Y-ECCO Interview Corner: Maria Abreu

What is your background? Where did you grow up?

I was born and raised in New Jersey of Cuban parents who were recent immigrants at the time that they had me and my brother. And the particular town where I grew up (West New York, New Jersey) was really always a town of immigrants. I suppose that is the story of America anyway, right? And in my generation, it was mostly Italian and Cuban immigrants that came to this town. I think, in hindsight, it was because there were so many factories in America then. My mother was a schoolteacher. She was really so smart. She passed away a year ago. But she was the brains of the family. In Cuba my father was a farmer. And here, in the United States, he worked at a chemical factory in New Jersey.

This was a time in America when it was possible to be an immigrant and have a living wage. I have really very fond memories of that. Then we moved to Miami when I was a teenager. And so, I feel Miami's home, even though I've lived away from this home for long stretches of time.

Maria Abreu

What kind of kid were you?

I think probably nerdy, very nerdy. I studied a lot and I was very disciplined about my grades and intense. Now I am into running and I was talking recently with someone who asked me, "Oh, did you always like to run?" But actually, I did absolutely nothing like this until I was in my mid-forties – my parents made education a priority. And that was my job. My job was to get good grades and try to make them proud.

And was there an impact on you in having parents from that background?

Well, I always describe myself as the typical first born of immigrant parents, an overachiever – it was always going to be medicine or something like that. My brother's an engineer; I think that's not a coincidence. You have constant reminders that you have to study to get ahead. I certainly don't want to go so far as to say there was a need to break out of poverty, rather a desire to use education to escape from the difficulty of the day-to-day life of an immigrant who is just managing to get by. And all that shapes you. Mostly I view it in positive ways. I almost feel sorry for people who can't find a motivation like that.

So, it sounds like your parents were quite keen for you to become a doctor. Were you also enamoured of that idea from early on?

Oh, very early on. I knew that's what I wanted to do from very, very early on. But in general terms, the privilege of getting into people's lives and knowing about them in such an intimate way and trying to help them has always resonated with me.

And once you came into medicine, how did it end up being IBD and gastroenterology?

I did this accelerated program where I only did two years of college instead of four, and then went straight to medical school. Once I did rotations, I realised that I was an internist. And then once I did a rotation in gastroenterology, I unexpectedly absolutely loved it. I loved the spectrum of illness that is encompassed by gastroenterology. In that particular rotation, I got to work with famous people from advanced endoscopists to people who were very well known in acid-related disorders. And then IBD: I think everything in life is serendipity and being exposed to people that you want to emulate and that you admire. In this case, it was Steph Targan. He's a brilliant physician scientist and prescient in a lot of his concepts related to IBD. I met him when I was looking for a lab to work in when I was a GI fellow and I really fell in love with his passion for the disease. And so, I thought, "Well, if this super cool guy can do this, maybe I should do this too." I also always loved immunology; it was one of my favourite subjects in medical school. IBD is a nice marriage of those two things. Over time, you realise that IBD is so special because you're treating patients who are young or middle-aged; they have lives, they're professional people and they just want to get on with it.

Now I can say I've been doing IBD for more than half of my life. And I have patients that I've followed since I was in Los Angeles, which was now over 20 years ago. People that have seen my children grow up, quite literally. One extreme would be being an emergency room doctor where you have no bonds with people. And then at the other extreme are the chronic diseases, where you really establish a bond with people. And I think that suits my personality and what I think is one of the nice things about taking care of patients with IBD.

And then I chose to do my GI fellowship at UCLA. There were a lot of terrific physician scientists at UCLA. At UCLA, in the training programme, we rotated just a month or two at a time at different types of hospital. In the United States, we have safety net hospitals, we have private hospitals, we have hospitals for veterans, VA hospitals. So, it was a little bit of all of those experiences at all these different hospitals. So, it was a really rich place to train. Then I joined Steph Targan at a hospital in Los Angeles called Cedars-Sinai, and I worked in his lab until I eventually had my own lab.

And while there, had the opportunity as a GI fellow to work in the labs of other people besides Steph, including a scientist called Charles Sawyers. Charles is a very famous physician scientist in oncology who has done a lot of work on chronic myelogenous leukaemia, but also prostate cancer. And coincidentally my first substantial grant was on prostate cancer before I looped back into using some of the same strategies to study GI-related diseases or IBD-specific diseases.

 What has your clinical working week been like?

Well, this week I was the inpatient attending at our safety net hospital, which means that I would drag my tired body out of work every night at eight o'clock. It has been a very intense week. In the United States, unfortunately, we don't have a national health service. So, there are people who are uninsured. They put off going to seek medical attention for a long time and present at advanced stages of disease. They have no other choice. So, you want to do the best by them because otherwise they have no other access to healthcare.

And is most of your clinical work in that setting or do you also have clinical work elsewhere?

Mostly when I'm seeing patients, we have our private clinic. We have a beautiful Crohn's and Colitis centre that we set up in 2013. The physical space is very warm and embracing for our patients that come there. We have exam rooms and we have four infusion chairs for the patients getting iv drugs. So that's where I see patients primarily. We are now five IBD physicians and two nurse practitioners. The multidisciplinary model is essential because otherwise the math doesn't work out. To see all these new patients and follow them longitudinally you need a team. Another area that makes IBD challenging is the mountain of additional work outside of the context of seeing the patient. The labs, the MRI results, the pathology results, the writing the orders for all the infusions. In the United States one of the things that's changing very quickly is that insurance companies aren't paying, or don't want to pay, for patients to get infusions in a clinic setting. They'd prefer it either at home or in less expensive settings, which makes it hard to track what is happening to patients. I see patients at least one full day a week. I've added half a day of doing telemedicine and I scope one full day a week. So, so at least two and a half days out of the week, I'm doing clinical work.

So, what do you do your other two and a half days of the week? How do they look?

I have a basic science lab. We have lab meetings and I have two graduate students and three post-docs. I'm vice chair for research for the department of medicine. And so, that creates activity. For example, we've just finished having our research day, which we couldn't do in person due to the pandemic. But it turned out to be accidentally awesome – we had record attendance at all the different activities. Really, we're going to have to hold on to some of that virtual part because it's just much more efficient. It's really with the goal of inspiring the residents to get into doing research. And so to that end, they didn't have to leave the wards. They could just log in to Zoom and watch the presentations. So, it was actually really very good.

You are also the chair for the IOIBD. Could you tell us about that organisation?

IOIBD stands for the International Organisation for the Study of Inflammatory Bowel Diseases. It started in the 1980s with leaders in the field, including John Wright in South Africa, Salvador Peña in the Netherlands, Sidney Truelove in England and John Singleton in the United States. This group wanted to have standards by which they did clinical trials and work towards a lot of the same things that we discuss now. Most ECCO Members probably know that these figures in our world of IBD really led the way in developing clinical trials and trial methodology, and not just for IBD or for GI; rather, the whole concept of placebo-controlled studies came from Truelove and Witts’ initial studies of hydrocortisone for Ulcerative Colitis. If you look at their papers on IV hydrocortisone, this was lifesaving at the time – the mortality from having a colectomy was still very high in those days. In these trials they did look at the mucosa, and they did rigid sigmoidoscopy to determine response to steroids - they were very rigorous. And I hope we've carried on that tradition.

The society is by invitation only, in that we're capped at 55 active members and then we have senior members over the age of 65. It’s important to highlight that many of our senior members are quite active. As a historical note, IOIBD is a Swedish organisation. It's officially registered in Sweden and by the rules of the organisation, the treasurer always has to be a Swede. Currently it’s Jonas Halfvarson, who has been amazing as treasurer.

Who are the members of the IOIBD and how do people get to be members?

One of the unique things about the society is that it includes adult and paediatric gastroenterologists, but it also includes colorectal surgeons and pathologists. We invite individuals who are really contributing to the field. Members are nominated by someone outside of their own country and there needs to be someone to second the nomination. Historically there has perhaps been an over-representation of North Americans and Europeans because there are so many more physicians that do IBD in those countries. But in the last couple of years, and in particular in the last two years, we really wanted to get better representation from the parts of the world that are having an increase in the incidence of IBD. So, we now have Siew Ng from Hong Kong, who has been a member for several years, and also Zhihua Ran, who is in Shanghai. We have two members from India and a new member for Mexico City who does a lot of IBD epidemiological research. New members give a 20-minute talk about their research and their lives and what got them into this society. I think the strength of the group is the fact that we do have an international perspective on how IBD is practiced all over the world, as well as the unique aspect of pathologists and surgeons, who add to the discussion.

So, what are the goals of the IOIBD? What are the aims of the organisation?

It's primarily to support research and advances in our knowledge of IBD. For example, we had a lot of COVID-related work providing guidance that was informed by all of these different practice settings. We came out with vaccine guidelines because so many doctors and patients were confused. At first, a lot of these guidelines are based on our best guess. And I feel like our collective best guess is probably better than a lot of other people's individual best guesses. We had a very famous vaccinologist who helped think through some of these guidelines for IBD patients. Although, I must say that I'm surprised at the extent to which the humoral immune response has been affected in anti-TNF-treated patients according to the early publications. We know from the large studies of Moderna and Pfizer that even after one shot of the vaccine, when the antibody titres are still quite low, patients are still protected from symptomatic infection. So, that would indicate that immunosuppressed patients may be protected in spite of not achieving a very high titre.

COVID has been a Darwinian big evolutionary push – in technology, in the way we approach each other and life. Although there has been a huge amount of tragedy, I also think it's been a time for tremendous creativity.

What have been the other important projects for the IOIBD?

So, among the recent things that IOIBD has done is updating the STRIDE guidelines. The first STRIDE was the most highly cited of all the papers from IOIBD, I think because it conceptualises or contextualises all these different publications on mucosal healing. However, when we talk about mucosal healing, this is still, in some contexts, an aspirational goal. We'd love for everyone to achieve mucosal healing, but that is still mostly aspirational. Moreover, I think that with new therapies for IBD, patients either achieve this goal in a different timeframe or there is a discordance between how well a person feels and what their mucosa looks like. So mucosal healing may have a different significance in the context of such a treatment. Based on anecdotal observations with some of the newer drugs such as ustekinumab, for example, people will feel great, but their mucosa doesn't look so great until later. In retrospect I think we accidentally hit it out of the park with anti-TNFs in terms of all the different points in the inflammatory cascade that anti-TNFs inhibit and that this translates robustly into mucosal healing.

What projects would you like IOIBD to be involved with in the future?

I'm really passionate about the structure of clinical trials. They're overly complicated. The inclusion criteria are way too restrictive. It's unnecessarily burdensome to patients - these long wash-out periods are cruel. I sincerely don't know if that's truly the EMA or the FDA that's requiring this of the drug companies or whether it is pharmaceutical companies wanting to protect themselves from the potential that a patient will have a side effect that will be blamed on them. However, it's become such a big business, these clinical research organisations. Many drug companies will use secondary organisations to actually run the studies – to provide the platforms, training, data entry systems and so on. But often this just adds another layer of complexity that doesn't necessarily translate into better quality of data. And the administrative burden is awful: it's absolutely no fun to do these clinical trials. Moreover, we need to use inclusion/exclusion criteria that reflect more of the patients that we actually see. Why shouldn't we take people who have stomas or proctitis? Why should patients with fistulas be excluded from clinical trials? Then we don't have any of these data. Also, with age restrictions. People are living longer.

If someone doesn't have a lot of very substantial co-morbidities, let them into the clinical trial. And then I think endpoints in clinical trials need to be addressed – it has become a business: central reading of endoscopy, central reading of pathology. That adds a lot of cost to these clinical trials but it's not clear what value it adds. We didn't have that in the era of the first infliximab studies, and we did okay. Ultimately, it was obvious that the drug worked. I think IOIBD has a pulpit in its role as an international organisation to have some influence on this issue and to think it through strategically. We are also working on diet guidelines, basing them on common sensical things. We have also been working on a diet screener that would be good for IBD. The diet surveys are too long. We want to have something that will be more relevant to IBD that could be used widely in clinical practice.

You've been involved with highlighting GI health for patients with minority backgrounds and also supporting trainees from minority backgrounds. Is that something that you still work with?

The first thing to say is that it's hard to define a minority here in South Florida, since more than half of the people who are here are Hispanic. The term Hispanic is a very vague term. But most people are either born in Latin America or their parents are from Latin America and actually Spanish is spoken everywhere. But since coming back to Miami, it was readily apparent that there was this huge spike in IBD in people from Latin America. Here in Miami there are still a lot of Cubans. That population has been coming for a long period of time compared to other immigrants from Latin America and that gives us an opportunity to monitor what is happening over time. So, then they come to the United States, and what my colleague found was that in the 1950s, 60s, 70s, it took an average of almost 30 years for someone from Cuba who came to the United States to develop IBD. Over the last two decades the mean time is eight years. Obviously, I think something is probably changing on the island of Cuba as well, but there's something here in this environment that is jump starting IBD.

Also, in the United States there are of course ongoing problems of inequality and racism. But you have to say, "I'm going to do everything in my power to change what I can change", and to make sure that everyone has an opportunity, that everyone has a seat at the table, that we take talented people and we support them. Because when you are different or when people have looked down at you for a large part of your life, that marks you. I want to make sure that we foster all these intelligent, energetic people to replace me and replace my generation of physicians. And some of those are people from underrepresented backgrounds. One of the things that is clear in IBD pathogenesis is that having a decrease in microbial diversity is bad. And I think that's symbolic; it's metaphorical for life and civilisation and for societies. And it’s no different in medicine. With women in GI, once you have women faculty in a programme, all of a sudden you have all these women fellows that come to your programme. And then all of a sudden, now it's like more than 50% of the fellows are women whereas previously there were no women fellows or women faculty in a lot of institutions.

What do you do when you’re not working?

I'm married and I have two grown children who, because of COVID and all these things, are back to living at home. In the last 10 years or so, I've fallen in love running and then I started cycling and swimming and doing triathlons. So, I enjoy having these perpetual challenges. I'm terrible at all these things. I'm always forcing myself to do things that are ridiculously uncomfortable, right? Like, "Let's jump into the ocean with 100 people hitting you and whacking you over the head and you're the worst swimmer." But these challenges keep me grounded. And not surprisingly, I like to have purpose in everything I do. I also love to dance salsa. Before the pandemic it was a way to have the opportunity to dance, even during the week.

What tips would you have for budding IBD doctors trying to balance family life and career?

Well, I would advise that you have to throw all of your disposable income at as much help as possible to do absolutely everything that can be done equally well by someone other than you. If you can pay for help then that buys you time for the things that only you can do, be that spending time with your kids or working on your career. Grocery delivery, people to clean the house, people to do everything that doesn't need your intellect and your physicality to do. Because you have to be present for your children, you have to be present for them with whatever time you have when you get home. If your disposable income is limited you might be lucky enough to have family close by who can help out – parents, grandparents. Whatever help you can get!

Are you a reader?

Yes, I’m reading Hamnet now. What a fantastic author. I may be a third of the way through, something like that. The description of the little girl who gets the plague, her physical findings and her breathing and everything, I thought that was just incredible – it should be in a medical textbook. It's really beautifully written.

What's in the future for you? What's next?

I think one of my things that I really want to do next is to go on a sabbatical. I am hoping to get to Italy. That's my next intermediate-term goal – to go on a sabbatical to learn ultrasound, and scientifically I want to do more microbiome stuff. And more of the statistical methods for analysing complex data sets. You rely on great statistical support for that, but many bioinformaticians don't have the clinical experience to understand what the clinical questions are or what the scientific questions are. So, I would like to be able to speak their language better – to better communicate how we should interrogate the data from a clinical perspective. Also, I would love to perfect my Italian before I die!