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Skeletal Muscle Composition Predicts Outcome in Critically Ill Patients

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Parameters of patients' body composition have been suggested as prognostic markers in several clinical conditions including cancer and liver transplantation, but only limited data on its value in critical illness exist to date. In this study, we aimed at evaluating a potential prognostic value of the skeletal muscle mass and skeletal muscle myosteatosis of critically ill patients at admission to the ICU. Design: Exploratory observational cohort study. Setting: An urban, academic medical institution. Patients: One-hundred fifty-five patients treated for critical illness on a medical ICU. Interventions: None. Measurements and main results: We used routine CT scans to assess the patients' individual body composition. The skeletal muscle index as a surrogate for sarcopenia was defined as the total skeletal muscle area at the level of the third lumbar vertebra on axial CT scan, normalized for the patient's height. Myosteatosis was evaluated by assessing the mean skeletal muscle attenuation measured in Hounsfield unit at the same sectional plane. The skeletal muscle index and mean skeletal muscle attenuation at admission to the ICU were significantly higher in patients with long-term survival (180-day or 1-year mortality), while both parameters were comparable between short-term survivors and nonsurvivors (ICU mortality or 30-d mortality). Patients with a skeletal muscle index or mean skeletal muscle attenuation below our established ideal cutoff values (74.95 mm2/cm and 29 Hounsfield unit) showed a significantly reduced overall survival. These findings were confirmed in univariate and multivariate Cox regression analyses. Furthermore, myosteatosis significantly correlated with the time of mechanical ventilation, the duration of hospital stay, and the presence of sepsis. Conclusions: Our data suggest that sarcopenia and myosteatosis represent important prognostic factors in critically ill patients that can be easily obtained from routine CT scans. Both parameters at admission to the ICU yield important information on the patients' long-term outcome and might be used for early clinical decision-making in these patients.
Critical Care Explorations www.ccejournal.org 1
Critical Care
Explorations
Crit Care Expl 2020; 2:e0171
DOI: 10.1097/CCE.0000000000000171
Skeletal Muscle Composition Predicts
Outcome in Critically Ill Patients
Sven H. Loosen, MD1,2; Maximilian Schulze-Hagen, MD3; Tobias Püngel, MD1; Lukas Bündgens, MD1;
eresa Wirtz, MD1; Jakob N. Kather, MD1; Mihael Vucur, PhD4; Pia Paenholz, MD5; Münevver Demir, MD6;
Philipp Bruners, MD3; Christiane Kuhl, MD3; Christian Trautwein, MD1; Frank Tacke, MD, PhD6;
Tom Luedde, MD, PhD2,4; Alexander Koch, MD1; Christoph Roderburg, MD6
Objectives: Parameters of patients’ body composition have been sug-
gested as prognostic markers in several clinical conditions including
cancer and liver transplantation, but only limited data on its value in
critical illness exist to date. In this study, we aimed at evaluating a
potential prognostic value of the skeletal muscle mass and skeletal
muscle myosteatosis of critically ill patients at admission to the ICU.
Design: Exploratory observational cohort study.
Setting: An urban, academic medical institution.
Patients: One-hundred fifty-five patients treated for critical illness on
a medical ICU.
Interventions: None.
Measurements and Main Results: We used routine CT scans to
assess the patients’ individual body composition. The skeletal muscle
index as a surrogate for sarcopenia was defined as the total skel-
etal muscle area at the level of the third lumbar vertebra on axial CT
scan, normalized for the patient’s height. Myosteatosis was evalu-
ated by assessing the mean skeletal muscle attenuation measured
in Hounsfield unit at the same sectional plane. The skeletal muscle
index and mean skeletal muscle attenuation at admission to the ICU
were significantly higher in patients with long-term survival (180-day
or 1-year mortality), while both parameters were comparable between
short-term survivors and nonsurvivors (ICU mortality or 30-d mortal-
ity). Patients with a skeletal muscle index or mean skeletal muscle
attenuation below our established ideal cutoff values (74.95 mm2/
cm and 29 Hounsfield unit) showed a significantly reduced overall
survival. These findings were confirmed in univariate and multivariate
Cox regression analyses. Furthermore, myosteatosis significantly cor-
related with the time of mechanical ventilation, the duration of hospital
stay, and the presence of sepsis.
Conclusions: Our data suggest that sarcopenia and myosteatosis rep-
resent important prognostic factors in critically ill patients that can be
easily obtained from routine CT scans. Both parameters at admission to
the ICU yield important information on the patients’ long-term outcome
and might be used for early clinical decision-making in these patients.
Key Words: biomarker; cachexia; intensive care unit; prognosis;
sarcopenia
Despite intensive research eorts, prediction of long-term
prognosis in critically ill patients has remained poor. In
this context, the body composition was identied as a
potential factor determining the outcome of patients treated on
an ICU. Dierent authors have suggested a link between low skel-
etal muscle mass and patients´ ICU mortality (1–3). However, the
term “low skeletal muscle mass” is only poorly dened and oen
used synonymous to sarcopenia. e latter is dened as the “pro-
gressive loss of muscle mass and strength with a risk of adverse
outcomes such as disability, poor quality of life and death” by
the Special Interest Group of the European Sarcopenia Working
Group in 2010 (4). Since both muscle strength and muscle mass
are dicult to measure in clinical routine, many authors have
dened sarcopenia as a skeletal muscle area index below the 5th
percentile of the of a healthy control population (5). However,
using this denition, the role of sarcopenia as a prognostic marker
Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc.
on behalf of the Society of Critical Care Medicine. This is an open-access
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the journal.
Original Clinical Report
1Department of Medicine III, University Hospital Rheinisch-Westfälische
Technische Hochschule Aachen, Aachen, Germany.
2Clinic for Gastroenterology, Hepatology and Infectious Diseases, University
Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf,
Düsseldorf, Germany.
3Department of Diagnostic and Interventional Radiology, University Hospital
Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
4Division of Gastroenterology, Hepatology and Hepatobiliary Oncology,
University Hospital RWTH Aachen, Aachen, Germany.
5Department of Urology, University Hospital Cologne, Cologne, Germany.
6Department of Hepatology and Gastroenterology, Charité University Medicine
Berlin, Berlin, Germany.
Loosen et al
2 www.ccejournal.org 2020 • Volume 2 • e0171
for critically ill patients remains controversial (5), which might be
due to the fact that functional aspects such as muscle strength and
muscle composition are not properly reected. Recently, Faron et
al (6) showed the clinical potential of fat-free muscle area (FFMA)
in MRI scans to predict outcome in patients with colorectal can-
cer, suggesting that FFMA might be a new and easily accessible
prognostic biomarker for prognosis.
In this study, we aimed at analyzing whether sarcopenia,
assessed by the skeletal muscle index (L3SMI), and the mean skel-
etal muscle attenuation (MMA) as a surrogate for muscular fat
deposition, represent prognostic factors in critically ill patients
treated on a medical ICU.
PATIENT AND METHODS
Study Design and Patient Characteristics
A total of 155 patients who were admitted to the medical ICU at
the Department of Medicine III at University Hospital Rheinisch-
Westfälische Technische Hochschule (RWTH) Aachen between
2006 and 2015 were enrolled in this study (detailed patient char-
acteristics are given in Tab le  1). e study was approved by the
local ethics committee (EK 150/06) of the University Hospital
RWTH Aachen, Germany, and written informed consent was
obtained from every participant or authorized relatives in the case
of unconsciousness.
Assessment of Body Composition and Definition of the
Skeletal Muscle Index
We only used CT scans in venous phase with a slice thickness of
5 mm for this study. We included CT scans that were performed
upon ICU admission. e total skeletal muscle area, as well as the
MMA, were segmented at the center plane of the third lumbar ver-
tebra on axial CT scans. We used this approach as it was recently
shown that single-slice measurements of the skeletal muscle area
and adipose tissue at anatomical landmarks are strongly associated
with total compartment volumes and therefore provide compara-
bility of results (7). All parameters were assessed manually using
a semi-automatically segmentation tool, 3D slicer, an open source
soware platform for medical image informatics (8). e following
muscle groups were segmented: rectus abdominis, external and
internal obliques, transversus abdominis, quadratus lumborum,
as well as the psoas major and erector spinae (Supplemental Fig.
1, Supplemental Digital Content 1, http://links.lww.com/CCX/
A240; legend, Supplemental Digital Content 8, http://links.lww.
com/CCX/A247). All muscles were identied and quantied with
cuto values of –29 to 150 Hounseld units (HUs). e MMA was
automatically calculated by the soware. e L3SMI was further
normalized for the patients’ height as follows:
Skeletal muscle indexL3SMI (mm=
skeletalmusclearea
2
()
/cm)
��
atthird� LV mm
bodyheight (cm)
2
()
Statistical Analysis
Statistical analyses were performed as recently described (9)
(Supplemental Patients and Methods, Supplemental Digital
Content 2, http://links.lww.com/CCX/A241). A p value of less
than 0.05 was considered statistically signicant (*p < 0.05;
**p < 0.01; ***p < 0.001).
RESULTS
The Individual Body Composition Does Not Predict
Short-Term Mortality or ICU Survival in Critically Ill
Patients
A total of n = 155 patients who were admitted to the medical
ICU for treatment of critical illness were included in this study
(Table1). e median L3SMI that we used as a surrogate for sarco-
penia was 76.983 mm2/cm (range, 43.78–1,001.75 mm2/cm). e
median skeletal muscle attenuation (MMA) that we used a sur-
rogate parameter for muscular fat deposition was 30 HU (range,
–21 to 54 HU). We hypothesized that the patients’ individual body
composition might predict short-term mortality in ICU patients.
We therefore compared the L3SMI between patients who survived
the ICU stay and were admitted to standard care (ICU survivors)
and patients who deceased during the ICU stay (ICU nonsurvi-
vors). Interestingly, we did not see a signicant dierence between
these two groups (Supplemental Fig. 2, A and B, Supplemental
Digital Content 3, http://links.lww.com/CCX/A242; legend,
Supplemental Digital Content 8, http://links.lww.com/CCX/
A247). In a second step, we evaluated whether or not an increased
fat deposition in the skeletal muscle might be a negative predictor
for short-term outcomes. erefore, we determined the MMA of
the skeletal muscle area that was used to calculate the L3SMI as a
surrogate for fatty muscle depositions. However, when comparing
the MMA of patients who did or did not survive the ICU stay,
we did not observe a signicant dierence between ICU survivors
and nonsurvivors (Supplemental Fig. 2C, Supplemental Digital
Content 3, http://links.lww.com/CCX/A242; legend, Supplemental
Digital Content 8, http://links.lww.com/CCX/A247). In line, there
was no signicant association between the MMA and the 30-day
mortality (Supplemental Fig. 2D, Supplemental Digital Content
3, http://links.lww.com/CCX/A242; legend, Supplemental Digital
Content 8, http://links.lww.com/CCX/A247).
The Individual Body Composition Is Associated With
Long-Term Outcome of ICU Patients
Hypothesizing that an unfavorable body composition (low
amount of skeletal muscle, high amount of muscular fat deposi-
tion) might be associated with an impaired long-term survival
rather than predicting short-term mortality, we next compared
the L3SMI between patients who did or did not survive for 180
days and 1 year, respectively. Strikingly, we observed signicantly
higher L3SMI values in patients who survived for 180 days com-
pared to patients who deceased during this time (Fig. 1A). e
median L3SMI was 79.05 mm2/cm for the 180 days survivors and
72.65 mm2/cm for nonsurvivors. In line, the L3SMI was signi-
cantly associated with the 1-year mortality rate of ICU patients
as patients who survived for at least 1 year had signicantly
higher L3SMI values compared to patients who died within the
rst year aer ICU admission (79.81 vs 74.05 mm2/cm; Fig. 1B).
Subsequently, we compared the MMA between patients who
Original Clinical Report
Critical Care Explorations www.ccejournal.org 3
survived for 180 days or 1 year aer ICU admission and nonsurvi-
vors. Interestingly, we found signicantly lower MMA in patients
who died within the rst 180 days or rst year following ICU
admission (Fig.1, C and D) compared to patients who survived
this time period, suggesting that a higher amount of muscular
fat deposition (low MMA) also represents a negative predictor of
long-term ICU survival. In line, binary logistic-regression analysis
revealed both the L3SMI and the MMA as prognostic factors for
180-day mortality (odds ratio [ORL3SMI], 0.979; 0.961–0.997; p =
0.025 and ORHU, 0.964; 0.937–0.993; p = 0.014).
Finally, we compared the predictive power of the L3SMI and
the MMA regarding long-term survival with circulating predictive
markers that have previously been associated with ICU survival,
such as the C-reactive protein (CRP), procalcitonin, and creati-
nine using receiver operating characteristic curve analyses. Here,
we observed higher area under the curve (AUC) values for the
L3SMI and the MMA for both prediction of 180-day (AUCL3SMI:
0.654, AUCMMA: 0.657) and 1-year (AUCL3SMI: 0.654, AUCMMA:
0.657) mortality when compared to established predictive serum
parameters (Fig.1, E and F). Importantly, the predictive power for
long-term mortality was even higher when we combined param-
eters of body composition with established prognostic serum
markers such as the MMA and CRP levels, revealing a higher
AUC of 0.682 (Fig. 1G).
The L3SMI and Myosteatosis Are Predictors of Overall
Survival in ICU Patients
We subsequently evaluated if L3SMI and the MMA are also indic-
ative for the patients’ overall survival (OS). erefore, we subdi-
vided our cohort of patients into two groups with either high or
low L3SMI or MMA values (50th percentile cuto) and compared
the OS between groups using Kaplan-Meier curve analysis. is
analysis revealed a signicantly impaired OS for patients with a
L3SMI below 76.98 mm2/cm compared to patients with an L3SMI
value above this cuto (Fig. 2A). In line, patients showing a larger
amount of muscular fat deposition with an MMA below 31 HU
had a signicantly impaired OS compared to patients with an
MMA above 31 HU (Fig. 2B). When using ideal cuto values
(L3SMI: 74.95 mm2/cm and MMA: 29 HU), the L3SMI and the
MMA both showed a highly signicant discriminatory potential
for the identication of ICU patients with an unfavorable long-
term prognosis (Fig.2, C and D). e median OS both in the low
L3SMI and in low MMA group was only 8.4 weeks compared with
64.8 weeks in the L3SMI high and 62.1 weeks in the MMA high
group. In line, Cox regression analyses revealed a L3SMI (hazard
ratio [HR], 1.850; 1.259–2.719; p = 0.002) as well as an MMA (HR,
1.690; 1.167–2.446; p = 0.005) below these cuto values as negative
prognostic factors for OS. Importantly, multivariate Cox regres-
sion analysis showed that the prognostic potential of the L3SMI
was independent of various clinicopathological parameters such
as the patients’ age, markers of systemic inammation (leucocyte
count and CRP), and parameters of organ dysfunction (bilirubin,
hemoglobin) (Table 2). Importantly, the combinational use of
the L3SMI and the MMA (low L3SMI/low MMA vs high L3SMI/
high MMA) revealed an even better prognostic potential to pre-
dict OS in critically ill patients (Fig. 2E). Finally, the association
of the patients’ body composition with outcome is further sup-
ported by quartile analyses, showing, for example, that a gradually
decreasing skeletal muscle density leads to increasingly reduced
TABLE 1. Characteristics of Study Cohort
Parameter Study Cohort
ICU patients 155
Gender (%)
Male–female 60.6–39.4
Age, yr, median (range) 60 (21–88)
Body mass index, kg/m2, median (range) 25.21 (13.89–69.92)
Skeletal muscle index, mm2/cm,
median (range) 76.983 (43.78–1,001.75)
Hounsfield unit, median (range) 31 (–21 to 54)
ICU stay, d, median (range) 11 (1–147)
Hospital stay, d, median (range) 32 (3–199)
Mechanical ventilation, hr, median (range) 193.0 (0–3,499)
Sepsis (no–yes, %) 42.9–57.1
Cause of ICU admission (%)
Pulmonary sepsis 25.2
Abdominal sepsis 7.7
Urosepsis 5.2
Other sepsis 12.3
Liver cirrhosis 7.1
Acute liver failure 4.5
Liver transplantation 2.6
Gastrointestinal bleeding 7.7
Cardiopulmonary 13.5
Acute pancreatitis 5.2
Other 9.0
Medical conditions (no–yes, %)
Diabetes mellitus 75.7–24.3
Arterial hypertension 48.5–51.5
Chronic alcohol intake 71.4–28.6
Chronic obstructive pulmonary disease 83.6–16.4
Liver cirrhosis 76.1–23.9
Malignant disease 67.2–32.8
Survival rates (yes–no, %)
ICU survival 71.2–28.8
30-d survival 73.4–26.6
180-d survival 48.5–51.5
1-yr survival 39.6–60.4
Follow-up survival 25.2–74.8
Loosen et al
4 www.ccejournal.org 2020 • Volume 2 • e0171
OS (median OSMMA: 132.6 wk if MMA > 75th percentile [39 HU],
47.0 wk if MMA between 75th and 50th percentile [31–39 HU],
31.4 wk if MMA between 50th and 25th percentile [21–31 HU],
and 13.1 wk if MMA < 25th percentile [< 21 HU]).
Subsequently, we aimed at identifying potential underlying
factors which contributed to an impaired OS in patients with an
unfavorable body composition. As the time of mechanical ventila-
tion on the ICU is a well-established prognostic factor for OS (10),
we correlated the MMA with the duration of ventilation and
observed a signicant negative correlation between the HU and
the total hours of mechanical ventilation on the ICU (Fig. 3A).
us, a higher degree of myosteatosis (lower MMA) was associ-
ated with a longer necessity of mechanical ventilation, potentially
leading to an impaired OS. Besides the duration of mechani-
cal ventilation, we also found a signicant negative correlation
between the MMA and the duration of hospital stay, including the
stay on the ICU and standard care (Fig. 3B). Finally, we compared
the MMA in patients who did or did not fulll the criteria of sep-
sis, representing another well-established prognostic parameter in
ICU patients. Here, we observed signicantly lower MMA values
in septic patients compared with patients with nonseptic disease
(Fig. 3C). On the contrary, the L3SMI did not correlate with any
of these parameters (Fig.3 DF).
Body Composition and Patient Characteristics
To evaluate a potential association between the patients’ body
composition and clinicopathological parameters, we compared
the L3SMI and the MMA between patients with dierent medi-
cal conditions (diabetes, arterial hypertension, chronic obstruc-
tive pulmonary disease [COPD], liver cirrhosis, chronic alcohol
intake, and malignant disease). While patients with diabetes mel-
litus showed signicantly higher L3SMI values than nondiabetic
patients, we did not observe a signicant dierence of the L3SMI
between patients with or without arterial hypertension, COPD,
liver cirrhosis, chronic alcohol intake, or malignant disease. e
L3SMI was also not signicantly altered when patients were strati-
ed with respect to their acute medical condition that led to ICU
admission (Supplemental Fig. 3 AG, Supplemental Digital
Figure 1. The ICU patients’ body composition predicts long-term outcome. A, Patients with 180-d survival have significantly higher skeletal muscle index
(L3SMI) values compared to patients who deceased during this time. B, The L3SMI is significantly higher in patients who survive for at least one after ICU
admission. Patients who die within the first 180 d (C) or first year (D) following ICU admission have significantly lower mean skeletal muscle attenuation (MMA).
The area under the curve values for the L3SMI and Hounsfield unit (HU) for prediction of 180-d (E) and 1-yr (F) mortality are higher compared to established
predictive serum parameters. G, The prediction of 180-d mortality is highest when the MMA and C-reactive protein (CRP) levels are combined.
PCT = procalcitonin.
Original Clinical Report
Critical Care Explorations www.ccejournal.org 5
Content 4, http://links.lww.com/CCX/A243; legend, Supplemental
Digital Content 8, http://links.lww.com/CCX/A247). Similarly, we
observed signicantly lower MMA levels in patients with preexist-
ing diabetes mellitus. We also found higher grades of myosteatosis
(low MMA) in patients with arterial hypertension, while patients
with or without COPD, liver cirrhosis, chronic alcohol intake, or
malignant disease had similar MMA values. e MMA was also
not altered between the dierent disease etiologies that led to
ICU admission (Supplemental Fig. 4 AG, Supplemental Digital
Content 5, http://links.lww.com/CCX/A244; legend, Supplemental
Digital Content 8, http://links.lww.com/CCX/A247).
Furthermore, we performed extensive correlation analysis
between the L3SMI as well as the MMA and various clinical labo-
ratory parameters of organ dysfunction (Supplemental Table 1,
Supplemental Digital Content 6, http://links.lww.com/CCX/A245).
Here, we found a signicant negative correlation between the MMA
and serum cholesterol levels (rS: –0.185; p = 0.040), arguing that
hypercholesterolemia is associated with a higher degree of fatty
muscle deposition and myosteatosis. Furthermore, we observed a
negative correlation between the MMA and the creatinine as well
as NT-pro brain natriuretic peptide (NT-proBNP). Circulating
interleukin (IL)–6 levels positively correlated with the L3SMI (rS: 0.182;
p = 0.047), which corroborates the nding that IL-6 is released by
skeletal muscle tissue during systemic stress response (11). In addi-
tion, the L3SMI negatively correlated with serum levels of alka-
line phosphatase (alkaline phosphatase [rS: –0.275; p = 0.001] and
NT-proBNP [rS: –0.242; p = 0.011]).
DISCUSSION
e body composition of an individual patient might be deter-
mined by very dierent techniques such as bioelectrical imped-
ance analysis or air displacement plethysmography, just to name a
few (12, 13). However, in case of critically ill patients oen receiv-
ing extensive hydration, the value of these methods to determine
skeletal muscle quantity and quality is hampered by consecu-
tive uid overload (13). Furthermore, in such patients, classical
functional tests for estimating body composition and physical
strength (body weight, waist circumference, body mass index,
ability to walk or physical activity, and handgrip) do not provide
reliable results (13). erefore, CT, available for almost all ICU
patients, represents the gold standard for assessing muscle mass
Figure 2. The body composition correlates with the patients’ overall survival (OS). A, ICU patients with a low skeletal muscle index (L3SMI) (below 50th
percentile) show a significantly reduced OS. B, A low mean skeletal muscle attenuation (MMA) (below 50th percentile) is associated with a significantly reduced
OS. When using the optimal prognostic cutoff values, both the L3SMI (C) and the mean skeletal Hounsfield unit (HU) (D) show a highly significant prediction of
OS. E, The combinational use of the L3SMI and the MMA (L3SMI low/MMA low vs L3SMI high/MMA high) reveals the highest prognostic potential.
Loosen et al
6 www.ccejournal.org 2020 • Volume 2 • e0171
and muscle quality in critically ill patients (13–15). So far, the role
of sarcopenia and myosteatosis as prognostic factors in critical
illness is unclear. Within this study, we quantied both the skel-
etal muscle mass and the amount of skeletal muscle fat deposi-
tion and evaluated the prognostic value of these parameters. At
the respective optimal cuto values that we established using a
recently described biometric soware (16), both a low L3SMI and
a low MMA turned out as powerful predictors of OS. Importantly,
when both markers were combined (e.g., L3SMI low/MMA low
vs L3SMI high/MMA high patients), the prognostic potential was
even further increased (Fig.2).
Sarcopenia is a common characteristic of elderly and mori-
bund patients. Muscle wasting can be triggered by manifold dis-
ease conditions, including disuse, denervation, fasting, cancer,
cardiac failure, and renal dysfunction (17). As all of these factors
are frequently found in critically ill patients and might themselves
limit patients’ prognosis, systematic research on the role of an
impaired muscle mass and strength bears a risk of important bias.
In our analysis, however, L3SMI/MMA values were comparable
within the dierent etiologies of critical illness (Supplemental Fig.
3, Supplemental Digital Content 4, http://links.lww.com/CCX/
A243; and Supplemental Fig. 4, Supplemental Digital Content 5,
http://links.lww.com/CCX/A244 [legend, Supplemental Digital
Content 8, http://links.lww.com/CCX/A247]). Furthermore, mul-
tivariate analysis including the patients’ age as well as parameters
of systemic inammation (leucocyte count and CRP) and organ
dysfunction (bilirubin and hemoglobin), identied the L3SMI as
an independent prognostic factor in critically ill patients (Table2).
Nevertheless, both L3SMI, as well as the MMA, were linked to
metabolic and/or cardiovascular diseases since diabetics dem-
onstrated higher L3SMI and lower MMA values and the L3SMI/
MMA were correlated with cholesterol serum concentrations and
NT-proBNP serum levels. While our data clearly argue for a role
of the L3SMI and the MMA as prognostic markers in patients
undergoing ICU treatment, it remains unclear if these factors
might also have a predictive value in ICU patients of dierent
disease etiologies (e.g., trauma patients) or ICU patients receiv-
ing dierent treatment modalities (e.g., extracorporeal membrane
oxygenation therapy). us, further studies are warranted to not
only conrm their prognostic role in the context of critical illness
but also to assess if the L3SMI and the MMA could support future
biomarker-driven clinical decision algorithms in the multimodal
treatment of critical illness. Importantly, our analysis only gave
information on the prognosis of these patients but had no pre-
dictive value, meaning that it is unclear if those patients with an
unfavorable prognosis in terms of their individual L3SMI/MMA
levels might have benetted to a greater extent from a specic
therapy or even represent candidates for active symptom control
who should not been admitted to the ICU. Furthermore, we only
evaluated L3SMI/HU values at ICU admission but longitudinal
measurements of L3SMI/MMA could also be important to answer
the question whether therapeutic interventions aecting body
composition might inuence patients’ outcome.
Our data are in line with previous studies demonstrating an asso-
ciation of sarcopenia and an impaired prognosis in patients with
nonalcoholic liver disease (18), liver cirrhosis (19), cardiovascular
(20), and lung diseases (21). Furthermore, it was demonstrated that
sarcopenia might predict outcome of patients undergoing therapeu-
tic interventions such as transcatheter arterial chemoembolization
(TACE) (22), liver transplantation (23), or colorectal cancer sur-
gery (24). Within our study, we not only analyzed the association
between sarcopenia and patient’s outcome but also of myosteatosis
and patients´ outcome. Low skeletal muscle radiodensity is related
to the accumulation of fat deposits within muscle (25, 26). It was
recently demonstrated that sarcopenia and myosteatosis are inde-
pendent abnormalities that represent two separate biological pro-
cesses and that at least in patients with pancreatic and periampullary
adenocarcinomas they frequently do not occur coincidentally (27).
In contrast, we observed that the L3SMI and the MMA signicantly
correlated with each other in patients with critical illness (r: 0.168;
TABLE 2. Univariate and Multivariate Cox Regression Analysis of the Skeletal Muscle Index
and Several Clinicopathological Parameters for the Prediction of Overall Survival
Parameter
Univariate Cox Regression Multivariate Cox Regression
pHazard Ratio (95% CI) pHazard Ratio (95% CI)
Skeletal muscle index (L3SMI) <
74.95 mm2/cm 0.002 1.850 (1.259–2.719) 0.008 1.762 (1.160–2.678)
Age < 0.001 1.035 (1.020–1.051) < 0.001 1.033 (1.016–1.049)
Sex 0.893 0.974 (0.660–1.437)
Body mass index 0.458 0.998 (0.992–1.004)
Leukocytes 0.014 1.031 (1.006–1.057) 0.081 1.023 (0.997–1.050)
Hemoglobin 0.121 0.994 (0.986–1.002) 0.477 0.997 (0.989–1.005)
Bilirubin 0.210 0.979 (0.946–1.012) 0.561 0.988 (0.951–1.028)
Procalcitonin 0.288 1.004 (0.996–1.012)
C-reactive protein 0.151 1.002 (0.999–1.004) 0.370 1.001 (0.999–1.004)
Creatinine 0.876 0.995 (0.929–1.065)
Original Clinical Report
Critical Care Explorations www.ccejournal.org 7
p = 0.044; Supplemental Fig. 5, Supplemental Digital Content 7,
http://links.lww.com/CCX/A246 [legend, Supplemental Digital
Content 8, http://links.lww.com/CCX/A247]). Furthermore, the
combinational use of the L3SMI and MMA was superior to either
marker alone (Fig.2), highlighting that sarcopenia and myosteato-
sis might not represent simple prognostic markers but might reect
specic aspects within dierent diseases.
e pathophysiological relation between sarcopenia/myosteatosis
and impaired patients’ prognosis is not fully clear at present. Stretch
et al (27) used microarray analysis to identify canonical pathways
deregulated in samples from patients with sarcopenia and myoste-
atosis. Interestingly, in patients with sarcopenia, most dierentially
regulated genes were part of the antigen presentation pathway, while
in patients with myosteatosis genes of the oxidative phosphoryla-
tion pathway were most regulated. Additionally, genes of the lipid
metabolism pathway, potentially contributing to lipid accumulation
(e.g., adiponectin receptor 2, apolipoprotein L1, apolipoprotein L2,
apolipoprotein O, and paraoxonase 3), were regulated in myosteato-
sis but not (or to a much lesser extent) in sarcopenia (27).
As the direct association between sarcopenia and outcome is gain-
ing increasing attention in dierent clinical conditions, a reliable,
cost-eective, and easily applicable method for the evaluation of sar-
copenia is essential. Although our method of sarcopenia assessment
is easily performed in patients undergoing CT scans for clinical indi-
cations, the mere determination of the patients’ skeletal muscle status
would not justify a CT scan due to radiation exposure and costs. In
this line of thinking, assessment of sar-
copenia using ultrasound might repre-
sent a noninvasive, radiation-free, and
inexpensive alternative. As such, ultra-
sound measurement of rectus femoris
muscle thickness has been suggested
as a quick screening test for sarcopenia
assessment (28). In addition, dier-
ent dynamic features of muscle qual-
ity such as microcirculation, perfusion
during rest and activity, as well as the
muscle elasticity could be assessed
using ultrasound techniques (29).
Our study was limited by some
points. First of all, the study was
conducted in an exploratory, single-
center design, including a total of
n = 155 patients treated a single ICU.
Although this design might reduce
the inter-hospital bias, our data
clearly need further validation from
larger multicenter studies. Second,
our study included more than 50%
of patients fullling the criteria for
sepsis, which might represent a con-
founder of results. In addition, the
heterogeneity regarding the underly-
ing disease etiology could also inu-
ence the results on OS in our study
cohort. Finally, our study cohort was
heterogeneous in terms of duration of ICU stay, duration of hos-
pital stay, and duration of mechanical ventilation. Although this
aspect argues for a rather general validity of results among dier-
ent ICU patients, larger control studies including further multi-
variate analyses on confounding parameters on OS are warranted
to fully elucidate the role of sarcopenia in better-dened cohorts
of ICU patients. Nevertheless, our study is the rst to demonstrate
a potential prognostic value of myosteatosis in the context of criti-
cally ill patients. Furthermore, our study for the rst time dem-
onstrates that simultaneous assessment and combined analysis of
dierent parameters of the patients’ individual body composition
in critically ill patients might be superior over a single marker for
estimating the long-term outcome of these ICU patients. Such
data might provide important information for early clinical deci-
sion-making on patients in emergency departments or ICUs.
Drs. Loosen, Schulze-Hagen, and Püngel shared first authorship. Drs. Tacke,
Luedde, Koch, and Roderburg shared last authorship.
Drs. Loosen, Tacke, Koch, and Roderburg designed the study. Dr. Schulze-
Hagen performed analysis of body composition. Drs. Loosen, Püngel,
Bündgens, and Wirtz performed data acquisition. Drs. Loosen and Püngel
performed statistical analysis. Dr. Loosen generated figures and tables. Drs.
Loosen and Roderburg drafted the article and performed its revision. Drs.
Wirtz, Vucur, Paffenholz, Bruners, Kuhl, Trautwein, Tacke, Luedde, and Koch
provided intellectual input. All authors approved the final version of the article.
Supplemental digital content is available for this article. Direct URL citations
appear in the HTML and PDF versions of this article on the journal’s website
(http://journals.lww.com/ccejournal).
Figure 3. Increased levels of myosteatosis are associated with sepsis and duration of mechanical ventilation.
A, There is a significant negative correlation between the mean skeletal muscle attenuation (MMA) and the
duration of mechanical ventilation. B, The duration of hospital stay negatively correlates with the degree of
myosteatosis (MMA). C, Patients who fulfill the criteria of sepsis have significantly lower MMA. D–F, The
skeletal muscle index (L3SMI) does not correlate with any of these parameters. HU = Hounsfield unit, n.s. = not
significant.
Loosen et al
8 www.ccejournal.org 2020 • Volume 2 • e0171
Dr. Luedde was funded from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation program through the
ERC Consolidator Grant Phase Control (Grant Agreement n° 771083). Dr.
Luedde was further supported by the German Cancer Aid (Deutsche Kreb-
shilfe 110043 and a Mildred-Scheel-Professorship), the German-Research-
Foundation (SFB-TRR57/P06 and LU 1360/3-1), the Ernst-Jung-Foundation
Hamburg, the Interdisciplinary Center of Clinical Research (IZKF) Aachen,
and a grant from the medical faculty of the Rheinisch-Westfälische Technische
Hochschule Aachen.
For information regarding this article, E-mail: christoph.roderburg@charite.de
REFERENCES
1. Jaitovich A, Khan MMHS, Itty R, et al: ICU Admission muscle and fat
mass, survival, and disability at discharge: A prospective cohort study.
Chest 2019; 155:322–330
2. Moisey LL, Mourtzakis M, Cotton BA, et al; Nutrition and Rehabilitation
Investigators Consortium (NUTRIC): Skeletal muscle predicts ventilator-
free days, ICU-free days, and mortality in elderly ICU patients. Crit Care
2013; 17:R206
3. Ji Y, Cheng B, Xu Z, et al: Impact of sarcopenic obesity on 30-day mortal-
ity in critically ill patients with intra-abdominal sepsis. J Crit Care 2018;
46:50–54
4. Fielding RA, Vellas B, Evans WJ, et al: Sarcopenia: An undiagnosed con-
dition in older adults. Current consensus denition: Prevalence, etiology,
and consequences. International working group on sarcopenia. J Am Med
Dir Assoc 2011; 12:249–256
5. van der Werf A, Langius JAE, de van der Schueren MAE, et al: Percentiles
for skeletal muscle index, area and radiation attenuation based on com-
puted tomography imaging in a healthy Caucasian population. Eur J Clin
Nutr 2018; 72:288–296
6. Faron A, Pieper CC, Schmeel FC, et al: Fat-free muscle area measured by
magnetic resonance imaging predicts overall survival of patients under-
going radioembolization of colorectal cancer liver metastases. Eur Radiol
2019; 29:4709–4717
7. Faron A, Luetkens JA, Schmeel FC, et al: Quantication of fat and skeletal
muscle tissue at abdominal computed tomography: Associations between
single-slice measurements and total compartment volumes. Abdom
Radiol (NY) 2019; 44:1907–1916
8. Fedorov A, Beichel R, Kalpathy-Cramer J, et al: 3D Slicer as an image
computing platform for the Quantitative Imaging Network. Magn Reson
Imaging 2012; 30:1323–1341
9. Loosen SH, Roderburg C, Kauertz KL, et al: Elevated levels of circulating
osteopontin are associated with a poor survival aer resection of cholan-
giocarcinoma. J Hepatol 2017; 67:749–757
10. Herer B: Outcomes of prolonged mechanical ventilation before and aer
implementation of a respiratory ICU. Respir Care 2020; 65:1011–1018
11. Welc SS, Clanton TL: e regulation of interleukin-6 implicates skeletal
muscle as an integrative stress sensor and endocrine organ. Exp Physiol
2013; 98:359–371
12. Eslamparast T, Montano-Loza AJ, Raman M, et al: Sarcopenic obe-
sity in cirrhosis-the conuence of 2 prognostic titans. Liver Int 2018;
38:1706–1717
13. Montano-Loza AJ, Meza-Junco J, Baracos VE, et al: Severe muscle deple-
tion predicts postoperative length of stay but is not associated with sur-
vival aer liver transplantation. Liver Transpl 2014; 20:640–648
14. Montano-Loza AJ, Angulo P, Meza-Junco J, et al: Sarcopenic obesity and
myosteatosis are associated with higher mortality in patients with cirrho-
sis. J Cachexia Sarcopenia Muscle 2016; 7:126
15. Merli M, Berzigotti A, Zelber-Sagi S, et al: EASL Clinical Practice
Guidelines on nutrition in chronic liver disease. J Hepatol 2019;
70:172–193
16. Budczies J, Klauschen F, Sinn BV, et al: Cuto Finder: A comprehensive
and straightforward Web application enabling rapid biomarker cuto
optimization. PLoS One 2012; 7:e51862
17. Schefold JC, Bierbrauer J, Weber-Carstens S: Intensive care unit-acquired
weakness (ICUAW) and muscle wasting in critically ill patients with
severe sepsis and septic shock. J Cachexia Sarcopenia Muscle 2010;
1:147–157
18. Koo BK, Kim D, Joo SK, et al: Sarcopenia is an independent risk factor
for non-alcoholic steatohepatitis and signicant brosis. J Hepatol 2017;
66:123–131
19. Buchard B, Boirie Y, Cassagnes L, et al: Assessment of malnutrition, sar-
copenia and frailty in patients with cirrhosis: Which tools should we use
in clinical practice? Nutrients 2020; 12:186
20. Santana NM, Mendes RML, Silva NFD, et al: Sarcopenia and sarcope-
nic obesity as prognostic predictors in hospitalized elderly patients with
acute myocardial infarction. Einstein (Sao Paulo) 2019; 17:eAO4632
21. Hirai K, Tanaka A, Homma T, et al: Comparison of three frailty models
and a sarcopenia model in elderly patients with chronic obstructive pul-
monary disease. Geriatr Gerontol Int 2019; 19:896–901
22. Loosen SH, Schulze-Hagen M, Bruners P, et al: Sarcopenia is a negative
prognostic factor in patients undergoing transarterial chemoemboliza-
tion (TACE) for hepatic malignancies. Cancers (Basel) 2019; 11:1503
23. Czigany Z, Kramp W, Bednarsch J, et al: Myosteatosis to predict inferior
perioperative outcome in patients undergoing orthotopic liver transplan-
tation. Am J Transplant 2020; 20:493–503
24. Nakanishi R, Oki E, Sasaki S, et al: Sarcopenia is an independent pre-
dictor of complications aer colorectal cancer surgery. Surg Today 2018;
48:151–157
25. Stephens NA, Skipworth RJ, Macdonald AJ, et al: Intramyocellular lipid
droplets increase with progression of cachexia in cancer patients. J
Cachexia Sarcopenia Muscle 2011; 2:111–117
26. Aubrey J, Esfandiari N, Baracos VE, et al: Measurement of skeletal muscle
radiation attenuation and basis of its biological variation. Acta Physiol
(Oxf) 2014; 210:489–497
27. Stretch C, Aubin JM, Mickiewicz B, et al: Sarcopenia and myosteatosis
are accompanied by distinct biological proles in patients with pancreatic
and periampullary adenocarcinomas. PLoS One 2018; 13:e0196235
28. Rustani K, Kundisova L, Capecchi PL, et al: Ultrasound measurement of
rectus femoris muscle thickness as a quick screening test for sarcopenia
assessment. Arch Gerontol Geriatr 2019; 83:151–154
29. Ivanoski S, Vasilevska Nikodinovska V: Future ultrasound biomarkers for
sarcopenia: Elastography, contrast-enhanced ultrasound, and speed of
sound ultrasound imaging. Semin Musculoskelet Radiol 2020; 24:194–200
... In line with this, Loosen et al. (48) have demonstrated, by using a biometric software, the role of sarcopenia and myosteatosis as prognostic factors in critical ICU patients. Through L3-SMI and mean skeletal muscle attenuation (MMA) assessment, the authors showed that low MMA and low L3-SMI together are able to predict the overall survival in critical ill patients. ...
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... 21 22 The MMA, Clinical care/Education/Nutrition reflecting muscle density, was shown as the CT attenuation of L3 cross-sectional skeletal muscle in HU and automatically calculated by the software. 22 The FMI was first proposed by VanItallie et al as an indicator of nutritional status and calculated by normalizing fat mass in kg by height in m 2 . 21 23 24 Statistical analysis Continuous variables are summarized using the median and IQR if not normally distributed and the mean±SD if normally distributed. ...
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: Background and Aims: While transarterial chemoembolization (TACE) represents a standard of therapy for intermediate-stage hepatocellular carcinoma (HCC) and is also routinely performed in patients with liver metastases, it is still debated which patients represent the ideal candidates for TACE therapy in terms of overall survival. Sarcopenia, the degenerative loss of skeletal muscle mass and strength, has been associated with an adverse outcome for various malignancies, but its role in the context of TACE has largely remained unknown. Here, we evaluated the role of sarcopenia on the outcome of patients undergoing TACE for primary and secondary liver cancer. Methods: The patients' psoas muscle size was measured on axial computed tomography (CT) scans and normalized for the patients' height squared. This value was referred to as the psoas muscle index (PMI). The PMI was correlated with clinical and laboratory markers. Results: While pre-interventional sarcopenia had no impact on the direct tumor response to TACE, sarcopenic patients with a pre-interventional PMI below our ideal cut-off value of 13.39 mm/m2 had a significantly impaired long-term outcome with a median overall survival of 491 days compared to 1291 days for patients with a high PMI. This finding was confirmed by uni- and multivariate Cox-regression analyses. Moreover, a progressive rapid decline in muscle mass after TACE was a predictor for an unfavorable prognosis. Conclusion: Our data suggest that sarcopenia represents a previously unrecognized prognostic factor for patients undergoing TACE therapy which might yield important information on the patients' post-interventional outcome and should therefore be implemented into clinical stratification algorithms.
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Muscle wasting, and alterations of body composition (BC) are linked to clinical outcomes in numerous medical conditions. The role of myosteatosis in post‐transplant outcomes remains to be determined. Here we investigated skeletal muscle mass and myosteatosis as prognostic factors in patients undergoing orthotopic liver transplantation (OLT). The data of 225 consecutive OLT‐recipients from a prospective database were retrospectively analysed (05/2010‐12/2017). Computed‐tomography‐based skeletal‐muscle‐index/SMI (muscle mass), visceral‐fat‐area/VFA (visceral adiposity) and mean skeletal‐muscle‐radiation‐attenuation/SM‐RA (myosteatosis) were calculated using a segmentation tool. Cut‐off values of myosteatosis resulted in a good stratification of patients into low‐ and high‐risk groups in terms of morbidity (Clavien‐Dindo≥3b). Patients with myosteatosis had significantly higher complication‐rates (90‐days CCI 68±32 vs. 44±30, p<0.001) and also displayed significantly longer intensive‐care (18±25 vs. 11±21 days, p<0.001) and hospital stay (56±55 vs. 33±24 days, p<0.001). Estimated costs were 44% higher compared to patients without myosteatosis. Multivariable analysis identified myosteatosis as an independent prognostic factor for major morbidity (OR:2.772, CI:1.516‐5.066, p=0.001). Adding myosteatosis to the well‐established Balance‐of‐Risk‐(BAR)‐score resulted in an increased prognostic value compared to the original BAR‐score. Myosteatosis may be a useful parameter to predict perioperative outcome in patients undergoing OLT, supporting the role of muscle quality (myosteatosis) over quantity (muscle mass) in this setting. This article is protected by copyright. All rights reserved.
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Objective: To investigate the potential value of sarcopenia and sarcopenic obesity as prognostic predictors in hospitalized elderly patients with acute myocardial infarction. Methods: A cross-sectional study based on data collected from elderly patients with acute myocardial infarction, admitted to a public hospital located in the Northeastern region of Brazil, from April to July 2015. The diagnosis of sarcopenia was based on muscle mass, muscle strength and physical performance measurements. Cardiovascular risk and prognostic markers, such as troponin and creatine kynase MB isoenzyme values, acute myocardial infarction classification according to ST segment elevation, and thrombolysis in myocardial infarction score were used. Results: The sample comprised 99 patients with mean age of 71.6 (±7.4) years. Prevalence of sarcopenia and sarcopenic obesity was 64.6% and 35.4%, respectively. Sarcopenia was more prevalent among males (p=0.017) aged >80 years (p=0.008). Thrombolysis in myocardial infarction was the only marker of cardiovascular risk significantly associated with sarcopenia (p=0.002). Conclusion: Prevalence of sarcopenia was high and associated with thrombolysis in myocardial infarction risk score. Sarcopenic obesity affected approximately one-third of patients and was not associated with any of the prognostic predictors.
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Purpose Body composition is of great prognostic value in several severe diseases, including different types of cancer as well as cardiometabolic disorders. We aimed to investigate the correlations of skeletal muscle mass and abdominal adipose tissue compartments between volumetric and single-slice measurements to study the usefulness of several anatomical landmarks for estimation of total compartment volumes using abdominal CT-scans. Methods In this retrospective study volumetric quantifications of paraspinal skeletal muscles (SM) and adipose tissue compartments (visceral adipose tissue, VAT; subcutaneous adipose tissue, SAT) were performed in 50 consecutive patients (26 male; mean age, 63 ± 15 years) who underwent abdominal multislice-CT for diagnostic purposes using an in-house software. Associations between total volumes of SM, VAT, and SAT with single-slice measurements at eight predefined anatomical landmarks (median intervertebral disk spaces T12/L1 to L5/S1; level of the umbilicus (U); level of the radix of the superior mesenteric artery (SMA)) were studied using correlation coefficients. Results Statistical analysis revealed a strong association between single-slice measurements of adipose tissue compartments with total VAT and SAT volume (VAT: all r > 0.89, P < 0.001; SAT: all r > 0.95, P < 0.001). The strongest associations with total SM volume were found for single-slice measurements obtained at L3/4 (r = 0.94, P < 0.001) and were further improved by normalization to height (r = 0.98, P < 0.001). Conclusions Single-slice measurements of SM, VAT, and SAT at several anatomical landmarks are strongly associated with total compartment volumes and therefore allow for easy and simultaneous assessment of skeletal muscle mass and adipose tissue compartment volumes.
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Sarcopenia is the advanced and generalized loss of muscle mass and strength among the elderly population and is a cause of adverse outcomes. Methods used for the diagnosis of sarcopenia are either unavailable or expensive in everyday clinical settings. Ultrasound presents an inexpensive, convenient, and available method that offers advantages for the evaluation of skeletal muscle. Muscle quality will probably be the most important factor in defining sarcopenia in the future. Different features of muscle quality, including muscle elasticity, microcirculation and muscle perfusion during rest and physical activity, and the content of intramuscular adipose tissue can be measured using emerging and promising ultrasound techniques such as elastography, contrast-enhanced imaging, and speed of sound ultrasound technology. This article reviews the recent evidence on the use of ultrasound techniques in the assessment of muscle quality and the possibilities for the future evaluation of sarcopenia.
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Background: Respiratory ICUs (RICUs) have recently been implemented in France to fill the gap between ICUs and respiratory wards for patients who will require prolonged mechanical ventilation (PMV). The aim of this study was to describe the outcomes of subjects with tracheostomy who were undergoing PMV before and after implementing a RICU in our hospital. Methods: Two cohorts were studied and followed up for 1 year. Cohort 1 included 66 subjects from December 2010 to December 2012, before implementing the RICU. Cohort 2 included 103 consecutive subjects included in the RICU from January 2016 to June 2017. Results: In cohort 2, lung and airway diseases were the main causes of chronic respiratory failure in 91.3% of the subjects versus 47.0% of the subjects in cohort 1 (P < .001). During the follow-up, 34.8% and 24.3% of the subjects in cohorts 1 and 2, respectively, were readmitted at least once (P = .14), which corresponded to 109 and 137 stays for cohorts 1 and 2. The median (95% CI) length of stay was 42 (37-50) d in the pre-RICU period versus 29 (26-33) d in the RICU period (P < .001). A complete or partial weaning was achieved in 30.3% of stays in the pre-RICU period versus 69.3% of stays in the RICU period (P < .001). The in-hospital mortality rate was 14.7% and 7.3% in the pre-RICU and RICU periods, respectively (P = .10). The 1-year survival did not differ between cohorts: 60.6% versus 53.9% in cohorts 1 versus 2; P = .42). Conclusions: Implementing a RICU improved the outcomes of the subjects with tracheostomy who were undergoing PMV by reducing the length of stay and increasing complete or partial weaning. However, the 1-year survival remained unchanged.
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Aim: Frailty and sarcopenia affect the prognosis and quality of life of patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain which model is the most suitable for evaluating vulnerability in patients with COPD. We evaluated the validity of three frailty models - the Kihon Checklist (KCL), the Japanese version of the Cardiovascular Health Study and the Study of Osteoporotic Fractures - and one sarcopenia model for older patients with COPD. Methods: This cross-sectional study included 201 older (aged ≥65 years) outpatients with COPD. We used three frailty models and one sarcopenia model to identify their correlation with various indices that can evaluate the status of COPD and determine the most ideal model for evaluating vulnerability in patients with COPD. Results: The highest prevalence of frailty (38%) and lowest prevalence of robustness (26%) were observed using the KCL. Although all models reflected the characteristics of COPD, the KCL yielded the strongest correlations with clinically important physical, psychological and prognostic indices. The KCL yielded statistically significant differences in almost all indices among the three intergroup comparisons (robust, pre-frailty and frailty). The KCL was superior in extracting mood disorders to the other models. Conclusion: Although all investigated models were useful, the KCL was the most suitable for evaluating the frailty status and might enable interventions in patients with COPD. Geriatr Gerontol Int 2019; ••: ••-••.
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Introduction: Sarcopenia is a geriatric syndrome related to loss of muscle mass and function, leading to disability, frailty and higher mortality. According to European Working Group on Sarcopenia in Older People (EWGSOP) the diagnosis of sarcopenia requires the assessment of muscle mass, muscle force and function, that is time-consuming and not easily at hand in everyday clinical practice. We propose the B-mode ultrasound measurement of muscle thickness as a quick screening test to assess the presence of sarcopenia. Methods: A cross-sectional study was realized, 119 patients (average age 82 years, 50.4% females) from the Department of Internal Medicine of the University Hospital of Siena (Italy) were enrolled. The diagnosis of sarcopenia was assessed according to EWGSOP criteria. Rectus femoris muscle (RFM) thickness (in cm) was measured by ultrasound B-mode scanning. Sensibility and specificity of the test was evaluated and Receiver Operating Analysis (ROC) was performed to assess the accuracy of the test. Results: Average RFM thickness was 0.78 ± 0.26, significantly lower in sarcopenic patients (0.55 ± 0.2 vs. 0.9 ± 0.3; Mann-Whitney; p < 0.001) and females (0.7 ± 0.3 vs 0.86 ± 0.3; Mann-Whitney; p < 0.001). The cut-off point of 0.7 cm for females and 0.9 cm for males was established as a threshold to assess the presence of sarcopenia by ultrasound. Sensibility of ultrasound measurement of RFM thickness was 100%, specificity 64%, positive predictive value (PPV) 64.3% and negative predictive value (NPV) 100%. ROC analysis was performed in order to quantify how accurately RFM thickness can discriminate between sarcopenia and non-sarcopenia state. AUC for all patients was 0.9 and after a comparative analysis for gender higher values for males (0.94 vs. 0.92) were observed. Conclusion: We suggest a screening test for sarcopenia based on the ultrasound measurement of RFM thickness, as a not invasive and easy to perform method even in elderly patients with functional or cognitive impairment.
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Objectives To investigate the clinical potential of fat-free muscle area (FFMA) to predict outcome in patients with liver-predominant metastatic colorectal cancer (mCRC) undergoing radioembolization (RE) with ⁹⁰Yttrium microspheres. Methods Patients with mCRC who underwent RE in our center were included in this retrospective study. All patients received liver magnetic resonance imaging including standard T2-weighted images. The total erector spinae muscle area and the intramuscular adipose tissue area were measured at the level of the origin of the superior mesenteric artery and subtracted to calculate FFMA. Cutoff values for definition of low FFMA were 3644 mm² in men and 2825 mm² in women. The main outcome was overall survival (OS). For survival analysis, the Kaplan-Meier method and Cox regressions comparing various clinic-oncological parameters which potentially may affect OS were performed. Results Seventy-seven patients (28 female, mean age 60 ± 11 years) were analyzed. Mean time between MRI and the following RE was 17 ± 31 days. Median OS after RE was 178 days. Patients with low FFMA had significantly shortened OS compared to patients with high FFMA (median OS: 128 vs. 273 days, p = 0.017). On multivariate Cox regression analysis, OS was best predicted by FFMA (hazard ratio (HR) 2.652; p < 0.001). Baseline bilirubin (HR 1.875; p = 0.030), pattern of tumor manifestation (HR 1.679; p = 0.001), and model of endstage liver disease (MELD) score (HR 1.164; p < 0.001) were also significantly associated with OS. Conclusions FFMA was associated with OS in patients receiving RE for treatment of mCRC and might be a new prognostic biomarker for survival prognosis. Key Points • Fat-free muscle area (FFMA) as a measure of lean muscle area predicts survival in metastatic colorectal liver cancer following radioembolization. • FFMA can easily be assessed from routine pre-interventional liver magnetic resonance imaging. • FFMA might be a new promising biomarker for assessment of sarcopenia.