122 research outputs found

    Atherosclerotic Pre-Conditioning Affects the Paracrine Role of Circulating Angiogenic Cells Ex-Vivo

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    In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenitor cells (eEPC), are thought to participate mainly in a paracrine fashion by promoting the recruitment of other cell populations such as late EPC, or endothelial colony-forming cells (ECFC), to the injured areas. There, ECFC replace the damaged endothelium, promoting neovascularization. However, despite their regenerative role, the number and function of EPC are severely affected under pathological conditions, being essential to further understand how these cells react to such environments in order to implement their use in regenerative cell therapies. Herein, we evaluated the effect of direct incubation ex vivo of healthy CAC with the secretome of atherosclerotic arteries. By using a quantitative proteomics approach, 194 altered proteins were identified in the secretome of pre-conditioned CAC, many of them related to inhibition of angiogenesis (e.g., endostatin, thrombospondin-1, fibulins) and cell migration. Functional assays corroborated that healthy CAC released factors enhanced ECFC angiogenesis, but, after atherosclerotic pre-conditioning, the secretome of pre-stimulated CAC negatively affected ECFC migration, as well as their ability to form tubules on a basement membrane matrix assay. Overall, we have shown here, for the first time, the effect of atherosclerotic factors over the paracrine role of CAC ex vivo. The increased release of angiogenic inhibitors by CAC in response to atherosclerotic factors induced an angiogenic switch, by blocking ECFC ability to form tubules in response to pre-conditioned CAC. Thus, we confirmed here that the angiogenic role of CAC is highly affected by the atherosclerotic environment

    IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

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    Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

    Socio-Demographic Health Determinants Are Associated with Poor Prognosis in Spanish Patients Hospitalized with COVID-19

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    Introduction Social vulnerability is a known determinant of health in respiratory diseases. Our aim was to identify whether there are socio-demographic factors among COVID-19 patients hospitalized in Spain and their potential impact on health outcomes during the hospitalization. Methods A multicentric retrospective case series study based on administrative databases that included all COVID-19 cases admitted in 19 Spanish hospitals from 1 March to 15 April 2020. Socio-demographic data were collected. Outcomes were critical care admission and in-hospital mortality. Results We included 10,110 COVID-19 patients admitted to 18 Spanish hospitals (median age 68 (IQR 54–80) years old; 44.5% female; 14.8% were not born in Spain). Among these, 779 (7.7%) cases were admitted to critical care units and 1678 (16.6%) patients died during the hospitalization. Age, male gender, being immigrant, and low hospital saturation were independently associated with being admitted to an intensive care unit. Age, male gender, being immigrant, percentile of average per capita income, and hospital experience were independently associated with in-hospital mortality. Conclusions Social determinants such as residence in low-income areas and being born in Latin American countries were associated with increased odds of being admitted to an intensive care unit and of in-hospital mortality. There was considerable variation in outcomes between different Spanish centers.JPA is under contract within the Ramón y Cajal Program (RYC-2016-20155, Ministerio de Economía, Industria y Competitividad, Spain). Investigators of Spanish Social-Environmental COVID-19 Register: Steering Committee: F. Javier Martín-Sánchez, Adrián Valls Carbó, Carmen Martínez Valero, Juan de D. Miranda, Juan Pedro Arrebola, Marta Esteban López, Annika Parviainen, Òscar Miró, Pere Llorens, Sònia Jiménez, Pascual Piñera, Guillermo Burillo, Alfonso Martín, Jorge García Lamberechts, Javier Jacob, Aitor Alquézar, Juan González del Castillo, Amanda López Picado and Iván Núñez. Participating centers: Oscar Miró y Sonia Jimenez. Hospital Clinic de Barcelona. José María Ferreras Amez. Hospital Clínico Universitario Lozano Blesa. Rafael Rubio Díaz. Complejo Hospitalario de Toledo. Julio Javier Gamazo del Rio. Hospital Universitario de Galdakao. Héctor Alonso. Hospital Universitario Miguel de Valdecilla. Pablo Herrero. Hospital Universitario Central de Asturias. Noemí Ruiz de Lobera. Hospital San Pedro de Logroño. Carlos Ibero. Complejo Hospitalario de Navarra. Plácido Mayan. Hospital Clínico Universitario de Santiago. Rosario Peinado. Complejo Hospitalario Universitario de Badajoz. Carmen Navarro Bustos. Hospital Universitario Virgen de la Macarena. Jesús Álvarez Manzanares. Hospital Universitario Rio Hortega. Francisco Román. Hospital Universitario General de Alicante. Pascual Piñera. Hospital Universitario Reina Sofia de Murcia. Guillermo Burillo. Hospital Universitario de Canarias de Tenerife. Javier Jacob. Hospital Universitario de Bellvitge. Carlos Bibiano. Hospital Universitario Infanta Leonor.Peer reviewe
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