# Inflammation Phenotypes in Pediatric Sepsis Induced Multiple Organ Failure Renewal

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $500,320

## Abstract

Carcillo R01 Project Abstract
Every year over 1 million American adults and children develop overwhelming infection leading
to a rotting of their body we call ‘sepsis’, and death in up to 1 of 3 afflicted
(www.nigms.nih.gov>NIGMS Home>Science Education). National efforts emphasizing early
recognition, intravenous fluids to help organs, and antibiotics to kill infection, have reduced
mortality so that now 1 of 4 die. We and others have asked the question “why do patients
continue to die despite these national efforts?’ In the previous funding period we showed in
401 children with sepsis that those who developed organ shut down despite these efforts, did so
because they were a) unable to fight germs causing unending infection, b) unable to stop
clotting off their body causing kidney failure, and/or c) unable to kill viruses causing liver failure;
all of which led to death from uncontrolled inflammation with clotting, bleeding and liver failure.
Fortunately, each of these organ shutdown groups has hopeful treatments. With the new
information we collected in the previous funding period we have already designed and started
clinical trials testing these treatments including immune boosters for children unable to kill
germs, plasma removal and replacement using plasma exchange for children unable to stop
clotting, monoclonal antibodies to kill viruses and their homes to reverse liver failure in children
unable to do so on their own, and anti-inflammatory proteins to reverse uncontrollable
inflammation, in hopes of helping save many of the 1 of 4 children still dying from sepsis related
organ shutdown. In this next funding period, we propose to use the clinical information and
samples already obtained in our previous study to take advantage of the wonderful advances
made this millenia in computer technology, big data, bioinformatics, and the study of human and
virus genetics to perform Specific Aim 1) use a ‘Watson’ like approach to ask the computer to
help us figure out if the children with sepsis have any other causes of organ shutdown that we
can help, Specific Aim 2) use an ‘Ancestry.com’-like or ‘23 and me’-like approach to identify
‘precision medicine’ therapies for causes of organ shutdown that we can treat on a patient by
patient basis, and Specific Aim 3) use a bedside molecular biology test approach to identify
individualized therapies to kill DNA viruses and reduce cytokine inflammation. We think that
DNA viruses are the unappreciated co-infection which causes uncontrolled cytokine
inflammation and leads to organ shutdown. Our long term objective is to plan ‘precision’
medicine and ‘individualized’ medicine clinical trials testing therapies on an individual patient
basis in order to further reduce death from sepsis organ shutdown in children.

## Key facts

- **NIH application ID:** 10017690
- **Project number:** 5R01GM108618-06
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** JOSEPH A CARCILLO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $500,320
- **Award type:** 5
- **Project period:** 2014-03-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017690

## Citation

> US National Institutes of Health, RePORTER application 10017690, Inflammation Phenotypes in Pediatric Sepsis Induced Multiple Organ Failure Renewal (5R01GM108618-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017690. Licensed CC0.

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