Early results of high tibial osteotomy versus combined arthroscopic surgery.

Objective: To investigate the early effect of high tibial osteotomy (HTO) compared with combined arthroscopic surgery. Methods: A retrospective study was conducted on patients who underwent HTO at The First Affiliated Hospital of Shandong First Medical University from January 2018 to January 2022. 138 patients (163 knees) with knee osteoarthritis (KOA) treated with HTO were selected. The medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), femoral tibial angle (FTA), hip-knee-ankle (HKA) angle, weight-bearing line (WBL) ratio of the knee joint, opening gap, opening angle, American Knee Society score (KSS), US Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were measured to determine the different effects between HTO and HTO combined with arthroscopic by logistic regression analysis. Results: Patients with HTO combined with arthroscopic surgery have improved functional scores as well as imaging perspectives compared to preoperative. By multivariate logistic analysis, it was concluded that arthroscopic surgery and gender are influential factors in the outcome of HTO surgery. The postoperative KSS score was 2.702 times more likely to be classified as excellent in the HTO combined with arthroscopy group than in the HTO group [Exp (ß) = 2.702, 95% CI (1.049-6.961), P = 0.039]; the postoperative KSS score was 0.349 times more likely to be classified as excellent in women than in men [Exp (ß) = 0.349, 95% CI (0.138-0.883), P = 0.026]. Conclusion: Better results with HTO combined with arthroscopic surgery. HTO combined with arthroscopy is a better choice in the surgical treatment of KOA.

Dynamic nanoassemblies derived from small-molecule homodimeric prodrugs for in situ drug activation and safe osteosarcoma treatment.

Supramolecular prodrug self-assembly is a cost-effective and powerful approach for creating injectable anticancer nanoassemblies. Herein, we describe the self-assembly of small-molecule prodrug nanotherapeutics for tumor-restricted pharmacology that can be self-activated and independent of the exogenous stimuli. Covalent dimerization of the anticancer agent cabazitaxel via reactive oxygen species (ROS)- and esterase-activatable linkages produced the homodimeric prodrug diCTX, which was further coassembled with an ROS generator, dimeric dihydroartemisinin (diDHA). The coassembled nanoparticles were further refined in an amphiphilic matrix, making them suitable for in vivo administration. The ROS obtained from the coassembled diDHA synergized with intracellular esterase to activate the neighboring diCTX, which in turn induced potent cytotoxicity. In a preclinical orthotopic model of human osteosarcomas, nanoparticle administration exhibited durable antitumor efficacy. Furthermore, this smart, dual-responsive nanotherapeutic exhibited lower toxicity in animals than those of free drug combinations. We predict that this platform has great potential for further clinical translation.

Bone regeneration after marginal bone resection in two-stage treatment of chronic long bone infection - a combined histopathological and clinical pilot study.

INTRODUCTION: In chronic bone infection, marginal bone resection avoids large and difficult to reconstruct bone defects. However, there is still a lack of knowledge on bone regeneration during chronic bone infection and bone healing capability after marginal bone resection. Therefore, the purpose of this study was to investigate the clinical and histopathological outcomes after marginal bone resection in chronic long bone infection. We hypothesized that there is a regenerative bone healing potential after marginal bone resection that results in an acceptable clinical outcome and improved pathohistological bone healing parameters during treatment. MATERIALS AND METHODS: Nine patients were treated for chronic bone infections in a two-stage manner with marginal bone resection of the infected area and the placement of an antibiotic-loaded polymethyl methacrylate (PMMA) spacer at stage one followed by bone reconstruction at stage two combined with systemic antibiotic therapy. Comparable bone samples were harvested at the border region between vital and necrotic bone area during stage one and the identical location during stage two. Control bone samples were harvested from five healthy patients without bone infection. Clinical outcome in terms of infection eradication and bone consolidation were assessed. The phenotypic changes of osteocyte and morphological changes of lacunar-canalicular network were investigated by histological and immunohistochemical staining between the two observation periods. Furthermore, expression levels of major bone formation and resorption markers were investigated by immunohistochemical and tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: The clinical results with a follow-up of 12.9 months showed that eight of nine patients (88.9%) achieved bone consolidation after a planned two-stage procedure of marginal resection of necrotic bone and consecutive reconstruction. In four of the nine patients (44.4%), additional marginal debridements after stage two had to be performed. After marginal resection at stage one, the improved bone formation ability at stage two was demonstrated by significantly lower percentage of empty lacunae, significantly more mature osteocytes and higher BMP-2 positive cell density, whereas decreased resorption was indicated by significantly lower osteoclast density and RANKL/OPG ratio. In patients requiring additional debridement compared to patients without additional debridements, a significantly higher percentage of empty lacunae was found at stage one. CONCLUSION: Marginal bone resection combined with local and systemic antibiotic therapy is a feasible treatment option to avoid large bone defects as bone from the marginal resection area seems to have good regenerative potential. Despite a high revision rate of 44.4%, this technique avoids large bone resection and revisions can be done by further marginal debridements.

IgM+CD27+ B cells possessed regulatory function and represented the main source of B cell-derived IL-10 in the synovial fluid of osteoarthritis patients.

Synovial inflammation is observed in patients with osteoathritis (OA) and likely contributed to its exacerbation. Regulatory B (Breg) cells are shown to suppress inflammation in various diseases, including rheumatoid arthritis (RA). To examine whether Breg cells also participated in OA, we examined the synovial fluid from OA patients, and compared with that in RA patients. In OA synovial fluid, IL-10-producing B cells were present directly ex vivo and were increased upon stimulation, indicating that B cells were a source of IL-10 directly at the affected site of OA patients. Interestingly, the frequency of IL-10+ cells in synovial B cells was higher in OA patients than in RA patients, but the total number of IL-10+ B cells in OA was lower than that in RA, suggesting that OA patients presented lower B cell infiltration than RA patients. Phenotypical analysis demonstrated that the IL-10+ B cells were IgM+ and CD27+, but not CD24hi or CD38hi. To allow functional analysis of IgM+CD27+ B cells, the IgM+CD27+ B cells in the blood of OA patients were examined. These blood IgM+CD27+ B cells expressed more IL-10, but less CD80 and CD86 than non-IgM+CD27+ B cells. Blood IgM+CD27+ B cells suppressed the proliferation and IFN-γ expression of autologous T cells, and this effect could be reverted if IL-10 was inhibited. Furthermore, we found that patients with more severe OA presented lower levels of IL-10+ B cells in the synovial fluid. Together, our study described an IgM+CD27+ B cell subset in OA patients, which represented the major IL-10-secreting B cell type in the synovial fluid of OA patients and possessed regulatory function.

Tim3+ Foxp3 + Treg Cells Are Potent Inhibitors of Effector T Cells and Are Suppressed in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Earlier studies have demonstrated that regulatory T (Treg) cells, the main cell type mediating immune tolerance, appeared to be enriched in the inflamed synovial tissues. It is still unclear why the Treg cells in RA patients are unable to limit exacerbated inflammation. Here, we found that the frequency of Tim3+Foxp3+ Treg cells, which were potent suppressors of proinflammatory responses, was downregulated in RA patients. Reduction in Tim3+Foxp3+ Treg frequency was correlated with increased RA disease activity. Furthermore, we observed that Tim3+Foxp3+ Tregs were expressed more interleukin (IL)-10 than Tim3-Foxp3+ Tregs. CD4+CD25+Tim3+ T cells had higher capability of inhibiting interferon (IFN)-γ and tumor necrosis factor (TNF)-α secretion from T cells and peripheral blood mononuclear cells (PBMCs) than CD4+CD25+Tim3- T cells. Compared to that in healthy individuals, CD4+CD25+ T cells in RA patients were less potent in suppressing IFN-γ and TNF-α production from PBMCs. Blocking Tim3 on CD4+CD25+ T cells from healthy controls resulted in an elevation of IFN-γ and TNF-α production from PBMCs, suggesting that Tim3 expression on CD4+CD25+ T cells was required for optimal Treg function. However, this phenomenon was not observed in RA patients. In conclusion, our study suggested that the CD4+CD25+Foxp3+ Treg cells from RA patients demonstrated a reduction of Tim3 and were less functional than Treg cells from healthy controls in a Tim3-related manner.