Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgDCD27 (double negative, DN) and CD21CD11c (CD21) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21 B cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21 (9/41) B cells compared with age-matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age-associated B cells in MS patients. The majority of DN B cells had an IgG memory phenotype, whereas CD21 B cells consisted of a mixed population of CD27 naive, CD27 memory, IgG, and IgM cells. DN B cells showed similar (MS patients) or increased (healthy donors) MHC-II expression as class-switched memory B cells and intermediate costimulatory molecule expression between naive and class-switched memory B cells, indicating their potential to induce (proinflammatory) T cell responses. Further, DN B cells produced proinflammatory and cytotoxic cytokines following ex vivo stimulation. Increased frequencies of DN and CD21 B cells were found in the cerebrospinal fluid of MS patients compared with paired peripheral blood. In conclusion, a proportion of MS patients showed increased peripheral expansions of age-associated B cells. DN and CD21 B cell frequencies were further increased in MS cerebrospinal fluid. These cells could contribute to inflammation by induction of T cell responses and the production of proinflammatory cytokines.
IntroductionThe aims of this study were to explore the incidence of in-hospital inappropriate empiric antibiotic use in patients with severe infection and to identify its relationship with patient outcomes.MethodsMedline (from 2004 to 2014) was systematically searched by using predefined inclusion criteria. Reference lists of retrieved articles were screened for additional relevant studies. The systematic review included original articles reporting a quantitative measure of the association between the use of (in)appropriate empiric antibiotics in patients with severe in-hospital infections and their outcomes. A meta-analysis, using a random-effects model, was conducted to quantify the effect on mortality by using risk ratios.ResultsIn total, 27 individual articles fulfilled the inclusion criteria. The percentage of inappropriate empiric antibiotic use ranged from 14.1% to 78.9% (Q1-Q3: 28.1% to 57.8%); 13 of 27 studies (48.1%) described an incidence of 50% or more. A meta-analysis for 30-day mortality and in-hospital mortality showed risk ratios of 0.71 (95% confidence interval 0.62 to 0.82) and 0.67 (95% confidence interval 0.56 to 0.80), respectively. Studies with outcome parameter 28-day and 60-day mortality reported significantly (P ≤0.02) higher mortality rates in patients receiving inappropriate antibiotics. Two studies assessed the total costs, which were significantly higher in both studies (P ≤0.01).ConclusionsThis systematic review with meta-analysis provides evidence that inappropriate use of empiric antibiotics increases 30-day and in-hospital mortality in patients with a severe infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0795-y) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.