Sarcopenia in cirrhosis: from pathogenesis to interventions

Journal of Gastroenterology - Sarcopenia (severe muscle depletion) is a prevalent muscle abnormality in patients with cirrhosis that confers poor prognosis both pre- and post-liver transplantation....     

Clinical Implications of Sarcopenic Obesity in Cancer

Sarcopenia has been associated with several negative clinical outcomes in cancer. However, the consequences of sarcopenic obesity, a condition of combined sarcopenia and obesity burden, have been less extensively investigated. The aim of this paper was to review the current evidence on the prevalence and clinical implications of sarcopenic obesity in cancer. A total of 14 studies linking sarcopenic obesity to a clinical outcome in cancer were included. There is considerable inconsistency in methods used to evaluate body composition as well as in the criteria used to define sarcopenic obesity, which limits comparison among studies. Therefore, the prevalence of sarcopenic obesity varied substantially: between 1 and 29 % in studies including individuals from all body mass index categories and between 15 and 36 % for those including obese individuals only. Negative clinical outcomes reported to be associated with sarcopenic obesity included higher risk of dose-limiting toxicity, surgical complications, physical disability, and shorter survival.     

The effect of treating infected skin grafts with Acticoat on immune cells

A study was conducted to determine the effect of Acticoat placed on an infected skin graft on parameters of immunity. Two partial thickness wounds (2 cm x 4 cm) were created on the dorsal midline of Hartley guinea pigs (n=28). Wounds were covered with autologous skin graft and maintained either aseptically (Noninoculated, n=8), inoculated with Staphylococcus aureus (Surgery-Inoculated, n=8) with or without Acticoat bandage (Surgery-Inoculated-Acticoat, n=6). Five days later, splenocytes and blood were collected to estimate natural killer cell (NK) cytotoxicity, proliferative response to T and B cell mitogens and neutrophil oxidative burst. Animals that did not undergo surgery were included as a nonsurgery control group. [(3)H]-thymidine incorporation in response to a variety of T and B cell mitogens was significantly lower for all groups undergoing surgery compared to the nonsurgery control group (p<0.0001) and no additional effect was observed on this immune measure by applying the Acticoat bandage. The Surgery-Inoculated-Acticoat group exhibited greater NK cytotoxic activity (as assessed as the ability to lyse K562 tumor cells) compared to the Surgery-Inoculated group (p<0.006). The Surgery-Inoculated-Acticoat group had higher neutrophil oxidative burst at 5 min post stimulation, but was not different from controls after 15 min. In conclusion, the application of an Acticoat bandage to an inoculated surgery wound did not alter the low cell-mediated immune response that followed surgery, but appeared to increase parameters (NK cytotoxic activity and neutrophil function) of innate immunity.     

Influence of eicosapentaenoic acid supplementation on lean body mass in cancer cachexia

Cancer cachexia is characterised by a progressive loss of muscle, resulting in functional impairment and shorter survival. Eicosapentaenoic acid, an n-3 polyunsaturated fatty acid found in fish, has been studied for its role as an anti-cachexia therapy. Initial results of eicosapentaenoic supplementation in advanced cancer were promising with improvements in lean body mass (LBM), appetite and quality of life. However, subsequent larger phase III clinical trials reported minimal benefits of supplementation. Recently, several studies have used different study designs, which may provide insight on the effectiveness of eicosapentaenoic in cancer cachexia and also on potential sources of divergent results in previous trials. This review examines the potential benefit of eicosapentaenoic supplementation on LBM and discusses limitations with current studies to identify methods which may aid in progressing the research of future clinical trials.     

A Meal High in Saturated Fat Evokes Postprandial Dyslipemia,Hyperinsulinemia, and Altered Lipoprotein Expression in Obese Children With and Without Nonalcoholic Fatty Liver Disease

Background: Hyperinsulinemia and altered lipid and lipoprotein metabolism induced by fast‐food diets may contribute to nonalcoholic fatty liver disease (NAFLD). We hypothesized that a high saturated fat (SFA) meal would evoke prolonged postprandial lipemia and hyperinsulinemia, increased inflammation, and altered lipoprotein expression in obese children with NAFLD when compared with healthy children. Methods: We prospectively studied 31 children (NAFLD, 13.1 ± 2.6 years, n = 11; age‐matched obese, 14.3 ± 1.7 years, n = 9; lean, 13.6 ± 2.6 years, n = 11) following consumption of a high SFA (18.8%) meal. Prior to and at 1, 3, and 6 hours after meal consumption, blood was collected for analysis of alanine aminotransferase (ALT); aspartate aminotransferase (AST); γ‐glutamyltransferase; leptin; C‐reactive protein; (fasting) insulin; glucose; triglycerides (TGs); total, high‐density lipoprotein, and low‐density lipoprotein cholesterol; adiponectin; nonesterified fatty acids (NEFAs); inflammatory markers (TNF‐α, IL‐6, IL‐10); apolipoproteins‐B48, B100, and CIII; and fatty acid (FA) composition of TG fractions. Results: Children with NAFLD had significantly higher fasting levels of ALT (87 ± 54 U/L), AST (52 ± 33.5 U/L), and apolipoprotein‐CIII (20.6 ± 11.3 mg/dL) with postprandial hyperinsulinemia (iAUC insulin: 225 ± 207 [NAFLD] vs 113 ± 73 [obese] vs 47 ± 19.9 [lean] mU/L‐h; P < .001); suppression of NEFA (iAUC‐NEFA: 1.7 ± 0.9 [NAFLD] vs 0.6 ± 0.3 [obese] vs 1 ± 0.7 [lean] mEq/L‐h); and prolonged elevations in apolipoprotein‐B48 3–6 hours after meal consumption when compared with obese and lean controls (P < .05). Conclusion: A meal high in saturated fat evokes postprandial dyslipemia, hyperinsulinemia, and altered lipoprotein expression in obese children with and without NAFLD.     

Chemotherapy diminishes lipid storage capacity of adipose tissue in a preclinical model of colon cancer

Background

Accelerated loss of adipose tissue in cancer is associated with shorter survival, and reduced quality of life. Evidence is emerging suggesting tumour association with alterations in adipose tissue, but much less is known about drug-related mechanisms contributing to adipose atrophy. Identification of mechanisms by which tumour and cancer treatments, such as chemotherapy, affect adipose tissue are required to develop appropriate therapeutic interventions to prevent fat depletion in cancer. This pre-clinical study aimed to assess alterations in adipose tissue during the clinical course of cancer.

Methods

Fischer 344 rats bearing the Ward colorectal tumour were euthanized before chemotherapy, after 1- cycle, or 2-cycles of a combination chemotherapy consisting of Irinotecan (CPT-11) combined with 5-fluorouracil (5-FU), which recapitulates first line treatment for human colorectal cancer. Periuterine adipose tissue was isolated. Healthy rats served as a reference group. Histological analysis (hematoxylin and eosin), Real-time PCR (TaqMan) and proteomic analysis (LC-MS/MS) were performed.

Results

Larger adipocytes (3993.7?±?52.6 μm²) in tumour-bearing animals compared to the reference group (3227.7?±?36.7 μm²; p?<?0.001) was associated with reduced expression of proteins involved in mitochondrial fatty acid oxidation. The presence of a tumour has a significant effect on phospholipid but not triglyceride fatty acid composition. There were greater proportions of saturated fatty acids concurrent with lower monounsaturated fatty acids within the PL fraction of adipocytes in tumour-bearing animals. Chemotherapy treatment decreased the size of adipocytes (2243.9?±?30.4 μm²; p?<?0.001) and led to depletion of n-3 polyunsaturated fatty acids in adipose tissue triglyceride. Evaluation of the proteome profile revealed decreased expression of proteins involved in ATP generation, β-oxidation, and lipogenesis. Overall, adipose tissue may not be able to efficiently oxidize fatty acids to provide energy to maintain energy demanding pathways like lipogenesis inside the tissue.

Conclusions

In conclusion, metabolic adaptations to mitochondrial impairment may contribute to diminished lipid storage capacity of adipose tissue following chemotherapy delivery.

     

Does Persistent Inflammatory Catabolic Syndrome Exist in Critically Ill Neonates?

Background: Persistent inflammatory catabolic syndrome (PICS) has not been described in the infant population. This study proposes a definition of PICS in critically ill infants. Methods: A published adult criterion of PICS was modified using anthropometric and biochemical reference ranges for infants. A prospective chart review of admissions to a tertiary surgical neonatal intensive care unit (NICU) was performed over 65 days. Demographic, anthropometric, biochemical, and other clinical variables such as length of stay and medication use were collected daily throughout admission. Infants were categorized as having or not having PICS. Results: Twenty percent of admitted infants (n = 15) developed PICS using the proposed criteria. Infants with PICS were more likely to be classified as failure to thrive (53%), meeting only 75% of their anticipated weight gain. Significantly more infants with PICS had undergone surgery (100%; P = .01), received inotropic medication (40%; P = .05), and had longer NICU and total hospital length of stay (P < .001 and P < .001). Infants with PICS had higher peak glucose levels (11.8 ± 7.3 mmol/L) and elevated urea concentrations (7.9 ± 4.6 mmol/L). Conclusions: PICS does exist in a critically ill neonatal population and may be identified using the definition proposed in this study. Infants with PICS displayed metabolic dysregulation, impaired expected growth velocity, and longer length of stay despite no differences in severity scores or diagnosis between the groups. Validation of this work is required, and research into timely identification of infants with PICS is needed to inform whether these infants would benefit from earlier and novel nutrition intervention.