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Background Many studies have assessed different malnutrition screening tools in oncologic patients. However, very few have been carried out using the new GLIM criteria for malnutrition. The objective of our study is to compare the most recommended screening tools with respect to the new GLIM criteria for malnutrition in cancer patients. Methods Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department at the Lozano Blesa Hospital in Zaragoza. We recruited 165 patients with tumors of the upper-gastrointestinal-tract, colorectal, and head-and-neck region undergoing outpatient treatment. All of them received MST, MUST, Nutriscore, MNA and CONUT screening tools, as well as the GLIM diagnostic criteria, which was used as the gold standard. Results MNA-SF showed the best sensitivity (0.99) and lowest specificity while CONUT had the best specificity (0.89) and lowest sensitivity to detect cancer-related malnutrition. We observed high variability in the diagnostic capabilities of Nutriscore when tumor location was considered, reducing sensitivity in patients with colorectal cancer compared to those with tumors of the upper-gastrointestinal-tract or head-and-neck location (0.25, 0.83, and 0.91 respectively). The highest index of agreement between the screening tools was found between MST, MUST and Nutriscore tests. Regarding the GLIM criteria, the highest agreement index was presented by MUST tool (0.66), while CONUT presented the lowest (0.12). Conclusions Selecting the screening tool according to the type of cancer and its location may allow us to optimize its use and increase its performance, exploiting the advantages of each of them in the different populations.

Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency.

Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.

Introduction Immune checkpoint inhibitors (ICIs) are effective agents against several malignancies. However, they are associated with gastrointestinal and liver immune-related adverse events (GI-IrAEs and LI-IrAEs), which can lead to their temporary or permanent discontinuation. Aim The aim of this study was to evaluate the efficacy and gastrointestinal and liver toxicity of ICIs in oncological treatments in actual clinical practice. Material and methods Patients with advanced cancer who received at least 1 ICI dose between May 2015 and September 2018 were retrospectively assessed. Results 132 patients with non-small cell lung cancer (65.15%, n = 86); melanoma (22.7%, n = 30); renal carcinoma (9.09%, n = 12); and other tumours (3%, n = 4) were included. The treatments administered were nivolumab (n = 82), pembrolizumab (n = 28), atezolizumab (n = 13), durvalumab (n = 2), ipilimumab (n = 1) and the antiCTLA-4/PD-1 combination (n = 6). In total, 51 patients (38.6%) developed IrAEs, 17 (12.9%) of which experienced GI-IrAEs. Of these, 8 (47%) needed steroids and 1 patient required surgery due to intestinal perforation. Grade I Li-IrAEs were observed in 4 patients (3.03%): 2 (50%) required corticosteroids and 1 patient had to discontinue treatment. Four patients (66.6%) who received combination therapy experienced GI-IrAEs. IrAE incidence were not associated with age, gender or drug response. Conclusions GI-IrAEs are one of the most common adverse events in patients receiving ICIs. A multidisciplinary approach and a greater understanding of these events could help to reduce morbidity and therapy discontinuation.

Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, have immunomodulatory properties, show great ex vivo expansion capacity and differentiation to other cell types, and release a wide variety of angiogenic factors and bioactive molecules, such as growth factors and adipokines. However, despite the positive results obtained in some pre-clinical studies, the actual clinical efficacy of ADMSCs still remains controversial. Transplanted ADMSCs present a meager rate of survival and proliferation, possibly because of the damaged microenvironment of the affected tissues. Therefore, there is a need for novel approaches to generate more functional ADMSCs with enhanced therapeutic potential. In this context, genetic manipulation has emerged as a promising strategy. In the current review, we aim to summarize several adipose-focused treatments of obesity, including cell therapy and gene therapy. Particular emphasis will be given to the continuum from obesity to metabolic syndrome, diabetes, and underlying non-alcoholic fatty liver disease (NAFLD). Furthermore, we will provide insights into the potential shared adipocentric mechanisms involved in these pathophysiological processes and their remediation using ADMSCs.

Oral phase dysphagia is dependent on ability to chew. As people age, general muscle atrophy contributes to decreased masseter strength. The main objective of this study was to assess the relationship between the thickness of the masseter muscle measured by ultrasonography and the presence of dysphagia in a group of institutionalized elderly people. As a secondary objective, we aimed to establish cutoff points of masseters muscle thickness (MMT) to identify elderly individuals at risk of oral dysphagia. Cross-sectional study of all residents from 3 nursing homes. All individuals underwent ultrasonographic measurements of left and right MMT and were classified according to the presence of dysphagia assessed by both the EAT-10 screening questionnaire and the volume‐viscosity swallow test (V‐VST). 469 patients (69% women, mean age 84.7 yrs) were recruited. Dysphagia was present in 41.6% and 26% of individuals according the EAT-10 and V-VST, respectively. Multivariate logistic regression showed that 1 mm increase in MMT reduced the risk of dysphagia by 21% according to the EAT-10 tool and by 30% using the V-VST after adjusting for age, sex, mini-nutritional assessment score, and body mass index. We used receiver operative characteristic (ROC) curves to identify cutoff points of MMT to detect dysphagic individuals according to either EAT-10 or V-VST. The MMT measured by ultrasonography is reduced in elderly individuals with dysphagia. Based on MMT, clinicians may be better informed about the patients'´ ability to masticate solid foods and identify potential nutrient deficiencies in geriatric settings

Background Diabetes and older age are associated with an increased risk of malnutrition and mortality. Recently, the Global Leadership Initiative on Malnutrition (GLIM) provided a 2-step approach for the malnutrition diagnosis. In this study, we aimed to determine whether GLIM nutrition status at admission was associated with long-term survival in elderly patients with type 2 diabetes mellitus (T2DM). Additionally, we aimed to identify which GLIM criteria were more able to become prognostic indicators of early or late death. Methods Our study included a convenience sample of 159 patients with T2DM older than 65 years and admitted to the internal medicine wards of different Spanish hospitals: the VIDA-survival cohort. Nutrition status was retrospectively assessed with the new GLIM criteria. The main outcome was long-term mortality in the cohort during an 8-year follow-up. Bivariate tables summarized the variables of interest. Kaplan-Meier survival curves and adjusted Cox regressions were also performed. Results According to the GLIM criteria, we observed that the 35.8% and 16.3% of the VIDA-survival cohort were categorized as having moderate and severe malnutrition, respectively. Severe malnutrition was associated with increased mortality (hazard ratio [HR] = 2.09; 95% CI, 1.29-3.38), compared with nonmalnourished participants. Moderate malnutrition had a neutral effect on all-cause mortality (HR = 1.30; 95% CI, 0.88-1.92). Low plasma albumin levels, a surrogate marker of inflammation, were strongly associated with early mortality. Conclusion Our study provides evidence that severe malnutrition according to GLIM criteria is associated with increased long-term all-cause mortality among elderly individuals with T2DM.

Jasonia glutinosa (L.) DC., also known in Spain as "te de roca" (rock tea, RT), is an endemic plant species of the Iberian Peninsula and Southern France. Traditionally, it is used in infusions, prepared with the flowering aerial parts, as a digestive and anti-inflammatory herbal tea. Despite the traditional knowledge of this plant as a digestive after meals, there are hardly any scientific studies that support its use. The aim of this study is to assess the effects of RT extract on physiological targets related to metabolic diseases such as obesity. For this purpose, enzyme inhibition bioassays of lipase, α-glucosidase and fatty acid amide hydrolase were carried out in cell-free systems. Similarly, adipocytes derived from 3T3-L1 cells were employed to study the effects of the extract on adipocyte differentiation and triglyceride (TG) accumulation. RT extract was able to inhibit lipase, α-glucosidase and fatty acid amide hydrolase. Furthermore, the extract displayed anti-adipogenic properties in a dose-dependent manner as it significantly reduced TG accumulation during adipocyte differentiation. These results may explain from a molecular perspective the beneficial effects of RT in the prevention of metabolic-associated disorders such as obesity, diabetes and related complications.

IntroductionThere is a growing interest in the emotional state of cancer patients. The main objective of this pilot study is to assess the feasibility, acceptability, and preliminary efficacy of Meaning-Centered Psychotherapy and Essential Care (MCP-EC) in patients with advanced cancer compared with usual psychological support. We define “Essential Care” as the promotion of patient care and self-care through the recall of good care experiences and discussion of the concepts: responsibility, self-compassion, kindness, and attitude.MethodPilot, single-center, and prospective study of 30 patients with advanced cancer and emotional distress. Our adaptation consisted in three session Meaning-Centered Psychotherapy-Palliative Care, plus a fourth session named “Essential Care”. The study was carried out in two phases. First, 20 patients were randomized to one of the two arms: individual MCP-EC (experimental, n = 10) or usual psychological supportive (control, n = 10). In a second phase, 10 patients were assigned consecutively to Group MCP-EC (n = 10). All patients were evaluated at baseline (pre-) and post-intervention with questionnaires for sociodemographic data and clinical scales.ResultsNineteen patients completed the 4 sessions of MCP-EC, 9 individual format and 10 group format. Usual supportive intervention was delivered to 10 control patients. Total 28 patients completed pre- and post-treatment evaluations. There were no pre- vs. post-differences in the evaluations of the control group. In the experimental group, significant pre- vs. post-differences were found in EQ-5D-3L, HADS, FACIT, DM, HAI, SCS-SF, and TD questionnaires. These results indicated that MCP-EC reduced anxiety and depression symptoms, hopelessness, demoralization, as well as increased spiritual well-being and sense of meaning. Participants were satisfied and found the MCP-EC intervention positively.ConclusionsThis pilot study suggests that the MCP-EC has feasibility, acceptability, and preliminary efficacy reducing the emotional distress in advanced cancer patients. Larger studies are warranted to clarify the strengths and limitations of this psychotherapy.

Objective Adipose tissue stores a substantial amount of body cholesterol in humans. Obesity is associated with decreased concentrations of serum cholesterol. During weight gain, adipose tissue dysfunction might be one of the causes of metabolic syndrome. The aim of this study is to evaluate cholesterol storage and oxidized metabolites in adipose tissue and their relationship with metabolic clinical characteristics. Methods Concentrations of cholesterol and oxysterols (27-hydroxycholesterol and 24S-hydroxycholesterol) in subcutaneous and visceral adipose tissue were determined by high-performance liquid chromatography with tandem mass spectrometry in 19 adult women with body mass index between 23 and 40 kg/m2 from the FAT expandability (FATe) study. Tissue concentration values were correlated with biochemical and clinical characteristics using nonparametric statistics. Results Insulin correlated directly with 24S-hydroxycholesterol in both adipose tissues and with 27-hydroxycholesterol in visceral tissue. Leptin correlated directly with 24S-hydroxycholesterol in subcutaneous adipose tissue. Tissue cholesterol correlated directly with 27-hydroxycholesterol in both adipose tissues and with 24S-hydroxycholesterol in visceral tissue, where cholesterol correlation with 24S-hydroxycholesterol was higher than with 27-hydroxycholesterol. In addition, some tendencies were observed: serum high-density lipoprotein cholesterol tended to be inversely correlated with visceral adipose tissue cholesterol; high-sensitivity C-reactive protein tended to be correlated directly with subcutaneous adipose 24S-hydroxycholesterol and inversely with visceral 27-hydroxycholesterol. Conclusions Adipose tissue oxysterols are associated with blood insulin and insulin resistance. Tissue cholesterol correlated more with 27-hydroxycholesterol in subcutaneous adipose tissue and with 24S-hydroxycholesterol in visceral adipose tissue. Levels of adipose 24S-hydroxycholesterol seem to be correlated with some metabolic syndrome symptoms and inflammation while adipose 27-hydroxycholesterol could represent some protection against them.

β-Hydroxy-β-methylbutyrate (HMB) supplementation increases muscle and strength mass in some muscle-wasting disorders. Malnutrition and sarcopenia are often present in liver cirrhosis. We aimed to investigate the effects of oral HMB supplementation on changes in body composition and liver status in patients with cirrhosis and malnutrition. In a randomized, controlled, double-blind trial, 43 individuals were randomized to receive twice a day and for 12 weeks an oral nutritional supplement (ONS) enriched with 1.5 g of calcium HMB per bottle or another supplement with similar composition devoid of HMB. Inclusion criteria were liver cirrhosis with at least one previous decompensation and clinical malnutrition. Liver function, plasma biochemistry analyses, and physical condition assessment were carried out at baseline, then after six and 12 weeks of supplementation. A total of 34 patients completed the clinical trial. An improvement in liver function and an increase in fat mass index were observed in both groups. None of the two ONS changed the fat-free mass. However, we observed an upward trend in handgrip strength and a downward trend in minimal hepatic encephalopathy in the HMB group. At the end of the trial and regardless of the supplement administered, fat mass content increased with no change in fat-free mass, while liver function scores and nutritional analytic markers also improved.

Low plasma levels of branched chain amino acids (BCAA) in liver cirrhosis are associated with hepatic encephalopathy (HE). We aimed to identify a metabolic signature of minimal hepatic encephalopathy (MHE) in malnourished cirrhotic patients and evaluate its modification with oral nutritional supplements (ONS) enriched with ß-Hydroxy-ß-methylbutyrate (HMB), a derivative of the BCAA leucine. Post hoc analysis was conducted on a double-blind placebo-controlled trial of 43 individuals with cirrhosis and malnutrition, who were randomized to receive, for 12 weeks, oral supplementation twice a day with either 220 mL of Ensure® Plus Advance (HMB group, n = 22) or with 220 mL of Ensure® Plus High Protein (HP group, n = 21). MHE evaluation was by psychometric hepatic encephalopathy score (PHES). Compared to the HP group, an HMB-specific treatment effect led to a larger increase in Val, Leu, Phe, Trp and BCAA fasting plasma levels. Both treatments increased Fischer’s ratio and urea without an increase in Gln or ammonia fasting plasma levels. MHE was associated with a reduced total plasma amino acid concentration, a reduced BCAA and Fischer´s ratio, and an increased Gln/Glu ratio. HMB-enriched ONS increased Fischer´s ratio without varying Gln or ammonia plasma levels in liver cirrhosis and malnutrition, a protective amino acid profile that can help prevent MHE. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot’s metabolic differences. Further studies are necessary to fully corroborate this hypothesis.

Various amino acid (AA) metabolites are used as supplements to facilitate metabolic control and enhance responsiveness of insulin-sensitive tissues. β-hydroxy-β-methylbutyrate (HMB) is a leucine metabolite proposed to prevent muscle wasting and to mitigate insulin resistance. Taurine, commonly added to energizing drinks, is a metabolite of methionine and cysteine present in bile juice, and proposed to be involved in lipid digestion and to be pro-lipolytic in adipocytes. N-methyltyramine (NMT) is a phenylalanine metabolite found in orange juices at 0.1–3 ppm while its effects on lipid mobilization remain controversial. Here, the putative lipolytic effects of these AA metabolites were studied and it was tested whether they could enhance insulin antilipolytic response in adipocytes. Release of glycerol and non-esterified fatty acids (NEFAs) was measured after a 2-h incubation of adipocytes obtained from control and diet-induced obese mice or from obese patients. In mouse, none of the tested AA derivatives was lipolytic from 1 μM to 1 mM. These compounds did not improve insulin antilipolytic effect or isoprenaline lipolytic action, except for 1 mM NMT that impaired triacylglycerol breakdown in obese mice. In human adipocytes, HMB and taurine were not lipolytic, while NMT weakly activated glycerol and NEFA release at 1 mM. However, 100 μM NMT impaired isoprenaline-stimulated lipolysis in a manner that was hardly added to insulin antilipolytic effect. Since none of these AA derivatives acutely helped or replaced insulin antilipolytic effect in adipocytes, the present in vitro observations do not support their proposed insulin-sensitizing properties. Moreover, NMT, HMB, and taurine were not notably lipolytic.

Background: The aim of this work was to assess whether the muscle thickness and echogenicity were associated with dysphagia, malnutrition, sarcopenia, and functional capacity in acute hospital admission for a hip fracture. Methods: Observational study that assessed nutritional status by Global Leadership Initiative on Malnutrition, risk of dysphagia and sarcopenia by European Working Group on Sarcopenia in Older People and Barthel functional index. We measured muscle thickness and echogenicity of masseter, bicipital, and quadriceps rectus femoris (RF) and vastus intermedius (VI) by ultrasound. Results: One hundred and one patients were included in the study (29.7% sarcopenia and 43.8% malnutrition). Logistic regression models adjusted for age, sex, and body mass index showed an inverse association of the masseter thickness with both sarcopenia (OR: 0.56) and malnutrition (OR: 0.38) and quadriceps with sarcopenia (OR: 0.74). In addition, patients at high risk of dysphagia had lower masseter thickness (p: 0.0001) while patients able to self-feeding had thicker biceps (p: 0.002) and individuals with mobility on level surfaces higher thickness of biceps (p: 0.008) and quadriceps (p: 0.04). Conclusion: Thickness of the masseter was associated with risk of dysphagia, biceps with the ability to self-feed, and that of the quadriceps RF-VI with mobility.

Physical activity (PA) reduces the risk of cognitive decline (CD) in the general population. However, little is known about whether the presence of the apolipoprotein E epsilon 4 allele (APOE e4) could modify this beneficial effect. The aim of this systematic review was to analyze and synthetize the scientific evidence related to PA levels and CD risk in cognitively healthy APOE e4 carriers. Four electronic databases were analyzed. Only original articles with longitudinal study design were selected to analyze the relationship between PA and CD in APOE e4 carriers. Five studies were included in the systematic review. All studies except one stated that PA is a protective factor against CD in APOE e4 carriers. Moreover, partial support was found for the hypothesis that a greater amount and intensity of PA are more beneficial in CD prevention. The results support the idea that PA is a protective factor against CD in APOE e4 carriers. Nevertheless, it would be necessary to carry out further studies that would allow these findings to be contrasted.

Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency.

Summary Background & aims Malnutrition is one of the most prevalent problems among oncological patients. It reduces the response to treatments and negatively impacts survival. In 2019, a consensus criteria for diagnosing malnutrition (GLIM criteria) were proposed by most scientific nutrition societies. The objective of our work is 1) to assess the diagnostic capacity of the GLIM criteria in ambulatory patients with cancer and 2) to compare the GLIM with the ESPEN criteria to evaluate the contributions of these new criteria with respect to the existing ones. Methods Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department in the Lozano Blesa Clinical Hospital in Zaragoza (Spain). One hundred and sixty-five outpatients with tumors in the upper gastrointestinal tract, head and neck, and colorectal locations were recruited. All of them received the MST, MUST, and Nutriscore screening tools along with the ESPEN and GLIM diagnostic criteria. Results The prevalence of malnutrition was 46.7% according to the GLIM criteria and 21.2% using the ESPEN tool. Patients diagnosed by GLIM had a higher body mass index (BMI, 24.3 kg/m2) and muscle mass (MM, 16.1 kg/m2) than those diagnosed by ESPEN (21.2 kg/m2 and 14.3 kg/m2 respectively, both p = 0.001). The MST, MUST, and Nutriscore tools had a higher degree of concordance with GLIM compared to ESPEN (MST 0.53 vs 0.26; MUST 0.36 vs 0.66; Nutriscore 0.28 vs 0.54). Conclusions The found prevalence of malnutrition in cancer patients is higher using the GLIM instead of ESPEN criteria. This disparity can be explained at least in part by the difficulty of the ESPEN criteria for malnutrition to diagnose patients with high baseline BMI or MM. The use of criteria with greater sensitivity, such as the new GLIM criteria, could help early diagnosis and thus early intervention in cancer patients.

Background The prevalence of dysphagia is very high in institutionalized elderly. Knowledge of the rheological and sensory characteristics of the various thickeners in elderly is limited, although it has been seen that there are differences between the rheological behaviors of gum-based thickeners with different composition. Moreover, we have not found sensory studies of viscosity in institutionalized elderly. Our hypothesis was that viscosity ranges established by the scientific societies, such as the National Dysphagia Diet Task Force (NDD), seem to be very wide and individuals might be able to detect small differences within the same texture range. The objectives of our study were 1) comparing the rheological characteristics of two commercial gum-based thickeners with different composition, dissolved in water under standard conditions, and 2) perform a sensory analysis (with both adults and institutionalized elderly) to detect different viscosities within the same texture (nectar and honey). Methods Two commercial thickeners based on gums (NC and RC) were studied analyzing their viscosity in water with different concentrations (shear rate: 50 s− 1; temperature: 22–25 °C). A sensory analysis involving 26 elderly and 29 adult controls was carried out to evaluate whether differences within nectar and honey textures among gum-based thickeners could be distinguished. Results As the shear rate increases, viscosity decreases (non-Newtonian and pseudoplastic behavior). At the same concentration, each thickener produces a different viscosity (p p p p p p Conclusions Our results suggest that the accepted viscosity ranges by NDD for the different textures might be too wide because institutionalized elderly and their caregivers are able to discern small differences in viscosity in nectar and honey textures. Gum-based thickeners with different composition showed differences in viscosity capacity, so they are not interchangeable.

Sarcopenia is a progressive and generalized loss of skeletal muscle mass and strength. It is frequently associated with malnutrition and dependence in nursing homes. Masticatory muscle strength could be the link between sarcopenia, malnutrition and dependence. We aimed to study the relation between sarcopenia, malnutrition and dependence with masseter muscle thickness measured by ultrasound. A cross-sectional study was realized, with 464 patients from 3 public nursing homes in Zaragoza (Spain). The diagnosis of sarcopenia was assessed according to the EuropeanWorking Group on Sarcopenia in Older People 2 criteria, malnutrition by the Mini Nutritional Assessment (MNA) and the Global Leadership Initiative on Malnutrition (GLIM) criteria and functional capacity by the Barhel Index and the texture diet. Masseter muscle thickness (MMT) was measured by ultrasound. The median age was 84.7 years, and 70% of the participants were women. Sarcopenia was confirmed in 39.2% of patients, malnutrition in 26.5% (risk 47.8%), total dependence in 37.9% and diet texture was modified in 44.6%. By logistic regression, once the model was adjusted for age, sex, Barthel index and texture diet, our analyses indicated that each 1 mm decrease in MMT increased the risk of sarcopenia by ~57% (OR: 0.43), the risk of malnutrition by MNA by ~63% (OR: 0.37) and the risk of malnutrition by GLIM by ~34% (OR: 0.66). We found that MMT was reduced in sarcopenic, malnourished and dependent patients, and it could be the common point of a vicious cycle between sarcopenia and malnutrition. Further studies are needed to establish causality. © 2021 by the authors.

Introducción Los inhibidores del punto de control inmunitario (immune checkpoint inhibitors [ICI]) son fármacos eficaces en el tratamiento de diversas neoplasias. Sin embargo, se han relacionado con eventos adversos inmunomediados (EAI) gastrointestinales y hepáticos que pueden desencadenar su interrupción temporal o definitiva. Objetivo Evaluar, en condiciones de práctica real, la eficacia y la toxicidad gastrointestinal y hepática de los ICI en tratamientos oncológicos. Material y métodos Estudio retrospectivo con inclusión de pacientes con diagnóstico de neoplasia avanzada que habían recibido al menos una dosis de ICI entre mayo de 2015 y septiembre de 2018. Resultados Se incluyeron 132 pacientes con neoplasia de pulmón no microcítico (65, 15%, n = 86), melanoma (22, 7%, n = 30), carcinoma renal (9, 09%, n = 12) y otros tumores (3%, n = 4). Los fármacos empleados fueron nivolumab (n = 82), pembrolizumab (n = 28), atezolizumab (n = 13), durvalumab (n = 2), ipilimumab (n = 1) y la combinación anti-CTLA-4/PD-1 (n = 6). El 38, 6% (n = 51) desarrollaron EAI, de tipo gastrointestinal en el 12, 9% (n = 17). De ellos, el 47% (n = 8) requirieron esteroides, y un paciente precisó cirugía por perforación intestinal. En el 3, 03% (n = 4) se objetivaron EAI hepáticos grado I: el 50% (n = 2) requirieron corticoterapia y en un paciente fue preciso interrumpir el tratamiento. Entre los pacientes con tratamiento combinado, el 66, 6% (n = 4) presentaron EAI gastrointestinales. La incidencia de EAI no se relacionó con la edad, ni con el sexo, ni con la respuesta al fármaco empleado. Conclusiones Los EAI gastrointestinales figuran entre los más frecuentemente observados en pacientes en tratamiento con ICI. El manejo multidisciplinar y un mayor conocimiento de dichos eventos podrían ayudarnos a reducir su morbilidad, así como las interrupciones del tratamiento. Introduction Immune checkpoint inhibitors (ICIs) are effective agents against several malignancies. However, they are associated with gastrointestinal and liver immune-related adverse events (GI-IrAEs and LI-IrAEs), which can lead to their temporary or permanent discontinuation. Aim The aim of this study was to evaluate the efficacy and gastrointestinal and liver toxicity of ICIs in oncological treatments in actual clinical practice. Material and methods Patients with advanced cancer who received at least 1 ICI dose between May 2015 and September 2018 were retrospectively assessed. Results 132 patients with non-small cell lung cancer (65.15%, n = 86); melanoma (22.7%, n = 30); renal carcinoma (9.09%, n = 12); and other tumours (3%, n = 4) were included. The treatments administered were nivolumab (n = 82), pembrolizumab (n = 28), atezolizumab (n = 13), durvalumab (n = 2), ipilimumab (n = 1) and the antiCTLA-4/PD-1 combination (n = 6). In total, 51 patients (38.6%) developed IrAEs, 17 (12.9%) of which experienced GI-IrAEs. Of these, 8 (47%) needed steroids and 1 patient required surgery due to intestinal perforation. Grade I Li-IrAEs were observed in 4 patients (3.03%): 2 (50%) required corticosteroids and 1 patient had to discontinue treatment. Four patients (66.6%) who received combination therapy experienced GI-IrAEs. IrAE incidence were not associated with age, gender or drug response. Conclusions GI-IrAEs are one of the most common adverse events in patients receiving ICIs. A multidisciplinary approach and a greater understanding of these events could help to reduce morbidity and therapy discontinuation.

Background The Global Leadership Initiative on Malnutrition (GLIM) provided a new approach for the diagnosis of malnutrition based on a number of phenotypic and etiologic criteria. However, different diagnostic criteria could potentially lead to heterogeneity in the diagnosis. We identified different subsets of criteria to define malnutrition in a cohort of elder nursing-home residents and investigated their clinical utility in terms of 1-year survival. Methods Our study included all residents (n = 485) from 3 nursing homes. We proposed 12 GLIM models based on different phenotypic and etiologic criteria. The main outcome was 1-year all-cause mortality. We also assessed the sensitivity and specificity for different phenotypic criteria using time-dependent receiver operating characteristic curves, and cutoff values were calculated. Results During 1 year of follow-ups, 94 deaths occurred. The prevalence of malnutrition was 13.5% for models based on reduced food intake (RFI) and 10.45% for models based on inflammation associated with acute disease (IAD). Unadjusted Cox regression analyses showed that malnutrition was associated with a 2.31- to 4.64-fold increase in mortality when diagnosed using IAD-dependent models or with a 1.37- to 1.78-fold increase in mortality using RFI-dependent models. Cutoffs associated with mortality for the phenotypic criteria were lower than those recommended in the GLIM criteria. Conclusion This study describes the association of several variations of the GLIM model with 1-year mortality in nursing-home residents. However, our data suggest a high heterogeneity to fulfill the GLIM criteria and the necessity of finding specific, tailored cutoff points for the studied populations.

Oral phase dysphagia is dependent on ability to chew. As people age, general muscle atrophy contributes to decreased masseter strength. The main objective of this study was to assess the relationship between the thickness of the masseter muscle measured by ultrasonography and the presence of dysphagia in a group of institutionalized elderly people. As a secondary objective, we aimed to establish cutoff points of masseters muscle thickness (MMT) to identify elderly individuals at risk of oral dysphagia.Cross-sectional study of all residents from 3 nursing homes. All individuals underwent ultrasonographic measurements of left and right MMT and were classified according to the presence of dysphagia assessed by both the EAT-10 screening questionnaire and the volume-viscosity swallow test (V-VST).469 patients (69% women, mean age 84.7 yrs) were recruited. Dysphagia was present in 41.6% and 26% of individuals according the EAT-10 and V-VST, respectively. Multivariate logistic regression showed that 1 mm increase in MMT reduced the risk of dysphagia by 21% according to the EAT-10 tool and by 30% using the V-VST after adjusting for age, sex, mini-nutritional assessment score, and body mass index. We used receiver operative characteristic (ROC) curves to identify cutoff points of MMT to detect dysphagic individuals according to either EAT-10 or V-VST.The MMT measured by ultrasonography is reduced in elderly individuals with dysphagia. Based on MMT, clinicians may be better informed about the patients'´ ability to masticate solid foods and identify potential nutrient deficiencies in geriatric settings.

Adipose tissue (AT) expands under obesogenic conditions. Yet, when the growth exceeds a certain limit, AT becomes dysfunctional and surplus lipids start depositing ectopically. Polymerase I and transcription release factor (PTRF) has been proposed as a mechanism leading to a dysfunctional AT by decreasing the adipogenic potential of human adipocyte precursors. However, whether or not PTRF can be secreted by the adipocytes into the bloodstream is not yet known. For this work, PTRF presence was investigated in plasma. We also produced a recombinant PTRF (rPTRF) and examined its impact on the functional interactions between the adipocyte and the hepatocyte in vitro. We demonstrated that PTRF can be found in human plasma, and is at least in part, carried by exosomes. In vitro treatment with rPTRF increased the hypertrophy and senescence of 3T3-L1 adipocytes. In turn, those rPTRF-treated adipocytes increased lipid accumulation in hepatocytes. Lastly, we found a positive correlation between circulating PTRF and the concentration of PTRF in the visceral fat depot. All these findings point toward the presence of an enlarged and dysfunctional visceral adipose tissue which secretes PTRF. This circulating PTRF behaves as an adipokine and may partially contribute to the well-known detrimental effects of visceral fat accumulation.

The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds. To study the influence of the ribosomal antibiotic linezolid on adipokine production, we analyzed its effects on adipocyte secretome. Linezolid, at therapeutic concentrations, modifies the levels of apolipoprotein E and several adipokines and proteins related with the extracellular matrix. This antibiotic also alters the global methylation status of human adipose tissue-derived stem cells and, therefore, its effects are not limited to the exposure period. Besides their consequences on other tissues, xenobiotics acting on the adipocyte oxidative phosphorylation system alter apolipoprotein E and adipokine production, secondarily contributing to their systemic effects., Graphical abstract fx1, Highlights • Linezolid decreases oxidative phosphorylation system capacity. • Linezolid reduces adipocyte differentiation from human adipose-derived stem cells. • Linezolid modifies APOE, adipokine and extracellular matrix proteins levels. • Linezolid changes DNA methylation of human adipose tissue-derived stem cells. • Xenobiotics, acting on adipocyte oxidative phosphorylation, affect human health.

Pomegranate juice (PJ) is a beverage with potential beneficial effects due to its high content of polyphenols. The objective of this study is to explore at a molecular level the direct properties of PJ and its two main polyphenolic components, punicalagin and ellagic acid, on adipocyte functions. Increasing doses of PJ were tested using radiometric methods to determine amine oxidase activities in human adipose tissue preparations. The influences on lipogenic and lipolytic activity were also assessed by radiochemical and colorimetric assays. The results showed a dose-dependent capacity of PJ to inhibit the monoamine oxidase and the semicarbazide-sensitive amine oxidase activities present in human adipose tissue. PJ also inhibited lipogenesis and lipolysis in mouse and human adipose cells, while punicalagin and ellagic acid inhibited lipolysis rather than lipogenesis. However, the combination of punicalagin and ellagic acid resulted in a synergistic action in impairing MAO activity or basal glucose incorporation into lipids.

Aim The facilitative glucose transporter GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. GLUT12 is expressed in insulin-sensitive tissues such as adipose tissue. The aim of this work was to investigate GLUT12 expression and hormonal regulation in 3T3-L1 adipocytes and in adipose tissue of lean and diet-induced obese mice. Methods Uptake studies were performed using radio-labelled sugars; α-methyl-d-glucose (αMG) was used as specific substrate of GLUT12. Expression and localization of GLUT12 in adipocytes were investigated by western blot and immunohistochemical methods. Results GLUT12 is expressed in the peri-nuclear region of mouse adipocytes. Insulin, by AKT activation, and TNF-α, by AMPK activation, increase αMG uptake by inducing GLUT12 translocation to the membrane. In contrast, leptin and adiponectin decrease GLUT12 activity through its internalization. Under hypoxia conditions GLUT12 expression is upregulated. The response of GLUT12 to TNF-α, leptin, adiponectin and hypoxia is the opposite to that of GLUT4. In diet-induced obese mice and obese subjects, GLUT12 protein is decreased. Intraperitoneal injection of insulin increases AKT phosphorylation and GLUT12 expression, but this effect is lost in obese animals. Conclusion We hypothesize that GLUT12 would contribute to modulate sugar absorption in physiological and pathophysiological situations such as obesity.

The juices of berries or red fruits are appreciated as a source of antioxidants with potential health effects. However, they are rich in carbohydrates, an aspect that could be considered negative in view of diabetes and obesity epidemics. Indeed, it is the high polyphenol content of these beverages that is beneficial. When drinking such natural beverages, the consumers have the feeling of following a diet rich in fruit, recognized to reduce the risk of oxidative stress, cardiovascular injury, cancer, and neurodegenerative disorders. In this chapter, the polyphenol content will be compared between cranberry (Vaccinium macrocarpon), blueberry (Vaccinium myrtillus), sour cherry (Punica granatum), and pomegranate (P. granatum) juices. These juices are not a source of resveratrol, the most known polyphenol found in red wines, but the phenolic compounds they contain (punicalagins, ellagic acid, phenolic acids, and kuromanin) are more than mere antioxidants. These polyphenols exhibit superoxide radical scavenging activity and bacteriostatic properties and are protective for their plant of origin. Once ingested, they interact with various enzymes in human tissues, and with intestinal microbiota. We will focus attention on the interplay between extracts of such juices and monoamine oxidase (MAO) activity. MAO is involved in the metabolism of brain neurotransmitters and is expressed in peripheral tissues such as adipose tissue and produces hydrogen peroxide when degrading dietary amines (e.g., tyramine). We report that lyophilisates of fruit juices and their polyphenols inhibit human MAO. In addition, the red fruit polyphenols inhibit alpha-glucosidase, a key enzyme of glucose metabolism. Thus, polyphenols of red fruits juices should have beneficial effects on consumers not only in terms of antioxidant potential, but also as a consequence of modulation of amine degradation and metabolism, potentially acting on the mood and adiposity of the consumers.

e24065 Background: Malnutrition is one of the most prevalent problems among oncological patients. It reduces the response to treatments and negatively impacts survival. In 2019, a consensus criteria for diagnosing malnutrition (GLIM criteria) were proposed by most scientific nutrition societies. The objective of our work is 1) to assess the diagnostic capacity of the GLIM criteria in ambulatory patients with cancer and 2) to compare the GLIM with the ESPEN criteria to evaluate the contributions of these new criteria with respect to the existing ones. Methods: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department in the Lozano Blesa Clinical Hospital in Zaragoza (Spain). One hundred and sixty-five outpatients with tumors in the upper gastrointestinal tract, head and neck, and colorectal locations were recruited. All of them received the MST, MUST, and Nutriscore screening tools along with the ESPEN and GLIM diagnostic criteria. Results: The prevalence of malnutrition was 46.7% according to the GLIM criteria and 21.2% using the ESPEN tool. Patients diagnosed by GLIM had a higher body mass index (BMI, 24.3 kg/m2) and muscle mass (MM, 16.1 kg/m2) than those diagnosed by ESPEN (21.2 kg/m² and 14.3 kg/m2 respectively, both p = 0.001). The MST, MUST, and Nutriscore tools had a higher degree of concordance with GLIM compared to ESPEN (MST 0.53 vs 0.26; MUST 0.36 vs 0.66; Nutriscore 0.28 vs 0.54). Conclusions: The found prevalence of malnutrition in cancer patients is higher using the GLIM instead of ESPEN criteria. This disparity can be explained at least in part by the difficulty of the ESPEN criteria for malnutrition to diagnose patients with high baseline BMI or MM. The use of criteria with greater sensitivity, such as the new GLIM criteria, could help early diagnosis and thus early intervention in cancer patients. [Table: see text]

The Apolipoprotein E (APOE) gene encodes for three isoforms in the human population (APOE2, APOE3 and APOE4). Whereas the role of APOE in lipid metabolism is well characterized, the specific metabolic signatures of the APOE isoforms during metabolic disorders, remain unclear.To elucidate the molecular underpinnings of APOE-directed metabolic alterations, we tested the hypothesis that APOE4 drives a whole-body metabolic shift toward increased lipid oxidation.We employed humanized mice in which the Apoe gene has been replaced by the human APOE*3 or APOE*4 allele to produce human APOE3 or APOE4 proteins and characterized several mechanisms of fatty-acid oxidation, lipid storage, substrate utilization and thermogenesis in those mice.We show that, whereas APOE4 mice gained less body weight and mass than their APOE3 counterparts on a Western-type diet (P0.001), they displayed elevated insulin and homeostatic model assessment, markers of insulin resistance (P=0.004 and P=0.025, respectively). APOE4 mice also demonstrated a reduced respiratory quotient during the postprandial period (0.95±0.03 versus 1.06±0.03, P0.001), indicating increased usage of lipids as opposed to carbohydrates as a fuel source. Finally, APOE4 mice showed increased body temperature (37.30±0.68 versus 36.9±0.58 °C, P=0.039), augmented cold tolerance and more metabolically active brown adipose tissue compared with APOE3 mice.These data suggest that APOE4 mice may resist weight gain via an APOE4-directed global metabolic shift toward lipid oxidation and enhanced thermogenesis, and may represent a critical first step in the development of APOE-directed therapies for a large percentage of the population affected by disorders with established links to APOE and metabolism.

Background and aims The human Apolipoprotein E ( APOE ) gene is polymorphic. The APOE*4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (MetS) as it may affect all MetS components. We hypothesize that the common APOE4 polymorphism differentially regulates MetS risk and that this association might be modulated by body fatness. Methods & results We used body mass index (BMI) as surrogate of fatness and cross-sectionally studied the prevalence of MetS in 4408 middle-aged men of the Aragon Workers Health Study (AWHS). Our analysis revealed i) a gene dose-dependent association between APOE*4 allele and increased risk for MetS, ii) this association primarily derived from the overweight subjects. For these individuals, the MetS risk was higher in APOE*4 carriers than in non-carriers (Odds Ratio = 1.31; 95% CI, 1.03-1.67). Additionally, we examined 3908 healthy young individuals from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, followed-up for 25 years. Compared with APOE*4 non-carriers, APOE*4 presence significantly increased the risk of developing MetS (Hazard Ratio, 1.12; 95% CI, 1.00-1.26). Again, an interplay between APOE*4 and the longitudinal development of fatness towards the onset of MetS occurred throughout the study. For individuals with BMI gain below the median, the cumulative onset rate of MetS was significantly higher in APOE*4 carriers than in the non-carriers (HR, 1.29; 95% CI, 1.07-1.55). Conclusions Carrying APOE*4 alleles increases MetS in a dose-dependent manner, characterizing individual's APOE genotype might help identify at-risk subjects for preventive intervention.

Various amino acid (AA) metabolites are used as supplements to facilitate metabolic control and enhance responsiveness of insulin-sensitive tissues. β-hydroxy-β-methylbutyrate (HMB) is a leucine metabolite proposed to prevent muscle wasting and to mitigate insulin resistance. Taurine, commonly added to energizing drinks, is a metabolite of methionine and cysteine present in bile juice, and proposed to be involved in lipid digestion and to be pro-lipolytic in adipocytes. N-methyltyramine (NMT) is a phenylalanine metabolite found in orange juices at 0.1-3 ppm while its effects on lipid mobilization remain controversial. Here, the putative lipolytic effects of these AA metabolites were studied and it was tested whether they could enhance insulin antilipolytic response in adipocytes. Release of glycerol and non-esterified fatty acids (NEFAs) was measured after a 2-h incubation of adipocytes obtained from control and diet-induced obese mice or from obese patients. In mouse, none of the tested AA derivatives was lipolytic from 1 μM to 1 mM. These compounds did not improve insulin antilipolytic effect or isoprenaline lipolytic action, except for 1 mM NMT that impaired triacylglycerol breakdown in obese mice. In human adipocytes, HMB and taurine were not lipolytic, while NMT weakly activated glycerol and NEFA release at 1 mM. However, 100 μM NMT impaired isoprenaline-stimulated lipolysis in a manner that was hardly added to insulin antilipolytic effect. Since none of these AA derivatives acutely helped or replaced insulin antilipolytic effect in adipocytes, the present in vitro observations do not support their proposed insulin-sensitizing properties. Moreover, NMT, HMB, and taurine were not notably lipolytic.

Objectives Anthropometry is an easy and noninvasive method to evaluate nutritional status in institutionalized elderly people who are often bedridden. The aim of this study was to investigate the relationship between the neck circumference (NC) and nutritional status of elderly nursing home residents and to find cutoff points for NC size to identify individuals at risk of malnutrition. Methods A cross-sectional study was developed with data collected from 352 elderly people living in five public nursing homes. Different anthropometric measures and the Mini Nutritional Assessment (MNA) were used to determine nutritional status. Receiver operating characteristic (ROC) curves were built for each anthropometric variable to determine their sensitivity and specificity for predicting the risk of malnutrition according to the MNA. Results The mean age of the participants (59% females) was 83 years old. In total, 48.3% of women and 45.5% of men were at risk of malnutrition according to their MNA scores. All anthropometric measurements were highly intercorrelated in both men and women, indicating a high degree of collinearity. Bootstrapped linear regression was used to assess the strength of the association between an individuals' nutritional status and their anthropometric parameters. Calf circumference and NC presented the best predictive value with the highest sensitivity for diagnosing the risk of malnutrition in both institutionalized elderly men and women. The best cutoff points of NC to identify elderly nursing home residents at risk of malnutrition were 35.2 cm for females and 37.8 cm for males. Conclusions NC is associated with other classical anthropometric parameters and malnutrition status in elderly people living in nursing homes.

Purpose Oral squamous cell carcinoma (OSCC) is a highly prevalent type of immunogenic cancer with a low survival rate in patients with comorbidities owing to toxic habits. Materials and Methods A retrospective cohort study was conducted of patients with resectable OSCC at a tertiary Spanish hospital from 2011 to 2014. The primary predictor variables were comorbidity and immune biomarkers. Comorbidity was assessed using the Adult Comorbidity Evaluation–27 (ACE-27) and scored from 1 to 3 (mild to severe decompensation, respectively). The immune biomarkers were neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The primary outcome variable was 5-year overall survival (OS). Other study variables were stage, margin, and neck management. Receiver operating characteristic curves were built for each ratio. For the survey of immune biomarkers, area under the curve was computed to determine cutoff points and investigate their association with OS. Kaplan-Meier estimates of survival and Cox proportional hazards models were used for longitudinal analysis. Results Overall 215 patients were identified (median age, 67 yr; range, 32 to 96 yr; median follow-up, 31 months; range, 7 to 78 months); 159 patients had at least 1 comorbid condition. Results showed that a severe comorbidity (according to the ACE-27) increased the risk of death by 4 times in patients with OSCC regardless of stage. NLR, dNLR, LMR, and PLR were associated with OS in the univariate study. Cutoff points to predict increased mortality were 3, 1.9, 2.6, and 66 for NLR, dNLR, LMR, and PLR, respectively. Age, comorbidity, stage, margins, and management of the neck were important independent predictors of decreased OS in OSCC. PLR was marginally associated with OS in the multivariate model. Conclusion These results suggest that comorbidity and NLR, dNLR, LMR, and PLR are associated with 5-year OS in patients with resectable OSCC.

Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty mu M of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPAR gamma, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity. This project has been partially supported by grants from Interreg POCTEFA, European Union, via Refbio-the Pyrenees Biomedical Network, also by the project PI17/02268 (Instituto de Salud Carlos III. Madrid, Spain) and by Fondo Europeo de Desarrollo Regional (FEDER) funds: "Una manera de hacer Europa".