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A study was conducted to determine the effect of Acticoattrade mark placed on an infected skin graft on parameters of immunity. Two partial thickness wounds (2cmx4cm) 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 Acticoattrade mark 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 5min post stimulation, but was not different from controls after 15min. In conclusion, the application of an Acticoattrade mark 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. [ABSTRACT FROM AUTHOR]

Background & Aims: Exocrine pancreatic insufficiency (EPI) contributes to malnutrition, marked by muscle loss during chemotherapy for advanced pancreatic cancer (aPC). Pancreatic enzyme replacement therapy (PERT) is recommended for patients with EPI; however, it's efficacy for attenuating muscle loss has not been demonstrated. We aimed to delineate the impact of PERT dose on muscle loss using a 7-year population-based cohort with aPC who were provided PERT at the discretion of their oncologist or dietitian according to clinical indications of EPI., Methods: All patients treated with chemotherapy for aPC from 2013 to 2019 in Alberta, Canada (population ∼4.3 million) were included if they had computed tomography (CT) scans both prior to and 12 ± 4 weeks after chemotherapy initiation. Change in muscle area (cm 2 ) was measured at 3rd lumbar level on repeated CT scans. Muscle loss was defined by measurement error (loss >2.3 cm 2 ). Clinical and pharmaceutical data were retrieved from provincial registries. For patients who were dispensed PERT -8 to +6 weeks from chemo start (PERT users), estimated dose consumed per day was calculated as: (total dose dispensed) / (days, first to last dispensation). PERT users were categorized as high dose or low dose users according to the median estimated dose consumed. Non-users were classified as No PERT. Association between PERT use and muscle loss was analyzed with multivariable logistic regression., Results: Among 210 patients, 81 (39%) were PERT users. Median estimated dose consumed per day of 75 000 USP lipase units defined the cutoff between low dose and high dose uses. There were no significant differences in baseline characteristics between high dose and low dose groups. Muscle loss was more prevalent among low dose compared to both high dose and No PERT groups (88% vs. 58% and 67%, p < 0.05). In the multivariable model predicting muscle loss, low dose PERT was independently associated with greater odds of muscle loss (OR 5.4, p = 0.004) vs. high dose, independent of tumour response, disease stage, and chemotherapy regimen., Conclusion: In patients with clinical indications of EPI during chemotherapy for aPC, low doses of PERT were insufficient to prevent muscle loss. Patients with EPI consuming higher doses of PERT had similar odds of muscle maintenance to patients without clinical indications of EPI. Provider education for optimal PERT dosing in patients with EPI should be prioritized, and resources must be allocated to support dose titration., Competing Interests: Conflict of interest Vickie Baracos is a consultant for Pfizer and Nestle Health Science. Michael B. Sawyer and Jessica Kasnik have been engaged as speakers and advisors for Viatris Canada. These agencies had no role in the funding or design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The remaining authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

It is important for allocation of resources to predict those COVID patients at high risk of dying or organ failure. Early signals to initiate cellular events of host immunity can be derived from essential fatty acid metabolites preceding the cascade of proinflammatory signals. Much research has focused on understanding later proinflammatory responses. We assessed if remodelling of plasma phospholipid content of essential fatty acids by the COVID-19 virus provides early markers for potential death and disease severity. Here we show that, at hospital admission, COVID-19 infected subjects who survive exhibit higher proportions of C20:4n-6 in plasma phospholipids concurrent with marked proinflammatory cytokine elevation in plasma compared to healthy subjects. In contrast, more than half of subjects who die of this virus exhibit very low C18:2n-6 and C20:4n-6 content in plasma phospholipids on hospital admission compared with healthy control subjects. Moreover, in these subjects who die, the low level of primary inflammatory signals indicates limited or aberrant stimulation of host immunity. We conclude that COVID-19 infection results in early fundamental remodelling of essential fatty acid metabolism. In subjects with high mortality, it appears that plasma n-6 fatty acid content is too low to stimulate cellular events of host immunity., (© 2023. The Author(s).)

Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta-analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative-intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta-analysis. Studies that measured computed tomography-defined SM and/or AT change in adult patients during palliative-intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm 2 /m 2 , cm 2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex-specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta-analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Oxidative stress caused by free radicals contributes to the pathogenesis of multiple chronic health conditions. Phytochemicals protect against oxidative stress; however, low bioavailability from dietary sources limits their health benefits. This study aimed to assess the effects of anthocyanins and gingerols' combination on the cellular antioxidant response of Caco-2 cells against oxidative stress. A strong synergism was observed for anthocyanin-gingerol (Ac-G) w/w combined ratios of 8:1 and 2:1 (dosages of (1 + 0.125) and (1 + 0.5) μg/mL) in the cellular antioxidant activity (CAA) and cytoprotective effects, with synergistic effect indicator (SE) values of 1.41 and 1.61, respectively. The synergism of Ac-G combinations promoted cellular antioxidant defense systems and cytoprotective effects by reducing the induced GPx enzyme activity, protecting SOD enzyme activity, reducing cellular ROS generation, increasing glutathione content, and inhibiting lipid peroxidation. Thus, Ac-G combinations showed potential in supporting the endogenous antioxidant systems to protect cells from oxidation and restore physiological redox status. The Ac-G formulation is a promising healthy option that can be developed into functional foods or nutraceutical products. Furthermore, it could help address the low bioavailability of these phenolics, as higher effects were achieved when combining the same doses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abdurrahim, Mazurak and Chen.)

Muscle and adipose wasting during chemotherapy for advanced pancreatic cancer (aPC) are associated with poor outcomes. We aimed to quantify the contributions of chemotherapy regimen and tumour progression to muscle and adipose wasting and evaluate the prognostic value of each tissue loss. Of all patients treated for aPC from 2013-2019 in Alberta, Canada ( n = 504), computed-tomography (CT)-defined muscle and adipose tissue index changes (∆SMI, ∆ATI, cm 2 /m 2 ) were measured for patients with CT images available both prior to and 12 ± 4 weeks after chemotherapy initiation ( n = 210). Contributions of regimen and tumour response to tissue change were assessed with multivariable linear regression. Survival impacts were assessed with multivariable Cox's proportional hazards models. Tissue changes varied widely (∆SMI: -17.8 to +7.3 cm 2 /m 2 , ∆ATI: -106.1 to +37.7 cm 2 /m 2 ) over 116 (27) days. Tumour progression contributed to both muscle and adipose loss (-3.2 cm 2 /m 2 , p < 0.001; -12.4 cm 2 /m 2 , p = 0.001). FOLFIRINOX was associated with greater muscle loss (-1.6 cm 2 /m 2 , p = 0.013) and GEM/NAB with greater adipose loss (-11.2 cm 2 /m 2 , p = 0.002). The greatest muscle and adipose losses were independently associated with reduced survival (muscle: HR 1.72, p = 0.007; adipose: HR 1.73, p = 0.012; tertile 1 versus tertile 3). Muscle and adipose losses are adverse effects of chemotherapy and may require regimen-specific management strategies.

Cancer treatment evokes impediments to liver metabolism that culminate in fatty liver. This study determined hepatic fatty acid composition and expression of genes and mediators involved in lipid metabolism following chemotherapy treatment. Female rats bearing the Ward colon tumor were administered Irinotecan (CPT-11) +5-fluorouracil (5-FU) and maintained on a control diet or a diet containing eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (2.3 g/100 g fish oil). Healthy animals provided with a control diet served as a reference group. Livers were collected one week after chemotherapy. Triacylglycerol (TG), phospholipid (PL), ten lipid metabolism genes, leptin, and IL-4 were measured. Chemotherapy increased TG content and reduced EPA content in the liver. Expression of SCD1 was upregulated by chemotherapy, while dietary fish oil downregulated its expression. Dietary fish oil down-regulated expression of the fatty acid synthesis gene FASN, while restoring the long chain fatty acid converting genes FADS2 and ELOVL2, and genes involved in mitochondrial β-oxidation (CPT1α) and lipid transport (MTTP1), to values similar to reference animals. Neither leptin nor IL-4 were affected by chemotherapy or diet. Depletion of EPA is associated with pathways evoking enhanced TG accumulation in the liver. Restoring EPA through diet may pose a dietary strategy to attenuate chemotherapy-associated impediments in liver fatty acid metabolism.

GM3 is implicated in cell signaling, inflammation and insulin resistance. The intestinal mucosa metabolizes ganglioside and provides gangliosides for uptake by peripheral tissues. Gangliosides downregulate acute and chronic inflammatory signals. It is likely that transport of intestinal derived gangliosides to other tissues impact the same signals characteristic of inflammatory change in other chronic conditions such as Type 2 Diabetes (T2DM). The postprandial ceramide composition of GM3 and other gangliosides in plasma and chylomicrons has not been examined in T2DM. The present study assessed if diet or T2DM alters ganglioside components in plasma and chylomicrons secreted from the intestinal mucosa after a meal. GD1, GD3, and GM3 content of chylomicrons and plasma was determined by LC/triple quad MS in non-diabetic (control) and T2DM individuals in the fasting and postprandial state after 2 days of consuming a low or high fat diet in a randomized blinded crossover design. Diet fat level did not alter baseline plasma or chylomicron ganglioside levels. Four hours after the test meal, plasma monounsaturated GD3 was 75% higher, plasma saturated GD3 was 140% higher and plasma polyunsaturated GM3 30% lower in diabetic subjects compared to control subjects. At 4 h, chylomicron GD1 was 50% lower in T2DM compared to controls. The proportion of d34:1 in GD3 was more abundant and d36:1 in GD1 less abundant in T2DM compared to control subjects at 4 h. The present study indicates that T2DM alters ceramide composition of ganglioside available for uptake by peripheral tissues.

Irinotecan (CPT-11) and 5-fluorouracil (5-FU) are commonly used to treat metastatic colorectal cancer, but chemotherapy-associated steatosis/steatohepatitis (CASSH) frequently accompanies their use. The objective of this study was to determine effect of CPT-11+5-FU on liver toxicity, liver oxylipins, and cytokines, and to explore whether these alterations could be modified by dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oil (EPA+DHA). Tumor-bearing animals were administered CPT-11+5-FU and maintained on a control diet or a diet containing EPA+DHA (2.3 g/100 g). Livers were collected one week after chemotherapy for the analysis of oxylipins, cytokines, and markers of liver pathology (oxidized glutathione, GSSH; 4-hydroxynonenal, 4-HNE, and type-I collagen fiber). Dietary EPA+DHA prevented the chemotherapy-induced increases in liver GSSH (p < 0.011) and 4-HNE (p < 0.006). Compared with the tumor-bearing animals, ten oxylipins were altered (three/ten n-6 oxylipins were elevated while seven/ten n-3 oxylipins were reduced) following chemotherapy. Reductions in the n-3 fatty-acid-derived oxylipins that were evident following chemotherapy were restored by dietary EPA+DHA. Liver TNF-α, IL-6 and IL-10 were elevated (p < 0.05) following chemotherapy; dietary EPA+DHA reduced IL-6 (p = 0.09) and eotaxin (p = 0.007) levels. Chemotherapy-induced liver injury results in distinct alterations in oxylipins and cytokines, and dietary EPA+DHA attenuates these pathophysiological effects.

Structural plasticity in the brain often necessitates dramatic remodeling of neuronal processes, with attendant reorganization of the cytoskeleton and membranes. Although cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural plasticity remains unclear. We show that specific glial cells in Drosophila produce glucocerebrosidase (GBA) to locally catabolize sphingolipids. Sphingolipid accumulation drives lysosomal dysfunction, causing gba1b mutants to harbor protein aggregates that cycle across circadian time and are regulated by neural activity, the circadian clock, and sleep. Although the vast majority of membrane lipids are stable across the day, a specific subset that is highly enriched in sphingolipids cycles daily in a gba1b-dependent fashion. Remarkably, both sphingolipid biosynthesis and degradation are required for the diurnal remodeling of circadian clock neurites, which grow and shrink across the day. Thus, dynamic sphingolipid regulation by glia enables diurnal circuit remodeling and proper circadian behavior., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background & Aims: Association between sarcopenia and mortality in cirrhosis is well recognised; however, little is known about the clinical implications of adipose tissue radiodensity, indicative of biological features. This study aimed to determine an association between high subcutaneous adipose tissue (SAT) radiodensity and survival, compare the prevalence of high SAT radiodensity between healthy population and patients with cirrhosis, and identify an association between computed tomography (CT)-measured SAT radiodensity and histological characteristics., Methods: Adult patients with cirrhosis (n = 786) and healthy donors (n = 129) with CT images taken as part of the liver transplant (LT) assessment were included. Abdominal SAT biopsies (1-2 g) were harvested from the incision site at the time of LT from 12 patients with cirrhosis., Results: The majority of patients were male (67%) with a mean model for end-stage liver disease (MELD) score of 15 ± 8. SAT radiodensity above -83 HU in females (sub-distribution hazard ratio [sHR] 1.84, 95% CI 1.20-2.85, p  = 0.006) and higher than -74 HU in males (sHR 1.51, 95% CI 1.05-1.18, p  = 0.02) was associated with the highest mortality risk after adjusting for confounders in competing risk analysis. The frequency of high SAT radiodensity was 26% for those with cirrhosis, compared with 2% in healthy donors ( p <0.001). An inverse correlation was found between SAT radiodensity and the mean cross-sectional area of SAT adipocytes ( r  = -0.67, p  = 0.02). Shrunken, smaller adipocytes with expanded interstitial space were predominant in patients with high SAT radiodensity, whereas larger adipocytes with a thin rim of cytoplasm were observed in patients with low SAT radiodensity (744 ± 400 vs. 1,521 ± 1,035 μm 2 , p <0.001)., Conclusion: High SAT radiodensity frequently presents and is associated with a higher mortality in cirrhosis. SAT morphological rearrangement in patients with high SAT radiodensity might indicate diminished lipid stores and alterations in tissue characteristics., Lay Summary: Poor quality of subcutaneous adipose tissue (fat under the skin) is associated with higher mortality in patients with end-stage liver disease. Fat cells are smaller in patients with poor adipose tissue quality., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

Myosteatosis (pathological fat accumulation in muscle) is defined by lower mean skeletal muscle radiodensity in CT. We aimed to determine the optimal cut-offs for myosteatosis in a cohort of 855 patients with cirrhosis. CT images were used to determine the skeletal muscle radiodensity expressed as Hounsfield Unit (HU). Patients with muscle radiodensity values below the lowest tertile were considered to have myosteatosis. Competing-risk analysis was performed to determine associations between muscle radiodensity and pre-transplant mortality. Muscle radiodensity less than 33 and 28 HU in males and females, respectively, were used as cut-offs to identify myosteatosis. In the univariate analysis, cirrhosis etiology, MELD score, refractory ascites, variceal bleeding, hepatic encephalopathy, sarcopenia and myosteatosis were predictors of mortality. Myosteatosis association with mortality remained significant after adjusting for confounding factors (sHR 1.47, 95% CI 1.17−1.84, p = 0.001). Patients with concurrent presence of myosteatosis and sarcopenia constituted 17% of the patient population. The cumulative incidence of mortality was the highest in patients with concomitant sarcopenia and myosteatosis (sHR 2.22, 95% CI 1.64−3.00, p < 0.001). In conclusion, myosteatosis is common in patients with cirrhosis and is associated with increased mortality. The concomitant presence of myosteatosis and sarcopenia is associated with worse outcomes.

Myosteatosis, or pathological excess fat accumulation in muscle, has been widely defined as a lower mean skeletal muscle radiodensity on computed tomography (CT). It is reported in more than half of patients with cirrhosis, and preliminary studies have shown a possible association with reduced survival and increased risk of portal hypertension complications. Despite the clinical implications in cirrhosis, a standardized definition for myosteatosis has not yet been established. Currently, little data exist on the mechanisms by which excess lipid accumulates within the muscle in individuals with cirrhosis. Hyperammonemia may play an important role in the pathophysiology of myosteatosis in this setting. Insulin resistance, impaired mitochondrial oxidative phosphorylation, diminished lipid oxidation in muscle and age-related differentiation of muscle stem cells into adipocytes have been also been suggested as potential mechanisms contributing to myosteatosis. The metabolic consequence of ammonia-lowering treatments and omega-3 polyunsaturated fatty acids in reversing myosteatosis in cirrhosis remains uncertain. Factors including the population of interest, design and sample size, single/combined treatment, dosing and duration of treatment are important considerations for future trials aiming to prevent or treat myosteatosis in individuals with cirrhosis.

Emerging studies are reporting associations between skeletal muscle abnormalities and survival in cancer patients. Cancer prognosis is associated with depletion of essential fatty acids in erythrocytes and plasma in humans. However the relationship between skeletal muscle membrane fatty acid composition and survival is unknown. This study investigates the relationship between fatty acid content of phospholipids in skeletal muscle and survival in cancer patients. Rectus abdominis biopsies were collected during cancer surgery from 35 patients diagnosed with cancer. Thin-layer and gas chromatography were used for quantification of phospholipid fatty acids. Cutpoints for survival were defined using optimal stratification. Median survival was between 450 and 500 days when patients had arachidonic acid (AA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipid below the cut-point compared to 720-800 days for patients above. Cox regression analysis revealed that low amounts of AA, EPA and DHA are risk factors for death. The risk of death remained significant for AA [HR 3.5 (1.11-10.87), p = 0.03], EPA [HR 3.92 (1.1-14.0), p = 0.04] and DHA [HR 4.08 (1.1-14.6), p = 0.03] when adjusted for sex. Lower amounts of essential fatty acids in skeletal muscle membrane is a predictor of survival in cancer patients. These results warrant investigation to restore bioactive fatty acids in people with cancer., (© 2021. The Author(s).)

Fatty liver is a side effect of chemotherapy that limits the ability to treat colorectal cancer (CRC) patients in the most effective way. The aim of this study was to determine hepatic fatty acid composition and expression of genes involved in lipid metabolism at two time points following sequential chemotherapy treatment with Irinotecan (CPT-11)+5-fluorouracil (5-FU), agents commonly used to treat human colorectal cancer. Female Fischer 344 rats were provided a semi-purified AIN-76 basal diet with modified fat component. One cycle of chemotherapy consisted of CPT-11+5-FU and was initiated 2 weeks after tumor implantation (D0); a second cycle was given one week later. Two days after each cycle (Day 2 and Day 9), animals were euthanized, and livers collected. Triacylglycerol (TAG) and phospholipid (PL) fractions were isolated using thin layer chromatography and fatty acids (FAs) were quantified using gas chromatography. Expression of 44 lipid metabolism genes were analyzed by qPCR. Total liver TAG level was lowest after the second cycle D0 and D2 (P = 0.05) characterized by lower content of n-6 and n-3 polyunsaturated fatty acids (PUFAs). N-6 PUFAs significantly declined with subsequent treatments. Of 44 genes analyzed, 13 genes were altered with CPT-11+5-FU treatment. Expression of genes VLCAD and DGAT1, involved in fatty acid oxidation as well as DGAT1 in TAG synthesis, were significantly elevated after each cycle, whereas expression of genes ELOVL2 and FADS2, involved in fatty acid elongation and desaturation were significantly lower at D9 compared to D2 and D0 (P < 0.03). Hepatic total TAG PUFA was depleted, and genes involved in pathways of PUFA synthesis were down-regulated by chemotherapy treatment. This observation suggests impediments in lipid metabolism in the liver that could potentially impact peripheral availability of essential fatty acids., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Low functional capacity may lead to the loss of independence and institutionalization of older adults. A nutritional intervention within a rehabilitation program may attenuate loss of muscle function in this understudied population., Objective: This pilot study assessed the feasibility for a larger RCT of a nutritional supplementation in older adults referred to an outpatient assessment and rehabilitation program., Methods: Participants were randomized to receive a supplement (EXP: 2g fish oil with 1500 IU vitamin D3 1x/d + 20-30g whey protein powder with 3g leucine 2x/d) or isocaloric placebo (CTR: corn oil + maltodextrin powder) for 16 weeks. Handgrip and knee extension strength (using dynamometry), physical performance tests and plasma phospholipid n-3 fatty acids (using GCMS) were evaluated at weeks 0, 8 and 16; and lean soft tissue mass (using DXA), at weeks 0 and 16., Results: Over 2 years, 244 patients were screened, 46 were eligible (18.9%), 20 were randomized, 10 completed the study (6 CTR, 4 EXP). Median age was 87 y (77-94 y; 75% women) and gait speed was 0.69 m/s; 55% had low strength, and all performed under 420m on the 6-minute walk test, at baseline. Overall self-reported compliance to powder and oil was high (96% and 85%) but declined at 16 weeks for fish oil (55%). The EXP median protein intake surpassed the target 1.2-1.5 g/kg/d, without altering usual diet. Proportions of plasma phospholipid EPA and DHA increased significantly 3- and 1.5-fold respectively, at week 8 in EXP, with no change in CTR. Participants were able to complete most assessments with sustained guidance., Conclusion: Because of low eligibility, the pilot study was interrupted and deemed non-feasible; adherence to rigorous study assessments and to supplements was adequate except for long-term fish oil. The non-amended protocol may be applied to populations with greater functional capacity., Trial Registration: ClinicalTrials.gov NCT04454359., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: Dietary gangliosides are present in human milk and consumed in low amounts from organ meats. Clinical and animal studies indicate that dietary gangliosides attenuate signaling processes that are a hallmark of inflammatory bowel disease (IBD). Gangliosides decrease pro-inflammatory markers, improve intestinal permeability, and reduce symptoms characteristic in patients with IBD. The objective of this study was to examine mechanisms by which dietary gangliosides exert beneficial effects on intestinal health. Methods: Studies were conducted in vitro using CaCo-2 intestinal epithelial cells. Gangliosides were extracted from milk powder and incubated with differentiated CaCo-2 cells after exposure to pro-inflammatory stimuli. Gut barrier integrity was assessed by electron microscopy, epithelial barrier function was examined by measuring transepithelial electric resistance, and content of HBD-2, IL-23, NF-κB, and sPLA 2 was assessed by ELISA. Results: Ganglioside attenuated the decrease in integrity of tight junctions induced by pro-inflammatory stimuli and improved epithelial barrier function ( P < 0.05). Ganglioside decreased the basolateral secretion of sPLA 2 ( P ≤ 0.05), lowered HBD-2 and IL-23 levels ( P ≤ 0.05), and inhibited NF-κB activation ( P ≤ 0.05). Conclusions: In summary, the present study indicates that ganglioside GD3 improves intestinal integrity by altering sPLA 2 trafficking, and the production of pro-inflammatory mediators is mitigated by decreasing assembly of the NF-κB complex. Dietary gangliosides may have promising potential beneficial effects in IBD as decreased inflammatory signaling, improved intestinal integrity, and maintenance of epithelial barrier function have been demonstrated in vitro ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miklavcic, Li, Skolnick, Thomson, Mazurak and Clandinin.)

During cancer therapy many patients experience significant malnutrition, leading to decreased tolerance to chemotherapy and decreased survival. Dietary citrulline supplementation improves nutritional status in situations such as short bowel syndrome and aging, and is of potential interest in oncology. However, a mandatory prerequisite is to test this amino acid for interaction with tumor growth and chemotherapy response. Dietary citrulline (Cit; 2%), or an isonitrogenous mix of non-essential amino acids (control), was given to Ward colon tumor-bearing rats the day before chemotherapy initiation. Chemotherapy included 2 cycles, one week apart, each consisting of one injection of CPT-11 (50 mg/kg) and of 5-fluorouracil (50 mg/kg) the day after. Body weight, food intake and tumor volume were measured daily. The day after the last injection, rats were killed, muscles (EDL, gastrocnemius), intestinal mucosa, tumor, spleen and liver were weighed. Muscle and intestinal mucosa protein content were measured. Phosphorylated 4E-BP1 was measured in muscle and tumor as a surrogate for biosynthetic activation. FRAPS (Ferric Reducing Ability of Plasma) and thiols in plasma, muscle and tumor were evaluated and plasma amino acids and haptoglobin were measured. Numerous parameters did not differ by diet overall: a) response of tumor mass to treatment, b) tumor antioxidants and phosphorylated 4E-BP1 levels, c) relative body weight and relative food intake, d) weight of EDL, gastrocnemius, intestinal mucosa, spleen and liver and e) plasma haptoglobin concentrations. Moreover, plasma citrulline concentration was not correlated to relative body weight, only cumulated food intake and plasma haptoglobin concentrations were correlated to relative body weight. Citrulline does not alter the tumor response to CPT-11/5FU based therapy but, has no effect on nutritional status, which could be due to the anorexia and the low amount of citrulline and protein ingested., Competing Interests: Conflict of interest CB, LC and CM are shareholders of Citrage company; AG, NN, AdR, VM and VB: no conflict to declare., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Sarcopenia is defined as reduced skeletal muscle mass (SMM) or myopenia and altered muscle function and physical performance. It is unknown whether myopenia in children with end-stage liver disease (ESLD) adversely impacts clinical outcomes. We hypothesized that myopenia was prevalent in children with ESLD and related to suboptimal nutrition intake contributing to gross motor and growth delay, increased hospitalization, and medical complications., Methods: This retrospective study evaluated abdominal imaging (computed tomography/magnetic resonance imaging) for SMM (total, psoas, paraspinal, abdominal wall muscle; cm 2 /height 2 ) and adipose tissue (total, visceral, subcutaneous adipose tissue [SAT], ) determinations at the third and fourth lumbar vertebrates during liver transplantation (LTx) assessment. ESLD children (n = 30) were age- and gender-matched to healthy controls (n = 24). Myopenia was defined as SMM index z score <-2 and low SAT was defined as SAT index z-score <-1.5. Anthropometric, biochemical, and clinical data (hospitalization, complications, growth, neurodevelopment, energy/protein intake) were collected at LTx assessment, LTx, and post LTx (first hospitalization, 6 months, 12 months)., Results: Four distinct body composition phenotypes in children with ESLD were found: (1) myopenia with low SAT (17%;5 of 30), (2) myopenia (3%;1 of 30), (3) low SAT (20%;6 of 30), (4) normal muscle mass and SAT (60%;18 of 30). Myopenia with low SAT was prevalent in older (>2 years), male children and was associated with gross motor delay, reduced energy intake, and increased hospitalization and infections (total/viral/fungal)., Conclusions: Myopenia, accompanied by low SAT in children with ESLD, is associated with adverse clinical outcomes. Rehabilitation strategies aimed at combating myopenia in children are important., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Skeletal muscle is composed of multinuclear cells called myofibres, which are formed by the fusion of myoblasts during development. The size of the muscle fiber and mass of skeletal muscle are altered in response to several pathological and physiological conditions. Skeletal muscle regeneration is primarily mediated by muscle stem cells called satellite cells (SCs). In response to injury, these SCs replenish myogenic progenitor cells to form new myofibers to repair damaged muscle. During myogenesis, activated SCs proliferate and differentiate to myoblast and then fuse with one another to form muscle fibers. A reduced number of SCs and an inability to undergo myogenesis may contribute to skeletal muscle disorders such as atrophy, cachexia, and sarcopenia. Myogenic regulatory factors (MRF) are transcription factors that regulate myogenesis and determines whether SCs will be in the quiescent, activated, committed, or differentiated state. Mitochondria oxidative phosphorylation and oxidative stress play a role in the determination of the fate of SCs. The potential activation and function of SCs are also affected by inflammation during skeletal muscle regeneration. Omega-3 polyunsaturated fatty acids (PUFAs) show promise to reduce inflammation, maintain muscle mass during aging, and increase the functional capacity of the muscle. The aim of this critical review is to highlight the role of omega-3 PUFAs on the myogenic differentiation of SCs and pathways affected during the differentiation process, including mitochondrial function and inflammation from the current body of literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Isesele and Mazurak.)

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Standardized sex-specific cut-offs for sarcopenia in cirrhosis are needed to identify the risk of clinical complications and to discriminate the severity of sarcopenia. We aimed to compare clinical characteristics between patients with cirrhosis categorized according to the severity of sarcopenia. Computed tomography images were taken at the 3rd lumbar vertebra from 603 patients with cirrhosis and 129 adult donors for living liver transplantation. Patients with skeletal muscle index (SMI) two standard deviations (SD) below the sex-specific mean value of young donors (18-40 years old) were categorized as having severe sarcopenia whereas patients with SMI between -1 and -2 SD of the sex-specific young adult mean values were categorized as having sarcopenia. In the cirrhosis group, 408 patients (68%) were male with the mean age of 57 ± 0.4 years, and MELD score of 14 ± 0.4. Patients were divided into three groups: severe-sarcopenic (SMI < 30 cm 2 /m 2 in females and <42 cm 2 /m 2 in males), sarcopenic (30 ≤ SMI < 37 cm 2 /m 2 in females and 42 ≤ SMI < 50 cm 2 /m 2 in males) and non-sarcopenic (SMI ≥ 37 cm 2 /m 2 in females and ≥50 cm 2 /m 2 in males). Patients with cirrhosis and severe sarcopenia had lower muscle radiodensity and higher plasma neutrophil as well as neutrophil to lymphocyte ratio levels than both non- and sarcopenic groups. The frequency of alcohol-induced cirrhosis, refractory ascites, hepatic encephalopathy, CRP > 20 mg/mL, and severe malnutrition was also higher in severe-sarcopenic patients. The interval between sarcopenia and severe sarcopenia may reflect a window of opportunity in which to intervene and mitigate muscle wasting to improve patient outcomes.

Background: Identifying children at malnutrition risk on admission to hospital is considered best practice; however, nutrition screening in pediatric populations is not common. The aim of this study was to determine which screening tool is able to identify children with malnutrition on admission to hospital., Methods: A nurse administered 2 pediatric nutrition screening tools, Screening Tool for Risk on Nutritional Status and Growth (STRONGkids) and Pediatric Nutrition Screening Tool (PNST) to patients admitted to medicine and surgery units (n = 165). The Subjective Global Nutritional Assessment (SGNA) was then completed by a dietitian, blinded to the results of the screens. Sensitivity, specificity, and κ were calculated for both screening tools against the SGNA. A receiver operating characteristic (ROC) curve assessed alternate cutoffs for each tool. Length of hospital stay (LOS) was used to assess prospective validity., Results: Using the recommended cutoffs, the sensitivity of STRONGkids was 89%, specificity 35%, and κ 0.483. The sensitivity of PNST was 58%, specificity 88%, and κ 0.601. Using adjusted cutoffs, PNST's sensitivity improved to 87%, specificity 71%, and κ 0.681, and STRONGkids specificity improved to 61%, sensitivity 80%, and κ 0.5. Children identified at nutrition risk had significantly longer LOS (P < 0.05)., Conclusion: This study showed neither tool was appropriate for clinical use based on published cutoffs. By adjusting the cutoffs using ROC curve analysis, both tools improved overall agreement with the SGNA without significantly impacting the prospective validity. PNST with adjusted cutoffs is the most appropriate for clinical use in this population., (© 2019 The Authors. Nutrition in Clinical Practice published by Wiley Periodicals, Inc. on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: Low muscle radiodensity is associated with mortality in a variety of cancer types. Biochemical and morphological correlates are unknown. We aimed to evaluate triglyceride (TG) content and location as a function of computed tomography (CT)-derived measures of skeletal muscle radiodensity in cancer patients., Methods: Rectus abdominis (RA) biopsies were collected during cancer surgery from 75 patients diagnosed with cancer. Thin-layer chromatography and gas chromatography were used for quantification of TG content of the muscle. Axial CT images of lumbar vertebra were used to measure muscle radiodensity. Oil Red O staining was used to determine the location of neutral lipids in frozen muscle sections., Results: There was wide variation in RA radiodensity in repeated measures (CV% ranged from 3 to 55% based on 10 serial images) as well as within one slice (CV% ranged from 6 to 61% based on 10 subregions). RA radiodensity and total lumbar muscle radiodensity were inversely associated with TG content of RA (r = -0.396, P < 0.001, and r = -0.355, P = 0.002, respectively). Of the total percentage area of muscle staining positive for neutral lipid, 54 ± 17% was present as extramyocellular lipids (range 23.5-77.8%) and 46 ± 17% (range 22.2-76.5%) present as intramyocellular lipid droplets., Conclusions: Repeated measures revealed wide variation in radiodensity of RA muscle, both vertically and horizontally. Low muscle radiodensity reflects high level of TG in patients with cancer. Non-uniform distribution of intramyocellular and extramyocellular lipids was evident using light microscopy. These results warrant investigation of mechanisms resulting in lipid deposition in muscles of cancer patients., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose of Review: Providing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the form of fish oils, to benefit muscle is an emerging area of interest. The aim of this work was to evaluate the current literature that has assessed muscle mass as an outcome during a fish oil intervention in any chronic disease., Recent Findings: The vast majority of studies published in the last 3 years (12 of 15) have been conducted in the oncological setting, in patients undergoing treatment for cancers of the gastrointestinal tract, breast, head and neck, lung, cervix, and hematological cancers. Three studies were conducted in patients with chronic obstructive pulmonary disease (COPD). Fish oil was provided as part of nutrient mixtures in 12 studies and as capsules in three studies., Summary: Overall, the evidence for an effect of fish oil supplementation on muscle mass in patients with cancer undergoing treatment and in COPD remains unequivocal and reveals limited new knowledge in the area of fish oil supplementation in the cancer setting. Recent literature continues to provide mixed evidence on the efficacy of fish oil on muscle mass and function. The present review highlights challenges in comparing and interpreting current studies aimed at testing fish oil supplementation for muscle health.

Sarcopenia is a muscle disease characterized by reduced skeletal muscle mass (SMM), muscle strength, and physical performance. Reduced SMM has been identified in children after liver transplantation (LT), but no information related to muscle strength/physical performance or lifestyle factors contributing to sarcopenia is available. We hypothesized that sarcopenia, as determined by measures of SMM, muscle strength, and physical performance, is highly prevalent in children after LT and is related to poor diet quality (DQ) and physical inactivity. A cross-sectional study in post-LT children (n = 22) and age-matched healthy controls (n = 47) between the ages of 6 and 18 years examining body composition (dual energy X-ray absorptiometry and multiple skinfold), measures of muscle strength (handgrip, sit-to-stand, and push-ups), physical performance (6-minute walk test and stair climb test), diet (3-day food intake), and physical activity (accelerometer) was conducted. Low muscle strength/physical performance and SMM (SMM z scores ≤-1.5) were defined by values 2 standard deviations below the mean values for age- and sex-matched controls. Sarcopenia occurred in 36% of children who underwent LT, and they had significantly lower scores for muscle strength (sit-to-stand and push-up tests) and physical performance (stair climb test) than controls (P < 0.05). Deficits in physical performance in children with sarcopenia were predominantly revealed by longer stair climbing times (P = 0.03), with no differences in other muscle tests. Low SMM, muscle strength, and physical performance were associated with a lower amount of time spent in fairly and very active physical activity, but no associations with DQ were found. Sarcopenia is highly prevalent in children after LT and is related to lower moderate-to-vigorous physical activity. Development of effective rehabilitation strategies to treat sarcopenia are needed in post-LT children., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Purpose of Review: Recommendations for intakes of n - 3 fatty acids (FAs) in patients who are receiving chemotherapy for cancer are based on weak evidence. This review highlights themes within the emergent literature to suggest improvements in the design of studies that provide n - 3 FA supplements concurrent with cytotoxic agents., Recent Findings: Following earlier research in animal models and human pilot studies, recent human studies have evaluated the effect of providing n - 3 FAs during delivery of single agent and multiagent chemotherapy regimens for breast and gastro-intestinal cancers. Regimens were based on platinum compounds, fluoropyrimidines or both, and a variety of additional agents. Tumor location and stage, supplement dose and duration, and endpoints were dissimilar across studies. Overall, the recent research continues to support the safety and tolerability of n - 3 FA supplementation with chemotherapy and provides additional evidence, albeit weak, for enhanced tumor response, maintenance of weight and muscle, and reduction in inflammation and toxicities in the host across multiple cancer sites and chemotherapy regimens., Summary: The barriers to implementation in practice remain small study sizes, variations in supplement dosage and methodology, and differences in primary endpoints. Randomized, blinded trials with a justifiable sample size, adequate doses, monitored compliance and measures of clinically important endpoints are required to move these findings to a higher level of evidence for implementation into clinical practice.

Background: Researchers increasingly use intraoperative muscle biopsy to investigate mechanisms of skeletal muscle atrophy in patients with cancer. Muscles have been assessed for morphological, cellular, and biochemical features. The aim of this study was to conduct a state-of-the-science review of this literature and, secondly, to evaluate clinical and biological variation in biopsies of rectus abdominis (RA) muscle from a cohort of patients with malignancies., Methods: Literature was searched for reports on muscle biopsies from patients with a cancer diagnosis. Quality of reports and risk of bias were assessed. Data abstracted included patient characteristics and diagnoses, sample size, tissue collection and biobanking procedures, and results. A cohort of cancer patients (n = 190, 88% gastrointestinal malignancies), who underwent open abdominal surgery as part of their clinical care, consented to RA biopsy from the site of incision. Computed tomography (CT) scans were used to quantify total abdominal muscle and RA cross-sectional areas and radiodensity. Biopsies were assessed for muscle fibre area (μm 2 ), fibre types, myosin heavy chain isoforms, and expression of genes selected for their involvement in catabolic pathways of muscle., Results: Muscle biopsy occurred in 59 studies (total N = 1585 participants). RA was biopsied intraoperatively in 40 studies (67%), followed by quadriceps (26%; percutaneous biopsy) and other muscles (7%). Cancer site and stage, % of male participants, and age were highly variable between studies. Details regarding patient medical history and biopsy procedures were frequently absent. Lack of description of the population(s) sampled and low sample size contributed to low quality and risk of bias. Weight-losing cases were compared with weight stable cancer or healthy controls without considering a measure of muscle mass in 21 out of 44 studies. In the cohort of patients providing biopsy for this study, 78% of patients had preoperative CT scans and a high proportion (64%) met published criteria for sarcopenia. Fibre type distribution in RA was type I (46% ± 13), hybrid type I/IIA (1% ± 1), type IIA (36% ± 10), hybrid type IIA/D (15% ± 14), and type IID (2% ± 5). Sexual dimorphism was prominent in RA CT cross-sectional area, mean fibre cross-sectional area, and in expression of genes associated with muscle growth, apoptosis, and inflammation (P < 0.05). Medical history revealed multiple co-morbid conditions and medications., Conclusions: Continued collaboration between researchers and cancer surgeons enables a more complete understanding of mechanisms of cancer-associated muscle atrophy. Standardization of biobanking practices, tissue manipulation, patient characterization, and classification will enhance the consistency, reliability, and comparability of future studies., (© 2019 The Authors Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Children are at risk for malnutrition in hospital, and a contributing factor may be poor oral intake. Barriers to intake have been studied in adults, but there is a lack of research in children. The purpose of this study was to identify the potential barriers to oral intake for children in hospital. Patients and families (n = 58) admitted to surgery and medicine units at the Stollery Children's Hospital completed a survey on barriers to oral food intake. Barriers were classified into 6 domains and major barriers were those identified by at least 30% of the population. On average each patient was affected by 22% of the barriers. Within each domain, the proportion of patients identifying at least 1 barrier was as follows: organization (74%), hunger (67%), quality (60%), effects of illness (53%), choice (38%), and physical limitations (29%). Having food brought in from home due to hunger, not wanting what was ordered once it arrives, food quality, decreased appetite, sickness, fatigue, and pain were identified as major barriers. Children have unique barriers to oral food intake in hospital which have not been previously identified. Food service models should consider these barriers to better meet the needs of this population.

The relationship between dietary intake and body composition changes during cancer treatment has not been well characterized. The aim of this study was to compare dietary intake at diagnosis and end of treatment in relation to changes in muscle mass and adiposity in head and neck cancer (HNC) patients. Dietary intakes (three-day food record) and body composition using computed tomography (CT) were assessed at diagnosis (baseline) and after treatment completion (post-treatment). Skeletal muscle (SM) loss was explored as a consequence of energy and protein intake in relation to the minimum and maximum European Society of Parenteral and Enteral Nutrition (ESPEN) guidelines. Higher energy intakes (kcal/kg/day) and increases in energy intake (%) from baseline to post-treatment were correlated with attenuated muscle loss (r = 0.62, p < 0.01; r = 0.47, p = 0.04, respectively). Post-treatment protein intake demonstrated a weak positive correlation (r = 0.44, p = 0.05) with muscle loss, which did not persist when controlling for covariates. Meeting minimum ESPEN energy guidelines (25 kcal/kg/day) did not attenuate SM loss, whereas intakes >30 kcal/kg/day resulted in fewer participants losing muscle. Greater baseline adiposity correlated with greater SM loss ( p < 0.001). Energy intakes of 30 kcal/kg/day may be required to protect against SM loss during treatment in HNC patients. The influence of adiposity on SM loss requires further exploration.

Sarcopenia (severe muscle depletion) is a prevalent muscle abnormality in patients with cirrhosis that confers poor prognosis both pre- and post-liver transplantation. The pathogenesis of sarcopenia is multifactorial and results from an imbalance between protein synthesis and breakdown. Nutritional, metabolic, and biochemical abnormalities seen in chronic liver disease alter whole body protein homeostasis. Hyperammonemia, increased autophagy, proteasomal activity, lower protein synthesis, and impaired mitochondrial function play an important role in muscle depletion in cirrhosis. Factors including cellular energy status, availability of metabolic substrates (e.g., branched-chain amino acids), alterations in the endocrine system (insulin resistance, circulating levels of insulin, insulin-like growth factor-1, corticosteroids, and testosterone), cytokines, myostatin, and exercise are involved in regulating muscle mass. A favored atrophy of type II fast-twitch glycolytic fibers seems to occur in patients with cirrhosis and sarcopenia. Identification of muscle biological abnormalities and underlying mechanisms is required to plan clinical trials to reverse sarcopenia through modulation of specific mechanisms. Accordingly, a combination of nutritional, physical, and pharmacological interventions might be necessary to reverse sarcopenia in cirrhosis. Moderate exercise should be combined with appropriate energy and protein intake, in accordance with clinical guidelines. Interventions with branched chain amino acids, testosterone, carnitine, or ammonia-lowering therapies should be considered individually. Various factors such as dose, type, duration of supplementations, etiology of cirrhosis, amount of dietary protein intake, and compliance with supplementation and exercise should be the focus of future large randomized controlled trials investigating both prevention and treatment of sarcopenia in this patient population.

Background: Inflammation is a recognized contributor to muscle wasting. Research in injury and myopathy suggests that interactions between the skeletal muscle and immune cells confer a pro-inflammatory environment that influences muscle loss through several mechanisms; however, this has not been explored in the cancer setting. This study investigated the local immune environment of the muscle by identifying the phenotype of immune cell populations in the muscle and their relationship to muscle mass in cancer patients., Methods: Intraoperative muscle biopsies were collected from cancer patients (n = 30, 91% gastrointestinal malignancies). Muscle mass was assessed histologically (muscle fiber cross-sectional area, CSA; μm 2 ) and radiologically (lumbar skeletal muscle index, SMI; cm 2 /m 2 by computed tomography, CT). T cells (CD4 and CD8) and granulocytes/phagocytes (CD11b, CD14, and CD15) were assessed by immunohistochemistry. Microarray analysis was conducted in the muscle of a second cancer patient cohort., Results: T cells (CD3+), granulocytes/phagocytes (CD11b+), and CD3-CD4+ cells were identified. Muscle fiber CSA (μm 2 ) was positively correlated (Spearman's r = > 0.45; p = < 0.05) with the total number of T cells, CD4, and CD8 T cells and granulocytes/phagocytes. In addition, patients with the smallest SMI exhibited fewer CD8 T cells within their muscle. Consistent with this, further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively associated (Pearson's r = ≥ 0.5; p = <0.0001) with key genes within muscle catabolic pathways for signaling (ACVR2B), ubiquitin proteasome (FOXO4, TRIM63, FBXO32, MUL1, UBC, UBB, UBE2L3), and apoptosis/autophagy (CASP8, BECN1, ATG13, SIVA1)., Conclusion: The skeletal muscle immune environment of cancer patients is comprised of immune cell populations from the adaptive and innate immunity. Correlations of T cells, granulocyte/phagocytes, and CD3-CD4+ cells with muscle mass measurements indicate a positive relationship between immune cell numbers and muscle mass status in cancer patients. Further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively correlated with components of muscle catabolism.

Malnutrition is a common complication in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). Malnutrition and sarcopenia overlap in etiology and outcomes, with sarcopenia being defined as reduced skeletal muscle mass and muscle function. The purpose of this review was to identify the prevalence of sarcopenia with and without obesity in adults and children with ESLD and to assess the methodological considerations in sarcopenia diagnosis and the association of sarcopenia with pre- and post-LT outcomes. A total of 38 articles (35 adult and 3 pediatric articles) retrieved from PubMed or Web of Science databases were included. In adults, the prevalence rates of pre-LT sarcopenia, pre-LT sarcopenic obesity (SO), post-LT sarcopenia, and post-LT SO were 14%-78%, 2%-42%, 30%-100%, and 88%, respectively. Only 2 adult studies assessed muscle function in patients diagnosed with sarcopenia. The presence of pre-LT sarcopenia is associated with higher wait-list mortality, greater postoperative mortality, higher infection risk and postoperative complications, longer intensive care unit (ICU) stay, and ventilator dependency. The emerging pediatric data suggest that sarcopenia is prevalent in pre- and post-LT periods. In 1 pediatric study, sarcopenia was associated with poor growth, longer perioperative length of stay (total/ICU) and ventilator dependency, and increased rehospitalization in children after LT. In conclusion, there is a high prevalence of sarcopenia in adults and children with ESLD. Sarcopenia is associated with adverse clinical outcomes. The present review is limited by heterogeneity in the definition of sarcopenia and in the methodological approaches in assessing sarcopenia. Future studies are needed to standardize the sarcopenia diagnosis and muscle function assessment, particularly in the pediatric population, to enable early identification and treatment of sarcopenia in adults and children with ESLD., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Background: Neonates with intestinal failure dependent on parenteral nutrition (PN) are at risk of intestinal failure-associated liver disease (IFALD). PN lipid composition relates to the risk of IFALD, but the mechanisms are poorly understood. We investigated the effects of soybean oil (SO), a mixed-lipid (ML) emulsion containing fish oil (FO), and a pure FO. We hypothesized FO-containing PN lipids would result in increased gene expression of canalicular bile acid transporters and a larger, more hydrophilic bile acid pool, predictive of increased bile flow., Methods: Neonatal piglets were allocated to receive 1 of SO, ML, or FO throughout 14 days of PN feeding. Relative expression of genes involved in bile acid synthesis and transport were determined through quantitative polymerase chain reaction. Bile secreted from the liver was collected and measured. Bile acid composition was determined using tandem mass spectrometry. Regression analysis was used to determine predictors of bile flow., Results: PN reduced bile acid secretion (P < .001). FO-containing PN lipids were associated with greater expression of bile acid and organic solute transport genes (P < .05) and greater secretion of hydrophobic bile acids (P < .001). Farnesoid X receptor (P = .01), bile salt export pump (P < .01), multidrug resistant protein 2 (P < .01), and unconjugated hyocholic acid (P < .001) independently predicted bile flow., Conclusions: PN lipid modulation altered bile acid metabolism and composition. These alterations may explain the hepatoprotective effects of FO-containing PN lipids and support their use in the prevention and treatment of IFALD., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Objectives: In parenteral nutrition-dependent infants and children, intestinal failure (IF)-associated liver disease (IFALD) remains an important problem. A comparative study was undertaken of parenteral mixed lipid (ML), ω-3 predominant fish oil (FO), and ω-6 predominant soybean oil (SO) emulsions in regards to hepatic phytosterol, neutral lipid, fatty acid (FA) content, and the relationship to cholestasis in piglets., Methods: Neonatal piglets received parenteral nutrition, varying in lipid dose (5 or 10 g· kg · day) and formulation: SO5 (n = 5), SO10 (n = 5), FO5 (n = 5), and ML10 (n = 5). On day 14, liver chemistry, bile flow, histology and neutral lipid staining were assessed. Hepatic triglyceride FA content was determined using thin layer and gas chromatography, and phytosterol content was assessed using gas chromatography-mass spectrometry., Results: SO groups had higher prevalence of biochemical cholestasis (P < 0.04) and lower bile flow (P < 0.0001). Hepatic campesterol, stigmasterol, and β-sitosterol were highest in SO10 (P < 0.0001). Hepatic FA (P < 0.03) and ω-6/ω-3 FA ratio (P < 0.0001) were higher in the SO groups. Neutral lipid accumulation (P = 0.3) and liver histology (P = 0.16) were not different between groups. Univariate predictors of bile flow were: campesterol (r = -0.77, P = 0.001), β-sitosterol (r = -0.74, P = 0.002), stigmasterol (r = -0.74, P = 0.002), ω-6 FA (r = -0.72, P = 0.002), and ω-3 FA (r = 0.59, P = 0.02). Only campesterol independently predicted bile flow., Conclusions: ML and FO lipid emulsions reduce cholestasis in association with lowered hepatic phytosterol and lipid content. Lower hepatic phytosterol and ω-6 FA content, and higher ω-3 FA content are hepatoprotective. Multivariate analysis suggests reduced phytosterol accumulation may best explain the hepatoprotective effect of fish oil-containing lipids.

Background: Most prognostic scoring systems for colorectal liver metastases (CRLMs) account for factors related to tumour biology. Little is known about the effects of the host phenotype to the tumour. Our objective was to delineate the relationship of systemic inflammation and body composition features [i.e. low skeletal muscle mass (sarcopenia) and low visceral adipose tissue (VAT)], two well-described host phenotypes in cancer., Methods: Clinical data and pre-operative blood samples were collected from 99 patients who underwent resection of CRLM. Pre-operative computed tomography scans were available for 97 patients; body composition was analysed at the L3 level, stratified for sex and age. Clinicopathological variables, serum C-reactive protein (CRP), and various body composition variables were evaluated. Overall survival was evaluated as a function of these same variables in multivariate Cox regression analysis., Results: Skeletal muscle was significantly correlated with VAT (r = 0.46, P < 0.001). Of patients with sarcopenia, 35 (65%) also had low VAT. C-reactive protein was elevated (≥5 mg/mL) in 42 patients (43.3%). Elevated CRP was more common in patients with sarcopenia (73.8% vs. 51.1%, P = 0.029). The most significant prognostic factors were the coincidence of elevated CRP and adverse body composition features (sarcopenia and/or low VAT; hazard ratio 4.3, 95% confidence interval 1.5-13.0, P = 0.008), as well as Fong clinical prognostic score (hazard ratio 2.9, 95% confidence interval 1.5-5.5, P = 0.002)., Conclusions: Body composition in patients with CRLM is not directly linked to the presence of systemic inflammation. However, when systemic inflammation coincides with sarcopenia and/or low VAT, prognosis is adversely affected, independent of the Fong clinical prognostic score., (© 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose: Oral nutritional supplements and fortified foods, here considered supplemented food products (SFP), are recommended as part of nutrition therapy guidelines to treat malnutrition among cancer patients. However, their successful use is limited by patients' failure to meet recommended intakes. This systematic review aimed to identify sensory preferences for SFP among cancer patients and evaluate the methodologies employed in sensory preference assessment., Methods: A systematic search was conducted in several relevant databases yielding 1056 papers of which 19 met the inclusion criteria. Two authors independently selected papers and extracted findings. The included papers were categorized according to the focus of the preference assessment., Results: Studies comparing sensory preferences for SFP of cancer patients with those of a control group suggested that the liking for SFP by cancer patients differs from healthy participants. Patient heterogeneity in site and stage of tumor, variation in study methodologies, and type of treatment complicated a conclusion regarding the effects of cancer treatment and taste changes on taste preferences. However, some general results were observed among the studies, such as the preference for fresh milk-based supplements when compared with other supplement types., Conclusion: This review highlighted the need for consistent reporting and control of variables that influence the sensory characteristics of SFP when sensory preferences are assessed in the clinical setting. Attention to these methodological details will enhance the reliability and accuracy of sensory preference assessment among cancer patients for realistic evaluation of SFP targeted to their nutritional needs.

Background: Vitamin D deficiency has been implicated in the outcome of chronic liver disease., Aim: To determine the frequency of severe vitamin D deficiency in autoimmune hepatitis (AIH), assess its association with treatment non-response, and evaluate the relationship between vitamin D status and liver-related mortality and need for transplantation., Methods: Two hundred and nine patients were evaluated by liver tissue examination at presentation. Serum vitamin D levels were determined, and serum levels <25 nmol/L (10 ng/mL) were considered severely deficient. Treatment non-response was defined as non-normalised aspartate aminotransferase/alanine aminotransferase and immunoglobulin G levels during conventional immunosuppressive therapy. Univariate and multivariate analyses were performed using binary logistic regression and Cox proportional hazards model., Results: The mean vitamin D level was 60 ± 38 nmol/L (range, 3-263 nmol/L), and 42 patients (20%) had severe vitamin D deficiency. Treatment non-response was more common in patients with severe vitamin D deficiency than in patients without (59% vs 41%, P = 0.04). Severe vitamin D deficiency was also independently associated with a higher risk of developing cirrhosis (HR 3.40; 95% CI 1.30-8.87, P = 0.01) and liver-related mortality or requirement for liver transplantation (LT; HR 5.26, 95% CI, 1.54-18.0, P = 0.008). Patients with persistent severe deficiency following vitamin D supplementation continued to have poor outcomes., Conclusions: Severe vitamin D deficiency is associated with treatment non-response, progression to cirrhosis, and liver-related death or need for LT. Severe vitamin D deficiency is a prognostic biomarker in AIH., (© 2018 John Wiley & Sons Ltd.)

Since 2007, a quantitative, specific and precise approach to the detection of muscle loss has become accessible with the advent of image-based assessments. Computed tomography images acquired as part of standard cancer care are the serendipitous substrate for these analyses. Three radiologically-determined abnormalities, sarcopenia (severe muscle depletion), catabolic loss of muscle over time, and reduced muscle radiation attenuation associate with progressive functional impairment, treatment-related complications, reduced quality of life, and mortality. Fundamental understanding of muscle wasting in cancer cachexia has been developed on a base of clinical and experimental studies, which have identified alterations in muscle protein synthesis, autophagy and ubiquitin-mediated proteolysis as key contributors to muscle loss. The etiology of cancer-associated muscle wasting is multifactorial. Tumor metabolism captures energy fuels and amino acids, and a suite of tumor-derived molecules elicits catabolic pathways at the tissue level in muscle. Endocrine, neural and inflammatory derangements add further catabolic drive. Antineoplastic agents make a substantial contribution to muscle wasting by directly action on muscle cells, as well as secondarily via their systemic side effects. Encouraging data is emerging as to the potential reversibility of muscle loss and/or reduced muscle radiation attenuation through modulation of specific mechanisms. In the first line, pain and symptom management is a key element of the prevention of catabolic loss of muscle. Intake of intake of high-quality proteins and ω-3 polyunsaturated fatty acids support retention or gain of muscle mass. While there is no approved drug therapy for the indication of cancer-associated muscle wasting, there is preliminary evidence for robust gain of skeletal muscle mass in research studies of new therapeutics including inhibitors of mitogen-activated protein kinase kinases and ghrelin receptor agonists.

Mucositis and muscle wasting are two common toxicity effects of cancer treatment in head and neck cancer (HNC). There is limited data evaluating cancer treatment toxicities in relation to vitamin status. This study aimed to assess changes in vitamin status during HNC treatment in relation to body composition, inflammation and mucositis. In this prospective cohort study, dietary intakes (3-day food record), plasma levels of vitamins and C-reactive protein (CRP) were assessed at baseline (at diagnosis) and post-treatment (after 6⁻8 weeks of radiation therapy with or without chemotherapy). Computed tomography images were used to quantify body composition. Mucositis information was collected from health records of patients. Twenty-eight HNC patients (age 60 ± 10 years) completed both study time points. Patients who developed mucositis had significantly lower dietary intake of vitamins and plasma 25-hydroxy vitamin D (25-OHD) and all-trans retinol levels ( p < 0.02). Patients lost a considerable amount of muscle mass (3.4 kg) and fat mass (3.6 kg) over the course of treatment. There was a trend toward greater muscle loss in patients with 25-OHD < 50 nmol/L compared to patients with 25-OHD ≥ 50 nmol/L ( p = 0.07). A significant negative correlation was found between plasma all-trans retinol and CRP level at the end of treatment ( p = 0.03). Poor vitamin status could be a contributing factor in developing treatment-induced toxicities.

Background & Aims: Two major body compartments, skeletal muscle and adipose tissue, exhibit independent functions. We aimed to explore the prognostic significance of skeletal muscle, visceral and subcutaneous adipose tissue, according to sex, in patients with cirrhosis assessed for liver transplantation (LT)., Methods: CT images taken at the 3rd lumbar vertebra from 677 patients were quantified for three body composition indexes (cm 2 /m 2 ), visceral adipose tissue index, subcutaneous adipose tissue index (SATI), and skeletal muscle index (SMI). Cox proportional and competing-risk analysis hazard models were conducted to assess associations between mortality and body composition., Results: The majority of patients were male (67%) with a mean age of 57 ± 7 years, model for end-stage liver disease (MELD) score of 14 ± 8 and mean body mass index of 27 ± 6 kg/m 2 . Despite similar body mass index between the sexes, male patients had greater SMI (53 ± 12 vs. 45 ± 9 cm 2 /m 2 ), whereas SATI (67 ± 52 vs. 48 ± 37 cm 2 /m 2 ) was higher in females (p <0.001 for each). In sex stratified multivariate analyses after adjustment for MELD score and other confounding variables, SATI in females (hazard ratio [HR] 0.99; 95% CI 0.98-1.00; p = 0.01) and SMI in males (HR 0.98; 95% CI 0.96-1.00; p = 0.02) were significant predictors of mortality. Female patients with low SATI (<60 cm 2 /m 2 ) had a higher risk of mortality (HR 2.06; 95% CI 1.08-3.91; p = 0.03). Using competitive risk analysis in female patients listed for LT, low SATI was also an independent predictor of mortality (subdistribution HR 2.80; 95% CI 1.28-6.12; p = 0.01) after adjusting for MELD, and other confounding factors., Conclusions: A lower SATI is associated with higher mortality in female patients with cirrhosis. Subcutaneous adipose tissue has a favorable metabolic profile - low SATI may reflect depletion of this major energy reservoir, leading to poor clinical outcomes., Lay Summary: We looked at the importance of two of the main body compartments, skeletal muscle and adipose tissue (fat) on the prognosis of males and females with end-stage liver disease. Lower amounts of subcutaneous fat but not visceral fat (around internal organs), are associated with higher mortality in female patients with end-stage liver disease. However, low skeletal muscle predicts mortality in male patients with end-stage liver disease., (Copyright © 2018. Published by Elsevier B.V.)

This study assessed dietary and micronutrient intakes of head and neck cancer (HNC) patients at key points in the disease trajectory and evaluated the contribution of oral nutritional supplements (ONS) to micronutrient intake. HNC patients (n = 114) completed a three-day dietary record and a tool to assess Nutrition Impact Scores (NIS) at baseline, post-treatment, and follow-up. Foods were classified into food categories. Micronutrient, protein, and energy intakes were compared to European Society for Parenteral and Enteral Nutrition guidelines for cancer patients. The majority of patients did not meet recommended dietary intakes for vitamins D, E, C, folate, and magnesium at any study time point. Relative to baseline, the proportion of calories from milk, soup, and ONS significantly increased at post-treatment, while grain, meat, potato, baked dessert, and oil and sugar decreased (P < 0.03). At all study time points, patients categorized as high ONS consumers (>15% of total daily calories from ONS) had higher intakes of micronutrients (P < 0.003). They also had a higher NIS (P = 0.006) and experienced greater weight loss (P < 0.04) during the study, despite having similar energy intake to patients consuming <15% kcal from ONS. Fortification of usually consumed foods to improve micronutrient intake among cancer patients should be evaluated.

Although obesity is a well-known risk factor for cancer, the association between obesity and cancer survival remains controversial. This is partially due to the inability of conventional obesity measures to directly assess adiposity or adipose tissue distribution. As a metabolic organ, visceral adipose tissue (VAT) secrets a variety of cytokines and cytokine-like factors, potentially affecting cancer survival. The objective of this review was to investigate the influence of imaging-assessed VAT on cancer survival. A total of 22 studies assessing the impact of visceral adiposity on survival were included. Negative associations between VAT and survival were more frequently observed among patients with colorectal (four of six studies) and pancreatic (three of five studies) cancers, compared to higher VAT predicting longer survival in most studies of renal cell carcinoma patients (four of five studies). Methodological limitations, including unstandardised VAT measurement methods, lack of other body composition measurement (i.e. muscle mass), small sample size and heterogeneous cohort characteristics, may explain controversial findings related to the impact of VAT on cancer survival., (© 2016 John Wiley & Sons Ltd.)

Visceral adipose tissue (VAT) is a metabolically active organ, associated with higher risk of malignancies. We evaluated whether VAT is associated with the risk of hepatocellular carcinoma (HCC) in patients presenting with cirrhosis as well as HCC recurrence after liver transplantation (LT). Patients with cirrhosis (n = 678; 457 male) who were assessed for LT (289 with HCC) were evaluated for body composition analysis. Patients who underwent LT (n = 247, 168 male) were subsequently evaluated for body composition, and 96 of these patients (78 male) had HCC. VAT, subcutaneous adipose tissues, and total adipose tissues were quantified by computed tomography at the level of the third lumbar vertebra and reported as indexes (cross-sectional area normalized for height [square centimeters per square meter]). At the time of LT assessment, the VAT index (VATI) was higher in male patients with HCC compared to non-HCC patients (75 ± 3 versus 60 ± 3 cm 2 /m 2 , P = 0.001). The VATI, subcutaneous adipose tissue index, and total adipose tissue index were higher in male patients with HCC compared to non-HCC patients. By multivariate analysis, male patients with VATI ≥65 cm 2 /m 2 had a higher risk of HCC (hazard ratio, 1.90; 95% confidence interval, 1.31-2.76; P = 0.001). In male patients with HCC who underwent LT, a VATI ≥65 cm 2 /m 2 adjusted for Milan criteria was independently associated with higher risk of HCC recurrence (hazard ratio, 5.34; 95% confidence interval, 1.19-23.97; P = 0.03)., Conclusion: High VATI is an independent risk factor for HCC in male patients with cirrhosis and for recurrence of HCC after LT. (Hepatology 2018;67:914-923)., (© 2017 by the American Association for the Study of Liver Diseases.)

Background: Patients admitted to pediatric intensive care units (PICUs) often experience prolonged periods without nutrition support, which may result in hospital-induced malnutrition and longer length of stay. Nurse-driven feeding protocols have been developed to prevent unnecessary interruptions or delays to nutrition support. The primary objective of this study was to identify compliance and reasons for noncompliance to a feeding protocol at a tertiary care hospital PICU in Canada. The secondary aim was to determine the mean time (hours) spent without any form of nutrition and to identify reasons for time spent without nutrition., Materials and Methods: This was a prospective cohort audit, consisting of 150 consecutive PICU admissions (January-February 2016). Exclusion criteria consisted of patient mortality within 48 hours (n = 1) and patients who were still admitted at the end of the data collection timeframe (n = 7). The remaining cohort consisted of 142 consecutive admissions. Data collection took place in real time and included patient demographics, diagnostic categories, time spent without nutrition, reasons for interruptions to nutrition support, and reasons for noncompliance to the protocol. Observations were obtained through paper and computer charts and conversing with clinicians., Results: There was a 95% compliance rate to the protocol and an average of 25.6 hours spent without nutrition per patient. The most prevalent reason for noncompliance was an avoidable delay to restart feeds before/after procedures or after surgery., Conclusions: A nurse-driven feeding protocol may reduce time spent without nutrition. Future research is required to examine the relationship between adherence to feeding protocols and clinical outcomes., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Background: Early diagnosis of colorectal cancer (CRC) simplifies treatment and improves treatment outcomes. We previously described a diagnostic metabolomic biomarker derived from semi-quantitative gas chromatography-mass spectrometry. Our objective was to determine whether a quantitative assay of additional metabolomic features, including parts of the lipidome could enhance diagnostic power; and whether there was an advantage to deriving a combined diagnostic signature with a broader metabolomic representation., Methods: The well-characterized Biocrates P150 kit was used to quantify 163 metabolites in patients with CRC (N = 62), adenoma (N = 31), and age- and gender-matched disease-free controls (N = 81). Metabolites included in the analysis included phosphatidylcholines, sphingomyelins, acylcarnitines, and amino acids. Using a training set of 32 CRC and 21 disease-free controls, a multivariate metabolomic orthogonal partial least squares (OPLS) classifier was developed. An independent set of 28 CRC and 20 matched healthy controls was used for validation. Features characterizing 31 colorectal adenomas from their healthy matched controls were also explored, and a multivariate OPLS classifier for colorectal adenoma could be proposed., Results: The metabolomic profile that distinguished CRC from controls consisted of 48 metabolites (R 2 Y = 0.83, Q 2 Y = 0.75, CV-ANOVA p-value < 0.00001). In this quantitative assay, the coefficient of variance for each metabolite was <10%, and this dramatically enhanced the separation of these groups. Independent validation resulted in AUROC of 0.98 (95% CI, 0.93-1.00) and sensitivity and specificity of 93% and 95%. Similarly, we were able to distinguish adenoma from controls (R 2 Y = 0.30, Q 2 Y = 0.20, CV-ANOVA p-value = 0.01; internal AUROC = 0.82 (95% CI, 0.72-0.93)). When combined with the previously generated GC-MS signatures for CRC and adenoma, the candidate biomarker performance improved slightly., Conclusion: The diagnostic power for metabolomic tests for colorectal neoplasia can be improved by utilizing a multimodal approach and combining metabolites from diverse chemical classes. In addition, quantification of metabolites enhances separation of disease-specific metabolomic profiles. Our future efforts will be focused on developing a quantitative assay for the metabolites comprising the optimal diagnostic biomarker.

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 μm 2 ) in tumour-bearing animals compared to the reference group (3227.7 ± 36.7 μm 2 ; 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 μm 2 ; 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.