Sepsis is a major public health problem globally. In the US, millions of patients have sepsis annually and it accounts for 1 in 2 to 3 deaths in hospitalized patients. Severe sepsis or sepsis with organ dysfunction is the leading cause of ICU admission and carries a mortality rate of almost 30%.
The Clinical Epidemiology program has been at the forefront of conducting epidemiologic studies to understand the public health burden and consequences of sepsis and to develop strategies to improve outcomes of sepsis patients. We conduct epidemiology and translational studies and clinical trials in sepsis patients. Current funding is over $8 million and most of it is through the National Institute of Health.
The Clinical Epidemiology program conducts studies across the following research themes:
We are working on a multifaceted strategy to identify and treat sepsis during the prehospital care. Our work is primarily observational, conducting both small translational and large cohort studies to understand the contribution of prehospital biomarkers and clinical data to sepsis phenotyping. We further extend this program by testing the association between various prehospital treatments, advance notification tools, and system strategies with outcomes.
Prehospital identification of high-risk sepsis (K23GM104022-01, PI: Seymour)
ThinkSepsis Prehospital recognition tool (University of Pittsburgh CTSI, PI: Seymour)
Immune regulation by RNA metabolites in sepsis (University of Pittsburgh CTSI, PI: Seymour)
“Very early” goal directed therapy in sepsis: a murine model (Surgical Infection Society, PI: Lewis / Seymour)
We focus on understanding why some individuals are at higher risk of infection, and once infection occurs, why they develop severe sepsis or die. In particular, we have focused on the role of advanced age, race, and genetic factors. This research theme leverages NIH and industry-funded studies housed in the Department of Critical Care Medicine (GenIMS), population-based cohort studies (Health, Aging, and Body Composition study, Cardiovascular Health Study, Atherosclerosis and Risk in Communities Study) housed in the Department of Epidemiology, clinical trials (ProCESS and ACCESS trials) and administrative databases (State Hospital Discharge Databases). Finally, we use animal models of sepsis, such as cecal-ligation and puncture models, to understand the role of novel pathways that may play in role in sepsis.
Combined Viral and Bacterial Infection and Zinc Homeostasis in Distal Lung (NHLBI R01HL126711, PI: Kaynar)
Neutrophil collagenase in sepsis and ventilator-induced lung injury (K08-HL086671, PI: Kaynar)
Genetic and Inflammatory Markers of Sepsis (GenIMS, R01-GM61992, PI: Angus)
Predicting risk of pneumonia in the general population (K23-GM083215, PI: Yende)
HMGB-1 in sepsis (Funded by Medimmune Inc, PI: R Delude; Co-PI Yende, completed)
Survivors of severe sepsis hospitalization have high long-term morbidity and mortality. More than one-half of all deaths that occur within one year after severe sepsis hospitalization happen after hospital discharge and those who survive often have impaired quality of life. Long-term consequences after sepsis will continue to increase with the rising incidence of sepsis and reduced short-term mortality after critical illness. This research theme focuses on two main areas using clinical epidemiologic studies and translational approaches (animal models of long-term outcomes of sepsis): cardiovascular outcomes and cognitive and mood disorders after sepsis.
Cardiovascular consequences of sepsis (ConsequenceS, R01GM097471, PI: Yende)
Cardiovascular consequences of infection and sepsis (CTSI, Basic science PI: Kaynar, Clinical PI: Yende; completed)
Prolonged Outcomes of Nitric Oxide for Ventilated Premature Babies (PrONOx, HL69991, PI: Angus, completed)
Economic Analysis of the Pulmonary Artery Catheter Use (EA-PAC, R01-HS11620, PI: Angus, completed)
Multicenter randomized clinical trials (RCTs) are the gold standard of clinical research. Investigators in the clinical epidemiology program lead or have been intimately involved in coordinating important aspects of several RCTs for sepsis. These include ProCESS, a trial testing the role of a TLR-4 antagonist, Eritoran (ACCESS), and activated protein C (PROWESS) for severe sepsis. We also are currently launching the ProACT trial, and jointly with Denver investigators, a national trial of early neuromuscular blockade for ARDS via the NIH PETAL Network.
Immunotherapy of sepsis using anti-PDL1 antibody (NIGMS R34GM107650, PI: Yende)
Procalcitonin Antibiotic Consensus Trial (ProACT) (NIGMS R01GM101197, PI: Huang)
Prevention and Early Treatment of Acute Lung Injury (PETAL Network, NHLBI) (Site PIs: Angus, Yealy [Emergency Medicine]. Protocol PIs: Huang, Moss [Denver])
Platform foR European Preparedness Against (Re-) emerging Epidemics (PREPARE, European Commission’s FP7 program 602525, PI: Goossens H, Co-PI: Angus D).
Protocolized Care for Early Septic Shock (ProCESS, P50-GM076659, PI: Angus, completed)
Director: Sachin Yende, MD MS
Melanie Scott, PhD