When facing a life-threatening infection, the “yuck factor” is a minor concern. Fecal microbiota transplant (FMT for short) has become an accepted treatment for recurrent Clostridium difficile infection, which can cause severe diarrhea and intestinal inflammation.
In a new video, Emory physicians Colleen Kraft and Tanvi Dhere explain how FMT restores microbial balance when someone’s internal garden has been disrupted.
C. difficile or “C diff” is a hardy bacterium that can barge into the intestines after another infection has been treated with antibiotics, when competition for real estate is low. In the last few years, doctors around the world have shown that FMT can resolve recurrent C diff infection better than antibiotics alone.
At Emory, Kraft and Dhere have performed almost 300 FMTs and report a 95 percent success rate when treating recurrent C diff. They have established a standard slate of stool donors, whose health is carefully screened.
Building on their experience with the procedure, Kraft and Dhere are studying whether FMT can head off other antibiotic-resistant infections besides C diff in kidney transplant patients. They have teamed up with infectious disease specialists Aneesh Mehta and Rachel Friedman-Moraco to conduct this study. Read more
Are you experienced? Your immune system undoubtedly is. Because of vaccinations and infections, we accumulate memory T cells, which embody the ability of the immune system to respond quickly and effectively to bacteria or viruses it has seen before.
Mandy Ford has teamed up with Craig Coopersmith to investigate sepsis, a relatively new field for her, and the collaboration has blossomed in several directions
“This is an issue we’ve been aware of in transplant immunology for a long time,” says Mandy Ford, scientific director of Emory Transplant Center. “Real life humans have more memory T cells than the mice that we usually study.”
In late-stage sepsis patients, dormant viruses that the immune system usually keeps under control, such as Epstein-Barr virus and cytomegalovirus, emerge from hiding. The situation looks a lot like that in kidney transplant patients, who are taking drugs to prevent immune rejection of their new organ, Ford says.
Twenty years of research and you start toÂ improve outcomesÂ for transplant patients.
TheÂ Nature paperÂ from Chris Larsen and Tom PearsonÂ on “costimulation blockers” and their ability to head off graft rejection in rodentsÂ first appeared in 1996.
Almost 20 years later, a seven-year study of kidney transplant recipients has shown that the drug belatacept, a costimulation blocker based on Larsen and Pearson’s research, has a better record of patient and organ survival than a calcineurin inhibitor, previously the standard of care.
Kidney transplant recipients need to take drugs to prevent their immune systems from rejecting their new organs, but the drugs themselves can cause problems. Long-term use of calcineurin inhibitors, such as tacrolimus, can damage the transplanted kidneys and lead to cardiovascular disease and diabetes.
In the accompanying video, Larsen -Â now dean of Emory University School of Medicine – and Pearson -Â executive director of Emory Transplant Center – explain.
To go with the paper, NEJM has an editorial with some revealing statistics (more than 14,000 of the 101,000 patients listed for kidney transplantation are waiting for a repeatÂ transplant) and a explanatory video.Â MedPage Today has an interview with Larsen, and HealthDay has a nice discussion of the issues surrounding post-transplant drugs. Read more
A recent Associated Press story highlighted clinical trials aimed at helping kidney transplant recipients give up their anti-rejection drugs:
The experimental approach: Transplant the seeds of a new immune system along with a new kidney. Itâ€™s the 21st-century version of a bone marrow transplant, and possible for now only if the transplanted kidney comes from a living donor.
How does it work? Doctors cull immune system-producing stem cells and other immunity cells from the donorâ€™s bloodstream. They blast transplant patients with radiation and medications to wipe out part of their own bone marrow, far more grueling than a regular kidney transplant. That makes room for the donated cells to squeeze in and take root, creating a sort of hybrid immunity that scientists call chimerism, borrowing a page from mythology.
Emory Transplant Center scientific director Allan Kirk is leading a studyÂ that takes a similar approach, involvingÂ a depletion of the recipient’s immune cells andÂ an infusion of bone marrow, which introduces new immune cells from the donor.
â€œThe impetus to take the risk and pull people off immunosuppressants completely is lower now,â€ says Kirk… â€œIt’s all about risk-benefit ratios and about making smart decisions with the tools we haveâ€”and we have a lot more tools now.â€
Why go through so much trouble to avoid anti-rejection drugs?Â The most common drugs taken by transplant recipients, called calcineurin inhibitors, can reduce an individual’s ability to fight infections, lead to high blood pressure and high blood sugar and, ironically, tend to damage the kidney over time. Emory scientists played a major role in developing an alternative,Â belatacept, which was approved last year by the FDA.
Emory transplant surgeon Ken Newell was also mentioned in the AP story for his study of rare individuals who were able to go “cold turkey” and avoid having their immune systems reject their donated kidneys. One of these individuals, Lisa Robinson, had an interesting story to tell about how came to that point:
Three years after her kidney transplant, she found it hard to tolerate the side effects of the immunosuppressive drugs, which included swelling, weight gain and depression. On top of that, her creatinine levels were rising, indicating that her donated kidney was losing function. Without explicit approval from her doctor, she decided to taper off her drugs, first cyclosporine and then steroids.
“This turned out to be the right choice for me, but I’m not suggesting that others do what I did,” she says. “Everyone has to figure out what works for them. My main motivation was that I didn’t want to go through another kidney transplant.”
Based on data from Robinson and other people who had similar experiences, Newell has been able to identify a pattern of genes turned on in their immune cells that may predict whether someone could be able to become “tolerant.”Â Much of transplant biology focuses on one type of immune cell (T cells), but Newell found that the cells that may make the biggest difference for long-term tolerance are different, B cells. This makes sense because of B cells’ role in chronic rejection, Emory’s Stuart Knechtle has written.
Healthcare Heroes award winners Dean Thomas Lawley and Dr. Ursula Kelly
This weekâ€™s issue of the Atlanta Business Chronicle spotlights the winners of its annual Healthcare Heroes Awards, recognizing the contributions of top medical professionals in the Atlanta health care community. Emory was well represented again this year among the impressive list of winners and finalists. Winners included:
Linda Cendales, MD, assistant professor of Surgery at Emory University School of Medicine, nominated in the Healthcare Innovations category for successfully performing the stateâ€™s â€“ and one of the nationâ€™s â€“ first hand transplants on a college student from Orlando, Fla. (see Emory article)
Katherine L. Heilpern, MD, professor and chair of the department of emergency medicine, nominated in the Physician category for her contributions to emergency and trauma care and for her leadership among 5 hospitals in Metro Atlanta which receive 250,000 patient visits per year.
Curtis Lewis, MD, assistant professor of radiology, Emory University School of Medicine, nominated in the Physician category for his management and training of physicians and residents in his role as chief of staff and senior vice president of medical affairs at Grady.
When Jon Pomenville of Anderson, SC, decided to donate a kidney altruistically to someone â€“ anyonein need, anywhere in the country â€“ little did he know his selfless sacrifice would in turn change the lives of not one, but numerous individuals and their families, including one little boy from Atlanta.
And little did he know that the selfless, anonymous act would quickly become not so anonymous. During a recent post-surgical clinic visit to Emory University Hospital, Pomenville met by accident â€“ right in the transplant clinic waiting room â€“ many of the individuals whose lives were changed. Soon the patients â€“ recipients and donors â€“ two father and son combinations and Pomenville, the man who would give to anyone â€“ were hugging, shaking hands, and recounting their backgrounds and experiences.
Pomenville and the others, who were all part of what is called a paired kidney exchange, were unwittingly scheduled for appointments within a short period of one another. As one person began recounting the experience, eyes and ears began to focus on the tale being told from across a crowded room.
A chance meeting in a doctors’ waiting room led to a meeting between most of the people involved in the paired kidney exchange.
The Emory Transplant Center created and opened its innovative Paired Donor Kidney Exchange Program in 2009, providing greater hope for patients in need of kidney transplants. According to Kenneth Newell, MD, director of Emory’s living donor program, a paired exchange donation allows healthy individuals to donate a kidney to either a friend, loved one, or even altruistically to a stranger, despite incompatible blood matches. In paired donation, a donor and recipient are matched with another incompatible donor and recipient and the kidneys are exchanged between the pairs.
The procedure is another form of living donor transplantation. Donated kidneys also come from recently deceased donors. While most kidneys from deceased donors function well, studies have shown that a kidney from a living donor, either a blood relative or an unrelated person, provides the greatest chance for long-term success.
“Paired donor exchanges allow us to cast a much wider net to find compatible donors and recipients,” says Newell. “With a paired kidney transplant, one incompatible donor-pair is able to give a healthy kidney to a compatible recipient. In exchange, the second donor-recipient pair will give a compatible kidney to the first donor-recipient pair, making two compatible living donor transplants possible and increasing the potential number of available donor kidneys. This option can help those patients waiting for kidney transplants who have family members or friends willing to be donors and who are medically suitable, but who have an ABO blood type that is incompatible with the recipient’s blood type.”
Because of Pomenvilleâ€™s donation, a 7-year-old boy named Zion was able to receive a lifesaving kidney from an unrelated donor because his dad, Mike, was able to donate. His surgery took place at Children’s Healthcare of Atlanta at Egleston.
And Gerald Smith of Five Points, Ala., would receive his life-saving kidney because his son, Matt, a recent University of Alabama graduate, would donate his to Zion. And finally, 20 year-old Edward Hill of Macon, a young man with a history of health challenges, would also receive his transplant at Childrenâ€™s Healthcare of Atlanta â€“ completing the six-person cycle, although the donor of Edwardâ€™s kidney is still unknown.
And Zion and Matt Smith will not only share a common bond and connection throughout life in the form of a kidney, but something even sweeter that that â€¦ blue Powerade.
â€œIâ€™ve always really enjoyed drinking Powerade, particularly the blue flavor,â€ says Smith. Shortly after Zion awoke from his surgery, he inexplicably began requesting the blue-tinted soft drink too.
Other powerful kidney transplant stories out of Emory:
Nearly 45 years after she cared for Georgia’s first organ transplant recipient, Millie Elliott, 84, visited the Emory Transplant Center outpatient transplant clinic to see how things have changed since her time at Emory. Elliott, who was Millie Burns at the time, worked at Emory University Hospital first as an obstetrics nurse, then as head nurse of an NIH-sponsored clinical research unit at Emory from 1961 to 1967. She served as a dialysis nurse on that unit and may have been the Southeast’s first renal transplant coordinator.
During her recent visit to Emory, this former Cadet Nurse Corps nurse and World War II veteran regaled the transplant center staff and kidney transplant program director Thomas Pearson, MD, PhD, with her stories about the first transplant at Emory. Elliott recalled spending a lot of time researching medical sources to prepare herself and her nurses for that remarkable day. The first transplant patient was a 16-year -old boy with renal failure who received a donor kidney from his father.
Islet transplantation may offer people with type I diabetes the ability to produce their own insulin again
As with other types of transplantation, the challenge with islet transplantation is to avoid rejection of the donated organ and to balance that goal against side effects from the drugs needed to control the immune system. These papers illustrate how that balancing act is especially complex.
In the last decade, transplant specialists developed a method for islet transplantation named the â€œEdmonton protocolâ€ after pioneers at the University of Alberta. While the emergence of this method was a major step forward, there are limitations:
B cells are workhorses of the immune system. Their main function is to produce antibodies against bacteria or viruses when they encounter something that they recognize.Â But recently researchers have been getting hints that certain kinds of B cells can also have a calming effect on the immune system. This property could come in handy with hard-to-treat conditions such as graft-vs-host disease, multiple sclerosis, or Crohn’s disease.
Hematologist Jacques Galipeau has found that B cells treated with an artificial hybrid molecule called GIFT15 turn into “peacemakers”. These specially treated B cells can tamp down the immune system in an experimental animal model of multiple sclerosis, suggesting that they could accomplish a similar task with the human disease.
Galipeau’s paper inÂ Nature Medicine from August 2009 says succinctly: “We propose that autologous GIFT15 B regulatory cells may serve as a new treatment for autoimmune ailments.”Â Galipeau, a recent arrival to Emory from McGill University in Montreal, explains this tactic and other aspects of personalized cell therapy in the video above. Read more
A multi-patient organ swap, known as a paired donor exchange, can now save the lives of numerous people while matching each patient with the very best kidney for his or her blood profile.
Nearly 85,000 Americans are on a waiting list for a donated kidney â€“ nearly 3,000 in Georgia alone. The opportunity to quickly identify and match more organ donors and recipients is critical to saving more lives.
This month, Emoryâ€™s transplant team performed this type of exchange involving a total of six patients â€“ three donors and three recipients – from Texas, Colorado and Georgia.
In April, Howard Irving Scott, III, received a new kidney at Emory University Hospital. The kidney came to him as part of a six-person paired kidney transplant “chain,” in which three recipients and three donors were cross-matched. One of the participants was a friend of his, Casey Campbell. Although Scott did not receive Campbell’s kidney, her participation in the program made the “chain” transplant possible, saving Scott the possibility of waiting five years on a kidney.