Hospital General Universitario Gregorio Marañón

About: Hospital General Universitario Gregorio Marañón is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Transplantation. The organization has 11975 authors who have published 12386 publications receiving 244847 citations.

Documento de consenso sobre el fenotipo mixto EPOC-asma en la EPOC

Abstract: Resumen Introduccion Aunque asma y EPOC son enfermedades distintas, muchos pacientes comparten caracteristicas de ambas entidades. Estos casos pueden tener una evolucion y una respuesta al tratamiento diferente. Sin embargo, la evidencia disponible es escasa, y es necesario valorar si representan un fenotipo diferencial y aportar recomendaciones sobre su diagnostico y tratamiento, ademas de identificar posibles lagunas de conocimiento. Metodo Consenso nacional de expertos en EPOC en dos etapas: 1) Se establecieron los bloques tematicos a tratar y se elaboro una primera propuesta de aseveraciones, mediante una reunion presencial con metodologia de «tormenta de ideas» estructurada. 2) Se realizaron dos rondas de consenso via correo electronico, utilizando una escala tipo Likert. Resultados Se consensua la existencia de un fenotipo clinico diferencial denominado «fenotipo mixto EPOC-asma», cuyo diagnostico se realizara si se cumplen 2 criterios mayores o uno mayor y 2 menores (criterios mayores: prueba broncodilatadora muy positiva [aumento del FEV 1 ≥ 15% y ≥ 400 ml], eosinofilia en esputo y antecedentes personales de asma; criterios menores: IgE total elevada, antecedentes personales de atopia y prueba broncodilatadora positiva [aumento del FEV 1 ≥ 12% y ≥ 200 ml] en dos o mas ocasiones). Se recomienda el uso precoz de corticoides inhalados (CI) ajustados individualmente, ser cautos con la retirada brusca de CI y, en casos graves, valorar el uso de la triple terapia. Finalmente, queda patente la falta de estudios especificos sobre la historia natural y el tratamiento de estos pacientes. Conclusiones Es preciso profundizar en el conocimiento de este fenotipo para establecer pautas y recomendaciones adecuadas para su diagnostico y tratamiento.

Tetraspanins CD9 and CD81 Modulate HIV-1-Induced Membrane Fusion

Abstract: Protein organization on the membrane of target cells may modulate HIV-1 transmission. Since the tetraspanin CD81 is associated to CD4, the receptor of HIV-1 envelope protein (Env; gp120/gp41), we have explored the possibility that this molecule may modulate the initial steps of HIV-1 infection. On the other hand, CD81 belongs to the tetraspanin family, which has been described as organizers of protein microdomains on the plasma membrane. Therefore, the role of CD81 and other related tetraspanin, CD9, on the cell-to-cell fusion process mediated by HIV-1 was studied. We found that anti-tetraspanin Abs enhanced the syncytia formation induced by HIV-1 envelope proteins and viral entry in human T lymphoblasts. In addition, anti-CD81 Abs triggered its clustering in patches, where CD4 and CXCR4 were included. Moreover, the knocking down of CD81 and CD9 expression resulted in an increase in syncytia formation and viral entry. Accordingly, overexpression of CD81 and CD9 rendered cells less susceptible to Env-mediated syncytia formation. These data indicate that CD9 and CD81 have an important role in membrane fusion induced by HIV-1 envelope.

Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.

Abstract: Aims Cardiopoietic cells, produced through cardiogenic conditioning of patients’ mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. Methods and results This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischemic heart failure on guideline-directed therapy ( n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells ( n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter ( n = 157) or sham procedure ( n = 158). Procedures were performed as randomized in 271 patients ( n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. Conclusion The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.

Abstract: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183–12.968], 0.025), viral RNA load (N1) (1.962 [1.244–3.096], 0.004); viral RNA load (N2) (2.229 [1.382–3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.