Micro-CT, Mechanical, and Histological Examination of the Effect of Local Adjuvants on Porcine Cortical Bone Following Intralesional Curettage of Bone Tumors.

BACKGROUND AND OBJECTIVES: Curettage is the removal of a tumor from the bone while preserving the surrounding healthy cortical bone, and is associated with higher rates of local recurrence. To lower these rates, curettage should be combined with local adjuvants, although their use is associated with damage to nearby healthy bone. OBJECTIVE: The purpose of this analysis is to determine the effect of local adjuvants on cortical porcine bone by using micro-computed tomography (micro-CT) along with histological and mechanical examination. METHODS: Local adjuvants were applied to porcine specimens under defined conditions. To assess changes in bone mineral density (BMD), a micro-CT scan was used. The pixel gray values of the volume of interest (VOI) were evaluated per specimen and converted to BMD values. The Vickers hardness test was employed to assess bone hardness (HV). The depth of necrosis was measured histologically using hematoxylin and eosin-stained tissue sections. RESULTS: A noticeable change in BMD was observed on the argon beam coagulation (ABC) sample. Comparable hardness values were measured on samples following electrocautery and ABC, and lowering of bone hardness was obtained in the case of liquid nitrogen. Extensive induced depth of necrosis was registered in the specimen treated with liquid nitrogen. CONCLUSION: This study determined the effect of local adjuvants on cortical bone by using micro-CT along with histological and mechanical examination. Phenolization and liquid nitrogen application caused a decrease in bone hardness. The bone density was affected in the range of single-digit percentage values. Liquid nitrogen induced extensive depth of necrosis with a wide variance of values.

Biomechanical comparison of all-polyethylene total knee replacement and its metal-backed equivalent on periprosthetic tibia using the finite element method.

BACKGROUND: Total knee arthroplasty (TKA) with all-polyethylene tibial (APT) components has shown comparable survivorship and clinical outcomes to that with metal-backed tibial (MBT). Although MBT is more frequently implanted, APT equivalents are considered a low-cost variant for elderly patients. A biomechanical analysis was assumed to be suitable to compare the response of the periprosthetic tibia after implantation of TKA NexGen APT and MBT equivalent. METHODS: A standardised load model was used representing the highest load achieved during level walking. The geometry and material models were created using computed tomography data. In the analysis, a material model was created that represents a patient with osteopenia. RESULTS: The equivalent strain distribution in the models of cancellous bone with an APT component showed values above 1000 µÎµ in the area below the medial tibial section, with MBT component were primarily localised in the stem tip area. For APT variants, the microstrain values in more than 80% of the volume were in the range from 300 to 1500 µÎµ, MBT only in less than 64% of the volume. CONCLUSION: The effect of APT implantation on the periprosthetic tibia was shown as equal or even superior to that of MBT despite maximum strain values occurring in different locations. On the basis of the strain distribution, the state of the bone tissue was analysed to determine whether bone tissue remodelling or remodelling would occur. Following clinical validation, outcomes could eventually modify the implant selection criteria and lead to more frequent implantation of APT components.

Implant Preference and Clinical Outcomes of Patients with Staged Bilateral Total Knee Arthroplasty: All-Polyethylene and Contralateral Metal-Backed Tibial Components.

Numerous studies have compared metal-backed components (MBTs) and all-polyethylene tibial components (APTs), but none of them specifically analysed the clinical results and the overall patient preference in patients who had undergone a staged bilateral knee replacement. The purpose of this study is to compare clinical results, perceived range of motion, and overall implant preference among patients who had undergone staged bilateral knee replacement with an APT and contralateral knee replacement with MBTs. A dataset of 62 patients from a single centre who underwent staged bilateral TKA between 2009 and 2022 was selected and retrospectively analysed. Tibial component removal was performed in three knees overall, all of which had MBTs. The mean measured Knee Score (KS) of knees with APTs was 78.37 and that of contralateral knees with MBTs was 77.4. The mean measured Function (FS) of knees with APTs was 78.22, and that of contralateral knees with MBs was 76.29. The mean flexion angle of knees with APTs was 103.8 and that for knees with MBTs was 101.04 degrees. A total of 54.8% of the patients preferred the knee that received APTs over contralateral MBTs. In our cohort, TKA with an APT in one knee and an MBT in the contralateral knee recorded similar clinical results and perceived ranges of motion. Patients in general preferred the knee that received an APT over contralateral knee with an MBT.

Proximal Tibia Tumour Location and Curettage Are Major Risk Factors of Local Recurrence in Giant Cell Tumour of Bone.

Giant cell tumour of bone (GCTB) is one of the most common local aggressive tumourous lesions with a wide variety of biological behaviour. However, there are no clear indicative criteria when choosing the type of procedure and the complication rates remain high, especially in terms of local recurrence. The purpose of the study was to (1) identify the main risk factors for local recurrence, (2) evaluate the recurrence-free survival in dependence on neoadjuvant denosumab use and the type of procedure, and (3) compare the functional outcomes after curettage and en bloc resection. The group included 102 patients with GCTB treated between 2006 and 2020. The mean age of patients was 34.4 years (15-79). The follow-up period was 8.32 years (2-16) on average. Local recurrence occurred in 14 patients (29.8%) who underwent curettage and in 5 patients (10.6%) after en bloc resection. Curettage was shown to be a factor in increasing recurrence rates (OR = 3.64 [95% CI: 1.19-11.15]; p = 0.023). Tibial location was an independent risk factor for local recurrence regardless of the type of surgery (OR = 3.22 [95% CI: 1.09-9.48]; p = 0.026). The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments at five years postoperatively (p = 0.0307). Functional ability and pain as reported by patients at the latest follow-up were superior after curettage compared to resection for upper and lower extremity (mean difference: -4.00 [95% CI: -6.81 to -1.18]; p < 0.001 and mean difference: -5.36 [95% CI: -3.74 to -6.97]; p < 0.001, respectively). Proximal tibia tumour location and curettage were shown to be major risk factors for local recurrence in GCTB regardless of neoadjuvant denosumab treatment. The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments. The functional outcome of patients after curettage was better compared to en bloc resection.

Targeted treatment of severe vascular malformations harboring PIK3CA and TEK mutations with alpelisib is highly effective with limited toxicity.

This was a prospective cohort study of eighteen patients with large and debilitating vascular malformations with one or more major systemic complications. In all patients, we discovered activating alterations in either TEK or PIK3CA. Based on these findings, targeted treatment using the PI3K inhibitor alpelisib was started with regular check-ups, therapy duration varied from 6 to 31 months. In all patients, marked improvement in quality of life was observed. We observed radiological improvement in fourteen patients (two of them being on combination with either propranolol or sirolimus), stable disease in 2 patients. For 2 patients, an MRI scan was not available as they were shortly on treatment, however, a clinically visible response in size reduction or structure regression, together with pain relief was observed. In patients with elevated D-dimer levels before alpelisib administration, a major improvement was noted, suggesting its biomarker role. We observed overall very good tolerance of the treatment, documenting a single patient with grade 3 hyperglycemia. Patients with size reduction were offered local therapies wherever possible. Our report presents a promising approach for the treatment of VMs harboring different targetable TEK and PIK3CA gene mutations with a low toxicity profile and high efficacy.

Clinical outcomes and survival comparison between NexGen all-poly and its metal-backed equivalent in total knee arthroplasty.

PURPOSE: This study aims to compare total knee replacement (TKA) with NexGen All-Poly (APT) and NexGen Metal-Backed (MBT) in terms of implant survivorship, reasons leading to implant failure and functional results of defined age categories. METHODS: A single-centre, retrospective evaluation of 812 patients who underwent knee replacement with NexGen CR between 2005 and 2021, comparing a modern congruent APT component to a modular MBT equivalent component using a similar surgical technique at a notable mean follow-up duration. Implant survival, functional outcomes using the Knee Society Score and range of motion were evaluated and compared in different age categories. RESULTS: Of the 812 NexGen CR TKAs performed at our institution, 410 (50.4%) used APT components and 402 (49.6%) MBT components. The survival rate of NexGen APT was 97.1% and that of NexGen MBT was 93.2% (p = 0.36). Removal of the implant occurred overall in 15 cases, for MBT in ten cases, and for APT in four cases. The FS was proved to be significantly higher when APT components were implanted in younger patients than for MBT (p = 0.005). A similar range of motion between the components was recorded (p = 0.1926). CONCLUSION: Under defined conditions, we measured the clinical results of implants from a single manufacturer implanted in a single department using a similar surgical technique. Considering the limitations, we suggest that all-polyethylene tibial components are equal or even superior to metal-backed ones across the examined age categories.

Outcomes of Intercalary Endoprostheses as a Treatment for Metastases in the Femoral and Humeral Diaphysis.

BACKGROUND: The purpose of this study was to evaluate the implant survival, functional score and complications of intercalary endoprostheses implanted for metastatic involvement of the femoral and humeral diaphysis. METHODS: The selected group covered patients with bone metastasis who were surgically treated with an intercalary endoprosthesis between 2012 and 2021. The functional outcome was evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system, and complications were evaluated by using the failure classification for prosthetics designed by Henderson. RESULTS: The mean follow-up was 29.8 months. In our group of 25 patients with 27 intercalary endoprostheses (18 femurs, 9 humeri), there were 7 implant-related complications (25.9%), which were more common on the humerus (4 cases, 44.4%) than on the femur (3 cases, 16.7%). Only type II failure-aseptic loosening (5 cases, 18.5%)-and type III failure-structural failure (2 cases, 7.4%)-occurred. There was a significantly higher risk of aseptic loosening of the endoprosthesis in the humerus compared with that in the femur (odds ratio 13.79, 95% confidence interval 1.22-151.05, p = 0.0297). The overall cumulative implant survival was 92% 1 year after surgery and 72% 5 years after surgery. The average MSTS score was 82%. The MSTS score was significantly lower (p = 0.008) in the humerus (75.9%) than in the femur (84.8%). CONCLUSIONS: The resection of bone metastases and replacement with intercalary endoprosthesis has excellent immediate functional results with an acceptable level of complications in prognostically favourable patients.

Biomechanical analysis of all-polyethylene total knee arthroplasty on periprosthetic tibia using the finite element method.

BACKGROUND AND OBJECTIVE: Total knee arthroplasty (TKA) with modern all-polyethylene tibial (APT) components has shown high long-term survival rates and comparable results to those with metal-backed tibial components. Nevertheless, APT components are primarily recommended for older and low-demand patients. There are no evidence-based biomechanical guidelines for orthopaedic surgeons to determine the appropriate lower age limit for implantation of APT components. A biomechanical analysis was assumed to be suitable to evaluate the clinical results in patients under 70 years. The scope of this study was to determine biomechanically the appropriate lower age limit for implantation of APT components. METHODS: To generate data of the highest possible quality, the geometry of the computational models was created based on computed tomography (CT) images of a representative patient. The cortical bone tissue model distinguishes the change in mechanical properties described in three parts from the tibial cut. The cancellous bone material model has a heterogeneous distribution of mechanical properties. The values used to determine the material properties of the tissues were obtained from measurements of a CT dataset comprising 45 patients. RESULTS: Computational modeling showed that in the majority of the periprosthetic volume, the von Mises strain equivalent ranges from 200 to 2700 µÎµ; these strain values induce bone modeling and remodeling. The highest measured deformation value was 2910 µÎµ. There was no significant difference in the induced mechanical response between bone models of the 60-year and 70-year age groups, and there was <3% difference from the 65-year age group. CONCLUSIONS: Considering in silico limitations, we suggest that APT components could be conveniently used on a bone with mechanical properties of the examined age categories. Under defined loading conditions, implantation of TKA with APT components is expected to induce modeling and remodeling of the periprosthetic tibia. Following clinical validation, the results of our study could modify the indication criteria of the procedure, and lead to more frequent implantation of all-polyethylene TKA in younger patients.

New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRß Signaling.

Giant-cell tumor of bone (GCTB) is an intermediate type of primary bone tumor characterized by locally aggressive growth with metastatic potential. The aim of this study was to identify new druggable targets among the cell signaling molecules involved in GCTB tumorigenesis. Profiles of activated signaling proteins in fresh-frozen tumor samples and tumor-derived cell lines were determined using phosphoprotein arrays. Analysis of the obtained data revealed epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor beta (PDGFRß) as potential targets, but only the PDGFR inhibitor sunitinib caused a considerable decrease in stromal cell viability in vitro. Furthermore, in the case of a 17-year-old patient suffering from GCTB, we showed that the addition of sunitinib to the standard treatment of GCTB with the monoclonal antibody denosumab resulted in the complete depletion of multinucleated giant cells and mononuclear stromal cells in the tumor tissue. To summarize, the obtained data showed that a specific receptor tyrosine kinase (RTK) signaling pattern is activated in GCTB cells and plays an important role in the regulation of cell proliferation. Thus, activated RTKs and their downstream signaling pathways represent useful targets for precision treatment with low-molecular-weight inhibitors or with other types of modern biological therapy.

Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy - Observational prospective single institution analysis.

PURPOSE: Conventional osteosarcoma is an orphan disease. Current treatment approaches include combining a three drug chemotherapy schedule and surgery. The 3- and 5-year event-free survival (EFS) in localized disease is roughly 65 and 60%, respectively. The registration study of mifamurtide reported survival benefit, but some methodological controversies have been insufficient for FDA market authorization in contrast to EMA. METHODS: prospective single centre survival analysis of a mifamurtide addition to conventional therapy in 23 patients over a 5.5 year enrolment period is reported and compared to a historical control of 26 patient with localized disease. Bias arising from observational methodology was addressed using Landmark analysis and time-dependent Cox models. Blood count dynamics were analysed during the treatment. RESULTS: The adverse event profile was as expected with no dose limiting toxicities. There were no local relapses observed, one patient died in the first complete remission due to doxorubicin cardiotoxicity, one patient had pulmonary metastatic relapse. The observed 3- and 5-year EFS was 87.4% (CI 72.4-100%) and 87.4% (CI 72.4-100%), progression free survival (PFS) was 92.9% (CI 80.3-100%) and 92.9% (CI 80.3-100%), overall survival was 94.1% (CI 83.6-100) and 80.7% (CI 58.3-100), respectively. Comparison to the historical control showed statistically significant better PFS for mifamurtide patients (Landmark analysis; p = 0.044). Risk of progression was 5-times lower for the mifamurtide group (Cox model; HR 0.21, p = 0.136). Only subtle differences in lymphocyte counts were observed across treatment. CONCLUSION: the PFS benefit of mifamurtide is reported herein. The addition of mifamurtide could be considered as a best treatment option for localized osteosarcoma.