Epidemiological studies have shown protective effects of fruits and vegetables (F&V) in lowering the risk of developing cardiovascular diseases (CVD) and cancers. Plant-derived dietary fibre (non-digestible polysaccharides) and/or flavonoids may mediate the observed protective effects particularly through their interaction with the gut microbiota. The aim of this study was to assess the impact of fruit and vegetable (F&V) intake on gut microbiota, with an emphasis on the role of flavonoids, and further to explore relationships between microbiota and factors associated with CVD risk. In the study, a parallel design with 3 study groups, participants in the two intervention groups representing high-flavonoid (HF) and low flavonoid (LF) intakes were asked to increase their daily F&V intake by 2, 4 and 6 portions for a duration of 6 weeks each, while a third (control) group continued with their habitual diet. Faecal samples were collected at baseline and after each dose from 122 subjects. Faecal bacteria enumeration was performed by fluorescence in situ hybridisation (FISH). Correlations of dietary components, flavonoid intake and markers of CVD with bacterial numbers were also performed. A significant dose X treatment interaction was only found for Clostidium leptum-Ruminococcus bromii/flavefaciens with a significant increase after intake of 6 additional portions in the LF group. Correlation analysis of the data from all 122 subjects independent from dietary intervention indicated an inhibitory role of F&V intake, flavonoid content and sugars against the growth of potentially pathogenic clostridia. Additionally, we observed associations between certain bacterial populations and CVD risk factors including plasma TNF-α, plasma lipids and BMI/waist circumference.
Additive manufacturing of lightweight or functional structures by selective laser beam (SLM) or electron beam melting (EBM) is widespread, especially in the field of medical applications. SLM and EBM processes were applied to prepare Ti6Al4V test specimens with different surface orientations (0°, 45° and 90°). Roughness measurements of the surfaces were conducted and cell behavior on these surfaces was analyzed. Hence, human osteoblasts were seeded on test specimens to determine cell viability (metabolic activity, live-dead staining) and gene expression of collagen type 1 (Col1A1), matrix metalloprotease (MMP) 1 and its natural inhibitor, TIMP1, after 3 and 7 days. The surface orientation of specimens during the manufacturing process significantly influenced the roughness. Surface roughness showed significant impact on cellular viability, whereas differences between the time points day 3 and 7 were not found. Collagen type 1 mRNA synthesis rates in human osteoblasts were enhanced with increasing roughness. Both manufacturing techniques further influenced the induction of bone formation process in the cell culture. Moreover, the relationship between osteoblastic collagen type 1 mRNA synthesis rates and specimen orientation during the building process could be characterized by functional formulas. These findings are useful in the designing of biomedical applications and medical devices.
In aseptic loosening of endoprosthetic implants, metal particles, as well as their corrosion products, have been shown to elicit a biological response. Due to different metal alloy components, the response may vary depending on the nature of the released corrosion product. Our study aimed to compare the biological effects of different ions released from metal alloys. In order to mimic the corrosion products, different metal salts (CoCl2, NiCl2 and CrCl3 × 6H2O) were dissolved and allowed to equilibrate. Human osteoblasts were incubated with concentrations of 10 µM to 500 µM metal salt solutions under cell culture conditions, whereas untreated cells served as negative controls. Cells exposed to CoCr28Mo6 particles served as positive controls. The cell activity and expression of osteogenic differentiation and pro-osteolytic mediators were determined. Osteoblastic activity revealed concentration- and material-dependent influences. Collagen 1 synthesis was reduced after treatment with Co(2+) and Ni(2+). Additionally, exposure to these ions (500 µM) resulted in significantly reduced OPG protein synthesis, whereas RANKL as well as IL-6 and IL-8 secretion were increased. TLR4 mRNA was significantly induced by Co(2+) and CoCr28Mo6 particles. The results demonstrate the pro-osteolytic capacity of metal ions in osteoblasts. Compared to CoCr28Mo6 particles, the results indicated that metal ions intervene much earlier in inflammatory processes.
Device-related infections in orthopaedic and trauma surgery are a devastating complication with substantial impact on morbidity and mortality. Systemic suppressive antibiotic treatment is regarded an integral part of any surgical protocol intended to eradicate the infection. The optimal duration of antimicrobial treatment, however, remains unclear. In a multicenter case-control study, we aimed at analyzing the influence of the duration of antibiotic exposure on reinfection rates 1 year after curative surgery. This investigation was part of a federally funded multidisciplinary network project aiming at reducing the spread of multi-resistant bacteria in the German Baltic region of Pomerania. We herein used hospital chart data from patients treated for infections of total joint arthroplasties or internal fracture fixation devices at three academic referral institutions. Subjects with recurrence of an implant-related infection within 1 year after the last surgical procedure were defined as case group, and patients without recurrence of an implant-related infection as control group. We placed a distinct focus on infection of open reduction and internal fixation (ORIF) constructs. Uni- and multivariate logistic regression analyses were employed for data modelling. Of 1279 potentially eligible patients, 269 were included in the overall analysis group, and 84 contributed to an extramedullary fracture-fixation-device sample. By multivariate analysis, male sex (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.08 to 3.94, p = 0.029) and facture fixation device infections (OR 2.05, 95% CI 1.05 to 4.02, p = 0.036) remained independent predictors of reinfection. In the subgroup of infected ORIF constructs, univariate point estimates suggested a nearly 60% reduced odds of reinfection with systemic fluoroquinolones (OR 0.42, 95% CI 0.04 to 2.46) or rifampicin treatment (OR 0.41, 95% CI 0.08 to 2.12) for up to 31 days, although the width of confidence intervals prohibited robust statistical and clinical inferences. The optimal duration of systemic antibiotic treatment with surgical concepts of curing wound and device-related orthopaedic infections is still unclear. The risk of reinfection in case of infected extramedullary fracture-fxation devices may be reduced with up to 31 days of systemic fluoroquinolones and rifampicin, although scientific proof needs a randomized trial with about 1400 subjects per group. Concerted efforts are needed to determine which antibiotics must be applied for how long after radical surgical sanitation to guarantee sustainable treatment success.
Osteolysis in the periprosthetic tissue can be caused by metallic wear particles and ions that can originate from implant surface corrosion. These products influence cellular behavior and stimulate the expression of proinflammatory cytokines. The purpose of this study was to evaluate the impact of CoCr29Mo6 ions on cell survival, differentiation, and cytokine expression in human osteoblasts and peripheral blood mononuclear cells (PBMCs). Thus, we exposed cells with a mixture of 200 µg/L ion solution and determined cell viability and apoptosis/necrosis. Gene expression analyses of osteoblastic and osteoclastic differentiation markers as well as pro-osteolytic mediators (IL-6, IL-8, TNF-α, MCP-1, MMP1, TIMP1) were performed. These markers were also investigated in mixed cultures of adherent and non-adherent PBMCs as well as in co-cultures of human osteoblasts and PBMCs. The ion solution induced necrosis in osteoblasts and PBMCs in single cultures. All examined mediators were highly expressed in the co-culture of osteoblasts and PBMCs whereas in the single cell cultures only IL-6, IL-8, and MMP1 were found to be stimulated. While the applied concentration of the CoCr29Mo6 ion solutions had only marginal effects on human osteoblasts and PBMCs alone, the co-culture may provide a comprehensive model to study osteolytic processes in response to Co and Cr ions.
The treatment of periprosthetic joint infections (PJI), and especially of re-infections, poses a highly complex problem in orthopaedic surgery. While fungal infections are rare, they present a special challenge. The therapy is often protracted and based on limited evidence. A total of 510 hip and knee revision surgeries were analysed for the occurrence of bacterial and fungal PJI. In patients with PJI, the duration of the hospital stay and the incidence of disarticulation of the infected joint were recorded. Out of the analysed revision arthroplasties, 43.5% were due to PJI. Monomicrobial infection occurred in 55.2%, dual microbial infection in 21.4%, and polymicrobial (≥3 different bacterial or fungal species) infection in 17.2% of the cases. Overall, Candida species were detected in 12.4% cases. Candida albicans was the main fungal pathogen. In 6.9% of cases, disarticulation of the joint was the only option to control PJI. The detection of polymicrobial infection more than doubled in follow-up revisions and there was a strong association between detection of Candida infection and disarticulation (OR 9.39). The majority of fungal infections were mixed infections of bacteria and Candida albicans. The choice of a biofilm penetrating antimycotic, e.g., caspofungin, together with a sufficient standard procedure for detection and surgical treatment can help to control the infection situation. Fungal infection often proves to be more difficult to treat than anticipated and is more frequent than expected.