Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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The ongoing coronavirus disease 2019 (COVID-19) pandemic has swept over the world and causes thousands of deaths. Although the clinical features of COVID-19 become much clearer than before, there are still further problems with the pathophysiological process and treatments of severe patients. One primary problem is with the paradoxical immune states in severe patients with COVID-19. ⋯ Therefore, discussing the specific status of immunity in COVID-19 will contribute to the understanding of its pathophysiology and the search for appropriate treatments. Here, we review all the available literature concerning the different immune states in COVID-19 and the underlying pathophysiological mechanisms. In addition, the association between immune states and the development and severity of disease as well as the impact on the selection of immunotherapy strategies are discussed in our review.
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Review Comparative Study
Sex- and Gender-Dependent Differences in Clinical and Preclinical Sepsis.
In this mini-review we provide an overview of sex- and gender-dependent issues in both clinical and preclinical sepsis. The increasing recognition for the need to account for sex and gender in biomedical research brings a unique set of challenges and requires researchers to adopt best practices when conducting and communicating sex- and gender-based research. This may be of particular importance in sepsis, given the potential contribution of sex bias in the failures of translational sepsis research in adults and neonates. ⋯ Significant knowledge gaps still exist in this field. Future investigations can address these gaps through careful consideration of sex and gender in clinical studies, and the use of clinically accurate preclinical models that reflect sex differences. A better understanding of sex-and gender-dependent differences may serve to increase translational research success.
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Hemolysis that occurs in intravascular hemolytic disorders, such as sickle cell disease and malaria, is associated with inflammation and platelet activation. Alveolar hemorrhage, for example following primary blast lung injury or acute respiratory distress syndrome, results in the escape of erythrocytes (RBCs) into alveolar spaces, where they subsequently lyse and release their intracellular contents. However, the inflammatory effects of RBCs in the airways are not fully understood. ⋯ To identify specific platelet-dependent signaling pathways involved in neutrophil recruitment, anti-P-selectin ligand and anti-PSGL1 blocking antibodies were tested; however, neither affected neutrophil recruitment. These findings implicate an involvement for other, as yet unidentified platelet-dependent signaling and adhesion mechanisms. Further understanding of how platelets contribute to lung inflammation induced by the presence of RBCs could offer novel therapeutic approaches to attenuate inflammation that occurs in conditions associated with alveolar hemorrhage.
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Host cells recognize molecules that signal danger using pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are the most studied class of PRRs and detect pathogen-associated molecular patterns and danger-associated molecular patterns. ⋯ Here, we review the expression, regulation, and function of different TLRs, with an emphasis on TLR-4, and how TLR adaptor protein binding directs intracellular signaling resulting in activation or termination of an innate immune response. Finally, we highlight the recent progress of research on the involvement of S100 proteins as ligands for TLR-4 in inflammatory disease.
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Lactic acidosis after cardiac surgery with cardiopulmonary bypass is common and associated with an increase in postoperative morbidity and mortality. A number of potential causes for an elevated lactate after cardiopulmonary bypass include cellular hypoxia, impaired tissue perfusion, ischemic-reperfusion injury, aerobic glycolysis, catecholamine infusions, and systemic inflammatory response after exposure to the artificial cardiopulmonary bypass circuit. Our goal was to examine the relationship between early abnormalities in microcirculatory convective blood flow and diffusive capacity and lactate kinetics during early resuscitation in the intensive care unit. We hypothesized that patients with impaired microcirculation after cardiac surgery would have a more severe postoperative hyperlactatemia, represented by the lactate time-integral of an arterial blood lactate concentration greater than 2.0 mmol/L. ⋯ Low perfused vessel density and high microcirculatory heterogeneity are associated with an increased intensity and duration of lactic acidosis after cardiac surgery with cardiopulmonary bypass.