Author: yec14002

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.

UConn Health Offers Largest Emergency Dental Service in CT

patient in dental chair

UConn Health sees an average of 60 dental emergencies in a 24-hour period.


Dental emergencies can strike at any time. That’s why UConn Health has offered around-the-clock coverage for dental emergencies since the early 1970s and recently opened a specialized patient room within the new emergency department at UConn John Dempsey Hospital.

“We have the largest dental emergency service in the state,” says Dr. Steven Lepowsky, senior associate dean for education and patient care at the UConn School of Dental Medicine. “The service exists to address a significant unmet need.”

Even those who receive regular dental care can face emergency situations at any time. On average, UConn Health sees nearly 60 dental emergencies in 24 hours. The most common are toothaches related
to a cavity, root canal, or abscess.

On weekdays from 8:30 a.m. to 10 p.m., urgent dental care is provided by students and residents from the UConn School of Dental Medicine who staff UConn Health’s dental clinics under faculty supervision.

The training component makes the emergency dental service a crucial piece of the dental school’s academic mission.

The service exists to address a significant unmet need.

“It helps the students and residents build skills in terms of how to diagnose a problem quickly, identify the source of the problem, and provide care that immediately addresses someone’s needs,” Lepowsky says.
After 10 p.m., patients who present with a dental emergency are assessed by medical staff, who can bring in the dental resident on call, if necessary.

Although the hours are nothing new, the after-hours setting is.

The new room and dental chair “replicate a full dental operatory, so it expanded the scope of what we could offer on an emergency basis after hours,” Lepowsky says. “It’s a much more pleasant environment for the patient.”

It’s not, however, meant to replace primary dental care, according to Lepowsky.

Sometimes, after-hours care involves just relieving pain and sending the patient home, asking them to return in the morning when the dental clinics open for a specific dental treatment.

“You want someone to have an established relationship with a dental provider so there’s someone coordinating all their annual dental health care and maintenance needs,” Lepowsky says.

Hand, Wrist, and Elbow Team Brings Innovation

3 doctors stand together, Dr. Craig Rodner (left), Dr. Joel Ferreira (center), and  Dr. Anthony Parrino (right) Farmington, Southington

Dr. Anthony Parrino (left) – Farmington, Southington
Dr. Craig Rodner (center) – Avon, Farmington
Dr. Joel Ferreira (right) – Farmington, Storrs Center

Photo: Janine Gelineau


Hands, wrists, and elbows are complex and fragile. No matter our age or profession, we are prone to upper extremity injuries throughout our lifetime, along with diseases such as arthritis and tendonitis as we age.

Dr. Craig Rodner and new recruits Dr. Joel Ferreira and Dr. Anthony Parrino, who are both former UConn orthopaedic surgery residents, form the UConn Musculoskeletal Institute’s team, offering patients comprehensive surgical and non-surgical care in this area. All three specialists have completed advanced training during prestigious fellowships in hand, wrist, and elbow orthopedic surgery.

The Hand, Wrist, and Elbow Program at UConn Health offers advanced care for both children and adults for all bone and soft-tissue conditions of the upper extremity. The team cares for people from all walks of life who have pain from repetitive activity, acute trauma, or sports-related injury — from weekend warriors to the elite athletes of the UConn Huskies sports teams. Comprehensive care approaches include patient activity modification, physical therapy, bracing, steroid injections, and, if necessary, surgery.

Innovative surgical interventions are offered for arthritis, carpal tunnel syndrome, fractures, tendon and nerve damage, sports injuries, Dupuytren’s contractures, hand deformities, and more. These interventions include enhanced minimally invasive, arthroscopic, and microscopic surgical techniques leading to faster, less painful recovery.

The expansion of the team this past year to include Ferreira and Parrino brought specialized training in all aspects of elbow surgery, daily access to the hand surgeon experts, as well as expanded patient access to cutting-edge “wide-awake” painless hand surgery for certain conditions. Using a localized numbing medication in “wide-awake” procedures allows patients, if they so choose, to drive to and from the procedure, avoid the use of sedation, and recover more rapidly.

“Our goal at the UConn Musculoskeletal Institute is to get our patients back to functioning where they were before injury or disease affected them,” says Parrino. Ferreira adds: “We offer the absolute highest-quality, personalized care that there is to each and every patient to find the best surgical or non-surgical solution for an individual problem.”

While the number one focus of the hand, wrist, and elbow team is providing the highest possible level of compassionate care to each patient, Rodner, Ferreira, and Parrino are also dedicated to upper extremity research and education and are actively involved in teaching the students at the UConn School of Medicine and the residents of the UConn orthopedic surgery program about all facets of upper extremity care.

Lab Notes – Spring 2017

For MRSA, Resistance is Futile

UConn medicinal chemists have designed experimental antibiotics that kill Methicillin-resistant Staphylococcus aureus (MRSA), a common and often deadly bacteria that causes skin, lung, and heart infections. The new antibiotics disable the bacteria’s vitamin B9 enzyme. Without vitamin B9, the bacteria can’t make essential amino acids and they die. Not only do the new antibiotics kill regular MRSA, they also kill types of the bacteria with unusual antibiotic-resistance genes that had never been seen before in the U.S. And that’s no accident: the chemists designed the antibiotics to latch on to the enzyme so cleverly that if it changed enough to elude them, it would no longer be able to do its job with vitamin B9. This could make the new antibiotics resistant to, well, resistance. The research was published in the Dec. 22, 2016 issue of Cell Chemical Biology.

MRSA colonies are shown on a blood agar plate.


State’s Leading Institutions Launch International Effort to Advance Metabolic Research

overweight 3D model running with target on metabolic area

UConn, Yale University, and The Jackson Laboratory (JAX) have partnered with the Weizmann Institute of Science, a prestigious counterpart in Israel, to fill a research void in metabolic diseases that affect billions of people worldwide. The goal of the newly formed Metabolic Research Alliance is to unite the expertise of the institutions on research projects that swiftly move investigations into clinical application and commercialization. The Alliance will employ a novel approach to coordinating existing and new expertise in the areas of immunology, cell biology, microbiota, and the rapidly evolving field of genomics. While investigations will initially focus on obesity and diabetes, the research projects will eventually pursue solutions to additional metabolic diseases.


Innovative Imaging Could Save Sight

Connecticut Innovations has awarded $500,000 to a team of UConn researchers to speed the process to commercialization of the biomarker probe they’re developing to detect a precursor to blindness. The team — led by Royce Mohan, associate professor of neuroscience at UConn Health, and including assistant professor of neuroscience Paola Bargagna-Mohan and UConn School of Pharmacy medicinal chemistry professor Dennis Wright — is developing a fluorescent small molecule imaging reagent to help identify preclinical stages of ocular fibrosis, which is associated with an aggressive form of age-related macular degeneration (AMD) that causes rapid vision loss. AMD is the leading cause of blindness in the U.S. The method would both enable earlier intervention and allow physicians to monitor the progress and effectiveness of interventions before it’s too late.


DOACs Safer Than Warfarin, Study Shows

Patients who suffered blunt traumatic intracranial hemorrhage (ICH) associated with direct oral anticoagulants (DOACs) had significantly lower mortality rates and lower rates of operative intervention compared with a similar group taking warfarin, a study published in the November issue of Trauma and Acute Surgery by researchers from UConn, Saint Francis Hospital and Medical Center, and Trinity College shows. Although DOACs have been an increasingly popular alternative to warfarin for anticoagulation, physicians have worried their use might lead to an increase in patient mortality from uncontrollable bleeding, according to the study. The study, based on data on 162 patients in the St. Francis Trauma Quality Improvement Program database, aimed to help close a gap in research on DOAC safety.

bloodclot in vein

Honor Roll – Spring 2017

Lakshmi S. Nair, M.Phil., Ph.D. has been elected a Fellow of the National Academy of Inventors.


UConn School of Dental Medicine has been awarded by Special Olympics Connecticut a 2016 Golisano Health Leadership Award of the Special Olympics and its major supporter, The Golisano Foundation.


Dr. Marja Hurley has been appointed a member of the Special Programs Committee of The Endocrine Society for a three-year term.


Four UConn professors, including UConn Health Emeritus Professor of Dental Medicine Dr. Arthur Hand, have been named fellows of the American Association for the Advancement of Science.


UConn John Dempsey Hospital is the only academic medical center in the state to receive an ‘A’ grade from The Leapfrog Group, the premier nonprofit hospital safety advocate in the nation, for fall 2016.


Dr. Stormy Chamberlain has been named the new Scientific Advisory Committee Chair for the Angelman Syndrome Foundation.


Dr. Johnny Wu has been appointed to the board of directors of the National Commission on Correctional Health Care.


Laurinda Jaffe, Ph.D., will receive the 2017 Pioneer in Reproduction Research Leadership Award from the Board of Scientific Counselors of the Frontiers in Reproduction Program.


Dr. Bruce E. Gould has been selected by the U.S. Secretary of Health and Human Services to serve on the Advisory Committee on Interdisciplinary, Community-Based Linkages.


UConn researcher Jianjun Sun received a $100,000 Grand Challenge Explorations Phase I award from the Bill & Melinda Gates Foundation to pursue an approach to contraceptives without extreme side effects.