Q&A with Todd Costantini

Todd Costantini, MD FACS, is assistant director of UC San Diego Health's Level 1 Trauma Center , an assistant professor in the Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery , and an alum of the UC San Diego general surgery residency program and trauma/surgical critical care fellowship. In this interview, he discusses his ground-breaking research into ways to counteract organ-damaging inflammation; UCSD's Trauma Center and San Diego's unparalleled Trauma System; and how he balances teaching, clinical care, and teaching.

June 29, 2017 | Interview by Lindsay Morgan

You went to medical school in Minnesota before you came to UCSD in 2004, to do a general surgery residency. How did you get interested in medicine?

I was always interested in physiology, even at a young age. And I knew I was interested in taking care of people. But I wasn't sure if I wanted to be a physician or something else. I was interested, but I thought, well, it takes too long, and it's too hard. But you just keep going down the route, learn more, and the next thing you know…

You're a surgeon!

And there you are!

How did you decide to come to UCSD for your general surgery residency?

I met my wife in medical school, and we graduated in the same year, so we went looking for residency programs together. We interviewed widely and both really liked UCSD.

What did you like about UCSD?

When I was looking, my med school mentors—who were acute care surgeons and trauma surgeons—said: you've really got to look at UCSD because San Diego is a unique place for trauma care. Dr. Hoyt was in charge of trauma here at the time and a leader in the field.

And part of it was the personality of the program and the faculty. There was a sense of collegiality. You could tell that the interactions among the residents and between residents and faculty were very familiar. It seemed like a place where people would take an interest in me, get to know me.

Given that your mentors in medical school were trauma surgeons, it sounds like your interest in trauma goes pretty far back.

It does, even to before I was in med school. I had a summer job volunteering in an urban level 1 trauma center in a technician role. I always found myself gravitating towards the trauma bay—those were the patients I was most interested in, and the dynamic that most interested me.

I wonder why?

Everything has its own pace and personality. The way the day is shaped, the way people approach problems, is all very unique when you look at surgery versus medicine. I think you can figure out fairly quickly where your personality fits within that structure.

The same is true within surgery; there are differences between the way the sub-specialties approach things. Trauma is unpredictable. You don't know who's coming in the door next. You're dealing with sometimes very sick patients that you need to make immediate decisions about based on limited information.

Sounds like there's a bit of adrenaline to it.

Yeah there is. I like the trauma bay atmosphere when you have a sick patient. I enjoy making critical decisions, acting quickly, being decisive. Part of the great thing in general surgery residency is that we get exposure to a lot of different kinds of surgery, and work with a lot of great mentors, so you have time to figure out where you fit.

You're the assistant director of UC San Diego Health's Level 1 Trauma Center with Dr. Raul Coimbra, the Director. The San Diego Trauma System has been recognized as one of the strongest, most effective trauma systems in the country. In fact, a person who has sustained a life-threatening injury in San Diego County stands twice the chance of surviving than if the injury had occurred in nearly any other part of the U.S.

That's just astounding. Why are you guys so good?

Our success is rooted partly in the success of the San Diego trauma system, which includes all of the trauma centers in San Diego. The system here is very well defined and mature. It gets people to where they need to be in the shortest amount of time.

Another thing San Diego does differently is that we have a monthly gathering of all the leaders of the trauma centers in the county where we talk about how to make the system better; share complications, patient care issues, triage issues, and try to improve the quality of everybody's care.

From a UCSD standpoint, one of our unique characteristics is that trauma patients are brought directly to our trauma bay, which is attached to the surgical ICU and staffed by the trauma team and SICU nurses. Patients are not taken to the emergency room as is common elsewhere. This model allows us great continuity of care; gives us ownership of the patients from the beginning; and allows us to have really well-defined protocols.

You have several ongoing clinical and translational research projects. One of them deals with ways to counteract organ-damaging inflammation, which can occur in patients who have experienced trauma and can lead to death. Can you tell me more about this research stream?

I'm interested in what's called the systemic inflammatory response. When people are severely injured—they get hit by a car, they get shot—there are some people who will bleed to death and die immediately and there's not much you can do about it. But that's not the majority of people. The majority of people who die after trauma or suffer complicated recoveries, develop multiple organ failure. Basically, once there's an injury, your immune system goes wild and becomes over activated. We need our immune system to respond to some degree; the problem is when that response becomes over-exaggerated, and your immune system actually starts attacking your vital organs. This is something we see frequently in our patients who are severely injured.

The translational question is: why does that happen, and why can two people with the same injury have completely different hospital courses? I'm interested in this variability and ultimately what can we do to limit that inflammatory response.

Your research has shown that stimulating the vagus nerve can mitigate that inflammatory response. But not always. How come?

When I was a resident, starting in 2007, I spent two years in the research lab with Dr. Coimbra, which is when we first started doing experiments on the vagus nerve. Prior to that, the vagus nerve had been studied in severe infection, and it was discovered—and this was fairly revolutionary—that by stimulating this nerve that we all have in our neck, we can basically tone down that inflammation response. We were the first to look at using the vagus nerve to limit the response to trauma injury and burn injury. We found that if we stimulate the vagus nerve in an injured animal for 10 minutes after they are injured, they do better. They have less inflammation. They have less organ injury. It's pretty dramatic. And this has been shown by other groups in sepsis and other injuries.

How do you bring that to patients?

We've thought about electrical stimulation, but that's difficult to do in acute settings. So, we looked at pharmacologic means, tested that in animals, and it worked very well. But drugs aimed at stimulating the vagus nerve to limit inflammation haven't worked very well in humans. It works in some patients, but it doesn't work at all in a lot of patients, and you can't predict who it's going to work in and no one knows why.

That led us to this idea of uniquely human genes. The gene I'm interested in specifically is called CHRFAM7A. It's actually a human variant of the gene that mediates this vagal anti-inflammatory signal and may be responsible for the variability we see in patients.

This is potentially really significant. If you could have a pill that limits this inflammatory response, those implications are huge.

The holy grail for the trauma surgeon is having a drug or solution in the ambulance that people can get on the way to the hospital, or in the trauma bay, that's going to prevent this inflammatory response from happening in advance.

And this gene is standing between you and the holy grail?

It's certainly a good candidate.

What's the ultimate translational goal of this gene work?

A place to start is to have a screening test where I can measure a patients CHRFAM7A gene expression to determine their potential to respond favorably to a vagus nerve agonist. But that's not the whole answer, because we don't want to treat only half of the population. The next step would be developing a therapy that silences that gene.

Tell me about the research team.

Our team in the lab includes Drs. Andrew Baird, Brian Eliceiri, as well as Dr. Raul Coimbra, as the principal investigators. We also have surgical residents, research technicians, and international research fellows on the team. We were fortunate to receive some modest funding from surgical societies and UC San Diego along the way to help build some preliminary data, and we were recently awarded a grant from the NIH to carry this on for the next 5 years.

What's really exciting is, we've actually placed this human gene into a mouse, which will allow us to perform injury experiments and see how the gene affects the injury response. It should lead to some really interesting work.

As a surgeon at UCSD, not only do you perform surgeries; you also teach and conduct research. How do you make this tripartite identify work?

What I really love about my job is that I can take care of patients, and do operations, and work in the trauma bay, but I can also take the observations that I make there and walk across the street to the lab and ask some very basic, fundamental questions about why is that happening. Now those things we're studying aren't going to help the patients we're taking care of now, but it may contribute to finding those therapeutic targets that can make a difference in the future. This is what makes the surgeon-scientist role fulfilling: being able to wear both hats.

A few weeks ago, Dr. Allan Kirk, Chair of the Department of Surgery at Duke University, spoke to us as part of the 6 ^thAnnual Surgical Sciences Research Symposium. In his remarks, he discussed the decline in research funding to surgical departments, and suggested that the problem is incentives: "The financial rewards of doing research are limited," he said. "And in surgery, the gap between the fiscal rewards of research and clinical practice is the widest."

Do you agree? And if that is the problem, then how do you incentivize research?

It depends how you define incentive. There is rarely a monetary incentive to being a basic researcher. There's more pressure to be clinically active, and less ability for health centers to monetarily support your non-clinical time. And I don't think that's going to change.

There is a great incentive from the research standpoint, though. Where else can you have an idea, develop that idea, put a grant together, and have a funding agency give you a million dollars to develop the science that you are interested in? That's an incentive.

What has been a particularly rewarding moment in your career?

I always think about one patient I met taking a call one night here in the hospital who was on the breathing machine and on dialysis and frankly dying. There was talk about whether we should do anything at all or should we operate on her? We decided to operate, and found a big problem that looked pretty dire. We operated on her several more times, and, in the end, she lived. She walked out of the hospital and now she sends me cards from places she travels, and recipes around Thanksgiving. On the days when you're feeling tired or a little burnt out, it's good to have those experiences.

In the trauma bay, you encounter people of widely varied circumstances—someone who is poor, someone who is rich. Someone who lives here, someone who lives there. And that's just really interesting.

Yeah it really is. We serve a certain safety net function here, which I take pride in. It's nice to just take care of patients no matter what. We have scenarios where we are taking care of a homeless person next to a billionaire in the next room – it happens. You just take care of the patient and do what's best for them.

If you weren't a surgeon, what would you be doing?

I'd either be a pilot or I'd be a chef. Both are active, you're thinking on your feet, and there's a certain teamwork involved in it. I don't think I would be happy working in a solo environment. I'm not a sit-behind-a-desk-all-day person.