Mitchell Sally, M.D. is an assistant professor of surgery, Division of Trauma, Critical Care, and Acute Care Surgery at OHSU. He is also assigned to the section of surgical critical care, and is the GME site director, Surgical ICU with the VA Portland Health Care System. His research focus is identifying factors that contribute to organ donation success.
Where were you before coming to OHSU and what brought you here?
I grew up in Chapel Hill, N.C., and attended the University of Pennsylvania for undergraduate studies, majoring in English. I’d always had an interest in medicine; I minored in biology and chemistry at Penn. After graduating, I decided to switch gears by taking more classes and spending a year in a lab doing gene therapy research. I went to medical school at the University of North Carolina and then came to OHSU for my residency, working with Markus Grompe, M.D., for a couple of years during training. After completing residency, I worked as a general surgeon at Kaiser in Portland but decided that wasn’t what I wanted to do, ultimately. There was little time for research, and I missed the academic environment. I returned to OHSU for a trauma and critical care fellowship. Now my job is just fantastic because I get to do a little bit of everything. I feel very lucky.
What areas of research are you involved in?
I’ve always been drawn to the field of transplant surgery and associated immunology. When I first started training, I was interested in becoming a transplant surgeon. But along the way, I discovered critical care and really enjoyed being able to care for patients in that setting. Fortunately, one of the surgeons at the Portland VA, Darren Malinoski, M.D., had a tremendous background in research on potential organ donors, looking at the critical care of these patients and the immunologic process behind the determination of “death by neurologic criteria,” commonly referred to as “brain death.” I was able to stay connected to the field by getting involved with his research. I first worked with Darren during my fellowship, and was able to expand on some of the work that he had initiated, using a robust database looking at critical care values as they relate to organ outcomes. Darren and his collaborators had developed a system of donor management goals – critical care endpoints to potentially maximize the number and quality of organs from each donor. Early studies showed that if you targeted these basic normal physiologic variables in the donor, outcomes were much better in terms of the number of organs donated, as well as the success of the organs after they’re transplanted.
To illustrate, a study that I completed was to determine the optimal threshold for glucose control in organ donors after neurologic determination of death. Before the study, a standard baseline of 150 mg/dL was considered optimal, but was inconsistent with critical care guidelines. So we looked at what would happen if we raised levels. It turns out we have better outcomes when donors have slightly higher glucose levels, which was consistent with current standards of care in the ICU. These types of projects bring together my interests and experience as both a critical care physician and someone who is interested in organ donation research.
The evolution of the overall project began by looking at how meeting critical care endpoints results in more organs transplanted per donor. A database of roughly 70 to 80 values at different time points in a donor’s course was established, examining many critical care parameters and interventions. We were able to analyze the number of organs procured and the transplantation success. This database is constantly evolving, and to-date, has focused mainly on organ usage. What we’ve done in the last year or so is taken those data and combined them with data from the Scientific Registry of Transplant Recipients (SRTR), which provides information on organ recipient outcomes. This gives us a more complete picture. We can now look at certain donor characteristics, how those impact the number of organs transplanted, and, of those transplanted, how many showed long-term success in recipients. We can then make associations and create different models as to what really does affect organ utilization and organ outcomes. It’s an evolving process that started maybe six or seven years ago, and we’ve made a lot of progress. But there’s still much to do.
So the main project is ongoing and started by piecing together the big picture, and we’re now focusing on individual organs and trying to figure out what will predict successful grafts with each. One of these focused studies I’m working on right now is examining the factors that predict pancreatic graft success, which may be completely different than what makes for a successful cardiac or liver graft, based on management in the donor.
What avenues of research do you plan to explore next?
All of my research has been very clinically based so far, but my interest lies in going to the bench and examining more closely what happens during the process of “death by neurologic criteria.” We know a tremendous inflammatory reaction occurs, but we don’t fully understand what’s happening on a molecular or cellular level. So the first step is to learn more about the process, and then look at whether there’s some way to manipulate it to improve outcomes. For instance, living donor kidneys do much better than deceased donor kidneys when transplanted, so there are clearly processes at work that we have yet to fully appreciate. I’m interested in looking at epigenetic and genomic regulation around the time of “death by neurologic criteria” – what happens during and after, and is that a modifiable process?
I’m also involved in a smaller study examining coagulation in donor patients. Most appear to be hypercoaguable, and there is evidence of graft failure due to thrombosis (clotting), possibly as a result of this hypercoaguable state. My question centers on there being a way to anti-coagulate donors, which we currently don’t do, to improve success.
On a practical level, my goal is to help people waiting for organs, and make the possibility of transplantation more likely to be successful. There is a huge organ shortage in the United States with the number of people needing organs climbing, but the number of organs being donated staying the same. I want to help bridge that ever-widening gap and potentially, help narrow it.
What do you do when you’re not at work?
Spend time with my wife and daughters, four and six years old, doing normal, Northwest parent things. What could be better?