Association of exposure to perfluoroalkyl substances (PFAS) and phthalates with thyroid hormones in adolescents from HBM4EU aligned studies.

BACKGROUND: Perfluoroalkyl substances (PFAS) and phthalates are synthetic chemicals widely used in various types of consumer products. There is epidemiological and experimental evidence that PFAS and phthalates may alter thyroid hormone levels; however, studies in children and adolescents are limited. AIM: To investigate the association of exposure to PFAS and phthalate with serum levels of thyroid hormones in European adolescents. METHODS: A cross-sectional study was conducted in 406 female and 327 male adolescents (14-17 years) from Belgium, Slovakia, and Spain participating in the Aligned Studies of the HBM4EU Project (FLEHS IV, PCB cohort, and BEA, respectively). Concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) were measured in sera from study participants, and urinary metabolites of six phthalates (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP) and the non-phthalate plasticizer DINCH® were quantified in spot urine samples. Associations were assessed with linear regression and g-computational models for mixtures. Effect modification by sex was examined. RESULTS: In females, serum PFOA and the PFAS mixture concentrations were associated with lower FT4 and higher FT3 levels; MEP and the sums of DEHP, DiNP, and DINCH® metabolites (∑DEHP, ∑DiNP, and ∑DINCH) were associated with higher FT4; ∑DEHP with lower FT3; and the phthalate/DINCH® metabolite mixture with higher FT4 and lower FT3. In males, PFOA was associated with lower FT4 and the PFAS mixture with higher TSH levels and lower FT4/TSH ratio; MEP and ∑DiNP were associated with higher FT4; and MBzP, ∑DEHP, and the phthalate/DINCH® metabolite mixture with lower TSH and higher FT4/TSH. PFOA, mono-(2-ethyl-5-hydroxyhexyl) phthalate (OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (oxo-MEHP), and monocarboxyoctyl phthalate (MCOP) made the greatest contribution to the mixture effect. CONCLUSIONS: Results suggest that exposure to PFAS and phthalates is associated with sex-specific differences in thyroid hormone levels in adolescents.

Exposure to perfluoroalkyl substances (PFAS) and association with thyroid hormones in adolescent males.

BACKGROUND: Perfluoroalkyl substances (PFAS) are found in a wide range of consumer products. Exposure to PFAS in children and adolescents may be associated with alterations in thyroid hormones, which have critical roles in brain function. OBJECTIVE: This study investigated the association between plasma concentrations of PFAS and serum levels of total triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) in adolescent males. METHODS: In 2017-2019, 151 boys from the Environment and Childhood (INMA)-Granada birth cohort, Spain, participated in a clinical follow up visit at the age of 15-17 years. Plasma concentrations of ten PFAS (PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFOS, and PFHxS) and serum thyroid hormones were measured in 129 of these boys. Linear regression analysis was performed to determine associations of individual PFAS with total T3, free T4, TSH, and free T4/TSH ratio, and quantile g-computation models were performed to assess the mixture effect. Additional models considered iodine status as effect modifier. RESULTS: PFOS was the most abundant PFAS in plasma (median = 2.22 µg/L), followed by PFOA (median = 1.00 µg/L), PFNA (median = 0.41 µg/L), and PFHxS (median = 0.40 µg/L). When adjusted by confounders (including age, maternal schooling, and fish intake), PFOA and PFUnDA were associated with an increase in free T4 (ß [95% CI] = 0.72 [0.06; 1.38] and 0.36 [0.04; 0.68] pmol/L, respectively, per two-fold increase in plasma concentrations), with no change in TSH. PFOS, the sum of PFOA, PFNA, PFOS, and PFHxS, and the sum of long-chain PFAS were marginally associated with increases in free T4. Associations with higher free T4 and/or total T3 were seen for several PFAS in boys with lower iodine intake (<108 µ/day) alone. Moreover, the PFAS mixture was association with an increase in free T4 levels in boys with lower iodine intake (% change [95% CI] = 6.47 [-0.69; 14.11] per each quartile increase in the mixture concentration). CONCLUSIONS: Exposure to PFAS, considered individually or as a mixture, was associated with an increase in free T4 levels in boys with lower iodine intake. However, given the small sample size, the extent of these alterations remains uncertain.

Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge.

Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2'-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.

Kisspeptin as potential biomarker of environmental chemical mixture effect on reproductive hormone profile: A pilot study in adolescent males.

BACKGROUND: Kisspeptin has been proposed as an effect biomarker to understand the mechanisms by which some environmental chemicals adversely affect the human reproductive system. OBJECTIVE: To ascertain whether kisspeptin serum protein and DNA methylation levels are associated with exposure to several environmental chemicals (individually and as a mixture) and serum reproductive hormone levels in adolescent males. METHODS: Three phenols (bisphenol A [BPA], methyl-paraben [MPB], and benzophenone-3 [BP3]); two toxic metals (arsenic and cadmium); and four metabolites of non-persistent pesticides, including insecticides (2-isopropyl-6-methyl-4-pyrimidinol [IMPy], malathion diacid [MDA], and dimethylcyclopropane carboxylic acid [DCCA]) and fungicides (ethylene thiourea [ETU]) were measured in first-morning urine samples of 133 adolescent males aged 15-17 years from the INMA-Granada cohort. In blood samples collected on the same day, KISS1 gene DNA methylation was measured at four CpGs from the Exon IV, as well as serum levels of kiss54 protein, total testosterone (T), estradiol (E2), sex hormone binding-globulin, dehydroepiandrosterone sulfate, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Multiple linear regression and mixture (quantile g-computation) models were fit. RESULTS: Urinary MDA and DCCA concentrations were associated with higher kiss54 levels [% change (95%CI) for each log-unit increase in concentration = 2.90 (0.32;5.56), and 1.93 (0.45,3.43), respectively]; IMPy with lower DNA methylation percentage at CpG1 and total CpGs [% change (95%CI) = -1.15 (-1.96;-0.33): -0.89 (-1.73;-0.01), respectively]; and BP3 and DCCA with lower total CpGs methylation [-0.53 (-1.04;-0.01) and - 0.69 (-1.37;-0.01), respectively]. The pesticide mixture and the whole chemical mixture were associated with higher kiss54 [% change (95%CI) = 9.09 (3.29;15.21) and 11.61 (3.96;19.82), respectively] and lower methylation levels at several CpGs. Additionally, serum kiss54 in the third tertile was associated with higher LH levels [% change (95%CI) = 28.69 (3.75-59.63)], and third-tertile CpG1, CpG2, and total CpG methylation percentages were associated with lower FSH and E2. CONCLUSION: The findings of the present study and the negative correlation between serum kiss54 levels and KISS1 DNA methylation percentages suggested that kisspeptin may be a promising effect biomarker.

The Mixture of Bisphenol-A and Its Substitutes Bisphenol-S and Bisphenol-F Exerts Obesogenic Activity on Human Adipose-Derived Stem Cells.

Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and S (BPS), have previously shown in vitro obesogenic activity. This study was designed to investigate their combined effect on the adipogenic differentiation of human adipose-derived stem cells (hASCs). Cells were exposed for 14 days to an equimolar mixture of bisphenols (MIX) (range 10 nM-10 µM). Oil Red staining was used to measure intracellular lipid accumulation, quantitative real-time polymerase chain reaction (qRT-PCR) to study gene expression of adipogenic markers (PPARγ, C/EBPα, LPL, and FABP4), and Western Blot to determine their corresponding proteins. The MIX promoted intracellular lipid accumulation in a dose-dependent manner with a maximal response at 10 µM. Co-incubation with pure antiestrogen (ICI 182,780) inhibited lipid accumulation, suggesting that the effect was mediated by the estrogen receptor. The MIX also significantly altered the expression of PPARγ, C/EBPα, LPL, and FABP4 markers, observing a non-monotonic (U-shaped) dose-response, with maximal gene expression at 10 nM and 10 µM and lesser expression at 1 µM. This pattern was not observed when bisphenols were tested individually. Exposure to MIX (1-10 µM) also increased all encoded proteins except for FABP4, which showed no changes. Evaluation of the combined effect of relevant chemical mixtures is needed rather than single chemical testing.

Development and validation of brain-derived neurotrophic factor measurement in human urine samples as a non-invasive effect biomarker.

Background: Brain-derived neurotrophic factor (BDNF), a neurotrophic growth factor mainly expressed in the brain, has been proposed as a potential effect biomarker; that is, as a measurable biomarker whose values could be associated with several diseases, including neurological impairments. The European Human Biomonitoring Initiative (HBM4EU) has also recognized effect biomarkers as a useful tool for establishing link between exposure to environmental pollutants and human health. Despite the well-establish protocol for measuring serum BDNF, there is a need to validate its assessment in urine, a non-invasive sample that can be easily repeated over time. The aim of this study was to develop, standardize and validate a methodology to quantify BDNF protein levels in urine samples before its implementation in biomonitoring studies. Methods: Different experimental conditions and non-competitive commercial enzyme-linked immunosorbent assay (ELISA) kits were tested to determine the optimal analytical procedure, trying to minimize the shortcomings of ELISA kits. The fine-tune protocol was validated in a pilot study using both upon awakening (n = 150) and prior to sleeping (n = 106) urine samples from the same Spanish adolescent males in a well-characterized study population (the Spanish INMA-Granada cohort). Results: The best results were obtained in 0.6 ml of urine after the acidification and extraction (pre-concentration) of samples. The highest reproducibility was obtained with the ELISA kit from Raybiotech. Urinary BDNF concentrations of adolescent males were within the previously reported range (morning = 0.047-6.801 ng/ml and night = 0.047-7.404 ng/ml). Urinary BDNF levels in the awakening and pre-sleep samples did not follow a normal distribution and were not correlated. Conclusion: The developed methodology offers good sensitivity and reproducibility. Having reliable markers in urine may facilitate both diagnosis and monitoring possible diseases (and treatment). Further studies are needed to implement urinary BDNF in biomonitoring studies to further elucidate its usefulness and biological significance for neurological impairments.

Bisphenol-A exposure and risk of breast and prostate cancer in the Spanish European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. RESULTS: Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. CONCLUSIONS: We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk.

Inflammatory Potential of the Diet and Incidence of Crohn's Disease and Ulcerative Colitis in the EPIC-Spain Cohort.

Diet may influence the development of inflammatory bowel disease through the modulation of inflammation. We investigated whether the inflammatory potential of the diet is associated with the risk of Crohn's disease (CD) and ulcerative colitis (UC) in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The study included 32,633 participants aged 29-69 years. The inflammatory potential of the diet was measured by using an inflammatory score of the diet (ISD) based on a baseline dietary history questionnaire. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 21 years (674,547 person-years) of follow-up, 32 and 57 participants developed CD and UC, respectively. In multivariable analysis, a one-standard deviation (SD) increment in the ISD (two-unit increase) was associated with a higher risk of CD (HR of 1.71; 95% CI: 1.05-2.80; p = 0.031). By contrast, ISD was not associated with UC (HR for one-SD increment of 0.89; 95% CI: 0.66-1.19; p = 0.436). Our results suggest that consuming a more pro-inflammatory diet may contribute to the risk of CD, supporting that a healthy diet might be beneficial in its prevention. Further, larger studies are needed to verify these findings.

Concentrations of bisphenol-A in adults from the general population: A systematic review and meta-analysis.

BACKGROUND: Human bisphenol-A (BPA) exposure has been linked to adverse health effects even at low doses, which may be of potential public health concern. OBJECTIVE: To summarize BPA concentrations in general human population and their variability according to sex, geographic area, and analytical method. METHODS: Systematic review and meta-analysis of studies reporting BPA concentrations in adult human populations. Separate meta-analyses of median values were carried out for BPA in serum, creatinine-adjusted urinary BPA, and unadjusted urinary BPA concentrations using a random-effects model. Cochran's Q-statistic, I2 index, 95% prediction intervals (PIs), between-studies standard deviation (τ), and forest plots were applied to verify study heterogeneity. Sensitivity and subgroup analyses and weighted ANOVAs and meta-regressions were conducted. Funnel plots and Egger's tests were used to examine publication bias. RESULTS: Fifteen studies were included in the meta-analysis, totaling 28,353 participants. BPA was detected in over 90% of participants. The pooled creatinine-adjusted urinary BPA concentration was 1.76 µg/g (95% PI: 0.79-2.73), with individual estimates ranging between 1.20 and 2.41. The pooled estimate for unadjusted urinary BPA was 1.91 µg/l (95% PI: 0-3.97), ranging between 0.81 and 3.50, while the pooled estimate for serum BPA was 1.75 µg/l (95% PI: 0-10.58), ranging between 0.34 and 3.76. No differences were found by sex, geographic area or analytical technique. Larger sample sizes were associated with lower BPA concentrations. There was large heterogeneity across studies, whereas data for urinary BPA levels suggested a publication bias affecting research in low exposed populations. CONCLUSION: This first meta-analysis of human BPA concentrations highlights a widespread population exposure to BPA. Although there was high heterogeneity across studies, the expected range of estimated human BPA concentrations suggests that potential health risks are unlikely. Further studies are warranted to better characterize the epidemiology of human BPA exposure, accounting for ethnic, geographic, individual and environmental variability.

Protocolo del Estudio Poblacional Multinivel de las Desigualdades Socioeconómicas en la Distribución Geográfica de la Incidencia, la Mortalidad y la Supervivencia Neta del Cáncer en España: Estudio DESOCANES / Study protocol on Socioeconomic and Geographic Inequalities in Cancer Incidence, Mortality and Survival in Spain: Multilevel Population-Base Study: DESOCANES study

La incidencia y la mortalidad brindan información sobre la carga de la morbilidad del cáncer y los años potenciales de vida perdidos debido al cáncer. Se ha desarrollado el Índice de Privación (IP) como una medida estandarizada para medir la privación socioeconómica en España a nivel de sección censal. Además, se puede combinar la información del IP con variables ecológicas poblacionales y los datos de los Estudios Europeos de Alta Resolución en Cáncer. El objetivo de este estudio es caracterizar las desigualdades socioeconómicas en la incidencia, el exceso de mortalidad, la mortalidad prematura y la supervivencia neta para tres de los cánceres más incidentes (pulmón, colon-recto y mama) en España usando el IP. Este estudio nacional multinivel de base poblacional evaluará el impacto de las desigualdades socioeconómicas. Se usarán el análisis espacial, la modelización multinivel, la supervivencia neta y la evaluación del impacto económico. Los resultados serán útiles para el apoyo a la toma de decisiones y la planificación y la gestión de intervenciones en salud pública destinadas a reducir el impacto de las desigualdades socioeconómicas en el diagnóstico y el pronóstico de los pacientes de cáncer en España. (AU)

Incidence and mortality provide information on the burden of cancer morbidity and the potential years of life lost due to cancer. The Spanish Deprivation Index (SDI) has been developed as a standardized measure to study socioeconomic deprivation in Spain at the census tract level. In addition, SDI information can be combined with ecological variables at the population level and data from the High-Resolution European Studies in Cancer. The aim of this study is to characterize socioeconomic inequalities in incidence, excess mortality, premature mortality and net survival for three of the most incident cancers (lung, colon-rectum and breast) in Spain using the SDI. This national population-based study will assess the impact of socioeconomic inequalities using a multilevel modelling approach. Spatial analysis, multilevel modeling, net survival and economic impact assessment will be used. The results will be useful for supporting decision-making, planning, and management of public health interventions aimed at reducing the impact of socioeconomic inequalities in the diagnosis and prognosis of cancer patients in Spain. (AU)

[Influence of environmental temperature and air pollution on the transmission of SARS-CoV-2.] / Influencia de la temperatura ambiental y la contaminación en la transmisión del SARS-CoV-2.

The transmission of SARS-CoV-2 is a major Public Health problem that is influenced by a number of factors. Recently it has been hypothesized that this transmission may be reduced during the summer due to the warm temperatures. On the other hand, the potential association between the high number of SARS-CoV-2 infections and air pollution is being studied. This relationship was already proven during the SARS outbreak in 2002. This article reviewed the scientific evidence to date regarding the possible influence of environmental temperature and air pollution on the transmission of SARS-CoV-2. It is concluded that the annual seasons and, therefore, the temperature do not seem to influence the spread of the virus. In addition, air pollutants facilitate infection and mortality from the virus.

La transmisión del SARS-CoV-2 es un problema de Salud Pública de máxima importancia que está influido por diversos factores. Recientemente se ha planteado la hipótesis de que esta transmisión puede reducirse durante el verano debido a la temperatura cálida. Por otro lado, se está estudiando la posible relación entre el elevado número de contagios de SARS-CoV-2 y la contaminación atmosférica. Dicha relación ya fue probada durante el brote de SARS en 2002. En este artículo se revisó la evidencia científica hasta la fecha en relación con la posible influencia de la temperatura ambiental y la contaminación en la transmisión del SARS-CoV-2. Se concluye que las estaciones anuales y, por tanto, la temperatura parecen no influir en la propagación del virus. Además, los contaminantes del aire facilitan el contagio y la mortalidad por el virus.

[Study protocol on Socioeconomic and Geographic Inequalities in Cancer Incidence, Mortality and Survival in Spain: Multilevel Population-Base Study: DESOCANES study]. / Protocolo del Estudio Poblacional Multinivel de las Desigualdades Socioeconómicas en la Distribución Geográfica de la Incidencia, la Mortalidad y la Supervivencia Neta del Cáncer en España: Estudio DESOCANES.

Incidence and mortality provide information on the burden of cancer morbidity and the potential years of life lost due to cancer. The Spanish Deprivation Index (SDI) has been developed as a standardized measure to study socioeconomic deprivation in Spain at the census tract level. In addition, SDI information can be combined with ecological variables at the population level and data from the High-Resolution European Studies in Cancer. The aim of this study is to characterize socioeconomic inequalities in incidence, excess mortality, premature mortality and net survival for three of the most incident cancers (lung, colon-rectum and breast) in Spain using the SDI. This national population-based study will assess the impact of socioeconomic inequalities using a multilevel modelling approach. Spatial analysis, multilevel modeling, net survival and economic impact assessment will be used. The results will be useful for supporting decision-making, planning, and management of public health interventions aimed at reducing the impact of socioeconomic inequalities in the diagnosis and prognosis of cancer patients in Spain.

Greenhouse gases emissions from the diet and risk of death and chronic diseases in the EPIC-Spain cohort.

BACKGROUND: Evidence from the scientific literature shows a significant variation in greenhouse gas (GHG) emissions from the diet, according to the type of food consumed. We aim to analyze the relationship between the daily dietary GHG emissions according to red meat, fruit and vegetables consumption and their relationship with risk of total mortality, and incident risk of chronic diseases. METHODS: We examined data on the EPIC-Spain prospective study, with a sample of 40 621 participants. Dietary GHG emission values were calculated for 57 food items of the EPIC study using mean emission data from a systematic review of 369 published studies. RESULTS: Dietary GHG emissions (kgCO2eq/day), per 2000 kcal, were 4.7 times higher in those with high red-meat consumption (>140 g/day) than those with low consumption (<70 g/day). The average dietary GHG emissions were similar in males and females, but it was significantly higher in youngest people and in those individuals with lower educational level, as well as for northern EPIC centers of Spain. We found a significant association with the risk of mortality comparing the third vs. the first tertile of dietary GHG emissions [hazard ratio (HR) 1.095; 95% confidence interval (CI) 1.007-1.19; trend test 0.037]. Risk of coronary heart disease (HR 1.26; 95% CI 1.08-1.48; trend test 0.003) and risk of type 2 diabetes (HR 1.24; 95% CI 1.11-1.38; trend test 0.002) showed significant association as well. CONCLUSIONS: Decreasing red-meat consumption would lead to reduce GHG emissions from diet and would reduce risk of mortality, coronary heart disease and type 2 diabetes.

La obesidad como factor de riesgo en personas con COVID-19: posibles mecanismos e implicaciones / Obesity as a risk factor in COVID-19: Possible mechanisms and implications

Varios artículos recientes sugieren que la obesidad es un factor de riesgo para una enfermedad más grave por coronavirus. En este artículo se resume la evidencia científica disponible sobre el papel de la obesidad en COVID-19, con especial atención en las personas más jóvenes y los mecanismos biológicos propuestos para explicar tanto el mayor riesgo observado como la posible mayor contagiosidad de esta población. Se consideran varias implicaciones de la pandemia sobre las personas con obesidad, en relación con las posibles dificultades en el manejo de los pacientes ingresados, las implicaciones del confinamiento sobre el control y tratamiento de la obesidad, y el estigma que sufren estas personas por su condición, y que puede verse aumentado si se confirma la relación de la obesidad con COVID-19. Comprender el papel de la obesidad en COVID-19 debería ser una prioridad de salud pública, dada la alta prevalencia de esta condición en nuestro país

Recent reports suggest that obesity is a risk factor for more severe coronavirus disease. This article summarizes the available scientific evidence on the role of obesity in COVID-19. We focus on implications for younger patients and the proposed biological mechanisms that could explain both the higher risk observed and the possible higher contagiousness of people with obesity. We consider implications of the pandemic for people with obesity in relation to: difficulties in managing hospitalized patients, implications of confinement for the control and treatment of obesity, and the stigma people with obesity suffer, that could increase should the relationship between obesity and COVID-19 be confirmed. Understanding the role of obesity in COVID-19 should be a public health priority, given the high prevalence of this condition in our country

Relationship between exposure to mixtures of persistent, bioaccumulative, and toxic chemicals and cancer risk: A systematic review.

Environmental risks are responsible for one in five of all deaths worldwide. Persistent, bioaccumulative, and toxic substances are chemicals that can subsist for decades in human tissues and the environment. They include heavy metals, organochlorines, polychlorinated biphenyls, organobromines, organofluorines, and polycyclic aromatic hydrocarbons among others. Although humans are often exposed to multiple pollutants simultaneously, their negative effects on health have generally been studied for each one separately. Among the most severe of these harmful effects is cancer. Here, to compile and analyze the available evidence on the relationship between exposure to mixtures of persistent, bioaccumulative, and toxic chemicals and the risk of developing cancer in the general population, we provide a systematic review based on the main databases (Cochrane, PubMed and Embase), together with complementary sources, using the general methodology of the PRISMA Statement. The articles analyzed were selected by two researchers working independently and their quality was evaluated by reference to the Newcastle-Ottawa scale. The initial search yielded 2379 results from the main sources of information and 22 from the complementary ones. After the article selection process, 22 were included in the final review (21 case-control studies and one cohort study). Analysis of the selected studies revealed that most of the mixtures analyzed were positively associated with risk of cancer, especially that of the breast, colon-rectum or testis, and more strongly so than each contaminant alone. In view of the possible stronger association observed with the development of cancer for some mixtures of pollutants than when each one is present separately, exposure to mixtures should also be monitored and measured, preferably in cohort designs, to complement the traditional approach to persistent, bioaccumulative, and toxic chemicals. The results presented should be taken into account in public health policies in order to strengthen the regulatory framework for cancer prevention and control.

Socioeconomic Inequalities in Colorectal Cancer Survival in Southern Spain: A Multilevel Population-Based Cohort Study.

BACKGROUND: Colorectal cancer (CRC) is the most frequently diagnosed cancer in Spain. Socioeconomic inequalities in cancer survival are not documented in Spain. We aim to study the association of socioeconomic inequalities with overall mortality and survival among CRC patients in southern Spain. METHODS: We conducted a multilevel population-based cohort study, including CRC cases for the period 2011-2013. The study time-to-event outcome was death, and the primary exposure was CRC patients' socioeconomic status assessed by the Spanish deprivation index at the census tract level. We used a mixed-effects flexible hazard model, including census tract as a random intercept, to derive overall survival estimates by deprivation. RESULTS: Among 3589 CRC patients and 12,148 person-years at risk (pyr), 964 patients died before the end of the follow-up. Mortality by deprivation showed the highest mortality rate for the most deprived group (96.2 per 1000 pyr, 95% CI: 84.0-110.2). After adjusting for sex, age, cancer stage, and the area of residence, the most deprived had a 60% higher excess mortality risk than the less deprived group (excess mortality risk ratio: 1.6, 95% CI: 1.1-2.3). CONCLUSIONS: We found a consistent association between deprivation and CRC excess mortality and survival. The reasons behind these inequalities need further investigation in order to improve equality cancer outcomes in all social groups.

The Impact of Plant-Based Dietary Patterns on Cancer-Related Outcomes: A Rapid Review and Meta-Analysis.

Long-term cancer survivors represent a sizeable portion of the population. Plant-based foods may enhance the prevention of cancer-related outcomes in these patients. We aimed to synthesize the current evidence regarding the impact of plant-based dietary patterns (PBDPs) on cancer-related outcomes in the general population and in cancer survivors. Considered outcomes included overall cancer mortality, cancer-specific mortality, and cancer recurrence. A rapid review was conducted, whereby 2234 original articles related to the topic were identified via Pubmed/Medline. We selected 26 articles, which were classified into studies on PBDPs and cancer outcomes at pre-diagnosis: vegan/vegetarian diet (N = 5), provegetarian diet (N = 2), Mediterranean diet (N = 13), and studies considering the same at post-diagnosis (N = 6). Pooled estimates of the associations between the aforementioned PBDPs and the different cancer outcomes were obtained by applying random effects meta-analysis. The few studies available on the vegetarian diet failed to support its prevention potential against overall cancer mortality when compared with a non-vegetarian diet (e.g., pooled hazard ratio (HR) = 0.97; 95% confidence interval (CI): 0.88-1.06). The insufficient number of studies evaluating provegetarian index scores in relation to cancer mortality did not permit a comprehensive assessment of this association. The association between adherence to the Mediterranean diet and cancer mortality reached statistical significance (e.g., pooled HR = 0.84; 95% CI: 0.79-0.89). However, no study considered the influence of prognostic factors on the associations. In contrast, post-diagnostic studies accounted for prognostic factors when assessing the chemoprevention potential of PBDPs, but also were inconclusive due to the limited number of studies on well-defined plant-based diets. Thus, whether plant-based diets before or after a cancer diagnosis prevent negative cancer-related outcomes needs to be researched further, in order to define dietary guidelines for cancer survivors.

Bisphenol A exposure and risk of ischemic heart disease in the Spanish European Prospective Investigation into cancer and nutrition study.

BACKGROUND: Cardiovascular disease, particularly ischemic heart disease (IHD), is the leading cause of mortality worldwide. Bisphenol A (BPA) is considered an endocrine disruptor and obesogen, present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident IHD in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We designed a case-cohort study within the EPIC-Spain cohort. The population consisted of 4636 participants from 4 EPIC-Spain centers (946 IHD cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Follow-up was performed by linking with national and regional databases and reviewing patients' clinical records. Cox Proportional Hazards Models were used for the statistical analyses. RESULTS: Median follow-up time was 16 years and 70% of the participants showed detectable BPA values (>0.2 ng/ml). Geometric mean (GM) values of cases and sub-cohort were 1.22 ng/ml vs 1.19 ng/ml respectively (p = 0.90). Cox regression models showed no significant association of BPA serum levels and IHD, acute myocardial infarction or angina pectoris risk. CONCLUSIONS: We evidenced a similar percentage of detection of BPA among cases and sub-cohort participants from our population, and no clear association with IHD risk was observed. However, further investigation is needed to understand the influence of BPA on IHD risk.

[Obesity as a risk factor in COVID-19: Possible mechanisms and implications]. / La obesidad como factor de riesgo en personas con COVID-19: posibles mecanismos e implicaciones.

Recent reports suggest that obesity is a risk factor for more severe coronavirus disease. This article summarizes the available scientific evidence on the role of obesity in COVID-19. We focus on implications for younger patients and the proposed biological mechanisms that could explain both the higher risk observed and the possible higher contagiousness of people with obesity. We consider implications of the pandemic for people with obesity in relation to: difficulties in managing hospitalized patients, implications of confinement for the control and treatment of obesity, and the stigma people with obesity suffer, that could increase should the relationship between obesity and COVID-19 be confirmed. Understanding the role of obesity in COVID-19 should be a public health priority, given the high prevalence of this condition in our country.

Multimorbidity and short-term overall mortality among colorectal cancer patients in Spain: A population-based cohort study.

BACKGROUND: Numerous studies have analysed the effect of comorbidity on cancer outcomes, but evidence on the association between multimorbidity and short-term mortality among colorectal cancer patients is limited. We aimed to assess this association and the most frequent patterns of multimorbidity associated with a higher short-term mortality risk among colorectal cancer patients in Spain. METHODS: Data were obtained from two Spanish population-based cancer registries and electronic health records. We estimated the unadjusted cumulative incidence of death by comorbidity status at 6 months and 1 year. We used a flexible parametric model to derive the excess mortality hazard ratios (HRs) for multimorbidity after adjusting for sex, age at diagnosis, cancer stage and treatment. We estimated the adjusted cumulative incidence of death by comorbidity status and identified multimorbidity patterns. RESULTS: Among the study participants, 1,048 cases were diagnosed with cancers of the colon and rectum, 2 cases with cancer of the anus with overlapping sites of the rectum and 11 cases with anal adenocarcinomas but treated as colorectal cancer patients. Among 1,061 colorectal cancer patients, 171 (16.2%) died before 6 months, 246 (23.3%) died before the 1-year follow-up, and 324 (30.5%) had multimorbidity. Patients with multimorbidity had two times higher mortality risk than those without comorbidities at 6 months (adjusted HR: 2.04; 95% confidence interval [CI]: 1.30-3.20, p = 0.002). The most frequent multimorbidity pattern was congestive heart failure + diabetes. However, patients with rheumatologic disease + diabetes had two times higher 1-year mortality risk than those without comorbidities (HR: 2.23; 95% CI: 1.23-4.07, p = 0.008). CONCLUSIONS: Multimorbidity was a strong independent predictor of short-term mortality at 6 months and 1 year among the colorectal cancer patients in Spain. The identified multimorbidity pattern was consistent. Our findings might help identify patients at a higher risk for poor cancer and treatment outcomes.