Skeletal Muscle Wasting: Clinical implications and experimental treatment

Cachexia is a clinical condition characterized by muscle wasting, anorexia and metabolic change. It is associated with a wide variety of clinical conditions, including cancer. Clinically it is rarely recognized prior to end-stage disease. Computed tomography (CT) imaging has made it possible to detect differences in skeletal muscle mass early on in the course of disease. The aim of the studies in this thesis was to describe the clinical impact of low skeletal muscle mass on overall survival and disease-free survival in surgical oncology and liver transplant patients. And to investigate potential treatment strategies in experimental cancer-associated cachexia animal models

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

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

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

Utility of preoperative CT-based body metrics in relation to postoperative complications in pediatric liver transplant recipients

BACKGROUND: Computed tomography (CT) derived body metrics such as skeletal muscle index (SMI), psoas muscle index (PMI), and subcutaneous fat 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 the value in pediatric populations. This study assessed the relation between preoperative CT-based body metrics and postoperative short-term outcomes in pediatric LT recipients. METHODS: 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 (10 years old). An optimal threshold for test performance was defined using Youden's J-statistic and receiver operating characteristic curve as appropriate. RESULTS: ScFI was significantly (P=0.001) correlated with moderate to severe postoperative infections (CD grade 3-5) in children <1 year old, 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=-0.33, P=0.010) and intensive care unit stay (R=-0.32, P 0.013) was observed in children <1 year old. No other associations between CT-based body metrics and postoperative outcomes were shown. CONCLUSIONS: In children <1 year old with cirrhotic liver disease undergoing LT, pre-operative 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

Quercetin supplementation attenuates muscle wasting in cancer-associated cachexia in mice

BACKGROUND: Quercetin is a flavonoid with reported antioxidant, anti-inflammatory and anti-aging effects, and may limit muscle wasting in cancer cachexia. OBJECTIVE: To investigate the effect of quercetin on muscle wasting in the murine C26 cancer-cachexia model and assess the feasibility of non-invasive micro-CT analysis of skeletal muscle. MATERIALS AND METHODS: Custom CRM(P) diets supplemented with 250 mg/kg quercetin (Q) were obtained. Thirty CD2F1 mice were equally randomized to non-tumor-bearing (NTB), C26 tumor-bearing (TB), TB + Q. All groups started their allocated diet and underwent hindlimb micro-CT. Bodyweight, food intake, and grip-strength were recorded periodically. After 21 days, repeat micro-CT was performed. Gastrocnemius (GCM) and tibialis anterior (TA) muscles were resected. mRNA expression of MuRF1, Atrogin-1, myogenin, and MyoD was determined

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

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 befor

Muscle wasting and survival following pre-operative chemoradiotherapy for locally advanced rectal carcinoma

Background & aims: Neoadjuvant chemoradiotherapy (NACRT) has increased local control in locally advanced rectal cancer. Reduced skeletal muscle mass (sarcopenia), or ongoing muscle wasting, is associated with decreased survival in cancer. This study aims to assess the change in body composition during NACRT and its impact on outcome using computed tomography (CT) imaging in locally advancedrectal cancer (LARC) patients. Methods: LARC patients treated with NACRT were selected from a prospectively maintained database and retrospectively analyzed. One-hundred twenty-two patients who received treatment between 2004 and 2012 with available diagnostic CT imaging obtained before and after NACRT were identified. Cross-sectional areas for skeletal muscle was determined, and subsequently normalized for patient height. Differences between skeletal muscle areas before and after NACRT were computed, and their influenceon overall and disease-free survival was assessed. Results: A wide distribution in change of body composition was observed. Loss of skeletal muscle mass during chemoradiotherapy was independently associated with disease-free survival (HR0.971; 95% CI:0.946e0.996; p¼0.025) and distant metastasis-free survival (HR0.942; 95% CI: 0.898e0.988; p¼0.013).No relation was observed with overall survival in the current cohort. Conclusions:Loss of skeletal muscle mass during NACRT in rectal cancer patients is an independent prognostic factor for disease-free survival and distant metastasis-free survival following curative intentresection

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 al