Graphical Abstract Highlights d Severe COVID-19 patients display immune dysregulation or macrophage activation syndrome d Severe respiratory failure is associated with a major decrease of HLA-DR on CD14 monocytes d CD4 cell and NK cell cytopenias are characteristics of severe COVID-19 d IL-6 blocker Tocilizumab partially rescues SARS-CoV-2associated immune dysregulation
Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.
Background and aimsIn the absence of classical features (fever, cardiac murmur, and peripheral vascular stigmata) the diagnosis of infective endocarditis (IE) may be difficult. Current clinical guidelines for the diagnosis and management of IE recommend the use of modified Duke criteria. Correct and prompt diagnosis of IE is crucial for the treatment and outcome of the patients.The aim of this study was to evaluate the presence and the individual value of each criterion of the modified Duke criteria in our patients with infective endocarditis.MethodsWe performed a prospective observational study between January 2008 – June 2014, in which we enrolled consecutive adult patients admitted for suspicion of IE to the Hospital of Infectious Diseases and at the Heart Institute . We used and extensive database in order to collect demographic data, laboratory and echocardiography results, evolution and outcome of the patients. Using the modified Duke criteria we identified 3 categories of IE: definite, possible and rejected. In order to evaluate the importance of each criterion in the diagnosis of IE we tested two hypotheses. First, we excluded each criterion from the final diagnosis and we counted how many cases felt into a lower category. Second, after adding each major and minor criterion, we tested how many cases would have been classifiable as definite IE.ResultsThe study included 241 adult patients with a mean age 58.16 years and sex ratio male/female 1.94. According to the modified Duke criteria 137 patients had definite IE, 79 patients had possible IE and 25 cases had rejected IE We had blood cultures positive IE in 109 cases and blood culture negative IE (BCNE) in 132 (71.21%) cases. Antibiotic treatment prior to blood culture was recorded in 152 (63.07%) patients. In the absence of the echocardiography major criterion, 43% of cases would become possible. After extraction of major microbiological criterion, only one third of definite cases would become possible. Minor criteria such as fever and predisposition contributed to the diagnosis only in 10% of cases. In the presence of vascular or immunological phenomena, or in the presence of minor microbiological criterion, half of the possible IE cases could become possible.ConclusionTwenty-years after their launch, the Duke criteria for the diagnosis of IE continue to be important tools. Low index of suspicion of IE and inappropriate use of antibiotics may have a great negative impact on the diagnosis of IE. Nowadays, the scarcity of classical Osler manifestations - bacteremia, fever and peripheral stigmata - makes the diagnosis of IE a challenge.
Despite the importance of immune variation for the symptoms and outcome of Lyme disease, the factors influencing cytokine production during infection with the causal pathogen Borrelia burgdorferi remain poorly understood. Borrelia infection-induced monocyte- and T cell-derived cytokines were profiled in peripheral blood from two healthy human cohorts of Western Europeans from the Human Functional Genomics Project. Both non-genetic and genetic host factors were found to influence Borrelia-induced cytokine responses. Age strongly impaired IL-22 responses, and genetic studies identified several independent QTLs that impact Borrelia-induced cytokine production. Genetic, transcriptomic, and functional validation studies revealed an important role for HIF-1α-mediated glycolysis in the cytokine response to Borrelia. HIF-1α pathway activation and increase in glycolysis-derived lactate was confirmed in Lyme disease patients. In conclusion, functional genomics approaches reveal the architecture of cytokine production induced by Borrelia infection of human primary leukocytes and suggest a connection between cellular glucose metabolism and Borrelia-induced cytokine production.
Pathogen-induced changes in host cell metabolism are known to be important for the immune response. In this study, we investigated how infection with the Lyme disease-causing bacterium () affects host metabolic pathways and how these metabolic pathways may impact host defense. First, metabolome analysis was performed on human primary monocytes from healthy volunteers, stimulated for 24 h with at low multiplicity of infection (MOI). Pathway analysis indicated that glutathione (GSH) metabolism was the pathway most significantly affected by Specifically, intracellular levels of GSH increased on average 10-fold in response to exposure. Furthermore, these changes were found to be specific, as they were not seen during stimulation with other pathogens. Next, metabolome analysis was performed on serum samples from patients with early-onset Lyme disease in comparison with patients with other infections. Supporting the in vitro analysis, we identified a cluster of GSH-related metabolites, the γ-glutamyl amino acids, specifically altered in patients with Lyme disease, and not in other infections. Lastly, we performed in vitro experiments to validate the role for GSH metabolism in host response against We found that the GSH pathway is essential for -induced cytokine production and identified glutathionylation as a potential mediating mechanism. Taken together, these data indicate a central role for the GSH pathway in the host response to GSH metabolism and glutathionylation may therefore be important factors in the pathogenesis of Lyme disease and potentially other inflammatory diseases as well.
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