Standard Hypercaloric, Hyperproteic vs. Leucine-Enriched Oral Supplements in Patients with Cancer-Induced Sarcopenia, a Randomized Clinical Trial.

(1) Background: Malnutrition frequently affects patients with cancer, and it negatively impacts treatment tolerance, clinical outcomes and survival. Thus, appropriate nutritional screening and early nutrition support are extremely recommended. Currently, a significant number of oral supplements (OS) are commercially available; despite this, there is a lack of evidence for recommending specific OS, including leucine-enriched OS, for nutritional support in patients with cancer. (2) Aim: To compare the clinical evolution of patients with cancer (undergoing systemic treatment) that received standard hypercaloric, whey protein-based hyperproteic oral supplements vs. hypercaloric, hyperproteic leucine-enriched OS using a novel morphofunctional nutritional evaluation. (3) Patients and methods: This paper details an open-label, controlled clinical study in which patients were randomly assigned to receive nutritional treatment with whey protein-based hyperproteic oral supplements (control group) vs. hypercaloric, hyperproteic leucine-enriched OS (intervention group) during a twelve-week period. Forty-six patients were included; epidemiological, clinical, anthropometric, ultrasound (muscle echography of the rectus femoris muscle of the quadriceps and abdominal adipose tissue) and biochemical evaluation were performed. All patients received additional supplementation with vitamin D. (4) Results: Nutritional parameters (including bioimpedance, anthropometric, ultrasound and biochemical variables) of all included patients remained stable after the nutritional intervention. Extracellular mass tended to increase in the patients that received the leucine-enriched formula. Functionality (evaluated through the stand-up test) improved in both groups (p < 0.001). Prealbumin, transferrin levels and superficial adipose tissue increased in the control group (p < 0.05), while self-reported quality of life improved in all the evaluated patients (p < 0.001). (5) Conclusions: Nutritional support with hypercaloric, hyperproteic (with whey protein) OS and vitamin D supplementation were associated with the maintenance of body composition and improvements in functionality and in quality of life in the patients with cancer undergoing systemic treatment. No significant benefits were observed when a leucine-enriched formula was used.

Body composition and sexual hormones for the glucose control of autoimmune diabetes in males: are they necessary to predict diabetes-related complications?

Background: Glucose control in diabetes is essential for avoiding diabetes-related complications. Aim: To determine the impact of body composition and sexual hormones in glucose control and diabetes-related complications, in males with autoimmune diabetes. Patients and methods: Thirty-nine patients with autoimmune diabetes and flash glucose monitoring were included. A morphofunctional nutritional evaluation with bioelectrical impedance vector analysis (BIVA), abdominal adipose tissue ultrasound, rectus femoris ultrasound and biochemical parameters, was performed. Results: Strong, positive correlations were observed between body composition parameters, biochemical variables and sexual hormones (p<0.05). Adipose tissue measured by BIVA and ultrasound was more significantly associated with glucose control (including time in range >70%, glucose variability <36% determined by flash glucose monitoring; p<0.05) and the presence of microvascular/macrovascular complications (p<0.05) than lean mass. After adjusting by the duration of diabetes, BMI, abdominal circumference, fat mass and phase angle increased the risk for microvascular complications (OR 1.32(1.00 - 1.73), OR 1.06(1.00 - 1.12), OR 1.14(1.01 - 1.20), 0R 0.3(0.10 - 0.91) respectively; for macrovascular complications: BMI OR 1.38(1.04 - 1.84) and fat mass OR 1.26(1.00 - 1.58)]. Sexual hormone levels did not influence on glucose control or the development of diabetes-related complications. Conclusion: Anthrpometric parameters, especially adipose tissue, were associated with glucose control and variability determined by flash glucose monitoring. Furthermore, changes in fat and lean mass were associated with the presence of microvascular and macrovascular complications. Thus, a comprehensive nutritional evaluation might be useful for the evaluation of males with autoimmune diabetes, in order to identify patients with increased risk of complications.

Morphofunctional and Molecular Assessment of Nutritional Status in Head and Neck Cancer Patients Undergoing Systemic Treatment: Role of Inflammasome in Clinical Nutrition.

Malnutrition in patients with head and neck cancer is frequent, multifactorial and widely associated with clinical evolution and prognosis. Accurate nutritional assessments allow for early identification of patients at risk of malnutrition in order to start nutritional support and prevent sarcopenia. We aimed to perform a novel morphofunctional nutritional evaluation and explore changes in inflammasome-machinery components in 45 patients with head and neck cancer who are undergoing systemic treatment. To this aim, an epidemiological/clinical/anthropometric/biochemical evaluation was performed. Serum RCP, IL6 and molecular expression of inflammasome-components and inflammatory-associated factors (NOD-like-receptors, inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, cell-cycle and DNA-damage regulators) were evaluated in peripheral-blood mononuclear-cells (PBMCs). Clinical-molecular correlations/associations were analyzed. Coherent and complementary information was obtained in the morphofunctional nutritional assessment of the patients when bioimpedance, anthropometric and ultrasound data were analyzed. These factors were also correlated with different biochemical and molecular parameters, revealing the complementary aspect of the whole evaluation. Serum reactive C protein (RCP) and IL6 were the most reliable parameters for determining patients with decreased standardized phase angle, which is associated with increased mortality in patients with solid malignancies. Several inflammasome-components were dysregulated in patients with malnutrition, decreased phase angle and dependency grade or increased circulating inflammation markers. A molecular fingerprint based on gene-expression of certain inflammasome factors (p27/CCL2/ASC) in PBMCs accurately differentiated patients with and without malnutrition. In conclusion, malnutrition induces a profound alteration in the gene-expression pattern of inflammasome-machinery components in PBMCs. A comprehensive nutritional assessment including novel morphofunctional techniques and molecular markers allows a broad characterization of the nutritional status in cancer patients. Profile of certain inflammasome-components should be further studied as potential targets for nutrition-focused treatment strategies in cancer patients.

Dysregulation of Components of the Inflammasome Machinery After Bariatric Surgery: Novel Targets for a Chronic Disease.

BACKGROUND: Obesity is a metabolic chronic disease with important associated morbidities and mortality. Bariatric surgery is the most effective treatment for maintaining long-term weight loss in severe obesity and, consequently, for decreasing obesity-related complications, including chronic inflammation. AIM: To explore changes in components of the inflammasome machinery after bariatric surgery and their relation with clinical/biochemical parameters at baseline and 6 months after bariatric surgery. PATIENTS AND METHODS: Twenty-two patients with morbid-obesity that underwent bariatric surgery (sleeve gastrectomy and Roux-en-Y gastric bypass) were included. Epidemiological/clinical/anthropometric/biochemical evaluation was performed at baseline and 6 months after bariatric surgery. Inflammasome components and inflammatory-associated factors [nucleotide-binding oligomerization domain-like receptors (NLRs), inflammasome activation components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators) were evaluated in peripheral blood mononuclear cells (PBMCs) at baseline and 6 months after bariatric surgery. Clinical molecular correlations/associations were analyzed. Functional parameters (lipid accumulation/viability/apoptosis) were analyzed in response to specific inflammasome components silencing in liver HepG2 cells). RESULTS: A profound dysregulation of inflammasome components after bariatric surgery was found, especially in NLRs and cell-cycle and DNA damage regulators. Several components were associated with baseline metabolic comorbidities including type 2 diabetes (C-C motif chemokine ligand 2/C-X-C motif chemokine receptor 1/sirtuin 1), hypertension (absent in melanoma 2/ASC/purinergic receptor P2X 7), and dyslipidemia [C-X-C motif chemokine ligand 3 (CXCL3)/NLR family pyrin domain containing (NLRP) 7) and displayed changes in their molecular profile 6 months after bariatric surgery. The gene expression fingerprint of certain factors NLR family CARD domain containing 4 (NLRC4)/NLRP12/CXCL3)/C-C motif chemokine ligand 8/toll-like receptor 4) accurately differentiated pre- and postoperative PBMCs. Most changes were independent of the performed surgical technique. Silencing of NLRC4/NLRP12 resulted in altered lipid accumulation, apoptosis rate, and cell viability in HepG2 cells. CONCLUSION: Bariatric surgery induces a profound alteration in the gene expression pattern of components of the inflammasome machinery in PBMCs. Expression and changes of certain inflammasome components are associated to baseline metabolic comorbidities, including type 2 diabetes, and may be related to the improvement and reversion of some obesity-related comorbidities after bariatric surgery.