Skeletal muscle atrophy and myosteatosis are not related to long-term aneurysmal subarachnoid hemorrhage outcome.

The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) is highly variable. This study aims to investigate whether skeletal muscle atrophy and myosteatosis are associated with poor outcome after aSAH. In this study, a cohort of 293 consecutive aSAH-patients admitted during a 4-year period was retrospectively analyzed. Cross-sectional muscle measurements were obtained at the level of the third cervical vertebra. Muscle atrophy was defined by a sex-specific cutoff value. Myosteatosis was defined by a BMI-specific cutoff value. Poor neurological outcome was defined as modified Rankin Scale 4-6 at 2 and 6-month follow-up. Patient survival state was checked until January 2021. Generalized estimating equation was performed to assess the effect of muscle atrophy / myosteatosis on poor neurological outcome after aSAH. Cox regression was performed to analyze the impact of muscle atrophy and myosteatosis on overall survival. The study found that myosteatosis was associated with poor neurological condition (WFNS 4-5) at admission after adjusting for covariates (odds ratio [OR] 2.01; 95%CI 1.05,3.83; P = .03). It was not associated with overall survival (P = .89) or with poor neurological outcomes (P = .18) when adjusted for other prognostic markers. Muscle atrophy was not associated with overall survival (P = .58) or neurological outcome (P = .32) after aSAH. In conclusion, myosteatosis was found to be associated with poor physical condition directly after onset of aSAH. Skeletal muscle atrophy and myosteatosis were however irrelevant to outcome in the Western-European aSAH patient. Future studies are needed to validate these finding.

The Impact of Lower Extremity Skeletal Muscle Atrophy and Myosteatosis on Revascularization Outcomes in Patients with Peripheral Arterial Disease.

BACKGROUND: This study investigated whether lower extremity muscle atrophy and myosteatosis in patients with peripheral arterial disease (PAD) are correlated to postoperative outcomes, such as reintervention or amputation-free survival. METHODS: In this single-center retrospective cohort study of 462 patients treated for peripheral arterial disease scheduled for intervention, muscle mass and the presence of fattening of the lower extremity muscles were measured semiautomatically in a single computed tomography slice of the treated leg. Binary logistic regression models and Cox proportional hazards models were used to determine the effect of muscle atrophy and myosteatosis on reintervention and amputation. RESULTS: Muscle atrophy and myosteatosis increased in PAD patients with Fontaine class IV compared with Fontaine class IIa. In PAD patients with muscle atrophy or myosteatosis, no association was found with the reintervention rate or reintervention-free survival, but an association was found with amputation-free survival, even after adjustment for patient-related, disease-severity, and comorbidities-related factors. CONCLUSION: Muscle atrophy and mysosteatosis increased in PAD patients with increasing disease severity. Lower extremity muscle atrophy and myosteatosis are associated with amputation rate and amputation-free survival in PAD patients. No association with reintervention rate or reintervention-free survival was found. Muscle atrophy and myosteatosis may serve as additional risk factors in decision making in the often frail vascular patient.

Utility of Preoperative Computed Tomography-Based Body Metrics in Relation to Postoperative Complications in Pediatric Liver Transplantation Recipients.

Computed tomography (CT)-derived body metrics such as skeletal muscle index (SMI), psoas muscle index (PMI), and subcutaneous fat area index (ScFI) are measurable components of sarcopenia, frailty, and nutrition. While these body metrics are advocated in adults for predicting postoperative outcomes after liver transplantation (LT), little is known about their value in pediatric populations. This study assessed the relation between preoperative CT-based body metrics and postoperative short-term outcomes in pediatric LT recipients. Patients aged 0-18 years who underwent a primary LT were retrospectively included (n = 101; median age 0.5 years; range 0.2-17.1). SMI, PMI, and ScFI were derived from preoperative axial CT slices. Postoperative outcomes and complications within 90 days were correlated with the CT-based body metrics. To classify postoperative infections, the Clavien-Dindo (CD) classification was used. Subgroup analyses were performed for age groups (<1, 1-10, and >10 years old). An optimal threshold for test performance was defined using Youden's J-statistic and receiver operating characteristic curve as appropriate. ScFI was significantly (P = 0.001) correlated with moderate to severe postoperative infections (CD grade 3-5) in children aged <1 year, with the optimal ScFI threshold being ≤27.1 cm2 /m2 (sensitivity 80.4% and specificity 77.8%). A weak negative correlation between SMI and the total duration of hospital stay (R = -0.3; P = 0.01) and intensive care unit (ICU) stay (R = -0.3; P = 0.01) was observed in children aged <1 year. No other associations between CT-based body metrics and postoperative outcomes were shown. In children aged <1 year with cirrhotic liver disease undergoing LT, preoperative CT-based body metrics were correlated with moderate to severe postoperative infections (ScFI) and with longer duration of hospital and ICU stay (SMI), and thus can be considered important tools for pre-LT risk assessment.

Arterial thrombotic complications in COVID-19 patients.

The coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been described to predispose to thrombotic disease in both the venous and arterial circulations. We report four cases of an acute arterial occlusion in COVID-19 patients and literature review on the occurrence of arterial thrombosis in patients with COVID-19. Our findings demonstrate that physicians should be vigilant for signs of thrombotic complications in both hospitalized and new COVID-19 patients.

Effect of muscle depletion on survival in peripheral arterial occlusive disease: Quality over quantity.

OBJECTIVE: Patients with peripheral arterial occlusive disease (PAOD) have a poor prognosis and a high prevalence of comorbidity. This study investigated whether sarcopenia and/or myosteatosis negatively affect long-term survival in patients with PAOD. METHODS: This was a single-center, retrospective cohort study of 686 consecutive patients diagnosed and treated for PAOD and who underwent computed tomography scanning. Cross-sectional muscle measurements were obtained at the level of the third lumbar vertebra. Optimal stratification was used to define sex-specific and body mass index-specific cutoff values for sarcopenia and myosteatosis, respectively. The Cox proportional hazards model was used to determine the effect of sarcopenia and myosteatosis on overall survival. RESULTS: Sarcopenia was associated with age, body mass index, myosteatosis, malignancy, congestive heart failure, hemodialysis, and Fontaine 4 classification. Myosteatosis was associated with age, sarcopenia, type 2 diabetes mellitus, hypertension, chronic obstructive pulmonary disease, malignancy, congestive heart failure, ischemic stroke, and Fontaine 4 classification. Sarcopenia (hazard ratio [HR], 2.82; 95% confidence interval [CI], 2.05-3.86; P < .001) and myosteatosis (HR, 4.13; 95% CI, 3.03-5.63; P < .001) were both associated with reduced survival in univariable analysis. When adjusted for other prognostic markers, myosteatosis (HR, 2.09; 95% CI, 1.46-2.99; P < .001) was still associated with lower overall survival in the multivariable model, but sarcopenia (HR, 1.40; 95% CI, 0.97-2.01; P = .073) was not. CONCLUSIONS: Muscle depletion is independently associated with a poorer overall survival in patients with PAOD. Myosteatosis is a stronger predictor than sarcopenia, which indicates that quality is more important than quantity. Results should be interpreted with caution owing to missing data on medication usage.

Quantification of muscle mass in the legs of patients with peripheral arterial occlusive disease: associations between volumetric and cross-sectional single-slice measurements for identification of atrophy and focal sarcopenia.

BACKGROUND: Sarcopenia, commonly determined by measuring skeletal muscle mass index (SMI) at the third lumbar level, has been identified as a predictor of clinical outcome in a variety of diseases. For patients with peripheral arterial occlusive disease (PAOD), we hypothesized that lower extremity SMI (LESMI) might be a more precise predictor of outcome and the extent of chronic ischemia than the systemic muscle mass at the L3 level. We investigated the association between complete muscle volume and muscle area derived with single-slice 2-dimensional measurements in the legs to identify at which level cross-sectional single-slice measurements are most representative of the muscle volume and investigated whether LESMI is associated with systemic sarcopenia and PAOD severity. METHODS: Muscle volumes and areas were semiautomatically segmented from computed tomography (CT) scans of the affected and contralateral legs of 50 PAOD patients with Fontaine stage IIb and 50 PAOD patients with Fontaine stage IV. The muscle mass was determined for the complete volumes of the upper and lower legs and for cross-sectional slices at 40%, 50%, and 60% of the length of the femur and tibia. Patients were determined as sarcopenic based on sex-specific cut-off values at the L3 spinal segment. Two observers segmented 20 randomly selected patients to determine the interobserver reliability with the intraclass correlation coefficient. RESULTS: The correlation between the LESMI of the complete muscle volume and the three cross-sectional slices in all 200 upper and 200 lower legs was moderately strong to strong. Interobserver reliability of cross-sectional slice segmentation was excellent. The LESMI, both measured volumetrically and cross-sectionally, were significantly lower in patients with sarcopenia compared to patients without sarcopenia. The LESMI was lower in patients with Fontaine stage IV compared to patients with Fontaine stage IIb for both volumetric and cross-sectional measurements. CONCLUSIONS: Segmentation of skeletal muscle mass from cross-sectional single-slice CT in the upper and lower leg can accurately and precisely substitute complete volume segmentations. These findings warrant the use of measurements based on cross-sectional single-slice CT for assessing the LESMI. Patients with systemic sarcopenia are also at increased risk for muscle mass loss in the lower extremities. In the current study, LESMI was lower in patients with Fontaine class IV PAOD compared to patients with Fontaine class IIb PAOD. Future studies should assess the predictive value of the LESMI on clinical outcomes in PAOD patients.

Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment.

BACKGROUND: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. METHODS: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. RESULTS: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. CONCLUSION: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.

Caloric restriction is associated with preservation of muscle strength in experimental cancer cachexia.

Caloric restriction increases lifespan and healthspan, and limits age-associated muscle wasting. In this study, we investigate the impact of 30% caloric restriction (CR) in a murine cancer cachexia model. Forty CD2F1 mice were allocated as C26 tumor-bearing (TB) + ad libitum food intake (dietary reference intake [DRI]), TB CR, non-TB (NTB) CR, or NTB matched intake (MI). TB groups were inoculated subcutaneously with 0.5x106 C26 cells 14 days after initiating CR. Bodyweight, food intake, and grip-strength were recorded periodically. Gastrocnemius (GCM) and tibialis anterior (TA) muscles were resected and weighed 3 weeks after tumor inoculation. mRNA expression of MuRF1, Atrogin-1, myogenin, and MyoD was determined. At tumor inoculation, the mean body weight of TB CR was 88.6% of initial body weight and remained stable until sacrifice. TB DRI showed wasting before sacrifice. TB groups experienced muscle wasting compared with NTB MI. Grip-strength change was less severe in TB CR. Expression of MuRF1, Atrogin-1, and MyoD was similar between TB DRI and both CR groups. Expression of myogenin was increased in CR groups. In conclusion, caloric restriction limits loss of muscle strength but has no impact on muscle mass despite significant loss of body weight in an experimental cancer-associated cachexia model.

Contrast-enhancement influences skeletal muscle density, but not skeletal muscle mass, measurements on computed tomography.

BACKGROUND & AIMS: Low skeletal muscle mass and density have recently been discovered as prognostic and predictive parameters to guide interventions in various populations, including cancer patients. The gold standard for body composition analysis in cancer patients is computed tomography (CT). To date, the effect of contrast-enhancement on muscle composition measurements has not been established. The aim of this study was to determine the effect of contrast-enhancement on skeletal muscle mass and density measurements on four-phase CT studies. DESIGN: In this observational study, two observers measured cross-sectional skeletal muscle area corrected for patients' height (skeletal muscle index [SMI]) and density (SMD) at the level of the third lumbar vertebra on 50 randomly selected CT examinations with unenhanced, arterial, and portal-venous phases. The levels of agreement between enhancement phases for SMI and SMD were calculated using intra-class correlation coefficients (ICCs). RESULTS: Mean SMI was 42.5 (±9.9) cm2/m2 on the unenhanced phase, compared with 42.8 (±9.9) and 43.6 (±9.9) cm2/m2 for the arterial and portal-venous phase, respectively (both p < 0.01). Mean SMD was lower for the unenhanced phase (30.9 ± 8.0 Hounsfield units [HU]) compared with the arterial (38.0 ± 9.9 HU) and portal-venous (38.7 ± 9.2 HU) phase (both p < 0.001). No significant difference was found between SMD in the portal-venous and arterial phase (p = 0.161). The ICCs were excellent (≥0.992) for all SMIs and for SMD between the contrast-enhanced phases (0.949). The ICCs for the unenhanced phase compared with the arterial (0.676) and portal-venous (0.665) phase were considered fair to good. CONCLUSIONS: Statistically significant differences in SMI were observed between different enhancement phases. However, further work is needed to assess the clinical relevance of these small differences. Contrast-enhancement strongly influenced SMD values. Studies using this measure should therefore use the portal-venous phase of contrast-enhanced CT examinations.

Low skeletal muscle mass is associated with increased hospital expenditure in patients undergoing cancer surgery of the alimentary tract.

BACKGROUND: Low skeletal muscle mass is associated with poor postoperative outcomes in cancer patients. Furthermore, it is associated with increased healthcare costs in the United States. We investigated its effect on hospital expenditure in a Western-European healthcare system, with universal access. METHODS: Skeletal muscle mass (assessed on CT) and costs were obtained for patients who underwent curative-intent abdominal cancer surgery. Low skeletal muscle mass was defined based on pre-established cut-offs. The relationship between low skeletal muscle mass and hospital costs was assessed using linear regression analysis and Mann-Whitney U-tests. RESULTS: 452 patients were included (median age 65, 61.5% males). Patients underwent surgery for colorectal cancer (38.9%), colorectal liver metastases (27.4%), primary liver tumours (23.2%), and pancreatic/periampullary cancer (10.4%). In total, 45.6% had sarcopenia. Median costs were €2,183 higher in patients with low compared with patients with high skeletal muscle mass (€17,144 versus €14,961; P<0.001). Hospital costs incrementally increased with lower sex-specific skeletal muscle mass quartiles (P = 0.029). After adjustment for confounders, low skeletal muscle mass was associated with a cost increase of €4,061 (P = 0.015). CONCLUSION: Low skeletal muscle mass was independently associated with increased hospital costs of about €4,000 per patient. Strategies to reduce skeletal muscle wasting could reduce hospital costs in an era of incremental healthcare costs and an increasingly ageing population.

A comparative study of software programmes for cross-sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patients.

BACKGROUND: The association between body composition (e.g. sarcopenia or visceral obesity) and treatment outcomes, such as survival, using single-slice computed tomography (CT)-based measurements has recently been studied in various patient groups. These studies have been conducted with different software programmes, each with their specific characteristics, of which the inter-observer, intra-observer, and inter-software correlation are unknown. Therefore, a comparative study was performed. METHODS: Fifty abdominal CT scans were randomly selected from 50 different patients and independently assessed by two observers. Cross-sectional muscle area (CSMA, i.e. rectus abdominis, oblique and transverse abdominal muscles, paraspinal muscles, and the psoas muscle), visceral adipose tissue area (VAT), and subcutaneous adipose tissue area (SAT) were segmented by using standard Hounsfield unit ranges and computed for regions of interest. The inter-software, intra-observer, and inter-observer agreement for CSMA, VAT, and SAT measurements using FatSeg, OsiriX, ImageJ, and sliceOmatic were calculated using intra-class correlation coefficients (ICCs) and Bland-Altman analyses. Cohen's κ was calculated for the agreement of sarcopenia and visceral obesity assessment. The Jaccard similarity coefficient was used to compare the similarity and diversity of measurements. RESULTS: Bland-Altman analyses and ICC indicated that the CSMA, VAT, and SAT measurements between the different software programmes were highly comparable (ICC 0.979-1.000, P < 0.001). All programmes adequately distinguished between the presence or absence of sarcopenia (κ = 0.88-0.96 for one observer and all κ = 1.00 for all comparisons of the other observer) and visceral obesity (all κ = 1.00). Furthermore, excellent intra-observer (ICC 0.999-1.000, P < 0.001) and inter-observer (ICC 0.998-0.999, P < 0.001) agreement for all software programmes were found. Accordingly, excellent Jaccard similarity coefficients were found for all comparisons (mean ≥ 0.964). CONCLUSIONS: FatSeg, OsiriX, ImageJ, and sliceOmatic showed an excellent agreement for CSMA, VAT, and SAT measurements on abdominal CT scans. Furthermore, excellent inter-observer and intra-observer agreement were achieved. Therefore, results of studies using these different software programmes can reliably be compared.

Sarcopenia impairs survival in patients with potentially curable hepatocellular carcinoma.

BACKGROUND: A reduction in skeletal muscle mass (sarcopenia) independently predicts poor survival in patients with hepatocellular carcinoma (HCC) undergoing treatment with curative intent. Whether this is due to an increased risk of recurrence and disease specific death, or due to an increased risk of postoperative morbidity and mortality is currently unclear. In this study, we investigate the association between sarcopenia and death in a cohort of HCC patients undergoing treatment with curative intent. METHODS: Patients undergoing surgical resection or radiofrequency ablation for lesions ≤ 3 cm between 2002 and 2013 were identified. Clinicopathological characteristics, CT-assessed sarcopenia and outcomes were analyzed. RESULTS: Among 90 patients, 52 (57.8%) were found to be sarcopenic. Sarcopenic patients had a limited overall survival (median: 33 months vs. non-sarcopenic median: 105 months; P = 0.002), but not disease-free survival. Sarcopenia was an independent predictor for overall survival in multivariate Cox-regression analysis (HR 3.756; P = 0.001). Major complications (32.7% vs. 13.2%, P = 0.033) and treatment-related mortality (17.3% vs. 2.6%, P = 0.029) were more frequent in sarcopenic patients. CONCLUSION: Sarcopenia impairs survival in patients with potentially curable hepatocellular carcinoma, mainly due to an increase in treatment-related mortality.