Myosteatosis in a systemic inflammation-dependent manner predicts favorable survival outcomes in locally advanced esophageal cancer

Increased adiposity and its attendant metabolic features as well as systemic inflammation have been associated with prognosis in locally advanced esophageal cancer (LAEC). However, whether myosteatosis and its combination with systemic inflammatory markers are associated with prognosis of esophageal cancer is unknown. Our study aimed to investigate the influence of myosteatosis and its association with systemic inflammation on progression-free survival (PFS) and overall survival (OS) in LAEC patients treated with definitive chemoradiotherapy (dCRT). We retrospectively gathered information on 123 patients with LAEC submitted to dCRT at the University of Campinas Hospital. Computed tomography (CT) images at the level of L3 were analyzed to assess muscularity and adiposity. Systemic inflammation was mainly measured by calculating the neutrophil-to-lymphocyte ratio (NLR). Median PFS for patients with myosteatosis (n = 72) was 11.0 months vs 4.0 months for patients without myosteatosis (n = 51) (hazard ratio [HR]: 0.53; 95% confidence interval [CI], 0.34-0.83; P = .005). Myosteatosis was also independently associated with a favorable OS. Systemic inflammation (NLR > 2.8) was associated with a worse prognosis. The combination of myosteatosis with systemic inflammation revealed that the subgroup of patients with myosteatosis and without inflammation presented less than half the risk of disease progression (HR: 0.47; 95% CI: 0.26-0.85; P = .013) and death (HR: 0.39; 95% CI, 0.21-0.72; P = .003) compared with patients with inflammation. This study demonstrated that myosteatosis without systemic inflammation was independently associated with favorable PFS and OS in LAEC patients treated with dCRT81669676976FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2018/23428-

AdipoRon enhances healthspan in middle‐aged obese mice: striking alleviation of myosteatosis and muscle degenerative markers

BackgroundObesity among older adults has increased tremendously. Obesity accelerates ageing and predisposes toage-related conditions and diseases, such as loss of endurance capacity, insulin resistance and features of the metabolicsyndrome. Namely, ectopic lipids play a key role in the development of nonalcoholic fatty liver disease (NAFLD) andmyosteatosis, two severe burdens of ageing and metabolic diseases. Adiponectin (ApN) is a hormone, mainly secretedby adipocytes, which exerts insulin-sensitizing and fat-burning properties in several tissues including the liver and themuscle. Its overexpression also increases lifespan in mice. In this study, we investigated whether an ApN receptor ag-onist, AdipoRon (AR), could slow muscle dysfunction, myosteatosis and degenerative muscle markers in middle-agedobese mice. The effects on myosteatosis were compared with those on NAFLD.MethodsThree groups of mice were studied up to 62 weeks of age: One group received normal diet (ND), another,high-fat diet (HFD); and the last, HFD combined with AR given orally for almost 1 year. An additional group of youngmice under an ND was used. Treadmill tests and micro-computed tomography (CT) were carried out in vivo. Histolog-ical, biochemical and molecular analyses were performed on tissues ex vivo. Bodipy staining was used to assessintramyocellular lipid (IMCL) and lipid droplet morphology.ResultsAR did not markedly alter diet-induced obesity. Yet, this treatment rescued exercise endurance in obese mice(up to 2.4-fold,P<0.05), an event that preceded the improvement of insulin sensitivity. Dorsal muscles and liver den-sities, measured by CT, were reduced in obese mice ( 42% and 109%, respectively,P<0.0001), suggesting fatty in-filtration. This reduction tended to be attenuated by AR. Accordingly, AR significantly mitigated steatosis and cellularballooning at liver histology, thereby decreasing the NALFD activity score ( 30%,P<0.05). AR also strikingly reversedIMCL accumulation either due to ageing in oxidativefibres (types 1/2a, soleus) or to HFD in glycolytic ones (types2x/2b, extensor digitorum longus) ( 50% to 85%,P<0.05 or less). Size of subsarcolemmal lipid droplets, knownto be associated with adverse metabolic outcomes, was reduced as well. Alleviation of myosteatosis resulted from im-proved mitochondrial function and lipid oxidation. Meanwhile, AR halved aged-related accumulation of dysfunctionalproteins identified as tubular aggregates and cylindrical spirals by electron microscopy (P<0.05).ConclusionsLong-term AdipoRon treatment promotes‘healthy ageing’in obese middle-aged mice by enhancing en-durance and protecting skeletal muscle and liver against the adverse metabolic and degenerative effects of ageingand caloric excess.University College de Londres (UCL) de Reino Unido - FSR 2017Société Francophone du Diabète de Francia/Roche Diabetes Care de España 2020National Fund for Scientific Research de Bélgica - FNRS 35275437, 201

Pelvic ring injuries:recovery of patient-perceived physical functioning and quality of life

Sustaining a pelvic ring injury is a life event that is likely to have a major and long-lasting effect on the patient’s daily life. Even after two years, 25% of patients have not yet returned to their pre-injury level of physical functioning and quality of life. The physical and mental consequences require a holistic approach to both treatment and outcome evaluation. Valid and reliable patient-reported outcome measures (PROMs) on physical and mental functioning and quality of life should be the most important aspects in evaluation of treatment and rehabilitation protocols. These PROMs may be an important step toward further improving rehabilitation programs. Ideally, rehabilitation should be approached multidisciplinary and involves trauma surgeons, rehabilitations physicians, geriatricians, physiotherapists, psychologists and dieticians. By encouraging the patient to stay in charge of his own health, the focus can shift towards the patient’s strength rather than his weakness, and subsequently improve resilience. Special attention should be paid to the fragile elderly patient who is at risk for serious injuries, even after minor trauma, complications and high-mortality up to 27% within a year. This can be related to the pre-existing limited physical condition as a result of comorbidities or decreased muscle quality and quantity, of which the latter was found to be present in almost half of elderly patients with pelvic ring injuries. Surgical treatment of pelvic ring injuries can be improved by using three-dimensional assisted techniques which tend to have a positive influence on operating time, blood loss, radiation and screw accuracy

The decline in muscle strength and muscle quality in relation to metabolic derangements in adult women with obesity

Background &amp; aims: The metabolic and functional characteristics related to sarcopenic obesity have not been thoroughly explored in the earlier stages of the aging process. The aim of the present study was to examine the phenotype of sarcopenic obesity, in terms of lean body mass, muscle strength and quality, in adult women with and without the Metabolic Syndrome (MetS), and its relationship with the features of myosteatosis. Methods: Study participants were enrolled at the Sapienza University, Rome, Italy. Body composition was assessed by DXA. The Handgrip strength test (HGST) was performed. HGST was normalized to arm lean mass to indicate muscle quality; intermuscular adipose tissue (IMAT) and intramyocellular lipid content (IMCL) were measured by magnetic resonance imaging and spectroscopy, as indicators of myosteatosis. Different indices of sarcopenia were calculated, based on appendicular lean mass (ALM, kg) divided by height squared, or weight. The NCEP-ATPIII criteria were used to diagnose the MetS. HOMA-IR was calculated. The physical activity level (PAL) was assessed through the IPAQ questionnaire. Results: 54 women (age: 48 ± 14 years, BMI: 37.9 ± 5.4 kg/m 2 ) were included. 54% had the MetS (metabolically unhealthy, MUO). HGST/arm lean mass was lower in MUO women than women without the MetS (6.3 ± 1.8 vs. 7.8 ± 1.6, p = 0.03). No differences emerged in terms of absolute ALM (kg) or other indices of sarcopenia (ALM/h 2 or ALM/weight) between metabolically healthy (MHO) vs. MUO women (p &gt; 0.05). Muscle quality was negatively associated with HOMA-IR (p = 0.02), after adjustment for age, body fat, hs-CRP levels, and PAL. IMAT, but not IMCL, was significantly higher in obese women with the MetS compared to women without the MetS (p &gt; 0.05). No association emerged between HGST/arm lean mass and IMAT or IMCL when HOMA-IR was included in the models. Conclusion: Insulin resistance, and not sarcopenia or myosteatosis per se, was associated with muscle weakness, resulting in the phenotype of “dynapenic obesity” in middle-aged women with the metabolic syndrome

Sarcopenic Obesity and Myosteatosis Are Associated with Higher Mortality in Patients with Cirrhosis

Background and aims Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of sarcopenic obesity. Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis. In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients. Methods We analysed 678 patients with cirrhosis. Sarcopenia, sarcopenic obesity and myosteatosis were analysed by CT scan using the third lumbar vertebrae skeletal muscle and attenuation indexes, using previously validated gender-and body mass index-specific cutoffs. Results Patients were predominately men (n = 457, 67%), and cirrhosis aetiology was hepatitis C virus in 269 patients (40%), alcohol in 153 (23%), non-alcoholic steatohepatitis/cryptogenic in 96 (14%), autoimmune liver disease in 55 (8%), hepatitis B virus in 43 (6%), and others in 5 patients (1%). Sarcopenia was present in 292 (43%), 135 had sarcopenic obesity (20%) and 353 had myosteatosis (52%). Patients with sarcopenia (22 ± 3 vs. 95 ± 22 months, P = 0.04) were associated with mortality. Conclusions Sarcopenia, sarcopenic obesity and myosteatosis are often present in patients with cirrhosis, and sarcopenia and myosteatosis are independently associated with a higher long-term mortality in cirrhosis

The impact of myosteatosis on outcomes following surgery for gastrointestinal malignancy: a meta-analysis.

INTRODUCTION: The aim of this review was to evaluate the impact of preoperative myosteatosis on long-term outcomes following surgery for gastrointestinal malignancy. METHODS: We conducted a systematic search of the electronic information sources, including PubMed MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL and AMED. Studies were included if they reported the impact of preoperatively defined myosteatosis, or a similar term, on long-term survival outcomes following surgery for gastrointestinal malignancy. A subgroup analysis was performed for those studies reporting outcomes for colorectal cancer patients only. FINDINGS: Thirty-nine full-text articles were reviewed for inclusion, with 19 being retained after the inclusion criteria were applied. The total number of included patients across all studies was 14,481. Patients with myosteatosis had significantly poorer overall survival, according to univariate (hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.67-1.99) and multivariable (HR 1.66, 95% CI 1.49-1.86) analysis. This was also demonstrated for cancer-specific survival (univariate HR 1.62, 95% CI 1.18-2.22; multivariable HR 1.73, 95% CI 1.48-2.03) and recurrence-free survival (univariate HR 1.28, 95% CI 1.10-1.48; multivariable HR 1.38, 95% CI 1.07-1.77). CONCLUSIONS: This meta-analysis demonstrates that patients with preoperative myosteatosis have poorer long-term survival outcomes following surgery for gastrointestinal malignancy. Therefore, myosteatosis should be used for preoperative optimisation and as a prognostic tool before surgery. More standardised definitions of myosteatosis and further cohort studies of patients with non-colorectal malignancies are required

Myosteatosis predicts survival after surgery for periampullary cancer::a novel method using MRI

Background: Myosteatosis, characterized by inter-and intramyocellular fat deposition, is strongly related to poor overall survival after surgery for periampullary cancer. It is commonly assessed by calculating the muscle radiation attenuation on computed tomography (CT) scans. However, since magnetic resonance imaging (MRI) is replacing CT in routine diagnostic work-up, developing methods based on MRI is important. We developed a new method using MRI-muscle signal intensity to assess myosteatosis and compared it with CT-muscle radiation attenuation.Methods: Patients were selected from a prospective cohort of 236 surgical patients with periampullary cancer. The MRI-muscle signal intensity and CT-muscle radiation attenuation were assessed at the level of the third lumbar vertebra and related to survival.Results: Forty-seven patients were included in the study. Inter-observer variability for MRI assessment was low (R-2 = 0.94). MRI-muscle signal intensity was associated with short survival: median survival 9.8 (95%-CI: 1.5-18.1) vs. 18.2 (95%-CI: 10.7-25.8) months for high vs. low intensity, respectively (p = 0.038). Similar results were found for CT-muscle radiation attenuation (low vs. high radiation attenuation: 10.8 (95%-CI: 8.5-13.1) vs. 15.9 (95%-CI: 10.2-21.7) months, respectively; p = 0.046). MRI-signal intensity correlated negatively with CT-radiation attenuation (r=-0.614, p &lt;0.001).Conclusions: Myosteatosis may be adequately assessed using either MRI-muscle signal intensity or CT-muscle radiation attenuation.</p

Sarcopenia is a Significant Predictor of Mortality After Abdominal Aortic Aneurysm Repair

Aims Repair of abdominal aortic aneurysms (AAA) decreases the incidence of rupture and death. In cancer patients, sarcopenia has been associated with increased surgical complications and mortality. The impact of sarcopenia on survival after AAA repair has yet to be described. Methods and Results Patient demographic, laboratory, body composition measurements and survival data were obtained from patients undergoing AAA repair at the Indiana University medical campus over a 5-year period. Univariate and multivariate analyses were performed to identify factors associated with overall survival. Overall, 58.2% presented with sarcopenia. Sarcopenic patients were older (71.8±8.3 versus 66.8±8.1 years; p<0.001), had lower body mass index (BMI) (26.3±5.2 versus 31.5±5.9 kg/m2; p<0.001), higher rates of myosteatosis (84.4% versus 52.%; p<0.001), greater AAA diameter (60.6±14.0 versus 57.8±11.7 mm; p=0.016), higher Charlson Comorbidity Index (CCI) (32.3% versus 25.1% ≥6; p=0.034), and increased rates of rupture (8.2% versus 3.8%; p=0.047). Sarcopenic and nonsarcopenic patients had no difference in 30-day morbidity (8.5% versus 8.5%; p=0.991) or mortality (3.7% versus 0.9%; p=0.07). Univariate analysis demonstrated age, sarcopenia, myosteatosis, CCI, and BMI to be associated with long-term survival. There was no correlation between BMI and sarcopenia. Both sarcopenia and myosteatosis resulted in decreased one-, three-, and five-year survivals compared to their counterparts. On multivariate analysis sarcopenia is independently associated with survival, conferring a 1.6-fold increase in death (p=0.04). The combination of sarcopenia plus myosteatosis doubled the risk of death compared to sarcopenia alone. Conclusions This is the first study to demonstrate that over half of all patients undergoing AAA repair are sarcopenic, a condition associated with increased mortality. Sarcopenia with myosteatosis is associated with double the mortality of sarcopenia alone. CT scan, but not BMI, accurately identifies sarcopenia and myosteatosis. Defining the mechanisms through which sarcopenia contributes to late death after AAA repair is critical to developing novel interventions that may improve survival in this high risk population