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Pursuing Answers to Challenging Cases: Why Research Is Our Silver Lining

This article originally appeared in the May 2015 issue of the ASA Newsletter.

Learn your lesson. Look on the bright side. Search for the silver lining.

When faced with a medical situation that results in a bad outcome, a complication or even a mortality that we did not expect, physicians seek answers. How do we avoid and handle complications, prevent medical errors and manage unexpected outcomes? Was there something different that might have given us a better outcome? We review and reflect on what happened. By discussing a case, we identify ways to improve the quality of care and outcomes.

Arun Prakash, MD, PhD

Arun Prakash, MD, PhD, Assistant Professor, University of California San Francisco

The real-life scenarios that result in morbidity and mortality can, through case reports and M&M conferences, not only lead to clinical improvements, but they also often result in questions that can best be answered through scientific discovery. This is our silver lining. The connection between research and clinical care is a two-way street: Research improves our clinical care, and the experiences of our patients suggest important research problems.

Take, for example, traumatic lung injury. “Lung injury following trauma is a major cause of morbidity andmortality,” Arun Prakash, M.D., Ph.D. writes in the abstract of his NIH-funded study. “Severe trauma can often generate conditions of ischemia reperfusion (IR) and result in sterile inflammatory injury directly or indirectly affecting the lung. The situation can then be worsened by the later onset of infection.”

Dr. Prakash is an Assistant Professor in Residence in the Department of Anesthesia and Perioperative Care at the University of California, San Francisco, who received an NIH career development grant in 2015 after having completed a FAER Mentored Research Training Grant.

“We are currently unable to predict the strength of the inflammatory response within the lung to severe trauma and individual patients’ likelihood of developing lung injury, pneumonia and long-term multi-organ dysfunction,” his abstract states. “Moreover, we are unable to effectively influence these processes therapeutically.”

Intrigued by these questions, Dr. Prakash has focused his research on the interface between sterile and infectious inflammation and how the innate immune system is able to distinguish between the two and respond appropriately. “Given my clinical interest in trauma anesthesia, and specifically airway, respiratory and hemodynamic management of critically-ill trauma patients, my research focuses on lung injury in trauma and the pathophysiology of lung ischemia reperfusion (IR) injury,” he says.

Three years ago, Dr. Prakash received a Mentored Research Training Grant – Basic Science from FAER for his project, “Investigating the Role of Innate Immune Cells and Pathways in Ventilated Lung Ischemia Reperfusion (IR) Injury.” While working on his FAER-supported project alongside his mentor, Judith Hellman, M.D., Dr. Prakash found that sterile inflammation resulting from lung ischemia reperfusion is regulated by specific cell types (alveolar macrophages), pathways (TLR4, inflammasome, and ERK), and most intriguingly by commensal microbiota. “These results advance the topic of the role of the microbiome and specific signaling pathways in immune and inflammatory processes in patients,” he said.

Work from the FAER grant period directly led to Dr. Prakash’s successful application for grant funding from the National Institute of General Medical Sciences. He received an NIH K08 in 2015. The funding is allowing him to continue this research. “If successful, the proposed studies will benefit public health by identifying targets for therapies that can prevent unnecessary lung damage early in trauma while preserving the immune system’s ability to fight off infections,” he states.

Dr. Prakash is an example of how to use research to examine questions that arise in complicated medical cases we routinely encounter and discuss. The FAER Mentored Research Training Grant was a catalyst for him to pursue answers and an academic career.

To read more about Dr. Prakash and his research, visit http://arunprakashmdphd.wix.com/the-prakash-lab.