When comparing kidney failure outcomes of 379,257 kidney transplant recipients between ’99 and ’14 that were done in the US, UK Australia and New Zealand, the US had the higher rate of long term failure. Curiously, Australia and the US kidney transplant recipients did well the first year post transplant, while the UK and New Zealand did worse in this early bracket. But, long-term risk of kidney transplant failure was approximately 25% higher in the United States compared to Australia, New Zealand, and the United Kingdom. In fact, those in the US are losing 3 years of graft function on average.
The exact details of why those the US are having worse outcomes isn’t known. Is it due to worse donor kidneys, due to other comorbidities or poor post transplant follow up? I would hedge a bet that it is due to the latter. With this knowledge that our kidney transplant recipients are doing worse I think we should focus on how centers practice and deliver post-transplant long term care to figure out why we doing worse than other developed countries.
KDPI is a term that is applied to kidneys from donors to summarize how risky the donated organ is expected to be. Some of the components of KDPI include disease like hepatitis. The potential of carrying a blood borne disease makes a donor an increased risk donor or IRD. Guidelines have been published on reducing HIV, HBR and HCV transmission through organ transplantation.
Despite researchdemonstrating that these donors have equal or better post-transplant graft and patient, increased risk kidneys are less likely to be used than organs from non-increased risk donors. A study and editorial in the American Journal of Transplantation addresses this by looking at the transplant outcomes of these more riskier organs. This work ultimately comes from Dorry Segev and the group at Johns Hopkins, who are pioneering a lot of the IRD and HIV/hepatitis organ donor transplantation.
The authors looked at almost 105,000 kidney transplant candidates who were initially offered an IRD kidney. About 1/3 of these who were offered an IRD but refused had to wait 5 years before they were offered a non-IRD kidney. Furthermore, the median KDPI of the offered non-IRD kidney was higher than the original IRD they declined, 52 and 21 respectively. That means they had to wait 5 years to get a overall worse kidney! The following graph represents this last point.
Those who accepted the initial IRDs did better too. They had a 1/3 less risk of death at 6 months and a 50% lower risk of death after 6 months. Again the following graph represents this outcome.
There will never not be any risk of transmitting HCV or HIV from organ to recipient. It is a low, however, present risk. The risk of disease transmission of HCV ranges from <1 in 1,000 and for HIV to <1 in 10,000 transplants. But accepting an IRD kidney has a clear long‐term survival benefit; and we should be counseling patients to consider taking IRD offers as the benefits outweigh the risks.
The last several years has seen the pendulum swing from operative to nonoperative to operative management of acute appendicitis. In this month’s Journal of Trauma and Acute Care Surgery, a systematic review of 5 randomized control trials was summarized. The study included over 1,430 patients with uncomplicated acute appendicitis. 7272 underwent nonoperative treatment and 703 underwent operative management.
Here’s a summary of the findings:
How effective is operative management vs. nonoperative treatment at 1 year follow up?
The nonoperative, or antibiotics, group had a efficacy of 63.8%.
The operative or surgery, group had a efficacy of 93%
Risk ratio is 0.68; 95% CI, 0.60–0.77 with a p < 0.001
The operative or surgery, group had a complication rate of 23.6%
The nonoperative, or antibiotics, group had a complication rate of 7.7%
Risk ratio is 0.32; 95% CI, 0.24–0.43; with a p < 0.001
There was no difference in outcomes for perforated appendicitis, length of hospital stay, duration of pain and sick leave. Leading one to summarize that operative management of acute appendicitis is more efficacious but prone to more complications. At this point, I will still just opt to take out the appendix for my patients. What will you do based upon this information?
A new discovery from Pitt, in collaboration with the University of Toronto, was published in Friday in the journalScience Immunology that outlines how inactivating dendritic cells ultimately prevents T-Cell mediated rejection of donor allografts. This has profound implications on transplant rejection.
The model is based off the premise that SIRP-α, a marker protein on donor allograft binds to the CD47 receptor on recipient monocytes, inducing them to become dendritic cells which in turn create recipient T cells that attack the donor allograft. Inhibiting this interaction can prevent the attack on the donor allograft, thereby inhibiting rejection without depleting T cells. The video provides this in diagram.
Senior author, Fadi Lakkis, MD scientific director of the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh wants to confirm this by,
“…sequenc(ing) the SIRP-α gene in many humans who are donors and recipients of organ or bone marrow, and then ask whether a mismatch affects the outcome after transplantation.”
Every ten minutes, a person is added to the national waiting list for organ transplants. And every day, 22 people on that list die without the organ they need. Juan Carlos Izpisúa Belmonte, a Salk Institute research, wrote an article for the November 2016 issue of Scientific American describing his dream of using chimeric animals to grow human organs for patients needing transplants. Earlier today, a report in the journal Cell emerged that researchers at the Salk Institute had, for the first time, successfully created human/pig chimera embryos. A big step toward solving the organ donor shortage!
Traditionally severe heart failure patients have had their cardiac function supported by ventricular assist devices. I won’t get into too much detail on how that works, but imagine it as an external pump bypassing some blood flow from the ventricle into the aorta. The involved cannulas and bulky devices.
This week a new device, without cannulas was showcased in Science Translational Medicine. The device is a silicone sleeve ribbed with inflatable tubes. The tubes wrap around a waning heart and provides extra muscle. In early tests, the heart-snuggling sleeve restored blood flow in six living pigs after they had suffered acute cardiac arrest. If the thumping tech passes further testing, it could one day help prolong the lives of people with heart failure, an affliction that strikes around 40 million people worldwide.
In March, 2016, 21 year old Kris suffered a traumatic injury to his cervical spine when his car fishtailed on a wet road, hit a tree and slammed into a telephone pole. It left him paralyzed from the neck down.
Fast forward to summer. 10 million AST-OPC1 stem cells were injected into his paralyzed. cervical spine.
Two weeks after surgery, Kris showed some improvements. And three months later, he’s able to feed himself, use his cell phone, write his name, operate a motorized wheelchair and hug his friends and family.
AST-OPC1 cells are made from embryonic stem cells by carefully converting them into oligodendrocyte progenitor cells (OPCs), which are cells found in the brain and spinal cord that support the healthy functioning of nerve cells. This study is a part of a Phase 1/2a clinical trial that is evaluating the safety and efficacy of escalating doses of AST-OPC1 cells developed by Fremont, California-based Asterias Biotherapeutics.
When I scrub into cases it is often hard to estimate how much blood was lost between the sponges, vacuum suction, and drops. Gauss Surgical just received FDA approval for its Triton Fluid Management System, an iPad app that estimates, via a proprietary algorithm, blood loss in surgical sponges just by looking at them. Looks interesting, I wonder when it’ll be implemented at my hospital?
Odra Noel, artist and doctor, painted this map of human cells representing continents and nations. It is on show from 2 July at the Royal Society’s Summer Science Exhibition in London. Here’s a paraphrased explanation of what each cell type symbolizes, which I swiped from the exhibition’s website:
North America struggles with rising obesity, and this adipose tissue is more beautiful close up than you would imagine.
Pulmonary tissue represent Central and South America where smoking and respiratory infections are a leading cause of death.
Europe, with its ageing population, suffers greatly from neurodegenerative diseases, including dementia and is represented with neurones, brain tissue.
Cardiac muscle cells represent the Middle East and Asia as these regions have rising levels of hypertension and other causes of heart and cardiovascular failure.
The far East and the Pacific look beautiful in pancreatic acinar tissue; representing pancreatic failure or diabetes, a major problem in this area, often described as a diabetes epidemic.
Greenland is sparse, dotted with a few sperm cells because infertility is a big problem there.
The only artery is in the middle of the Amazon rainforest, the largest river in the world.
Hidden are five mitochondria, the organelle responsible for producing energy and the current focus of much research into their key roles in death, disease and ageing.
My life has much changed since leaving the world of molecular biology and into clinical medicine. I do not miss the long hours pipetting over the lab bench, frustrated over a failed 4 hour PCR. Instead, I look forward to quickly working up and treating patients. On the other hand, I have found far too many uninspired clinical publications. I miss reading an outstanding publication in the journal Nature or Science on a new second messenger system and imagining up all changes now because of this discovery.
So when the two intersect, I love it. Today, I’ll be sharing with you an example of this intersection; an example of translational medicine, the conversion of scientific discovery into what I believe will be overall health improvement…