Microglial cells in the healthy adult CNS possess a characteristic ramified morphology and show little or no expression of major histocompatibility complex (MHC) or adhesion molecules. In contrast, microglial cells isolated from newborn rat brains inevitably show a nonramified amoeboid morphology and express immunoeffector molecules, such as MHC class I and II, and various adhesion molecules thought to be markers of microglial activation. Furthermore, they produce large amounts of oxygen radicals. Treatment of cultured microglial cells with the antioxidants vitamin E (α‐tocopherol) and vitamin C (ascorbic acid) induced a ramified microglial morphology after 48 h in vitro, otherwise only seen in healthy adult CNS tissue or in co‐culture with astrocytes. Morphological transformation of microglial cells was quantified by morphometric analysis and was found to be statistically significant. Ramification of microglia induced by vitamin E was accompanied by downregulated expression of adhesion molecules leukocyte function antigen‐1, very late antigen‐4, and intercellular adhesion molecule‐1, as assessed by FACS analysis and immunocytochemistry. Moreover, cell numbers of microglia treated with vitamin E remained stable within 7 days in vitro, whereas untreated controls showed a cell loss of 81.5%. These data show that vitamin E acts as a protective compound in dissociated microglial cell cultures. In conclusion, our results suggest that vitamin E and vitamin C shift microglial morphology toward ramification and induce an immunological deactivation. These changes seem to be mediated by oxidative mechanisms. GLIA 22:180–188, 1998. © 1998 Wiley‐Liss, Inc.

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Background Before the creation of the Swedish Fracture Register (SFR), there was no national quality register that prospectively collects data regarding all types of fractures regardless of treatment in an emergency setting. Observational data on fractures registered in a sustainable way may provide invaluable tools for quality improvements in health care and research. Description Ten years after its implementation, the Swedish Fracture Register has 100% coverage among orthopaedic and trauma departments in Sweden. The completeness of registrations reached in 2020 69–96% for hip fractures at the different departments, with the majority reporting a completeness above 85%. The Swedish Fracture Register is a fully web-based national quality register created and run by orthopaedic professionals, with financial support from public healthcare providers and the government. All users have full access to both the registration platform and all aggregated statistics in real time. The web-based platform was created for use in health quality registers and it has easily gained acceptance among users. The register has gradually developed by the addition of more fracture types and skeletal parts. Research activity is high and 31 scientific publications have been published since 2016. The strategy from the start was to publish validation data and basic epidemiological data. However, over the past few years, publications on outcomes, such as re-operations and mortality, have been published and four register-based, randomised, controlled trials are ongoing. Conclusion It is possible to create a fracture register, to gain professional acceptance and to collect fracture data in a sustainable way on a national level if the platform is easy to use. Such a platform can also be used as a randomisation platform for prospective studies.

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Level III, prognostic study.

We hypothesized that CNS tissue has the potential to deactivate invading monocytes/macrophages in order to maintain the immune privilege of the brain, and furthermore, that astrocytes are the cells that initiate monocyte/macrophage deactivation. To test this hypothesis, fluorescent prelabeled rat spleen macrophages with typical amoeboid morphology were transferred into organotypic hippocampal slice cultures (OHSCs), where they gradually developed a ramified morphology similar to the appearance of resting microglial cells. This morphological transformation also occurred if macrophages or monocytes were co-cultured with mixed glial cultures or with astrocytoma cells, and ramification was accompanied by reduced expression of adhesion molecules leukocyte function antigen (LFA)-1, intercellular adhesion molecule (ICAM)-1, and major histocompatibility complex (MHC)-class-II molecules. Moreover, treatment of macrophages with astrocyte culture supernatant effectively down-regulated the LPS-induced expression of adhesion-and MHCclass-II-molecules. Astrocyte supernatant-induced inhibition of adhesion and MHC-class-II-moleculeexpression was mimicked by transforming growth factor (TGF)-␤1, furthermore, this inhibitory effect was diminished by simultaneous treatment with neutralizing anti-TGF-␤-antibodies. In conclusion, our results suggest that astrocyte-derived, soluble fac-tors that are present in the CNS microenvironment deactivate invading macrophages, thus contributing to the maintenance of CNS immune-privilege following impairment of blood-brain-barrier (BBB) integrity.

Purpose To develop a parsimonious risk prediction model for periprosthetic joint infection (PJI) within 90 days after total hip arthroplasty (THA). Patients and Methods We used logistic LASSO regression with bootstrap ranking to develop a risk prediction model for PJI within 90 days based on a Swedish cohort of 88,830 patients with elective THA 2008–2015. The model was externally validated on a Danish cohort with 18,854 patients. Results Incidence of PJI was 2.45% in Sweden and 2.17% in Denmark. A model with the underlying diagnosis for THA, body mass index (BMI), American Society for Anesthesiologists (ASA) class, sex, age, and the presence of five defined comorbidities had an area under the curve (AUC) of 0.68 (95% CI: 0.66 to 0.69) in Sweden and 0.66 (95% CI: 0.64 to 0.69) in Denmark. This was superior to traditional models based on ASA class, Charlson, Elixhauser, or the Rx Risk V comorbidity indices. Internal calibration was good for predicted probabilities up to 10%. Conclusion A new PJI prediction model based on easily accessible data available before THA was developed and externally validated. The model had superior discriminatory ability compared to ASA class alone or more complex comorbidity indices and had good calibration. We provide a web-based calculator ( https://erikbulow.shinyapps.io/thamortpred/ ) to facilitate shared decision making by patients and surgeons.

Periprosthetic joint infection (PJI) and implant loosening are the most common complications after joint replacement surgery. Due to their increased surface area, additively manufactured porous metallic implants provide optimal osseointegration but they are also highly susceptible to bacterial colonization. Antibacterial surface coatings of porous metals that do not inhibit osseointegration are therefore highly desirable. The potential of silver coatings on arthroplasty implants to inhibit PJI has been demonstrated, but the optimal silver content and release kinetics have not yet been defined. A tight control over the silver deposition coatings can help overcome bacterial infections while reducing cytotoxicity to human cells. In this regard, porous titanium sputtered with silver and titanium nitride with increasing silver contents enabled controlling the antibacterial effect against common PJI pathogens while maintaining the metabolic activity of human primary cells. Electron beam melting additively manufactured titanium alloys, coated with increasing silver contents, were physico-chemically characterized and investigated for effects against common PJI pathogens. Silver contents from 7 at % to 18 at % of silver were effective in reducing bacterial growth and biofilm formation. Staphylococcus epidermidis was more susceptible to silver ions than Staphylococcus aureus. Importantly, all silver-coated titanium scaffolds supported primary human osteoblasts proliferation, differentiation, and mineralization up to 28 days. A slight reduction of cell metabolic activity was observed at earlier time points, but no detrimental effects were found at the end of the culture period. Silver release from the silver-coated scaffolds also had no measurable effects on primary osteoblast gene expression since similar expression of genes related to osteogenesis was observed regardless the presence of silver. The investigated silver-coated porous titanium scaffolds may thus enhance osseointegration while reducing the risk of biofilm formation by the most common clinically encountered pathogens.