Subtrochanteric nonunion after intramedullary nailing due to pathological fracture: proximal femoral replacement as a salvage approach.

PURPOSE: To assess proximal femoral replacement as a treatment solution for nonunion of pathologic subtrochanteric fractures after cephalomedullary nailing in patients with pathological fracture and previously irradiated bone. METHODS: Retrospective review of five patients with pathological subtrochanteric femoral fractures that were treated with cephalomedullary nailing and developed a nonunion, which was revised with conversion to a proximal endoprosthetic replacement. RESULTS: All five patients had previously been treated with radiation. One patient had the latest follow-up at 2 months postoperatively. At that time, the patient was walking with a walker for assistance, with no evidence of hardware failure or loosening on imaging. The remaining four patients had the latest follow-up ranging from 9 to 20 months after surgery. At their latest follow-up, three of the four patients were ambulatory with no pain, using only a cane for assistance with longer distances. The other patient demonstrated pain in his affected thigh, utilizing a walker for assistance with ambulation at latest follow-up, but not requiring further surgical interventions. There were no hardware failures or implant loosening through the follow-up period. None of the patients required revision, and there were no postoperative complications observed at their last follow-up. CONCLUSIONS: In patients with pathological fractures in the subtrochanteric region that is treated with cephalomedullary nailing and developed a nonunion, treatment with conversion to a proximal femoral replacement with a mega prosthesis is a valuable treatment with good functional results and low risk for complications. LEVEL OF EVIDENCE: Therapeutic level IV.

SKP2 Knockout in Rb1/p53-Deficient Mouse Models of Osteosarcoma Induces Immune Infiltration and Drives a Transcriptional Program with a Favorable Prognosis.

Osteosarcoma is an aggressive bone malignancy with a poor prognosis. One putative proto-oncogene in osteosarcoma is SKP2, encoding a substrate recognition factor of the SCF E3 ubiquitin ligase. We previously demonstrated that Skp2 knockout in murine osteosarcoma improved survival and delayed tumorigenesis. Here, we performed RNA sequencing (RNA-seq) on tumors from a transgenic osteosarcoma mouse model with conditional Trp53 and Rb1 knockouts in the osteoblast lineage ("DKO": Osx1-Cre;Rb1lox/lox;p53lox/lox) and a triple-knockout model with additional Skp2 germline knockout ("TKO": Osx1-Cre;Rb1lox/lox;p53lox/lox;Skp2-/-), followed by qPCR and immunohistochemistry validation. To investigate the clinical implications of our results, we analyzed a human osteosarcoma patient cohort ("NCI-TARGET OS") with RNA-seq and clinical data. We found large differences in gene expression after SKP2 knockout. Surprisingly, we observed increased expression of genes related to immune microenvironment infiltration in TKO tumors, especially the signature genes for macrophages and to a lesser extent, T cells, B cells, and vascular cells. We also uncovered a set of relevant transcription factors that may mediate these changes. In osteosarcoma patient cohorts, high expression of genes upregulated in TKO was correlated with favorable overall survival, which was largely explained by the macrophage gene signatures. This relationship was further supported by our finding that SKP2 expression was negatively correlated with macrophage infiltration in the NCI-TARGET osteosarcoma and the TCGA Sarcoma cohorts. Overall, our findings indicate that SKP2 may mediate immune exclusion from the osteosarcoma tumor microenvironment, suggesting that SKP2 modulation in osteosarcoma may induce antitumor immune activation.

Orthopedic approaches for bone sarcoma: A bibliometric review of the 50 most cited papers.

Background: Curative treatment of bone sarcoma is primarily based on operative management. The Orthopedic Oncology approach towards this disease has evolved greatly to the breakthrough in systemic treatment options as well as unique implant designs favoring limb salvage over amputations. The purpose of this study was to perform a bibliometric analysis of the top 50 most cited papers related to the orthopedic the approach to bone sarcomas. Methods: We queried the ISI Web of Knowledge database in July 2022. Keywords utilized were: ""Bone Sarcoma" OR "Osteosarcoma" OR "Ewing Sarcoma" OR "Chondrosarcoma" OR "Chordoma". The top 50 articles pertaining to the orthopedic approach to bone sarcoma were included for analysis and included manuscript title, authors, citation count, journal and publication year. Results: The mean number of citations are 187.06 (Range 125-400; SD 67.83). The average citations per year is 10.03 (Range 47.86-3.43; SD 8.05). Many articles were published from 2000 to 2009 (n = 20) and 1990-1999 (n = 13). The majority of the articles were published by institutions within the United States (n = 32). The most common level of evidence was level IV (n = 37). Majority of the articles focused on treatment outcome (n = 22). Conclusion: This study offers a comprehensive review of the most cited literature regarding orthopedic approaches to bony sarcomas. Modern treatment approaches for bone sarcoma has resulted in an increased focus within the literature on achieving disease free survival wide tissue margins. Understanding the trends of available studies allows for physicians and researchers to target and innovate future areas of study.

SKP2 knockout in Rb1/p53 deficient mouse models of osteosarcoma induces immune infiltration and drives a transcriptional program with a favorable prognosis.

Purpose: Osteosarcoma (OS) is an aggressive bone malignancy with a poor prognosis. One putative proto-oncogene in OS is SKP2, encoding a substrate recognition factor of the SCF E3 ubiquitin ligase. We previously demonstrated that SKP2 knockout in murine OS improved survival and delayed tumorigenesis. Here we aim to define the SKP2 drives transcriptional program and its clinical implication in OS. Experimental Design: We performed RNA-sequencing (RNA-seq) on tumors from a transgenic OS mouse model with conditional Trp53 and Rb1 knockouts in the osteoblast lineage ("DKO": Osx1-Cre;Rb1lox/lox;p53lox/lox) and a triple-knockout model with additional Skp2 germline knockout ("TKO": Osx1-Cre;Rb1lox/lox;p53lox/lox;SKP2-/-). We validated our RNA-seq findings using qPCR and immunohistochemistry. To investigate the clinical implications of our results, we analyzed a human OS patient cohort ("NCI-TARGET OS") with RNA-seq and clinical data. Results: We found large differences in gene expression after SKP2 knockout. Strikingly, we observed increased expression of genes related to immune microenvironment infiltration in TKO tumors. We observed significant increases in signature genes for macrophages and to a lesser extent, T cells, B cells and vascular cells. We also uncovered a set of relevant transcription factors that may mediate the changes. In OS patient cohorts, high expression of genes upregulated in TKO was correlated with favorable overall survival, which was largely explained by the macrophage gene signatures. This relationship was further supported by our finding that SKP2 expression was negatively correlated with macrophage infiltration in the NCI-TARGET OS and the TCGA Sarcoma cohort. Conclusion: Our findings indicate that SKP2 may mediate immune exclusion from the OS tumor microenvironment, suggesting that SKP2 modulation in OS may induce anti-tumor immune activation.

The efficacy of patient specific instrumentation (PSI) in total hip arthroplasty (THA): A systematic review and meta-analysis.

Background: Patient-specific instrumentation (PSI) has been suggested to reduce improper component positioning, though the effectiveness of PSI in total hip arthroplasty (THA) remains inconclusive. The purpose of this study was to evaluate the radiographic parameters and clinical outcomes comparing PSI and standard instrumentation (SI). Methods: This systematic review and meta-analysis was conducted in accordance with the 2020 PRISMA statement and was registered on PROSPERO. PubMed, Embase, Scopus, Google Scholar, and ClinicalTrials.gov were searched for relevant studies pertaining to the use of PSI in THA. Inclusion criteria included PSI used in THA, PSI was directly compared to SI, and publication in English. Exclusion criteria included non-primary THA, review articles, abstracts, book chapters, and animal models. Results: 2,458 studies were initially identified, with 13 studies (677 THAs: 338 controls, 339 PSI) meeting all criteria. PSI was favored for the deviation from the preoperative plan for acetabular cup position for anteversion (p = 0.04) and inclination (p = 0.0002); risk of acetabular cup positioning outside the Lewinnek safe zone for anteversion (p = 0.005) and inclination (p < 0.0001); and postoperative Harris Hip Score (p = 0.0002). No significant differences were found for the deviation from the preoperative plan for femoral stem position for anteversion (p = 0.74) or varus/valgus (p = 0.15); intraoperative time (p = 0.55); or intraoperative blood loss (p = 0.62). Conclusion: The use of PSI in THA is effective in improving acetabular component positioning and postoperative functional outcomes, without increasing intraoperative time or blood loss, compared to SI.

Surgical Management of Benign Tumors of the Proximal Fibula.

Benign tumors of the proximal fibula are clinically notable, often resulting in pain, cosmetic defects, and potential neurovascular compromise. These symptomatic lesions warrant surgical consultation, but specific procedure selection remains a topic of ongoing discussion. The fibula is widely considered an expendable bone, which permits a greater variety of surgical options relative to other skeletal locations. As a result, some authors suggested en bloc resections without reconstruction as a viable first-line option to decrease tumor recurrence risk. However, wide resections may still result in diminished postoperative functionality compared with the standard intralesional and marginal approaches. Thus, surgical management remains a multifactorial decision, and often orthopaedic surgeons rely on past clinical experience or surgical preference within this unique tumor location. This detailed review will summarize the published literature and discuss the outcomes and indications of various surgical approaches for benign tumors of the proximal fibula. Emphasis will be placed on balancing tumor recurrence risk and postoperative functionality within the context of histologic diagnoses and surgical approaches.