidics. The prototype provides a gentle, automated, point-of-care system that allows a single-step, on-chip isolation of exosomes from whole biological fluids with a high rate of purity and yield.
Casual Meeting Turns into Scientific Pursuit
The idea for the research that led up to this prototype device originated in a casual meeting at a conference in Washington, D.C., in 2014 between Drs. Yoel Sadovsky, executive director of MWRI, and Subra Suresh, then president of CMU. Suresh had been working with Drs. Tony Jun Huang, then professor of bioengineering science and mechanics at Pennsylvania State University, and Ming Dao, director of the nanomechanics laboratory at MIT, to isolate tumor cells from the blood to enhance cancer diagnostics.
A conversation between the two Pittsburgh researchers about how exosomes could be used as a window into tissue health turned into an intense scientific pursuit, with the idea of scaling down the assays already engineered by Huang, Suresh and Dao. The results, representing the engineering development lead by Huang and colleagues with additional testing in Sadovsky’s lab at MWRI, could help researchers and clinicians learn more about exosomes and form the foundation for diagnostic or therapeutic devices.
Tissue injury, cancer and other diseases in relatively inaccessible organs — such as the placenta, brain, kidney and liver — could, in theory, be diagnosed and monitored through a simple blood draw, dubbed a “liquid biopsy.”
Death rates from sepsis have stalled, contrary to previous analyses that showed mortality falling, according to new research conducted in part by University of Pittsburgh Department of Critical Care Medicine scientists. The finding, announced in the Journal of the American Medical Association, coincided with World Sepsis Day.
On the heels of the dismal news, a newly funded project at Pitt seeks to find out if policy-driven changes to hospital care may be able to reverse this trend and save lives. The results could impact regulations being crafted in multiple states, including Pennsylvania.
“Sepsis is a public health crisis,” said Dr. Jeremy Kahn, professor of critical care medicine and health policy and management at Pitt. “It is extremely appropriate to address a public health crisis through regulation. However, regulations can have unintended consequences, and when it comes to sepsis – a complicated condition – it is important to get it right.”
Sepsis arises when the body’s response to an infection injures its own tissues and organs. It is the leading killer of hospital patients. According to the Centers for Disease Control and Prevention, more than 1.5 million people get sepsis each year in the United States.
Kahn was recently awarded a $1.5 million grant from the U.S. Department of Health and Human Services to conduct a four-year study analyzing Rory’s Regulation, which put a protocol in place for New York hospitals to follow when confronted with potential sepsis cases. The regulation was instituted following the tragic and widely publicized death of Rory Staunton, 12, from sepsis. Kahn and his team will dive into data collected on patient outcomes as a result of the regulation and conduct in-depth observations of how clinicians enact the protocols in order to determine what aspects of the regulation work and what, if any, may be potentially costly and time-consuming without saving lives. (more…)
Kate Middleton, Duchess of Cambridge, and her husband, Prince William, recently announced that she is pregnant with the couple’s third child.
Since the duchess has struggled in the past with hyperemesis gravidarum, which causes severe nausea and vomiting and can sometimes last the entire pregnancy, we asked maternal-fetal medicine expert Dr. Hyagriv Simhan, medical director of Obstetrical Services at Magee-Womens Hospital of UPMC, about the condition.
A. This condition is an extreme manifestation of typical pregnancy nausea, which is commonly called “morning sickness.” Normal nausea starts at the beginning of pregnancy and usually ends at about 13 to 14 weeks. Hyperemesis can last much longer, but most women will feel significantly better by 20 weeks. It is characterized by vomiting, dehydration and, in some instances, malnutrition, electrolyte abnormalities and weight loss.
How common is hyperemesis gravidarum?
A. Hyperemesis complicates about 1 to 3 percent of pregnancies. In contrast, morning sickness affects about one-third of pregnant women and two-thirds of pregnant women will have at least some vomiting. Hyperemesis may run in families and recur from pregnancy to pregnancy.
What causes it?
A. Hyperemesis is thought to occur because of the brain’s response to the pregnancy hormone, hCG. Conditions where the hCG level is very high, such as in twins and triplets, can make hyperemesis more likely. Also, some women are more sensitive to hCG than others. We don’t understand why that may be, but some women experience much more severe nausea and vomiting than others, despite having a comparable hCG level. There tends to be a general perception that the nausea is in a woman’s head. It is not. It is not a minor annoyance. It is debilitating.
How is it treated?
A. Treatment of hyperemesis focuses on therapies to reduce the feeling of nausea, treatment of associated conditions (such as reflux), correction of dehydration and electrolyte abnormalities with oral or IV hydration, and nutritional replacement therapy. To alleviate the nausea, we generally start with behavioral therapy – altering food choices and timing of meals, as well as strategies like acupressure. When necessary, we move on to anti-nausea medications or to other forms of feeding, some of which avoid the stomach.
Does it affect the baby?
A. For a fetus, the only source of nutrition is its mother. And, for the mother and the fetus, nutrition is essential. The good news is that, in most instances, we can treat hyperemesis successfully.
The Food and Drug Administration (FDA) recently approved the very first cancer treatment that uses genetically engineered cells as therapy. The treatment is approved for use in children and young adults with a blood cancer known as acute lymphoblastic leukemia (ALL), and marks the start of a new way to treat cancer. The therapy, called CAR-T, is made by using a patient’s own white blood cells, then re-engineering them to find and attack cancer tumors.
We asked Dr. Alison Sehgal, UPMC Hillman Cancer Center oncologist and assistant professor of medicine at the University of Pittsburgh School of Medicine, about this important advancement in cancer treatment.
What is immunotherapy and what are CAR-T cells?
A. Immunotherapy is a type of cancer treatment that uses a patient’s own immune system to attack cancer tumors. CAR-T cell therapy is just one of the emerging immunotherapy treatments currently being researched. T cells are part of our immune system and have the ability to fight infections and kill cancer cells. CAR-T cell immunotherapy involves removing a patient’s T cells from the blood, modifying them with an inactivated virus so that they can find molecules on the surface of cancer cells, and returning the T cells to the body to directly attack the cancer cells. Until this recent FDA approval, CAR-T cell immunotherapy has been available only in clinical trials, including those here at UPMC.
Why is this therapy and approval such an important advancement?
A. This is the first approved adoptive cellular therapy that has shown significant results in clinical trials. The therapy is approved for the treatment of children and adults up to 25 years old who have ALL, which is one of the most common cancers in children. In clinical trials, CAR-T therapy has been effective for these kids who are essentially out of options to treat their cancer because the standard approaches have not worked for them. This will surely mark the start of other cellular immunotherapies that are showing promising results in treating additional types of cancer. It’s an exciting time to be involved in cancer research for scientists, physicians and patients.
How can cancer patients learn more or become involved?
A. UPMC Hillman Cancer Center has many clinical trials in cancer, including these novel immunotherapy trials. We are one of just 41 of the nation’s National Cancer Institute designated Comprehensive Cancer Centers, an elite group of institutions dedicated to cancer research by developing more effective approaches to prevention, diagnosis and treatment of cancer. Our research takes place right here in Pittsburgh, and these trials are made available to cancer patients throughout the more than 60 UPMC Hillman Cancer Centers. Any patient interested in clinical trials can find more information here.
UPMC East Board Chair Sean Logan believes the cure for Parkinson’s disease – a neurodegenerative condition with which he has recently been diagnosed – will come out of Pittsburgh.
“After a Parkinson’s diagnosis, one can pull back and feel sorry for themselves – or they can get motivated,” Logan said.
At age 47, he picked the latter and made it his life mission is to raise funds and awareness for research into Parkinson’s disease, which about 60,000 Americans are diagnosed with annually.
About one in four Pennsylvanians will suffer from a neurodegenerative disease in their lifetime, and nearly everyone will have a family member diagnosed with one of these conditions. This year marks the second annual Pittsburgh Institute for Neurodegenerative Diseases 5K Run/Walk, which took place Monday.
PIND was established at the University of Pittsburgh and brings together in one place scientists and clinician-scientists from diverse disciplines and perspectives to collaborate on studies of neurodegenerative disorders including Parkinson’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease, stroke, and Alzheimer’s disease.
“Everyone’s going to be touched by a neurodegenerative disease, even if it’s just remotely,” said Logan’s doctor, Dr. Amber Van Laar, UPMC neurologist and assistant professor of neurologist at the Pitt School of Medicine.
The complex disease is currently not well understood by scientists, and the goal of the race was to raise funds for PIND’s cutting-edge research.
Last year, the race had 417 participants and raised nearly $100,000. The funds help researchers quickly pursue new ideas without strings attached, and accumulate data needed to qualify for larger grants such as those given by the National Institutes of Health.
To donate, visit http://pind5k.org/.