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On the other hand, some endogenously formed or therapeutically applied EVs demonstrate protective effects pointing toward their usefulness as emerging treatment strategy in kidney disease.Glucocorticoids (GCs) are stress hormones that regulate developmental and physiological processes and are among the most potent anti-inflammatory drugs to suppress chronic and acute inflammation. GCs act through the glucocorticoid receptor (GR), a ubiquitously expressed ligand-activated transcription factor, which translocates into the nucleus and can act via two different modes, as a GR monomer or as a GR dimer. These two modes of action are not clearly differentiated in practice and may lead to completely different therapeutic outcomes. Detailed aspects of GR mechanisms are often not taken into account when GCs are used in different clinical scenarios. Patients, with critical illness-related corticosteroid insufficiency, treated with natural or synthetic GCs are still missing a clearly defined therapeutic strategy. This review discusses the different modes of GR function and its importance on organ function in vivo.Immune cell activation leads to the acquisition of new functions, such as proliferation, chemotaxis, and cytokine production. These functional changes require continuous metabolic adaption in order to sustain ATP homeostasis for sufficient host defense. The bioenergetic demands are usually met by the interconnected metabolic pathways glycolysis, TCA cycle, and oxidative phosphorylation. Apart from glucose, other sources, such as fatty acids and glutamine, are able to fuel the TCA cycle.Rising evidence has shown that cellular metabolism has a direct effect on the regulation of immune cell functions. Thus, quiescent immune cells maintain a basal metabolic state, which shifts to an accelerated metabolic level upon immune cell activation in order to promote key effector functions.This review article summarizes distinct metabolic signatures of key immune cell subsets from quiescence to activation and demonstrates a methodical concept of how to assess cellular metabolic pathways. It further discusses why metabolic functions are of rising interest for translational research and how they can be affected by the underlying pathophysiological condition and/or therapeutic interventions.Darts are constantly gaining in popularity. However, their risk of injury is often underestimated. This report is about a juvenile who suffered from a severe eye injury including the opening of the eye bulb. The attending ophthalmologists ruled out the possibility that this kind of injury could be caused by a dart with a plastic point. However, by reconstructing the course of action and throwing darts at porcine eyes, the forensic medical advisory opinion was able to state that darts with damaged plastic points may cause the exact same form of injury. This casuistic illustrates the essential significance of forensic-traumatological knowledge and, especially in the case of rare injury patterns, case-related practical experiments.Sepsis is a syndrome of shock and dysfunction of multiple vital organs that is caused by an uncontrolled immune response to infection and has a high mortality rate. There are no therapies for sepsis, and it has become a global cause for concern. see more Advances in patient care and management now mean that most patients survive the initial hyper-inflammatory phase of sepsis but progress to a later immunosuppressed phase, where 30% of patients die due to secondary infection. Deficits in the adaptive immune response may play a major role in sepsis patient mortality. The adaptive immune response involves a number of cell types including T cells, B cells and dendritic cells, all with immunoregulatory roles aimed at limiting damage and returning immune homeostasis after infection or insult. However, in sepsis, adaptive immune cells experience cell death or exhaustion, meaning that they have defective effector and memory responses ultimately resulting in an ineffective or suppressed immune defence. CD4+ T cells seem to be the most susceptible to cell death during sepsis and have ensuing defective secretory profiles and functions. Regulatory T cells seem to evade apoptosis and contribute to the immune suppression observed with sepsis. Preclinical studies have identified a number of new targets for therapy in sepsis including anti-apoptotic agents and monoclonal antibodies aimed at reducing cell death, exhaustion and maintaining/restoring adaptive immune cell functions. While early phase clinical trials have demonstrated safety and encouraging signals for biologic effect, larger scale clinical trial testing is required to determine whether these strategies will prove effective in improving outcomes from sepsis.Septic arthritis and spondylodiscitis, especially in immunocompromised patients, constitute a major differential diagnosis of joint or back pain. This results in the invasion of a joint or spinal disc and its adjacent vertebral body by a pathogen. In most cases this is manifested as unspecific symptoms, such as local joint or back pain, fever and malaise. If this is clinically suspected the bacterial infection of the joint can be confirmed by joint puncture and blood culture. For the diagnosis of spondylodiscitis magnetic resonance imaging should be used for visualization. In addition to adequate pain treatment and empirical antibiotic treatment, an arthroscopic removal of infected intra-articular tissue and debris is imperative. When complications caused by spondylodiscitis arise a surgical removal and stabilization should be performed. The following case report presents the findings of septic polyarthritis and spondylodiscitis in an immunocompromised patient with an HIV infection and provides insights into the occurrence of complications due to the delay of adequate treatment.
The primary aim of this study was to see whether perianal abscess rate differs between patients with type 1 and type 2 diabetes. A secondary aim was to determine whether poor glycemic control increases the risk for perianal abscess.
Data from the Swedish National Diabetes Registry and the Swedish National Patient Registry between January 2008 and June 2015 were matched. The risk for anal abscess was evaluated in univariate and multivariate analyses with type of diabetes, HbA1c level, BMI, and various diabetes complications as independent factors.
Patients with type 1 diabetes had a lower rate of perianal abscess than patients with type 2 diabetes when adjusted for HbA1c, sex, and age (OR 0.65; 95% CI 0.57-0.73). The risk for perianal abscess increased with higher HbA1c. Incidence of perianal abscess was also elevated in diabetes patients with complications related to poor glycemic control such as ketoacidosis and coma (OR 2.63; 95% CI 2.06-3.35), gastroparesis, and polyneuropathy (OR 1.81; 95% CI 1.41-2.
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