Altered surface expression of insulin-degrading enzyme on monocytes and lymphocytes from COVID-19 patients both at diagnosis and after hospital discharge

Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4+ and CD4−), and, to a lower extent, in B-cells from healthy controls. Notably, IDE’s surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE’s surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4+ T-cells, and CD4− T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4+ T-cells and CD4− T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.This work was funded by the European Commission–NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global) and Junta de Castilla y León (Proyectos COVID 07.04.467B04.74011.0) to D.B. The project leading to these results had received funding from the “La Caixa” Foundation under agreement LCF/PR/PR18/51130007 to G.P. and grant PID2019-110496RB-C22 funded by MCIN/AEI/10.13039/501100011033 to G.P. This research was funded by the Programa Estratégico Instituto de Biología y Genética Molecular (IBGM), Junta de León and the European Social Fund (ORDER EDU/574/2018)

Four chamber right ventricular longitudinal strain versus right free wall longitudinal strain. Prognostic value in patients with left heart disease

Background: There is no consensus on which right ventricle (RV) strain parameter should be used in the clinical practice: four chamber RV longitudinal strain (4CH RV-LS) or free wall longitudinal strain (FWLS). The aim of this study was to analyze which RV strain parameter better predicts prognosis in patients with left heart disease. Methods: One hundred and three outpatients with several degrees of functional tricuspid regurgitation severity secondary to left heart disease were prospectively included. 4CH RV-LS and FWLS were assessed using speckle tracking. Left ventricular (LV) systolic function was determined using LV ejection fraction and RV systolic function using tricuspid annular plane systolic excursion (TAPSE). Patients were followed up for 23.1 ± 12.4 months for an endpoint of cardiac hospitalization due to heart failure. Results: The cutoff value related to RV dysfunction (TAPSE < 17 mm) was lower, in absolute value, for 4CH RV-LS (4CH RV-LS = –17.3%; FWLS = –19.5%). There were 33 adverse events during the follow-up. Patients with 4CH RV-LS > –17.3% (log rank [LR] = 22.033; p < 0.001); FWLS > –19.5% (LR = 12.2; p < 0.001), TAPSE < 17 mm (LR = 17.4; p < 0.001) and LV systolic dysfunction (LR = 13.3; p < 0.001) had lower event-free survival (Kaplan Meier). In Cox multivariate analysis, 4CH RV-LS > –17.3% (hazard ratio [HR] = 3.593; p < 0.002), TAPSE < 17 (HR = 2.093; p < 0.055) and LV systolic dysfunction (HR = 2.087; p < 0,054) had prognostic value, whereas FWLS did not reach significance. Conclusions: Although both 4CH RV-LS and FWLS have prognostic value, 4CH RV-LS is a better predictor of episodes of heart failure in patients with left heart disease, providing additional information to that obtained by TAPSE.

Inappropriate antibiotic use in the COVID-19 era: Factors associated with inappropriate prescribing and secondary complications. Analysis of the registry SEMI-COVID

Background: Most patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use. Methods: The SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified. Results: Out of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18-2.00), age (OR 0.98, 95%CI 0.97-0.99), absence of comorbidity (OR 1.43, 95%CI 1.05-1.94), dry cough (OR 2.51, 95%CI 1.94-3.26), fever (OR 1.33, 95%CI 1.13-1.56), dyspnea (OR 1.31, 95%CI 1.04-1.69), flu-like symptoms (OR 2.70, 95%CI 1.75-4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00-1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001). Conclusion: The inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful

Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy

Background: Since December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection. Methods: This work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality. Results: Of 13,932 patients, antibiotics were used in 12,238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21-1.62; p < .001) except macrolides, which had a higher survival rate (OR 0.70, 95% CI 0.64-0.76; p < .001). The decision to start antibiotics was influenced by presence of increased inflammatory markers and any kind of infiltrate on an x-ray. Patients receiving antibiotics required respiratory support and were transferred to intensive care units more often. Conclusions: Bacterial co-infection was uncommon among COVID-19 patients, yet use of antibiotics was high. There is insufficient evidence to support widespread use of empiric antibiotics in these patients. Most may not require empiric treatment and if they do, there is promising evidence regarding azithromycin as a potential COVID-19 treatment

Anales de Edafología y Agrobiología Tomo 42 Número 7-8

Suelos. Características petroquímicas y micromorfológicas de suelos gley y tierra parda con pseudogley en la sierra de Guadarrama, por J. Gallardo, P. Arévalo y J. Benayas.-- Adición de residuos vegetales a suelos calizos. IV. Estudio de ácidos húmicos, por J. Cegarra, M. T. Hernández. A. Lax y F. Costa.-- Caracterización físico-química. y mineralógica de los suelos del Moncayo, por M. A. Hoyos, J. Casas y J. L. Martín de Vidales.-- Balances mineralógicos y texturales en la formación de suelos de toposecuencias típicas de la parte central del Valle de los Pedroches (Cordoba), por M. A. Parra, J. Torrent, J. Barrios y L. Montealegre.-- Aplicación de diversos tipos de cromatografía en columna al fraccionamiento de un ácido húmico de tipo P, por G. Almendros, A. Polo y M. C. Lobo.-- Estudio genético de dos suelos desurollados bajo hayas y sobre material original ácido, en la provincia de Santander, por Hoyos de Castro, A., Palomar García Villamil, M. L., Hernando Massanet,I. y Guemes García, M.-- Compuestos Montmorillonita-Metilvinilsiloxano, por F. Aragón de la Cruz y C. Vitón Barbolla Fraccionamiento de sustancias húmicas en suelos ácidos de Valsaín (Segovia), por A. Hoyos, M. A. Candas y J. González Parra.-- Contribución al estudio de los suelos del Calar del Mundo (Albacete, II. Mineralogía de arcillas, por L. J. Alias Perez, J. Hemández Bastida y M. a Teresa Fernández Tapia.-- Aislamiento y caracterización de la unidades de estructura del suelo, por González Carcedo, S., Rojo Camara, M. J. y Perez,.Mateos, M.-- Procesos de alteración, génesis y estabilidad mineral de suelos volcánicos (volcán de Piedrabuena, Ciudad Real). 111. Mineralogía de las rocas, arenas y limos, por Casas, J., Guijarro, J. y Martín de Vidales, J. L.-- . Suelos AC sobre granitos de Galicia (n.o. de España) con especial referencia al ranker Atlántico. l. Factores de formación y morfología, por Carballas, M., Guitian Ojea, F. y Carballas, T.-- Estimación de parámetros en isotermas de adsorción por el método del Simplex. Aplicación a la isoterma de Freundlich para la adsorción de fosfato por suelos, por M. G. Guillén, F. Santa Cruz y M. C. Bolarin.—Fertilidad del suelo. Estudio del plomo en el sistema suelo-planta. Relación con factores edáficos pH, textura y materia orgánica, por A. Garate y J. J. Lucena.—Nutrición y Fisiología Vegetal. Estudio de mostos de vendimia y fermentados de la zona Montilla-Motiles: l. Azucares reductores acidez total, acidez volatil, cenizas y grado alcohólico, por R. Ordoñez, G. Paneque, M. Medina y L. Corral.-- Estudio de mostos de vendimia y fermentados de la zona Montilla-Motiles: II. K, Ca, Na, Mg, Fe, Cu, Zn y Mn, por R. Ordoñez, G. Paneque, M. Medina y L. Corral.--Análisis factorial de variables relacionadas con la maduración de la uva en el marco Montilla· Moriles, por Tirado Coello, J. L., Moreno Vigara, J. J., Medina Carnicer, M., Corral Mora, L. y Paneque Guerrero, G.--Cambios metabólicos de proteínas durante el Proceso de germinación de semilla de Pinus Pinea L. sometida a un periodo de estratificación, por Arce, C., Buenadicha, P. y Sanz, M.-- Condiciones de extracción de nutrientes en tejidos vegetales. l. Estudio del tiempo de extracción, por A. Molina-Díaz y E. Esteban.-- Efectos de la irradiación con UV cercano sobre la actividad del enzima PAL (Fenilalanina amonio liasa) en plantulas de ononis spinosa L., por J. Baztan.-- Efectos de las cubiertas de plástico sobre la temperatura del suelo y sobre el desarrollo de las plantas de tomate, por A. Cerda, A. A. Contreras, F. G. Fernández y M. Caro.-- Estudio por criofractura de plasmalema del ficobionte en diferentes condiciones ambientales, por S. Rapsch y C. Ascaso.-- Arupación intraespecifica en variedades de pimiento, por J. Cuartero, M. L. Gómez-Guillamón, J. J. Simón y E. Carbonell.-- Formación de la espiga, interceptación y uso de la luz y Producción de grano en respuesta a la fecha de siembra y el fertilizante nitrogenado en el trigo, por R. Martínez-Carrasco y P. Perez.-- Modificaciones de la micro flora edáfica del ciclo del nitrógeno bajo Myrica Gale L., por F. J. Gutierrez Mañero y F. Bermudez de Castro.-- Análisis foliar en cultivos hortícolas. Berenjena (Solanum Melongena L.), por S. Jaime Palacio, J. Ruiz Muñoz y E. Esteban Velasco.-- Desarrollo y composición mineral de las plantas de tomate (Lycopersicum Esculentum Mili) en relación con la concentración de S04 en el medio de raíces, por V. Martinez, A. Cerda, M. Caro y F. G. Femández.—Meteorología. Descensos de temperatura mínima y olas de frío. Predicción, por Eulogio L. García y José Garmendia.-- El potencial de Montgomery como variable climatológica asociada a los días estadísticamente fríos, por C. Tomás Sánchez, E. Gorda Díez y J. Garmendla Iraundegui.--Trabajos recapitulativos. Mecanismo de acción de herbicidas con actividad antifotosintética, por J. López Gorge, A. Chueca y M. Barón.-- Extractantes químicos de elementos traza en suelos de cultivo. Plantas indicadoras, por A. Aguilar y L. Romero.-- Notas.-- BibliografíaPeer reviewe

Demographic, clinical, and functional determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation

Altres ajuts: Alliance Bristol-Myers Squibb/Pfizer.Background: This study assessed the sociodemographic, functional, and clinical determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation (NVAF) attended in the internal medicine setting. Methods: A multicenter, cross-sectional study was conducted in NVAF patients who attended internal medicine departments for either a routine visit (outpatients) or hospitalization (inpatients). Results: A total of 961 patients were evaluated. Their antithrombotic management included: no treatment (4.7%), vitamin K antagonists (VKAs) (59.6%), direct oral anticoagulants (DOACs) (21.6%), antiplatelets (6.6%), and antiplatelets plus anticoagulants (7.5%). Permanent NVAF and congestive heart failure were associated with preferential use of oral anticoagulation over antiplatelets, while intermediate-to high-mortality risk according to the PROFUND index was associated with a higher likelihood of using antiplatelet therapy instead of oral anticoagulation. Longer disease duration and institutionalization were identified as determinants of VKA use over DOACs. Female gender, higher education, and having suffered a stroke determined a preferential use of DOACs. Conclusions: This real-world study showed that most elderly NVAF patients received oral anticoagulation, mainly VKAs, while DOACs remained underused. Antiplatelets were still offered to a proportion of patients. Longer duration of NVAF and institutionalization were identified as determinants of VKA use over DOACs. A poor prognosis according to the PROFUND index was identified as a factor preventing the use of oral anticoagulation

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field