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

Modulation of the xenobiotic transformation system and inflammatory response by ochratoxin A exposure using a co-culture system of Caco-2 and HepG2 cells

Cytotoxicity of ochratoxin A (OTA) was evaluated using the MTS assay, and membrane integrity was measured using transepithelial electrical resistance (TEER). A transwell system was used to investigate the effect of OTA on the expression of the CYP450 (1A1, 2A6, 2B6, 3A4 and 3A5), NAT2, COX-2, LOX-5, and MRP2 genes in Caco-2 and HepG2 cells. TEER decreased by a mean of 63.2% after 24 h in Caco-2 differentiated cells without inducing cell detachment; revealing damage to the intestinal epithelial cell tight junction proteins and an increase in cell permeability. Gene expression analysis showed that modulation of gene expression by OTA was higher in Caco-2 cells than in HepG2 cells, and generally, the duration of exposure to OTA had a more significant effect than the OTA dose. A general OTA down-regulation effect was observed in Caco-2 cells, in contrast with the down- and up-regulation observed in HepG2 cells. In Caco-2 cells, CYP1A1 was the gene with the highest regulation, followed by CYP3A4 and CYP3A5. Conversely, in HepG2 cells, CYP2B6 was highly regulated at 3 and 12 h compared to the other cytochromes; CYP1A1 was slightly modulated during the first 12 h, but an overexpression was observed at 24 h. Our data support the involvement of the COX-2 and 5-LOX genes in liver metabolism of OTA. On the basis of the gene expression analysis, the results suggest a possible impairment in OTA secretion at the intestinal and hepatic level due to MRP2 repression. In addition, we provide evidence of the effect of OTA on NAT2 gene expression, which had not been reported before

African and Latin American family reunifications in Mediterranean Spain: dynamics and socio-demographic structures

Los extranjeros autorizados en 2006-2009 a residir en España por motivos de reagrupación familiar, muestran la importancia que ha alcanzado esta forma de inmigración en el total de nuevos extranjeros empadronados. La investigación se basa en una encuesta específica a reagrupantes africanos y latinoamericanos, que también informan sobre sus familiares reagrupados, hayan utilizado, o no, las leyes de reagrupación. Africanos y latinoamericanos ofrecen dinámicas y estructuras sociodemográficas muy diferentes, a resultas, entre otras causas, de la antigüedad de sus flujos, su fecundidad, su dominio del idioma español, su nivel de instrucción, sus posibilidades de ingresos, su estructura por sexo y edad, tamaño de las familias reagrupadas, etc. Se ofrece información para los dos colectivos continentales y para los subgrupos familiares —reagrupantes, cónyuges, hijos, progenitores y otros familiares—, y se utilizan escalas del conjunto estudiado y de ámbitos territoriales —Cataluña litoral, Comunidad Valenciana, Murcia-Almería—. Los africanos concentran los aspectos estructurales más negativos —idioma español, instrucción, ingresos,…—, pero también son los que declaran intenciones más firmes y generalizadas de permanencia en España. Las conclusiones orientan sobre el futuro de estos flujos.The amount of foreigners authorised to live in Spain as residents between 2006 and 2009 due to family reunification reflects the significance of this type of immigration in the number of new registered foreigners. This research is based on a specific survey carried out on Africans and Latin Americans, who also provide information on the family members who have joined them here, in accordance with reunification laws or not. Africans and Latin Americans have very different dynamics and socio-demographic structures due, amongst other reasons, to the antiquity of their flows, their fertility rates, their command of Spanish, their level of education, their possibility of income, their structure by sex and age, the size of the reunited families, etc. Information is provided on both continental groups and family subgroups —those who reunite the family, spouses, children, parents and other family members— using scales for the group studied and for the geographical area —coastal Catalonia, the Region of Valencia, Murcia and Almeria—. Africans report the most negative structural aspects —Spanish language, education, income, etc.—; nevertheless it is this group that claim to have more firm and generalised intentions of staying in Spain. The conclusions in this paper give an indication of future flows for these two groups.Investigación realizada dentro del Proyecto «La reagrupación familiar de los inmigrantes africanos y latinoamericanos en la España mediterránea», Ref. CSO2008-01796, financiado por el Ministerio de Ciencia e Innovación