As part of Sepsis Awareness Month, the University of Florida Department of Surgery is looking at some of the work being done at the Sepsis and Critical Illness Research Center.
As many as 30-50% of surgical sepsis patients never return to their previous health status, according to Guoshuai Cai, Ph.D., an assistant professor and director of the UF Surgery Genomics Core. They instead develop what has been recently described as chronic critical illness, or CCI, battling persistent inflammation, immune suppression and poor long-term outcomes.
Cai is working to decode why two patients who develop sepsis can leave the hospital on two very different paths: one recovering steadily and the other sliding into long-term weakness, repeat infections, rehospitalizations and other setbacks.
“Precision medicine is not only vital but also very complex and requires a significant amount of investment,” said Philip Efron, MD, a professor in the Department of Surgery and director of the Sepsis and Critical Illness Research Center.
The National Institutes of Health has recognized that Cai and his lab are worth that investment, committing a total of $2,110,625 over 5 years to his research via a prestigious Maximizing Investigators’ Research Award grant.
Cai’s two-pronged approach considers two important questions: why do patients with similar in-hospital health profiles have significantly different outcomes after sepsis, and is there a way to identify biologically distinct endotypes that respond to different treatments?
Cai’s team will take a broad “multi-omic” approach, combining carefully curated clinical data with statistical modeling and artificial intelligence to spot relationships between genomics and outcomes.
His research will focus on myeloid-derived suppressor cells. These cells can drive both persistent inflammation and immune suppression in some CCI patients. His lab will map how myeloid-derived suppressor cells interact with T-cells in sepsis patients and test whether those interactions can sort patients into endotypes: actionable categories that predict who may need targeted interventions should they develop an infection.
Cai said it’s important to understand that the work has two arms: one that generates data and one that examines it.
The surgery genomics core has been continually establishing protocols for bulk, single-cell and spatial genomic sequencing, offering a centralized resource for all investigators in the Department of Surgery.
“I am excited about the department’s technology infrastructure and look forward to the collaboration with Dr. Cai on single-cell and single-extracellular vesicle multi-omics experiments,” said Robert Maile, Ph.D., an associate professor in the Department of Surgery and co-director of the Sepsis and Critical Illness Research Center.
“The data we have is very rich,” Cai said. “Part of what we’re doing is building a pipeline between clinicians, scientists and data science experts to build multi-omic analytical tools and AI modeling to turn vast clinical and genomic data into actionable insights.”
“Artificial intelligence has the power to capture patterns our own eyes can’t,” he added. “It’s very good at using data to make predictions and explore underlying mechanisms. That means patients who might otherwise face months of weakness and complications could instead receive earlier, more personalized care.”
Tyler Loftus, M.D., Ph.D., an associate professor and program director of the General Surgery Residency Program, said this first step of curating data is incredibly important.
“We have to have a specific repository of human-curated data that’s been identified as a source of ground truth for the AI to work with,” he said. “AI models can learn from that information and represent associations among those things that we wouldn’t have necessarily thought of.”
As the Sepsis and Critical Illness Research Center continues to push the bounds of sepsis research, it looks ahead to health care that treats sepsis intervention as unique to each individual rather than as a monolith. Untangling the genetic and molecular factors that lead to sepsis outcomes means patients at higher risk of CCI can be flagged early and treated quickly, improving outcomes and quality of care.