SEOM Clinical Guidelines For Endometrial Cancer (2017)

Endometrial cancer (EC) is the most common gynecological cancer in developed countries. Most patients are diagnosed at an early stage with a low risk of relapse. However, there is a group of patients with a high risk of relapse and poor prognosis. Despite the recent publication of randomized trials, the adjuvant treatment of high-risk EC is still to be defined and there are many open questions about the best approach and the right timing. Unfortunately, the survival of metastatic or recurrent EC is short, due to the poor results of chemotherapy and the lack of a second line of treatment. Advances in the knowledge of the molecular abnormalities in EC have permitted the development of promising targeted therapies

Seasonal dynamics of natural Ostreococcus viral infection at the single cell level using VirusFISH

Ostreococcus is a cosmopolitan marine genus of phytoplankton found in mesotrophic and oligotrophic waters, and the smallest free-living eukaryotes known to date, with a cell diameter close to 1 μm. Ostreococcus has been extensively studied as a model system to investigate viral–host dynamics in culture, yet the impact of viruses in naturally occurring populations is largely unknown. Here, we used Virus Fluorescence in situ Hybridization (VirusFISH) to visualize and quantify viral-host dynamics in natural populations of Ostreococcus during a seasonal cycle in the central Cantabrian Sea (Southern Bay of Biscay). Ostreococcus were predominantly found during summer and autumn at surface and 50 m depth, in coastal, mid-shelf and shelf waters, representing up to 21% of the picoeukaryotic communities. Viral infection was only detected in surface waters, and its impact was variable but highest from May to July and November to December, when up to half of the population was infected. Metatranscriptomic data available from the mid-shelf station unveiled that the Ostreococcus population was dominated by the species O. lucimarinus. This work represents a proof of concept that the VirusFISH technique can be used to quantify the impact of viruses on targeted populations of key microbes from complex natural communities.Preprint5,84

On building physics-based AI models for the design and SHM of mooring systems

Expert systems in industrial processes are modelled using physics-based approaches, data-driven models or hybrid approaches in which however the underlying physical models generally constitute a separate block with respect to the Artificial Intelligence (AI) technique(s). This work applies the novel concept of “imbrication”-a physics-based AI approach-to the mooring system of offshore renewable energy devices to achieve a complete integration of both perspectives. This approach can reduce the size of the training dataset and computational time while delivering algorithms with higher generalization capability and explicability. We first undertake the design of the mooring system by developing a surrogate model coupled with a Bayesian optimiser. Then, we analyse the structural health monitoring of the mooring system by designing a supervised Deep Neural Network architecture. Herein, we describe the characteristics of the imbrication process, analyse preliminary results of our investigation and provide considerations for orienting further research work and sector applicability

Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients

BACKGROUND: Ambulatory blood pressure provides a more comprehensive assessment than clinic blood pressure, and has been reported to better predict health outcomes than clinic or home pressure. We aimed to examine associations of clinic and 24-h ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of primary care patients referred for assessment of hypertension. METHODS: We did an observational cohort study using clinic and ambulatory blood pressure data obtained from March 1, 2004, to Dec 31, 2014, from the Spanish Ambulatory Blood Pressure Registry. This registry included patients from 223 primary care centres from the Spanish National Health System in all 17 regions of Spain. Mortality data (date and cause) were ascertained by a computerised search of the vital registry of the Spanish National Institute of Statistics. Complete data were available for age, sex, all blood pressure measures, and BMI. For each study participant, follow-up was from the date of their recruitment to the date of death or Dec 31, 2019, whichever occurred first. Cox models were used to estimate associations between usual clinic or ambulatory blood pressure and mortality, adjusted for confounders and additionally for alternative measures of blood pressure. For each measure of blood pressure, we created five groups (ie, fifths) defined by quintiles of that measure among those who subsequently died. FINDINGS: During a median follow-up of 9·7 years, 7174 (12·1%) of 59 124 patients died, including 2361 (4·0%) from cardiovascular causes. J-shaped associations were observed for several blood pressure measures. Among the top four baseline-defined fifths, 24-h systolic blood pressure was more strongly associated with all-cause death (hazard ratio [HR] 1·41 per 1 - SD increment [95% CI 1·36-1·47]) than clinic systolic blood pressure (1·18 [1·13-1·23]). After adjustment for clinic blood pressure, 24-h blood pressure remained strongly associated with all-cause deaths (HR 1·43 [95% CI 1·37-1·49]), but the association between clinic blood pressure and all-cause death was attenuated when adjusted for 24-h blood pressure (1·04 [1·00-1·09]). Compared with the informativeness of clinic systolic blood pressure (100%), night-time systolic blood pressure was most informative about risk of all-cause death (591%) and cardiovascular death (604%). Relative to blood pressure within the normal range, elevated all-cause mortality risks were observed for masked hypertension (HR 1·24 [95% CI 1·12-1·37]) and sustained hypertension (1·24 [1·15-1·32]), but not white-coat hypertension, and elevated cardiovascular mortality risks were observed for masked hypertension (1·37 [1·15-1·63]) and sustained hypertension (1·38 [1·22-1·55]), but not white-coat hypertension. INTERPRETATION: Ambulatory blood pressure, particularly night-time blood pressure, was more informative about the risk of all-cause death and cardiovascular death than clinic blood pressure. FUNDING: Spanish Society of Hypertension, Lacer Laboratories, UK Medical Research Council, Health Data Research UK, National Institute for Health and Care Research Biomedical Research Centres (Oxford and University College London Hospitals), and British Heart Foundation Centre for Research Excellence

Association between high and very high albuminuria and nighttime blood pressure: Influence of diabetes and chronic kidney disease

This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes Care. The American Diabetes Association (ADA), publisher of Diabetes Care, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes Care 39.10 (2016): 1729-1737 in print and online at http://care.diabetesjournals.orgNighttime blood pressure (BP) and albuminuria are two important and independent predictors of cardiovascularmorbidity andmortality. Here, we examined the quantitative differences in nighttime systolic BP (SBP) across albuminuria levels in patients with and without diabetes and chronic kidney disease. RESEARCH DESIGN AND METHODS A total of 16,546 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry cohort (mean age 59.6 years, 54.9% men) were analyzed. Patients were classified according to estimated glomerular filtration rate (eGFR), as ≥60 or <60 mL/min/1.73 m2 (low eGFR), and urine albumin-to-creatinine ratio, as normoalbuminuria (<30 mg/g), high albuminuria (30-300 mg/g), or very high albuminuria (>300 mg/g). Office and 24-h BP were determined with standardized methods and conditions. RESULTS High albuminuria was associated with a statistically significant and clinically substantial higher nighttime SBP (6.8 mmHg higher than with normoalbuminuria, P < 0.001). This association was particularly striking at very high albuminuria among patients with diabetes and low eGFR (16.5 mmHg, P < 0.001). Generalized linear models showed that after full adjustment for demographic, lifestyles, and clinical characteristics, nighttime SBP was 4.8 mmHg higher in patients with high albuminuria than in those with normoalbuminuria (P < 0.001), and patients with very high albuminuria had a 6.1 mmHg greater nighttime SBP than those with high albuminuria (P < 0.001). These differences were 3.8 and 3.1 mmHg, respectively, among patients without diabetes, and 6.5 and 8 mmHg among patients with diabetes (P < 0.001). CONCLUSIONS Albuminuria in hypertensive patients is accompanied by quantitatively striking higher nighttime SBP, particularly in those with diabetes with very high albuminuria and low eGFRSpecific funding for this study analysis was obtained from FIS grants PI10/01011 PI11/02432, PI13/02321, PIE13/00045, PI14/01841, CP15/0129, and also from Fundación SENEFRO, Fondos FEDER, and by Cátedra UAM de Epidemiología y Control del Riesgo Cardiovascula

Action guide for community pharmacist in patients with hypertension and cardiovascular risk. Consensus Document

La hipertensión arterial (HTA) es un problema de salud estrechamente relacionado con un aumento del riesgo de padecer una enfermedad cardiovascular. Además, la HTA puede producir o empeorar la lesión de ciertos órganos diana, lo que también puede influir negativamente en el pronóstico cardiovascular del paciente. En España, la HTA es una condición muy frecuente, afectando a unos 10 millones de sujetos adultos.Por su accesibilidad y formación especializada en materia de medicamentos, el farmacéutico comunitario puede jugar un papel clave en la detección y seguimiento del paciente con HTA. Hasta la fecha, se han publicado numerosas guías clínicas sobre la atención a pacientes con HTA, dirigidas principalmente a médicos. Sin embargo, cada vez es más evidente la necesidad de que todos los profesionales de la salud participen en la atención integral a los pacientes con HTA y riesgo cardiovascular (RCV). La cooperación entre farmacéutico, médico, personal de enfermería y otros profesionales sanitarios es imprescindible para conseguir resultados que optimicen la prevención cardiovascular y mejoren la calidad de vida del paciente. Así, a fin de promover la gestión compartida de los pacientes con HTA y RCV se publica este documento, cuyo principal destinatario es el farmacéutico comunitario.El presente documento pretende ser una herramienta de referencia que dé soporte a los programas de Atención Farmacéutica al paciente con HTA y RCV que se están desarrollando actualmente en las oficinas de farmacia. El texto ha sido desarrollado de forma consensuada entre expertos de la Sociedad Española de Hipertensión- Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA), la Sociedad Española de Farmacia Comunitaria (SEFAC) y el Grupo de Investigación en Atención Farmacéutica de la Universidad de Granada (GIAF-UGR).Arterial hypertension (AH) is an important health-related problem, as responsible for an important part of cardiovascular disorders. Moreover, AH is related to the development and progression of organ damage, which has indeed a negative influence in the cardiovascular prognosis of the individual. In Spain, AH is a frequent condition, affecting about 10 millions of the adult population.Due to their accessibility and specific background on drug management, the community pharmacist could play a key role in the detection and follow-up of the hypertensive patient. To date, several guidelines on hypertension management have been released, although almost invariably have been addressed to the medical community. However, it has become more evident the need for a global management of hypertension and cardiovascular risk with the participation of several health-care providers, such as pharmacists and nurses, with the aim of improving cardiovascular prevention and the quality of life of subjects affected. The present document, particularly addressed to the community pharmacist, is intended to provide current knowledge with the aim of a better shared management of patients with hypertension and cardiovascular risk.The present document pretends to serve as a tool for currently developed programs supporting the involvement of the community pharmacy in the care of patients with hypertension and cardiovascular risk. The document has been developed after a consensus between members from the Spanish Society of Hypertension, the Spanish Society of Community Pharmacy and the Research Group on Pharmaceutical Care from the University of Granada

Guía de actuación para el farmacéutico comunitario en pacientes con hipertensión arterial y riesgo cardiovascular. Documento de Consenso (versión extendida)

La hipertensión arterial (HTA) es un problema de salud estrechamente relacionado con un aumento del riesgo de padecer una enfermedad cardiovascular. Además, la HTA puede producir o empeorar la lesión de ciertos órganos diana, lo que también puede influir negativamente en el pronóstico cardiovascular del paciente. En España, la HTA es una condición muy frecuente, afectando a unos 10 millones de sujetos adultos. Por su accesibilidad y formación especializada en materia de medicamentos, el farmacéutico comunitario puede jugar un papel clave en la detección y seguimiento del paciente con HTA. Hasta la fecha, se han publicado numerosas guías clínicas sobre la atención a pacientes con HTA, dirigidas principalmente a médicos. Sin embargo, cada vez es más evidente la necesidad de que todos los profesionales de la salud participen en la atención integral a los pacientes con HTA y riesgo cardiovascular (RCV). La cooperación entre farmacéutico, médico, personal de enfermería y otros profesionales sanitarios es imprescindible para conseguir resultados que optimicen la prevención cardiovascular y mejoren la calidad de vida del paciente. Así, a fin de promover la gestión compartida de los pacientes con HTA y RCV se publica este documento, cuyo principal destinatario es el farmacéutico comunitario. El presente documento pretende ser una herramienta de referencia que dé soporte a los programas de Atención Farmacéutica al paciente con HTA y RCV que se están desarrollando actualmente en las oficinas de farmacia. El texto ha sido desarrollado de forma consensuada entre expertos de la Sociedad Española de Hipertensión- Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA), la Sociedad Española de Farmacia Comunitaria (SEFAC) y el Grupo de Investigación en Atención Farmacéutica de la Universidad de Granada (GIAF-UGR).Arterial hypertension (AH) is an important health-related problem, as responsible for an important part of cardiovascular disorders. Moreover, AH is related to the development and progression of organ damage, which has indeed a negative influence in the cardiovascular prognosis of the individual. In Spain, AH is a frequent condition, affecting about 10 millions of the adult population. Due to their accessibility and specific background on drug management, the community pharmacist could play a key role in the detection and follow-up of the hypertensive patient. To date, several guidelines on hypertension management have been released, although almost invariably have been addressed to the medical community. However, it has become more evident the need for a global management of hypertension and cardiovascular risk with the participation of several health-care providers, such as pharmacists and nurses, with the aim of improving cardiovascular prevention and the quality of life of subjects affected. The present document, particularly addressed to the community pharmacist, is intended to provide current knowledge with the aim of a better shared management of patients with hypertension and cardiovascular risk. The present document pretends to serve as a tool for currently developed programs supporting the involvement of the community pharmacy in the care of patients with hypertension and cardiovascular risk. The document has been developed after a consensus between members from the Spanish Society of Hypertension, the Spanish Society of Community Pharmacy and the Research Group on Pharmaceutical Care from the University of Granada

R1441G but not G2019S mutation enhances LRRK2 mediated Rab10 phosphorylation in human peripheral blood neutrophils

Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1–2% of all cases of Parkinson’s disease (PD) albeit with incomplete and age-dependent penetrance. All pathogenic LRRK2 mutations reside within the two catalytic domains of LRRK2—either in its kinase domain (e.g. G2019S) with modest effect or its ROC-COR GTPase domain (e.g. R1441G/H) with large effect on LRRK2 kinase activity. We have previously reported assays to interrogate LRRK2 kinase pathway activity in human bio-samples measuring phosphorylation of its endogenous substrate Rab10, that mirrors LRRK2 kinase activation status. Here, we isolated neutrophils from fresh peripheral blood from 101 participants including 42 LRRK2 mutation carriers (21 with the G2019S and 21 with the R1441G mutations), 27 patients with idiopathic PD, and 32 controls. Using a dual approach, LRRK2 dependent Rab10 phosphorylation at Threonine 73 (pRab10(Thr73)) was measured by quantitative multiplexed immunoblotting for pRab10(Thr73)/total Rab10 as well as targeted mass-spectrometry for absolute pRab10(Thr73) occupancy. We found a significant over fourfold increase in pRab10(Thr73) phosphorylation in carriers of the LRRK2 R1441G mutation irrespective of clinical disease status. The effect of the LRRK2 G2019S mutation did not reach statistical significance. Furthermore, we show that LRRK2 phosphorylation at Serine 935 is not a marker for LRRK2 kinase activity in human neutrophils. When analysing pRab10(Thr73) phosphorylation in post-mortem brain samples, we observed overall high variability irrespective of clinical and LRRK2 mutation status and attributed this mainly to the adverse effect of the peri- and post-mortem period on the stability of posttranslational modifications such as protein phosphorylation. Overall, in vivo LRRK2 dependent pRab10(Thr73) phosphorylation in human peripheral blood neutrophils is a specific, robust and promising biomarker for significant LRRK2 kinase hyperactivation, as with the LRRK2 R1441G mutation. Additional readouts and/or assays may be needed to increase sensitivity to detect modest LRRK2 kinase activation, as with the LRRK2 G2019S mutation. Our assays could be useful for patient stratification and target engagement studies for LRRK2 kinase inhibitors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00401-021-02325-z