Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV-2 infection: Retrospective cohort study

Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching. Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Macrobenthic communities in a fishery exclusion zone and in a trawled area of the middle Adriatic Sea (Italy)

Macrobenthic communities in a commercial fishing ground (middle Adriatic Sea) exploited by otter trawling were compared with communities living in an area closed to fishing for over 10 years located near a gas platform. Our data highlighted significant differences in macrofaunal community structure between the two areas. In addition, the macrofaunal communities in the fished area displayed evidence of a higher level of stress compared with the other one. Several taxa reported in the literature as being sensitive to trawling (e.g., Ebalia tuberosa, Callianassa subterranea) were markedly more abundant in the area not affected by fishing. Macrofaunal community analysis using the index of multivariate dispersion and k-dominance curves provided evidence of stress in the fished area; however, it is not possible to predict whether the patterns observed will remain consistent over time based on only two temporal replicates. It is likely that the magnitude of the macrofaunal community response to fishing changes during the year according to season and fishing effort.

Effects of chronic trawling disturbance on the secondary production of suprabenthic and infaunal crustacean communities in the Adriatic Sea (NW Mediterranean)

Towing gears are known to produce several kinds of effects on benthic ecosystems. As small organisms and benthic species with faster growth rates and shorter life histories can withstand the fishing mortality and benefit from reduced competition or predation, trawl fishing can enhance their proliferation. Thus, trawl fishing can lead to biomass loss and production increase, since smaller specimens are more productive than bigger ones. In the present study we evaluate the effects, if any, of trawling on benthic crustacean macrofaunal production rates. Sampling was carried out in two neighbouring sites in the central Adriatic Sea (central Mediterranean), one affected by fishing activity and one not. Production and production/biomass (P/B) ratio of 13 species of peracarid and eucarid crustaceans were estimated using the Hynes size-frequency method. Estimates measured at both sites were compared in order to test the hypothesis that higher production and P/B values should occur in the fished area rather than in the unfished one. Our results indicated that the effects on the species are more complex than expected in regard to this hypothesis, and that they depend on the ecological and behavioural characteristics of the selected species.

Spatial heterogeneity in the distribution of plants and benthic invertebrates in the lagoon of Orbetello (Italy)

Many studies in marine coastal lagoons have focused on the marine-to-terrestrial gradient as a main source of variation for the structure of assemblages. In this paper, the magnitude of differences among locations arranged along the marine-to-terrestrial gradient of the western lagoon of Orbetello (Grosseto, Italy) was contrasted with the amount of spatial variability occurring among sets of locations that were not positioned along this axis. We propose that if the most important processes influencing assemblages were those associated with the external-internal gradient of the lagoon, as usually supposed, then assemblages should differ more among these locations than among any other locations. To test the above proposition, four locations arranged along the two major axes of the lagoon were established in November 2000. Each location was sampled three times (November 2000, April 2001, August 2001) to test for temporal consistency in spatial patterns. At each time of sampling, three replicate sites were established in each location. This design enabled estimates of spatial variability to be obtained at three scales: among locations hundreds of meters apart, among sites tens of meters apart and among quadrats hundreds of centimeters apart. Non-metric multidimensional scaling (nMDS) ordination plots on abundance data revealed differences among assemblages hundreds of meters apart. Assemblages in the inner part of the lagoon were separated from those closer to the sea inlet, depending on the marine-to-terrestrial gradient. In addition to this pattern, differences also occurred among assemblages hundreds of meters apart, but positioned at a similar distance from the sea. Multifactorial Anovas on abundance of the most common taxa showed significant differences in mean values at the scales of location and site, with patterns changing over time. These results indicated that spatial structure in assemblages was not a distinctive feature of locations arranged along the marine-to-terrestrial gradient in the lagoon of Orbetello. Similar differences also occurred among other sets of locations at the scale of hundreds of meters, regardless of their position in the lagoon.Beaucoup de recherches sur les lagunes côtières se sont focalisées sur le gradient terre-mer comme principale source de variation de la structure des assemblages. Dans cet article, l'importance des différences d'un lieu à l'autre le long d'un tel gradient dans la partie ouest de la lagune d'Orbetello (Grosseto, Italie) est comparée avec l'importance de la variabilité spatiale de sites qui ne sont pas situés sur cet axe. Si l'influence dominante était bien liée à ce gradient interne-externe, les assemblages devraient différer plus nettement au sein de ces lieux, comparé à tout autre lieu. Pour tester cette proposition, quatre lieux le long des deux axes majeurs de la lagune ont été échantillonnés à trois reprises : novembre 2000, avril 2001 et août 2001. À chaque sortie, trois sites-répliques ont été établis pour chaque lieu. Cette stratégie permet d'estimer la variabilité spatiale à trois échelles : au sein des lieux à des distances de 100 mètres, au sein des sites à des distances de 10 mètres et au sein des quadrats à des distances d'un mètre. Des diagrammes d'abondance classés suivant une échelle multidimensionnelle non métrique révèlent des différences au sein des assemblages distants de centaines de mètres. Les assemblages dans la partie intérieure de la lagune sont séparés de ceux plus près du grau, en accord avec le gradient terre-mer. À côté de ce schéma, des différences apparaissent également parmi les assemblages distants de plusieurs centaines de mètres mais situés à une même distance de la mer. Une analyse multifactorielle utilisant le test Anovas sur l'abondance des taxons les plus fréquents montre des différences significatives des valeurs moyennes aux échelles du lieu et du site, avec des schémas d'organisation variant au cours du temps. Ces résultats montrent que la structure spatiale des assemblages n'est pas un trait caractéristique des lieux bâti autour du terre-mer dans la lagune d'Orbetello. Des différences similaires se rencontrent également parmi les autres ensembles de lieux à l'échelle des centaines de mètres, ceci dépendant de leur position dans la lagune