Author: yec14002

Scientists Pave Path for Tackling Rare Cancers

An earlier study by Dr. Andrew Arnold (center) provided the basis for the new research on parathyroid carcinoma genes.

An earlier study by Dr. Andrew Arnold (center) provided the basis for the new research on parathyroid carcinoma genes.


An international team of scientists led by the UConn School of Medicine and Icahn School of Medicine at Mount Sinai sequenced a genome for an extremely rare form of cancer, demonstrating the utility of this approach in opening the door for therapy options for rare diseases that are neglected due to scarcity of patients or lack of resources.

The team’s findings were published by JCI Insight, a journal of the American Society for Clinical Investigation.

Leading genomic scientists from UConn, Mount Sinai, and other collaborating institutions performed exome sequencing on tumors and matched normal samples from 17 patients with parathyroid carcinoma, an ultra-rare form of cancer for which there is no effective treatment.

Researchers found several mutations in known cancer-related genes and pathways. This in-depth characterization provides a clear view of genetic mechanisms involved in parathyroid carcinoma and could lead to the first therapy options for patients.

The genetic variants identified in this study have been detected in other cancers and are the subject of ongoing “basket” trials, or clinical trials focused on specific mutations rather than the tissue where the cancer formed.

“This is the largest genomic sequencing study to date for this rare and deadly cancer, and we believe it serves as important validation for using this approach to uncover clinically relevant information in any number of neglected diseases,” said Rong Chen, senior author of the paper and assistant professor in the Department of Genetics and Genomic Sciences at Mount Sinai. “Genomic analysis is opening the doors to diseases that could never have been understood through traditional biomedical research because there simply aren’t enough patients to observe.”

Mount Sinai’s work built upon research by Dr. Andrew Arnold of UConn, published in the New England Journal of Medicine in 2003. In the earlier study, Arnold reported on the first gene discovered in non-familial parathyroid cancer.

“Some of the tumor-specific genomic vulnerabilities we found turn out to be shared with much more common cancers, so drugs already being developed for other cancers may prove valuable in parathyroid cancer,” said Arnold, the study’s co-leader, who serves as the Murray-Heilig Chair in Molecular Medicine, director of the Center for Molecular Medicine, and chief of endocrinology at UConn School of Medicine. “This offers new hope for our patients and serves as a model for approaching other rare and neglected diseases.”

The study was funded by the Icahn Institute of Genomics and Multiscale Biology at Mount Sinai and the Murray-Heilig Fund in Molecular Medicine at UConn School of Medicine through the UConn Foundation.

UConn Health research image of a parathyroid gland (darker) located on the thyroid gland (pink background) during a research experiment where scientists genetically engineered mouse models, knocking out the CDC73 gene to test if cancer would then develop.

UConn Health research image of a parathyroid gland (darker) located on the thyroid gland (pink background) during a research experiment where scientists genetically engineered mouse models, knocking out the CDC73 gene to test if cancer would then develop.

Fitbit Helps Save Patient’s Life

UConn Doctor checks patient's heart


This January, Patricia Lauder of Harwinton, Connecticut, had an illness she just couldn’t shake. Visits to doctors, testing, and X-rays came back negative for pneumonia or any other health issues.

Lauder started experiencing shortness of breath and fatigue after walking short distances. She noticed that her Fitbit fitness tracker — which the 73-year-old purchased after retiring to help her get in shape — was showing her resting heart rate increasing by five points a day.

On the day her resting heart rate spiked to 140 beats per minute, she called an ambulance.

A CT scan at UConn John Dempsey Hospital revealed she was suffering from two large blood clots in her lung arteries, known as pulmonary embolisms.

According to Dr. JuYong Lee, director of vascular and endovascular medicine at UConn Health’s Pat and Jim Calhoun Cardiology Center, the mortality rate of a pulmonary embolism is more than 30 percent when it is massive.

Lee decided to intervene right away with an innovative, minimally invasive solution, applying clot-blusting drugs directly into the clots through a catheter.

The next day, Lauder’s blood clots were gone and her lung and heart health totally normalized.

“If I didn’t have a Fitbit on my wrist, I might not be here to tell my story,” Lauder says.

Follow-Up – Summer 2017

Research doesn’t stop when we report it. Here are updates on past UConn Health Journal stories:


Ovarian Cancer Vaccine

UConn Health is recruiting patients for the world’s first personalized genomics-driven ovarian cancer vaccine clinical trial. The FDA-approved trial will test the experimental vaccine Oncoimmune, which was invented by Neag Comprehensive Cancer Center Director Dr. Pramod Srivastava. The vaccine aims to boost the immune response of patients with ovarian cancer to prevent relapse. To learn more, call Quratulain Ali at 860.679.7648.

An iPad displaying 'How much will Robert pay? You'r answer is probably incorrect.' artfully

Spring 2016, “Individualized”


Dr. Cato T. Laurencin

A team led by Dr. Cato T. Laurencin, who in 2016 received a number of prestigious honors including a National Medal of Technology and Innovation, has found a way to regenerate rotator cuff tendons after they’re torn using stem cells and a “nano-mesh” material. Laurencin’s team has also joined the New Hampshire–based Advanced Regenerative Manufacturing Institute to speed the development of human limb growth.

Dr. Cato Laurencin

Spring 2016, “Honors Pour In for Leading UConn Surgeon-Scientist”


Health Disparities Institute

A recent survey conducted by UConn’s Health Disparities Institute found that patients across the state have poor health insurance literacy. The results of a poll of 516 adult Connecticut residents enrolled in a qualified health plan through Access Health CT showed that the surveyed population struggled to understand how to use their benefits as well as understand basic health insurance terminology, including “premium,” “deductible,” and “co-pay.”

illustration of fingerprints overlayed on top of a woman's ovaries

Summer 2016, “Fighting for Equity”


Connecticut’s Effective Formula for Cystic Fibrosis Screening

small child held in the arms of mother while doctor (in background) consults


While all states require newborns to be screened for cystic fibrosis, Connecticut does it differently than most.

A unique collaboration — in which UConn Health screens the newborns, Connecticut Children’s Medical Center provides timely clinical intervention, and University of Florida Health (UF Health) offers genetic counseling via telemedicine — leads to early diagnosis and treatment, which can add years to patients’ lives.

Cystic fibrosis (CF) is a progressive genetic disease. A thick mucus buildup forms in the lungs, making patients prone to infections, lung damage, and respiratory failure. The pancreas doesn’t release enzymes, inhibiting the body’s ability to digest food and absorb nutrients.

If UConn Health screenings within days of birth show a CF gene mutation, a sweat test — considered the most reliable way to diagnose CF — is recommended to determine whether the baby is a carrier or has the disease.

And it’s at this stage when the process becomes unique.

On the same visit as the sweat test, parents have a no-cost, private, video consultation with a UF Health genetic counselor, made possible by a grant from the Cystic Fibrosis Foundation, to help them understand the implications of
the mutations.

Three other clinical sites in the U.S. partner with UF Health. UConn Health screens 7 of 10 infants born in the state, accounting for more than half the screenings done under the UF Health partnerships.

Though it wasn’t mandated by state law until 2009, UConn Health has screened newborns for CF since 1993. The collaboration with UF started in 2014.

“With the addition of the genetic counseling piece, our program has significantly decreased the time to sweat test and ultimately CF diagnosis,” says Dr. Melanie Sue Collins, associate director of the Central Connecticut Cystic Fibrosis Center at Connecticut Children’s.

The approach is well received by parents, says Sidney Hopfer, UConn professor in the Department of Pathology and Laboratory Medicine.

“We have all the pieces: the tests are easily obtainable; the patients don’t have to travel far; there is coordination between the lab, CF Center, and primary care physician regarding testing and genetic counseling,” Hopfer says. “In my opinion, this is something that should be done nationally.”

Aches, Age & Influenza:

What We Know About Flu-Induced Muscle Loss and How to Prevent It

By Kim Krieger

the Flu


Why does age impact flu-related muscle loss, and how can we prevent it? UConn Health researchers are on the case.

Muscle mystery

Most of us have seen it happen to a relative, friend, or patient. A formerly healthy senior gets a bad case of the flu. When they recover, they’re weak from muscle loss, sometimes permanently disabled. We don’t know exactly why the muscle loss happens, but UConn researchers are finding ways to prevent it.

It used to be that losing muscle was just a part of getting old. It’s considered normal aging. You can’t get a drug approved by the FDA to treat aging, because aging isn’t considered a disease. But influenza, the virus that causes the flu, is. If getting the flu speeds up muscle loss in seniors, then muscle loss is potentially preventable. But how could a virus that only infects the lungs cause muscle loss?

Wasting away

When immunologist Laura Haynes first came to UConn Health, she knew that when mice get the flu, they lose weight. In fact, that’s the way researchers can tell that a mouse has the virus. Some mice lose more, some less. Haynes’ work had previously shown that older mice with the flu not only get much sicker, but also lose more weight than younger mice. But as an immunologist, her research focused on how aging immune systems decline. Differences in weight loss were an afterthought. But when she sat down with Dr. George Kuchel, director of the UConn Center on Aging, they made the connection that weight loss might indicate future disability.

Haynes teamed up with kinesiologist Jenna Bartley to further investigate. They confirmed that a significant amount of the weight lost by mice infected with the flu was muscle. And older mice infected with influenza lost more muscle than younger mice, and continued to lose it over a longer period of time.

It’s really hard to improve elderly immune response. So if we can’t prevent them from getting the flu, maybe we could at least prevent muscle loss and future disability.

“In mice there are changes in gene expression in muscle during influenza infection. Genes that degrade muscle go up, genes that build muscle go down. But in young mice, the gene expression goes back to normal more quickly,” says Haynes. The older mice, on the other hand, had higher levels of inflammation, muscle wasting, and atrophy, and it all persisted longer.

Exacerbated muscle loss wasn’t the only problem experienced by the older mice recovering from the flu. They also moved less and took fewer, narrower steps. It was as if they had become frailer and more easily tired. Decreasing gait speed, or how fast someone walks, indicates increasing frailty in humans, and taking narrower steps also increases the risk of falling. [See ‘UConn Pilots Quick Gait-Speed Measurement’]

Haynes and Bartley’s research was the first that directly linked flu-induced inflammation in a controlled setting to muscle atrophy and functional impairment. It was published in the April 2016 issue of the journal Aging. But now that they knew flu really was causing muscle wasting, how could they stop it? Even yearly vaccination doesn’t provide 100-percent protection.

“It’s really hard to improve elderly immune response. So if we can’t prevent them from getting the flu, maybe we could at least prevent muscle loss and future disability,” says Bartley.

Stemming the tide

Haynes and Bartley suspected that influenza-induced inflammation was related to, and possibly the cause of, the destruction of muscle tissue in the elderly mice. They theorized that if they could stem the tide of inflammation in the body, they might prevent the muscle tissue from degrading so much. But there was a catch: inflammation helps mobilize the immune system. If you block inflammation totally, you block the body’s defense against the flu virus. So Haynes and Bartley needed a more subtle tool.

In mice there are changes in gene expression in muscle during influenza infection. Genes that degrade muscle go up, genes that build muscle go down. But in young mice, the gene expression goes back to normal more quickly.

The first drugs Bartley and Haynes found that might be good candidates are COX-2 inhibitors. They’re non-steroidal anti-inflammatories, like aspirin and ibuprofen, but COX-2 inhibitors are very specific. They block just one molecule in the body’s web of inflammatory responses. Other researchers have shown that COX-2 inhibitors can slow muscle wasting in cancer patients. And most importantly, COX-2 inhibitors don’t seem to block the body’s antiviral immune reaction.

Haynes and Bartley are currently testing the COX-2 inhibitors to see if they prevent muscle loss in geriatric mice after the flu. They’re also testing whether improving immune memory of the flu in mice — that is, vaccinating them — protects them against muscle wasting.

Their work is intriguing, but Kuchel cautions that adult humans are more complicated than lab mice.

“Factors that may contribute to an older individual becoming more vulnerable to losing muscle function during or after flu infection are complex but may include a sedentary lifestyle, slow walking speed at baseline, low muscle mass, poor nutrition, plus chronic inflammation as a result of any number of chronic infections, being frail, etc.,” he says.

Bartley and Haynes agree. They’re applying for more grant money to explore how COX-2 inhibitors interact with other factors such as exercise. And they hope to eventually test muscle-protection strategies in people. Because while influenza is one of the most common serious infections in the elderly, it probably isn’t alone in causing muscle wasting.

“We’re trying to establish the relationship between any infection and inflammation, and how it leads to muscle loss and disability,” says Bartley. “Overall, we’re trying to help people get better and stay stronger for longer.”

Free to Be Imperfect

For patients and their families who live with Glycogen Storage Disease, a new gene therapy nearing clinical trial at UConn Health will mean freedom from the constant countdown to the next dose of medication.

By Julie Bartucca
Photography by Peter Morenus

Alyssa Temkin, 11, takes a break during a basketball game

Alyssa Temkin, 11, takes a break during a basketball game to drink Tolerex, the special formula that keeps her blood sugar from crashing to dangerously low levels. Alyssa has Glycogen Storage Disease and must drink the formula every 90 minutes to stay alive. Photo: Peter Morenus


Imagine never being able to hit the snooze button or oversleep, never being able to cheat on your diet or fall asleep in front of the TV because it could mean life or death — for you, or worse, your child.

That’s what the 1 in 100,000 people worldwide with Glycogen Storage Disease (GSD), a genetic liver disorder — and their parents — live with every day.

Dr. David Weinstein, who in January moved his world-renowned GSD program from the University of Florida to UConn Health and Connecticut Children’s Medical Center, has dedicated his life to giving these families hope. Although a life-saving treatment was discovered in the 1970s — taking a cornstarch mixture every few hours — research had halted for decades after that. And today, patients are still slaves to the clock; the effects of cornstarch last only a few hours, and even an extended-release form has its pitfalls.

But soon, that could change. Weinstein and his team are on the verge of testing in a human clinical trial the first GSD gene therapy, which has worked for canines and mice with the illness.

For the patients and their families who live in a constant countdown to the next feeding, the new therapy would mean freedom. A normal life, where mistakes can be made. Where they no longer have to be perfect.

There was no research going on anywhere in the world in this disease. And if there’s no research, that means there’s no hope.

Fatal Mistakes

Healthy livers store excess sugar from food and release it into our bloodstreams when we need it, as processed sugar enzymes called glycogen. However, in the seven forms of GSD, the liver fails to break down glycogen into glucose, causing the body’s blood sugar levels to drop dangerously low, which can lead to seizure or death.

The discovery of cornstarch therapy was a huge turning point, but it wasn’t enough.

“The problem with this disease is that people need cornstarch every four hours. People have died because their parents overslept,” says Weinstein. One missed alarm and a patient could die. A malfunctioning piece of medical equipment could mean a dangerous seizure.

“One of the parents was giving a talk recently and said, ‘Do you know what it’s like to have to be perfect all the time?’” Weinstein says. “And that’s what these families live with. It’s extreme stress.”

Weinstein and his team have made great strides. GSD was once considered a childhood disease — this generation is the first to survive to adulthood. Now, patients are doctors, athletes, mothers — more than 50 babies have been born to mothers with GSD since the first in 2003. But they still live under constant pressure. The disease is relentless, unforgiving.

For the patients and their families who live in a constant countdown to the next feeding, the new therapy would mean freedom. A normal life, where mistakes can be made. Where they no longer have to be perfect.

The Temkin family of West Hartford knows all too well what can happen.

When Gayle and Steve Temkin brought baby Alyssa home from the hospital at three days old, Gayle knew something was wrong with her daughter. By the time they got to a hospital that night, Alyssa was in full liver and renal failure. Her sugars were undetectable. Without intervention, she wouldn’t survive an hour, doctors said.

It was six months, several hospitals, countless invasive tests, and second and third opinions before Alyssa was diagnosed with GSD at Mount Sinai Hospital in New York City.

Alyssa is now 11, a smiling, soft-spoken sixth-grader who enjoys playing sports, acts in plays, and is learning to play guitar and dance. She gets good grades and loves her friends. But every 90 minutes, every single day, she must check her blood sugar and drink Tolerex, a special formula that keeps her sugar up. Alyssa is the only known GSD patient who can’t tolerate cornstarch, and Tolerex doesn’t last as long, so the time between her feedings is even shorter than it is for most GSD patients.

While the Temkins do everything they can to make Alyssa’s life normal, there are constant reminders that it is anything but.

Gayle spends every day at Alyssa’s school. For years, she would go into the classroom to feed Alyssa, first through a feeding tube and, more recently, with a drinkable formula. This year, Alyssa has gained some freedom. An Apple Watch reminds her when it’s time to test her blood and drink, and she reports her sugar level to her mom via a walkie talkie. Gayle, a former social worker, stays close, just in case.

If Alyssa’s sugar gets too low, she doesn’t feel it. Unlike most people, GSD patients don’t feel shaky or get headaches when their sugar drops — at least not until it’s too late. By then, they could be moments from having a seizure.

In 2015, Alyssa suffered a near-fatal seizure after the pump that feeds her dextrose through the night failed. “There is nothing about this disease that’s forgiving,” says Gayle. “It doesn’t matter what regimen you’re on; it could be a bad batch of something — We think we’re doing everything right, and the pump malfunctions.”


Dr. David Weinstein, head of the Glycogen Storage Disease Program at UConn Health and Connecticut Children’s Medical Center, walks with Alyssa Temkin through the new clinic at Connecticut Children’s.

Dr. David Weinstein, head of the Glycogen Storage Disease Program at UConn Health and Connecticut Children’s Medical Center, walks with Alyssa Temkin through the new clinic at Connecticut Children’s. Weinstein has treated Alyssa since she was diagnosed with GSD at 6 months old. Her family and other Hartford-area philanthropists supported the move of Weinstein’s program from Florida to Connecticut. Photo: Peter Morenus


No Research, No Hope

Weinstein had no intention of dedicating his life to curing GSD. As a young physician at Boston Children’s Hospital specializing in sugar disorders in 1998, Weinstein was caring for just two patients with GSD when he was invited to a national conference of the Association for Glycogen Storage Disease.

“I showed up at this meeting and was shocked by what I saw,” he says. The conference started with a moment of silence and a reading of the names of all the children who had died from GSD that year. The research presented was decades old. And the only treatment option being discussed was liver transplantation to combat complications from the disorder.

“There was no research going on anywhere in the world in this disease,” Weinstein says. “And if there’s no research, that means there’s no hope.”

A conversation with a mother there changed the course of Weinstein’s life. Knowing no one at the conference, he sat down for lunch next to Kathy Dahlberg, who had one-year-old twin sons already on the liver transplant list. She told Weinstein how sick her children were, and that her only hope was that they’d live long enough to get their liver transplants.

“Over lunch at that conference, I decided that somebody had to care about these children. The children shouldn’t have to suffer just because it was a rare disease,” Weinstein says. “The world didn’t need another diabetes doctor. This is where I could make a difference.”


Gayle Temkin talks to her daughter Alyssa in a school stairwell.

Gayle Temkin talks to her daughter Alyssa in a school stairwell. Gayle attends school with Alyssa every day, waiting in a room off the main office for Alyssa to check in via walkie talkie every 90 minutes to report her blood sugar level and that she’s drunk her Tolerex. GSD patients don’t feel the signs of low sugar until they are moments from a seizure, so Gayle stays close around the clock. Photo: Peter Morenus


As soon as he returned to Boston, Weinstein shifted his research focus to GSD and built the program there before moving it to the University of Florida in 2005 in order to work with the veterinary program. He has successfully treated dogs with his gene therapy, turning a fatal disease into one where dogs born with GSD are thriving.

Today, Weinstein sees 500 patients from 49 states and 45 countries. With help from Alyssa’s Angel Fund — started by the Temkins when Alyssa was a baby — and other charities, he has established centers all over the world.

All the Way

In January, the GSD lab moved to UConn Health’s Farmington campus. At the same time, a clinical and research unit supported financially by the Temkins and other local philanthropists opened at Connecticut Children’s. Gayle Temkin, Alan Lazowski, and Barry Stein are the trustees for the Global Center for Glycogen Storage Disease, and through the new organization will continue to raise money to support Weinstein’s program. They are working to set up other forms of assistance for patients and their families, including a closet with free supplies at the clinic, and support programs for families once the clinical trials start.

Because GSD patients are now surviving well into adulthood, the partnership between the two institutions makes great sense. “We’re much stronger working together,” Weinstein says.

Although Weinstein is the only doctor in the world dedicated to curing GSD, he says he’s not doing it alone — far from it.

“I’ve never seen a program like ours. I only do one disease. Everybody on my team does just one disease,” he says. “This is personal. Most people have a connection to the condition, and so they’ll work until everything’s done. It’s just a dedication that I’ve never experienced anyplace else.”

The bulk of Weinstein’s Florida team came to Connecticut with him. His team includes GSD patients and parents, including several who have called him out of the blue to tell him all they want is to work with him. One, who moved to Connecticut from Minnesota to join the new center, is Kathy Dahlberg, the mother who changed Weinstein’s course all those years ago. Her twins are now sophomores in college.

And, after nearly two decades of dedicated research, Weinstein’s next step is the one he’s been working toward all along. Human safety trials of his gene therapy, in conjunction with Dimension Therapeutics out of Cambridge, Mass., are expected to start this year. UConn will coordinate the trials with collaborating centers all over the world. Full-treatment trials should start in 2020.

The ultimate goal for the gene therapy, according to Weinstein,
is to prevent low blood sugars, eliminate the dependence on cornstarch, and give patients normal lives where oversleeping isn’t the worst-case scenario.

“If we can accomplish that, we’ve come all the way,” he says.

“The cure is right at our fingertips. He knew he could do this,” says Gayle. “When we first brought Alyssa to him, he said, ‘By her Bat Mitzvah, by the time she’s 12 or 13, we should be able to cure her.’ And she’s 11.

“We’re almost there.”

The Power of MRI

A UConn Health physician is seen reviewing an MRI brain scan.

A UConn Health physician is seen reviewing an MRI brain scan. At UConn Health, doctors are pioneering ways to use MRI technology to diagnose and monitor a range of conditions affecting many parts of the body Photo: Peter Morenus


Magnetic resonance imaging (MRI) has come a long way since the technique was first used in the U.S. in the late 1970s. UConn Health is now taking this powerful, non-invasive imaging tool to the next level.

UConn Health physicians in a variety of specialties are using the technology — which captures images of the inside of the body using a large magnet rather than radiation — in new ways to detect and monitor illnesses.

Prostate Cancer

Dr. Peter Albertsen, chief of UConn Health’s Division of Urology, currently follows 100 patients with localized prostate cancer, which is slow-growing, using advanced multiple-parametric MRI imaging. The technology has now replaced ultrasound as the imaging method of choice for prostate cancer. The technique yields multiple imaging sequences of the prostate, providing information about the anatomy, cellular density measurement, and vascular supply.

There is growing evidence to support the idea that the best treatment plan for low-grade prostate cancer is “watchful waiting” to monitor its progression, instead of immediate surgery or radiation. Albertsen’s practice of active surveillance, and not intervention, for localized prostate cancer was reinforced by a recent long-term study published in September in the New England Journal of Medicine, on which Albertsen served as a consultant.

The technology is extraordinarily helpful, allowing us to avoid invasive biopsy testing and associated risks of bleeding and infection.

Liver Disease

UConn Health is the first in Greater Hartford to use MRI to measure the stiffness of patients’ livers to reveal disease without the need for biopsy. Its MR elastography technique involves placing a paddle on a patient’s skin over the liver during MRI to create vibrations and measure the velocity of the radio waves penetrating the organ. This can indicate a stiffer liver and help diagnose fibrosis, cirrhosis, a fatty liver, or inflammation associated with hepatitis. The initiative is led by Dr. Marco Molina, radiologist in the Department of Diagnostic Imaging and Therapeutics.

“The technology is extraordinarily helpful, allowing us to avoid invasive biopsy testing and associated risks of bleeding and infection,” Molina says. “Plus, with the obesity epidemic, patients developing nonalcoholic steatohepatitis (NASH), or fatty liver, can receive earlier diagnosis and take action to reverse their disease’s progression with diet and exercise.”

Breast Cancer

The new Women’s Center at UConn Health has opened its state-of-the-art Beekley Imaging Center, featuring advanced breast cancer screening. Dr. Alex Merkulov, associate professor of radiology and section head of women’s imaging, and his team are conducting research to test the effectiveness of using an abbreviated, five-minute MRI scan to confirm or rule out a breast cancer diagnosis. Typically, an MRI test takes 20 minutes, but researchers are seeing that a briefer MRI scan of just a few minutes can help provide a definitive answer to whether an abnormal breast growth is cancer or not — and potentially help women avoid the biopsy process.

Arthritis

The UConn Musculoskeletal Institute is now researching the use of MRI to assess and map the strength, weakness, and underlying makeup of a patient’s cartilage, especially for those with arthritis. The tool can allow orthopedic experts to identify any thinning or loss of cartilage in the body, which signifies moderate to late-stage disease. In early stages of arthritis, MRI can help pinpoint early morphological and subtle biochemical changes in cartilage.

Neurological Disorders

In neuroradiology, UConn Health is using the power of MRI to differentiate brain tumors, to detect strokes, to assess dementia, to diagnose multiple sclerosis, to evaluate traumatic brain injury, to find the source of epilepsy, and to guide brain surgery. In March 2017, leading neuroradiologist Dr. Leo Wolansky joins UConn Health to advance its research and chair the Department of Diagnostic Imaging and Therapeutics. Wolansky’s neuroimaging research has focused on enhancing understanding of MRI and its contrast agents, especially for multiple sclerosis and brain tumors. He also specializes in the hybrid imaging modality PET-MRI.

“Thanks to the power and advancement of MRI, doctors can see early evidence of disease and seize the opportunity to intervene and improve their patients’ health,” Molina says.

The Power of the Electronic Medical Record

Q&A with UConn Health’s first chief medical information officer (CMIO), Dr. Dirk Stanley

Q

How transformative is an EMR tool for hospitals and physician practices?

It’s not just the electronic medical record that is so powerful — it’s the medical record in general. In his 1968 New England Journal of Medicine article, “Medical Records that Guide and Teach,” Dr. Larry Weed posited that the way we store information changes the way we think about information, which in turn changes the way we act on information. So a properly designed medical record can lead to improvements in communication and care. Medical records have since gone electronic, opening up even more opportunities to streamline communication and patient care. To do this effectively, however, requires technical people who understand the needs of the patient, the physician, the entire care team, and the health care organization. That’s where it’s helpful to have a clinical informaticist guiding an organization through the process.


Q

How impactful is a single, comprehensive EMR system for improving patient care?

Overall, an EMR is a win for the patients and a win for health care. Putting all inpatient and outpatient health care providers, physicians, nurses, pharmacists, and other clinical staff on one EMR platform is both a great opportunity and a daunting challenge. It allows for a degree of communication that was never before possible, with the entire care team having immediate access to the same patient data. But it can also present unexpected operational challenges, such as determining who is responsible for which part of the patient’s clinical care. EMRs save time spent tracking down paper charts, are much more secure and legible, and can be easily shared with patients and their caregivers. They also provide researchers access to large volumes of clinical data, which can lead to further care improvements, new therapies, and patient-care standards.


Q

How can an EMR help practices become more clinically and financially efficient in their delivery of high-quality care?

One of the most powerful tools within an EMR system is clinical decision support (CDS). Those little electronic alerts and other design features help guide the physician to the latest guidelines, most recent evidence, and most effective care, since it can be hard to keep up with the heavy volume of new medical information that they need to know. CDS can be used in a wide range of areas, including patient care, patient safety, coordination of care, and for cost reductions. In an outcomes-driven environment, providing great patient care can help translate into improved financial health for an organization.


Q

What is on the horizon when it comes to EMR at UConn Health?

We are currently meeting with people across the organization to help us configure our new EMR system, called HealthONE (Epic). Creating the platform will also allow us to build other evidence-based tools to further improve care and research opportunities here at UConn Health, in the Hartford region, and beyond. We are planning to launch this to our patients and providers in April 2018.

Size Matters for Particles in Bloodstream

UConn Engineering Professor’s Findings Could Mean More Effective Cancer Drugs

UConn researchers used a fluorescence microscope to illuminate a microfluidic device that simulates a blood vessel to observe and measure how particles of different sizes behave in the bloodstream.

UConn researchers used a fluorescence microscope to illuminate a microfluidic device that simulates a blood vessel to observe and measure how particles of different sizes behave in the bloodstream. Their findings could aid the development of more effective cancer drugs. Photo: Anson Ma


A UConn engineering professor has uncovered new information about how particles behave in our bloodstream, an important advancement that could help pharmaceutical scientists develop more effective cancer drugs.

Making sure cancer medications reach the leaky blood vessels surrounding most tumor sites is a critical aspect of treatment and drug delivery. While surface chemistry, molecular interactions, and other factors come into play once drug-carrying particles arrive at a tumor, therapeutic medication doesn’t do much good if it never reaches its intended target.

Anson Ma, assistant professor of chemical and biomolecular engineering, used a microfluidic channel device to observe, track, and measure how individual particles behaved in a simulated blood vessel.

Ma says he wanted to learn more about the physics influencing a particle’s behavior as it travels in human blood, and to determine which particle size might be the most effective for delivering drugs to their targets. His experimental findings mark the first time such quantitative data has been gathered. The study appeared in the Oct. 4, 2016 issue of the Biophysical Journal.

Using a fluorescence microscope, Ma was able to see particles moving in the simulated blood vessel in what could be described as a vascular “Running of the Bulls.” Red blood cells race through the middle of the channel as the particles — highlighted under the fluorescent light — get carried along in the rush, bumping and bouncing off the blood cells until they are pushed to open spaces, called the cell-free layer, along the vessel’s walls.

What Ma found was that larger particles — the optimum size appeared to be about 2 microns — were most likely to get pushed closer to the blood vessel wall, where their chances of carrying medication into a tumor site are greatest. The research team also determined that 2 microns was the largest size that should be used if particles are going to have any chance of going through the leaky blood vessel walls into the tumor site.

Knowing how particles behave in our circulatory system should help improve targeted drug delivery, reducing the toxic side effects caused by potent cancer drugs missing their target and impacting the body’s healthy tissue.

“When it comes to using particles for the delivery of cancer drugs, size matters,” Ma says. “When you have a bigger particle, the chance of it bumping into blood cells is much higher, there are a lot more collisions, and they tend to get pushed to the blood vessel walls.”

The results were somewhat surprising. In preparing their hypothesis, the research team estimated that smaller particles were probably the most effective since they would move the most in collisions with blood cells, much like what happens when a small ball bounces off a larger one. But just the opposite proved true. The smaller particles appeared to skirt through the mass of moving blood cells and were less likely to experience the “trampoline” effect and get bounced to the cell-free layer, says Ma.

Ma proposed the study after talking to a UConn pharmaceutical scientist about drug development at a campus event five years ago.

“We had a great conversation about how drugs are made and then I asked, ‘But how can you be sure where the particles go?’” Ma recalls, laughing. “I’m an engineer. That’s how we think. I was curious. This was an engineering question. So I said, ‘Let’s write a proposal!’”

The proposal was funded by the National Science Foundation’s Early-concept Grants for Exploratory Research, or EAGER, program, which supports exploratory work in its early stages on untested, but potentially transformative, research ideas or approaches.

Knowing how particles behave in our circulatory system should help improve targeted drug delivery, Ma says, which in turn will further reduce the toxic side effects caused by potent cancer drugs missing their target and impacting the body’s healthy tissue.

The findings were particularly meaningful for Ma, who lost two of his grandparents to cancer and who has long wanted to contribute to cancer research in a meaningful way as an engineer.

The results may also be beneficial in bioimaging, where scientists and doctors want to keep particles circulating in the bloodstream long enough for imaging to occur. In that case, smaller particles would be better, says Ma.

Moving forward, Ma would like to explore other aspects of particle flow in the circulatory system, including how particles behave when they pass through a constricted area, such as from a blood vessel to a capillary. Capillaries are only about 7 microns in diameter. The average human hair is 100 microns.

“We have all of this complex geometry in our bodies,” says Ma. “Most people just assume there is no impact when a particle moves from a bigger channel to a smaller channel because they haven’t quantified it. Our plan is to do some experiments to look at this more carefully, building on the work that we just published.”

Ventilator-Associated Pneumonia Still a Concern, Study Says

mask holds oxygen mask to face


Contrary to data published by the Centers for Disease Control and Prevention, ventilator-associated pneumonia rates in hospital intensive care units have not declined significantly since 2005, according to a new study out of the UConn School of Medicine.

The study, published in the Journal of the American Medical Association, found that about 10 percent of critically ill patients placed on a ventilator develop ventilator-associated pneumonia (VAP). The finding is based on reviews of charts from hospitals across the country from 2005-2013.

“VAP is not going away; it still affects approximately one in 10 ventilated patients,” says the study’s lead author, Dr. Mark L. Metersky of UConn Health’s Division of Pulmonary and Critical Care Medicine. “Our findings are in stark contrast to the CDC’s report of a marked decline in VAP rates that had some believing it may no longer be an important problem.”

Researchers reviewed data compiled by the Medicare Patient Safety Monitoring System from a representative sampling of 1,856 critically ill Medicare patients, ages 65 and older, who needed two or more days of mechanical ventilation.

While the VAP rates were stable throughout that time, the rates did not correlate with the CDC’s National Healthcare Safety Network reported rates, which suggest declining rates between 2006 and 2012 in both medical and surgical ICUs. The rate of VAP is one of the metrics for patient safety and health care delivery quality that many hospitals are scored on nationally.

VAP is not going away … Our findings are in stark contrast to the CDC’s report of a marked decline in VAP rates that had some believing it may no longer be an important problem.

Patients in need of mechanical ventilation are often the most critically ill in a medical or surgical ICU hospital setting. Research has shown that up to 15 percent of patients who get it may die from VAP.
The study authors examined the prevalence of VAP in patients on a ventilator following a heart attack,
heart failure, pneumonia, or major surgery. These types of patients are at higher risk for developing pneumonia, a bacterial infection, due to the need for a tube extending down their throat and into their lungs to help them breathe.

“We have not beaten this,” says Metersky. “Current hospital interventions that are used in an attempt to prevent VAP are not working. VAP is still a significant issue, and needs more examination into how we survey its occurrence and report it, along with more research into how best to prevent this type of pneumonia in vulnerable patient populations.”

The higher-than-expected VAP rates may be leading patients to experience complications or death from their lung infection or spend more time on a ventilator or in the ICU, slowing recovery. It may also increase use of antibiotics, leading to potential resistance, and increase health care costs due to longer hospital stays.

Metersky collaborated on the study with colleagues at Qualidigm, Harvard Medical School, and Harvard School of Public Health. It was supported by the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.