New test predicts sepsis before blood clots cause permanent organ
damage, markedly increasing survival

Date:
March 28, 2022
Source:
University of California - Santa Barbara
Summary:
In a potential paradigm change for sepsis diagnostics, a new test
predicted sepsis soon after infection in mice -- well before blood
clotting and organ failure -- enabling early antibiotic treatment
and markedly increased survival. The findings provide a platform to
develop rapid and easy-to-perform clinical tests for early sepsis
detection and clinical intervention in human patients.



FULL STORY ==========================================================================
In a potential paradigm change for sepsis diagnostics, a new test
predicted sepsis soon after infection in mice -- well before blood
clotting and organ failure -- enabling early antibiotic treatment and
markedly increased survival.

The findings provide a platform to develop rapid and easy-to-perform
clinical tests for early sepsis detection and clinical intervention in
human patients.


==========================================================================
The collaborative effort by a research team including scientists from UC
Santa Barbara, UC San Diego, and Sanford Burnham Prebys Medical Discovery Institute (SBPMDI) is detailed in a new study published in the Lancet
journal, eBioMedicine. The team succeeded in detecting a catastrophic
shift in blood protein abundance soon after infection that can predict
sepsis well before disease symptoms and organ damage arise.

The project was led by professor Michael Mahan of UC Santa Barbara, along
with professors Dzung Le of UC San Diego, and Jeffrey Smith and Jamey
Marth of SBPMDI. Additional collaborators include UCSB scientists Douglas Heithoff and Scott Mahan, as well as SBPMDI scientists Genaro Pimienta and
Won Ho Yang, and University of Sydney veterinarian scientist John House.

Sepsis is the number one cause of death in U.S. hospitals. In the clinic, sepsis is diagnosed by a symptom-based approach that may include kidney or liver failure, blood clotting or bleeding -- which often occurs well after permanent organ damage. Thus, molecular diagnostics that detect infection
at early stages of disease to minimize host injury are sorely needed.

"The key finding was identifying proteins in the blood that arise very
soon after infection -- well before overt disease symptoms," Mahan
explained. "Early detection is critical for clinical intervention to
increase survival in sepsis patients." To carry out the test, a small
amount of blood was collected and analyzed for an increase in coagulation proteins that are induced but inactive at early stages of infection. Such detection enabled early antibiotic treatment -- well before activated coagulation proteins induced blood clotting -- resulting in markedly
increased survival in mice. The technology is open source and freely
accessible to all.

The study also demonstrated that antibiotics are less effective after
blood proteins increase in response to infection. Treatment failure may
be due to host injury triggered by excessive blood clotting, providing
insight into why delays in antibiotic treatment in human sepsis are
associated with increased risk for death.

"The future plan is to identify a biopanel of early sepsis blood proteins
for incorporation into existing blood tests, enabling sepsis prediction
well before excessive blood clotting and permanent organ damage,"
Heithoff explained.

The researchers demonstrated that the changes in blood proteins soon after infection observed in mice were similar to that reported for human sepsis.

Thus, they are optimistic that these findings are translatable for the
early detection and treatment of sepsis in humans.

"Currently, one in four patients die of sepsis, with many survivors experiencing lifelong debilitation with cognitive decline," Scott
Mahan said.

"We hope technologies like this offer new ways of delivering
state-of-the-art molecular diagnostics that predict sepsis before
permanent injury occurs." This research was funded by grants from the
National Institutes of Health's National Heart, Lung, and Blood Institute, Santa Barbara Cottage Hospital, and the U.S. Army Research Office via
the Institute for Collaborative Biotechnologies cooperative agreement
and contract.


========================================================================== Story Source: Materials provided by
University_of_California_-_Santa_Barbara. Original written by Sonia
Fernandez. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Douglas M. Heithoff, Genaro Pimienta, Scott P. Mahan, Won Ho
Yang, Dzung
T. Le, John K. House, Jamey D. Marth, Jeffrey W. Smith, Michael
J. Mahan.

Coagulation factor protein abundance in the pre-septic state
predicts coagulopathic activities that arise during late-stage
murine sepsis.

eBioMedicine, 2022; 78: 103965 DOI: 10.1016/j.ebiom.2022.103965 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220328133803.htm

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