[Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO) y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventana de oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos del embarazo y riesgo de enfermedad vascular.] / Consensus document of the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Opportunity window: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular disease.

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs), such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational age and/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developing vascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheral vascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOs when assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact, adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the other hand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality. Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOs could strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients. Various healthcare system options exist to improve the transition of care for women with APOs between different healthcare professionals and implement long-term VR reduction strategies. One potential process could involve incorporating the fourth-trimester concept into clinical recommendations and healthcare policies.

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE), tales como son los trastornos hipertensivos, el parto pretérmino, la diabetes gestacional, los defectos en el crecimiento fetal (feto pequeño para la edad gestacional y/o restricción del crecimiento), el desprendimiento de placenta y la pérdida fetal, y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura: cardiopatía coronaria, accidente cerebrovascular, enfermedad vascular periférica e insuficiencia cardíaca. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo y/o postparto y manteniéndolo a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto del cuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention.

We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm-SCORE2, SCORE-OP- is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (< 50, 50-69, ≥70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.

Intraputaminal Gene Delivery in Two Patients with Aromatic L-Amino Acid Decarboxylase Deficiency.

Background: Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, early-onset, dyskinetic encephalopathy mostly reflecting a defective synthesis of brain dopamine and serotonin. Intracerebral gene delivery (GD) provided a significant improvement among AADCD patients (mean age, ≤6 years). Objective: We describe the clinical, biological, and imaging evolution of two AADCD patients ages >10 years after GD. Methods: Eladocagene exuparvovec, a recombinant adeno-associated virus containing the human complimentary DNA encoding the AADC enzyme, was administered into bilateral putamen by stereotactic surgery. Results: Eighteen months after GD, patients showed improvement in motor, cognitive and behavioral function, and in quality of life. Cerebral l-6-[18F] fluoro-3, 4-dihydroxyphenylalanine uptake was increased at 1 month, persisting at 1 year compared to baseline. Conclusion: Two patients with a severe form of AADCD had an objective motor and non-motor benefit from eladocagene exuparvovec injection even when treated after the age of 10 years, as in the seminal study.

Correction: Evaluation Criteria for Weight Management Apps: Validation Using a Modified Delphi Process.

[This corrects the article DOI: 10.2196/16899.].

Correction: Assessment of the Efficacy, Safety, and Effectiveness of Weight Control and Obesity Management Mobile Health Interventions: Systematic Review.

[This corrects the article DOI: 10.2196/12612.].

Women with familial hypercholesterolemia phenotype are undertreated and poorly controlled compared to men.

Familial hypercholesterolemia (FH) is an autosomal dominant disease that has a prevalence of approximately 1/250 inhabitants and is the most frequent cause of early coronary heart disease (CHD). We included 1.343.973 women and 1.210.671 men with at least one LDL-c measurement from the Catalan primary care database. We identified 14.699 subjects with Familial hypercholesterolemia-Phenotype (FH-P) based on LDL-c cut-off points by age (7.033 and 919 women, and 5.088 and 1659 men in primary and secondary prevention, respectively). Lipid lower therapy (LLT), medication possession ratio (MPR) as an indicator of adherence, and number of patients that reached their goal on lipid levels were compared by sex. In primary and secondary prevention, 69% and 54% of women (P = 0.001) and 64% and 51% of men (P = 0.001) were on low-to-moderate-potency LLT. Adherence to LLT was reduced in women older than 55 years, especially in secondary prevention (P = 0.03), where the percentage of women and men with LDL-c > 1.81 mmol/L were 99.9% and 98.9%, respectively (P = 0.001). Women with FH-P are less often treated with high-intensity LLT, less adherent to LLT, and have a lower probability of meeting their LDL-c goals than men, especially in secondary prevention.

Identification of Secondary Prevention Patients Eligible for PCSK9 Inhibitors Therapy According to the Routine Clinical Practice in Spain.

INTRODUCTION: Many patients at very high risk of cardiovascular (CV) events would benefit from lipid-lowering therapies (LLT) intensification to decrease their risk. This study aimed to identify the real-world secondary prevention patients potentially eligible for proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) in Spain. METHODS: This retrospective cohort study included adult patients registered in the IQVIA Spanish Electronic Medical Records outpatient database (2014-2020), diagnosed with myocardial infarction (MI), unstable angina (UA), ischaemic stroke (IS), transient ischaemic attack (TIA) or peripheral artery disease (PAD) and with ≥ 1 low-density lipoprotein cholesterol (LDL-C) or total cholesterol measurements. Longitudinal data were collected from the initial diagnosis to the end of the study period or follow-up loss. RESULTS: The study included 9516 patients, 63.9% male, mean (SD) age 67.7 (12.5) years and mean LDL-C 117.3 (38.8) mg/dL. MI, IS and PAD were the most severe events reported during the study period (28.5%, 18.7% and 29.3% of patients, respectively). At the time of last available LDL-C assessment (≥ 3 months post-event), 64.4% patients were on LLT. Of those, 45.4%, 46.9% and 7.7% were on high-, moderate- and low-intensity LLT. Overall, 9.6% patients achieved LDL-C < 55 mg/dL (24.2% LDL-C < 70 mg/dL). Furthermore, 17.9% patients receiving optimized oral LLT showed LDL-C > 100 mg/dL (LDL-C reimbursement threshold for PCSK9i in Spain). CONCLUSION: Up to 82% of patients with atherosclerotic CV disease do not achieve LDL-C levels recommended by the 2019 ESC/EAS guidelines despite being on optimized oral LLT therapy. In 17.9% of these patients LDL-C levels exceed 100 mg/dL, being eligible for PCSK9i in Spain.

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention. / Comentario del CEIPV a las nuevas Guías Europeas de Prevención Cardiovascular 2021.

We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease Prevention in Clinical Practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global cardiovascular disease risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (steps 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After step 1, considering proceeding to the intensified goals of step 2 is mandatory, and this intensification will be based on 10-year cardiovascular disease risk, lifetime cardiovascular disease risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm ?SCORE2, SCORE2-OP? is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal cardiovascular disease events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according to different age groups (<50, 50-69, ≥70 years). Different flow charts of cardiovascular disease risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic cardiovascular disease, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.

Codesign and Feasibility Testing of a Tool to Evaluate Overweight and Obesity Apps.

BACKGROUND: Digital health interventions and mobile technologies can help to reduce the rates of obesity and overweight conditions. Although weight management apps are widely used, they usually lack professional content and evaluation, so the quality of these apps cannot be guaranteed. The EVALAPPS project aims to design and validate a tool to assess the safety and effectiveness of health-related apps whose main goal is to manage and prevent obesity and overweight conditions. OBJECTIVE: The aim of this paper is two-fold: (a) to co-create and codesign the EVALAPPS assessment tool and (b) to pilot its feasibility among overweight and obese individuals that use weight control apps. METHODS: A mixed-methods approach was used. A multidisciplinary team (n = 12) participated in a co-creation workshop to provide proposals and inputs about the look and feel of the content, usability aspects, appearance, sections, and main features of the EVALAPPS tool. The tool was tested for its feasibility among 31 overweight and obese individuals, attending the CP Endocrinologia i Nutrició SL Clinic for the first time. Participants were asked to use a specific weight control app [Yazio (YAZIO GmbH, Erfurt, Germany), My FitnessPal (MyFitnessPal, Austin, TX, USA) or MyPlate (MyPlate, Santa Monica, CA, USA)] for two weeks and then evaluate them by using the EVALAPPS (EVALAPPS, David Ganyan, Barcelona, Spain) (June 2020, David Ganyan, Barcelona, Spain) tool. Seven participants were phone interviewed to gain more insight into the use of the EVALAPPS tool. RESULTS: The co-creation workshop allowed conceptualizing the EVALAPPS tool. The feasibility study showed that all criteria from the Usability and Functionality dimensions had valid answers, while Reliability, Security, Privacy, and Health indicators were the dimensions with less valid answers. In all three apps, the dimension with the highest score was Usability/functionality, followed by app purpose. Clinical effectiveness and Development were the dimensions with the lowest scores in all three tested weight control apps. CONCLUSIONS: The participation of the multidisciplinary team and end-users in the conceptualization and testing of a tool to assess health apps was feasible and relevant for the usability of the tool.

Evaluation of Phenolic Compounds and Pigments Content in Yellow Bell Pepper Wastes.

Bell peppers are one of the most important species consumed and cultivated in Spain. Peppers are a source of carotenoids and phenolic compounds widely associated with biological activities such as antimicrobial, antiseptic, anticancer, counterirritant, cardioprotective, appetite stimulator, antioxidant, and immunomodulator. However, undersized and damaged fruits are usually wasted. Thus, in order to evaluate the phenolic content, a Box-Behnken design has been carried out to optimize the extraction from Capsicum annuum yellow pepper by ultrasound-assisted extraction (UAE). The independent factors were time (min), ethanol/water (% v/v) and solvent/sample ratio (v/w). The model was validated by ANOVA and confirmed. Furthermore, the whole pepper and the pepper without peduncles and seeds were extracted using optimal conditions and characterized by HPLC-ESI-TOF-MS. Moreover, their antioxidant activities, measured by three different methods (DPPH, ABTS, and FRAP), carotenoid composition, assessed by HPLC-MS, and chlorophyll content, assessed by a spectrophotometric method, were compared. A total of 38 polar compounds were found of which seven have been identified in pepper fruit extracts for the first time. According to the results, whole pepper (WP) samples presented higher content in phenolic acids; meanwhile, the edible portion (EP) was higher in flavonoids. No differences were found in the antioxidant activity except for the FRAP assay where the WP sample showed higher radical scavenging activity. EP samples showed the highest content of carotenoids and WP ones in chlorophylls.

[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention.] / Comentario del CEIPV a las nuevas Guías Europeas de Prevención Cardiovascular 2021.

We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm (SCORE2, SCORE-OP) is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (<50, 50-69, >70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.

Presentamos la adaptación española de las Guías Europeas de Prevención Cardiovascular 2021. En esta actualización además del abordaje individual, se pone mucho más énfasis en las políticas sanitarias como estrategia de prevención poblacional. Se recomienda el cálculo del riesgo vascular de manera sistemática a todas las personas adultas con algún factor de riesgo vascular. Los objetivos terapéuticos para el colesterol LDL, la presión arterial y la glucemia no han cambiado respecto a las anteriores guías, pero se recomienda alcanzar estos objetivos de forma escalonada (etapas 1 y 2). Se recomienda llegar siempre hasta la etapa 2, y la intensificación del tratamiento dependerá del riesgo a los 10 años y de por vida, del beneficio del tratamiento, de las comorbilidades, de la fragilidad y de las preferencias de los pacientes. Las guías presentan por primera vez un nuevo modelo para calcular el riesgo (SCORE2 y SCORE2 OP) de morbimortalidad vascular en los próximos 10 años (infarto de miocardio, ictus y mortalidad vascular) en hombres y mujeres entre 40 y 89 años. Otra de las novedades sustanciales es el establecimiento de diferentes umbrales de riesgo dependiendo de la edad (<50, 50-69, >70 años). Se presentan diferentes algoritmos de cálculo del riesgo vascular y tratamiento de los factores de riesgo vascular para personas aparentemente sanas, pacientes con diabetes y pacientes con enfermedad vascular aterosclerótica. Los pacientes con enfermedad renal crónica se considerarán de riesgo alto o muy alto según la tasa del filtrado glomerular y el cociente albúmina/creatinina. Se incluyen innovaciones en las recomendaciones sobre los estilos de vida, adaptadas a las recomendaciones del Ministerio de Sanidad, así como aspectos novedosos relacionados con el control de los lípidos, la presión arterial, la diabetes y la insuficiencia renal crónica.

Effect of statin therapy on SARS-CoV-2 infection-related mortality in hospitalized patients.

AIM: Assessing the effect of statin therapy (ST) at hospital admission for COVID-19 on in-hospital mortality. METHODS AND RESULTS: Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk. Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients [1234 men, 923 women; age: 67 y/o (IQR 54-78)] admitted to the hospital were retrieved from the clinical records in anonymized manner. Three hundred and fifty-three deaths occurred. Five hundred and eighty-one patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on ST than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: P = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared with the GM non-statin group (17.4%; P = 0.045). The Cox model applied to the CSH function [HR = 0.58(CI: 0.39-0.89); P = 0.01] and the competing-risks FG model [HR = 0.60 (CI: 0.39-0.92); P = 0.02] suggest that statins are associated with reduced COVID-19-related mortality. CONCLUSIONS: A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.

Consumption of water contaminated by nitrate and its deleterious effects on the human thyroid gland: a review and update.

Nowadays, the nitrates have been established as carcinogenic components due to the endogenous formation of N-nitroso compounds, however, the consumption of water contaminated with nitrates has only been strongly related to the presence of methemoglobinemia in infants, as an acute effect, leaving out other side effects that demand attention. The thyroid gland takes relevance because it can be altered by many pollutants known as endocrine disruptors, which are agents capable of interfering with the synthesis of hormones, thus far, it is known that nitrates may disrupt the amount of iodine uptake causing most of the time hypothyroidism and affecting the metabolic functions of the organism in all development stages, resulting in an important health burden for the exposed population. Here, this review and update highlighted the impact of consumption of water contaminated with nitrates and effects on the thyroid gland in humans, concluding that nitrates could act as true endocrine disruptor.

Long-term exposure to PM10 above WHO guidelines exacerbates COVID-19 severity and mortality.

BACKGROUND: Age, sex, race and comorbidities are insufficient to explain why some individuals remain asymptomatic after SARS-CoV-2 infection, while others die. In this sense, the increased risk caused by the long-term exposure to air pollution is being investigated to understand the high heterogeneity of the COVID-19 infection course. OBJECTIVES: We aimed to assess the underlying effect of long-term exposure to NO2 and PM10 on the severity and mortality of COVID-19. METHODS: A retrospective observational study was conducted with 2112 patients suffering COVID-19 infection. We built two sets of multivariate predictive models to assess the relationship between the long-term exposure to NO2 and PM10 and COVID-19 outcome. First, the probability of either death or severe COVID-19 outcome was predicted as a function of all the clinical variables together with the pollutants exposure by means of two regularized logistic regressions. Subsequently, two regularized linear regressions were constructed to predict the percentage of dead or severe patients. Finally, odds ratios and effects estimates were calculated. RESULTS: We found that the long-term exposure to PM10 is a more important variable than some already stated comorbidities (i.e.: COPD/Asthma, diabetes, obesity) in the prediction of COVID-19 severity and mortality. PM10 showed the highest effects estimates (1.65, 95% CI 1.32-2.06) on COVID-19 severity. For mortality, the highest effect estimates corresponded to age (3.59, 95% CI 2.94-4.40), followed by PM10 (2.37, 95% CI 1.71-3.32). Finally, an increase of 1 µg/m3 in PM10 concentration causes an increase of 3.06% (95% CI 1.11%-4.25%) of patients suffering COVID-19 as a severe disease and an increase of 2.68% (95% CI 0.53%-5.58%) of deaths. DISCUSSION: These results demonstrate that long-term PM10 burdens above WHO guidelines exacerbate COVID-19 health outcomes. Hence, WHO guidelines, the air quality standard established by the Directive 2008/50/EU, and that of the US-EPA should be updated accordingly to protect human health.

FOXE1 polymorphisms and chronic exposure to nitrates in drinking water cause metabolic dysfunction, thyroid abnormalities, and genotoxic damage in women.

Nitrates in drinking water has been associated to adverse health effects, including changes in glucose and lipid levels, thyroid hormone imbalance and adverse reproductive effects. We analyzed metabolic and thyroid hormone alterations and genotoxic damage in women with chronic exposure to nitrates in drinking water. The concentration of nitrates in drinking water was quantified and according to this parameter, participants were divided into three exposure scenarios. Blood and urine samples were collected from 420 women living in Durango, Mexico and biomarkers were determined. We found nitrates concentrations in drinking water above the permissible limit (>50 mg/L), and an increase in the percentage of methemoglobin (p=0.0001), nitrite in blood plasma and urine (p=0.0001), glucose (p=0.0001), total cholesterol (p=0.001), LDL (p=0.001) and triglycerides (p=0.0001). We also found alterations in TSH (p=0.01), fT3 (p=0.0003), T4T (p=0.01) and fT4 (p=0.0004) hormones. Frequency of subclinical hypothyroidism was 8.33%; differences in FOXE1 (rs965513, rs1867277) genotypes distribution were found and both polymorphisms were associated with a decrease in TSH. A high percentage of micronucleus in binucleate lymphocyte cells was found (35%, p=0.0001). In conclusion, the chronic exposure to nitrates in water for human consumption caused metabolic and hormonal alterations and genotoxic damage in women.

Regulation of the Tpo, Tg, Duox2, Pds, and Mct8 genes involved in the synthesis of thyroid hormones after subchronic exposure to sodium nitrate in female Wistar rats.

Nitrates are natural compounds present in soil and water; however, the intense use of fertilizers has increased their presence in groundwater with deleterious effects on human health. There is evidence of nitrates acting as endocrine disruptors; however, the underlying molecular mechanisms have not been fully described. Here, we investigated the effect of subchronic exposure to different concentrations of sodium nitrate in female Wistar rats, evaluating thyroid hormonal parameters, such as Nis transporter (Na+ /I- symporter, Slc5a5) and Tsh-R receptor protein expression, as well as transcription of the Tpo (thyroperoxidase), Tg (tiroglobulin), Duox2 (dual oxidase 2), Pds (pendrin), and Mct8 (Mct8 transporter, Slc16a2) genes. Hematological and histochemical changes in the liver and thyroid were also explored. Significant differences were found in platelet and leukocyte counts; although a significant increase in the weight of the thyroid gland was observed, no differences were found in the levels of the hormones Tsh, T3, and T4, but a modulation of the mRNA expression of the Tg, Tpo, Duox2, Mct8, and Pds genes was observed. Morphological changes were also found in liver and thyroid tissue according to the exposure doses. In conclusion, subchronic exposure to sodium nitrate induces leukocytosis consistent with an inflammatory response and upregulation of Sod2 in the liver and increases the expression of genes involved in the synthesis of thyroid hormones, keeping thyroid hormone levels stable. Histological changes in the thyroid gland suggest a goitrogenic effect.

El rastreo masivo de datos es una segunda oportunidad para mejorar el manejo de los pacientes con fenotipo de hipercolesterolemia familiar / Massive data screening is a second opportunity to improve the management of patients with familial hypercholesterolemia phenotype

Introducción: La Hipercolesterolemia Familiar (HF) es una enfermedad autósómica dominante con una prevalencia estimada entre 1/200-250. Se encuentra infra-tratada e infra-diagnosticada. El rastreo masivo de datos puede incrementar la detección de pacientes con HF. Métodos: Población a estudio: Residentes en la zona sanitaria de cobertura (N: 195.000 habitantes) y con al menos una determinación de colesterol ligado a lipoproteínas de baja densidad (C-LDL) realizada entre el 1 de Enero de 2010 y el 30 de Diciembre de 2019. Se seleccionaron los valores más altos de C-LDL. Criterios de exclusión: síndrome nefrótico, hipotiroidismo, tratamiento hipotiroideo o triglicéridos > 400 mg/dL. Se analizaron 7 algoritmos sugestivos de fenotipo de Hipercolesterolemia Familiar (F-HF).Se seleccionó el algoritmo más eficaz y de fácil traslación a la práctica clínica. Resultados: Partiendo de 6.264.877 asistencias y 288.475 pacientes tras aplicar los criterios de inclusión-exclusión se incluyeron 504.316 analíticas correspondiendo a 106.382 adultos y 10.509 < 18 años. El algoritmo seleccionado presentó una prevalencia de 0.62%.Se detectaron 840 pacientes con fenotipo de Hipercolestereolemia Familiar (F-HF) siendo el 55.8% mujeres y 178 <18 años, El 9.3% tenían antecedentes de enfermedad cardio-vascular (ECV) y 16.4% habían fallecido. El 65% de los pacientes en prevención primaria presentaron valores de C-LDL >130 mg/dL y el 83% en prevención secundaria valores >70mg/dL. Se obtuvo una ratio de 7.64 (1-18) pacientes con HF-P por médico solicitante de analítica.Conclusiones: El rastreo masivo de datos y el perfilado de pacientes son herramientas eficaces y fácilmente aplicables en práctica clínica para la detección de pacientes con HF.(AU)

Introduction: Familial Hypercholesterolemia (FH) is an autosomal dominant disease with an estimated prevalence between 1/200-250. It is under-treated and underdiagnosed. Massive data screening can increase the detection of patients with FH. Methods: Study population: Residents in the health coverage area (N: 195.000 inhabitants) and with at least one determination of cholesterol linked to low-density lipoproteins (LDL-C) carried out between January 1, 2010 and December 30, 2019. The highest LDL-C values were selected. Exclusion criteria: nephrotic syndrome, hypothyroidism, Hypothyroid treatment or triglycerides> 400 mg / dL. Seven algorithms suggestive of Familial Hypercholesterolemia Phenotype (HF-P) were analyzed, selecting the most efficient algorithm that could easily be translated into clinical practice. Results: Based on 6.264.877 assistances and 288.475 patients, after applying the inclusion-exclusion criteria, 504.316 tests were included, corresponding to 106.382 adults and 10.509 <18 years. The selected algorithm presented a prevalence of 0.62%. 840 patients with HF-P were detected, 55.8% being women and 178 <18 years old, 9.3% had a history of cardiovascular disease (CVD) and 16.4% had died. 65% of the patients in primary prevention had LDL-C values> 130 mg / dL and 83% in secondary prevention values> 70mg / dL. A ratio of 7.64 (1-18) patients with HF-P per analytical requesting physician was obtained. Conclusions. Massive data screening and patient profiling are effective tools and easily applicable in clinical practice for the detection of patients with FH.

Low HDL and high triglycerides predict COVID-19 severity.

Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.

Massive data screening is a second opportunity to improve the management of patients with familial hypercholesterolemia phenotype. / El rastreo masivo de datos es una segunda oportunidad para mejorar el manejo de los pacientes con fenotipo de hipercolesterolemia familiar.

INTRODUCTION: Familial Hypercholesterolemia (FH) is an autosomal dominant disease with an estimated prevalence between 1/200-250. It is under-treated and underdiagnosed. Massive data screening can increase the detection of patients with FH. METHODS: Study population: Residents in the health coverage area (N: 195.000 inhabitants) and with at least one determination of cholesterol linked to low-density lipoproteins (LDL-C) carried out between January 1, 2010 and December 30, 2019. The highest LDL-C values were selected. EXCLUSION CRITERIA: nephrotic syndrome, hypothyroidism, Hypothyroid treatment or triglycerides> 400 mg / dL. Seven algorithms suggestive of Familial Hypercholesterolemia Phenotype (HF-P) were analyzed, selecting the most efficient algorithm that could easily be translated into clinical practice. RESULTS: Based on 6.264.877 assistances and 288.475 patients, after applying the inclusion-exclusion criteria, 504.316 tests were included, corresponding to 106.382 adults and 10.509 <18 years. The selected algorithm presented a prevalence of 0.62%. 840 patients with HF-P were detected, 55.8% being women and 178 <18 years old, 9.3% had a history of cardiovascular disease (CVD) and 16.4% had died. 65% of the patients in primary prevention had LDL-C values> 130 mg / dL and 83% in secondary prevention values> 70mg / dL. A ratio of 7.64 (1-18) patients with HF-P per analytical requesting physician was obtained. CONCLUSIONS: Massive data screening and patient profiling are effective tools and easily applicable in clinical practice for the detection of patients with FH.

Polygenic Markers in Patients Diagnosed of Autosomal Dominant Hypercholesterolemia in Catalonia: Distribution of Weighted LDL-c-Raising SNP Scores and Refinement of Variant Selection.

Familial hypercholesterolemia (FH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes. A pathological variant has not been identified in 30-70% of clinically diagnosed FH patients, and a burden of LDL cholesterol (LDL-c)-raising alleles has been hypothesized as a potential cause of hypercholesterolemia in these patients. Our aim was to study the distribution of weighted LDL-c-raising single-nucleotide polymorphism (SNP) scores (weighted gene scores or wGS) in a population recruited in a clinical setting in Catalonia. The study included 670 consecutive patients with a clinical diagnosis of FH and a prior genetic study involving 250 mutation-positive (FH/M+) and 420 mutation-negative (FH/M-) patients. Three wGSs based on LDL-c-raising variants were calculated to evaluate their distribution among FH patients and compared with 503 European samples from the 1000 Genomes Project. The FH/M- patients had significantly higher wGSs than the FH/M+ and control populations, with sensitivities ranging from 42% to 47%. A wGS based only on the SNPs significantly associated with FH (wGS8) showed a higher area under the receiver operating characteristic curve, and higher diagnostic specificity and sensitivity, with 46.4% of the subjects in the top quartile. wGS8 would allow for the assignment of a genetic cause to 66.4% of the patients if those with polygenic FH are added to the 37.3% of patients with monogenic FH. Our data indicate that a score based on 8 SNPs and the75th percentile cutoff point may identify patients with polygenic FH in Catalonia, although with limited diagnostic sensitivity and specificity.