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Visfatin Serum Levels Predict Mortality in Critically Ill Patients


Abstract and Figures

The adipokine visfatin, also termed pre-B-cell colony-enhancing factor (PBEF), is mainly derived from adipose tissue but has been implicated in the regulation of innate immune responses. We hypothesized that visfatin could be a potential circulating biomarker in critical illness and sepsis. We therefore measured serum levels of visfatin in a cohort of 229 critically ill medical patients upon admission to the intensive care unit (ICU). In comparison to 53 healthy controls, visfatin levels were significantly elevated in medical ICU patients, especially in patients with sepsis. Visfatin serum concentrations were strongly associated with disease severity and organ failure but did not differ between patients with or without obesity or type 2 diabetes. Visfatin levels correlated with biomarkers of renal failure, liver dysfunction, and other adipokines (e.g., resistin, leptin, and adiponectin) in critically ill patients. High visfatin levels at ICU admission indicated an increased mortality, both at the ICU and during long-term follow-up of approximately two years. Our data therefore demonstrate that circulating visfatin is a valuable biomarker for risk and prognosis assessment in critically ill patients. Furthermore, visfatin seems to be involved in the pathogenesis of excessive systemic inflammation, supporting further research on visfatin as a therapeutic target.
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Research Article
Visfatin Serum Levels Predict Mortality in Critically Ill Patients
Alexander Koch,
Ralf Weiskirchen ,
Alexander Krusch,
Jan Bruensing,
Lukas Buendgens ,
Ulf Herbers,
Eray Yagmur,
Ger H. Koek,
Christian Trautwein,
and Frank Tacke
Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH-University Hospital Aachen,
Pauwelsstrasse 30, 52074 Aachen, Germany
Medical Care Center, Dr. Stein and Colleagues, Mönchengladbach, Germany
Section of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre (MUMC),
Maastricht, Netherlands
Correspondence should be addressed to Frank Tacke;
Received 24 January 2018; Accepted 22 July 2018; Published 26 August 2018
Academic Editor: Julie Bienertová-Vašků
Copyright © 2018 Alexander Koch et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The adipokine visfatin, also termed pre-B-cell colony-enhancing factor (PBEF), is mainly derived from adipose tissue but has been
implicated in the regulation of innate immune responses. We hypothesized that visfatin could be a potential circulating biomarker
in critical illness and sepsis. We therefore measured serum levels of visfatin in a cohort of 229 critically ill medical patients upon
admission to the intensive care unit (ICU). In comparison to 53 healthy controls, visfatin levels were signicantly elevated in
medical ICU patients, especially in patients with sepsis. Visfatin serum concentrations were strongly associated with disease
severity and organ failure but did not dier between patients with or without obesity or type 2 diabetes. Visfatin levels
correlated with biomarkers of renal failure, liver dysfunction, and other adipokines (e.g., resistin, leptin, and adiponectin) in
critically ill patients. High visfatin levels at ICU admission indicated an increased mortality, both at the ICU and during long-term
follow-up of approximately two years. Our data therefore demonstrate that circulating visfatin is a valuable biomarker for risk and
prognosis assessment in critically ill patients. Furthermore, visfatin seems to be involved in the pathogenesis of excessive systemic
inammation, supporting further research on visfatin as a therapeutic target.
1. Introduction
Besides their important roles in metabolism, adipocytokines
or adipokines, i.e., hormones released from adipose tissue,
are increasingly recognized as important regulators of immu-
nity [1]. It has been suggested that adipokines contribute to
the excessive systemic inammatory reaction commonly
observed in critical illness. We and others have previously
shown that serum levels of the adipokines resistin and adipo-
nectin are signicantly elevated in critically ill patients and
are associated with patientsmortality [26]. Relatively few
data exist on visfatin in the setting of critical illness. The adi-
pokine visfatin was initially identied in lymphocytes and is
therefore also called pre-B-cell colony-enhancing factor
(PBEF) [7]. Leukocytes have been identied as a major
source of circulating visfatin [8]. Moreover, visfatin is also
involved in activation and attraction of inammatory cells.
Experimental data obtained from human cells and mouse
models revealed that visfatin is a chemoattractant for neu-
trophils [9], promotes neutrophil survival [10], and induces
the dose-dependent release of cytokines in monocytes [11].
Interesting ndings obtained from smaller trials demon-
strated elevated visfatin serum levels in patients with respira-
tory diseases [1214] and neonatal sepsis [15] as well as in
patients with severe trauma or with critical neurological dis-
eases [2]. Based on these ndings, we analyzed circulating
visfatin levels in a large cohort of 229 prospectively enrolled
critically ill patients at our medical intensive care unit (ICU)
Disease Markers
Volume 2018, Article ID 7315356, 8 pages
in order to dene the potential pathogenic role of visfatin in
critical illness and its utility as a clinical biomarker in the
ICU setting.
2. Materials and Methods
2.1. Study Design and Patient Characteristics. Critically ill
patients were included at admission to the medical ICU at
the University Hospital Aachen, Germany. Patients, who
were admitted for postinterventional observational stay or
underwent an elective procedure, were excluded [16]. The
local ethics committee approved our study in accordance to
the ethical standards laid down in the Declaration of Helsinki
(reference number EK 150/06). The patients were catego-
rized as sepsis and nonsepsis according to the Third Inter-
national Consensus Denitions for Sepsis and Septic Shock
(Sepsis-3)[17] and were treated following the current guide-
lines for treatment of sepsis (Surviving Sepsis Campaign)
[18]. As a healthy control group, we analyzed blood donors
(36 male, 17 female, median age 37 years, range 2567 years,
BMI median 25 kg/m
, range 1934 kg/m
) with normal
blood counts, normal values of liver enzymes, and a negative
serology for viral hepatitis and HIV [19].
In order to determine long-term outcome, we contacted
the patients, their relatives, and/or the general practitioner
in approximately 6-month intervals after discharge from
hospital for two years [19].
2.2. Measurements of Visfatin and Adipokines. Blood samples
were collected at the time of admission (before specic thera-
peutic measures had been started at the ICU) and centrifuged,
and serum was stored at 80
C. Visfatin was analyzed with a
commercial ELISA kit (USCN Life Science, #E90638Hu,
BIOZOL Diagnostica, Eching, Germany). Measurements of
the other adipocytokines and related proteins resistin, adipo-
nectin, leptin, and leptin receptor were included as previously
reported [3, 4, 20].
2.3. Statistical Analysis. Due to the high range of visfatin
values, especially comparing healthy controls and critically
ill patients, all visfatin serum concentrations are presented
as logarithmic values. The Mann-Whitney U-test was used
to test dierences between the two groups; correlations were
tested according to Spearmans rank correlation method.
All values, including outside values as well as far out values,
were included. pvalues less than 0.05 were considered as
statistically signicant.
The prognostic value of visfatin on the outcome was
evaluated by Cox regression models. Survival curves were
generated by Kaplan-Meier analyses with a visfatin cuto
level calculated via the Youden Index [21]. All analyses were
performed with IBM SPSS Statistics (SPSS; Chicago, Illinois).
3. Results
3.1. Visfatin Serum Levels Are Signicantly Elevated in
Critically Ill Patients as Compared with Healthy Controls.
Visfatin serum levels were measured in a prospectively
recruited cohort of 229 critically ill medical patients. Visfatin
serum concentrations were approximately one log-fold higher
in critically ill patients (median visfatin log 2.61 ng/ml, range
0.784.25, Table 1) compared to healthy controls (n=53,
median visfatin log 1.66 ng/ml, range 0.303.21, p<0 001;
Figure 1(a)). Visfatin levels did not correlate with the age,
neither in patients (r=0 24,p=0723) nor in healthy con-
trols (r=0101,p=0474). Of the 229 ICU patients, 142
were admitted due to sepsis, while 87 patients had a critical
illness due to other origin such as cardiopulmonary,
Table 1: Baseline patient characteristics and visfatin serum measurements.
Parameter All patients Nonsepsis Sepsis
Number 229 87 142
Sex (male/female) 133/96 51/36 82/60
Age median (range) (years) 63 (1890) 61 (1885) 64 (2090)
APACHE II score median (range) 16 (243) 14.5 (233) 18 (343)
ICU days median (range) 7 (1137) 5 (145) 9.5 (1137)
Death during ICU n(%) 60 (26%) 15 (17%) 45 (32%)
Death during follow-up (total) n(%) 107 (47%) 31 (36%) 76 (54%)
Mechanical ventilation n(%) 157 (69%) 53 (61%) 104 (73%)
Preexisting diabetes n(%) 73 (32%) 27 (31%) 46 (32%)
Preexisting cirrhosis n(%) 23 (10%) 16 (18%) 7 (5%)
BMI median (range) (m
/kg) 25.9 (15.986.5) 25.5 (15.953.9) 26.0 (17.186.5)
WBC median (range) (×10
/μl) 12.8 (0149) 12.0 (1.829.6) 14.0 (0149)
CRP median (range) (mg/dl) 92 (5230) 17 (5230) 153 (5230)
Procalcitonin median (range) (μg/l) 0.7 (0.03207.5) 0.2 (0.03100) 2.3 (0.10207.5)
Creatinine median (range) (mg/dl) 1.35 (0.121.6) 1.0 (0.215.0) 1.7 (0.121.6)
INR median (range) 1.18 (0.913) 1.17 (0.96.7) 1.18 (0.913)
Log visfatin median (range) (ng/ml) 2.61 (0.784.25) 2.51 (0.783.89) 2.70 (1.084.25)
For quantitative variables, median and range (in parentheses) are given. APACHE: acute physiology and chronic health evaluation; BMI: body mass index;
CRP: C-reactive protein; ICU: intensive care unit; INR: international normalized ration; WBC: white blood cell.
2 Disease Markers
Visfatin log (ng/ml)
Controls (n = 53)
p < 0.001
Patients (n = 229)
Visfatin log (ng/ml)
No (n = 87)
p = 0.040
Ye s ( n = 142)
Visfatin log (ng/ml)
≤30 (n = 158)
>30 (n = 50)
BMI (kg/m2)
Visfatin log (ng/ml)
No (n = 152)
Ye s ( n = 73)
Visfatin log (ng/ml)
≤10 (n = 48) >10 (n = 131)
p = 0.001
Visfatin log (ng/ml)
40 50
r = 0.305
p < 0.001
Figure 1: Visfatin levels in critically ill patients. (a) Visfatin serum concentrations (displayed as log visfatin) are signicantly elevated in
critically ill patients compared with controls. (be) Subgroup analyses of visfatin levels in critically ill patients, according to sepsis (b),
obesity (c) (dened by body mass index (BMI) above 30 kg/m
), diabetes (d), or disease severity (APACHE II score above 10). (f) Visfatin
levels correlate with APACHE II score in critically ill patients.
3Disease Markers
gastrointestinal, or hepatic disorders (Table 2). Patients with
sepsis had further elevated visfatin levels compared to nonsep-
sis ICU patients (visfatin log 2.70 ng/ml versus 2.51 ng/ml,
p=004; Figure 1(b)). Within the sepsis patients, the site of
infection (e.g., pneumonia, bloodstream, abdominal, and
urogenital) did not aect visfatin concentrations.
3.2. Diabetes or Obesity Did Not Impact Visfatin Levels at
Admission to the ICU. As high visfatin levels have been
consistently associated with obesity, type 2 diabetes, and the
metabolic syndrome [7, 22, 23], we tested whether obesity
or type 2 diabetes as a comorbidity at ICU admission
impacted visfatin levels. Unexpectedly, neither obesity as
dened by a body mass index (BMI) above 30 kg/m
(Figure 1(c)) nor preexisting type 2 diabetes (Figure 1(d))
was associated with visfatin serum concentrations. Moreover,
serum glucose at ICU admission or glycosylated haemoglobin
A1 (HbA1c) did not correlate with visfatin levels in critically
ill patients (data not shown). In addition, n=23 patients
admitted to the ICU had preexisting liver cirrhosis. Their vis-
fatin levels (median log visfatin 2.88, range 1.823.74) did not
dier signicantly from ICU patients without liver cirrhosis
(median log visfatin 2.57, range 0.784.25, p=0 151).
3.3. Visfatin Serum Concentrations Are Strongly Associated
with Disease Severity. Based on our nding of high levels of
visfatin in ICU patients, we next tested the potential associa-
tion of visfatin with the severity of critical illness. In fact,
patients with an acute physiology and chronic health II
[APACHE II] score above 10 displayed signicantly higher
visfatin serum levels than patients with APACHE II values
below or equal to 10 (Figure 1(e)). Moreover, visfatin
levels directly correlated with APACHE II scores (r=0 305,
p<0001; Figure 1(f)), sequential organ failure assessment
(SOFA), or simplied acute physiology score 2 (SAPS2)
scores (Table 3).
3.4. Visfatin Levels Are Correlated with Biomarkers of Renal
Failure, Liver Failure, and Metabolic Disturbances in
Critically Ill Patients. Due to the well-established role of
Table 2: Disease etiology of the study population leading to
ICU admission.
Sepsis Nonsepsis
142 87
Etiology of sepsis critical illness
Site of infection n(%)
Pulmonary 82 (58%)
Abdominal 26 (18%)
Urogenital 4 (3%)
Other 30 (21%)
Etiology of nonsepsis critical illness n(%)
Cardiopulmonary disorder 29 (33%)
Acute pancreatitis 11 (13%)
Acute liver failure 4 (5%)
Decompensated liver cirrhosis 15 (17%)
Severe gastrointestinal hemorrhage 6 (7%)
Nonsepsis other 22 (25%)
Table 3: Correlations with visfatin (log) serum concentrations at
ICU admission (Spearman rank correlation test, only signicant
results are shown).
Parameters ICU patients
Disease severity
APACHE II score 0.305 <0.001
SOFA score 0.494 <0.001
SAPS2 score 0.406 <0.001
C-reactive protein 0.256 <0.001
Procalcitonin 0.379 <0.001
suPAR 0.418 <0.001
White blood cell count 0.131 0.048
Interleukin-6 0.291 <0.001
TNF 0.331 0.003
Interleukin-10 0.423 <0.001
Renal function
Creatinine 0.421 <0.001
GFR (creatinine) 0.427 <0.001
Cystatin C 0.383 <0.001
GFR (cystatin C) 0.372 <0.001
Urea 0.377 <0.001
Uric acid 0.231 <0.001
Liver function
Protein 0.352 <0.001
Albumin 0.365 <0.001
Pseudocholinesterase 0.316 <0.001
Bilirubin 0.167 0.012
Bilirubin (conjugated) 0.212 0.009
Alkaline phosphatase 0.218 0.001
AST 0.196 0.004
INR 0.315 <0.001
Prothrombin time 0.336 <0.001
aPTT 0.283 <0.001
D-dimers 0.380 <0.001
Antithrombin III 0.456 <0.001
Fibrinogen 0.385 <0.001
Leptin 0.340 0.001
Leptin receptor 0.318 0.002
Adiponectin 0.235 0.02
Resistin 0.313 0.002
APACHE: acute physiology and chronic health evaluation; aPTT: activated
prothrombin time; AST, aspartate aminotransferase; GFR: glomerular
ltration rate; INR: international normalized ratio; SAPS: simplied
acute physiology score; SOFA: sequential organ failure assessment;
suPAR: soluble urokinase plasminogen activator receptor; TNF: tumor
necrosis factor.
4 Disease Markers
circulating visfatin in systemic inammation and cytokine
release [24], we analyzed correlations of visfatin in ICU
patients with various biomarkers of inammation, organ
dysfunction, and metabolism (Table 3). Visfatin concentra-
tions correlated closely with markers of inammation
including C-reactive protein, procalcitonin, interleukin-6
(IL-6), and other cytokines (Table 3), conrming observations
obtained in neonatal sepsis [15]. Visfatin also correlated with
soluble urokinase plasminogen activator receptor (suPAR,
Figure 2(a)), a prognostic biomarker of inammation in the
ICU setting [25]. Circulating visfatin displayed a close associ-
ation with renal dysfunction, as indicated by several markers
including creatinine, cystatin C (Figure 2(b)), and their
glomerular ltration rates (Table 3). Similar results were
noted for markers reecting liver function like albumin
(Figure 2(c)), bilirubin, and coagulation factors (Table 3).
Visfatin levels correlated with the other adipocytokines
and related proteins assessed in our cohort, namely, leptin,
leptin receptor, adiponectin, and resistin (Table 3).
3.5. High Visfatin Serum Concentrations at ICU Admission
Are Associated with Adverse Prognosis. In critically patients,
who subsequently died during the ICU treatment (n=60),
we found signicantly elevated visfatin levels at admission
to the ICU (Figure 3(a)), suggesting that visfatin might serve
as a prognostic biomarker in critical diseases. In fact, Cox
regression analysis revealed that visfatin was a robust predic-
tor of ICU mortality (p<0001). Kaplan-Meier curves were
calculated with a cutovalue of log visfatin 2.89 ng/ml that
showed the optimal ratio of sensitivity and specicity for mor-
tality using the Youden Index. Here, visfatin levels clearly dis-
criminated between survivors and nonsurvivors (Figure 3(b)).
Even patients that are successfully discharged from the
ICU have a tremendous risk of mortality during the rst
years of follow-up [26]. We were able to assess long-term sur-
vival in 220 out of the 229 patients. Visfatin levels at ICU
admission were signicantly higher in patients that died
during the follow-up period of approximately two years
compared with survivors (Figure 3(c)). Cox regression anal-
ysis conrmed the prognostic value of visfatin as a predictor
of long-term mortality (p=0001). Using the calculated
optimal cuto(log visfatin 3.01), patients with high visfatin
demonstrated an unfavourable outcome, as depicted by
Kaplan-Meier survival curve analysis (Figure 3(d)). The
validity and performance of visfatin as a biomarker for the
prediction of ICU or overall survival in critically ill patients
are summarized in Table 4.
Notably, visfatin levels appeared more suited to predict
outcome in comparison to other adipocytokines. By receiver
operating characteristics (ROC) curve analyses, visfatin levels
reached an area under the curve (AUC) to predict ICU mor-
tality of 0.687, while resistin (0.562), adiponectin (0.623), lep-
tin (0.404), and leptin receptor (0.580) demonstrated lower
values. For overall mortality, visfatin reached a higher AUC
of 0.686 compared to resistin (0.563), adiponectin (0.638),
leptin (0.407), and leptin receptor (0.609).
4. Discussion
The dysregulation of adipocytokines has been widely noted
in critical illness and linked to systemic inammation.
Among interesting candidates of adipokines as biomarkers,
leptin, adiponectin, and resistin have been thoroughly
investigated [14, 20]. In this study, we focused on visfa-
tin, an adipocytokine with several metabolic but also
inammation-orchestrating functions [24]. In a large cohort
of prospectively enrolled critically ill medical patients, we
demonstrate that visfatin serum levels are highly elevated com-
pared to controls, associated with sepsis and disease severity,
correlated to organ dysfunction, and, most importantly, serve
as a reliable predictor of mortality. Our ndings are well in
agreement with smaller trials reporting elevated visfatin and
the association with poor outcome in patients with respiratory
diseases [1214] and neonatal sepsis [15]. Similar ndings
have also been reported from patients with severe trauma or
with critical neurological diseases [2].
The close association between high visfatin levels and
increased short- or long-term mortality in our study may be
well explained by the strong correlations between visfatin
and inammatory mediators and cytokines, disease severity
Visfatin log (ng/ml)
0 5.0 10.0
suPAR (ng/ml)
15.0 20.0
r = 0.418
p < 0.001
Visfatin log (ng/ml)
Cystatin C (mg/l)
0 2.0 4.0 6.0 8.0
r = 0.383
p < 0.001
Visfatin log (ng/ml)
Albumin (g/l)
0 2.0 4.0 60.0
r = 0.365
p < 0.001
Figure 2: Visfatin levels correlate with inammation and organ failure. (ac) Correlation analyses revealed associations between serum visfatin
and biomarkers of systemic inammation (e.g., soluble urokinase plasminogen activator receptor (suPAR)) (a), renal failure (e.g., cystatin)
(c, b), or hepatic dysfunction (e.g., albumin) (c).
5Disease Markers
(e.g., clinical scores), and biomarkers reecting organ failure.
However, there is increasing evidence emerging that visfatin is
directly involved in the pathogenesis of critical illness and sys-
temic inammation. Visfatin was found to be a chemoattrac-
tant for neutrophils [9] and has direct eects on neutrophil
survival [10], which could jointly promote excessive release
of cytokines [24], production of oxidative stress factors, and
subsequently result in tissue damage and organ failure [2].
In support of this hypothesis, the experimental inhibition of
visfatin in mouse models of ventilator-associated lung injury
reduced neutrophil inltration, organ injury, and mortality
[9]. Moreover, distinct single-nucleotide polymorphisms
(SNPs) in the visfatin gene have been identied in humans
[27, 28], of which the SNP 1543T was linked to a reduced risk
of mortality, while the SNP 1001G was associated with a
higher risk of mortality in patients with acute respiratory
distress syndrome [29].
In our cohort, 24% of the critically ill medical patients
were obese or morbidly obese, as dened by a BMI above
30 kg/m
. This is in line with observations in the United
States, where at least 25% of adult ICU patients are over-
weight, obese, or morbidly obese [30, 31]. Interestingly, we
did not nd dysregulated visfatin levels between ICU patients
with or without obesity, supporting that circulating visfatin
p < 0.001
Visfatin log (ng/ml)
Survivor ICU (n =169) Death ICU (n = 60)
Log rank 12.458
p < 0.001
ICU survival (%)
Time (days)
100 125
Visfatin log > 2.89 ng/ml
Visfatin log ≤ 2.89 ng/ml
p = 0.002
Visfatin log (ng/ml)
Survivor overall (n =113) Death overall (n =107)
Log rank 16.030
p < 0.001
0 200 400
Time (days)
Visfatin log > 3.01 ng/ml
Visfatin log ≤ 3.01 ng/ml
600 800 1000
Overall survival (%)
Figure 3: Visfatin is a biomarker for mortality in critically ill patients. (a) At the time of ICU admission, patients that died during the course of
ICU treatment had signicantly higher serum visfatin levels than survivors (p<0 001). (b) Patients with high or low visfatin levels displayed
dierent ICU mortalities by Kaplan-Meier survival curve analysis. (c) A similar observation was obtained when visfatin levels at ICU
admission were compared between patients that died during the total observation period and survivors (p=0 002). (d) High visfatin levels
at ICU admission predicted the overall mortality during long-term follow-up in critically ill patients (Kaplan-Meier survival curve analysis
for the optimal visfatin cutois displayed).
6 Disease Markers
levels in critical illness are primarily attributable to the extent
of inammation and not adiposity itself. Nonetheless, visfa-
tin levels were closely correlated with adiponectin, resistin,
and (inversely) leptin, indicating a concerted yet rectied
activation of adipose tissue inammation [1].
As outcome prediction is of major interest in the ICU
setting, there is a high medical need to complement current
prognostic models (e.g., APACHE II, SAPS, and SOFA) by
additional biomarkers that could indicate the long-term
prognosis beyond the acute critical illness [32]. Visfatin dem-
onstrated in our study an exceptional value to predict the
overall mortality during a two-year follow-up period. Thus,
our data indicated that visfatin could be possibly used, either
alone or in combination with other adipokines, for a more
accurate prognostication in critical illness.
5. Conclusions
We demonstrate in our study comprising 229 critically ill
medical patients that circulating levels of the adipokine visfa-
tin were signicantly elevated at admission to the ICU, as
compared with healthy controls. Visfatin serum concentra-
tions were strongly associated with disease severity, organ
failure, and sepsis, but not with obesity or type 2 diabetes.
High visfatin levels at ICU admission indicated an increased
mortality, both at the ICU and during long-term follow-up.
Further research should aim at implementing visfatin as a
prognostic biomarker in a comprehensive risk assessment
algorithm at the ICU. Moreover, the close association
between visfatin and prognosis as well as experimental data
on visfatin neutralization in animal models supports to
explore visfatin as a therapeutic target in excessive systemic
inammation and sepsis.
Data Availability
The data used to support the ndings of this study are
available from the corresponding author upon request.
Conflicts of Interest
The authors declare no conict of interest.
This work was supported by the German Research
Foundation (DFG; Ta434/5-1 and SFB/TRR57) and the Inter-
disciplinary Center for Clinical Research (IZKF) Aachen.
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Table 4: Serum visfatin (log) performance as a biomarker to predict
ICU or overall mortality.
ICU mortality Overall mortality
Visfatin (log) optimal cuto2.8882 3.0094
Sensitivity 0.63 0.45
Specicity 0.69 0.80
Positive predictive value 0.42 0.68
Negative predictive value 0.84 0.60
Youden Index 0.32 0.25
LHR+ 2.02 2.20
LHR0.53 0.69
Diagnostic odds ratio 3.77 3.18
LHR: likelihood ratio.
7Disease Markers
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8 Disease Markers
... Visfatin is secreted by a variety of cell types, including lymphocytes, neutrophils, macrophages, and epithelial cells [8], and is closely associated with various types of inflammatory diseases, including psoriasis [9], atherosclerosis [10] and acute lung injury [11], as well as sepsis [12]. Recently, a high level of serum Visfatin was observed in patients with sepsis, which was also positively associated with a high mortality, indicating that Visfatin might serve as a circulating biomarker of sepsis disease [13]. Nevertheless, studies on the specific role of Visfatin in sepsis and its mechanism have not been reported so far, nor has there been any study on its relationship with intestinal damage caused by sepsis. ...
... The intestine has always been regarded to play a critical role in the pathophysiology of sepsis and is usually considered as the "motor" of this systemic inflammatory response syndrome [29]. Visfatin, an adipocytokine with metabolic and immune functions, has been evidenced to directly participate into the pathogenesis of critical illness and systemic inflammation [13]. To our knowledge, there have been no studies focusing on the effect of Visfatin on sepsis-related diseases. ...
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Background The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism. Methods C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines. Results The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866. Conclusion In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.
... Their main surface receptors and molecules involved in the recognition of cells are shown. c Molecular mechanism of UCP1 in producing heat AT produces a wide range of adipokines that play key roles in the regulation of glucose and lipid metabolism [27], and their dysregulation has been linked to systemic inflammation [28]. (Table 1). ...
... [28] [28] [27] [29] Monocyte chemotactic protein-1 (MCP1) ...
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Excessive fatty acids and glucose uptake support the infiltration of adipose tissue (AT) by a variety of immune cells including neutrophils, pro-inflammatory M1 macrophages, and mast cells (MCs). These cells promote inflammation by releasing pro-inflammatory mediators. The involvement of MCs in AT biology is supported by their accumulation in the AT of obese individuals along with significantly higher serum levels of MC-derived tryptase. AT-resident MCs under the influence of locally derived adipokines such as leptin become activated and release pro-inflammatory cytokines including TNFα that worsens the inflammatory state. MCs support angiogenesis in AT by releasing chymase and inducing preadipocyte differentiation and also the proliferation of adipocytes through 15-deoxy-delta PGJ2/PPARγ interaction. Additionally, they contribute to the remodeling of the AT extracellular matrix (ECM) and play a role in the recruitment and activation of leukocytes. MC degranulation has been linked to brown adipocyte activation, and evidence indicates an important link between MCs and the appearance of BRITE/beige adipocytes in white AT. Cell crosstalk between MCs and AT-resident cells, mainly adipocytes and immune cells, shows that these cells play a critical role in the regulation of AT homeostasis and inflammation.
... Studies have shown that NAMPT was increased in inflammatory environment, such as diabetes, inflammatory bowel disease, rheumatoid arthritis, and myocardial infarction [21,22]. Koch et al. found that the level of NAMPT in serum can predict the mortality of patients with sepsis [23]. MiR-96-5p relieved inflammatory response by binging to NAMPT and inactivating NF-κB pathway sepsis [6]. ...
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Purpose: Present study is aimed to explore the role of miR-186-5p in sepsis-induced coagulation disorders and molecular mechanisms. Methods: Thirty-four sepsis patients and 34 respiratory infection/pneumonia patients were selected in the present study. Polymicrobial sepsis model was created by cecal ligation and puncture (CLP). The mRNA expression was detected by qRT-PCR. Western blot was utilized to measure protein expression. Thromborel S Reagent was applied to measure the prothrombin time (PT). Platelet count of blood was measured via LH 780. ELISA kits were utilized to evaluate the fibrinogen and PAI-1 concentration. Results: MiR-186-5p expression was lower and nicotinamide phosphoribosyltransferase (NAMPT) mRNA expression was higher in sepsis patients in contrast to control group. Coagulation time was markedly prolonged and platelet count was markedly decreased in CLP mice. In addition, fibrinogen concentration was obviously lower and PAI-1 concentration was obviously higher in CLP mice. MiR-186-5p mimic obviously decreased coagulation time and PAI-1 concentration, while raised platelet count and fibrinogen concentration. Targetscan predicted miR-186-5p might directly regulates NAMPT, and luciferase reporter assay verified this prediction. In addition, miR-186-5p mimic obviously inhibited the mRNA expression of NAMPT. Knockdown of NAMPT improved coagulation dysfunction in sepsis. Overexpression of NAMPT reversed the improvement effect of miR-186-5p on coagulation dysfunction. MiR-186-5p mimic markedly inhibited NF-κB pathway. Conclusion: MiR-186-5p inhibited sepsis-induced coagulation disorders via targeting NAMPT and inactivating NF-κB pathway.
... Various adipokines, i.e., hormones derived mainly from the adipose tissue, exert immunomodulatory actions, being implicated in the inflammatory response during sepsis [31][32][33][34]. Previous studies have highlighted that circulating adipokines are altered during sepsis in critically ill patients and may serve as diagnostic and prognostic biomarkers [35][36][37][38][39][40][41][42][43]. However, chemerin has not been thoroughly studied in sepsis. ...
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Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 μg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 μg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 μg/L, p < 0.001; one week after: 374.9 ± 95.3 vs. 261.6 ± 91.9 μg/L, p < 0.001), and in nonsurvivors than survivors (sepsis onset: 427.2 ± 96.7 vs. 306.9 ± 92.1 μg/L, p < 0.001; one week after: 414.1 ± 94.5 vs. 264.2 ± 79.9 μg/L, p < 0.001). Moreover, patients with septic shock and nonsurvivors, presented a significantly lower absolute and relative decrease in chemerin one week after sepsis onset compared to baseline (p < 0.001). Based on ROC curve analyses, the diagnostic performance of chemerin (AUC 0.78, 95% CI 0.69–0.87) was similar to C-reactive protein (CRP) (AUC 0.78, 95% CI 0.68–0.87) in discriminating sepsis severity. However, increased chemerin at sepsis onset and one week later was an independent predictor of 28-day mortality (sepsis onset: HR 3.58, 95% CI 1.48–8.65, p = 0.005; one week after: HR 10.01, 95% CI 4.32–23.20, p < 0.001). Finally, serum chemerin exhibited significant correlations with the severity scores, white blood cells, lactate, CRP and procalcitonin, as well as with biomarkers of glucose homeostasis, but not with cytokines and soluble urokinase-type plasminogen activator receptor (suPAR). Circulating chemerin is increased early in sepsis and its kinetics may have diagnostic and prognostic value in critically ill patients. Further studies are needed to shed light on the role of chemerin in sepsis.
... The serum adipocytokines as shown in Table 1 (8,(13)(14)(15)(16)(17)(18)(19)(20)(21) (adiponectin, leptin, resistin, chemerin, visfatin, vaspin, C-X-C motif chemokine-12/stromal cell-derived factor-1 [CXCL-12/SDF-1] and angiotensinogen) were measured with an enzyme-linked immunosorbent assay kit (R&D Systems, Minneapolis, MN). To evaluate endothelial damage, plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) were measured. ...
Introduction: Cytokines compose a network and play crucial roles in the pathogenesis and prognosis of sepsis. Adipose tissue is an important immune endocrine organ that releases adipocytokines. This study aimed to evaluate adipocytokines in sepsis from a network perspective. Materials and methods: This retrospective study of 37 patients with sepsis and 12 healthy controls was conducted from February 2014 to July 2015. Blood samples were collected from patients on days 1 (within 24 h of diagnosis), 2, 4, 6, 8, 11, and 15 and from healthy controls. Adipocytokines (adiponectin, leptin, resistin, chemerin, visfatin, vaspin, CXCL-12/SDF-1, angiotensinogen), inflammatory cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α, monocyte chemotactic protein [MCP-1]), and plasminogen activator inhibitor-1 were measured. Acute Physiology and Chronic Health Evaluation II score was evaluated on day 1, and Sequential Organ Failure Assessment (SOFA) score and Japanese Association for Acute Medicine (JAAM) and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation (DIC) scores were assessed at the times of blood sampling. Results: Hierarchical clustering analysis showed the cluster formed by resistin, IL-6, IL-8, MCP-1, and IL-10 on days 1, 2, and 4 represented the cytokine network throughout the acute phase of sepsis. Each cytokine in this network was significantly associated with SOFA and JAAM DIC scores over the acute phase. A Cox proportional hazards model focusing on the acute phase showed a significant relation of these five cytokines with patient prognosis. Conclusions: Adipocytokines and an inflammatory cytokine profile assessed over time in sepsis patients showed that resistin was involved in an inflammatory cytokine network including IL-6, IL-8, IL-10, and MCP-1 in the acute phase of sepsis, and this network was associated with severity and prognosis of sepsis.
... 63 High eNAMPT levels at the time of admission to the intensive care unit correlate with disease severity and may predict mortality in patients with sepsis and ARDS. 76,77 Unfortunately, no single biomarker has been shown to reliably provide information about the patient's overall disease outcome and thus stratify patients for enrollment in clinical trials. However, recent efforts to combine biomarkers demonstrate that prognostic ability can be greatly enhanced. ...
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Recent innovations in translational research have ushered an exponential increase in the discovery of novel biomarkers, thereby elevating the hope for deeper insights into “personalized” medicine approaches to disease phenotyping and care. However, a critical gap exists between the fast pace of biomarker discovery and the successful translation to clinical use. This gap underscores the fundamental biomarker conundrum across various acute and chronic disorders: how does a biomarker address a specific unmet need? Additionally, the gap highlights the need to shift the paradigm from a focus on biomarker discovery to greater translational impact and the need for a more streamlined drug approval process. The unmet need for biomarkers in acute respiratory distress syndrome (ARDS) is for reliable and validated biomarkers that minimize heterogeneity and allow for stratification of subject selection for enrollment in clinical trials of tailored therapies. This unmet need is particularly highlighted by the ongoing SARS-CoV-2/COVID-19 pandemic. The unprecedented numbers of COVID-19-induced ARDS cases has strained health care systems across the world and exposed the need for biomarkers that would accelerate drug development and the successful phenotyping of COVID-19-infected patients at risk for development of ARDS and ARDS mortality. Accordingly, this review discusses the current state of ARDS biomarkers in the context of the drug development pipeline and highlight gaps between biomarker discovery and clinical implementation while proposing potential paths forward. We discuss potential ARDS biomarkers by category and by context of use, highlighting progress in the development continuum. We conclude by discussing challenges to successful translation of biomarker candidates to clinical impact and proposing possible novel strategies.
... 22 Adipose tissue also produces a great number of other adipokines, including resistin and visfatin, 23,24 which affect the immune system and may be associated with adverse outcome of sepsis. 22,25,26 Of further relevance, at least with respect to leptin and adiponectin, it is known that plasma levels of both are decreased during severe sepsis, 27 making that the timing of measurement of plasma adipokines is of extreme importance. ...
The SARS‐CoV‐2 pandemic has led to worldwide research aiming to identify the risk factors for developing critical illness and mortality caused by COVID‐19. It quickly became apparent that besides older age, obesity is one of the most important risk factors for a more severe course of COVID‐19, although the mechanisms remain largely unknown [1‐3]. Notably, with respect to acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), evidence is mounting that obesity is a risk factor for ARDS/ALI, but among people with ARDS/ALI, obesity is associated with better outcome, a phenomenon which has been called the “obesity paradox” [4,5].
... In our study, we found no associations between resistin levels in patients with CA and history of coronary artery disease, stroke, diabetes mellitus, obesity, smoking or alcoholic beverages. This reinforces the idea that in an acute critical illness high levels of resistin (or other adipokines) are mostly due to inflammatory status and not to adipose tissue mass or preexisting unhealthy lifestyle [32]. ...
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. The systemic response to ischemia-reperfusion that occurs after a cardiac arrest (CA) followed by the return of spontaneous circulation leads to endothelial toxicity and cytokine production, both responsible for the subsequent occurrence of severe cardiocirculatory dysfunction and early death. Resistin is emerging as a biomarker of proinflammatory status and myocardial ischemic injury and as a mediator of endothelial dysfunction. The study aimed to analyze the possible associations between several clinical and biological variables and the serum levels of resistin in CA survivors. Forty patients with out-of-hospital resuscitated CA, were enrolled in the study. Demographic, clinical and laboratory data (including serum resistin measurements at admission and at 6, 12, 24, 48 and 72 h) were recorded. For resistin, we calculated the area under the curve (AUC) using the trapezoidal method with measurements from 0 to 12 h, 0 to 24 h, 0 to 48 h and 0 to 72 h. Fifteen (37.5%) patients died in the first 72 h after CA. Cardiovascular comorbidities were present in 65% of patients. The majority of patients had post-CA shock (29 (72.5%)). Resistin serum levels rose in the first 12–24 h and decreased in the next 48–72 h. In univariate analysis, advanced age, longer duration of resuscitation, high sequential organ failure assessment score, high lactate levels, presence of cardiovascular comorbidities and the post-CA shock were associated with higher resistin levels. In multivariate analysis, post-CA shock or cardiovascular comorbidities were independently associated with higher AUCs for resistin for 0–12 h and 0–24 h. The only identified variable to independently predict higher AUCs for resistin for 0–48 h and 0–72 h was the presence of post-CA shock. Our data demonstrate strong independent correlation between high serum resistin levels, cardiac comorbidities and post-CA shock. The impact of the post-CA shock on serum concentration of resistin was greater than that of cardiac comorbidities.
... Exogenous LPS may alter the expression of tolllike receptor (TLR)-4 and levels of many proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 [22]. Visfatin may be used as a potential clinical biomarker during sepsis and serious illness that is induced by severe systemic inflammation [24]. Inflammation is a series of host defense responses against endogenous and exogenous damaging factors [41]. ...
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Visfatin acts as a significant regulator of inflammatory cytokines. However, the immunological response and therapeutic effects of visfatin under bacterial stress in murine lung tissue are still not clear. To investigate the role of visfatin on lipopolysaccharide (LPS)-induced acute lung injury (ALI), thirty Kunming mice were divided into Saline, LPS, and LPS + visfatin groups. After routine blood examination, the effects of visfatin on inflammatory cytokines, lung tissue structure, and expression of inflammatory mediators were explored through hematoxylin-eosin (H&E), Masson and immunohistochemical staining, quantitative polymerase chain reaction (Q-PCR), and Western blotting. Compared with the Saline group, neutrophil percentage, peripheral blood neutrophil count, and the ratio of lymphocyte count (NLR) were upregulated in LPS group. Moreover, Masson staining showed alterations in lung tissue structure; the mRNA level of different cytokines (IL-6, IL-1β, TNF-α, IL-10, TLR4, IFN-γ) was upregulated; and the protein expression of interleukin (IL)-6, myeloperoxidase (MPO), and transforming growth factor-β1 (TGF-β) was significantly (p < 0.05) different in LPS group. Compared with LPS group, neutrophil percentage significantly decreased (p < 0.01), the numbers of lymphocytes significantly (p < 0.05) increased, NLR decreased, Masson staining of the lung was extremely different (p < 0.01), the structure of the lung was slightly damaged, and the myeloperoxidase values of lung showed no differences in LPS + visfatin. Hence, visfatin inhibits the lung inflammation induced by ALI. During the ALI, visfatin acts by decreasing NLR, downregulated the expression of MPO, enhanced antioxidant capacity, and regulated the inflammatory factors IL-1β, IL-6, IL-10, and TNF-α to reduce the lung injury.
Background & aims Intravenous lipid emulsions in parenteral nutrition may cause different metabolic responses and immune effects in critically ill patients with sepsis. The aim of this study is to investigate the effects of different lipid emulsions on changes in concentrations of adipokine and cytokine and their relationship with mortality in patients. Methods Patients enrolled in this prospective, single-center, observational cohort study, were estimated to require more than ten days of parenteral nutrition. They were treated with soybean oil-based or olive oil-based parenteral lipid emulsions. Adipokine and cytokine concentrations of septic patients were determined at enrollment and ten days after, in accordance with the diagnostic criteria of SEPSIS-3. The concentrations levels were measured in an enzyme-linked immunosorbent assay. Mortality was analyzed using the Kaplan-Meier method and Cox regressions. Results Over a 25-month period, 145 patients were assessed for eligibility and consequently, 40 patients were analyzed. On admission, both groups had comparable physiological scores, comorbidities, malnutrition risk, anthropometric measurements, metabolic/hematologic biomarkers and concentrations of adipokines and cytokines (p>.05). Serum leptin, resistin, and cytokines (IL-6, IL-10, IL-1β and TNF-α) decreased significantly in the entire cohort over ten days following sepsis (p<.05). Serum resistin decreased in both olive oil-based and soybean oil-based lipid emulsions groups. Serum adiponectin only decreased in soybean oil-based lipid emulsions group (p<.05). There was association between survival and percentage changes in adiponectin, resistin and visfatin concentrations (log rank test: p<.05). Conclusion Adipokine and cytokine responses are affected by medical nutritional therapy in the sepsis process and adipokines may represent functional prognostic biomarkers in critically ill patients with sepsis.
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Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor- β superfamily related to inflammation and macrophage activation. Serum concentrations of GDF-15 can predict poor survival in chronic diseases, but its role in sepsis is obscure. Therefore, we investigated GDF-15 as a prognostic biomarker in critically ill patients. We measured GDF-15 levels in 219 critically ill patients (146 with sepsis, 73 without sepsis) upon admission to the intensive care unit (ICU), in comparison to 66 healthy controls. GDF-15 levels were significantly increased in ICU patients compared to controls. GDF-15 was further increased in sepsis and showed a strong association with organ dysfunction (kidney, liver and lactate) and disease severity (APACHE II and SOFA score). High GDF-15 concentrations at admission independently predicted ICU (HR 3.42; 95% CI 1.33–8.78) and overall mortality (HR 2.02, 95% CI 1.02–3.88) in all ICU critically ill patients as well as in a large subgroup of sepsis patients (ICU mortality: HR 3.16; 95% CI 1.10–9.07; overall mortality: HR 2.62; 95% CI 1.14–6.02). Collectively, serum GDF-15 levels are significantly increased in critically ill patients, associated with sepsis, organ failure, and disease severity. High GDF-15 levels at ICU admission predict short- and long-term mortality risk.
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Background: Adipose tissue is an endocrine organ that plays a critical role in immunity and metabolism by virtue of a large number of hormones and cytokines, collectively termed adipokines. Dysregulation of adipokines has been linked to the pathogenesis of multiple diseases, but some questions have arisen concerning the value of adipokines in critical illness setting. The objective of this review was to evaluate the associations between blood adipokines and critical illness outcomes. Methods: PubMed, CINAHL, Scopus and the Cochrane Library databases were searched from inception through July 2016 without language restriction. Studies reporting the associations of adipokines, leptin, adiponectin, resistin and/or visfatin with critical illness outcomes mortality, organ dysfunction and/or inflammation were included. Results: A total of 38 articles were selected according to the inclusion/exclusion criteria of the study. Significant alterations of circulating adipokines have been reported in critically ill patients, some of which were indicative of patient outcomes. The associations of leptin and adiponectin with critical illness outcomes were not conclusive, in that blood levels of both adipokines did not always correlate with the illness severity scores or risks of organ failure and mortality. By contrast, studies consistently reported striking increase of blood resistin and visfatin, independently of the critical illness etiology. More interestingly, increased levels of these adipokines were systematically associated with severe inflammation, and high incidence of organ failure and mortality.CONCLUSIONS AND LEVEL OF EVIDENCEThere is strong evidence to indicate that increased levels of blood resistin and visfatin are associated with poor outcomes of critically ill patients, including higher inflammation, and greater risk of organ dysfunction and mortality. Level of evidence: Systematic review, level III.
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Background Endothelin 1 (ET-1) is a strong vasoconstrictor, which is involved in inflammation and reduced tissue perfusion. C-terminal proendothelin-1 (CT-proET-1) is the stable circulating precursor protein of ET-1. We hypothesized that CT-proET-1, reflecting ET-1 activation, is involved in the pathogenesis of critical illness and associated with its prognosis. Methods Two hundred seventeen critically ill patients (144 with sepsis, 73 without sepsis) were included prospectively upon admission to the medical intensive care unit (ICU), in comparison to 65 healthy controls. CT-proET-1 serum concentrations were correlated with clinical data and extensive laboratory parameters. Overall survival was followed for up to 3 years. ResultsCT-proET-1 serum levels at admission were significantly increased in critically ill patients compared to controls. CT-proET-1 serum levels showed significant correlations to systemic inflammation as well as multiple markers of organ dysfunction (kidney, liver, heart). Patients with sepsis displayed higher circulating CT-proET-1 than ICU patients with non-septic diseases. CT-proET-1 levels >74 pmol/L at ICU admission independently predicted ICU death (adjusted hazard ratio (HR) 2.66, 95% confidence interval (CI) 1.30–5.47) and overall mortality during follow-up (adjusted HR 2.19, 95%-CI 1.21–3.98). ConclusionsCT-proET-1 serum concentrations at admission are increased in critically ill patients and associated with sepsis, disease severity, organ failure, and mortality.
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Objective To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. DesignA consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. ResultsThe Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Conclusions Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
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Background At least 25 % of adults admitted to intensive care units (ICU) in the United States have an overweight, obese or morbidly obese body mass index (BMI). The effect of BMI on adjusted mortality in adults requiring ICU treatment for sepsis is unclear. We performed a systematic review of adjusted all-cause mortality for underweight, overweight, obese and morbidly obese BMIs relative to normal BMI for adults admitted to the ICU with sepsis, severe sepsis, and septic shock. Method PubMed, the Cochrane Library, and EMBASE electronic databases were searched through November 18, 2015, without language restrictions. We included studies that reported multivariate regression analyses for all-cause mortality using standard BMI categories for adults admitted to the ICU for sepsis, severe sepsis, and septic shock. Articles were selected by consensus among multiple reviewers. Electronic database searches yielded 10,312 articles, of which six were eligible. Data were extracted by one reviewer and then reviewed by three independent reviewers. For the meta-analyses performed, the adjusted odds ratios (aOR) of mortality were combined using a random-effects model. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale for cohort studies. ResultsFour retrospective (n = 6609 patients) and two prospective (n = 556) studies met inclusion criteria. Compared to normal BMI, across five studies each, overweight or obese BMIs reduced the adjusted odds ratio (95 % CI) of mortality [aOR] [0.83 (0.75, 0.91) p < 0.001 and 0.82 (0.67, 0.99) p = 0.04, respectively] with low or moderate heterogeneity (I2 = 15.7 %, p = 0.31 and I2 = 53.0 %, p = 0.07, respectively). Across three studies each, morbidly obese BMI and underweight BMI did not alter aOR [0.90 (0.59, 1.39), p = 0.64; I2 = 43.3 %, p = 0.17; and 1.24 (0.79, 1.95), p = 0.35; I2 = 15.6 %, p = 0.31 respectively]. Only one study clearly defined how and when height and weight measurements were calculated. Site of underlying infection and illness severity may have favored overweight and obese BMIs. Conclusions This is the first meta-analysis to show that overweight or obese BMIs reduce adjusted mortality in adults admitted to the ICU with sepsis, severe sepsis, or septic shock. More rigorous studies that address these limitations are needed to clarify the impact of BMI on sepsis ICU outcomes. Trial registrationPROSPERO International prospective register of systematic reviews 10.15124/CRD42014010556. Registered on July 11, 2014.
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Visfatin, protein secreted by visceral adipose tissue, exerts insulin-mimetic actions. Visfatin concentration increases in patients with longer-standing diabetes type 2 with progressive b-cell dysfunction. Data about the role of visfatin in newly diagnosed glucose metabolism abnormalities are limited. Evaluation of visfatin concentration in patients with obesity, in relation to the presence of newly diagnosed glucose metabolism disorders. The study included 68 subjects with obesity, without a previous diagnosis of abnormal glucose metabolism. In all subjects we performed an oral glucose tolerance test, and according to the results the group was divided into the subgroups: A (n = 31), with glucose metabolism disorders (impaired fasting glucose, impaired glucose tolerance and type 2 diabetes); and B (n = 37), without abnormalities. In all subjects serum lipids, uric acid, C-peptide, glycated haemoglobin (HbA1c), creatinine, and serum visfatin concentrations were measured. The control group comprised 30 lean, healthy individuals with normal glucose tolerance. We found elevated visfatin levels in obese individuals versus the control group (50.0 ± 48 vs. 26.7 ± 22.1 ng/mL; p = 0.01). Visfatin concentrations in both subgroups, A and B, did not differ (40.86 ± 27.84 vs. 57.7 ± 59.79 ng/mL; p = 0.19). In subgroup A visfatin concentration correlated significantly with triglycerides (r = 0.37, p = 0.038), HbA1c (r = -0.43, p = 0.02), C-peptide (r = -0.38,p = 0.048), and waist-hip ratio (r = -0.41, p = 0.036). The presence of newly diagnosed glucose metabolism abnormalities in obese subjects had no influence on the visfatin level, probably due to preserved endogenous insulin secretion and relatively short exposure to hyperglycaemia in patients with prediabetes or at early stage of type 2 diabetes. (Endokrynol Pol 2015; 66 (2): 108-113).
Objective: Predictors of long-term functional impairment in acute respiratory failure of all causes are poorly understood. Our objective was to assess the frequency and predictors of long-term functional impairment or death after invasive mechanical ventilation for acute respiratory failure of all causes. Design: Population-based, observational cohort study. Setting: Eight adult ICUs of a single center. Patients: All adult patients from Olmsted County, Minnesota, without baseline functional impairment who received mechanical ventilation in ICUs for acute respiratory failure of all causes from 2005 through 2009. Interventions: None. Measurements and main results: In total, 743 patients without baseline functional impairment received mechanical ventilation in the ICU. At 1- and 5-year follow-up, the rates of survival with return to baseline functional ability were 61% (366/597) and 53% (356/669). Among 71 patients with new functional impairment at 1 year, 55% (39/71) had recovered and were alive without functional impairment at 5 years. Factors predictive of new functional impairment or death at 1 year were age, comorbidities, discharge to other than home, mechanical ventilation of 7 days or longer, and stroke. Of factors known at the time of intubation, the following are predictive of new functional impairment or death: age, comorbidities, nonsurgical condition, Acute Physiology and Chronic Health Evaluation III score, stroke, and sepsis. Post hoc sensitivity analyses revealed no significant change in predictor variables in patient populations when stroke was excluded or who received more than 48 hours of mechanical ventilation. Conclusions: At 1- and 5-year follow-up, many patients who received mechanical ventilation for acute respiratory failure from all causes are no longer alive or have new moderate-to-severe functional impairment. Functional recovery between year 1 and year 5 is possible and common. Sepsis, stroke, illness severity, age, and comorbidities predict long-term functional outcome at intubation.
The prevalence of obesity has increased starkly during the last decades, and this trend includes every age, sex, race and socioeconomic group.(1,2) According to the most recent epidemiologic data,(1,2) approximately two thirds of the US population are either overweight or obese, of whom approximately 30% are obese and more than 5% are morbidly obese. Although some reports suggest that the trend of obesity may have begun to stabilize within some segments of the US population,(3) other studies project that obesity prevalence will continue to worsen, with as many as 50% of Americans potentially being obese by the year 2030.(4) Obesity has been linked to increased mortality resulting from acute and chronic comorbidities including diabetes, stroke, and cardiovascular diseases (CVDs).(5) The epidemic of obesity also has reached the intensive care unit (ICU), such that 33% of ICU patients are obese and 7% are morbidly obese.(6) Consequently, obesity complicates all aspects of health care in the ICU by increasing the complexity of management, nutritional support, and changes in the pattern of comorbidities.(7) Furthermore, obesity induces anatomic and physiologic changes that may interfere with the body response to injury and complicate any hospitalization.(7) In this article, we will review recent studies that have examined the impact of obesity in critical illness.
RESULTS: The plasma level of visfatin in group A was signifi cantly higher than that in groups B and C ( P<0.001), and the level of visfatin in group B was significantly higher than that in group C ( P<0.001). The plasma level of visfatin was positively correlated with CRP, TNF-", APACHE II and PMN% in patients with severe pneumonia ( rho =0.653, r=0.554, r=0.558, r=0.484, respectively, P<0.05 for all), while it was negatively correlated with PaO 2 and PaO 2/FiO 2 ( rho =$0.422, r=$0.543, respectively, P<0.05 for all). CONCLUSION: Visfatin may be involved in the systematic infl ammation response in patients with severe pneumonia as a pro-infl ammatory cytokine, and it is valuable in assessing the severity of pneumonia..