By carefully combining information from previous studies with the results from these two recent clinical trials, the researchers showed that the therapies tested in the recent trials now show stronger evidence of meaningfully improving outcomes in children with high-risk Group 3 medulloblastoma.

High-risk Group 3 medulloblastoma is a fast-growing and notoriously hard-to-treat childhood brain cancer. Because so few children are diagnosed each year, even large national studies can enroll only a handful of patients. In one of the trials, only 10 children with this tumor type received the new therapy. In another, only 43 children were treated, despite the fact that the trial was open in dozens of cancer centers in the United States.

Unfortunately, these numbers are too low to thoroughly evaluate a therapy’s effectiveness using traditional analysis methods.

“These small numbers make it extremely difficult for traditional statistical methods to show with certainty whether the therapies truly work,” said , a neurosurgeon and scientist at UofL and who led the reanalysis study. “As a result, promising treatments for these children can remain in limbo – not because they fail, but because the evidence isn’t strong enough using traditional approaches.”

To overcome this challenge, the UofL team used a novel statistical approach called dynamic borrowing via Bayesian models, which carefully “borrows” information from previous studies to strengthen the results of new trials. The idea is to let the model learn how similar the past and present data are, and to borrow more past data that match and less when they differ. The researchers ran 10,000 computer simulations using this process, ensuring that the findings remained both reliable and not artificially inflated.

Using this method, they reanalyzed data from two recent national trials and found a greater than 90% probability that the therapies tested in the clinical trials truly do provide benefit for children with high-risk Group 3 medulloblastoma. The therapies that had limited statistical power under traditional analyses now appear strongly promising under the new approach and as a result, may warrant renewed consideration as effective treatment options.

For children and families facing the devastating diagnosis of this aggressive cancer, these findings bring renewed hope that these treatments are not only worth trying but also are likely to be effective.

The research team in September.

“This work is part of a larger effort at UofL to modernize how we design, conduct and analyze clinical trial data, helping scientists and physicians learn as much as possible from the small, precious data that take years to collect in rare diseases,” Mistry said. “Our goal is to make the most of every patient’s experience – past and present – to improve the care of future patients. It is our way of honoring every child and adult who participates in clinical trials by ensuring their contributions continue to shape the treatments of tomorrow.”

Mistry, who was profiled in the  also led a team that recently published the , showing the composition of tumors at the genomic level, combined with clinical information such as patient age, tumor location and survival outcomes. This  is a free, publicly available tool that promises to speed up the discovery of treatments for brain and nerve tumors, especially rare ones that have had limited research attention, like Group 3 medulloblastomas.

This project was supported by the Kentucky Pediatric Cancer Research Trust Fund and the Kentucky Department for Public Health. Mistry’s work also is supported by the Louisville Clinical and Translational Research Center at UofL and by a UofL Presidential Scholars award.

According to the , more than 750,000 people in the U.S. will have a stroke each year. In Kentucky, strokes are the fifth leading cause of death, underscoring their significant impact both locally and nationally.

Recognizing the urgent need for improved therapies, and the University of Louisville are actively participating in a pivotal clinical trial known as the . This study focuses on patients who come to the emergency department 4.5 to 24 hours after the onset of an ischemic stroke and who are not candidates for standard treatment methods, such as previously approved clot-dissolving medications or mechanical interventions.

Upon arrival, patients undergo a comprehensive evaluation and advanced imaging to determine eligibility. If they meet all criteria, they may be enrolled in the study and randomly assigned to receive one of five doses of the investigational drug TS23, a type of clot-dissolving drug, or a placebo. The treatment is delivered through a single 20-minute infusion, followed by close monitoring and imaging at 30 hours post-treatment, with additional follow-up evaluations at 30 and 90 days to assess outcomes and recovery.

a neurosurgeon with , a part of , and associate professor in the Department of Neurological Surgery at the , leads the study at the Louisville site.

“By bringing this trial here, we are creating an opportunity for patients in town to get access to cutting-edge therapies that they otherwise could not access and at time windows during a stroke that typically prohibit them from getting a treatment drug. That is exciting,” Abecassis said.

Through innovative research initiatives like the SISTER trial, and UofL School of Medicine are working to enhance recovery, reduce long-term neurological damage and expand access to advanced stroke care. These efforts create opportunities for more personalized treatment, offering hope to patients and their families facing the life-altering effects of stroke.

Recognizing the signs and symptoms of a stroke is crucial. The acronym BE FAST can help you remember the most common warning signs:

• Balance lost – sudden loss of balance or coordination
• Eyes blur – sudden trouble seeing or blurred vision in one or both eyes
• Face drooping – one side of the face droops or is numb
• Arm weakness – sudden weakness or numbness of an arm or leg, especially on one side of the body
• Speech difficulty – sudden confusion, trouble speaking, or difficulty understanding speech
• Time – note the time the symptoms started and call 911 immediately

If you or someone around you experiences any of these symptoms, seek emergency medical care right away. Quick action can make a significant difference in treatment and recovery.

By Allison Dulin, UofL Health

result from a weakened area in an artery of the brain that fills with blood and causes outward bulging or ballooning.

The Saccular Endovascular Aneurysm Lattice System Interventional Pivotal Trial () focuses on the safety and effectiveness of the SEAL system, which can be used to treat patients with ruptured and unruptured brain aneurysms in a range of sizes.

“I’m excited to be a part of groundbreaking aneurysm treatment research, and for the opportunity to bring patients in Louisville and the surrounding region a novel treatment option not yet widely available,” said  a neurosurgeon with Brain & Spine Institute and assistant professor in the UofL Department of Neurological Surgery. “The device is small enough that we can use a minimally invasive technique via an artery in the groin to deliver the device and disrupt the blood flow to the aneurysm, causing it to clot and heal, while decreasing the need for more invasive procedures like a craniotomy.”

Patients with brain aneurysms are usually asymptomatic until their aneurysm ruptures. A ruptured aneurysm is a form of stroke and a potentially life-threatening condition that can result in brain damage or death.

“As an academic health care system affiliated with the University of Louisville, we are committed to providing our patients with the latest innovative treatments, including those offered through clinical trials,” said Joshua Beardsley, system vice president of neurosciences and spine. “I’m proud of our providers for helping to pioneer the next generation of aneurysm care.”

About SEAL IT

SEAL IT is a prospective, U.S. and international single-arm, multicenter, interventional study. The clinical trial seeks to establish the safety and effectiveness of the system in treating patients with wide neck unruptured or ruptured intracranial aneurysms that are less than or equal to 19 millimeters in widest diameter. Data such as imaging and patient presentation will be collected from participants immediately after their procedure in addition to three, six and 12 months after their procedure. Participants will receive follow-ups annually for five years.

A newly published clinical trial led by University of Louisville physicians has shown that a computer-assisted cognitive behavior (CCBT) therapy can overcome these barriers while providing effective treatment for depression.

Jesse Wright, professor of psychiatry at UofL and director of the , documented treatment results for a diverse group of 175 adults for depression. The study, published in in February, showed that patients in a primary care setting who participated in CCBT reported significantly greater improvement in their depressive symptoms than those receiving treatment as usual.

“With modest amounts of telephone support from a clinician, CCBT was associated with greater improvement in depression, anxiety and quality of life than usual treatment in a diverse group of primary care patients. We were pleased to see that CCBT had more than double the remission and response rates as usual treatment,” Wright said.

“There has been a historical lack of effective care for depression in the primary care setting,” he said. “Because this study population included people with lower income and lack of internet access, results suggest that this form of treatment can be acceptable and useful in diverse primary care settings.”

Rather than requiring frequent office visits, a patient can engage in CCBT online whenever their schedule allows and from the comfort of their home. A primary care provider can monitor and support the patient’s progress, helping patients who may not desire or be able to see a psychologist or psychiatrist for their therapy.

“Particularly during the COVID pandemic, we have seen how limited appointments are for mental health services and the rise of telemedicine has led to increasing comfort with utilizing technology to support health, which makes computer-assisted cognitive behavioral therapy a great option,” said Laura Bishop, an associate professor and internal medicine-pediatrics physician at UofL and a co-author of the study.

In the study, CCBT participants used the nine-lesson computer program “Good Days Ahead,” along with as many as 12 weekly telephone support sessions with a master’s level therapist, along with the treatment usually provided by the primary care sites.

“I think this is a preferable option for younger patients who often are more comfortable with self-reflection and working through the CCBT on a computer rather than meeting face-to-face with a provider,” Bishop said. “We’ve seen more and more familiarity with wellness and meditation apps over the past few years that have paved the way for CCBT to be widely accepted.”

Wright began work on computer-assisted therapy in the 1990s and led the initial development of Good Days Ahead. In addition to depression, Wright said CCBT also could be adapted to treatment for obsessive-compulsive disorder, anxiety, eating disorders or other conditions.

Patients in the Louisville area can request use of Good Days Ahead through the .

Good Days Ahead is being reviewed by the U.S. Food and Drug Administration under a new protocol for certification of therapeutic computer programs.

Wright retains an equity interest in MindStreet Inc., the company that now manages Good Days Ahead.

On one level, it was a dream come true, but he had to think carefully about it before accepting.

Before he enrolled, he took stock of his goals. Did he have expectations about what he might gain? Was he doing it only for himself? Finally, he was about to get married and it would require relocating to Louisville from his home in New York City for an extended period of time.

Ultimately, he decided his participation could benefit other older SCI patients and those longer post-injury – he was 55 years old and 39 years post injury. The possibility that he could benefit personally was a bonus – but an exciting one.

“My wife said I would be regretting it for the rest of my life if I didn’t do it,” Stifel said. “I admit I was like a kid in a candy shop – I wanted that candy! But I knew I would have to work extra hard.”

From philanthropist to participant

Stifel was 17 years old in 1982 when an auto accident left him paralyzed, unable to walk or use his hands. With support from his family and community, he got on with life, graduating from high school, then college with a degree in finance and pursuing a career on Wall Street.

Hoping to change the trajectory of spinal cord injury research, dubbed the “graveyard of neuroscience,” Stifel and his father started a foundation to raise money and fund research that would give hope for recovery to people with spinal cord injuries. That foundation eventually merged with the American Paralysis Association and later with what now is known as the Christopher and Dana Reeve Foundation, supporting research and advocacy for individuals with spinal cord injury (SCI).

As a board member of the foundation throughout its history, Stifel followed the work of SCI researchers, particularly UofL professor Susan Harkema and . He was impressed with the progress they made using implanted epidural stimulators, from Rob Summers, the first individual implanted with a stimulator for SCI research, to additional participants who experienced voluntary movement, improved cardiovascular function, the ability to stand and improved bowel, bladder and sexual function. Some even took steps because of the implant and specialized therapy developed by the UofL team.

Stifel, now in his 50s, was gratified to see this progress and support the work through the foundation, including “The Big Idea,” a 36-participant study of the benefits of epidural stimulation funded by the Reeve Foundation and led by Harkema. The previous participants were younger and had a shorter length of time since their injury. Although he had been to Louisville to participate in other studies, Stifel believed that because it had been nearly 40 years since his injury, it was unlikely he would be able to participate in the epidural stimulation studies.

Then in 2018, Stifel got a call to participate in The Big Idea. Since his deficits were stable, which gave the researchers a solid starting point to document any gains or changes he might experience, he qualified.

When he arrived in Louisville for the study in 2020, he knew that nothing was guaranteed.

“I understood that you need to go in with zero expectations,” Stifel said. “You can only have expectations if the therapy is proven, but it is still being tested. My goal was to be involved and represent others who are injured as long as me. I wanted to help the research progress.”

Blood pressure regulation and stand training

Stifel’s overall health had remained relatively stable in the years since his injury, without many of the comorbidities people with severe SCI often experience. The one side effect he did have was chronic low blood pressure.

“My blood pressure was typically 80/50, which can be debilitating,” he said. “I became used to it, but it is not a healthy way to live. When I was giving a presentation or having a conversation, I would find myself distracted.”

Once enrolled in the study, Stifel underwent preliminary assessments followed by the surgery to implant the electrode on his spine and the epidural stimulator in his abdomen. Then the researchers did a series of mapping sessions in which the stimulator was tested for each of the areas being studied: voluntary leg movement, trunk control and cardiovascular function.

Stifel was randomized into a cardiovascular arm of the study, which required that he monitor his blood pressure every 15 minutes for six hours a day, keeping his systolic blood pressure between 110 and 120. If it dropped below that, he was to adjust the stimulator to regain that level.

Those sessions brought significant improvement for Stifel.

“I didn’t realize how poorly I felt until it was fixed. I guess you have to feel bad to realize what good feels like,” he said. “When my blood pressure maintains a healthy level, it is like a breath of fresh air. My ability to engage, be proactive and live life is so much easier.”

Now, even when he turns off the stimulator, his blood pressure remains above its previous levels for several hours.

Stifel’s study protocol also included 160 two-hour stand training sessions in the lab at . Every weekday, he would stand upright in a standing frame with trainers supporting his back, chest and each knee. These sessions were to help Stifel gain strength and independence.

“At the end of the sessions, I could consistently stand for 10-to-16 minutes without knee support,” Stifel said. “The epidural stimulator is more intense and effective than anything else I have experienced.”

Moving the needle

Stifel’s time since injury is the longest of any of the participants in the UofL studies so far.

“I am more of an outlier on the low end, but at 56 years old and nearly 40 years post injury, I think I did great,” he said.

Even Harkema was somewhat surprised that Stifel regained voluntary movement as soon as his early sessions led by Claudia Angeli, assistant professor of bioengineering and director of the epidural stimulation program at KSCIRC.

“I admit we had low expectations of Henry being able to move voluntarily after almost four decades of no movement,” said Harkema, professor of neurological surgery and associate director for KSCIRC. “Even though it supported our theory of the sophistication of the human spinal circuitry, I was stunned when Dr. Angeli was able to find stimulation configurations for him to sit independently and move his toes, ankles, knees and hips in the first sessions. Importantly, this shows that under the right conditions, recovery can happen even decades after injury.”

Now that he has completed his initial part of the study, Stifel is taking part in another study arm in which he will complete another 80 sessions focusing on trunk control and voluntary leg movement.

Once he completes the additional studies, Stifel plans to incorporate training with the stimulator in his daily exercise routine. Although he is not steady enough to stand on his own at home, he will continue that training along with blood pressure regulating, core exercising and any other positive outcomes that might come from this new phase of the study.

“I don’t want to do this study and then shelve it. We accomplished a lot and I want to be able to do more.” Stifel said. “I feel like I won the senior golf tournament, but I still want to beat the kids that have won the Masters. It’s human nature to want more.”

He also is happy to have contributed personally to the overall body of research.

“I think I have helped them move the research needle,” Stifel said. “There have been so many exciting discoveries. Spinal cord injury research has moved from the graveyard of neurological research to interventions that are impacting lives today. This field of research is quickly moving from the traditional fundraising path to one of venture philanthropy and gaining the interest of true capital. Lives are being changed thanks to epidural stimulation, transcutaneous stimulation and the other work being done here and elsewhere.

“This is an amazing research study within the walls of an amazing university. I hope the Louisville community is aware of it and proud of the accomplishments coming from it. It is an amazing time for this field of research.”

Visit Henry Stifel’s blog about his journey with epidural stimulation research at .

To support spinal cord injury research at the University of Louisville, visit .

The investigational device, currently intended as a bridge to heart transplant, is part of an Early Feasibility Study (EFS) sponsored by CARMAT, a French medical device company, in partnership with UofL, UofL Health – Jewish Hospital and the UofL Health – Trager Transplant Center.

Led by cardiothoracic surgeons Mark Slaughter and Siddharth Pahwa, both of UofL Health – UofL Physicians and the UofL School of Medicine, the team performed the implant of the device on Sept. 14, 2021 at UofL Health – Jewish Hospital. The same team completed the nation’s second implantation in a male patient last month, also at Jewish Hospital.

“For the other half of the world’s population, completion of this procedure by the Jewish Hospital team brings new hope for extended life,” said Slaughter, UofL Health surgical director of heart transplant and professor and chair of the Department of Cardiovascular and Thoracic Surgery in the UofL School of Medicine. “Size limitations can make it harder to implant artificial hearts in women, but the Aeson artificial heart is compact enough to fit inside the smaller chest cavities more frequently found in women, which gives hope to a wider variety of men and women waiting for a heart transplant and increases the chances for success.”

More than 3,500 individuals are awaiting a heart transplant in the U.S. and 900 of them are women. There are few treatment options for patients with biventricular heart disease, meaning both the left and right sides of the heart are not pumping blood adequately. The Aeson device is designed to solve the limitations of current left-ventricular assist devices, which pump blood in just one chamber, by pumping blood in both heart chambers.

Aeson also contains pressure sensors that estimate the patient’s blood pressure and automatically adapts cardiac output according to the sensor information. It is fully implanted as a heart replacement and powered by a portable external power supply.

During this procedure, the Aeson total artificial heart was implanted into a 57-year-old Kentucky woman with severe biventricular heart failure during an eight-hour surgery. The recipient, whose identity is being withheld upon request, was referred to the Advanced Heart Failure Therapies Program at Jewish Hospital earlier this year with end-stage heart failure and had undergone cardiac surgery years before. The patient is recovering well in the cardiovascular intensive care unit. Jewish Hospital is just one of four programs in the nation approved to perform this clinical trial procedure.

“The varying pumping ability of the Aeson device increases its viability among more patients,” said Pahwa, UofL Physicians cardiothoracic surgeon and assistant professor in the UofL Department of Cardiovascular and Thoracic Surgery. “While other devices are set at a fixed rate or create a continuous flow, CARMAT has developed the Aeson to automatically adjust the flow, creating an improved performance to meet the body’s changing blood flow needs.”

Currently, the Aeson artificial heart is tested as a bridge to transplant for patients with end-stage biventricular heart failure, allowing more time for the patient to receive a permanent heart organ transplant. The device already has been approved for such use in Europe, where approximately 20 devices have been implanted. It currently is being tested in the U.S. as part of a feasibility study approved by the Food and Drug Administration. The first Aeson artificial heart in North America was implanted in a male patient in July at Duke University Medical Center. The second implantation, also in a male patient, was performed at Jewish Hospital in August. This third North American implantation is the first to involve a female patient.

“Even as we have fought this deadly pandemic, our researchers and health care providers have also been on the front lines of improving care and quality of life for not only Kentuckians, but for people around the world,” said Kentucky Gov. Andy Beshear. “I am proud that UofL, Jewish Hospital and their doctors are leading the world in implanting this promising and innovative device that could offer hope and time to thousands of people, including our wives, mothers and other loved ones, in coming years.”

Stéphane Piat, chief executive officer of CARMAT, said, “This third implant in the U.S. was a landmark event not only because it allowed us to finalize the enrollment of the first cohort of patients of the EFS, but very importantly because it is the first time ever that our device has helped a woman suffering from heart failure. This achievement confirms that the size limitations for adults are minimal, which makes us very confident in Aeson’s potential to become a therapy of choice for a broad patient population.”

Preclinical research for CARMAT’s artificial heart began at UofL more than five years ago. Researchers at UofL’s Cardiovascular Innovation Institute tested Aeson’s autoregulation capability, which allows the device to adapt its flows according to the patient’s needs by detecting changes of pressure in the device. UofL researchers have conducted preclinical testing of artificial heart components and mechanical assist devices at CII for many years, testing some portion of nearly every mechanical assist device that is commercially available today.

Jewish Hospital and the University of Louisville share a storied history in advancing heart care. Highlights include:

• Aug. 24, 1984: Kentucky’s first heart transplant performed at Jewish Hospital by UofL physicians
• July 2, 2001: The world’s first AbioCor artificial heart was implanted at Jewish Hospital by UofL physicians, led by cardiothoracic surgeon Laman Gray
• Dec. 21, 2011: Kentucky’s first transcatheter aortic-valve replacement performed at Jewish Hospital by UofL physicians
• Jan. 18, 2015: Kentucky’s first HeartMate 3 left ventricular assist device implanted at Jewish Hospital by UofL physicians
• Feb. 21, 2018: UofL Health – Trager Transplant Center’s 500^th heart transplant performed at Jewish Hospital
• June 14, 2019: The first EvaHeart2 LVAD implanted as bridge to transplant at UofL Health – Trager Transplant Center
• April 22, 2021: UofL Health – Trager Transplant Center’s 1000^th TAVR performed at Jewish Hospital

“This world-first artificial heart implant into a female patient is another demonstration of UofL Health’s commitment to provide both the world-class care of today and develop the world-class standards of tomorrow,” said John Walsh, chief administrative officer of Jewish Hospital. “We celebrate this first as a milestone and recognize the hard work of Drs. Slaughter and Pahwa and the entire team. The true impact of their work will be measured in the dozens, hundreds and thousands of lives improved in the years to come.”

The patient who received the nation’s second Aeson implant, on Aug. 20, 2021, continues to improve at Jewish Hospital. An update is expected in the coming weeks.

The team, led by Mark Slaughter, MD, professor and chair of the Department of Cardiovascular and Thoracic Surgery in the UofL School of Medicine and lead cardiothoracic surgeon at UofL Health – Jewish Hospital, performed the implant of the investigational device on Aug. 20.

The artificial heart, Aeson, developed by French medical device company CARMAT, serves as a bridge to transplant for patients with end-stage biventricular heart failure – heart disease affecting both left and right sides of the heart – allowing more time for the patient to receive a permanent heart organ transplant. More than 3,400 individuals in the U.S. currently are awaiting a heart transplant and there are few other treatment options for patients with biventricular heart disease.

“We are excited to provide this new technology to patients in Kentucky and the surrounding region and be one of the first U.S. centers to implant this new total artificial heart” Slaughter said. “This device has the potential to save the lives of critically ill patients suffering from biventricular heart failure who currently have very limited treatment options.”

The new total artificial heart was implanted into a middle-aged man from Southern Indiana with severe biventricular heart failure during a seven-and-a-half-hour surgery. The recipient, whose identity is being withheld upon request, was referred to the Advanced Heart Failure Therapies Program at Jewish Hospital. The patient currently is doing well in the cardiac surgery ICU. The Advanced Heart Failure Therapies Program at Jewish Hospital is the only program in the area that is performing heart transplants, the latest in mechanical circulatory support and cell-based therapies for advanced heart failure.

“Innovative care is what put Jewish Hospital on the world map,” said John Walsh, chief administrative officer at Jewish Hospital. “UofL Health was formed, in part, with a promise to preserve and build on the transplant legacy for generations to come. This procedure is another lifesaving milestone.” 

The new device is designed to solve limitations of left-ventricular assist devices (LVAD), which pump blood in just one chamber, by pumping blood in both heart chambers. Aeson also contains biosensors that detect the patient’s blood pressure and position and automatically adapts cardiac output according to the sensor information. It is fully implanted as a heart replacement and powered by a portable external power supply.

“We are honored that our device is implanted at UofL Health – Jewish Hospital, which is recognized throughout the United States for its quality of care and cardiovascular research” said Stéphane Piat, Chief Executive Officer of CARMAT. “I would like to congratulate the teams at Jewish Hospital, the University of Louisville, as well as our technical and medical staff, on this exceptional milestone for both patients and our company.”

The device is medically approved in Europe, where approximately 20 have been implanted. The first Aeson artificial heart in North America was implanted in July at Duke University.

This is not the first time University of Louisville physicians and Jewish Hospital have made artificial heart history. Just over 20 years ago, on July 2, 2001, UofL cardiothoracic surgeon Laman Gray led the surgical team that implanted the first self-contained artificial heart in the United States at Jewish Hospital. The AbioCor artificial heart was implanted into Robert Tools, who lived five months on the device. The UofL surgical team also performed the first heart transplant in Kentucky at Jewish Hospital in 1984.

“This is a very important advance in the field of cell therapy and in the management of heart failure. It suggests that a treatment, given only once, can produce long-term beneficial effects on the quality of life and prognosis of these patients,” said Roberto Bolli, director of the UofL Institute of Molecular Cardiology, who led the study at UofL. “The results pave the way for a larger, Phase 3 trial of cell therapy in heart failure.”

UofL led enrollment among seven institutions participating in CONCERT-HF, a Phase 2 clinical trial testing the safety, feasibility and efficacy of two types of adult cells, used alone and in combination, in patients with heart failure.

CONCERT-HF evaluated the use of two types of cells – autologous mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs) – alone or in combination, in patients with heart failure caused by chronic ischemic cardiomyopathy, a decrease in heart pumping effectiveness due to heart attacks and a lack of blood getting to the heart. Autologous MSCs are derived from the patient’s bone marrow and CPCs are from the patient’s heart tissue. Both are known as “autologous” cells because they come from the same patient in whom they are returned for the treatment.

In the study, patients treated with CPC cells alone had a significant reduction in major adverse cardiac events, particularly hospitalization. Patients treated with MSC cells alone and with a combination of both types of cells experienced significantly improved quality of life compared with patients who received no treatment. Quality of life was assessed using patient responses to the Minnesota Living with Heart Failure Questionnaire, which gauges the degree to which physical, emotional and socioeconomic effects of heart failure adversely affect the patient’s life and the extent to which they prevented the patient from living as they wanted to live.

“The results of this trial show for the first time that cell therapy reduces hospitalization for heart failure and improves clinical outcome, providing a cogent rationale for undertaking a pivotal Phase 3 trial” that could be the next step on the pathway to FDA approval, Bolli said.

The results of the were published in the . The Phase 2, randomized, placebo-controlled trial, funded by NIH National Heart, Lung and Blood Institute, was conducted by the Cardiovascular Cell Therapy Research Network, a network of clinical trial researchers involved in cell therapy for heart disease that includes UofL. UofL led enrollment in the study, accounting for 25% of the 125 trial participants.

Bolli’s expertise and long career in successful cardiac research led to the establishment of the CCTRN center at UofL in 2011. This consortium of leading cardiovascular research organizations includes Stanford University, the University of Miami, Indiana University, the Texas Heart Institute, the University of Florida and the Minneapolis Heart Institute Foundation, in addition to UofL. The School of Public Health at the University of Texas Health Science Center at Houston serves as the data coordinating center.

Bolli is a pioneer in research using adult stem cells for cardiac disease. Over the past two decades, he has shown that CPCs are beneficial in many preclinical models of heart failure, thus paving the way for the CONCERT-HF trial. He also led the recent – the first study to show safety and potential efficacy of cell therapy in cancer survivors with heart failure caused by anticancer therapy.

COPD causes restricted airflow from the lungs, resulting in breathing difficulty, cough, mucus production and wheezing. TLD involves the removal of tissue in the lungs that may be making symptoms worse. Performed via bronchoscopy, the procedure is designed to disrupt pulmonary nerve reflexes, which may have the potential to reduce COPD exacerbations.

AIRFLOW-3, a phase 3 clinical trial sponsored by , is enrolling patients with moderate-to-severe COPD, high symptom burden and a history of COPD exacerbations, including increased coughing, wheezing and breathing distress, to evaluate the safety and effectiveness of TLD.

Umair A. Gauhar, associate professor at the , led a medical team in the Division of Pulmonology that successfully treated a COPD patient with TLD therapy in one-hour-long outpatient procedure at . The patient returned home the same day.

“Many of our COPD patients experience exacerbations which cannot be controlled with their inhaler medications,” Gauhar said. “As a pulmonary community, we need to embrace the development of interventional therapies which may stabilize COPD patients and help reduce their risk of exacerbation. Based on the existing evidence, we are enthusiastic about the potential of TLD to meet a true unmet medical need and are proud to have treated our first patient in the AIRFLOW-3 clinical trial.”

Debbie Sowers, a 58-year-old resident of Madison, Indiana, said she participated in the trial at UofL to help develop better treatments for COPD.

“I participated to help everybody that has COPD and to try to better my breathing,” Sowers said. “There need to be more studies on COPD because it is a really bad disease. It stops your life.”

UofL is the only center in Kentucky enrolling COPD patients for AIRFLOW-3 and is one of up to 25 centers across the United States enrolling patients in the trial.

The Phase 3 trial enrolls residents and staff who live or work at facilities that have had a recently diagnosed case of COVID-19 and who now are at a high risk of exposure. The study, which included Essex Nursing and Rehabilitation Center in Louisville recently, is to evaluate the efficacy and safety of bamlanivimab for the prevention of COVID-19. The study also is exploring treatment of recently diagnosed SARS-CoV-2- and COVID-positive patients who are at high-risk of developing severe disease.

As the only Kentucky location for the Phase 3 clinical trial, UofL’s Division of Infectious Diseases worked with mobile units deployed by Lilly to the Louisville site to enroll and treat trial participants. Julio Ramirez, director of the division, leads the work, which includes follow-up monitoring for study participants at this facility and any others in Kentucky who may participate in the trial.

“We are thrilled to be partnering with NIH and Lilly for the implementation of their BLAZE-2 study in Kentucky. With nearly 30,000 residents in long-term care facilities in the state, there is an urgent need for therapeutic strategies to prevent the spread of COVID-19 in this vulnerable population. We are proud to be a part of this new type of clinical study for preventive treatment,” Ramirez said.

For this trial, Lilly deploys mobile research units to a long-term care site soon after an individual has tested positive for SARS-CoV-2. The unit team enrolls residents and staff members who volunteer to participate in the trial. The one-time study drug infusion and follow-up visits are administered to study volunteers at the long-term care facility. The UofL team works with the Lilly team during the initial site infusions and will monitor participants following the infusion for up to 25 weeks.

The first deployment in Kentucky was to Essex Nursing and Rehabilitation Center, where 20 residents and staff members were enrolled in the study in November.

“Our elderly population is at a much higher risk of complications from COVID-19 and our staff and residents are happy to be participating in this study. I have personally witnessed the negative impact COVID-19 has had on nursing facilities,” said Robert Flatt, Essex administrator. “I am extremely proud to be an active participant in this collaborative study in the hopes that we will soon put an end to this pandemic.”

The virus is known to spread rapidly among staff and residents of long-term care facilities, who account for a high percentage of hospitalizations and deaths resulting from the virus.

“I am glad to be a part of this research study with the University of Louisville to help find treatment and prevention options for COVID-19. As a member of our community, I am happy to participate in the hopes of helping others. I am also excited to participate as I am a huge fan of the University of Louisville,” said Patricia L. Rollie, an Essex resident and study participant.

Antibodies are produced naturally by the immune system in response to viruses and other foreign invaders and help the body neutralize and destroy these threats. However, it takes time for the body to produce its own antibodies. Bamlanivimab is an antibody engineered from a COVID-19 survivor. Testing and previous trials have shown that manufactured antibodies can speed recovery or possibly prevent SARS-CoV-2 infection.

“COVID-19 has had a devastating impact on nursing home residents. We’re working as fast as we can to create medicines that might stop the spread of COVID-19 to these vulnerable individuals,” said Daniel Skovronsky, Eli Lilly’s chief scientific officer and president of Lilly Research Laboratories. ”BLAZE-2 is a first-of-its-kind COVID-19 trial designed to address the challenging aspects of running a clinical trial in long-term care facilities, which normally do not conduct clinical trials.”

As a result of a separate clinical trial, Lilly has received an emergency use authorization from the FDA for bamlanivimab to treat higher-risk patients recently diagnosed with mild-to-moderate COVID-19.

Bamlanivimab targets the spike protein of the SARS-CoV-2 virus. It is designed to block viral attachment and entry into human cells, thus neutralizing the virus and potentially preventing and treating COVID-19. Bamlanivimab emerged from the collaboration between Lilly and AbCellera and was discovered by AbCellera and scientists at the National Institute of Allergy and Infectious Diseases Vaccine Research Center.