Immune Response to Persistent Staphyloccocus Aureus Periprosthetic Joint Infection in a Mouse Tibial Implant Model.

Staphyloccocus aureus is one of the major pathogens in orthopedic periprosthetic joint infection (PJI), a devastating complication of total joint arthroplasty that often results in chronic and persistent infections that are refractory to antibiotics and require surgical interventions. Biofilm formation has been extensively investigated as a reason for persistent infection. The cellular composition, activation status, cytokine profile, and role of the immune response during persistent S. aureus PJI are incompletely understood. In this study, we used histology, multiparametric flow cytometry, and gene expression analysis to characterize the immune response in a clinically relevant orthopedic PJI model. We tested the hypothesis that persistent S. aureus infection induces feedback mechanisms that suppress immune cell activation, thereby affecting the course of infection. Surprisingly, persistent infection was characterized by strikingly high cytokine gene expression indicative of robust activation of multiple components of innate and adaptive immunity, along with ongoing severe neutrophil-dominated inflammation, in infected joint and bone tissues. Activation and expansion of draining lymph nodes and a bone marrow stress granulopoiesis reaction were also maintained during late phase infection. In parallel, feedback mechanisms involving T-cell inhibitory receptors and exhaustion markers, suppressive cytokines, and regulatory T cells were activated and associated with decreased T-cell proliferation and tissue infiltration during the persistent phase of infection. These results identify the cellular and molecular components of the mouse immune response to persistent S. aureus PJI and indicate that neutrophil infiltration, inflammatory cytokine responses, and ongoing lymph node and bone marrow reactions are insufficient to clear infection and that immune effector mechanisms are suppressed by feedback inhibitory pathways. These immune-suppressive mechanisms are associated with diminished T-cell proliferation and tissue infiltration and can be targeted as part of adjuvant immunotherapeutic strategies in combination with debridement of biofilm, antibiotics, and other therapeutic modalities to promote eradication of infection. © 2021 American Society for Bone and Mineral Research (ASBMR).

Enfrentamiento quirúrgico de las lesiones del tendón de biceps distal / Surgical approach in distal biceps tendon lesions

Surgical treatment of distal biceps tendon ruptures is indicated in active patients, and its aim is to recover mainly the supination strength, and flexion secondarily, focusing the controversy on its approach and fixation systems. Objective: To present a patients series results operated on for this injury, with different surgical techniques. Methods: Ten patients were evaluated retrospectively analyzing descriptively: age, evolution time, approach and fixation types, grafts use, functional and satisfaction outcome, and complications. Results: It was considered excellent in all patients, despite the use of different types of fixation and approaches, either in acute or chronic, with few complications. Conclusion: According to our results, and the literature review, it can be obtained excellent functional results, with different approaches and fixation systems, allowing an early rehabilitation.

El tratamiento quirúrgico en las roturas del tendón de bíceps distal se indica en pacientes activos, e intenta recuperar principalmente la fuerza de supinación, y secundariamente de flexión, centrando la controversia en su abordaje y sistemas de fijación. Objetivo: Presentar los resultados en una serie de pacientes operados de esta lesión, con diferentes técnicas quirúrgicas. Métodos: Se evalúan retrospectivamente diez pacientes, analizando descriptivamente edad, tiempo de evolución, tipo de abordaje y fijaciones, uso de injertos, resultados funcionales, grado de satisfacción, y complicaciones. Resultados: Fueron considerados excelentes en todos los pacientes, a pesar del uso de distintos tipos de fijación y abordajes, en roturas agudas y crónicas, con escasas complicaciones. Conclusión: De acuerdo a lo presentado, y acorde a la literatura revisada, se pueden obtener excelentes resultados funcionales, con diferentes abordajes y sistemas de fijación, que permitan una rehabilitación precoz.

Effects of bisphosphonate treatment on bone repair under immunosuppression using cyclosporine A in adult rats.

UNLABELLED: The effect of cyclosporine A on bone turnover remains unclear. Using adult rats with vascularized bone transplantation, we show that long-term cyclosporine A administration increases bone turnover and zoledronic acid treatment enhances the reconstruction of cyclosporine A-administered skeleton. Bisphosphonates might be efficacious in human bone repair under immunosuppression using cyclosporine A. INTRODUCTION: Bisphosphonate treatment effectively prevents bone loss after transplantation. However, recent evidence from gain- and loss-of-function experiments has indicated that calcineurin inhibitors, such as cyclosporine A (CsA), reduce bone turnover, and severely suppressed bone turnover might delay the union of human fractured bone. The purpose of this study was to investigate the effects of bisphosphonate treatment on the repair of CsA-administered skeleton. METHODS: After skeletal reconstruction by vascularized tibial grafting, adult recipient rats were treated with intramuscular CsA (10 mg/kg/day) and low-dose (0.2 microg/kg/week) or high-dose (2 microg/kg/week) subcutaneous zoledronic acid alone or in combination for 8 weeks. Biochemical parameters were measured in blood and urine. The reconstructed skeleton was analyzed using soft X-ray, histology, dual energy X-ray absorptiometry, and three-point bending test. RESULTS: CsA induced mild renal dysfunction, hyperparathyroidism and high bone turnover. High-dose zoledronic acid delayed cortical bone union at the distal host-graft junction, but its combination with CsA did not cause such a delay. High-dose zoledronic acid prevented CsA-induced bone loss and bone fragility in the reconstructed skeleton. CONCLUSION: In this rat model, long-term CsA administration increases bone turnover, at least partly, through hyperparathyroidism and high-dose zoledronic acid treatment does not impair the union of CsA-administered bone.

BTB ACL reconstruction: femoral nerve block has no advantage over intraarticular local anaesthetic infiltration.

Fifty patients were randomly recruited to receive either femoral nerve block (0.375% Bupivacaine) or an intraarticular local anaesthetic injection for pain control for arthroscopically-assisted ACL reconstruction. Both groups were evenly matched for age ( t-test p >0.05). Tourniquet time did not differ significantly between the groups ( t-test p=0.24). The VAS pain levels were not significantly different at 4 h and the first morning postoperatively in both groups. Femoral block (Median VAS: 20 & 18.5) did not confer a significant advantage (Mann Whitney U test p =0.36, 0.67) over intraarticular injection of bupivacaine (Median VAS: 18 & 20). There was no correlation between tourniquet time and postoperative pain ( r=0.19, 0.08). All patients but one were discharged home on the first postoperative morning. Our study demonstrates that pain levels can be sufficiently controlled by intraarticular infiltration of bupivacaine coupled with oral analgesia. The level of pain relief achieved could allow this procedure to be performed in a day surgery setting.

Effects of vitamin D analog, 22-oxa-1,25-dihydroxyvitamin D(3), on bone reconstruction by vascularized bone allograft.

We previously reported that vascularized bone allograft using immunosuppressants, such as cyclosporine A (CsA), is one approach for reconstruction of large bone defects in both experimental animals (Microsurgery 15:663; 1994) and clinically in humans (Lancet 347:970, 1996). Because immunosuppressive agents such as CsA induce significant side effects, including bone loss, other therapeutic agents supporting successful vascularized bone allografts have been sought after. We investigated the effects of 22-oxa-1,25-dihydroxyvitamin D(3) (OCT) on vascularized bone allograft, and compared its effects with CsA. Twelve-week-old DA rats with the major histocompatibility antigen (MHC) RT-1(a) were used as donors and age-matched Lewis rats with MHC RT-1(l) used as recipients. Allografted bones in rats treated with vehicle were rejected completely. Soft X-ray examination demonstrated that administration of OCT (0.5 microg/kg per day) for 12 weeks after bone graft induced bone union as effective as treatment for 12 weeks with CsA (10 mg/kg per day). Transplanted bones in OCT-treated rats showed higher bone mineral density than that in CsA-treated rats. Histologically, transplanted bones in OCT-treated rats at 12 weeks were nonvital, but these bones united with recipient vital bones. After cessation of 12 week treatment with OCT, new bone formation occurred around the grafted nonvital bones during a 9 month period. Transplanted bones in CsA-treated rats were vital and formed union with recipient bones, whereas cortical bones became thin when compared with nonvital bones in OCT-treated rats. Urinary deoxypyridinoline levels in rats treated with CsA were significantly higher than levels in rats treated with OCT, suggesting accelerated bone resorption in CsA-treated rats. These results suggest that OCT exerts an anabolic action on bone reconstruction by allogeneic bone transplantation.