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Abstract Background Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. Methods 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 μg/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. Results Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. Conclusions A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling.

Abstract Background Allograft bone used in joint replacement surgery can additionally serve as a carrier for antibiotics and serve as a prophylaxis against infections. However, in vitro dose-response curves for bone chips impregnated with different kinds of antibiotics are not available. In addition, while it would be desirable to add the antibiotics to allograft bone chips before these are stored in a bone bank, the effects of different storage temperatures on antibiotics are unknown. Methods Five different antibiotics (cefazolin, clindamycin, linezolid, oxacillin, vancomycin) were stored, both as pills and as solutions, at -80°C, -20°C, 4°C, 20°C and 37°C; in addition, bone chips impregnated with cefazolin and vancomycin were stored at -80°C and -20°C. After 1 month, 6 months and 1 year, the activity of the antibiotics against Staphylococcus epidermidis was measured using an inoculated agar. The diameter of the S. epidermidis-free zone was taken as a measure of antibiotic activity. In a separate experiment, in vitro dose-response curves were established for bone chips impregnated with cefazolin and vancomycin solutions at five different concentrations. Finally, the maximum absorbed amounts of cefazolin and vancomycin were established by impregnating 1 g of bone chips with 5 ml of antibiotic solution. Results A decrease of the S. epidermidis-free zone was seen with oxacillin and cefazolin solutions stored at 37°C for 1 month, with vancomycin stored at 37°C for 6 months and with cefazolin and oxacillin solutions stored at 20°C for 6 months. The activity of the other antibiotic solutions, pills and impregnated bone chips was not affected by storage. The in vitro dose-response curves show that the free-zone diameter increases logarithmically with antibiotic concentration. The absorbed antibiotic amount of one gram bone chips was determined. Conclusions Storage of antibiotics in frozen form or storage of antibiotic pills at temperatures up to 37°C for 12 months does not affect their activity. However, storage of antibiotic solutions at temperatures above 20°C does affect the activity of some of the antibiotics investigated. The in vitro dose-response curve can be used to determine the optimal concentration(s) for local application. It provides the opportunity to determine the antibiotic content of bone chips, and thus the amount of antibiotics available locally after application.

Abstract Background The T cell attracting chemokine CCL18 is produced by antigen presenting cells and a role for CCL18 has been suggested in the pathogenesis of a variety of diseases. Rheumatoid arthritis (RA) is one of these conditions, in which abundant CCL18 production is present. Although Th2 cytokines and IL-10 are known to have an effect on CCL18 production, there are several gaps in our knowledge regarding the exact regulation of CCL18 secretion, both in general and in RA. In this study we provide new insights in the regulation of CCL18 secretion by monocytes and dendritic cells. Results In contrast to a large panel of pro-inflammatory stimuli (IL-1β, TNF-α, IL-10, IL-13, IL-15, IL-17, IL-18, IFN-γ), T cell mimicking molecules (RANKL, CD40L) or TLR driven maturation, the anti-inflammatory IL-10 strongly stimulated DC to secrete CCL18. On freshly isolated monocytes, CCL18 secretion was induced by IL-4 and IL-13, in strong synergy with IL-10. This synergistic effect could already be observed after only 24 hours, indicating that not only macrophages and dendritic cells, but also monocytes secrete CCL18 under these stimulatory conditions. A high CCL18 expression was detected in RA synovial tissue and incubation of monocytes with synovial fluid from RA patients clearly enhanced the effects of IL-4, IL-13 and IL-10. Surprisingly, the effect of synovial fluid was not driven by IL-10 of IL-13, suggesting the presence of another CCL18 inducing factor in synovial fluid. Conclusion In summary, IL-10 synergistically induces CCL18 secretion in combination with IL-4 of IL-13 on monocytes and monocyte derived cells. The effects of IL-14, IL-13 and IL-10 are strongly enhanced by synovial fluid. This synergy may contribute to the high CCL18 expression in RA.

Background: Recently, surgeons introduced a minimally invasive modification on the classic posterolateral approach (PLA) in total hip arthroplasty (THA): the direct superior approach (DSA). We investigated the association between surgeon's experience and the risk of early revision of the DSA in primary THA, using data from the Dutch Arthroplasty Register (LROI). Methods: We retrieved all primary THAs performed using the DSA in 4 hospitals between 2016 and 2022 (n = 1551). Procedures were sorted in 5 groups using the date of operation and number of previous procedures per surgeon: 1–25; 26–50; 51–75; 76–100; >100. Subsequently, data from different surgeons were pooled together and the risk of revision was calculated via a multilevel time-to-event analysis. Results: The overall revision rate was 1.5% after a mean follow-up of 2 years. Patients from the 1–25 group had comparable risks of revision compared to patients in the >100 group (hazard ratio [HR] 1.0 [CI, 0.3–3.2]). The risk for patients in groups 26–50, 51–75 and 75–100 was also not statistically different from the >100 group (resp. HR 1.5 [CI, 0.5–5.0], 1.8 [CI, 0.5–6.4] and 0.5 [CI, 0.1–4.0]). Main reasons of revision were dislocation (0.5%) and infection (0.4%). Conclusions: We did not identify an association between the surgeon's experience and the early risk of revision for the DSA in primary THA in the Netherlands. The DSA seems safe in the early adoption phases with a low risk of revision due to dislocation and revision for all other causes. [ABSTRACT FROM AUTHOR]

Purpose: Several controversies in the optimal treatment of femoral neck fractures persist, together with large variations in clinical practice. Methods: A narrative literature review covering 4 current controversies in the surgical management of femoral neck fractures (total hip arthroplasty (THA) versus hemiarthroplasty (HA), cemented versus uncemented HA, internal fixation versus arthroplasty, operative versus non-operative) was performed. Available literature was balanced against annual trends in the management of femoral neck fractures from the public domain of several national registries (Sweden, Norway, The Netherlands, Australia and New Zealand). Results: For most controversies, the literature provides stronger evidence than is reflected by variations encountered in daily practice. Implementation of clinical evidence tends to lag behind and important differences exist between countries. Conclusions: Trends of clinical practice from national registries indicate that implementation of available clinical evidence needs to be improved. [ABSTRACT FROM AUTHOR]

Background: Worldwide, the majority of total hip arthroplasties (THAs) placed in patients <55 years are uncemented. However, little is known about the preferred method of fixation in revision hip arthroplasty in young patients. The aim of this study was to assess potential differences in the method of fixation used between primary and revision THA in young patients using data from the Dutch Arthroplasty Register. Methods: All primary THA placed in patients younger than 55 years, registered in the LROI between 2007 and 2019 were included n = 28,516). Kaplan-Meier survival analyses were used to estimate the survival of primary THA by method of fixation. Additionally, survival of revision procedures that changed or did not change in method of fixation were estimated. McNemar's test was used to assess differences in the proportion of cemented and uncemented fixation between primary and revision THA. Results: In all acetabular revisions, the use of cemented fixation increased statistically significant with 39% (95% CI, 34–45, p < 0.001) from 23% in primary THA to 62% in revision procedures. In all femoral revisions, the increase of cemented fixation was also statistically significant with 25% (95% CI, 19–31, p < 0.001), from 11% in primary THA to 36% in revision surgery. For both revised acetabular and femoral components, we found no statistically significant difference in the 5-year survival between revision procedures that changed or did not change in method of fixation. Conclusions: There was a significant change towards cemented fixation between primary and revision THA in young patients in the Netherlands, which was especially pronounced in acetabular revisions. No significant difference in short-term survival was found between revision procedures that changed or did not change in method of fixation. Long-term follow-up data are needed to evaluate the effect of this change in fixation method on the outcome of revision procedures in young patients. [ABSTRACT FROM AUTHOR]

Background and purpose -- The direct superior approach (DSA) is a modification of the classic posterolateral approach (PLA) for total hip arthroplasty (THA), in which the iliotibial band and short external rotators are spared. The revision rate of the DSA has not been investigated previously using arthroplasty registry data. We examined the reasons and risk of revision of the DSA, compared with the direct anterior approach (DAA) and PLA. Patients and methods -- In this population-based cohort study we included 175,543 primary THAs performed between 2014 and 2020 (PLA, n = 117,576; DAA, n = 56,626; DSA, n = 1,341). Competing risk survival analysis and multivariable Cox proportional hazard analyses, adjusted for potential confounders, were performed. Results -- After 3 years, crude revision rates due to any reason were 2.1% (95% confidence interval [CI] 1.3-3.3) for DSA, and 2.9% (CI 2.8-3.0) for PLA. Crude dislocation revision rates were 0.3% (CI 0.1-0.8) for DSA, versus 1.0% (CI 0.9-1.0) for PLA. Dislocation revision rate for DSA did not differ from DAA (0.3% [CI 0.2-0.3]). Multivariable Cox regression analysis demonstrated no overall difference in revision rates for the DSA (HR 0.6 [CI 0.4-1.09) compared with the PLA. Lower risk of revision due to dislocation was found in patients operated on through the DSA (HR 0.3 [0.1-0.9]) compared with the PLA. Conclusion -- Early nationwide results suggest that the DSA for total hip arthroplasty seems to show a tendency towards a lower risk of revision for dislocation but no overall reduced revision risk compared with the PLA. [ABSTRACT FROM AUTHOR]