For more than two decades, Olivera Finn has tirelessly pursued one goal in her research: to develop a vaccine to prevent cancer. She has had this goal since 1989, when her research team discovered the first tumor antigen recognized by a type of immune cell that can kill cancer cells. That antigen—an abnormal version of a protein called MUC1—is produced by the cells of more than 80% of cancer types, including cancers of the breast, pancreas, colon, lung, and prostate.
Although she started her research career as an organ transplant immunologist, the discovery of MUC1 was a pivotal point in Olivera’s career trajectory. “Once we discovered tumor antigens,” she said, “I never looked back.” Olivera received her first NCI grant in 1991 and has been funded ever since to study the biology of tumor antigens and develop them as targets for cancer prevention.
Cancer can take many years—even decades—to develop. Some cancers arise from precursor growths that can be detected by current screening methods. For example, colorectal polyps called advanced adenomas, which can be detected by colonoscopy, can progress to colorectal cancer. These adenomas can be removed surgically, but in many patients, new ones continue to develop and some will become malignant. Olivera’s lab found that the cells of advanced adenomas and the precursors of pancreatic, lung, and many other types of cancer all produce abnormal MUC1 protein.
The presence of abnormal MUC1 on premalignant growths may make it a good target for a vaccine that would prevent their progression to cancer or the development of new precursors. To test this idea, Olivera’s group conducted the first ever clinical trial of a cancer prevention vaccine based on a tumor antigen in healthy people without cancer who were at increased risk of developing the disease.
In the NCI-funded trial, reported in 2013, individuals with a history of advanced adenomas were given an MUC1 vaccine. The vaccine was shown to be safe and to elicit a strong immune response and a long-lasting immune memory. NCI is currently sponsoring a phase II trial testing whether the vaccine will prevent the regrowth of colorectal polyps.
Looking forward, Olivera envisions, “If you are in your 60s and your doctor discovers you are at high risk for cancer, the idea would be to vaccinate to boost the immune system’s ability to keep any abnormal cells in check instead of waiting to see if cancer develops.”
Olivera says that funding from NCI is critical for her research and for cancer prevention research in general. Cancer prevention research is complex, and translating laboratory discoveries into new ways to prevent cancer requires sustained investments over many years—investments that the private sector is often reluctant to make. But “building the evidence that vaccines are an effective way of controlling cancer will go a long way toward getting companies interested,” she said.
The field of cancer immunology has expanded dramatically and has led to immunotherapies for the treatment of advanced cancers as well as vaccines against some viruses that cause cancer. Boosting the immune system to prevent cancers that are not caused by viruses may now be within reach. “The opportunities are amazing,” she added.
University of Pittsburgh and UPMC researcher Dr. Olivera Finn was featured in Stories of Impact by the National Cancer Institute. This story was originally published by the National Cancer Institute.
Every year, more than 44,000 Americans take their own lives, and suicide is the second-leading cause of death in adolescents between the ages of 15 to 24.
These alarming numbers beg for better identification of patients at risk for suicide to ensure they get the care they need, when they need it. That’s why two UPMC doctors – Dr. David Brent and Dr. Neal Ryan – and one University of Pittsburgh professor, Dr. Fuchiang (Rich) Tsui, are leading a project to better track patients at risk for suicide through the electronic health record (EHR).
“In many cases, the last clinical contact a suicide victim sees is a primary care physician or someone in the emergency room, not a mental health professional,” Brent said. “This project is working to change that.”
Using Brent’s background in child psychology, epidemiology and suicide prevention, Ryan’s experience in child psychology, and Tsui’s expertise in data science, the group set out to develop EHR algorithms to track patient patterns and flag those at high risk of suicide.
The algorithms combine diagnostic, machine learning and natural language processing information to analyze all relevant information about a patient, automating the process of analyzing records and searching for signs of suicide that often go undetected by humans. Patients at risk for suicide and suicidal behavior will be identified and their chart flagged so psychiatric professionals can provide the help patient needs.
“Our initial efforts will look just within the electronic medical records of the clinical sites involved in the study at UPMC,” Ryan said. “Once the algorithm is solidified at UPMC, we are hoping to expand it to other health systems and adapt the algorithms to fit their electronic health records.”
To help develop and expand the system, the research team was awarded a Bench to Bedside grant from The Beckwith Institute in June 2017. The program supports research that translates directly to patient care.
“As a data scientist, I am excited by this project that has developed a predictive system that automatically identifies relevant risk factors from potentially tens of thousands of clinical findings and computes a patient’s suicide risk accordingly,” Tsui said.
As the project expands across different health systems, the algorithms will need to be able to read all the data languages the various hospitals employ. After the system is up and running, it will need training every few years to update the algorithms.
“This project is a low-cost, low-risk method to yield better patient care,” Brent said. “This is an extra resource to guide physician decision making and referrals, which ultimately uses this predictive data approach to save lives.”
When it comes to caring for stroke patients, every minute counts. But, for ischemic stroke patients who have their blood clots surgically removed, timing can be even more important.
After having their clot surgically removed, patients with symptoms of a severe ischemic stroke are often immediately transported to a tertiary care hospital. Ischemic stroke patients can lose millions of brain cells each minute they are being transported, which could be upwards of 30 minutes. The more brain cells a stroke patient loses, the longer it takes them to heal.
To combat this problem, a team of researchers in the Applied Physiology Laboratory at the University of Pittsburgh’s Department of Emergency Medicine have designed an innovative new process to slow down brain cell loss in stroke patients. The study, called Dex III, involves lowering a patient’s core temperature.
Much like therapeutic hypothermia used in cardiac arrest patients, the patient’s core body temperature is lowered down to 93 degrees Fahrenheit, which is almost 6 degrees Fahrenheit cooler than the normal 98.6 degrees Fahrenheit. This works because when the brain cells are cooled, their need for oxygen and sugar drops. This process is similar to what happens to a bear during hibernation.
However, while this concept may seem simple, the process becomes more complicated because humans do not naturally hibernate.
“When you cool a person, their natural response is to shiver, so you need to give medications that will stop the shivering,” said Dr. Jon Rittenberger, associate professor of emergency medicine, occupational therapy, and clinical and translational science, and emergency physician at UPMC Presbyterian. “Unfortunately, most of those drugs also sedate patients. This makes it hard for the neurologist to properly evaluate them and see if removing the clot has improved their symptoms.”
A novel drug called dexmedetomidine, a sedative typically used during surgery, is used to prevent shivering. It makes the patient drowsy, but easily awakened so they can respond to neurological evaluations. Moreover, dexmedetomidine is an excellent medication for suppressing shivering.
In their prior work, the group found combining both cooling and dexmedetomidine drops the patient’s heart rate. To make the protocol safer, the group is now using a second drug called glycopyrrolate to prevent a lowered heart rate.
Rittenberger and his team have been working on Dex III since May 2017 thanks to a $25,000 grant from the Clinical and Translational Science Institute at Pitt. They hope to finish it by the end of the calendar year.
“My hope would be that after this research, we have a safe method to cool these patients,” Rittenberger said. “Then, we can see if it improves their outcomes.”
We spoke to Dr. Harold Wiesenfeld, director of gynecologic specialties and reproductive infectious disease at Magee-Womens Hospital of UPMC, about the recent U.S. Centers for Disease Control and Prevention “Sexually Transmitted Disease Surveillance Report,” which found sexually transmitted diseases are at a record high in the United States.
A. This is a very concerning report. This represents an ongoing, and perhaps increasing, threat to public health. This should serve as a warning and an alarm to our country that we have much more to do in getting this epidemic under control.
Why do you think syphilis rates increased by nearly 18 percent from 2015 to 2016?
A. There has been a surge in syphilis affecting new populations, and its rise is worrisome. While it disproportionately affects men who have sex with men, we are now seeing a nationwide increase in syphilis in women, and as a result, an increase in congenital syphilis. According to the report, congenital syphilis resulted in 40 deaths in 2016 and severe, lifelong health complications among newborns. While congenital syphilis carries devastating consequences, it is nearly completely preventable.
What could help lower these rates in the future?
A. As a society, we need to destigmatize STDs because they are quite common, and physicians need to be vigilant on discussing STD risks and screenings with their patients. People need to feel comfortable and educated on receiving routine care and requesting STD screening, which includes screening for HIV.
Every day in the U.S., more than four children die because of abuse. Of those, more than 70 percent are 2 years old or younger.
In response to this issue, two UPMC physicians are developing and disseminating a child abuse clinical decision support (CA-CDS) system within the electronic health record (EHR). The goal is to rapidly identify potential abuse that might otherwise be overlooked in a busy emergency department. The development team includes Dr. Srinivasan Suresh,pediatric emergency physician and chief medical information officer at Children’s Hospital of Pittsburgh of UPMC, and Dr. Rachel Berger, chief of the Children’s Child Advocacy Center and the director of child abuse research at the Safar Center for Resuscitation Research at the University of Pittsburgh.
“Emergency physicians care for patients who present with a wide spectrum of symptoms,” Suresh said. “The signs of abuse are not always clear. Triggers and visual alerts in an EHR can address this gap.”
The CA-CDS system, which includes a trigger system, provider alerts and a physical abuse order set, has been successfully developed and deployed at Children’s. When a child presents to the emergency department with a physical injury that could have come as a result of abuse, an alert pops up in the EHR to immediately notify the physician and the rest of the care team, bringing the possibility of abuse to their attention.
“The aim of this trigger is to increase the sensitivity of our suspicion for physical child abuse,” Suresh said.
Since the system is standardized, it can also eliminate biases.
“Our gut is not always right as it relates to child abuse,” Berger said. “By standardizing and reminding people to think about abuse, racial and other disparities can be decreased.”
Originally funded by the Patient-Centered Outcomes Research Institute, the CA-CDS project recently received a $99,900 grant from The Beckwith Institute, specifically through its Bench at the Bedside program. Bench at the Bedside allows doctors to take what they know and transform it into ideas that will further improve clinical practice.
The grant has helped the researchers expand the value of the toolkit.
“We have successfully implemented the decision support tool here in Pittsburgh,” Suresh said. “This grant now enables us to integrate the toolkit into the EHRs of a few large children’s hospitals across the country.”
“This is a powerful tool in helping doctors and nurses recognize the signs of abuse, intervene in a timely fashion and avoid having to treat the same children repeatedly for abuse,” Berger said. “The children are vulnerable and don’t have a voice. It’s our job to protect them.”
To learn more about The Beckwith Institute or the grants the organization offers, visit www.beckwithinstitute.org.