Macrophage-biomimetic porous Se@SiO2 nanocomposites for dual modal immunotherapy against inflammatory osteolysis

Background Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (porous Se@SiO2 nanospheres) to manage inflammatory osteolysis. Results Macrophage membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments. Conclusion Our findings suggest that M-Se@SiO2 have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty. Graphical Abstract

Demography of Total Joint Replacement Surgeries Performed in a Tertiary Care Hospital: A Cross-sectional Survey

Introduction: Total joint replacement of hip and knee is considered as one of the most successful orthopedic surgeries in the twenty-first century because of the only solution to end-stage arthritis of these joints. The real burden of the problem is yet to be established in developing countries like Nepal. This study aims to describe the demographic findings of the joint replacement surgeries among total lower limb surgeries in a tertiary care hospital. Methods: This cross-sectional survey was conducted using the hospital records of 73 total joint replacement surgeries of the lower limb in the Department of Orthopedics of a tertiary care hospital from November 2016 to November 2020. Ethical approval was taken from the Institutional Review Committee (reference number: 077/78-011). Convenience sampling was done. Data analysis was done using the Statistical Package for the Social Sciences version 20. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data. Results: There were 73 total joint replacement of hips and knees. Of which, 32 (43.84%) total hip replacements were done in which one (3.13%) patient had a simultaneous bilateral hip replacement in single-stage and the other one (3.13%) had two-stage bilateral hip replacement. Forty one (56.16%) total knee replacements were done in which 18 (24.65%) had a simultaneous bilateral knee replacement and five (6.85%) had a unilateral knee replacement. Conclusions: Total joint replacements of the hip were more common among the lower limb surgeries.

Risk Factors of Coexisting Septic Spondylitis and Arthritis: A Case-Control Study in a Tertiary Referral Hospital

Introduction: In patients under immunosuppression or severe sepsis, it is sometimes manifested as coexisting septic arthritis and spondylitis. The aim of this study is to evaluate and investigate the risk factors of infectious spondylitis associated with septic arthritis. Methods: The study retrospectively reviewed the patients diagnosed with infectious spondylitis between January 2010 and September 2018 for risk factors of coexisting major joint septic arthritis. Results: A total of 10 patients with infectious spondylitis and coexisting septic arthritis comprised the study group. Fifty matched patients with solely infectious spondylitis were selected as the control group. Major risk factors include preoperative C-reactive protein (p = 0.001), hypoalbuminemia (p = 0.011), history of total joint replacement (p < 0.001), duration of preoperative antibiotics treatment (p = 0.038) and psoas muscle abscess (p < 0.001). Conclusion: Infectious spondylitis and septic arthritis are thought of as medical emergencies due to their high mortality and morbidity. Our study evaluated 5 risk factors as significant major findings: hypoalbuminemia (<3.4 g/dL), higher preoperative CRP (>130 mg/L), psoas muscle abscess, longer preoperative antibiotics treatment (>8 days) and history of total joint replacement. Clinicians should pay attention to the patients with those five factors to detect the coexisting infections as early as possible.