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When it comes to transplant quality, the Scientific Registry of Transplant Recipients has consistently evaluated 网红黑料 Shands Hospital as a top destination for patients seeking high-quality care and outcomes. Comparable to a comprehensive report card, the registry assesses programs based on critical factors essential to patients seeking organ transplants, including one-year survival rates, transplant waiting times and patient survival rates while on the transplant list.

Now, researchers and surgeons at the University of Florida are working hand in scalpel to leverage their expertise and dedication to tackle new challenges, such as long-term outcomes, immunosuppression and other problems that have persisted across the field of transplantation despite its progress over the past several decades.

鈥淚n many ways, you could say the field of transplantation plateaued for some time,鈥� said Ali Zarrinpar, MD, PhD, a liver transplant surgeon and professor in the UF College of Medicine Department of Surgery. 鈥淚 think the field has matured to a point where we know how to do a lot, and we鈥檝e optimized many of those processes. Now many of us are looking toward what鈥檚 next 鈥� and deciding how we want to get there.鈥�

What鈥檚 next for patients undergoing a transplant differs with respect to the organ in question. Lung transplantation, for example, carries idiosyncratic problems unique to an organ that is constantly exposed to outside elements and stimuli, hastening its rejection by the recipient鈥檚 immune system. Other solid organs commonly transplanted, like hearts, livers and kidneys, have an average life expectancy of 10 years 鈥� almost double that of lungs.

鈥淟ung transplant has one of the worst outcomes of all the solid organ transplants,鈥� said Ashish K. Sharma, MD, PhD, a vascular surgeon and associate professor in the Department of Surgery, whose lab is dedicated to improving primary graft dysfunction, organ preservation and ischemia-reperfusion injury across lung transplant recipients. 鈥淭he truth of the matter is that almost 70% of lung transplant patients will die in 10 years, and half of them die at the five-year mark. Our lab鈥檚 goal is to delve into the problems behind why this area of transplantation has, historically, struggled so much.鈥�

One piece of the puzzle is the donor shortage. For some organs, living donors are more of a readily available solution. Take the kidney, for instance: A person can donate one of their bean-shaped organs to a friend, family member or stranger and observe no changes to their day-to-day functioning after the donation.

But other organs, like the lungs, are in shorter supply. Thanks to the advent of ex vivo lung perfusion, the quantity has increased slightly. The therapy, applied to donor lungs outside of the body before transplantation, improves organ quality and makes lungs that were previously unsuitable safe for implantation.

However, Sharma鈥檚 chief focus is one the specialty has grappled with since the first lung transplant in 1963: the issue of primary graft dysfunction, or why lung transplants have such poor long-term results in the first place.

Typically, within the first three days following a lung transplant, graft dysfunction occurs because of a process called ischemia reperfusion injury, in which blood supply that returns to tissue after a period of deprivation results in damage due to a lack of oxygen. This event dictates the outcomes of whether the patient will develop chronic graft dysfunction or survive. The purpose of Sharma鈥檚 lab is to understand how researchers and clinicians can mitigate the chances of both primary graft dysfunction and ischemia perfusion injury early on 鈥� ideally within the first 72 hours.

Top marks

The 网红黑料 Shands Transplant Center has achieved outstanding outcomes across multiple organ types, as reported by the Scientific Registry of Transplant Recipients in January.

• Liver: Top 5 in the nation 鈥� 99.7% estimated probability of patient survival post-transplant
• Kidney: Best in Florida 鈥� Top 10 in the nation
• Lung: Best in Florida 鈥� Top 5 in the nation

网红黑料鈥檚 transplant programs are among two nationally to achieve the top ranking in every assessment category.

Every year, 70 to 80 lung transplants are performed at 网红黑料 Shands Hospital.

鈥淭hat makes us one of the top centers in the country,鈥� Dr. Sharma said. 鈥淎nd with that comes its own layer of expertise and infrastructure where we can conduct robust, translational research.鈥�

To delve deeper, Dr. Sharma and his team conduct transbronchial biopsies from the lung tissue before and after transplant, analyzing lipids and biomarkers to try to identify the turning point. One area of potential investment, Dr. Sharma said, is the humble omega-3 fatty acid, which human bodies metabolize into specialized pro-resolving mediators. They typically occur in very low quantities in the lungs but add protective qualities 鈥� so much so, that Sharma and his team are noting an association between the lipids and outcomes of transplant patients.

Another respected foe is cell death, or apoptosis. If the research team can identify a means of staving it off, Dr. Sharma said, patient outcomes could also improve.

鈥淎s you can imagine, there鈥檚 a turnover of cells all the time, especially when there鈥檚 a transplant,鈥� he said. 鈥淎 lot of cells die because it鈥檚 a foreign graft for the recipient鈥檚 body. It鈥檚 a new lung coming in, and that is taken as a foreign object, and there鈥檚 a subsequent immune response. And because of that, there鈥檚 a lot of apoptosis.鈥�

In a way, the cell death is a precursor to a doomed domino effect. Typically, the body clears away dead cells through efferocytosis. But in the case of a lung transplant, the process stutters 鈥� and eventually stops. The culprit? A receptor, called tike, that is cleaved, leading to a communication gap that prevents the garbage trucks from cleaning up all the dead cells.

鈥淚f we can find a drug that will repair that gap in the process, it would enable some of the inflammation to subside,鈥� Dr. Sharma said. 鈥淚nstead, the dead cells accumulate, inflammation persists and so on.鈥�

While some challenges in transplantation are unique to the particular organ, others extend to all. One area ripe for problem-solving is the question of immunosuppressants.

For any transplant, an organ recipient鈥檚 immune system experiences a rude awakening, fighting off what it perceives as a foreign body. Immunosuppressants work 鈥� but sometimes, they work too well, quashing the body鈥檚 response to everything, including interlopers it should recognize as legitimate adversaries, like an infection or cancer.

鈥淥ur team is dedicated to the idea that one of the biggest obstacles we face is optimizing immunosuppression,鈥� said Sergio Duarte, PhD, an assistant professor in the Department of Surgery whose research focuses on transplantation and hepatobiliary surgery. 鈥淭hese drugs have very narrow therapeutic ranges, and it can be difficult to determine the right dose or combination for any individual patient.鈥�

Too much can lead to direct organ toxicity or to an immune system that cannot fight infections or malignancy 鈥� but too little can put a patient at risk of rejection and graft injury. In this case, researchers believe artificial intelligence can lend a helping hand in the form of platform phenotypic personalized medicine, or PPM. In theory the process will rely on nonlinear regression to mathematically relate each patient鈥檚 prescribed immunosuppressant dosing with quantitative measurements reflective of their phenotype 鈥� and their subsequent graft health.

鈥淚n other words, PPM will allow us to identify a functional relationship between a patient鈥檚 immunosuppressive treatment and response,鈥� Dr. Duarte said. 鈥淥nce we measure this relationship, we can optimize the phenotypic function to identify a combination of doses associated with the desired clinical outcome minimization of allograft injury.鈥�

The real hope for PPM, however, is its ability to be tailored to each patient.

鈥淲hen it comes to immunosuppression, this process is patient-specific and time-dependent on the clinical inputs we use,鈥� Dr. Zarrinpar said.

In both modeling and optimization processes, research values are constantly updated, allowing the phenotypic response function to change and reflect fluctuations in a patient鈥檚 immunosuppressive needs over time. But ultimately, it has the potential to revolutionize the way clinicians and researchers approach the question of immunosuppression 鈥� and long-term patient health.

鈥淚 think every transplant researcher is invested in problem-solving these questions that arise as we get to know the science better year after year,鈥� Dr. Sharma said. 鈥淎nd in many ways, it is how we show our commitment to our patients, who are at the heart of these questions we hope to continue to answer.鈥�

Lung lifeline

Darwin Dias nearly died from COVID-19 complications in 2021. Facing multi-organ failure, his only chance for survival was an Extracorporeal Membrane Oxygenation machine, or ECMO. After being airlifted from Orlando to 网红黑料 Shands Hospital in Gainesville, he remained connected to ECMO for 54 days and received treatment from lung transplant specialist Abbas Shahmohammadi, MD.

Recently, Dias pledged $500,000 to fund critical research within the abdominal transplant unit, where Dr. Shahmohammadi now serves as director.

鈥淚 have a forever bond with the hospital,鈥� Dias said. 鈥淚 will always give all the support I can to show how grateful I am for being reborn there.鈥�

To support 网红黑料鈥檚 transplant programs, contact benjamin.valentine@ufhealth.org or (352) 627-9047.