Background & aims: Optimal nutritional support during the acute phase of critical illness remains controversial. We hypothesized that patients with low skeletal muscle area and -density may specifically benefit from early high protein intake. Aim of the present study was to determine the association between early protein intake (day 2–4) and mortality in critically ill intensive care unit (ICU) patients with normal skeletal muscle area, low skeletal muscle area, or combined low skeletal muscle area and -density. Methods: Retrospective database study in mechanically ventilated, adult critically ill patients with an abdominal CT-scan suitable for skeletal muscle assessment around ICU admission, admitted from January 2004 to January 2016 (n = 739). Patients received protocolized nutrition with protein target 1.2–1.5 g/kg/day. Skeletal muscle area and -density were assessed on abdominal CT-scans at the 3rd lumbar vertebra level using previously defined cut-offs. Results: Of 739 included patients (mean age 58 years, 483 male (65%), APACHE II score 23), 294 (40%) were admitted with normal skeletal muscle area and 445 (60%) with low skeletal muscle area. Two hundred (45% of the low skeletal muscle area group) had combined low skeletal muscle area and -density. In the normal skeletal muscle area group, no significant associations were found. In the low skeletal muscle area group, higher early protein intake was associated with lower 60-day mortality (adjusted hazard ratio (HR) per 0.1 g/kg/day 0.82, 95%CI 0.73–0.94) and lower 6-month mortality (HR 0.88, 95%CI 0.79–0.98). Similar associations were found in the combined low skeletal muscle area and -density subgroup (HR 0.76, 95%CI 0.64–0.90 for 60-day mortality and HR 0.80, 95%CI 0.68–0.93 for 6-month mortality). Conclusions: Early high protein intake is associated with lower mortality in critically ill patients with low skeletal muscle area and -density, but not in patients with normal skeletal muscle area on admission. These findings may be a further step to personalized nutrition, although randomized studies are needed to assess causality.
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BACKGROUND: Muscle quantity at intensive care unit (ICU) admission has been independently associated with mortality. In addition to quantity, muscle quality may be important for survival. Muscle quality is influenced by fatty infiltration or myosteatosis, which can be assessed on computed tomography (CT) scans by analysing skeletal muscle density (SMD) and the amount of intermuscular adipose tissue (IMAT). We investigated whether CT-derived low skeletal muscle quality at ICU admission is independently associated with 6-month mortality and other clinical outcomes.METHODS: This retrospective study included 491 mechanically ventilated critically ill adult patients with a CT scan of the abdomen made 1 day before to 4 days after ICU admission. Cox regression analysis was used to determine the association between SMD or IMAT and 6-month mortality, with adjustments for Acute Physiological, Age, and Chronic Health Evaluation (APACHE) II score, body mass index (BMI), and skeletal muscle area. Logistic and linear regression analyses were used for other clinical outcomes.RESULTS: Mean APACHE II score was 24 ± 8 and 6-month mortality was 35.6%. Non-survivors had a lower SMD (25.1 vs. 31.4 Hounsfield Units (HU); p < 0.001), and more IMAT (17.1 vs. 13.3 cm(2); p = 0.004). Higher SMD was associated with a lower 6-month mortality (hazard ratio (HR) per 10 HU, 0.640; 95% confidence interval (CI), 0.552-0.742; p < 0.001), and also after correction for APACHE II score, BMI, and skeletal muscle area (HR, 0.774; 95% CI, 0.643-0.931; p = 0.006). Higher IMAT was not significantly associated with higher 6-month mortality after adjustment for confounders. A 10 HU increase in SMD was associated with a 14% shorter hospital length of stay.CONCLUSIONS: Low skeletal muscle quality at ICU admission, as assessed by CT-derived skeletal muscle density, is independently associated with higher 6-month mortality in mechanically ventilated patients. Thus, muscle quality as well as muscle quantity are prognostic factors in the ICU.TRIAL REGISTRATION: Retrospectively registered (initial release on 06/23/2016) at ClinicalTrials.gov: NCT02817646 .
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Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.
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The world population is ageing rapidly. As society ages, the incidence of physical limitations is dramatically increasing, which reduces the quality of life and increases healthcare expenditures. In western society, ~30% of the population over 55 years is confronted with moderate or severe physical limitations. These physical limitations increase the risk of falls, institutionalization, co-morbidity, and premature death. An important cause of physical limitations is the age-related loss of skeletal muscle mass, also referred to as sarcopenia. Emerging evidence, however, clearly shows that the decline in skeletal muscle mass is not the sole contributor to the decline in physical performance. For instance, the loss of muscle strength is also a strong contributor to reduced physical performance in the elderly. In addition, there is ample data to suggest that motor coordination, excitation-contraction coupling, skeletal integrity, and other factors related to the nervous, muscular, and skeletal systems are critically important for physical performance in the elderly. To better understand the loss of skeletal muscle performance with ageing, we aim to provide a broad overview on the underlying mechanisms associated with elderly skeletal muscle performance. We start with a system level discussion and continue with a discussion on the influence of lifestyle, biological, and psychosocial factors on elderly skeletal muscle performance. Developing a broad understanding of the many factors affecting elderly skeletal muscle performance has major implications for scientists, clinicians, and health professionals who are developing therapeutic interventions aiming to enhance muscle function and/or prevent mobility and physical limitations and, as such, support healthy ageing.
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Skeletal muscle-related symptoms are common in both acute coronavirus disease (Covid)-19 and post-acute sequelae of Covid-19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy, and post-viral fatigue syndrome. Patients with severe Covid-19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fibre atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid-19 include systemic inflammation, disuse, hypoxaemia, and malnutrition. These factors also contribute to post-intensive care unit (ICU) syndrome and ICU-acquired weakness and likely explain a substantial part of Covid-19-acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure. Direct severe acute respiratory syndrome coronavirus (SARS-CoV)-2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study. Both SARS-CoV-2-specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid-19 and PASC.
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Background & aims: Low muscle mass and -quality on ICU admission, as assessed by muscle area and -density on CT-scanning at lumbar level 3 (L3), are associated with increased mortality. However, CT-scan analysis is not feasible for standard care. Bioelectrical impedance analysis (BIA) assesses body composition by incorporating the raw measurements resistance, reactance, and phase angle in equations. Our purpose was to compare BIA- and CT-derived muscle mass, to determine whether BIA identified the patients with low skeletal muscle area on CT-scan, and to determine the relation between raw BIA and raw CT measurements. Methods: This prospective observational study included adult intensive care patients with an abdominal CT-scan. CT-scans were analysed at L3 level for skeletal muscle area (cm2) and skeletal muscle density (Hounsfield Units). Muscle area was converted to muscle mass (kg) using the Shen equation (MMCT). BIA was performed within 72 h of the CT-scan. BIA-derived muscle mass was calculated by three equations: Talluri (MMTalluri), Janssen (MMJanssen), and Kyle (MMKyle). To compare BIA- and CT-derived muscle mass correlations, bias, and limits of agreement were calculated. To test whether BIA identifies low skeletal muscle area on CT-scan, ROC-curves were constructed. Furthermore, raw BIA and CT measurements, were correlated and raw CT-measurements were compared between groups with normal and low phase angle. Results: 110 patients were included. Mean age 59 ± 17 years, mean APACHE II score 17 (11–25); 68% male. MMTalluri and MMJanssen were significantly higher (36.0 ± 9.9 kg and 31.5 ± 7.8 kg, respectively) and MMKyle significantly lower (25.2 ± 5.6 kg) than MMCT (29.2 ± 6.7 kg). For all BIA-derived muscle mass equations, a proportional bias was apparent with increasing disagreement at higher muscle mass. MMTalluri correlated strongest with CT-derived muscle mass (r = 0.834, p < 0.001) and had good discriminative capacity to identify patients with low skeletal muscle area on CT-scan (AUC: 0.919 for males; 0.912 for females). Of the raw measurements, phase angle and skeletal muscle density correlated best (r = 0.701, p < 0.001). CT-derived skeletal muscle area and -density were significantly lower in patients with low compared to normal phase angle. Conclusions: Although correlated, absolute values of BIA- and CT-derived muscle mass disagree, especially in the high muscle mass range. However, BIA and CT identified the same critically ill population with low skeletal muscle area on CT-scan. Furthermore, low phase angle corresponded to low skeletal muscle area and -density. Trial registration: ClinicalTrials.gov (NCT02555670).
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Background & aims: Accurate diagnosis of sarcopenia requires evaluation of muscle quality, which refers to the amount of fat infiltration in muscle tissue. In this study, we aim to investigate whether we can independently predict mortality risk in transcatheter aortic valve implantation (TAVI) patients, using automatic deep learning algorithms to assess muscle quality on procedural computed tomography (CT) scans. Methods: This study included 1199 patients with severe aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) between January 2010 and January 2020. A procedural CT scan was performed as part of the preprocedural-TAVI evaluation, and the scans were analyzed using deep-learning-based software to automatically determine skeletal muscle density (SMD) and intermuscular adipose tissue (IMAT). The association of SMD and IMAT with all-cause mortality was analyzed using a Cox regression model, adjusted for other known mortality predictors, including muscle mass. Results: The mean age of the participants was 80 ± 7 years, 53% were female. The median observation time was 1084 days, and the overall mortality rate was 39%. We found that the lowest tertile of muscle quality, as determined by SMD, was associated with an increased risk of mortality (HR 1.40 [95%CI: 1.15–1.70], p < 0.01). Similarly, low muscle quality as defined by high IMAT in the lowest tertile was also associated with increased mortality risk (HR 1.24 [95%CI: 1.01–1.52], p = 0.04). Conclusions: Our findings suggest that deep learning-assessed low muscle quality, as indicated by fat infiltration in muscle tissue, is a practical, useful and independent predictor of mortality after TAVI.
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Muscle fiber-type specific expression of UCP3-protein is reported here for the firts time, using immunofluorescence microscopy
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Echo intensity determined by muscle ultrasound has been proposed as an efficient method for the assessment of muscle quality. The influence of changing ultrasound parameter settings on echo intensity values was assessed using a standardized approach. In this repeated measures cross-sectional study, sixteen repeated scans of rectus femoris, gracilis, and rectus abdominis were taken in 21 middle-aged persons with a portable Mindray M7 premium ultrasound machine equipped with a linear 5.0–10.0 MHz transducer. The settings of three parameters were fixed: gain, depth, and frequency. The settings of the following adjustable parameters were changed over their entire range: dynamic range, gray map, line density, persistence, and IClear. Repeated measures analyses were performed to evaluate the effect of changing the settings on echo intensity values. In all three muscles, dynamic range, gray map, and IClear correlated significantly (rrm-values ranging between −0.86 and 0.45) with echo intensity. In all three muscles, the echo intensity values differed significantly across the dynamic range (p < 0.013), gray map (p < 0.003), and IClear (p < 0.003). In middle-aged subjects, echo intensity values of lower limb and trunk muscles are significantly related to ultrasound parameters and significantly differ across their respective setting range. For the assessment of muscle quality through ultrasound, it is suggested to fix parameter settings within their midrange in order to minimize the effect of setting-dependent factors on EI values.
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(1) Background: Recent research showed that subtypes of patients with type 2 diabetes may differ in response to lifestyle interventions based on their organ-specific insulin resistance (IR). (2) Methods: 123 Subjects with type 2 diabetes were randomized into 13-week lifestyle intervention, receiving either an enriched protein drink (protein+) or an isocaloric control drink (control). Before and after the intervention, anthropometrical and physiological data was collected. An oral glucose tolerance test was used to calculate indices representing organ insulin resistance (muscle, liver, and adipose tissue) and β-cell functioning. In 82 study-compliant subjects (per-protocol), we retrospectively examined the intervention effect in patients with muscle IR (MIR, n = 42) and without MIR (no-MIR, n = 40). (3) Results: Only in patients from the MIR subgroup that received protein+ drink, fasting plasma glucose and insulin, whole body, liver and adipose IR, and appendicular skeletal muscle mass improved versus control. Lifestyle intervention improved body weight and fat mass in both subgroups. Furthermore, for the MIR subgroup decreased systolic blood pressure and increased VO2peak and for the no-MIR subgroup, a decreased 2-h glucose concentration was found. (4) Conclusions: Enriched protein drink during combined lifestyle intervention seems to be especially effective on increasing muscle mass and improving insulin resistance in obese older, type 2 diabetes patients with muscle IR.
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