Baseline Sarcopenia is Associated with Lack of Response to Therapy, Liver Decompensation and High Mortality in Hepatocellular Carcinoma Patients.

OBJECTIVE: hepatocellular carcinoma (HCC) is a dreadful complication of liver cirrhosis. Aim was to study the effect of sarcopenia on the survival in patients with HCC. METHODS: we included 262 patients and were followed up for 12 months. Sarcopenia was calculated by skeletal muscle index (SMI). Sarcopenia was defined by SMI ≤39 cm2/m2 for women and ≤50 cm2/m2 for men. RESULTS: patients with sarcopenia (n= 113, 43.1%) were older, mainly males, Child-Pugh class B and smokers. Patients with sarcopenia had lower survival than those without (10.09 vs. 11.72 months). Survival was also lower in Barcelona clinic liver cancer stage C than B and A (9.02 vs. 11.21 vs. 11.89 months). Age and sarcopenia were hazardous of mortality (p <0.05). There was statistically significant difference of serial SMI in patients without baseline sarcopenia unlike patients with baseline sarcopenia. On follow up patients with sarcopenia had higher incidence of ascites (45% vs. 20.4%), spontaneous bacterial peritonitis (21.7% vs. 11.6%), hepatic encephalopathy (28% vs. 11.5%) and bleeding (22.9% vs. 12.7%). Totally patients with sarcopenia had higher incidence of progressive HCC (39% vs. 25.5%). CONCLUSION: Sarcopenia is associated with lack of response to therapy, liver decompensation and higher mortality in hepatocellular carcinoma patients.
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Association of Low Muscle Mass and Low Muscle Radiodensity With Morbidity and Mortality for Colon Cancer Surgery.

Importance: Given the risks of postoperative morbidity and its consequent economic burden and impairment to patients undergoing colon resection, evaluating risk factors associated with complications will allow risk stratification and the targeting of supportive interventions. Evaluation of muscle characteristics is an emerging area for improving preoperative risk stratification. Objective: To examine the associations of muscle characteristics with postoperative complications, length of hospital stay (LOS), readmission, and mortality in patients with colon cancer. Design, Setting, and Participants: This population-based retrospective cohort study was conducted among 1630 patients who received a diagnosis of stage I to III colon cancer from January 2006 to December 2011 at Kaiser Permanente Northern California, an integrated health care system. Preliminary data analysis started in 2017. Because major complication data were collected between 2018 and 2019, the final analysis using the current cohort was conducted between 2019 and 2020. Exposures: Low skeletal muscle index (SMI) and/or low skeletal muscle radiodensity (SMD) levels were assessed using preoperative computerized tomography images. Main Outcomes and Measures: Length of stay, any complication (≥1 predefined complications) or major complications (Clavien-Dindo classification score ≥3), 30-day mortality and readmission up to 30 days postdischarge, and overall mortality. Results: The mean (SD) age at diagnosis was 64.0 (11.3) years and 906 (55.6%) were women. Patients with low SMI or low SMD were more likely to remain hospitalized 7 days or longer after surgery (odds ratio [OR], 1.33; 95% CI, 1.05-1.68; OR, 1.39; 95% CI, 1.05-1.84, respectively) and had higher risks of overall mortality (hazard ratio, 1.40; 95% CI, 1.13-1.74; hazard ratio, 1.44; 95% CI, 1.12-1.85, respectively). Additionally, patients with low SMI were more likely to have 1 or more postsurgical complications (OR, 1.31; 95% CI, 1.04-1.65) and had higher risk of 30-day mortality (OR, 4.85; 95% CI, 1.23-19.15). Low SMD was associated with higher odds of having major complications (OR, 2.41; 95% CI, 1.44-4.04). Conclusions and Relevance: Low SMI and low SMD were associated with longer LOS, higher risk of postsurgical complications, and short-term and long-term mortality. Research should evaluate whether targeting potentially modifiable factors preoperatively, such as preserving muscle mass, could reverse the observed negative associations with postoperative outcomes.

The effect of nutritional counseling on muscle mass and treatment outcome in patients with metastatic colorectal cancer undergoing chemotherapy: A randomized controlled trial.

BACKGROUND & AIMS: A low muscle mass before start of treatment and loss of muscle mass during chemotherapy is related to adverse outcomes in patients with cancer. In this randomized controlled trial, the effect of nutritional counseling on change in muscle mass and treatment outcome in patients with metastatic colorectal cancer during first-line chemotherapy was studied. METHODS: Patients scheduled for first-line chemotherapy (n = 107) were randomly assigned to individualized nutritional counseling by a dietitian (NC) or usual care (UC). NC was aimed at sufficient protein- and energy intake, supported by oral supplements or enteral feeding if indicated. Furthermore, physical activity was encouraged. Outcomes were assessed at baseline (T0) and the time of the first (T1) and second (T2) regular follow-up computed tomography scans. The proportion of patients with a clinically relevant decrease in skeletal muscle area of ≥6.0 cm2, measured by computed tomography, was the primary outcome. Secondary outcomes included body weight, quality of life, treatment toxicity and progression free and overall survival. RESULTS: A total of 107 patients were enrolled (mean age, 65 years (SD, 11 years), 63% male). Mean change in skeletal muscle area from T0 till T1 was -2.5 (SD, 9.5) cm2, with no difference between NC versus UC (p = 0.891). The proportion of patients with a clinically relevant decrease in skeletal muscle area of ≥6.0 cm2 did not differ (NC 30% versus UC 31%, p = 0.467). NC compared with UC had a significant positive effect on body weight (B coefficient 1.7, p = 0.045), progression free survival (p = 0.039) and overall survival (p = 0.046). CONCLUSIONS: NC of patients undergoing chemotherapy for metastatic colorectal cancer had no effect on muscle mass. However, we found that NC may increase body weight and improve progression free survival and overall survival compared to UC in this group of patients. These findings need further evaluation in future clinical trials. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov NCT01998152; Netherlands Trial Register NTR4223.

Nutritional issues in patients with obesity and cirrhosis.

Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.

Non-musculoskeletal benefits of vitamin D.

The aim of this study is to determine and critically evaluate the plausible relationships of vitamin D with extra-skeletal tissues in humans. Severe vitamin D deficiency results in rickets in children and osteomalacia in adults; these beneficial effects in the musculoskeletal system and certain physiological functions are well understood. Nevertheless, mounting reports support additional beneficial effects of vitamin D, outside the musculoskeletal system. This review explores the recent advances in knowledge about the non-skeletal effects of vitamin D. Peer-reviewed papers were extracted from research databases using key words, to assess correlations between vitamin D and extra-skeletal diseases and conditions. As per the guidelines of the Preferred Reporting Items for Systematic Reviews (PRISMA); general interpretations of results are included; taking into consideration the broader evidence and implications. This review summarizes current knowledge of the effects of vitamin D status on extra-skeletal tissues with special attention given to relationships between vitamin D status and various diseases commonly affecting adults; the effects of intervention with vitamin D and exposure to sunlight. Evidence suggests that vitamin D facilitates the regulation of blood pressure; and cardiac; endothelial; and smooth muscle cell functions; playing an important role in cardiovascular protection. In addition; 1,25(OH)2D improves immunity; subdues inflammation; and reduces the incidence and severity of common cancers; autoimmune diseases and infectious diseases. Almost all adequately powered; epidemiological and biological studies that use; adequate doses of vitamin D supplementation in D-deficient populations have reported favorable outcomes. These studies have concluded that optimizing 25(OH)D status improves the functionality of bodily systems; reduces comorbidities; improves the quality of life; and increases survival. Although accumulating evidence supports biological associations of vitamin D sufficiency with improved physical and mental functions; no definitive evidence exists from well-designed; statistically powered; randomized controlled clinical trials. Nevertheless, most studies point to significant protective effects of vitamin D in humans when the minimum 25(OH)D serum level exceeds 30ng/mL and is maintained throughout the year.

Nutritional Deficiencies and Sarcopenia in Heart Failure: A Therapeutic Opportunity to Reduce Hospitalization and Death.

There is an expanding prevalence pool of heart failure (HF) due to the increasing prevalence of survivors of myocardial infarction, diabetes, hypertension, chronic kidney disease, and obesity. There is increasing interest in the role of nutrition in all forms of HF, given observations concerning micro- and macronutrient deficiencies, loss of lean body mass or sarcopenia, and their relationships with hospitalization and death. This review examines the relationships among loss of lean body mass, macro- and micronutrient intake, and the natural history of HF, particularly in the elderly, in whom the risks for all-cause rehospitalization, infection, falls, and mortality are increased. These risks are potentially modifiable through strategies that improve nutrition in this vulnerable population.

Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

BACKGROUND: Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS). RESULTS: Treatment-related mortality (21.7 vs. 5.0%, P = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group (P < 0.001). The 5 year OS rates were 37.3% in the sarcopenic group and 68.1% in the non-sarcopenic group (P < 0.001). Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P = 0.009; revised-IPI, 0.74, P < 0.001; National Comprehensive Cancer Network-IPI, 0.77, P = 0.062). CONCLUSIONS: Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.

Sarcopenia in patients undergoing maintenance hemodialysis: incidence rate, risk factors and its effect on survival risk.

BACKGROUND: Sarcopenia is a degenerative syndrome mainly characterized by the atrophy of skeletal muscle, along with the decrease of muscle strength and function. However, there are currently few studies concerning sarcopenia in patients undergoing maintenance hemodialysis dialysis (MHD). This study was aimed to investigate the incidence of sarcopenia in MHD patients and its influencing factors, as well as its impact on survival risk. METHOD: All 131 MHD patients enrolled in our study were tested with bioelectrical impedance analysis (BIA) and grip strength. Demographic data was collected and anthropometric measurement and laboratory examination were conducted. RESULTS: The total incidence of sarcopenia within the 131 MHD patients was 13.7% and the incidence of sarcopenia in patients over 60 years was 33.3%. The dialysis duration, with or without diabetes, serum phosphorus and pre-albumin levels of sarcopenic patients were significantly different from those of non-sarcopenicones; the modified quantitative subjective global assessment (MQSGA) scores of sarcopenic patients were higher than those without sarcopenia. Multivariate analysis showed that dialysis duration, diabetes and serum phosphorus level were independent risk factors for sarcopenia in MHD patients. Kaplan-Meier survival analysis showed a one-year survival of 88.9% in sarcopenic patients, which was significantly lower than non-sarcopenic patients. CONCLUSION: The incidence of sarcopenia in MHD patients was high and increased gradually with age. Dialysis duration, diabetes, serum phosphorus level and malnutrition predisposed the patients to sarcopenia. One-year follow-up found that the mortality risk of sarcopenic patients was higher than that of non-sarcopenic patients.

Sarcopenia impairs prognosis of patients with liver cirrhosis.

OBJECTIVE: Sarcopenia is characterized by the loss of skeletal muscle mass, and is reported to appear in patients with liver cirrhosis (LC). The aim of this study was to investigate the prevalence of sarcopenia in patients with LC, and to test the association between sarcopenia and patient outcomes. We also analyzed the effect of branched-chain amino acid (BCAA) supplementation on sarcopenic LC. METHODS: Clinical and blood biochemical data of 130 patients with LC who underwent abdominal computed tomography scan were analyzed in this retrospective study. The cross-sectional area of skeletal muscles was measured at the level of the third lumbar vertebra on the scan. The skeletal muscle index was calculated to identify sarcopenia. Cirrhotic patients who were treated with BCAA supplementation of 12 g/d for ≥ 1 y were defined as the BCAA group, and the effect of BCAA on sarcopenic LC was evaluated. RESULTS: Sixty-eight percent of all patients (82% of men and 50% of women) were diagnosed with sarcopenia. Male sex (P = 0.01) and body mass index (P < 0.0001) were predictors of sarcopenia. The multivariate Cox proportional hazards model found BCAA supplementation (hazard ratio [HR], 0.38; P = 0.01), sarcopenia (HR, 3.03; P < 0.01), and Child-Pugh classes B (HR, 2.39; P = 0.03) and C (HR, 5.49; P < 0.001) to be independently associated with mortality. The mortality of sarcopenic LC was significantly higher than that of non-sarcopenic LC (P = 0.01). Moreover, BCAA supplementation improved the survival of sarcopenic patients in subgroup analysis (P < 0.01). CONCLUSIONS: Sarcopenia is significantly associated with mortality in patients with LC. BCAA supplementation might be associated with improved survival of such patients.

Porvoo sarcopenia and nutrition trial: effects of protein supplementation on functional performance in home-dwelling sarcopenic older people - study protocol for a randomized controlled trial.

BACKGROUND: Age-related muscle loss (that is, sarcopenia) is a common health problem among older people. Physical exercise and dietary protein have been emphasized in prevention and treatment of sarcopenia. Rigorous trials investigating the effects of protein supplementation on physical performance in sarcopenic populations are still scarce. The aim of this study is to investigate the effects of protein supplementation along with simple home-based exercises on physical performance among home-dwelling sarcopenic older people. METHODS/DESIGN: During 2012 the entire 75 and older population (N = 3,275) living in Porvoo, Finland was contacted via a postal questionnaire. Persons at risk of sarcopenia are screened with hand grip strength and gait speed. Poorly performing persons are further examined by segmental bioimpendance spectroscopy to determine their skeletal muscle index. Sarcopenic patients (target N = 250) will be enrolled in a 12-month randomized controlled trial with three arms: 1) no supplementation, 2) protein supplementation (20 grams twice a day), and 3) isocaloric placebo. All the participants will receive instructions on simple home-based exercises, dietary protein, and vitamin D supplementation (20 µg/d). The recruitment of patients will be completed during 2013. The primary endpoint of the trial is the change in short physical performance battery score and percentage of patients maintaining or improving their physical performance. Secondary endpoints will be, among other things, changes in muscle functions, nutritional status, body composition, cognition, quality of life, use of health care services, falls, and mortality. The assessment times will be 0, 6, 12 and 24 months. DISCUSSION: To our knowledge, this is the first large scale randomized controlled trial among community dwelling older people with sarcopenia that focuses on the effects of protein supplementation on physical performance. TRIAL REGISTRATION: ACTRN12612001253897, date of registration 28 October 2012, first patient was randomized 11 April 2012.