Inflammatory pseudotumor around metal-on-polyethylene total hip arthroplasty in patients with ankylosing spondylitis: description of two cases and review of literature.

Inflammatory pseudotumor has been commonly reported in patients undertaking total hip replacement (THR) for different reasons. The precise etiology of this biological reaction and whether the primary disease has an influence on pseudotumor formation remain unclear. There seems to be a consensus that metal ions and debris do play an important role during this process. Recently, however, compared to metal particles along, immune response induced by metal particles attracts more attention. We present two cases of pseudotumor who have accepted THR for ankylosing spondylitis (AS) and later required revision surgery and hindquarter amputation, respectively. By thorough literature review, we tried to investigate the association between inflammatory pseudotumors and immunology.

Enhanced Osteosarcoma Immunotherapy via CaCO3 Nanoparticles: Remodeling Tumor Acidic and Immune Microenvironment for Photodynamic Therapy.

Osteosarcoma (OS) is a "cold" tumor enriched in noninflammatory M2 phenotype tumor-associated macrophages (TAMs), which limits the efficacy of immunotherapy. The acidic tumor microenvironment (TME), generated by factors such as excess hydrogen (H+) ions and high lactate levels, activates immunosuppressive cells, further promoting a suppressive tumor immune microenvironment (TIME). Therefore, a multitarget synergistic combination strategy that neutralizes the acidic TME and reprograms TAMs can be beneficial for OS therapy. Here, a calcium carbonate (CaCO3)/polydopamine (PDA)-based nanosystem (A-NPs@(SHK+Ce6)) is developed. CaCO3 nanoparticles are used to neutralize H+ ions and alleviate the suppressive TIME, and the loaded SHK not only synergizes with photodynamic therapy (PDT) but also inhibits lactate production, further reversing the acidic TME and repolarizing TAMs to consequently lead to enhanced PDT-induced tumor suppression and comprehensive beneficial effects on antitumor immune responses. Importantly, A-NPs@(SHK+Ce6), in combination with programmed cell death protein 1 (PD-1) checkpoint blockade, shows a remarkable ability to eliminate distant tumors and promote long-term immune memory function to protect against rechallenged tumors. This work presents a novel multiple-component combination strategy that coregulates the acidic TME and TAM polarization to reprogram the TIME.

Contemporary adjuvant polymethyl methacrylate cementation optimally limits recurrence in primary giant cell tumor of bone patients compared to bone grafting: a systematic review and meta-analysis.

BACKGROUND: Reports of recurrence following restructuring of primary giant cell tumor (GCT) defects using polymethyl methacrylate (PMMA) bone cementation or allogeneic bone graft with and without adjuvants for intralesional curettage vary widely. Systematic review and meta-analysis were conducted to investigate efficacy of PMMA bone cementation and allogeneic bone grafting following intralesional curettage for GCT. METHODS: Medline, EMBASE, Google Scholar, and Cochrane databases were searched for studies reporting GCT of bone treatment with PMMA cementation and/or bone grafting with or without adjuvant therapy following intralesional curettage of primary GCTs. Pooled risk ratios and 95% confidence intervals (CIs) for local recurrence risks were calculated by fixed-effects methods. RESULTS: Of 1,690 relevant titles, 6 eligible studies (1,293 patients) spanning March 2008 to December 2011 were identified in published data. Treatment outcomes of PMMA-only (n = 374), bone graft-only (n = 436), PMMA with or without adjuvant (PMMA + adjuvant; n = 594), and bone graft filling with or without adjuvant (bone graft + adjuvant; n = 699) were compared. Bone graft-only patients exhibited higher recurrence rates than PMMA-treated patients (RR 2.09, 95% CI (1.64, 2.66), Overall effect: Z = 6.00; P <0.001), and bone graft + adjuvant patients exhibited higher recurrence rates than PMMA + adjuvant patients (RR 1.66, 95% CI (1.21, 2.28), Overall effect: Z = 3.15, P = 0.002). CONCLUSIONS: Local recurrence was minimal in PMMA cementation patients, suggesting that PMMA is preferable for routine clinical restructuring in eligible GCT patients. Relationships between tumor characteristics, other modern adjuvants, and recurrence require further exploration.

Sarcoma-Targeting Peptide-Decorated Polypeptide Nanogel Intracellularly Delivers Shikonin for Upregulated Osteosarcoma Necroptosis and Diminished Pulmonary Metastasis.

PURPOSE: Osteosarcoma is the most common primary bone cancer and is notorious for pulmonary metastasis, representing a major threat to pediatric patients. An effective drug targeting osteosarcoma and its lung metastasis is urgently needed. DESIGN: In this study, a sarcoma-targeting peptide-decorated disulfide-crosslinked polypeptide nanogel (STP-NG) was exploited for enhanced intracellular delivery of shikonin (SHK), an extract of a medicinal herb, to inhibit osteosarcoma progression with minimal systemic toxicity. RESULTS: The targeted, loaded nanogel, STP-NG/SHK, killed osteosarcoma cells by inducing RIP1- and RIP3-dependent necroptosis in vitro. Necroptosis is a novel cell death form that could be well adapted as an efficient antitumor strategy, the main obstacle of which is its high toxicity. After intravenous injection, STP-NG/SHK efficiently suppressed tumor growth and reduced pulmonary metastasis, offering greater tumor necrosis and higher RIP1 and RIP3 upregulation compared to free SHK or untargeted NG/SHK in vivo. Additionally, the treatment with NG/SHK or STP-NG/SHK showed minimal toxicity to normal organs, suggesting low systemic toxicity compared to free SHK. CONCLUSION: The STP-guided intracellular drug delivery system using the necroptosis mechanism showed profound anti-osteosarcoma activity, especially eliminated lung metastasis in vivo. This drug formulation may have great potential for treatment of osteosarcoma.

Self-assembled WO3-x hierarchical nanostructures for photothermal therapy with a 915 nm laser rather than the common 980 nm laser.

Photothermal therapy (PTT) is limited by unsuitable photothermal agents and near-infrared (NIR) light. Herein, self-assembled PEGylated WO3-x hierarchical nanostructures, which could serve as excellent laser-cavity mirrors, were successfully prepared via a simple one-pot solvothermal route. The as-prepared WO3-x hierarchical nanostructures displayed strong near-infrared absorption. The absorption of pure water at 980 nm is 30 times higher than that at 915 nm, and the temperature of water only increased by 3.4 °C under the irradiation of a 915 nm laser with a power density of 1.0 W cm(-2) for 10 min, while the temperature of water increased as much as 15.1 °C for the 980 nm laser. With continuous excitation by 915 nm light, the photothermal conversion efficiency of these WO3-x hierarchical nanostructures was evaluated to be 28.1%. Thus, the WO3-x hierarchical nanostructures could serve as excellent laser-cavity mirrors of a 915 nm laser. The PTT study on cancer cells in vivo demonstrated that the WO3-x hierarchical nanostructures can generate enough heat for efficient photothermal therapy of cancer cells under the irradiation of a 915 nm laser with a power density of 1.2 W cm(-2) over a short period (5-10 min).