TAG: "Transplants"

New organ transplant strategy aims to better prevent rejection

UCSF approach might end lifelong drug treatment.

Qizhi Tang, UC San Francisco

Organ-transplant recipients often reject donated organs, but a new, two-pronged strategy developed by UC San Francisco researchers to specifically weaken immune responses that target transplanted tissue has shown promise in controlled experiments on mice.

The hope is that using this novel treatment strategy at the time of transplantation surgery could spare patients from lifelong immunosuppressive treatments and their side effects. The approach might also be used to treat autoimmune diseases such as type 1 diabetes, the researchers said. The study is published and commented upon in a recent issue of American Journal of Transplantation.

The study was conducted in mouse studies of islet-cell transplantation — a procedure used to restore insulin secretion and control over glucose levels in the blood in patients with life-threatening diabetes. The treatment allowed more than 70 percent of mice to accept transplants without requiring any long-term treatment with immunosuppressive drugs.

The approach, led by Diabetes Center member Qizhi Tang, Ph.D., involved using cells from donors to activate immune cells called donor-reactive effector T cells. The researchers then gave the mice a drug called cyclophosphamide, known to specifically kill activated cells.

Up to 80 percent of the donor-reactive effector T cells, which play a major role in transplant rejection, were eliminated by this treatment. However, that procedure alone did not prolong survival of transplanted tissue.

That required a second step: Some of the mice also received cell therapy — an expanded population of cells called TREGs that quell immune activity. Seventy percent to 80 percent of these mice accepted the transplants, without requiring any long-term immunosuppressive drugs.

Significantly, when the cell therapy was used only in those cells that specifically target donor tissue, only one-fifth as many cells were needed to prevent transplant rejection, the UCSF researchers found. The bigger bang per cell may bode well for clinical protocols, Tang suggested.

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Blood test serves as ‘crystal ball’ for heart transplant patients

Test can predict potential rejection-related problems in the future.

Mario Deng, UCLA

A new UCLA-led study shows that a blood test commonly used to determine whether heart transplant recipients are rejecting their new organ can also predict potential rejection-related problems in the future.

Reporting in the online edition of the peer-reviewed journal Transplantation, researchers demonstrate how the AlloMap test, which uses a blood sample to measure changes in the expression of roughly a dozen genes, can be used over a period of time to assess the risk of dysfunction or rejection of a transplanted heart — months before such an event may occur.

“For the first time, we can use genomic testing over multiple patient visits to go beyond intuition to understand not just how patients are doing now but how they are likely to be a few months from now,” said Dr. Mario Deng, medical director of UCLA’s Integrated Advanced Heart Failure–Mechanical Support–Heart Transplant Program and the study’s principal investigator. “It’s another step toward personalized medicine.”

The discovery that transplant recipients’ white blood cells contain this prognostic information on rejection, independent of how their transplanted heart may be functioning currently, could potentially improve care and outcomes, the researchers said. The findings represent a significant step in the movement toward using genomic-based testing to predict future clinical events and bolster the importance of similar tests being developed for recipients of other organs.

In the U.S., approximately 2,000 patients receive lifesaving heart transplants each year, and monitoring their immune systems for signs of rejection is a critical part of follow-up care. Until recently, however, the only way to diagnose rejection was through a heart-muscle biopsy, a painful and potentially risky procedure in which a heart catheter is inserted through a vein in the neck.

That changed with the development of the AlloMap gene-expression profiling test, which received clearance from the Food and Drug Administration in 2008. The test is now routinely used by a majority of U.S. heart transplant centers to monitor low-risk patients during follow-up care, resulting in a substantial reduction in the number of biopsies.

AlloMap, which is based on research Deng led in conjunction with more than a dozen of the largest U.S. heart transplant centers and the Brisbane–based biotech company XDx, measures the expression levels of 11 genes from a patient’s blood sample, each of which is known to be associated with rejection risk.

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Lifesaving surgery makes for an extra special Valentine’s Day

Minimally invasive heart procedure followed by lung transplant.

All smiles, Mike Boyle and his wife, Ellen, are looking forward to celebrating a special Valentine's Day.

Mike Boyle has good reason to give his wife and family extra hugs on Valentine’s Day.

Just two months ago, he was slowly suffocating from pulmonary fibrosis, a condition with no cure that causes scar tissue build-up in the lungs, making it difficult to breathe. In addition, his main heart valve was so clogged with calcium deposits that it couldn’t open wide enough to adequately pump blood through his body.

Feeling exhausted, the Thousand Oaks resident had curtailed all his activities and needed to carry around an oxygen tank to help him breathe.

Given his declining heart condition, it was too risky for him to receive a much needed lung transplant, a factor that the UCLA lung transplant committee took into consideration before turning him down. Given that UCLA handles the most advanced, serious patient cases and he still didn’t qualify, it looked like Boyle had truly run out of options.

But fortunately, there was one left. The heart team at UCLA was offering a new procedure that is designed for patients who are too sick to have the conventional surgery needed to replace the main heart valve. Luckily, Boyle qualified.

The minimally invasive procedure, called Transcatheter Aortic Valve Replacement (TAVR), involves far fewer surgical risks. TAVR allows doctors for the first time to replace the aortic valve without open heart surgery. It’s an attractive alternative for patients like Boyle, who aren’t candidates for traditional surgery.

The usual TAVR approach is to deliver the valve to the heart via an artery in the groin using a catheter, which is a hollow delivery tube. But in Boyle’s case, these arteries had blockages that made this approach impossible. Alternatively, a small incision is made on the side of the chest, and the valve is delivered through the lowest part of the heart called the apex. Once in place, the valve is opened, and it starts working immediately.

Boyle had the TAVR procedure using this alternative approach last June with a heart team led by Dr. Richard Shemin, chief of cardiothoracic surgery, and Dr. William Suh, assistant clinical professor of medicine and interventional cardiology, both with UCLA’s David Geffen School of Medicine and UCLA Health System.

Boyle’s heart was doing so well after the valve replacement that he was encouraged to try to get listed again for a lung transplant. This time he was approved by the UCLA committee and received his lifesaving lung transplant in late November with a team led by Dr. Abbas Ardehali, a professor of cardiothoracic surgery and director of the heart and lung transplantation program at UCLA.

Today, Boyle is progressing nicely, say his doctors — and he couldn’t be happier.

“I don’t feel as physically limited as before and have a new lease on life,” said Boyle, who doesn’t need to carry oxygen anymore and has started to exercise as well.

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UC Davis Transplant Center opens Fresno location

Clinic will expand access to kidney, pancreas transplant care in Central California.

Luke Preczewski, UC Davis

Luke Preczewski, UC Davis

The UC Davis Transplant Center — one of the nation’s premier transplant programs — has opened a new clinic in Fresno to expand access to kidney and pancreas transplant care in Central California.

The clinic provides pre- and post-transplant medical evaluations for recipients and kidney donors. Transplant surgery will still be provided at the center’s main location at UC Davis Medical Center in Sacramento.

The Fresno clinic is located at 1189 E. Herndon Ave. and will be open one day per month. The number of clinic days will increase based on patient need. To arrange for a referral or schedule an evaluation, call toll free (800) 821-9912.

Fresno is the largest city in California without a transplant center within 25 miles, yet about 17 percent of California’s kidney transplant patients are in the Fresno region. One of the closest centers is at UC Davis Medical Center, which is about 170 miles away.

“We wanted to reduce that travel time as much as possible for patients and their families,” said Luke Preczewski, executive director of the transplant program.

UC Davis performed 339 kidney transplants in 2013, making it by volume the second-largest program in the nation. According to 2012 data from the Scientific Registry of Transplant Recipients, UC Davis offers the shortest average adult kidney transplant wait time (37.2 months) of any California hospital.

For information about the UC Davis Transplant Center, visit www.ucdmc.ucdavis.edu/transplant.

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Football fans team up for organ match

Random stadium seat assignment leads to lifesaving transplant surgery.

Louis Munoz (left) donated one of his kidneys to William Lynch - the match between the childhood friends occurred after they happened to sit next to each other at a Chargers game.

Louis Munoz (left) donated one of his kidneys to William Lynch - the match between the childhood friends occurred after they happened to sit next to each other at a Chargers game.

In October, Louis Munoz donated one of his kidneys to William Lynch. The organ match would not have occurred without a bit of serendipity and a big love of football. Munoz and Lynch had been childhood friends, but hadn’t seen each other in years – then they found themselves randomly seated next to each other at a Chargers game.

“Louis and I knew each other as kids and then lost touch. Years later, by surprise, we ended up sitting right next to each other at Chargers games,” said William, a middle school teacher. “When I started missing games, Louis asked me why and I explained that due to kidney complications, I’d been unwell. His wife half-jokingly suggested that he give me a kidney.”

Louis immediately volunteered to be tested as a possible donor. William initially declined his friend’s offer, believing another donor would come through. But when that didn’t happen, Louis followed through and proved to be a match.

“I am so blessed that Louis has chosen to give me this new lease on life,” said William. “I can’t express to him how grateful I am. I promised Louis I will take care of this kidney the best that I can.”

Prior to the transplant surgery, William had been on dialysis, a treatment option to filter the blood and rid the body of harmful wastes and excess salt and water. Dialysis is a tough regimen that requires a patient to be tethered to a machine three to four times per week for hours at a time.

“I had been on dialysis for more than two years. Mentally and physically it was the hardest part I had to endure,” said William whose kidney failure was caused by a rare disease that attacks the organ’s filtering system. “Getting off of dialysis is wonderful.”

William and Louis had their surgeries performed at UC San Diego Health System, which boasts the region’s largest kidney transplant program. The program has performed more than 2,270 kidney transplants. Approximately 35 percent of the donations come from living donors.

“In San Diego, of all the people waiting for an organ transplant, more than 85 percent need a kidney,” said Alan Hemming, M.D., transplant surgeon, UC San Diego Health System. “Living donors can dramatically shorten the time to wait for a donated kidney. The gift is truly lifesaving.”

Currently, there are more than 770 patients at UC San Diego Health System awaiting a kidney transplant. Nearly 98,000 people in the United States are on kidney transplant wait lists, including 17,784 in California. The average wait for a kidney from a deceased donor is typically six years in San Diego and ten years in Los Angeles.

The transplant surgery was performed in two phases in adjacent operating rooms. In one room, the kidney was carefully removed from Louis; in the second, it was transplanted into William.

Santiago Horgan, M.D., chief of minimally invasive surgery at UC San Diego Health System, removed the kidney aided by a robot. With robotic guidance, the vessels of the kidney were precisely isolated and the kidney was removed with less trauma. And because smaller incisions were made, the risk of subsequent pain was also reduced. Hemming then transplanted the removed kidney into William during a two-hour procedure.

“I am excited for William,” said Louis. “I think the decision to donate is pretty simple. I don’t think too much about it – just a little inconvenience to help somebody out who really needs it.”

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Award recognizes impact of anthropologist’s work on human organs trade

UC Berkeley’s Nancy Scheper-Hughes honored for watchdog role.

UC Berkeley anthropologist Nancy Scheper-Hughes is shown here talking with Alberty Alfonso da Silva in the Recife, Brazil, slum he called home before after being transported to South Africa to sell his kidney to a recipient flown there from New York City. (Photo by John Maier)

UC Berkeley anthropologist Nancy Scheper-Hughes is shown here talking with Alberty Alfonso da Silva in the Recife, Brazil, slum he called home before after being transported to South Africa to sell his kidney to a recipient flown there from New York City. (Photo by John Maier)

UC Berkeley anthropologist Nancy Scheper-Hughes has been honored by the American Anthropological Association with its first ever Anthropology in Public Policy Award for her trailblazing work shedding light on the dark practice of human organs trafficking.

The award, recognizing anthropologists whose work has had a significant and positive influence on government decision-making, was announced at a recent American Anthropological Association conference in Chicago.

In 1999, Scheper-Hughes, director of UC Berkeley’s medical anthropology program, helped found the Berkeley Organs Watch project. It monitors the organ-transplant trade for abuses among the transnational networks that connect patients, transplant surgeons, brokers, medical facilities and live donors, who often live in the poorest parts of the world.

“When I began the Organs Watch project, it was heretical to suggest that human trafficking for organs was not just a hyperbolic metaphor of human exploitation, but was actually happening in many parts of the world,” Scheper-Hughes said in her acceptance remarks.

But the project generated international headlines, particularly as Scheper-Hughes has called for more accountability from the medical profession in the field of medical anthropology. She also has been asked to testify before national and international governmental and medical panels, and has helped law enforcement agencies uncover illicit organs trafficking around the globe.

In recent years, Scheper-Hughes has advised the European Union, the United Nations and the Human Trafficking Office of the World Health Organization. She has also testified before Congress, the Council of Europe and the British House of Lords. In addition, she has consulted on several documentary as well as commercial films exploring organ trafficking.

In accepting the award, the self-proclaimed “agent provocateur” acknowledged that the complex social issues that anthropologists explore often have no single, simple solution, and one answer can prompt a new problem.

“So, yes,” Scheper-Hughes said in her speech, “I did help interrupt kidney trafficking in Moldova, only to have the international brokers use my Organs Watch website … to set up a robust scheme in illicit transplants using Afro-Brazilian men from the slums of Recife to service Israeli and European transplant tourists to South African hospitals … And, yes, I contributed to the ban on the use of executed prisoners in China as organ suppliers, only to learn that new organ suppliers could be found in China among rural village girls and Vietnamese immigrants.”

Scheper-Hughes said agent provocateurs must continue “to put their bodies, as well as their words, on the line, and work on behalf of communities and populations under siege…”

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UCSF’s pediatric transplant picnic celebrates life

Former patients reunite with each other and the medical staff who cared for them.

Several hundred people gathered for a picnic at McNears Beach in San Rafael to celebrate something much bigger than just the end of summer. Each family there was celebrating the life of a loved one who has undergone an organ transplant surgery at UCSF Benioff Children’s Hospital.

The annual event, now in its 18th year, also is a way for former patients to reunite with each other and the medical staff who saw them through so much of their childhoods.

“When I first came to the hospital, I had a 2-percent chance to live, and I survived,” said Bradrick Thurman, who was born with a rare life-threatening autoimmune disease.

Thanks to the team at UCSF, Thurman not only survived, but 19 years later, he’s excelling as a college student studying psychology. “I feel really special for being put here,” he said. “And I feel like I was put here for a purpose now that God let me survive what I was going through.”

Justin Erickson was almost 10 when he needed liver transplant surgery due to biliary atresia, a life-threatening condition in which the bile ducts are blocked.

“I was terrified, downright terrified,” he said. “I didn’t know what to expect. I thought I was going to die.”

He spent almost a year at UCSF Benioff Children’s Hospital following his surgery, but he gradually recovered. Now, Erickson is a 30-year-old husband and soon-to-be father.

“From where I started as a child to where I am today, there’s no words for it,” he said. “You accept what you’ve been dealt, and you hope your child is healthy and happy.”

Picnic organizer Chris Mudge, who retired from UCSF just over a year ago, helped take care of both Thurman and Erickson when she was a pediatric nurse practitioner. Last year, the transplant picnic was renamed “The Annual Chris Mudge UCSF Pediatric Transplant Picnic,” to honor Mudge’s work and dedication to the transplant patients and their families.

“It’s been a privilege to take care of these kids and watch them grow up to be happy and successful young adults,” she said. “In the early days, the picnic was just a small gathering. We are grateful that it has become what it is today.”

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Discovery could improve liver transplant success

Natural substance found in blood vessels stimulates organ and tissue regeneration.

Bruce Hammock, UC Davis

Bruce Hammock, UC Davis

Researchers from multiple institutions, including UC Davis and Harvard Medical School, have discovered a novel and natural means that could increase the success of human liver transplants and speed the recovery of both the patient and the donor.

The study is especially significant because of the desperate shortage of livers among thousands of very ill patients, said lead researcher Dipak Panigrahy of Harvard Medical School, in work published online in the July 29 edition of Proceedings of the National Academy of Sciences (PNAS).

According to the American Liver Foundation website, 1,848 patients died in 2005 while waiting for a donated liver to become available. “Currently, about 17,000 adults and children have been medically approved for liver transplants and are waiting for donated livers to become available. The waiting list grows every year.”

The researchers found that a natural substance in blood vessels stimulates organ and tissue regeneration.

“The endothelium of blood vessels generate the lipid mediators called epoxyeicosatrienoic acids or EETs,” explained Panigrahy, assistant professor of pathology at Harvard Medical School and the Center of Vascular Biology Research at the Beth Israel Deaconess Medical Center, Boston. “EETs stimulate blood vessel formation, and organ regeneration is dependent on blood vessel formation. However, the role of EETs in organ regeneration is unknown. Our research shows that EETs stimulate organ and tissue regeneration.”

The 28-member discovered that “systemic administration of EETs significantly increased liver and lung regeneration by 23 percent to 46 percent when compared to control mice post partial liver resection,” Panigrahy said.

“This can be very useful in transplant both for the donor and the recipient in getting full function back with liver transplant,” said researcher and co-author Bruce Hammock, a distinguished professor of entomology with a joint appointment at the UC Davis Comprehensive Cancer Center.

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Comprehensive care benefits transplant patient, her family

Teen’s life renewed with new kidney.

The most recent statistics from the National Kidney Foundation indicate that there are more than 118,000 people waiting for lifesaving organ transplants around the country. A vast majority of those individuals are in need of new kidneys. In an 11-county region surrounding UC Davis Medical Center and covered by the organ donor network Sierra Donor Services, more than a thousand people now await lifesaving transplants for heart, liver, lung, kidney, intestine and pancreas. Locally and nationally the need for organs far exceeds the number of donations.

Working hard to address such daunting needs, the UC Davis Transplant Center has become one of the nation’s top sites for kidney transplantation. Its program, which received an excellence award in 2012 from the independent firm HealthGrades for superior clinical outcomes, is now the fourth-largest program of its kind in the nation.

The center offered the type of comprehensive expertise that young Berenice Jasso needed several years ago when a challenging illness became life-threatening and, ultimately, could only be cured with a new kidney. For nearly two years, the then-13 year old and her family lived in fear that at any moment Berenice could lapse into convulsions, wake up blind, fall into a coma or lose her memory because of the illness.

Lavjay Butani, a UC Davis specialist in pediatric kidney disease, helped identify Berenice’s condition and determined that she needed a transplant. Fortunately, in Berenice’s case, a donor was easily found. Her mother, Maria, turned out to be a perfect match and able to donate one of her kidneys.

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New approach to heart valve replacement wins at Big Bang business competition

ViVita Technologies includes UC Davis vet, three biomedical engineering doctoral students.

The winning team for both first place and People's Choice: (from left) Maelene Wong, biomedical engineering graduate student; Leigh Griffiths, assistant professor of veterinary medicine and epidemiology; Jeni Lee, biomedical engineering graduate student; and Gina MacBarb, biomedical engineering graduate student.

A new approach to tissue preparation that makes heart valve replacements less likely to be rejected by the body’s immune system — potentially giving transplant patients longer, healthier lives — was the clear favorite in this year’s UC Davis business plan competition — sweeping both the first prize and the People’s Choice award.

ViVita Technologies, a team comprising a UC Davis veterinarian and three biomedical engineering doctoral students, took home a total of $12,000 in the 13th annual Big Bang! Business Plan Competition, run by MBA students in the UC Davis Graduate School of Management: $10,000 for first place, decided by a team of judges, and $2,000 for the People’s Choice award, decided by a vote of the approximately 150 people who attended the awards ceremony Thursday evening (May 16) at the UC Davis Conference Center.

Second prize of $5,000 went to Davis Chem, a team that is working to commercialize a sustainable method of producing isobutryaldehyde, a common base chemical used in everything from paint to cosmetics, with genetically modified E. coli bacteria rather than with the petroleum products currently used in production.

ViVita Technologies was driven to create its product to address the current shortage of organs. “But unlike with current heart valve transplants, the patient would be free from a lifetime of drugs,” said Maelene Wong, chief executive officer of the nascent company.

The ViVita process removes substances that trigger patients’ immune response while preserving the structural integrity and functional properties of the replacement valve tissue. The method has been successfully tested on small animals, they said.

The proprietary process allows the patient’s own cells to join and grow with the transplant tissue — a process that the team says could eventually be used for any organ transplant. Such an organ transplant would allow the person to lead a normal, healthy life without fear of organ rejection and the need to spend a lifetime on anti-rejection medication. It would also allow for better transplant methods for children, who often need new transplants, and additional surgeries, when their bodies grow, Wong said.

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Nation’s first ‘breathing lung’ transplant recipient thankful for gift of life

Grandfather, 57, treated at UCLA, enjoying life with his family.

Fernando Padilla could barely breathe or walk more than a few steps. An incurable disease, pulmonary fibrosis, was causing his lungs to turn to hardened scar tissue, and he was permanently tethered to an oxygen tank. His only hope was a double lung transplant.

In November 2012, he got an early-morning call that a pair of donor lungs was available.

Upon arriving at Ronald Reagan UCLA Medical Center, he was told of a new study testing an experimental device — a portable organ-preservation system that keeps donor lungs functioning and “breathing” in a near-physiologic state outside the body during transport to a recipient, instead of the standard method, in which the organs are kept in an icebox in a non-functioning, non-breathing state.

Fernando Padilla and his wife

Padilla consented to participate in the study and was randomized to become the first patient at UCLA — and in the United States — to undergo the ‘breathing lung’ transplant using the TransMedics Organ Care System (OCS).

“If they’ve got new technology to deliver the lungs still breathing, I think that would be better than trying to wake them back up again after being on ice,” said the former construction worker, who had helped build the very same hospital where he was now a patient. “I’m just following technology.”

With the OCS, the lungs are removed from a donor’s body and are placed in a mobile high-tech box, where they are immediately revived to a warm, breathing state and perfused with oxygen and a special solution supplemented with packed red-blood cells. The device also features monitors that display how the lungs are functioning during transport.

“Lungs are very sensitive and can easily be damaged during the donation process,” said Dr. Abbas Ardehali, a professor of cardiothoracic surgery and director of the heart and lung transplantation program at UCLA. “The cold-storage method does not allow for reconditioning of the lungs, but this promising technology enables us to potentially improve the function of the donor lungs before they are placed in the recipient.”

In addition, the technology could help transplant teams better assess donor lungs, since the organs can be tested in the device, over a longer period of time. It could also help address the shortage of available organs by allowing donor lungs to be safely transported across longer distances, expanding the donor pool for the more than more than 1,650 Americans who are currently on the waiting list for a lung transplant.

Padilla’s donor lungs were transported, using the OCS, from a neighboring state to UCLA. His seven-hour transplant surgery was a success, and he now relishes every deep breath. The oxygen tanks are long gone. He walks several miles a day with his wife, plays with his grandkids and enjoys life with his family. They are immensely grateful to the organ donor who supplied him with the precious “gift of life.”

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Heart failure patient loses 100 pounds before transplant surgery

“If a patient is very obese, he bears a lot of risks and complications.”

Suitulaga “Sugi” Hunkin has been overweight most of his life. He attributes that to his love of food and his Samoan ancestry.

Because of his size, he also had trouble breathing and experienced irregular heartbeat – symptoms his doctors diagnosed as heart disease called cardiomyopathy, which usually leads to heart failure.

“Here I am thinking I’m on top of the world at the age of 27 and all of a sudden I ran into a brick wall,” said Hunkin, who tipped the scale at 350 pounds by his mid-20s. “I couldn’t believe it. I was in denial.”

He needed heart transplantation surgery to replace his failing heart, but before that could happen, he needed to lose at least 100 pounds.

“If a patient is very obese, he bears a lot of risks and complications, inter-operatively as well as post-operatively,” said Georg Wieselthaler, M.D., professor of surgery of UC San Francisco’s Division of Adult Cardiothoracic Surgery, and director and surgical chief of the UCSF Cardiac Transplantation and Mechanical Circulatory Support. “And therefore it’s absolutely favorable for patients to try and have a body mass index of below 35 before going into a complex operation.”

Body mass index (BMI) measures a person’s body fat based on height and weight. Normal BMI is between 18.5 and 24.9; overweight is 25-29.9; and obesity is BMI of 30 or greater.

Hunkin chose UCSF to help him with his heart failure. Its pioneering cardiothoracic surgery program was established 50 years ago by chair Leon Goldman, M.D., and Benson Roe, M.D.. The Heart and Lung Transplant Program has historically had high one-year survival outcomes among academic surgery programs nationally.

To help Hunkin stay alive, Wieselthaler installed a ventricular assist device (VAD), a mechanical device that helps a failing heart pump blood. The VAD allowed Hunkin stay alive, but it did not help him lose weight.

“A switch clicked in my head,” he said. “I need to get on the ball. It’s not fair to my wife and my kids, and it’s not fair to myself. It’s not fair to the doctors that are treating me. Everybody’s doing so much. It comes down to me.”

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