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Handled With Care

The breast cancer journey is a delicate one. The breast team at UConn Health strives to guide each patient through every step of their individual path with an unmatched level of attention and comfort.

 

By Kim Krieger
Photos by Peter Morenus

UConn medical oncologist Dr. Susan Tannenbaum initiated the multidisciplinary focus of the breast program, connecting patient care to research and bringing accreditation through the American College of Surgeons, before handing the reins to surgeon Dr. Christina Stevenson.

UConn medical oncologist Dr. Susan Tannenbaum initiated the multidisciplinary focus of the breast program, connecting patient care to research and bringing accreditation through the American College of Surgeons, before handing the reins to surgeon Dr. Christina Stevenson.


Some people need no urging to get medical screenings. These are the people who see their dentist twice a year like clockwork, who make that annual preventive care appointment, and who don’t put off a colonoscopy.

But most people are not like that. Even a mammogram can be a tough sell. Getting your breasts squeezed between two cold plates and X-rayed while wearing an ill-fitting gown is nobody’s idea of a good time. And when a patient has already found a suspicious lump, there’s an extra layer of stress.

The radiologists and staff at UConn Health’s Beekley Imaging Center, part of the Women’s Center, do their best to dispel that stress. Good service and a relaxing atmosphere go a long way toward evoking a spa-like ambience. There’s comfortable seating, private changing rooms, warmed gowns that fit, appointments that start on time — and cookies.

The patients appreciate it.

“I’m always in and out,” one woman says to another as they ride the elevator up to the imaging center. “I stay for the cookies and juice,” says the other. They both laugh. The first woman proclaims, “It’s really nice up there!”

Indeed it is. And if a woman cares to linger over her cookies and juice, she can get her results on the spot.

“One woman, here in 2013, 2015, 2017, 2019, always reports the same symptoms. Lumps, terrible breast pain. She wants our attention. She is worried about breast cancer,” says Dr. Alex Merkulov, head of women’s imaging and a radiologist in the Imaging Center. “Our job is to remind her of the prior years and assure her that everything is OK this time, too. We treat people the way we would want to be treated.”

Merkulov is intensely attentive when you talk to him, and although his phone dings constantly, he gives you the feeling that all his focus is on you. However much time you need. He says working with each patient “is a personal relationship.” And he means it.

All a woman needs to start this relationship is an order for a mammogram from her primary care doctor. She makes an appointment and fills out a short questionnaire when she arrives. Does she have a lump? Pain? Have any family members had breast cancer? Depending on her answers to the questionnaire and the results of her mammogram, the radiologists may recommend she come in for more frequent screenings or have a consultation with one of the genetic counselors.

After her low-dose mammogram, the woman dresses, gets her cookies and juice, and hears her results within 15 minutes. If she’s in a hurry, she can leave immediately and get a phone call within two days letting her know if she needs any follow-up tests.

Most of the time, those results are A-OK. The radiologist gives the all-clear and says, “See you in two years.”

Dr. Alex Merkulov

“We treat people the way we want to be treated,” says Dr. Alex Merkulov, head of women's imaging and a radiologist in the Beekley Imaging Center. The large screens in the Center's imaging suite allow radiologists to show patients exactly what they're seeing after a mammogram and explain why they are or are not concerned.

Intimate, Holistic Care

Only about 10% of women have something in the mammogram that might indicate a problem. When that happens, the radiologist recommends a follow-up ultrasound or a special mammogram to detect the calcium deposits that can signal early breast cancer.

“I’m a frequent flyer” at the Beekley Imaging Center, says a patient named Patricia. Because she’s at high risk for breast cancer, she’s had tests often over the last 10 years. At some places she’s had mammograms, “you go in a basement, you don’t talk to anyone, you get a letter a week later,” she says. But UConn Health is completely different.

When she first started going, they modeled her risk. Patricia’s was off the charts, so they had her meet with a medical oncologist at the Carole and Ray Neag Comprehensive Cancer Center who specializes in breast cancer to discuss preventive options. After examining Patricia’s history in detail, the oncologist, Dr. Susan Tannenbaum, advised her that actually, she didn’t need to proceed with preventive medical oncology. On other visits, the radiologist has invited her into his office to view the mammograms displayed on big screens so he can show her exactly what he sees and explain why he is or isn’t concerned.

“They give you a lot of information in a caring way,” Patricia says. “I have too much going on to have my primary care doctor and OB/GYN booking appointments randomly — I need a team treating me holistically. This feels like intimate care from really great doctors.”

That focus on intimate, holistic care is evident even when a woman has a benign breast condition. Women with breast pain, breast infections, fibroadenomas, and other lumps that aren’t cancer see Dr. Dana Scott, an OB/GYN who specializes in benign breast conditions. The benign breast disease program she leads is unique in the area.

“I try to really listen to my patients and spend the appropriate amount of time with them to hear all their concerns,” Scott says. Sometimes the women need treatment, sometimes even surgery. But just as often, it’s the care and attention they get that is the most valuable. For “a lot of patients who are really worried they have breast cancer and they don’t, having someone who can listen to them, examine them, and provide follow-up is really important,” Scott says.

Not All Women Are the Same

But what if a woman’s breast condition isn’t benign? If the follow-up scans reveal something that looks suspicious, the radiologists discuss the findings with the woman and advise her to come in for a biopsy, scheduled at her convenience for some time in the next day or two.

The tissue from the biopsy is evaluated by Dr. Poornima Hegde, a UConn Health pathologist who specializes in breast disease. A cancer diagnosis is only as precise at the pathologist who evaluates the suspicious cells, and Hegde is an expert. She looks at breast tissue all day, every day, and can make the call between cells that are just a little weird versus cells that mean malignancy.

“We try to reduce the ambiguity: either you’re OK, or you’re not,” says Merkulov, the radiologist. “Poornima is a godsend.”

If Hegde and the radiologists agree the woman has a cancerous mass, they spring into action. They contact the breast cancer nurse navigator and, often, the team’s social worker and bring them in to discuss the results of the biopsy with the patient. The nurse navigator will call the patient and answer any preliminary questions she has. The navigator also tries to identify any hurdles or barriers the woman might have to overcome to get treatment.

“You need to understand where people are coming from: people may have the exact same diagnosis but very different resources,” says Wendy Thibodeau, RN, one of the nurse navigators who works with breast cancer patients. Thibodeau speaks plainly, and intuitively grasps what you’re really asking with a question. Her role as a navigator is to coordinate care for the patient, offer her emotional support, evaluate any barriers to treatment, and help her get to the next step. She gives every patient her cell phone number and tells them they can call her anytime. Often, they call her to ask her to remind them what the doctor said, what they need to do. But other times, she must talk them down.

“Sometimes we have a patient whose first instinct is ‘Cut it off! Cut it out of me!’” Thibodeau says. “I have to call her and explain you can’t just cut; you need to do lots of tests to understand what we need to do to treat this.” Sometimes a woman will need chemotherapy before surgery to shrink the tumor. The nurse navigator can fit the woman for a cold cap to preserve her hair and meet her on the first day of chemotherapy for support. Or she might need other tests or treatments, and the nurse navigator can explain those and help her through them. Not all breast cancers are the same.

And not all women are the same, nor do they have the same needs. Both these points were highlighted during a tumor board meeting this summer.

The tumor boards are weekly meetings between the medical oncologist, the surgeons, the radiologists, pathologist, the nurses, and the social worker. Radiation oncologists, plastic surgeons, genetic counselors, and any others involved in the patients’ care also join. They discuss their cases that week. Typically, the radiologist will start off, to show the extent of the cancer in the breast and whether they believe it has spread. The pathologist will share and confirm with the team what she’s found.

The medical oncologist will discuss the best approach, the type of treatment this cancer responds to best, whether the patient will need chemotherapy. The surgeons consider the type of excisions they can offer the patient. The discussion about treatment is often collaborative, with the surgeons, radiologists, medical oncologist, and geneticists all weighing in. They also discuss cases post-surgery; did they find what they thought they would? Should treatment change
in any way?

Dr. Christina Stevenson

Dr. Christina Stevenson, surgical oncologist and breast program head, in the operating room.

The Road to the 'All-Clear' — and Beyond

And then there was a patient we’ll call Deborah. She was a 43-year-old single mother. She needed to come in for surgery, and soon. But she had no one to take care of her children for the 24 hours or so she would need for surgery and recovery. Everyone was worried about her.

Dr. Christina Stevenson, the surgical oncologist and head of the breast program at UConn Health, was the first person to bring up Deborah’s childcare predicament. She’d seen her the day before.

Typically, when Stevenson meets with a patient who needs surgery, they discuss surgical options: just the lump, or the whole breast? Perhaps the woman wants a reduction done at the same time, or implants put in for reconstruction, or her own tissue used instead of implants. Stevenson often consults with a plastic surgeon, and she does what is called oncoplastic surgery.

“I always try to preserve the breast in a lumpectomy to have the same size and shape we started with,” she says. “People worry they’ll have a divot. But we can move tissue around to help with the appearance.” She also has a few technological tricks, like the Biozorb sitting on her desk. It looks like an inch-long spring made of clear plastic. It’s actually resorbable suture material, studded with little metal clips. The sutures give a scaffold for the tissue to regrow upon, while the metal clips show up on a CAT scan or mammogram and help to focus radiation treatments, as well as follow-up in the future.

Stevenson is very calm describing all this; talking to her about breast surgery is almost soothing. Above her desk is an excerpt of a Christian prayer often attributed to Mother Teresa: “Dear Lord, Give skill to my hand, clear vision to my mind, kindness and meekness to my heart. Give me singleness of purpose and strength to lift up a part of the burden of my suffering fellow man.”

Stevenson brought up Deborah’s case at the tumor board. The social worker and nurse and community navigators stepped in. Although it’s more common for the community navigators to set up rides to appointments, provide gas cards, or fit patients for a nice wig, their goal is to make it possible for women to get treatment. The social worker focuses on psychosocial needs, and here was a woman with very limited social support. The social worker spoke with Deborah often, exploring who could care for her children within her family and community. Eventually Deborah worked past her anxiety and began to make concrete decisions. After much discussion, she found it in herself to speak with her sister and ask for assistance in caring for her kids while she was in recovery. Her friend drove her to and from surgery. Thanks to everyone stepping up, Deborah was able to successfully complete the initial phase of her treatment.

After surgery, Stevenson follows up with the patient at 1.5 weeks, then three months, then every three to six months for two years, often alternating visits with the medical oncologist. Then, if all is well, the patient comes back for yearly mammograms for life. She comes in for her scans and her cookies and juice and, hopefully, gets the all-clear. And if not, then Stevenson and the rest of the team at UConn Health’s breast program will help her take care of it.

“Because breast cancer is fairly easy to treat, typically. Especially when we catch it early,” Stevenson says. “And when we do regular mammograms, we catch it early.”

Nurse navigators and nurses like Minal Dave, RN, often offer patients emotional support.

Nurse navigators and nurses like Minal Dave, RN, often offer patients emotional support.

Unparalleled

By Chris DeFrancesco

Dr. David Choi

Dr. Choi points out spinal tumors needing critical care.


When a man in his sixties recently went to UConn John Dempsey Hospital after four days of severe back pain, an MRI revealed a rapidly growing spinal cord tumor that was placing extreme pressure on his spine.

He was sent straight to the emergency department where Dr. David Choi, the only neurosurgeon in Connecticut with fellowship training in spinal oncology, met him.

But not for the first time.

“Because we’re local, I had been seeing this gentleman for months before this tumor problem arose, so I already knew who he was, I already knew what treatments he was going through, I knew his general attitude about the quality of life that he would want for himself,” Choi recalls. “Now thankfully he did not have any neurologic deficits, but there was just so much compression on the spinal cord that I didn’t want to wait for anything bad to happen.”

Right away — in the middle of the night — Choi operated to decompress the tumor and stabilize the spine with rods and screws.

“The decision to do surgery was a no-brainer for both of us,” says Choi. Before Choi, the product of an elite complex spine surgery fellowship at Brown University, arrived at UConn Health, patients like this one had to travel to Boston or New York City for the same level of fellowship-trained expertise.

Having a comprehensive spine surgery specialist like Choi provides “real-time coverage — you’re getting things done right as they happen, and that gives the best chance for improved outcomes,” he says.

It’s an example of a patient already under the care of familiar providers being able to stay at UConn Health for continuation of that care, including treatment by a spine surgeon with unique subspecialty training in treating spinal tumors.

“In some cases, tumors cannot be entirely removed, requiring further treatments after surgery, such as chemotherapy and/or radiation therapy, coordinated by oncologists and radiation oncologists,” Choi says. “In cases of metastatic tumors, other surgical tumor specialists may continue their involvement in treating the primary tumor.”

Spinal tumors can metastasize to the spine or originate in or around the spinal cord or in the vertebrae. A tumor in the bone can cause fractures and a partial collapse of the spinal cord. In extreme cases, fractured pieces of bone may affect the spinal cord and cause neurologic deficits such as limb weakness or incontinence. Similar neurologic defects can result from a tumor in or around the spinal cord, which can compress the spinal cord or the nerve roots that exit it.

“The possible permanence of these deficits makes surgery necessary,” Choi says. “If you’re not able to walk around, or if you have bowel or bladder issues, that’s a pretty big impact on quality of life for the rest of your life.”

Choi says the opportunity to shape spinal oncology care at UConn Health is what drew him to Farmington.

“Few physicians will have a chance to help develop a new division in a well-established institution,” he says. “UConn Health is poised to become a leading destination center for a wide variety of neurosurgical conditions, and spinal oncology is a field that will serve our community and state well.”

Choi’s addition is a cornerstone of the vision of Dr. Ketan Bulsara, chief of the Division of Neurosurgery, to expand UConn Health’s neurosurgical care offerings and make UConn a world-class destination center.

“Dr. Choi’s expertise adds to the excellent work that was already being done at UConn Health in collaboration between neurosurgery and orthopedic surgery through our comprehensive spine center,” Bulsara says. “His level of training allows him to offer a unique perspective and potential treatment options for spine/spinal cord tumors.”

It also adds to a multidisciplinary team of spine surgeons at UConn Health.

“The recruitment of his talent and clinical expertise buttresses the vision of our comprehensive spine program,” says Dr. Hilary Onyiuke, neurosurgical director of UConn Health’s Comprehensive Spine Center.

The elite skill of the growing neurosurgery program is expanding in other ways as well.

Dr. Kevin Becker recently came from Yale to build a neuro-oncology program in collaboration with the Department of Neurology and the Carole and Ray Neag Comprehensive Cancer Center. Bulsara says the arrival of Becker “continues to build on our collaboration with the Preston Robert Tisch Brain Tumor Center at Duke, bringing an additional dimension to our treatment paradigm.”

Making the Connection

By Stacey Mancarella

Illustrations by Yesenia Carrero

illustration of photos of unconnected symptoms

A rare but debilitating condition, hereditary amyloidosis (hATTR) presents as seemingly unrelated illnesses that mask the root cause. But increased awareness and new treatment options bring hope for sufferers of this devastating genetic condition.


We hear of it too often in health care. Even with the most diligent doctors and patients, sometimes figuring out the correct diagnosis of a rare medical condition can be a challenge.

Unexplained weight loss and diarrhea. Shortness of breath during exercise. Carpal tunnel syndrome. Weakness and difficulty balancing that gets progressively worse. Tingling or numbness in the hands and feet. Symptoms like these point to different culprits, bringing patients to a variety of specialists and glimmers of hope as they find potential answers. But treating one symptom doesn’t help the others, and everything gets worse.

This particular collection of ailments, among other symptoms, points to hereditary amyloidosis (hATTR), a devastating genetic disease that, up until recently, was considered untreatable. Dr. Fernanda Wajnsztajn is all too familiar with the plight of her patients who have searched in vain for a diagnosis. A neurologist at the UConn Health neuropathy clinic, Wajnsztajn specializes in peripheral neuropathy, damage or disease of the peripheral nervous system.

“Because some of the symptoms of hereditary amyloidosis are also seen in a variety of diseases, some of my patients went to several doctors for years until hATTR was suspected,” she says. “With a detailed history, we are also able to trace the heritage of patients, and, often, patients realize during the interview that some their relatives also have similar symptoms.”

Now these families have options. New drug treatments have been approved to treat neuropathy, the nerve pain, tingling, or numbness that’s a symptom of this little-known disease, and doctors at UConn Health have assembled a team to tackle hATTR head on.

Interpreting the Evidence

Wajnsztajn has been aware of hATTR since her days at Columbia University, where she was involved in research and clinical trials for hATTR therapies. Only about 50,000 people worldwide are affected by hATTR, “but we suspect that many cases go undiagnosed or misdiagnosed,” Wajnzsztajn says. “Our goal is to reach those people.”

Hereditary amyloidosis is caused by a hereditary mutation of the TTR gene. If one parent carries the gene mutation, offspring have a 50 percent chance of inheriting the disease. Hereditary amyloidosis wreaks havoc on the body by depositing amyloid proteins into organs, most commonly the heart, nerves, and digestive tract. These deposits cause the organs to function improperly, which eventually leads to a myriad of debilitating symptoms.

Even though the gene mutation is present at birth, most patients don’t experience symptoms until well into adulthood. And even once symptoms start, it can take years for a proper diagnosis.

“Hereditary amyloidosis is not a well-known disease. The patient can present with a history of heart problems and receive a diagnosis of polyneuropathy, but if the doctor isn’t familiar with it, they won’t put it together. It’s easy to miss,” Wajnsztajn says.

For example, two of the most common symptoms of hereditary amyloidosis are carpal tunnel and cardiomyopathy, or heart muscle disease. Because these two diseases are seemingly unrelated and treated by different kinds of doctors, hereditary amyloidosis can go undetected. The average delay in diagnosis is four years, and in that time, amyloid is continuously deposited into the affected organs, causing symptoms to worsen.

Even with the new treatments, a timely diagnosis is important as the medications cannot reverse the symptoms but only prevent further protein deposits that cause the condition to worsen. The earlier a patient can be identified and a course of treatment initiated, the slower the disease will progress.

Dr. Fernanda Wajnzsztajn (left) and Dr. Sarah Tabtabai discuss a patient case.

Dr. Fernanda Wajnsztajn (left) and Dr. Sarah Tabtabai discuss a patient case.

Case Closed

UConn Health’s multidisciplinary approach can shorten this delay, giving patients relief sooner and stopping hATTR in its tracks. Cardiologists at the Pat and Jim Calhoun Cardiology Center work hand in hand with neurologists from the peripheral nerve disease clinic to examine a patient’s symptoms, get that crucial neuropathy or polyneuropathy diagnosis, and schedule them for genetic testing to confirm a hATTR diagnosis. Once the diagnosis is confirmed, treatment can begin very quickly, and the deposition of amyloid into the organs is halted within weeks — sometimes within days — thanks to neurologists, cardiologists, neuropathy testing, and an infusion center to administer treatment being all in one place.

Two treatment options currently exist, one that’s infused intravenously every three weeks, the other given by weekly subcutaneous injection. These new treatments work by inhibiting the body’s ability to create the amyloid protein. They reduce the amount of the protein the liver can make by 84 percent, improving the patient’s quality of life. Clinical trials are ongoing, with the hope that such medications can treat other types of amyloidosis as well.

“Before medicines like this came along, there was really no therapy for this particular heart disease. It’s progressive and very debilitating, and the hereditary type, in particular, occurs in younger people,” says Dr. Sarah Tabtabai, cardiologist at the Pat and Jim Calhoun Cardiology Center at UConn Health.

Previously attempted treatments for hATTR symptoms were drastic, sometimes including heart transplants or heart and liver transplants, Tabtabai says. But with the new medications, “patients have had good outcomes with both their neurologic disease and their heart disease, and it sort of keeps things at bay.”

Close collaboration between the departments makes everything go smoothly for patients who have already waited so long for answers, says Wajnsztajn.

“We work very closely with cardiology to obtain the appropriate exams for diagnosis as quickly as possible. Despite being a challenging or daunting diagnosis, our patients feel fortunate that they finally have answers, and we are able to provide the most advanced treatments along with the support necessary,” she says.

Because of the high rate of misdiagnosis, the companies that produce the new medications are currently offering free screenings for patients with suspected hereditary amyloidosis. A patient simply has to schedule the genetic test at UConn Health, and the billing is handled directly through the hospital, creating a streamlined process for the patient.

Early diagnosis of hATTR can also bring awareness to family members who might be afflicted.

“Once a patient is diagnosed with hereditary amyloidosis, we can test blood relatives as well to identify any members of their family who may also have this disease,” Tabtabai says. “The hope is that, down the line, we can offer medications like this sooner, before patients become symptomatic or right at the onset of symptoms so that they fare even better as time goes on.”

Taking Control

By Delker Vardilos

Photos by Tina Encarnacion

UConn Health is the first hospital in New England to use a new robotic technology to diagnose lung cancer sooner, getting patients the treatment they need and saving lives.

Product images courtesy of Auris Health

Lung cancer kills about 150,000 Americans each year. But when it is detected early, survival rates improve exponentially. UConn Health is the first hospital in New England to use a new robotic technology to diagnose cancer sooner, getting patients the treatment they need and saving lives.


Supporters of U.S. Supreme Court Justice Ruth Bader Ginsburg breathed a collective sigh of relief this winter after two cancerous nodules were successfully removed from her left lung through a lobectomy. Ginsburg’s cancer was found during the routine testing done after the fit 85-year-old fractured several ribs in a fall, and for a moment the diagnosis cracked the seemingly invincible façade of the octogenarian icon.

Although Ginsburg’s cancer was found by chance, her story is a great example of how early detection and swift action can improve the likelihood of survival for lung cancer, the deadliest cancer for both men and women in the U.S. by a wide margin. More people die of lung cancer each year than of colon, breast, and prostate cancers combined, and more than half of people with lung cancer die within a year of being diagnosed, according to the American Lung Association.

“The accuracy of this is going to pan out to be second to none. I think this is the tip of the iceberg in diagnosis.”

But when the cancer is detected early, before it spreads beyond the lungs, the five-year survival rate jumps from 5 percent to 56 percent. The problem is, just 16 percent of lung cancer diagnoses come at an early stage, American Lung Association statistics show. Since lung cancer is the second most common cancer in both men and women, proper screening for those at risk could save tens of thousands of lives.

A revolutionary precision technology now at UConn Health is making early diagnosis easier than ever.

UConn Health is the first hospital in New England and among the first in the nation to offer robotic bronchoscopy on the Monarch platform from Auris Health, allowing physicians to quickly diagnose lesions detected through low-dose CT scans, including those that are small or in hard-to-reach parts of the lung.

“Before this technology, the targets would’ve had to be bigger. I wouldn’t be able to make certain angles without the robotic arm to navigate,” says Dr. Omar Ibrahim, UConn Health director of thoracic oncology and interventional pulmonology. “I have a higher degree of confidence and accuracy with this than with prior equipment.

“The ability to diagnose the cancers at an earlier stage will allow us to surgically manage the disease,” he says. “This is the only chance for a cure.”

probe snaking through lung

The Monarch platform’s advanced, precision endoscope allows physicians to access hard-to-reach parts of the lungs and their bronchi and to diagnose lesions earlier than ever before.

With its user-friendly, video-game-style controller, the Monarch platform allows the physician to move the endoscope up and down, left and right, forward and backward through a lung and its bronchi. Buttons on the controller make the scope of view bigger or smaller, while others control suction or irrigation. Procedures are done in the operating room under general anesthesia. Within about an hour, the doctor will biopsy the suspicious nodule and a lymph node for analysis by a pathologist. The patient can go home the same day.

If cancer is confirmed in the lung, it will then be staged to see how far it has advanced. A team of cancer specialists then develop an individualized treatment plan that is ideal for the patient and their specific type and stage of cancer. A patient’s treatment plan might include surgery to remove a small portion of the lung or the entire lung, radiation therapy, chemotherapy, medications,
and immunotherapy.

Not only does earlier diagnosis improve patients’ chances for survival, but it also helps reduce unnecessary stress, says Wendy Thibodeau, the lung cancer nurse navigator at UConn Health’s Carole and Ray Neag Comprehensive Cancer Center.

“We have had patients where initial and subsequent biopsies are inconclusive. A decision then has to be made: remove the nodule surgically, or watch it for growth,” Thibodeau says.

“This can be stressful on a patient. They either have to go through a significant procedure they may not have needed or wait to see if the nodule gets worse. This technology will give us better accuracy for appropriate tissue sampling, making the decision more clear.”

A revolutionary precision technology is making early diagnosis easier than ever.

Routine screenings of high-risk patients — those with histories of smoking, especially — using low-dose CT scans and minimally invasive techniques help detect lesions and diagnose more people all the time.
The Monarch platform is the next step in improving outcomes for lung cancer patients, and Ibrahim sees even more groundbreaking advances on the horizon.

“Within the next year or two, this technology should allow us to treat lesions with radiofrequency ablation [a minimally invasive procedure that uses heat to destroy cancer cells],” Ibrahim says. “Diagnosis and treatment could be done all at the same time.”

In his time at UConn Health, Ibrahim has worked to improve the experience of UConn Health’s lung cancer patients, particularly through a multidisciplinary team that allows patients to come to one clinic to see a variety of doctors.

“Since we’ve enhanced and personalized the way we care for lung cancer, the number of lung cancer patients at UConn Health has quickly increased,” says Ibrahim. “Time to diagnosis and treatment is tremendously shorter, and patients are happier with the quality of their care.”

He believes the robotic bronchoscopy technology will allow the team to deliver even better results.

“The accuracy of this is going to pan out to be second to none,” says Ibrahim. “I think this is the tip of the iceberg in diagnosis, and the therapeutic aspect of it, which will evolve over time, is really exciting. Being at the forefront of that is amazing.”

Dr. Omar Ibrahim, UConn Health director of thoracic oncology and interventional pulmonology, demonstrates the Monarch technology.

Dr. Omar Ibrahim, UConn Health director of thoracic oncology and interventional pulmonology, demonstrates the Monarch technology.

Together for the Kids

By Lauren Woods

Dr. Emily  Germain-Lee  with a patient at the Albright Center at Connecticut Children's Medical Center.

Dr. Emily Germain-Lee with a patient at the Albright Center at Connecticut Children’s Medical Center.
Erin Blinn Curran/ Connecticut Children’s Medical Center


National recognition by external sources such as U.S. News & World Report comes as no surprise to the thousands who pass through Connecticut Children’s Medical Center each year.

What may be unexpected to those patients is that such success is the fruit of a more than 50-year legacy of the pediatric department at UConn School of Medicine advancing pediatric medicine, research, and education in Connecticut — and putting the health of the state’s tiniest residents first.

The life-changing work done by UConn’s Department of Pediatrics is made possible by a special partnership: Connecticut Children’s Medical Center is the teaching hospital where medical students, pediatric residents, and fellows are trained, as well as the home of the faculty’s clinical care work.

“UConn’s Department of Pediatrics’ strong relationship with Connecticut Children’s is excellent and seamless. There is no us and them. We are truly one, and we couldn’t excel without each other,” says Dr. Bruce T. Liang, the dean of the UConn School of Medicine since 2015. Liang has helped expand the two institutions’ joint recruitment of world-renowned physician-scientists and has led much of their growth in pediatric research.

For the Greater Good

The seeds of excellence in pediatric care in the Hartford area were planted in 1967 with the founding of UConn’s Department of Pediatrics, shortly before the medical school admitted its first class in 1968. UConn John Dempsey Hospital offered pediatric hospital care when it opened in 1975. Hartford-area hospitals had an informal agreement not to duplicate pediatric specialty services — patients were transferred among the hospitals based on their specialty care needs.

Connecticut Children’s was born in April 1996 after Newington Children’s Hospital, Hartford Hospital, and John Dempsey voluntarily closed their pediatric services so a comprehensive children’s hospital could open. It was established by state legislation and a 99-year lease of land on Hartford Hospital’s campus for 1 dollar per year. St. Francis Hospital and Medical Center’s pediatric programs were also incorporated. Uniquely, the leadership structure of the new pediatric hospital required that the same individual serve as both UConn’s Department of Pediatrics chair and Connecticut Children’s physician-in-chief.

“I am honored to have seen firsthand the strong evolution in pediatrics since my 1980s UConn pediatric residency training,” says Dr. Juan C. Salazar, who has served in that joint leadership role at UConn and Connecticut Children’s since 2013. “It is amazing that the strengths of four different Hartford hospitals came together for the greater good of our children and continue to offer the best pediatric care. It’s been an incredible success, allowing us to grow pediatrics clinically and educationally, along with our research mission.”

Salazar cites pediatric endocrinologists Dr. David Weinstein and Dr. Emily Germain-Lee as “two of several perfect examples of how the partnership of Connecticut Children’s and UConn really works seamlessly, with clinical services provided at Connecticut Children’s while robust laboratory research and clinical trials are under way at UConn.”

For 2018–19, U.S. News & World Report ranks Connecticut Children’s among the best hospitals in four pediatric specialties: cardiology and heart surgery, diabetes and endocrinology, neonatology, and urology. As one of the state’s largest care providers with 300 faculty members, UConn’s Department of Pediatrics has 31 medical and 13 surgical specialties.


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 with a patient
Peter Morenus


For a Brighter Future

In addition to translational research and top clinical care, UConn Health’s mission includes a third focus on teaching the practitioners of tomorrow. UConn is the largest educator for the state’s pediatric medicine workforce, as up to 60 percent of pediatricians in Connecticut have graduated from UConn’s medical school or its pediatric training programs.

Historically, UConn has also provided the largest pipeline of medical students into the state’s pediatric residency programs — each year up to 20 percent of UConn’s graduating medical school class chooses to specialize in pediatrics, entering residency training programs here or around the country.

“Along with research advancements, our significant focus is the education and training of our next generation of pediatricians and pediatric specialists, many of whom stay right here in Connecticut to serve the state,” says Liang.

UConn and Connecticut Children’s continue to strengthen their partnership in all three areas by building relationships with other organizations.

The two institutions in 2016 joined with another collaborator, The Jackson Laboratory (JAX) for Genomic Medicine located on UConn Health’s campus, to recruit Dr. Ching C. Lau, an internationally recognized pediatric brain and bone tumor clinician and researcher.

UConn and Connecticut Children’s look forward to growing their alliance, Liang says, and are planning joint physician-scientist recruitments in the fields of medical genetics and gastroenterology, as well as further collaborations in maternal-fetal medicine.


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World-renowned physician-scientists across specialties bring to life the vision of Connecticut Children’s Medical Center and UConn School of Medicine’s Department of Pediatrics. Read on to learn about three of the groundbreaking physician-scientists who are currently dedicated to improving the lives of children in Connecticut and around the world.


A Vision for the Future of Pediatric Cancer

In 2016, Connecticut Children’s and UConn joined with another collaborator, The Jackson Laboratory (JAX) for Genomic Medicine located on UConn Health’s campus, to recruit Dr. Ching C. Lau, an internationally recognized pediatric brain and bone tumor clinician and researcher, from Texas Children’s Hospital in Houston.

As medical director of hematology-oncology at Connecticut Children’s and head of the Division of Pediatric Hematology-Oncology in the Department of Pediatrics at UConn, Lau’s JAX-based laboratory aims to leverage new, sophisticated genomic medicine techniques, mouse models, and therapeutic treatments to choose the best therapy for patients and discover new treatments.

When he was awarded the inaugural Martin J. Gavin Endowed Chair in Hematology/Oncology at Connecticut Children’s, Lau said he was attracted to the vision and dedication of Connecticut Children’s Medical Center.

“I dream that one day when I look at a child diagnosed with cancer, I can look him or her in the eye and say, ‘You will be cured without having to come to the hospital for therapy. You just have to go home and take this medicine,’” he said.

Lau is focused on accelerating the pace and success rate of clinical trials in pediatric cancer patients. “Although the incidence of cancer among children is much lower than that in adults,” he says, “it can be just as deadly. And because of the smaller number of patients available, clinical trials of new treatments for pediatric cancers are conducted at a much slower pace. Typically patients are enrolled in clinical trials after their cancers progress or are found not to be responsive to standard therapy.”
As a result, he says, pediatric cancer patients are exposed to side effects of standard therapy without therapeutic benefit. “This is a particularly serious problem for children because they are still undergoing normal growth and are particularly vulnerable to the side effects of anticancer drugs.”

By using the combined approach of genomic medicine and accurate mouse models to choose the best therapy for each patient, Lau hopes to improve the speed and outcome of clinical trials as well as to reduce unnecessary side effects for children with cancer.

One way he’s speeding up the process is through Smash Childhood Cancer, an initiative he’s spearheading for the U.S. alongside international researchers and IBM to find prospective treatments for childhood cancers by conducting millions of virtual experiments to help pinpoint promising drug candidates for further study using IBM’s World Community Grid.

“This kind of research expedites finding new treatments for childhood cancers,” Lau says. “Crowdsourcing computer processing power enables us to perform millions of experiments virtually and will save us years of experiments. It is bringing us that much closer to finding the right drug for each type of cancer.”

 

Administering New Therapy — and Hope

In late July, a patient named Jerrod received a drug infusion that he’s been waiting for his entire life.

Jerrod was the first patient to receive a promising investigational gene therapy to treat glycogen storage disease type Ia, the rare, potentially deadly genetic disorder he was born with. Dr. David Weinstein, a world-renowned pediatric endocrinologist and director of the Glycogen Storage Disease Program at Connecticut Children’s Medical Center and UConn Health, has been working to develop the treatment for two decades and calls the trial “a big leap forward for GSD.”

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. Patients stay alive by consuming a cornstarch mixture every few hours to keep their blood sugar up.

The gene therapy undergoing the Phase 1/2 clinical trial, approved by the FDA in April, delivers a new copy of the gene to the patient’s liver to replace deficient sugar enzymes and jumpstart the body’s glucose control. Studies in animal models have already shown the promising gene therapy to be safe, effective, and long-lasting.

The clinical trial is in conjunction with the biopharmaceutical company Ultragenyx and will soon expand from UConn Health in the U.S. to other sites including Canada, Spain, and the Netherlands.

“This gene therapy is hope for all us GSD patients,” says Jerrod, who asked that his last name be withheld. “We are all extremely excited. Dr. Weinstein is a savior and so is the entire GSD program.”

Weinstein moved his GSD program — the largest in the world — to Connecticut Children’s and UConn Health in early 2017. His multidisciplinary team cares for 600 patients from 48 countries.

“The strong synergies and collaborative team science happening at UConn and Connecticut Children’s are world class and the most fertile ground to make a GSD cure reality,” says Weinstein.

 

Writing the Rulebook

Dr. Emily Germain-Lee, a professor of pediatrics and chief of pediatric endocrinology and diabetes, moved her first-of-its-kind Albright Center from Johns Hopkins School of Medicine and Kennedy Krieger Institute to UConn and Connecticut Children’s in October 2016. She has cared for more patients who have a specific rare set of endocrine diseases than any other doctor in the world.

“She has redefined the field of pediatric endocrinology,” Salazar said when the hire was announced. “Patients and families travel from all over the world seeking Dr. Germain-Lee’s care.”

Germain-Lee’s patients suffer from pseudohypoparathyroidism and its related disorders, including Albright hereditary osteodystrophy (AHO), a rare inherited bone disorder caused by a genetic mutation that often leads to short bones and short stature. It is also frequently accompanied by severe multihormonal dysfunction in the body.

This summer, Germain-Lee co-authored the first international guidelines to help doctors around the globe diagnose and manage patients with the diseases. The new guidelines call for human growth hormone treatment for the vast majority of the patients who are at risk for short stature due to growth hormone deficiency. Germain-Lee was the first to discover that part of the reason why AHO patients are short is that two-thirds of them have a growth hormone deficiency.

Her long-term global clinical trial studies have shown the promising benefits of growth hormone treatment, including its ability to drastically increase a patient’s short stature to their original destined height potential while also improving their lipid levels and reducing obesity. With her research in the final stages, Germain-Lee is working toward gaining FDA approval of the therapy, which would be the first new therapy for the disorder in 70 years.

“I am thrilled to be a part of the combined power of UConn School of Medicine and Connecticut Children’s Medical Center for advancing children’s health and discovering new treatments of disease through research,” says Germain-Lee.

Curators Versus Cancer

By Kim Krieger | Illustrations by Kailey Whitman

illustration of scientist look over hundreds of books

A special team of medical literature experts are on the hunt for cancer’s kryptonite, one mutation at a time.


If the genetic code is like a book, then a mutation is like a typo. Some typos are meaningless. Others have such dramatic consequences for a book, or a life, that the error alone could have an entire novel written about it.

Cancer mutations are like that. As oncology moves toward precision medicine — the idea that if we knew exactly which genetic mutations make a particular cancer tick, we could pick exactly the right treatments — oncologists have to keep up with an ever-expanding library of mutations and the drugs that might foil them. The number of cancer research papers published increases every year; there were about 35,000 published in 2015 just in the U.S. It’s far more than any one person can keep up with.

In the same way that a university has research librarians who keep up with the literature in specific fields, JAX has experts who keep up with cancer gene and drug research, even studies that are ongoing and not yet published.

A new collaboration between UConn Health and The Jackson Laboratory (JAX) hopes to help oncologists find the right treatments by keeping up with research for them — and using the institutions’ combined expertise in cancer treatment, molecular biology, and genetics to improve patient outcomes for cancers that currently don’t have good treatments. In the same way that a university has research librarians who keep up with the literature in specific fields, JAX has experts who keep up with cancer gene and drug research, even studies that are ongoing and not yet published. JAX already successfully connects these experts with doctors in the Maine Cancer Genomics Initiative, a philanthropy-funded statewide precision medicine program. UConn Health and JAX hope to expand the concept and demonstrate its feasibility more widely.

A UConn Health researcher holds a tumor sample.

A UConn Health researcher holds a tumor sample. Kristin Wallace

Bull’s Eye Treatment

Imagine that a patient has surgery or a needle biopsy to diagnose a tumor. It’s a particularly ugly tumor, the surgeon, oncologist, and pathologist all agree. Invasive, spreading, and perhaps this isn’t the first time this patient has had to come in for cancer surgery. The tumor is sampled and sent for genetic testing. In about two weeks, the results come back: there are three genetic variants in the tumor that might be drug targets.

At UConn Health, oncologists can send portions of particularly malignant tumors to a team at the JAX Clinical Laboratory. JAX sends back a report with information the oncologist can use to pick a drug regimen with the best chance to shrink that ugly tumor. “The goal is to define the optimal treatment regimen for each individual patient” who may not have good options otherwise, says Dr. Ketan R. Bulsara, chief of neurosurgery at UConn Health and one of the principal investigators on the project.

At UConn Health, oncologists can send portions of particularly malignant tumors to a team at the JAX Clinical Laboratory. JAX sends back a report with information the oncologist can use to pick a drug regimen with the best chance to shrink that ugly tumor.

The report is intended to be a standalone reference an oncologist can use to inform a treatment plan. But if the oncologist is unfamiliar with one of the mutations identified in the report or just wants more information, they can request that a genomic tumor board be convened. The board is composed of surgeons, pathologists, and molecular oncologists who act as external advisors, sharing their opinions with the oncologist. In just 15 minutes, the oncologist can get a wealth of expert opinion to combine with their own expertise and judgment. In the end, the oncologist and patient decide on the best treatment, based on all the available information.

“In a multidisciplinary fashion, doctors and scientists work hand in hand in this with one common goal: identify the best treatment regimen for that particular patient’s pathology,” Bulsara says.
The focus is always on the patient. But behind the scenes, there’s an entire team of researchers whose work goes into the genetic tumor report. Scientists at JAX Clinical Laboratory sequence the tumor’s genetic code and report information on more than 200 cancer-related genes. The genes were picked because they are associated with both malignancy and potential drug treatments. Any mutations or variants in these genes might be a clue to the cancer’s weakness. Or a red herring.

“A typical tumor might have 2,000 mutations. Not all of them really matter,” says Andrey Antov, the program director for the Maine Cancer Genome Initiative at JAX. Finding the key mutations that matter, the two or ten or twenty that could possibly inform treatment and a better outcome for the patient, is the job of the clinical genomic curators.

Personal Librarians

The clinical genomic curators are specialists in fields such as molecular oncology and oncological pharmacology. They’re dedicated to keeping up with the literature on cancer genes and the drugs that target them. More and more of these drug-gene connections are being discovered every day. It’s exciting, but the sheer volume of papers can be overwhelming. Navigating that ocean of scientific papers is the medical curators’ full-time job. They’re like librarians curating a Boston Public Library–size collection of genes and drugs with no cross references in the card catalog and only an imperfect search function. The hope is that just as a good librarian’s knowledge of the subject matter can unearth texts a researcher would never otherwise find, a medical curator’s grasp of oncological genetics and pharmacology can identify potential treatments that would otherwise remain obscure.

Each mutation identified by the genetic panel might require 10 to 20 scientific publications to understand. Once the curators have a handle on the variants’ significance, the clinical laboratory decides which two or three should be described in the report to the oncologist.

illustration of books in a library cart

Sifting the information down to something relevant and digestible is the ultimate goal.

“Today, all this information is disorganized and may not all be in the oncologist’s head. We’re trying to bring it together,” says Jens Rueter, medical director for the Maine Cancer Genome Initiative.

The ideal outcome of a tumor genetic analysis would be to identify a mutation such as the HER2 gene that is turned on in the most aggressive breast cancers. HER2 is responsible for the cancer’s malignancy. But it’s also the cancer’s Achilles’ heel. Once drugs were developed to block the HER2 protein, survival rates climbed sharply.

The goal of the Maine Cancer Genomics Initiative is to enable oncologists to identify other drug-gene connections as potent as the ones found for HER2. Although more and more of these drug-gene connections are being discovered, it remains difficult to provide a patient with access to these drugs. Many of them are only available if a patient participates in a clinical trial. And often, there are barriers to accessing clinical trials, and getting drugs off-label is the only way to get patients to treatments. That’s another benefit that Antov, Bulsara, and Rueter hope UConn Health’s collaboration with JAX will bring.

Positive Outcomes

Ultimately, the researchers hope to demonstrate that this approach leads to better outcomes for patients. During the past year more than 350 patients and 70 oncology practitioners (more than 80 percent of the Maine oncology community) enrolled in the Maine Cancer Genomics Initiative study protocol. A few patients have already been offered a targeted treatment through a trial or a compassionate drug access program as a result of enrollment in the program. And Maine health care professionals have logged more than 1,200 certified education hours through 35 genomic tumor boards, online modules, and annual forums held by JAX.

So far, five patients have done this at UConn Health within the last two months. Generous donors have given enough to fund 20 more.

The hope is that just as a good librarian’s knowledge of the subject matter can unearth texts a researcher would never otherwise find, a medical curator’s grasp of oncological genetics and pharmacology can identify potential treatments that would otherwise remain obscure.

“We hope to get funding for at least 100 patients to show the feasibility of this approach,” Bulsara says. “We want to show we can do this reliably, and that it reliably improves patient care.”

UConn Health already has the infrastructure to do this, in particular a biorepository for tumors set up by Neag Cancer Center Director Dr. Pramod Srivastava and pathologist Dr. Melinda Sanders. With that foundation and support from UConn medical school Dean Dr. Bruce Liang and UConn Health CEO Dr. Andrew Agwunobi, the program was piloted in the Department of Surgery by Bulsara, its chief of neurosurgery, with support from Department of Surgery Chairman Dr. David McFadden, hematology and oncology chief Dr. Susan Tannenbaum, anatomical pathology chief Dr. Qian Wu, and JAX Clinical Laboratory Director Honey Reddi.

If the UConn Health–JAX initiative does prove its feasibility, the approach will continue to spread and become a standard of care.

More oncologists could have access to the library of knowledge and advice of a genetic tumor board, and more cancer patients could benefit from longer, healthier lives.

Tumor samples are housed in UConn Health's research biorepository.

Tumor samples are housed in UConn Health’s research biorepository. Kristin Wallace

Better Ways to Heal Bones

Julie Bartucca

illustration of engineers going over blueprint of human skeleton with engineering notes on the hip bones

UConn Health is engineering innovative solutions for bone and joint problems, promoting faster recovery and less trauma to the body.


We’ve all signed a child’s colorful cast on their broken arm, gotten a call to inform us an elderly relative fell and broke a hip, or been laid up with back spasms ourselves. Maybe you’ve had a knee replacement or dealt with joint pain from years of athletic activity. It’s practically inescapable — 1 in 2 American adults suffers from a musculoskeletal disorder or injury such as arthritis, chronic back pain, fractures, or osteoporosis, according to 2016 data from the United States Bone and Joint Initiative (USBJI).

This is compounded by the fact that the U.S. has a rapidly aging population and, as people age, they lose bone density and the risks increase. Experts say the incidence of and costs to treat such issues are in danger of spiraling out of control.

But researchers at UConn and UConn Health are using a host of materials and technologies — from stem cells to spider-spun silk fibers to hydrogel to ultrasound waves — to strengthen bones and joints and accelerate recovery from musculoskeletal diseases and injuries.

“Musculoskeletal injuries are among the most common reasons to see a doctor. If we can take care of those faster and more effectively, patients can get back to their activities and work faster.”

“Musculoskeletal injuries are among the most common reasons to see a doctor. If we can take care of those faster and more effectively, patients can get back to their activities and work faster, which helps everybody,” says Dr. Augustus D. Mazzocca, director of the UConn Musculoskeletal Institute (MSI) and chair of the Department of Orthopaedic Surgery at UConn Health.

“There’s the economic impact of having people out of work, and the emotional problems of people who lose mobility and are isolated,” he says. “We’re trying to bring you back into society and get you back to what you like to do.”

To that end, UConn Health doctors also are developing ways to get you home faster after any musculoskeletal procedure, including spearheading same-day joint replacements.

Faster, Safer Recovery

UConn Health hip and knee replacement patients don’t have to wait for our clinical innovations to come to market. They can benefit from new approaches to the surgeries right now — and “right now” might also describe when they can go home post-op.

“Nearly 100 percent of my patients go home within 24 hours, and some now the same day,” says Dr. Mo Halawi, a new UConn Health orthopaedic surgeon who specializes in joint reconstruction and is spearheading an effort to minimize the time these patients spend in the hospital recuperating.

“The criteria for discharge are identical whether a patient leaves on the day of surgery or several days later. But with minimally invasive techniques, regional anesthesia, blood-conserving strategies, opioid-sparing analgesia, and immediate mobilization, patients are now achieving recovery milestones a lot quicker than before,” he says.

According to Halawi, the ideal candidate for same-day total joint replacement is one who is independent, motivated, has a good support system, and has no major risk factors for surgical complications. Much of the work is done in advance to optimize patients’ health and prepare them for surgery, allowing for the
speedy discharge.

After surgery, Halawi takes a less-is-more approach. Patients get on their feet right away and have no IV medications, drains, catheters, dressing changes, braces, or laboratory tests. Very rarely do his patients get discharged to nursing homes or rehabilitation facilities. Studies have shown that “patients recover better and have fewer complications in the comfort
of their homes,” he says.

“Hip- and knee-replacement surgery is constantly evolving, and we need to always deliver safe, effective, efficient, and evidence-based medicine to our patients. Soon, more surgeons and patients will realize that long hospital stays and recovery times are outdated,” Halawi says.

Engineering Cartilage

Though it is in the very early stages of development, UConn Health tissue engineer Syam Nukavarapu and his team have created a hybrid hydrogel system that they hope is the first step toward forming a hypertrophic cartilage template with all the right ingredients to initiate bone tissue formation, vascularization, remodeling, and ultimately the establishment of functional bone marrow to repair long bone defects.

How the more than 200 bones in an adult human skeleton form and how they are repaired if injured varies and has posed a challenge for many researchers in the field of regenerative medicine.

The cartilage template Nukavarapu and his team created appears to overcome hurdles that make it difficult for regenerative scientists to help the body’s long bones regenerate.

Two processes involved with human skeletal development help all the bones in our body form and grow. These processes are called intramembranous and endochondral ossification: IO and EO respectively.

While they are both critical, IO is the process responsible for the formation of flat bones, and EO is the process that forms long bones like femurs and humeri.

For both processes, generic mesenchymal stem cells (MSCs) are needed to trigger the growth of new bone. Despite this similarity, IO is significantly easier to re-create in the lab since MSCs can directly differentiate, or become specialized, into bone-forming cells without any additional steps.

However, this relative simplicity comes with limitations. To circumvent the issues associated with IO, Nukavarapu’s team set out to develop an engineered extracellular matrix that uses hydrogels to guide and support the formation of bone through EO.

“Thus far, very few studies have been focused on matrix designs for endochondral ossification to regenerate and repair long bone,” says Nukavarapu, who holds joint appointments in the departments of Biomedical Engineering and Materials Science and Engineering. “By developing a hybrid hydrogel combination, we were able to form an engineered extracellular matrix that could support cartilage-template formation.”

Nukavarapu’s team’s findings could be the first step to initiating the proper healing of long bones with biomedical help.

Using the Wisdom of Spider Webs

When someone breaks a load-bearing bone — the femur, for instance — doctors might install a metal plate to support the bone as it fuses and heals. But the metal can cause inflammation and irritation, and since metals are very stiff, the new bone may grow back weaker and more vulnerable to fracture.

UConn materials scientist and biomedical engineer Mei Wei and her team have developed an alternative to metal: a composite made with silk fibroin, a protein found in the silk fibers spun by spiders and moths and a common component in medical sutures and tissue engineering because of its strength and biodegradability.

Wei’s study found that the high-performance biodegradable composite showed strength and flexibility characteristics that are among the highest ever recorded for similar bioresorbable materials.

Working with UConn mechanical engineer Dianyun Zhang, Wei’s lab created a mix of silk and polylactic acid fibers coated in bioceramic particles. The new composite lasts about a year — large, adult leg bones can take many months to heal — and then starts to degrade. No surgery is required for removal.


Tissue engineer Syam Nukavarapu (left) examines a specimen of his hybrid hydrogel in his UConn Health lab.


Capturing the Power of Ultrasound

In the Department of Orthopaedic Surgery and the Institute for Regenerative Engineering at the UConn School of Medicine, researchers Yusuf Khan, Bryan Huey, and Lakshmi Nair are studying the combined power of gel-encapsulated bone cells and ultrasound waves to help fractured bones heal.

Physical force has been shown to stimulate bone cell regeneration for full healing, but immobilizing the fracture with a cast doesn’t allow for any movement. Khan believes that adding cells to the fracture site early on, and then directing a transdermal physical force toward the cells via low-intensity ultrasound, could accelerate fracture repair. In cases where a fracture can’t heal on its own, the therapy could provide the necessary stimulus to complete the healing process.

The team’s lab has already demonstrated the successful placement of bone cell hydrogels in mice and is working with the Department of Materials Science and Engineering to optimize the gel capsules for human use.

Harnessing Stem and Amniotic Cell Strength

Dr. Cato T. Laurencin, the Albert and Wilda Van Dusen Distinguished Professor of Orthopaedic Surgery and the director of the Institute for Regenerative Engineering at UConn Health, is developing clinical therapies to treat — and potentially reverse the effects of — osteoarthritis using human amniotic tissue, stem cells, and new combinations of the two.

An estimated 20 percent of Americans suffer from osteoarthritis, the most common degenerative joint disease and the leading cause of disability worldwide. Although current surgical and non-surgical therapies can provide some relief, none treat the root cause of the disease.

Stem cells have been proven to reduce pain and improve function in osteoarthritis patients. New studies suggest that the use of stem cells may heal cartilage, but results vary. Thanks to the host of powerful cytokines contained in amniotic tissue, many of which have been shown to decrease inflammation, Laurencin believes human amniotic tissue may overcome the limitations of current stem cell therapies, providing an ideal delivery system with added benefits.

“Soon, more surgeons and patients will realize that long hospital stays and recovery times are outdated.”

In its initial studies, Laurencin’s team has found its amnion-based delivery system can support stem cell survival, growth, and proliferation, and that the combination of amnion matrices and stem cells have immunosuppressive and anti-inflammatory effects on knee tissue cells.

“We believe amniotic tissue growth factors help drive human development and regeneration,” says Laurencin. “We are hopeful that harnessing this powerful new cell combination will help us further advance regenerative engineering for patients, especially those with arthritis or sports injuries, who want to avoid steroid treatments or are interested in next-generation therapies.”

Although it is not yet covered by insurance, amnion tissue treatment is available now to Laurencin’s patients. Laurencin’s team hopes to make the combination amnion¬stem cell therapy available within the next three years.

From the advanced research that’s changing the care of the future to the clinical changes happening now, Musculoskeletal Institute head Mazzocca says the Institute is uniquely positioned to provide the best possible care to patients.

“We try to take all the clinical people that treat musculoskeletal disease — rheumatology, osteoporosis, comprehensive spine, orthopaedics — and put it in one place, and combine them with all the researchers so they can cross-pollinate and make care better for the people of the state of Connecticut,” he says. “And there’s nobody else in the state of Connecticut that does what we do.”

Jessica McBride, Colin Poitras, and Lauren Woods contributed to this story.

Unraveling

By Kim Krieger | Illustrations by Yesenia Carrero

illustration; two silhouettes, one with a scribble pattern overlayed over top. looks to scribbled circular dot between them

PTSD can undo a sufferer’s life. MDMA may help patients untangle their trauma and find their way back to mental health.


When lasting trauma is caused by callous acts of violence, the key to recovery can be making meaning from meaninglessness.

This year UConn Health will host a phase 3 FDA trial that tests whether the drug MDMA, known on the street as ecstasy or molly, is a safe and effective treatment for post-traumatic stress disorder. The disorder is difficult to treat, and many people have a tough time handling the treatment. MDMA not only might make therapy more tolerable but it also may help open a window for patients into their own mind. The insight allows them to process a shattering, horrific event into something that makes them stronger.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders defines post-traumatic stress disorder, or PTSD, as when a person is traumatized in some way and then continues to reexperience the trauma through flashbacks, nightmares, or unwanted intrusive memories. The person with PTSD avoids people or places associated with the trauma; becomes overly negative in thoughts and speech about themselves and other people; and has heightened arousal that can include a hair-trigger startle reflex, inability to sleep, hypervigilance, irritability, and aggression. At its worst, people are unable to cope with everyday life and may even become suicidal.

Often the source of the trauma is a shocking event involving interpersonal violence, such as rape, combat, or sexual abuse. Racial discrimination and harassment, particularly when it is shocking or pervasive, can also cause PTSD. UConn psychologist Monnica Williams began focusing on race-based trauma when she was at the University of Pennsylvania and had a very successful, high-achieving, black client come in with PTSD stemming from racial discrimination she’d suffered on the job. Williams was taken aback and began studying the link between racism and post-traumatic stress disorder.

Deconstructing the Trauma

But no matter what type of trauma causes the PTSD, the most effective treatment for it is exposure-based therapy, such as “prolonged exposure.” Essentially, the therapist has the patient discuss the traumatic event in excruciating detail, over and over again, until it ceases to cause overwhelming fear and anxiety.

Prolonged exposure works — indeed, it has the most evidence behind it. But it’s terribly difficult for the patients, who often get visibly upset during sessions, and many quit therapy because the experience is too much like the original trauma.

The MDMA-assisted therapy session was utterly without the distress, tension, and fear PTSD patients typically show during prolonged exposure treatment.

MDMA-assisted psychotherapy could be one way to change that. The drug stimulates the release of neurotransmitters that promote a feeling of trust and well-being and might also help the brain rewire itself. But when Williams first heard of it, she was skeptical.

“It sounded weird, like junk science, and I didn’t want to be part of that,” she says. But she agreed to take a look at an article in Psychopharmacology. She was fascinated to see that researchers had used MDMA as an adjunct to psychotherapy for PTSD and had gotten really good results. She was pleasantly surprised again when she first watched a video of an MDMA-assisted therapy session.

“People were sitting in a chair, relaxed. They’re processing it on their own, and would sometimes share new insights with the therapist,” Williams says. It was utterly unlike the distress, tension, and fear PTSD patients typically show during prolonged exposure. “They would say things like, ‘Wow. Now I understand the trauma didn’t happen to me because I’m a bad person — I was just in the wrong place at the wrong time.’ And we’re like, ‘Yes! Yes! They finally get it!’” she recalls. The MDMA helps them look at the big picture, to understand that the violence against them didn’t mean what they thought it had.

‘It’s got to come out’

It takes a while for psychoactive drugs to work their way through the FDA approval process. MAPS has been testing MDMA-assisted therapy for PTSD for more than a decade. Many of the early participants experienced lasting improvement.

Rachel Hope, who experienced a cascade of abusive events as a child that left her with severe PTSD, “did 20 years of psychotherapy” prior to participating in an MDMA-assisted therapy session. “When I got into the outer limits of the really hardcore stuff, I’d start to destabilize and get sicker … I’d start vomiting or have to leave the room. I knew that I had to tell it — the story has a soul of its own. It’s got to be seen, got to be known. It’s got to come out. But I couldn’t get it out,” she says.

Hope had had good therapists and managed to run a real estate development company, but eventually the PTSD got so bad she couldn’t leave the house. Finally her personal assistant threatened to quit if she didn’t go back into therapy. And that’s how she came to participate in an MDMA-assisted psychotherapy trial in 2005. It was a revelation.

“The MDMA was a terrific antianxiety medicine,” she says; it didn’t make her fuzzy-headed like most antianxiety meds had. “It amplified access to memories and, really, I had access to everything, and I wasn’t terrified. I could actually tell someone, for the first time in my life, what had happened to me. I had so much access to my own mind.” She describes it as the perfect tool to help work through the trauma. “I was rebooting my mind under my own directive,” Hope says.

“They would say things like, ‘Wow. Now I understand the trauma didn’t happen to me because I’m a bad person — I was just in the wrong place at the wrong time.’ And we’re like, ‘Yes! Yes! They finally get it!’”

Williams agrees that the MDMA seems to help patients rapidly make connections and breakthroughs in a single therapy session. Typically, a patient in psychotherapy might have just one such realization every few months.

The participants in the phase 3 trial at UConn Health will have a total of 20 therapy sessions, three of which will include MDMA. Each session will have two therapists present. The MDMA-assisted sessions will be six to eight hours long, after which the participant will stay overnight in the hospital to rest, supervised by a night attendant. And as part of the effort to involve participants from communities of color, all but one of the therapists at UConn Health identifies as an ethnic, racial, and/or sexual minority.

“In Singapore, I was part of the majority, but I was curious how it felt to be Malay, Indian, or one of the other minorities,” says Terence Ching, a clinical psychology doctoral student involved in the study. Ching has also lived in Australia, New Zealand, and Kentucky, where he was not part of the majority ethnic group. “That led me to critically introspect my place in society as someone with many different identities. Having that multifaceted perspective allows me to experience a lot of empathy for people from marginalized groups in the U.S.,” Ching says.

To get a better understanding of what the MDMA-assisted psychotherapy would be like for study participants, Ching participated in a session himself as part of his training.

“It felt like a lot of insights happening constantly,” Ching says. “It’s been a year since the session, and every now and then I have a moment where I remember an insight from it, and/or have another one. It’s a wonderful thing.” Ching hopes that the participants benefit from their MDMA-assisted psychotherapy in the same way he did.

“For someone who has experienced trauma, MDMA-assisted psychotherapy might help them be able to make meaning of it. I really believe in this work,” Ching says.

Women on Women’s Health

By Kim Krieger

Photography by Tina Encarnacion

line art of woman doctor and patient

Women doctors were a rarity in the U.S. until just a few decades ago, and it wasn’t easy for a woman seeking a female obstetrician or general practitioner to find one. But times have changed — women surgeons, doctors, and health care practitioners of all sorts are everywhere.

At UConn Health, we’re proud to have an army of women caring for women in every specialty, as doctors, therapists, and nurses. Many have advanced degrees and research projects in addition to their clinical work.

We spoke to just a few of the many, many women who do research and provide clinical care for other women at UConn Health. We asked them why they do what they do, how caring for women is different than caring for men, and anything else they thought was important. This is what they said.


Gynecological Surgery

I need you to take it easy for just one week.

Dr. Danielle Luciano’s patients are usually younger women with pelvic pain or unmanageable periods related to uterine fibroids or endometriosis. Luciano tries medical treatments with the women first. If that doesn’t work, she offers minimally invasive surgery that solves the pain while sparing her patients’ fertility.

Dr. Danielle Luciano

Dr. Danielle Luciano cares for women throughout their lifespans.

“As an OB/GYN, I take care of my patients throughout their lifespan. I might remove their endometriosis when they are young,” and help them in menopause too. As a fellow woman, she can relate to her patients and perhaps give them more convincing advice than a male doctor might.

“I’ve had some babies, and I’ve had to have some things fixed afterwards, so I know where they’re coming from,” Luciano says. “I can say, ‘Look, I know you’re going to go home and try to do 1,000 things. But I need you to take it easy for just one week.’”

Fibroids and endometriosis affect a lot of women, around 10 percent. Oftentimes these conditions run in families, and a mom may normalize it when her daughter suffers, explaining the same thing happened to her. But if a woman has miserable periods with such heavy bleeding, terrible pain, or gastrointestinal symptoms that she can’t work or go to school, there could be something wrong that Luciano can help with.

Professions sometimes run in families, too. Luciano’s father, Dr. Anthony Luciano, is also an OB/GYN at UConn Health, specializing in reproductive endocrinology and minimally invasive surgery.

“Initially I didn’t want to do anything he did — but the more I learned, the more I wanted to have that skill and expertise,” Luciano says.

She and he now work together; he is a member of the Center of Excellence for Minimally Invasive Gynecologic Surgery at UConn Health. She is the director.

Breastfeeding

If lactation is a superpower, nursing is an art.

If lactation is like a superpower — a woman makes milk, and it’s perfectly nourishing, antibacterial, immunity-boosting, and always exactly the right temperature — then nursing is more of an art, a skill women learn by observation or instruction.

But fairly often in the U.S., women have trouble with it, and end up pumping or formula feeding even if they’d rather nurse.

“Whenever we talk about breastfeeding it becomes a very hot and emotional conversation,” UConn nurse-scientist Ruth Lucas, Ph.D., RN, says. She wants to cool that conversation off with data.

Lucas spent 20 years working as a nurse and lactation specialist, “supporting mom in whatever way she can feed her baby and feel good about herself.” But the more she saw, the more she wondered why for so many women breastfeeding just didn’t work. So she turned to research, and her first project has zeroed in on pain during nursing. Why does it happen, and how can we help women who want to nurse but find it agonizing?

She’s finishing up a pilot study that tracked women who initiated breastfeeding, their experiences, and their gene variants that might be linked with pain. And that’s just the start. She’s also interested in the baby side of the equation: different babies approach breastfeeding differently. Does this affect mom’s pain? Does the pain change the breastmilk? Does that affect the babies?

“We all want to grow and nurture our children,” Lucas says. She wants to nurture the women, too.

Pelvic Health

Cultural taboos prevent patients from admitting that they have issues.

Lauren Brennan and Cathy Trahiotis want you to talk to your patients about peeing. And sex. Also bowel movements. Like, how often does your patient poop?

“If they say ‘once a week,' you know there’s a problem,” Brennan says, laughing. She’s a family nurse practitioner who works in the urology practice at UConn Health. Trahiotis is a physical therapist who specializes in women’s pelvic health. And they’re on a mission to educate people — and alleviate people’s fears — about incontinence and other pelvic problems.

Recent studies have found that almost half of adult women experience either stress incontinence — involuntary urination when coughing or exercising — or urge incontinence, when they feel the urge to urinate but can’t get to a toilet in time.

“But it’s not normal to have incontinence! We can treat it,” says Trahiotis.

Dr. Cathy Trahiotis and Dr. Lauren Brennan

Cathy Trahiotis and Lauren Brennan want docs to talk to patients about peeing. And sex.

She notes that for some women, pregnancy can be the start of pelvic issues. The heavy, swelling uterus presses on nerves in the pelvis, stretches ligaments, and separates the abdominal muscles (a condition called diastasis recti). After birth, if the abdominals don’t knit back together, it leads to weakness that can force the pelvic muscles to compensate, stressing them and potentially causing pubic pain or incontinence.

Fortunately diastasis recti can usually be cured with physical therapy. Other issues involving the pelvic muscles can be similarly healed through specific exercise, stretching, and diet.

In her urology practice, Brennan often sees patients with dyspareunia, or painful sex. It can often be treated. But it’s almost never the reason the patient made the appointment, Brennan notes. She always has to ask.

Both Brennan and Trahiotis say cultural taboos against discussing bodily functions prevent patients from admitting to their doctor that they have issues. So doctors should bring it up first. Ask patients directly: “How’s sex for you? Is it comfortable? Do you have any issues you’d like to talk about?” Ask about peeing and bowel movements. Or if your patients are super shy about discussing it, perhaps a written questionnaire would be better.

No matter how you do it, Trahiotis and Brennan say, the bottom line is “know about it, talk about it, don’t be afraid! And fix it without surgery!”

Dermatology

Sometimes she’ll point out something I can’t see. That’s when I reassure her.

The trick to drawing out a patient’s concerns about her skin is to hand her a mirror, says UConn Health dermatologist Dr. Mona Shahriari.
“Sometimes she’ll point out something I can’t see. That’s when I reassure her. I’m a trained dermatologist, and if I can’t see it, the world probably can’t, either.”

Dr. Mona Shahriari

Dr. Mona Shahriari wants women to feel like at least once, they're being taken care of.

Shahriari has seen a lot. The year before she entered medical school, she volunteered to work with individuals exposed to radiation and chemicals during the Iran-Iraq War. They had a tendency to grow bizarre forms of skin cancer. Many of them would try to hide the growth and ignore it. And now, even though she’s practicing medicine on the other side of the planet with an entirely different population, some of her female patients have a similar problem.

“They’re so busy caring for their families they forget to care for themselves. Women often show up with undiagnosed skin diseases” they’ve been ignoring, says Shariari. When they finally do make it to her office, she gives them the time they need. Most of the time her women patients come to her with concerns about skin cancer, but there’s usually another underlying worry: aging.

“Society makes women very self-conscious about their appearance,” says Shahriari. And their skin is readily visible to the world. So she listens, and helps them. Ultimately, a patient may need bloodwork, a biopsy, laser treatment, or reassurance. But no matter what, “I make them feel like at least once, they’re being taking care of. Their concerns are the priority.”

Gynecologic Oncology

Some women say “I just can’t do this anymore.” But we have lots of options to help.

The patients keep her going. Many of the women are overweight. A lot of them have diabetes and high blood pressure. They don’t heal well; they’re greater surgical risks; they’re medically fragile. And yet, they keep going. And so does she.

“I love my patients,” says gynecologic oncologist Dr. Molly Brewer, chair of UConn Health’s Department of Obstetrics and Gynecology. “They endure so many incredibly hard treatments. They’re an inspiration.”

Dr. Molly Brewer

Dr. Molly Brewer says getting cancer patients healthy and back to their lives makes the challenges of her job worth it.

Typically, the women are referred to her by primary care physicians, gynecologists, or emergency room doctors when the women show up with a suspicious lump in their abdomen, cervix, or vulva. Such patients are usually urgent, and Brewer always gets them into her office within a week or less. If they don’t have cancer, she sends them back to their regular doctor. But if they do have cancer, she cares for them from the beginning to the end, performing surgery to remove the mass, treating it with anti-cancer drugs, and helping them through into remission. She also cares for certain breast cancer patients who suffer from unique gynecological issues. Certain drugs used to prevent a recurrence of the cancer can cause vaginal atrophy because they suppress estrogen, for example.

“Vaginal atrophy makes sex really painful. Some women say ‘I just can’t do this anymore.’ But we have lots of options” to help, Brewer says.

Her research centers on ovarian cancer and new technologies to diagnose it. She and her partner, newly arrived gynecologic oncologist Dr. Bradford Whitcomb*, are currently enrolling patients for an ovarian cancer vaccine study.

She chose gynecologic oncology because she loves it, and she loves it because of the patients. The challenge of taking care of women with difficult cancers, and the inspiration of watching them make
it through.

“When we get them into remission, they’re healthier, they feel better, they’re able to go back to their life. And that makes it all worth it.”

The Power of Our Women

By Lauren Woods

Photography by Peter Morenus

Dr. Molly Brewer, Dr. Marja Hurley, Dr. Cheryl Oncken, and Dr. Laurinda Jaffe are among the women leading UConn Health’s departments.

At UConn Health, dedication to the achievements of women in medicine and science dates back to our founding in 1968. Efforts to achieve gender parity in our student body and among faculty and staff and their positions as leaders have grown over the decades.

Dr. Molly Brewer, Dr. Marja Hurley, Dr. Cheryl Oncken, and Dr. Laurinda Jaffe are among the women leading UConn Health’s departments.


In 2017, the number of women enrolled in American medical schools surpassed the number of men for the first time, according to the Association of American Medical Colleges. And, UConn’s schools of Medicine and Dental Medicine were part of that demographic shift.

There are now more female than male students enrolled — 207 female medical students comprise 50.7 percent of the student body, while 94 female students make up 52.5 percent of the dental school’s student body.

Although the first class admitted to the UConn School of Medicine in 1968 was all men, the faculty has included women from the start. Over the years, the number and roles of women at UConn Health have grown significantly since four accomplished women stood among the founding faculty.

“Since UConn Health’s inception, highly accomplished and dedicated women have always driven UConn Health’s success in research, education, and the patient care mission,” says UConn Health CEO Dr. Andy Agwunobi. “These amazing professionals, and those who join us every day, are key to our past and future success.”

Today, 73 percent, or 4,098, of the total employees who fuel UConn Health’s clinical care, research, and education initiatives are female. Across the enterprise, 895 women hold faculty or community faculty appointments and 217 women are full-time UConn Health faculty. There are nearly 800 female nurses.

Among the women leading the charge are department chairs on the front lines of advancing medicine and cutting-edge research: Dr. Molly Brewer in Obstetrics and Gynecology, Dr. Cheryl Oncken in Medicine, Dr. Melinda Sanders in Pathology and Laboratory Medicine, Dr. Laurinda Jaffe in Cell Biology, and Dr. Sandra Weller in Molecular Biology. Many others serve as associate deans.

I have been able to achieve everything that I’ve wanted to at UConn Health, from becoming a leader to teaching and my efforts to enhance our student curriculum.

Dr. Marja Hurley, the School of Medicine’s associate dean for health career opportunity programs, was the first woman of color to attend UConn’s medical school in 1972 and one of eight female students in the class.

In addition to a stellar career as an NIH-funded physician-scientist conducting research on the molecular basis of osteoporosis and osteoarthritis, Hurley has dedicated the past three decades at UConn Health to advocating for women and other underrepresented groups in medicine and science. Through health career opportunity programs including the Doctors Academy, High School Mini Medical/Dental School Program, and the Summer Research Fellowship Program, Hurley also works to expand the interest of high school and college-aged women and men in science and medicine.

“It’s been a pleasure to spend my education, training, and career here at UConn and to help diversify the schools of Medicine and Dental Medicine with more underrepresented groups, including women,” says Hurley.

Currently, groups that are traditionally underrepresented in medicine and science comprise 22 percent of UConn Health’s student body.

“We have made tremendous progress,” she says.

As an American Association of Medical Colleges liaison, Hurley in 2011 launched a Group on Women in Medicine and Science (GWIMS) chapter at UConn Health. Its mission is to connect women at the institution and promote their career success within the academic medical center by addressing issues such as salary and gender equity, recruitment and retention, awards and recognition, career advancement toward full professor, and work-life balance.

Recently, GWIMS member Kristyn Zajac, Ph.D., assistant professor in the Department of Medicine, helped establish a “Mini Mentoring Program.” More than 70 senior faculty volunteered to serve as mentors to female junior faculty.

Dr. Ellen Nestler, internist and associate dean at UConn School of Medicine, was assigned to mentor Evelyn Neuber, Ph.D., an embryologist and clinical research coordinator at the UConn-affiliated Center for Advanced Reproductive Services.

“I was able to give her tips and tools on how to empower herself to lead and work more effectively with her new team members and management responsibilities in the laboratory,” Nestler says. “Women need mentors, and this new, unique program adds to a woman’s armamentarium.”

Says Neuber, “The mentoring program was really helpful. It was educational and also fun to meet with a fellow woman at work who has gone through similar work situations and to discuss the female experience relating to working in science and personal work-life balance.”

Melinda Sanders, chair of the Department of Pathology and Laboratory Medicine, joined UConn Health 26 years ago and was promoted to chair in 2010.

“I have been able to achieve everything that I’ve wanted to at UConn Health, from becoming a leader to teaching and my efforts to enhance our student curriculum,” she says.

Educating the new, more representative class is critical as they will be the next generation of providers.

“Here at UConn Health, we really do want to foster women and develop the careers of future generations of women in health and science,” she says.