• Willis Degn posted an update 2 days, 4 hours ago

    Trained immunity is the acquisition of a hyperresponsive phenotype by innate immune cells (such as monocytes and macrophages) after an infection or vaccination, a de facto nonspecific memory dependent on epigenetic and metabolic reprogramming of these cells. We have recently shown that induction of trained immunity is dependent on IL-1β. Here, we show that recombinant IL-38, an anti-inflammatory cytokine of the IL-1-family, was able to induce long-term inhibitory changes and reduce the induction of trained immunity by β-glucan in vivo in C57BL/6 mice and ex vivo in their bone marrow cells. IL-38 blocked mTOR signaling and prevented the epigenetic and metabolic changes induced by β-glucan. In healthy subjects, the IL1F10 associated single nucleotide polymorphism rs58965312 correlated with higher plasma IL-38 concentrations and reduced induction of trained immunity by β-glucan ex vivo. These results indicate that IL-38 induces long-term anti-inflammatory changes and also inhibits the induction of trained immunity. Recombinant IL-38 could therefore potentially be used as a therapeutic intervention for diseases characterized by exacerbated trained immunity.As culture-negative implant-associated infection denote a diagnostic challenge, sonicate fluid cultures of the explanted endoprosthesis and osteosynthesis components are frequently used. However, the effect of antibiotic treatment on pathogen detection by sonication fluid cultures in implant-associated infection has not been investigated. Thus, the aim of this study was to evaluate the influence of preoperative antibiotic prophylaxis (PAP) and antibiotic therapy (AT) on sonicate fluid cultures in patients with implant-associated infection. In this retrospective study three groups were compared (i) standard PAP, (ii) AT for at least one day, and (iii) no antibiotics before surgery. For the inclusion criteria, an established diagnostic protocol for implant-associated infection was used. Sonicate fluid cultures were validated by corresponding microbiological and histopathological samples. In 90 patients with single and multiple infections, 114 pathogens were detected. The detection rate by sonicate fluid cultures in patients receiving PAP (n = 27, 29 pathogens), AT before surgery (n = 33, 48 pathogens) and no antibiotics before surgery (n = 30, 37 pathogens) were 86.2%, 81.3%, and 86.5% (p = .778), respectively. Eleven of 114 infectious agents were detected exclusively by sonicate fluid cultures, while conventional tissue culture failed in these cases. PAP and AT do not affect intraoperative cultures in implant-associated infection. It is therefore not recommended to omit antibiotic prophylaxis in patients with implant-associated infection. Algorithms including both sonicate fluid cultures and tissue samples should be used for appropriate microbiological diagnosis of implant-associated infections.The intracellular tyrosine kinase inhibitor nintedanib has shown great efficacy for the treatment of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases. However, the incidence rate of myocardial infarction (MI) among participants in landmark IPF trials was remarkable, peaking at 3/100 patient-years. Although subjects with IPF often have a high cardiovascular (CV) risk profile, the occurrence of MI in nintedanib-treated patients may not be fully explained by clustering of CV risk factors. Nintedanib inhibits the vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor pathways, which play important roles in the biology of the atherosclerotic plaque and in the response of the heart to ischaemia. Hence, unwanted CV effects may partly account for nintedanib-related MI. We review the evidence supporting this hypothesis and discuss possible actions for a safe implementation of nintedanib in clinical practice, building on the experience with tyrosine kinase inhibitors acquired in cardio-oncology.The Baltic Sea is one of the most polluted seas in the world, with widespread eutrophication and radionuclide contamination. Using key species of the Baltic Sea, the effects of eutrophication on uptake and trophic transfer of the radioactive micronutrients commonly found in nuclear power plant effluents were investigated experimentally using the brown macroalgae Fucus vesiculosus and the grazers Idotea balthica and Theodoxus fluviatilis in a controlled environment. Rapid uptake of 54 Mn, 57 Co, and 65 Zn from water was observed in all biota; and eutrophication combined with grazing pressure strongly influenced the uptake in F. vesiculosus. Uptake of 54 Mn, 57 Co, and 65 Zn to I. balthica and T. fluviatilis grazing on F. vesiculosus were also observed. The results indicate that ecosystems could be open for further trophic transfer as radionuclides accumulate quickly in the producers and are transferred to primary consumers. Environ Toxicol Chem 2021;401694-1705. © 2021 The Authors. KC7F2 cost Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.The sacroiliac joint (SIJ) is a known pain generator that, in severe cases, may require surgical fixation to reduce intra-articular displacements and allow for arthrodesis. The objective of this computational study was to analyze how the number of implants affected SIJ stabilization with patient-specific characteristics such as the pelvic geometry and bone quality. Detailed finite element models were developed to account for three pelvises of differing anatomy. Each model was tested with a normal and low bone density (LD) under two types of loading compression only and compression with flexion and extension moments. These models were instrumented with one to three cylindrical, threaded and fenestrated implants through a posterior oblique trajectory, requiring less muscle dissection than the more common lateral trajectory used with triangular implants. Compared with the noninstrumented pelvis, the change in range of motion (ROM) and stress distribution were used to characterize joint stabilization. Noninstrumented mobility ranged from 0.86 to 2.55 mm and from 1.37° to 6.11°. Across patient-specific characteristics, the ROM reduction with one implant varied from 3% to 21% for vertical and 15% to 47% for angular displacements. With two implants, the ROM reduction ranged from 12% to 41% for vertical and from 28% to 61% for angular displacements. Three implants, however, did not further improve the joint stability (14% to 42% for vertical and 32% to 63% for angular displacements). With respect to patient characteristics, an LD led to a decreased stabilization and a higher volume of stressed bone (>75% of yield stress). A better understanding of how patient characteristics affect the implant performance could help improve surgical planning of sacroiliac arthrodesis.