Military Medical Research,
Год журнала:
2022,
Номер
9(1)
Опубликована: Окт. 9, 2022
Sepsis
is
a
common
complication
of
combat
injuries
and
trauma,
defined
as
life-threatening
organ
dysfunction
caused
by
dysregulated
host
response
to
infection.
It
also
one
the
significant
causes
death
increased
health
care
costs
in
modern
intensive
units.
The
use
antibiotics,
fluid
resuscitation,
support
therapy
have
limited
prognostic
impact
patients
with
sepsis.
Although
its
pathophysiology
remains
elusive,
immunosuppression
now
recognized
major
septic
death.
Sepsis-induced
resulted
from
disruption
immune
homeostasis.
characterized
release
anti-inflammatory
cytokines,
abnormal
effector
cells,
hyperproliferation
suppressor
expression
checkpoints.
By
targeting
immunosuppression,
especially
checkpoint
inhibitors,
preclinical
studies
demonstrated
reversal
immunocyte
dysfunctions
established
resistance.
Here,
we
comprehensively
discuss
recent
findings
on
mechanisms,
regulation
biomarkers
sepsis-induced
highlight
their
implications
for
developing
effective
strategies
treat
shock.
EBioMedicine,
Год журнала:
2022,
Номер
75, С. 103776 - 103776
Опубликована: Янв. 1, 2022
BackgroundInter-individual
variability
during
sepsis
limits
appropriate
triage
of
patients.
Identifying,
at
first
clinical
presentation,
gene
expression
signatures
that
predict
subsequent
severity
will
allow
clinicians
to
identify
the
most
at-risk
groups
patients
and
enable
antibiotic
use.MethodsBlood
RNA-Seq
data
were
collected
from
348
in
four
emergency
rooms
(ER)
one
intensive-care-unit
(ICU),
44
healthy
controls.
Gene
profiles
analyzed
using
machine
learning
mining
clinically
relevant
reflecting
disease
severity,
organ
dysfunction,
mortality,
specific
endotypes/mechanisms.FindingsGene
obtained
predicted
severity/organ
dysfunction
mortality
both
ER
ICU
with
accuracy/AUC
77–80%.
Network
analysis
revealed
these
formed
a
coherent
biological
program,
but
overlapping
mechanisms/pathways.
Given
heterogeneity
sepsis,
we
asked
if
could
be
assorted
into
discrete
distinct
mechanisms
(endotypes)
varying
severity.
Patients
early
stratified
five
novel
mechanistic
endotypes,
named
Neutrophilic-Suppressive/NPS,
Inflammatory/INF,
Innate-Host-Defense/IHD,
Interferon/IFN,
Adaptive/ADA,
each
based
on
∼200
unique
differences,
pathways/mechanisms
(e.g.,
IL6/STAT3
NPS).
Endotypes
had
overall
two
severe
(NPS/INF)
relatively
benign
(ADA)
groupings,
consistent
reanalysis
previous
endotype
studies.
A
40
gene-classification
tool
(accuracy=96%)
several
gene-pairs
(accuracy=89–97%)
accurately
status
validation
cohorts.InterpretationThe
indicate
immune
precede
onset
lethality,
providing
method
Critical Care Medicine,
Год журнала:
2021,
Номер
49(5), С. 748 - 759
Опубликована: Фев. 15, 2021
Sepsis
is
defined
as
a
dysregulated
host
response
to
infection
that
leads
life-threatening
acute
organ
dysfunction.
It
afflicts
approximately
50
million
people
worldwide
annually
and
often
deadly,
even
when
evidence-based
guidelines
are
applied
promptly.
Many
randomized
trials
tested
therapies
for
sepsis
over
the
past
2
decades,
but
most
have
not
proven
beneficial.
This
may
be
because
heterogeneous
syndrome,
characterized
by
vast
set
of
clinical
biologic
features.
Combinations
these
features,
however,
identify
previously
unrecognized
groups,
or
“subclasses”
with
different
risks
outcome
given
treatment.
As
efforts
subclasses
become
more
common,
many
unanswered
questions
challenges
arise.
These
include:
1)
semantic
underpinning
subclasses,
2)
conceptual
goal
3)
considerations
about
study
design,
data
sources,
statistical
methods,
4)
role
emerging
types,
5)
how
determine
whether
represent
“truth.”
We
discuss
present
framework
broader
subclasses.
intended
aid
in
understanding
interpretation
provide
mechanism
explaining
generated
methodologic
approaches,
guide
clinicians
consider
bedside
care.
