An Unusual Research Relationship and a Successful Project

Last year, as a PGY-1 in internal medicine, Petra Mamic, MD, knew she was interested in research and was casting about for a project. She talked with a number of faculty, including Errol Ozdalga, MD (assistant professor, general medicine) and Stephen Ruoss, MD (professor, pulmonary and critical care medicine), looking for suggestions about potential mentors and directions to follow. The name of Kristan Staudenmayer, MD (assistant professor, surgery), came up, so Mamic made an appointment to meet with her.

“I went to talk with Dr. Staudenmayer about potential research opportunities,” said Mamic. “I gave her some very broad ideas about things I was interested in, and within 30 minutes together we were able to brainstorm several very interesting and concrete research ideas. Through this brief interaction, Dr. Staudenmayer inspired confidence in me, and I had no doubt that I wanted to work with her, no matter what the project.”

From the other side of this mentoring equation, Staudenmayer summarized her mentoring approach: “I usually mentor someone who in interested in trauma surgery, emergency general surgery, or surgical critical care. But since I care for patients in the ICU, I also manage complex medical issues.  In addition, my research is in health services research. As a result, my research extends beyond surgical issues to broader medical subjects. I think that is why Petra was referred to me.”

With the mentoring relationship set, it was time to choose the right project.  Fortunately, Staudenmayer has access to data and a passion for teaching research methods.

“I have a number of databases that are ready to go.  They contain national-level data that are pretty easy to use, such as administrative data on emergency room visits and hospitalizations. These are ideal for residents who do not have a lot of time. Petra only had one month, so we needed to pick a reasonable study design using existing data. We first carved out a testable question.  Next, I bought her the software she needed to do analyses and taught her some very basic statistical skills.“

She continues: “What I find is that most residents are able to take it from there, because it’s a question that they are passionate about and because it fits into the trajectory for their future. It always surprises me just how independent they become so quickly.”

Looking through those databases, Mamic noticed that a lot of cardiac patients, especially heart failure patients, were being hospitalized with infections with Clostridium difficile, a dangerous and potentially deadly bacterium. So she read more about heart failure and the changes in the gut that are associated with this disease, and thought there might be a pathophysiological explanation behind the high rates of C. difficile in this particular population.

“The hemodynamics of heart failure result in significant venous congestion and microarterial hypoperfusion in the gut,” Mamic explains. “This basically sets the gut up to be more anaerobic, creating an environment with less oxygen than normal, and an environment in which an anaerobic bacterium such as C. difficile thrives. This is possibly one of the reasons why heart failure patients seem to be predisposed to C. difficile infection.”

Mamic continues: “So I started looking at it a little more closely and I brought what I found back to Dr. Staudenmayer and she was really excited by the results, which was somewhat surprising to me because she is a trauma surgeon and a critical care doctor and not a cardiologist. But she thought the results were interesting and definitely worthwhile looking into further.”

With a promising hypothesis, Mamic continued her research. “We decided to focus on the highest-risk patients, which would be heart failure patients who were hospitalized with other common bacterial infections, such as urinary tract infection, pneumonia, and sepsis. These patients were likely to have received antibiotics, which is the most significant risk factor for C. difficile infection.”

“We found that these patients had higher rates of C. difficile infection compared to patients hospitalized with the same bacterial infections but without heart failure. Furthermore, we found that heart failure was independently associated with higher rates of C. difficile infection.  We also found a significant impact of C. difficile on in-hospital mortality in patients with heart failure.”

Staudenmayer agrees: “When Petra came up with preliminary findings, we were surprised.  We re-analyzed and confirmed the results. There is biologic plausibility to what she found, and it has clinical implications for managing patients with congestive heart failure. Since I am not a cardiologist, I asked her to show the findings to her cardiology co-mentor Paul Heidenreich, MD (professor, cardiovascular medicine), and he agreed. “

Reflecting on her project, Mamic concludes: “This research project was great, and I think the results are pretty interesting. But I think it becomes even more significant if it can change clinical practice in a meaningful way. Clearly, there are more prospective studies to be done, but I really think that what we found may suggest one simple potential intervention through which we could improve outcomes for heart failure patients. One way of approaching this would be through routine C. difficile screening of the asymptomatic high-risk heart failure population, followed by a decolonization regimen.”

Staudenmayer is similarly pleased with the outcome of this mentoring relationship: “Petra’s fantastic. We are refining and confirming all analyses, and she already has a first draft of the manuscript done. There is still a lot of work to be done, but the bulk of it is finished.”

In summary, Staudenmayer reflects on this project with these words: “Petra did a fantastic job. She was very organized. She would take down all of the recommendations, go away, and come back having done everything that was recommended and so much more. She had all of her questions about next steps spelled out. 

“She wasn’t just interested in checking a box. She was really interested in understanding every step. She was a joy to work with and has done an amazing job.”

Late Bulletin: The European Society of Cardiology has accepted an abstract written about this research. Mamic has been invited to present it orally in London this summer.