Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Anuario de administración y tecnología para el diseño 2018

Publicación anual. Año 18, número 18 (mayo 2018 a mayo 2019)El Área de Administración y Tecnología para el Diseño quiere hacer un homenaje a la innovación y vanguardia arquitectónica representada por el despacho del Arq. Benjamín Romano y ha plasmado en la cubierta del Anuario una foto del edificio premiado. El edificio de oficinas de su autoría, Torre Reforma en la Ciudad de México ha ganado el premio al rascacielos más innovador del mundo otorgado por el Deutsches Architekturmuseum (DAM). Uno de los premios de arquitectura más importantes del mundo para edificios altos, el lnternational Highrise Award se otorga cada dos años al proyecto que mejor ejemplifica los criterios de diseño orientado al Muro, funcionalidad, tecnología de construcción innovadora, integración en esquemas de desarrollo urbano, sostenibilidad y rentabilidad. DAM describió el proyecto y la innovación de su diseño. En contraste con la tendencia internacional duradera hacia las torres residenciales, así como los proyectos de uso mixto cada vez más grandes en Asia, el ganador del premio de este año es una vez más un edificio de oficinas clásico. Sin embargo, se trata de un proyecto que atiende más que solo eso. El problema predominante de los terremotos en la Ciudad de México requiere un concepto de estructura de apoyo inteligente, que preste a la torre de oficinas de 246 metro5 de altura su sorprendente aspecto. Al hacerlo, Torre Reforma de L. Benjamín Romano coloca a la capital de México en el mapa mundial de Arquitectura de gran altura innovadora. Como resultado del trabajo de investigación del Área de Administración y Tecnología para el Diseño, se presenta en esta ocasión la edición 2018 del presente Anuario en la décimo novena versión que se publica y que es una muestra fehaciente del esfuerzo e interés de un grupo de académicos en este campo de estudio y como una plataforma de intercambio académico, exposición y debate de esta área del conocimiento. En este sentido, los artículos aquí presentados han sido producidos bajo los parámetros de evaluación como artículos científicos. La intención de los Anuarios es presentar la Administración y la Tecnología corno parte de la ciencia, desde el punto de vista objetivo, analítico y virtual, con énfasis en la innovación y vanguardia del conocimiento para el diseño y la producción arquitectónica, de diseño industrial y de ingeniería Presentamos colaboraciones interinstitucionales, en el ámbito internacional: La participación del Colegio de Ingenieros Topógrafos de Costa Rica, la intervención de investigadores nacionales del Instituto Politécnico Nacional (IPN), de la Ciudad de México, del Instituto Tecnológico y de Estudios Superiores de Occidente (ITESO) de Guadalajara, Jal. Asimismo, hay varios de los artículos del personal académico de la Universidad Autónoma Metropolitana (UAM) La División de Ciencias y Artes para el Diseño (CYAD), a la que pertenece el Área, sistemáticamente ha tenido vinculación con el Área de Construcción del Departamento de Materiales de la División de Ciencias Básicas e Ingeniería (CBI), así como colaboración interdepartamental con el Departamento de Evaluación del Diseño en el Tiempo

Quorum sensing network in clinical strains of A. baumannii : AidA is a new quorum quenching enzyme

Acinetobacter baumannii is an important pathogen that causes nosocomial infections generally associated with high mortality and morbidity in Intensive Care Units (ICUs). Currently, little is known about the Quorum Sensing (QS)/Quorum Quenching (QQ) systems of this pathogen. We analyzed these mechanisms in seven clinical isolates of A. baumannii. Microarray analysis of one of these clinical isolates, Ab1 (A. baumannii ST-2-clon-2010), previously cultured in the presence of 3-oxo-C12-HSL (a QS signalling molecule) revealed a putative QQ enzyme (α/β hydrolase gene, AidA). This QQ enzyme was present in all nonmotile clinical isolates (67% of which were isolated from the respiratory tract) cultured in nutrient depleted LB medium. Interestingly, this gene was not located in the genome of the only motile clinical strain growing in this medium (A. baumannii strain Ab421-GEIH-2010 [Ab7], isolated from a blood sample). The AidA protein expressed in E. coli showed QQ activity. Finally, we observed downregulation of the AidA protein (QQ system attenuation) in the presence of HO (ROS stress). In conclusion, most of the A. baumannii clinical strains were not surface motile (84%) and were of respiratory origin (67%). Only the pilT gene was involved in surface motility and related to the QS system. Finally, a new QQ enzyme (α/β hydrolase gene, AidA protein) was detected in these strains

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C : A prospective observational study

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with ≥2 clinical signs/symptoms of NP-C were considered 'suspected NP-C' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI ≥70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 [4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores ≥70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts