Study on the anomalous quartic W+W-yy couplings of electroweak bosons in e-p collisions at the LHeC and the FCC-he

In this paper, a study is carried out on the e−p --> e−y*p --> pW−ynu_e production to probe quartic W+W−yy couplings at the Large Hadron electron Collider (LHeC) with s= 1.30, 1.98 TeV and at the Future Circular Collider-hadron electron (FCC-he) with s= 3.46, 5.29 TeV. Production cross-sections are determined for both at leptonic and hadronic decay channels of the W-boson. With the data from future e−p colliders, it is possible to obtain sensitivity measures at 95% C.L

Documento de consenso interdisciplinar de expertos en el manejo de la disección aórtica tipo B: comentarios y novedades a la luz del INSTEAD-XL

ResumenAnte la ausencia de evidencia científica sólida, un comité de expertos europeos ha publicado en la revista Journal of the American College of Cardiology un documento de consenso sobre el manejo de los diferentes subgrupos de pacientes con disección aórtica tipo B. Este documento está basado en un metaanálisis que recopila toda la experiencia publicada en los últimos años sobre disección aórtica tipo B, incluyendo a más de 6.700 pacientes.A pesar de su mejor pronóstico en fase aguda que la disección aórtica tipo A, la disección aórtica tipo B presenta un mal pronóstico a medio y largo plazo. El manejo limitado al tratamiento médico con control estricto de la presión arterial y el tratamiento de los casos complicados mediante cirugía abierta o técnicas endovasculares está sometido a controversia, especialmente por la disponibilidad y los buenos resultados de las técnicas endovasculares. Este documento pretende apoyar a los cirujanos o médicos que tratan la disección aórtica tipo B, estableciendo algunos algoritmos de manejo.Recogemos en este artículo las conclusiones y los datos fundamentales de este documento de consenso.La aparición posterior de los resultados a 5 años del estudio INSTEAD añaden una fuerte evidencia científica en contra de alguna de las principales conclusiones alcanzadas en este consenso y retan este consenso logrado solamente un año antes.AbstractDue to a lack of solid scientific evidence, an european experts committee have published in Journal of the American College of Cardiology an consensus document about the management of different subgroups of patients with type B aortic dissection. This document is based on a meta-analisys including the recent published experience that includes more than 6700 patients with type B aortic dissection.In spite of the better prognosis compared to type A dissection in the short term, type B dissection has a bad long term prognosis. The conservative management limited to tight blood pressure control and close surveillance to treat complicated cases with open surgery or endovascular therapy is under discussion, specially due to the feasibility and good results of endovascular technique. This consensus intends to support surgeons or doctors who deal with type B dissection and stablishs some management algorithm.We present in this article the conclusions and main data from this consensus document.The posterior publication of 5 years results of INSTEAD study adds an strong scientific evidence against some of this consensus principal conclusions and challenge the consensus just one year later

HEMOGLOBINA GLUCOSILADA: PRUEBA DE LABORATORIO NECESARIA PARA EL CONTROL METABOLICO DE PACIENTES MEXICANOS CON DIABETES MELLITUS TIPO 2.

Además de la determinación de glucosa en sangre en ayunas (FBG), la prueba de hemoglobinaglucosilada (HbA1c) es un indicador que evalúa el grado de control metabólico de todo pacientecon diabetes mellitus tipo 2. Aunque ambas pruebas se determinan rutinariamente en muchospaíses en el mundo, para el buen control metabólico del paciente diabético, en las instituciones desalud en México solo se basan en la prueba de FBG. Conocer si los pacientes con diabetes queacudían al Hospital No. 25, IMSS en Monterrey para su control clínico (después de una evaluaciónfísica basada solamente en la prueba de FBG), estuvieron bajo un buen o mal control metabólico.Se llevo a cabo un estudio de serie de casos en el cual se midieron las concentraciones de FBG yde HbA1c en 93 pacientes diabéticos bajo tratamiento (46 mujeres y 47 hombres, con un promediode edad de 54 años) que acudían a la consulta externa del Hospital No. 25. Para evaluar el nivelde control metabólico se usaron los criterios de la Asociación Americana de Diabetes (ADA) (lacual recomienda que los niveles de HbA1c deben ser mantenidos < 7.0%) y el criterio Europeo(que recomienda que los niveles de HbA1c deben ser mantenidos < 7.6%). Las determinaciones deFBG se realizaron en el Hospital No. 25 y las de HbA1c en el Centro de Investigación Biomédicadel Noreste (CIBIN). De acuerdo a la prueba de FBG, los médicos clínicos detectaron que el 52%de los pacientes tuvieron cifras 140 mg/dl (mal control metabólico). Por otro lado, utilizando laprueba de HbA1c, los 93 pacientes (100%) registraron niveles > a 8.0%. La prueba de HbA1cmostró que todos los pacientes tuvieron un mal control metabólico. Por lo tanto, es prioritario quelas autoridades implementen rutinariamente la prueba de HbAc1 en las instituciones de salud deMéxico y especialmente en Nuevo León dado que este Estado posee la mayor tasa de mortalidadpor diabetes (45%) a nivel nacional.AbstractGlycosylated hemoglobin (HbA1c) is a blood test that gives an estimate of the average blood sugar(glucose) for the previous three months. The fasting blood glucose (FBG) and HbA1cdeterminations give a well idea about the metabolic control of the diabetics. Both tests aredetermined routinely in many countries but into the Mexican Institutes of Health only the FBG test iscarried out for this purpose. The aim of this study was to know if non-insulin-dependent diabeticmellitus (NIDDM) outpatients attending in a clinical hospital of the IMSS after the physicianevaluation based only on the FBG test were under a good or bad metabolic control. At the sametime, we carried out the HbA1c test independently of the physician evaluation in order to know if theNIDDM patients were well evaluated. A serial case study was undertaken in which concentrations ofFBG and HbA1c were measured in 93 diabetics (under treatment) at the outpatient clinic of theIMSS in Monterrey, Mexico. A structured, self-administrated questionnaire was used to obtain dataon age, gender, duration of diabetes, a recent history of polydipsia, polyuria and polyphagia, height,weight, blood pressure, treatment kind, and BMI. The American Diabetic Association (ADA)(currently recommends that the HbA1c be maintained under 7.0%) and the European criteria(currently recommends that the HbA1c be maintained under 7.6%) were used to evaluate the levelof metabolic control. The 93 patients had HbA1C levels higher than 8.0% and FBG levels between63 and 300 mg/dl. According to ADA criteria and European criteria all the patients were out of goodmetabolic control. These points towards the HbA1c and FBG confirm the doubts about theusefulness of FBG values as a tool for assessing metabolic control. These results suggest a lowlevel in the practice of monitoring indicators in NIDDM. We suggest that the HbA1c test must betaken in account by the Mexican Institutes of Health to improve a better metabolic control in theirdiabetic patients.Palabras Clave: Diabetes, Tipo 2, Hemoglobina glucosilada, Diabetes, Type 2, Glycosylated hemoglobi

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Dietary animal and plant protein intakes and their associations with obesity and cardio-metabolic indicators in European adolescents: The HELENA cross-sectional study

Background: Previous studies suggest that dietary protein might play a beneficial role in combating obesity and its related chronic diseases. Total, animal and plant protein intakes and their associations with anthropometry and serum biomarkers in European adolescents using one standardised methodology across European countries are not well documented. Objectives: To evaluate total, animal and plant protein intakes in European adolescents stratified by gender and age, and to investigate their associations with cardio-metabolic indicators (anthropometry and biomarkers). Methods: The current analysis included 1804 randomly selected adolescents participating in the HELENA study (conducted in 2006-2007) aged 12.5-17.5 y (47% males) who completed two non-consecutive computerised 24-h dietary recalls. Associations between animal and plant protein intakes, and anthropometry and serum biomarkers were examined with General linear Model multivariate analysis. Results: Average total protein intake exceeded the recommendations of World Health Organization and European Food Safety Authority. Mean total protein intake was 96 g/d (59% derived from animal protein). Total, animal and plant protein intakes (g/d) were significantly lower in females than in males and total and plant protein intakes were lower in younger participants (12.5-14.9 y). Protein intake was significantly lower in underweight subjects and higher in obese ones; the direction of the relationship was reversed after adjustments for body weight (g/(kg.d)). The inverse association of plant protein intakes was stronger with BMI z-score and body fat percentage (BF%) compared to animal protein intakes. Additionally, BMI and BF% were positively associated with energy percentage of animal protein. Conclusions: This sample of European adolescents appeared to have adequate total protein intake. Our findings suggest that plant protein intakes may play a role in preventing obesity among European adolescents. Further longitudinal studies are needed to investigate the potential beneficial effects observed in this study in the prevention of obesity and related chronic diseases

Relationship between self-reported dietary intake and physical activity levels among adolescents: The HELENA study

Background Evidence suggests possible synergetic effects of multiple lifestyle behaviors on health risks like obesity and other health outcomes. Therefore it is important to investigate associations between dietary and physical activity behavior, the two most important lifestyle behaviors influencing our energy balance and body composition. The objective of the present study is to describe the relationship between energy, nutrient and food intake and the physical activity level among a large group of European adolescents. Methods The study comprised a total of 2176 adolescents (46.2% male) from ten European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study. Dietary intake and physical activity were assessed using validated 24-h dietary recalls and self-reported questionnaires respectively. Analyses of covariance (ANCOVA) were used to compare the energy and nutrient intake and the food consumption between groups of adolescents with different physical activity levels (1st to 3rd tertile). Results In both sexes no differences were found in energy intake between the levels of physical activity. The most active males showed a higher intake of polysaccharides, protein, water and vitamin C and a lower intake of saccharides compared to less active males. Females with the highest physical activity level consumed more polysaccharides compared to their least active peers. Male and female adolescents with the highest physical activity levels, consumed more fruit and milk products and less cheese compared to the least active adolescents. The most active males showed higher intakes of vegetables and meat, fish, eggs, meat substitutes and vegetarian products compared to the least active ones. The least active males reported the highest consumption of grain products and potatoes. Within the female group, significantly lower intakes of bread and cereal products and spreads were found for those reporting to spend most time in moderate to vigorous physical activity. The consumption of foods from the remaining food groups, did not differ between the physical activity levels in both sexes. Conclusion It can be concluded that dietary habits diverge between adolescents with different self-reported physical activity levels. For some food groups a difference in intake could be found, which were reflected in differences in some nutrient intakes. It can also be concluded that physically active adolescents are not always inclined to eat healthier diets than their less active peers.The HELENA study took place with the financial support of the European Community Sixth RTD Framework Programme (Contract FOOD-CT: 2005-007034). This work was also partially supported by the European Union, in the framework of the Public Health Programme (ALPHA project, Ref: 2006120), the Swedish Council for Working Life and Social Research (FAS), the Spanish Ministry of Education (EX-2007-1124, and EX-2008-0641), and the Spanish Ministry of Health, Maternal, Child Health and Development Network (number RD08/0072) (JPRL, LAM)

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality