Hematopoietic Stem Cell Transplantation Impact on Patients' Perceived Quality of Life: A Longitudinal Study.

OBJECTIVE: The aim of this paper was to evaluate the quality of life of adult patients with onco-hematological disease treated with hematopoietic stem cell transplantation up to two years post-transplantation. METHOD: A quantitative, observational, longitudinal, and analytical study was conducted with 121 participants diagnosed with onco-hematological cancer who underwent hematopoietic stem cell transplantation between October 2017 and September 2019, with a 2-year post-transplantation follow-up, of whom only 39 completed the study. The Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire and its subscales, Functional Assessment of Cancer Therapy-General (FACT-BMT) and Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI), developed by the Functional Assessment of Chronic Illness Therapy (FACIT) and validated for Spain, were used to assess quality of life. RESULT: The average age for hematopoietic stem cell transplantation was 54 years, with a majority of male participants. The evaluation of quality of life showed a decrease at the time of hospital discharge, followed by a progressive improvement up to one year after the transplantation. There was a significant difference in the quality of life questionnaire scores between both sexes during all stages of the research, with higher scores in male participants. The length of hospital stay significantly affected patients' physical and functional well-being, and marital status was related to differences in the perception of quality of life. CONCLUSIONS: Despite the initial decrease in quality of life for patients undergoing hematopoietic stem cell transplantation, levels of quality of life similar to baseline are regained one year after the transplantation. Sociodemographic variables are related to how these patients perceive their quality of life. However, further studies with a larger sample size are needed for more precise results.

Diagnostic clues for hyalinizing trabecular tumor on fine needle aspiration cytology.

Objectives: The hyalinizing trabecular tumor (HTT) is a rare benign neoplasm of the thyroid gland. This neoplasm has overlapping cytological features with Papillary Thyroid Carcinoma, Medullary Carcinoma and Follicular Neoplasm with Nuclear Features of Papillary Carcinoma. This can lead to misdiagnosis of malignancy in fine needle aspiration (FNA) cytology specimens with unnecessary total thyroidectomy. The aim of this study is to determine if there are some cytological features that could help us to suspect HTT on FNA specimens and avoid radical surgery. Material and Methods: With this purpose we have collected 6 cases diagnosed of HTT in Hospital Clínico San Carlos of Madrid (Spain) in the last 10 years and reviewed the cytological specimens. Result: We conclude that the presence of hyaline material in FNA specimens of HTT is a constant feature being a diagnostic clue. We must be cautious not to confuse it with dense colloid or amyloid material, the latter seen in Medullary Carcinoma. Papillary architecture and fibrovascular cores are not present in a HTT. Special stains as ki-67, calcitonin and Congo Red staining could help us in achieving the correct diagnosis. Conclusion: We feel the cytopathologists must be aware of the distinguishing features of this lesion, mainly the typical hyaline material to achieve a proper diagnosis and be able to reduce unnecessary aggressive management of these patients.

Anal cytology: Diagnosis of intestinal spirochaetosis.

OBJECTIVE: A case of intestinal spirochaetosis diagnosed in anal cytology is presented. METHODS: An anal liquid-based cytology was performed and stained with Papanicolau and Warthin-Starry stains. RESULTS: An apical filamentous "fringe" was identified in columnar cells groups. CONCLUSION: Anal cytology is a potential tool for intestinal spirochaetosis diagnosis.

Circulating vitamin D levels and colorectal cancer risk: A meta-analysis and systematic review of case-control and prospective cohort studies.

The associations between circulating vitamin D concentrations and total and site-specific colorectal cancer (CRC) incidence have been examined in several epidemiological studies with overall inconclusive findings. The aim of this systematic review and meta-analysis of both case-control and prospective cohort studies was to evaluate the association between CRC and circulating levels of vitamin D. The main exposure and outcome were circulating total 25(OH)D and CRC, respectively, in the overall population (i.e., all subjects). Two reviewers, working independently, screened all the literature available to identify studies that met the inclusion criteria (e.g., case-control or prospective cohort studies, published in English, and excluding non-original papers). Data were pooled by the generic inverse variance method using a random or fixed effect model, as approriate. Heterogeneity was identified using the Cochran's Q-test and quantified by the I2 statistic. Results were stratified by study design, sex, and metabolite of vitamin D. Sensitivity and subgroup analyses were also performed. A total of 28 original studies were included for the quantitative meta-analysis. Meta-analyses comparing the highest vs lowest categories, showed a 39% lower risk between levels of total 25(OH)D and CRC risk (OR (95% CI): 0.61 (0.52; 0.71); 11 studies) in case-control studies; whereas a 20% reduced CRC risk in prospective cohort studies (HR (95% CI): 0.80 (0.66; 0.97); 6 studies). Results in women mirrored main results, whereas results in men were non-significant in both analyses. Our findings support an inverse association between circulating vitamin D levels and CRC risk.

Physical activity and metabolic syndrome severity among older adults at cardiovascular risk: 1-Year trends.

BACKGROUND AND AIMS: Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity (LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk. METHODS AND RESULTS: Prospective analysis of 55-75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses' Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time. CONCLUSION: Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk.

An Epigenetic Signature is Associated with Serum 25-Hydroxyvitamin D in Colorectal Cancer Tumors.

INTRODUCTION: Vitamin D has been widely associated with colorectal cancer (CRC) through different insights. This study aims to explore the association between serum 25-hydroxyvitamin D (25(OH)D) and the global DNA methylation in tumor from CRC patients. METHODS AND RESULTS: A genome-wide DNA methylation analysis is conducted in 20 CRC patients under categorical (10 patients have 25(OH)D <30 ng mL-1 ; 10 patients with 25(OH)D ≥30 ng mL-1 ) and continuous models of 25(OH)D. A total of 95 differentially methylated CpGs (DMCpGs) are detected under the categorical model (false discovery rate (FDR) < 0.05), while 16 DMCpGs are found under the continuous model. Regional analysis showed eight vitamin D-associated differentially methylated regions (DMR). Between them, a DMR is the most significant at cAMP-Dependent Protein Kinase Inhibitor Alpha (PKIA) locus. Furthermore, seven genes, including PKIA gene, have more or equal than two significant DMCpGs. The protein networking analysis found pathways implicated in cell adhesion and extracellular matrix, as well as signaling transduction. CONCLUSIONS: This study identifies novel epigenetic loci associated with serum 25(OH)D status. Interestingly, also, a positive association between vitamin D and DNA methylation in the CRC context is found, suggesting a role in CRC. Further studies are warranted to clarify and replicate these results.

Vitamin D Intake and the Risk of Colorectal Cancer: An Updated Meta-Analysis and Systematic Review of Case-Control and Prospective Cohort Studies.

Obesity, a sedentary lifestyle, high red meat consumption and alcohol, and tobacco are considered the driving factors behind colorectal cancer (CRC) worldwide. Both diet and lifestyle are recognized to play an important role in the prevention of CRC. Forty years later, the vitamin D-cancer hypothesis is considered consistent. However, the relationship between low vitamin D intake and CRC is still controversial. The aim of this meta-analysis is to determine the associations between Vitamin D intake and CRC. MEDLINE-PubMed and Cochrane databases were searched up to May 2020 for studies evaluating the association between vitamin D intake (from foods and supplements) and CRC. Two reviewers, working independently, screened all titles and abstracts to identify the studies that met the inclusion criteria (case-control or prospective cohort (PC) studies published in English). Data were pooled by the generic inverse variance method using a random or fixed effect model. Heterogeneity was identified using the Cochran Q-test and quantified by the I2 statistic. A total of 31 original studies were included for the quantitative meta-analysis, comprising a total 47.540 cases and 70.567 controls in case-control studies, and a total of 14.676 CRC-incident cases (out of 808.130 subjects in PC studies) from 17 countries. A significant 25% lower risk was reported comparing the highest vs. the lowest dietary vitamin D consumption and CRC risk (odds ratio (95% confidence interval): 0.75 (0.67; 0.85)) in case-control studies, whereas a non-significant association was reported in case of prospective studies (hazard ratio (95% confidence interval): 0.94 (0.79; 1.11). The present meta-analysis demonstrates that high dietary vitamin D is associated to CRC prevention. However, larger and high-quality prospective studies and clinical trials are warranted to confirm this association.

Dietary vitamin D intake and colorectal cancer risk: a longitudinal approach within the PREDIMED study.

PURPOSE: We evaluated whether the intake of dietary vitamin D is associated with the incidence of both colorectal cancer (CRC) and colon cancer in the framework of the PREDIMED cohort of older adults at high cardiovascular risk. METHODS: We analyzed data from 7216 men and women (55-80 years) without CRC at baseline from the PREvención con DIeta MEDiterránea study. Baseline consumption of vitamin D was assessed using a validated 137-item food frequency questionnaire. Cox proportional hazards ratios (HRs) of CRC and colon cancer incidence were estimated for quartiles and per 1-SD of baseline vitamin D intake. RESULTS: During a median follow-up of 6 years, we documented 97 incident CRC cases after the exclusion of subjects with no baseline dietary data and/or outliers of energy intake. A non-significant HRs and 95% confidence intervals (CIs) of CRC for the comparison of extreme quartiles (4th vs 1st) of vitamin D intake were observed [0.55 (0.30-1.00), P for trend = 0.072], whereas it was significant for colon cancer incidence alone [0.44 (0.22-0.90), P for trend = 0.032]. However, this association became significant in CRC and colon cancer incidence, after excluding 391 subjects consuming baseline vitamin D and/or calcium medication or prescribed supplements [0.52 (0.28-0.96) and 0.41 (0.12-0.85), respectively]. CONCLUSION: A higher dietary intake of vitamin D was significantly associated with a reduced CRC risk in individuals at high cardiovascular risk.

Choline Metabolism and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Study.

BACKGROUND: Few studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations. METHODS: Prospective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvención con DIeta MEDiterránea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO and its precursors were semi-quantitatively profiled with liquid chromatography tandem mass spectrometry. Odds ratios were estimated with multivariable conditional logistic regression models. RESULTS: After adjustment for classical risk factors and accounting for multiple testing, participants in the highest quartile vs. the lowest quartile of baseline choline and betaine levels had a higher risk of AF [OR (95% CI): 1.85 (1.30-2.63) and 1.57 (1.09-2.24), respectively]. The corresponding OR for AF for extreme quartiles of dimethylglycine was 1.39 (0.99-1.96). One SD increase in log-transformed dimethylglycine was positively associated with AF risk (OR, 1.17; 1.03-1.33). The corresponding ORs for HF for extreme quartiles of choline, betaine, and dimethylglycine were 2.51 (1.57-4.03), 1.65 (1.00-2.71) and 1.65 (1.04-2.61), respectively. TMAO and L-carnitine levels were not associated with AF or HF. CONCLUSIONS: Our findings support the role of the choline metabolic pathway in the pathogenesis of AF and HF.

Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk.

BACKGROUND AND AIMS: The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome. METHODS: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≤1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure. RESULTS: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≤1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48]). CONCLUSIONS: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed.

Association between Serum Vitamin B12 and Global DNA Methylation in Colorectal Cancer Patients.

Vitamin B12 has been widely related to methionine metabolism, which is an essential component for biological methylation reactions, including DNA methylation. However, the relationship between vitamin B12 and DNA methylation is still controversial. In addition, there is increasing evidence for the association between vitamin B12 and the risk of colorectal cancer (CRC), although results of this association need to be assessed with caution. For this purpose, we hypothesized that serum vitamin B12 could be associated with global DNA methylation in the CRC context. To test this hypothesis, we studied the association between global DNA methylation through long interspersed nuclear element-1 (LINE1) in CRC patients under the 25th percentile of serum vitamin B12. We found that the high vitamin B12 group had low LINE1 methylation in both tumor area and peripheral blood mononuclear cells (PBMCs) than the low serum vitamin B12 group. LINE1 methylation levels were significantly lower in tumor area compared to the adjacent tumor-free area, only in the high vitamin B12 group. LINE1 methylation in visceral adipose tissue (VAT) and PBMCs were correlated with tumoral, inflammatory, and insulin metabolism markers. However, the interaction between LINE1 methylation and vitamin B12 levels was associated with neoadjuvant therapy in the regression analysis only in men, suggesting a beneficial relationship. In conclusion, our results reported an inverse association between DNA methylation and vitamin B12 in the CRC context, which suggests that vitamin B12 may be implicated in an epigenetic state or mediation in CRC.

Association between variation of circulating 25-OH vitamin D and methylation of secreted frizzled-related protein 2 in colorectal cancer.

BACKGROUNDS: Colorectal cancer (CRC) results from the accumulation of epigenetic and genetic changes in colon cells during neoplasic transformation, which the activation of Wingless (Wnt) signaling pathway is a common mechanism for CRC initiation. The Wnt pathway is mainly regulated by Wnt antagonists, as secreted frizzled-related protein (SFRP) family. Indeed, SFRP2 is proposed as a noninvasive biomarker for CRC diagnosis. Vitamin D also antagonizes Wnt signaling in colon cancers cells. Several studies showed that vitamin D was able to alter DNA methylation, although this mechanism is not yet clear. Therefore, the aim of this study was to find an association between circulating 25-OH vitamin D (30th percentile of vitamin D) and the SFRP2 methylation. METHODS: A total of 67 CRC patients were included in the study. These patients were subdivided into two groups based on their 30th percentile vitamin D (20 patients were below, and 47 participants were above the 30th percentile of vitamin D). We investigated the SFRP2 methylation in peripheral blood mononuclear cells (PBMCs), visceral adipose tissue (VAT), CRC tumor tissue, and adjacent tumor-free area. We also determined the relationship between SFRP2 methylation and methylation of carcinogenic and adipogenic genes. Finally, we tested the effect of vitamin D on the SFRP2 methylation in human colorectal carcinoma cell lines 116 (HCT116) and studied the association of neoadjuvant therapy under the 30th percentile vitamin D with SFRP2 promoter methylation. RESULTS: SFRP2 methylation in tumor area was decreased in patients who had higher levels of vitamin D. SFRP2 promoter methylation was positively correlated in tumor area with insulin and homeostasis model assessment of insulin resistance (HOMA-IR) but negatively correlated with HDL-c. SFRP2 methylation was also correlated with T cell lymphoma invasion and metastasis 1 (TIAM1) methylation in tumor area and CCAAT/enhancer-binding protein alpha (C/EBPα) in VAT. Treatment with vitamin D did not affect SFRP2 methylation in HCT116 cell line. Finally, neoadjuvant treatment was correlated with higher circulating 25-OH vitamin D and SFRP2 methylation under linear regression model. CONCLUSION: Our results showed that higher circulating vitamin D is associated with low SFRP2 promoter methylation. Therefore, our results could suggest that vitamin D may have an epigenetic effect on DNA methylation. Finally, higher vitamin D could contribute to an improvement response to neoadjuvant treatment.

Association between the 2018 WCRF/AICR and the Low-Risk Lifestyle Scores with Colorectal Cancer Risk in the Predimed Study.

Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed to assess the association between CRC incidence and adherence to two emerging lifestyles indices (2018 WCRF/AICR score and another low-risk lifestyle (LRL) score comprising smoking status, alcohol consumption, physical activity, diet, and body mass index) in the Spanish PREvencion con DIeta MEDiterranea (PREDIMED) cohort. We studied 7216 elderly men and women at high cardiovascular risk. The 2018 WCRF/AICR and LRL scores were calculated. Multivariable Cox proportional regression models were fitted to estimate the HRs (hazard ratios) and 95% confidence intervals (CIs) for incident CRC events. During a median interquartile range (IQR) follow-up of 6.0 (4.4-7.3) years, 97 CRC events were considered. A significant linear association was observed between each 1-point increment in the WCRF/AICR score (score range from 0 to 7) and CRC risk (HR (95% CI) = 0.79 (0.63-0.99)). Similarly, each 1-point increment in the LRL score (score range from 0 to 5) was associated with a 22% reduction in CRC risk (0.78 (0.64-0.96)). Adhering to emergent lifestyle scores might substantially reduce CRC incidence in elderly individuals. Further longitudinal studies, which take different lifestyle indexes into account, are warranted in the future.

Adult congenital heart disease in Spain: health care structure and activity, and clinical characteristics.

INTRODUCTION AND OBJECTIVES: To assess the structure of health care delivery and the clinical characteristics of adults with congenital heart disease (ACHD) attending specialized centers in Spain. METHODS: A survey was conducted among 32 Spanish centers in 2014. The centers were classified into 2 levels based on their resources. In 2017, a clinical dataset was collected of all consecutive patients attended for a 2-month period at these centers. RESULTS: A total of 31 centers (97%) completed the survey. Seven centers without specialized ACHD clinics were excluded from the analysis. In 2005, only 5 centers met the requirements for specific care. In 2014, there were 10 level 1 and 14 level 2 centers, with a total of 19 373 patients under follow-up. Health care structure was complete in most centers but only 33% had ACHD nurse specialists on staff and 29% had structured transition programs. Therapeutic procedures accounted for 99% and 91% of those reported by National Registries of Cardiac Surgery and Cardiac Catheterization, respectively. Among attended patients, 48% had moderately complex lesions and 24% had highly complex lesions. Although 46% of patients attending level 2 centers had simple lesions, 17% had complex lesions. CONCLUSIONS: The structure for ACHD health care delivery in Spain complies with international recommendations and is similar to that of other developed countries. Congenital heart diseases under specialized care consist mostly of moderately and highly complex lesions, even in level 2 centers. It would be desirable to reorganize patient follow-up according to international recommendations in clinical practice.

Dietary Polyphenol Intake is Associated with HDL-Cholesterol and A Better Profile of other Components of the Metabolic Syndrome: A PREDIMED-Plus Sub-Study.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

Plant-Based Fat, Dietary Patterns Rich in Vegetable Fat and Gut Microbiota Modulation.

Diet is advocated as a key factor influencing gut microbiota. Several studies have focused on the effect of different carbohydrates, mainly fiber, on gut microbiota. However, what remains to be elucidated is the impact of a key component of diet that is widely debated upon: dietary fats. This review highlights the importance of understanding the source, quality, and type of fats that could differentially modify the intestinal microbiome. Fats from plant-based sources such as nuts, or vegetable oils have shown positive alterations in gut microbiota biodiversity both in in vivo and in vitro studies. Nuts and other plant-based fat sources, dietary patterns (e.g., Mediterranean diet) rich in polyunsaturated and monounsaturated fats and, in some cases, polyphenols, and other phytochemicals, have been associated with increased bacterial diversity, as well beneficial butyrate-producing bacteria imparting a positive metabolic influence. It is with this interest, this narrative review brings together evidences on different plant-based fat sources, dietary patterns rich in vegetable fats, and associated changes in gut microbiota.

Successful cryoablation of dual atrioventricular nodal nonreentrant tachycardia: First reported cases.

We describe two consecutive adult males with incessant dual atrioventricular nodal nonreentrant tachycardia and associated severe cardiomyopathy. After invasive diagnosis, this is the first published report showing the successful outcome of this rare tachycardia with effective cryoablation. Cryothermal lesions in the roof of the proximal coronary sinus and right midseptal area lead to complete resolution of the tachycardia-mediated cardiomyopathy in the mid-term follow-up of our patients.

The Expression/Methylation Profile of Adipogenic and Inflammatory Transcription Factors in Adipose Tissue Are Linked to Obesity-Related Colorectal Cancer.

Obesity is well accepted as crucial risk factor that plays a critical role in the initiation and progression of colorectal cancer (CRC). More specifically, visceral adipose tissue (VAT) in people with obesity could produce chronic inflammation and an altered profile expression of key transcription factors that promote a favorable microenvironment to colorectal carcinogenesis. For this, the aim of this study was to explore the relationship between adipogenic and inflammatory transcription factors in VAT from nonobese, obese, and/or CRC patients. To test this idea, we studied the expression and methylation of CCAAT-enhancer binding protein type alpha (C/EBP-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in VAT from non-obese control, non-obese CRC subjects, overweight/obese control, and overweight/obese CRC patients and their correlation with anthropometric and biochemical variables. We found decreased expression of C/EBP-α in overweight/obese CRC patients in comparison with overweight/obese control subjects. PGC-1α and NF-κB were overexpressed in CRC patients independently of the BMI. NF-κB promoter was hypomethylated in overweight/obese CRC patients when compared to overweight/obese control individuals. In addition, multiple significant correlations between expression, methylation, and biochemical parameters were found. Finally, linear regression analysis showed that the expression of C/EBP-α and NF-κB and that NF-κB methylation were associated with CRC and able to explain up to 55% of CRC variability. Our results suggest that visceral adipose tissue may be a key factor in tumor development and inflammatory state. We propose C/EBP-α, PGC-1α and NF-κB to be interesting candidates as potential biomarkers in adipose tissue for CRC patients.

Plasma Metabolites Associated with Frequent Red Wine Consumption: A Metabolomics Approach within the PREDIMED Study.

SCOPE: The relationship between red wine (RW) consumption and metabolism is poorly understood. It is aimed to assess the systemic metabolomic profiles in relation to frequent RW consumption as well as the ability of a set of metabolites to discriminate RW consumers. METHODS AND RESULTS: A cross-sectional analysis of 1157 participants is carried out. Subjects are divided as non-RW consumers versus RW consumers (>1 glass per day RW [100 mL per day]). Plasma metabolomics analysis is performed using LC-MS. Associations between 386 identified metabolites and RW consumption are assessed using elastic net regression analysis taking into consideration baseline significant covariates. Ten-cross-validation (CV) is performed and receiver operating characteristic curves are constructed in each of the validation datasets based on weighted models. A subset of 13 metabolites is consistently selected and RW consumers versus nonconsumers are discriminated. Based on the multi-metabolite model weighted with the regression coefficients of metabolites, the area under the curve is 0.83 (95% CI: 0.80-0.86). These metabolites mainly consisted of lipid species, some organic acids, and alkaloids. CONCLUSIONS: A multi-metabolite model identified in a Mediterranean population appears useful to discriminate between frequent RW consumers and nonconsumers. Further studies are needed to assess the contribution of these metabolites in health and disease.

Plasma Metabolites Associated with Coffee Consumption: A Metabolomic Approach within the PREDIMED Study.

Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (≥50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56-0.64), 0.78 (95% CI 0.75-0.81) and 0.52 (95% CI 0.49-0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption.