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.

Evolution of susceptibilities of Campylobacter spp. to quinolones and macrolides.

Abstract: Erythromycin, new macrolides, and quinolones are alternatives for the treatment of Campylobacter infections. Concerns related to the emergence of resistance to both groups of drugs have been raised. We studied the evolution of antimicrobial susceptibilities of 275 clinical isolates of microorganisms of the genus Campylobacter isolated in our institution during a 5-year period (1988 to 1992). The microorganisms studied were C. jejuni (n = 230), C. coli (n = 42), and C. fetus (n = 3). The overall resistance rates (determined by the agar dilution method and the recommendations of the National Committee for Clinical Laboratory Standards) were as follows: erythromycin, 2.3%; clarithromycin, 2.3%; azithromycin, 1.9%; ciprofloxacin, 28.5%; norfloxacin, 31%; ofloxacin, 26.3%; and nalidixic acid, 36.8%. The evolution of resistance (percent resistance in 1988 versus percent resistance in 1992) was as follows: erythromycin, 2.6 versus 3.1; clarithromycin, 2.6 versus 3.1; azithromycin, 2.6 versus 3.1; ciprofloxacin, 0 versus 49.5; norfloxacin, 2.6 versus 55.5; ofloxacin, 0 versus 45.6; nalidixic acid, 2.6 versus 56.8. Our data show stable macrolide activity against Campylobacter spp. and the rapid development of quinolone resistance over the last 5 years.

Moesin orchestrates cortical polarity of melanoma tumour cells to initiate 3D invasion

Abstract: Tumour cell dissemination through corporal fluids (blood, lymph and body cavity fluids) is a distinctive feature of the metastatic process. Tumour cell transition from fluid to adhesive conditions involves an early polarization event and major rearrangements of the submembrane cytoskeleton that remain poorly understood. As regulation of cortical actin-membrane binding might be important in this process, we investigated the role of ezrin and moesin, which are key crosslinking proteins of the ERM (ezrin, radixin, moesin) family. We used short interfering RNA (siRNA) to show that moesin is crucial for invasion by melanoma cells in 3D matrices and in early lung colonization. Using live imaging, we show that following initial adhesion to the endothelium or 3D matrices, moesin is redistributed away from the region of adhesion, thereby generating a polarized cortex: a stable cortical actin dome enriched in moesin and an invasive membrane domain full of blebs. Using Lifeact-GFP, a 17-amino-acid peptide that binds F-actin, we show the initial symmetry breaking of cortical actin cytoskeleton during early attachment of round cells. We also demonstrated that ezrin and moesin are differentially distributed during initial invasion of 3D matrices, and, specifically, that moesin controls adhesion-dependent activation of Rho and subsequent myosin II contractility. Our results reveal that polarized moesin plays a role in orienting Rho activation, myosin II contractility, and cortical actin stability, which is crucial for driving directional vertical migration instead of superficial spreading on the fluid-to-solid tissue interface. We propose that this mechanism of cortical polarization could sustain extravasation of fluid-borne tumour cells during the process of metastasis.

Factors associated with mortality in pediatric in-hospital cardiac arrest: a prospective multicenter multinational observational study

Abstract: To analyze prognostic factors associated with in-hospital cardiac arrest (CA) in children. A prospective, multicenter, multinational, observational study was performed on pediatric in-hospital CA in 12 countries and included 502 children between 1 month and 18 years. The primary endpoint was survival at hospital discharge. Univariate and multivariate logistic regression analyses were performed to assess the influence of each factor on mortality. Return of spontaneous circulation was achieved in 69.5 % of patients; 39.2 % survived to hospital discharge and 88.9 % of survivors had good neurological outcome. The pre-arrest factors related to mortality were lower Human Development Index [odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.28–4.21], oncohematologic disease (OR 3.33, 95 % CI 1.60–6.98), and treatment with inotropic drugs at the time of CA (OR 2.35, 95 % CI 1.55–3.56). CA and resuscitation factors related to mortality were CA due to neurological disease (OR 5.19, 95 % CI 1.49–18.73) and duration of cardiopulmonary resuscitation greater than 10 min (OR 4.00, 95 % CI 1.49–18.73). Factors related to survival were CA occurring in the pediatric intensive care unit (PICU) (OR 0.38, 95 % CI 0.16–0.86) and shockable rhythm (OR 0.26, 95 % CI 0.09–0.73). In-hospital CA in children has a low survival but most of the survivors have a good neurological outcome. Some prognostic risk factors cannot be modified, making it important to focus efforts on improving hospital organization to care for children at risk of CA in the PICU and, in particular, in other hospital areas.

SARS-CoV-2-RNA viremia is associated to hypercytokinemia and critical illness in COVID-19

Abstract: Background: Severe COVID-19 is characterized by clinical and biological manifestations typically observed in sepsis. SARS-CoV-2 RNA is commonly detected in nasopharyngeal swabs, however viral RNA can be found also in peripheral blood and other tissues. Whether systemic spreading of the virus or viral components plays a role in the pathogenesis of the sepsis like disease observed in severe COVID-19 is currently unknown. Methods: We determined the association of plasma SARS-CoV-2 RNA with the biological responses and the clinical severity of patients with COVID-19. 250 patients with confirmed COVID-19 infection were recruited (50 outpatients, 100 hospitalised ward patients, and 100 critically ill). The association between plasma SARS-CoV-2 RNA and laboratory parameters was evaluated using multivariate GLM with a gamma distribution. The association between plasma SARS-CoV-2 RNA and severity was evaluated using multivariate ordinal logistic regression analysis and Generalized Linear Model (GLM) analysis with a binomial distribution. Results: The presence of SARS-CoV-2 RNA viremia was independently associated with a number of features consistently identified in sepsis: 1) high levels of cytokines (including CXCL10, CCL-2, IL-10, IL-1ra, IL-15, and G-CSF); 2) higher levels of ferritin and LDH; 3) low lymphocyte and monocyte counts 4) and low platelet counts. In hospitalised patients, the presence of SARS-CoV-2 RNA viremia was independently associated with critical illness: (adjusted OR= 8.30 [CI95%=4.21-16.34], p < 0.001). CXCL10 was the most accurate identifier of SARS-CoV-2-RNA viremia in plasma (area under the curve (AUC), [CI95%], p) = 0.85 [0.80 0.89), <0.001]), suggesting its potential role as a surrogate biomarker of viremia. The cytokine IL-15 most accurately differentiated clinical ward patients from ICU patients (AUC: 0.82 [0.76 0.88], <0.001). Conclusions: systemic dissemination of genomic material of SARS-CoV-2 is associated with a sepsis-like biological response and critical illness in patients with COVID-19. RNA viremia could represent an important link between SARS-CoV-2 infection, host response dysfunction and the transition from moderate illness to severe, sepsis-like COVID-19 disease.