Background: The pelvis is one of the most common locations for metastatic bone disease. While many of the publications that describe surgical treatments focus on periacetabular lesions (Enneking zone II), there is a lack of investigation into lesions in the non-periacetabular areas (zones I, III, and IV). We recently described a minimally invasive percutaneous screw application for metastatic zone-II lesions with excellent results. In the present study, we aimed to extend this approach to the other pelvic areas. Methods: Twenty-two consecutive patients with painful non-periacetabular pelvic metastatic cancer were included based on retrospective chart review. There were 16 women and 6 men with an average age of 60 years (range, 36 to 81 years). The most common primary cancers were multiple myeloma (7 cases) and breast (5 cases). The most common locations were the sacrum and the ilium. A pathologic fracture was identified in 15 patients. Most of the lesions were treated with multiple large-diameter screws, except for the isolated zone-III lesions. All of the procedures were completed in a standard operating room without the need for special instruments. Radiation therapy was given to 19 patients; the average dose was 15 Gy. The studied outcomes were pain and functionality as assessed by a visual analog scale (VAS) score and the Eastern Cooperative Oncology Group score (ECOG), respectively. Results: There were no surgical complications and no need for blood transfusion. The average follow-up time was 7 months (range, 0.3 to 34.0 months). Two patients died within 4 weeks of surgery due to COVID-19 infection. There was significant improvement in the postoperative VAS pain score (p < 0.0001) and the ECOG score (p < 0.05) when compared with the preoperative scores. There was no implant failure or revision surgery. Local bone-healing was observed in 12 of 14 patients (86%) who survived for >3 months after surgery. Conclusions: Percutaneous screw application is safe and effective in the treatment of metastatic non-periacetabular pelvic lesions. Given the simplicity of the technique and the instrumentation and the tolerance for concomitant treatments, this approach is worthy of broader consideration. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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.

Introduction: The effect of post-operative patella tilt on functional outcomes after total knee arthroplasty remains unclear. Our study aimed to analyze the relationship of post-operative patellar tilt with functional outcome scores after total knee arthroplasty. Materials and Methods: Patient data were retrieved from our institution’s prospectively maintained total knee arthroplasty. Three hundred three patients who underwent unilateral TKA from Jan 2012 to March 2017 were included in the study. After excluding patients with incomplete and lost follow-up data, 213 patients were analyzed. Radiographs of pre-operative and post-operative skyline views were used for patella tilt and patella displacement measurement at pre-op, post-op 1 year, and post-op 2 years. Three functional outcome scoring systems, SF-36, KSS, and WOMAC, were applied for function evaluation at different post-operative time points. Patients were divided into three subgroups according to the patella tilt, which includes less than 5°, 5.1–10°, and more than 10°. Statistical analysis was done to identify the relationship between patella tilt and functional outcomes. Results: Mean post-operative patella tilt was significantly lower than the mean pre-operative patella tilt (3.35 ± 3.91 vs. 5.65 ± 4.41, p < 0.001). There was no significant difference in patella displacement among pre- and post-operative status. KSS functional score was significantly poor at post-op 1 year and KSS objective score at post-op 2 years in patients with more than 10° patella tilt. SF-36 and WOMAC were not significantly different among the groups. There was no significant difference in post-operative function between non-resurfaced and resurfaced patella patients evaluated with three scoring systems. Conclusion: We have found significantly less post-operative patella tilt after TKA than pre-operative patella tilt with or without patella resurfacing. Increased post-operative patella tilt of more than 10° can affect specific functional outcomes. Patella resurfacing does not affect the post-operative functional outcome compared to non-resurfacing of the patella post-op 2 years. Level of Evidence: III.

Purpose: Although multiple fixation constructs exist for patella fractures, postoperative complications are common, and optimal construct choice remains unclear. This study evaluated construct-specific complication rates in operatively treated patella fractures. Methods: A retrospective review was conducted of adult patients who underwent surgical fixation of patella fractures (AO/OTA 34) at a Level I trauma center between 2012 and 2022. Patients younger than 18 years, treated with isolated cerclage wiring, or with less than 90 days of follow-up were excluded. Patients were stratified by fixation construct: tension band wiring (TBW), plate, screws, tendon advancement, or multiple constructs. Demographic, injury, and clinical data were obtained from medical records. Primary outcomes included reoperation, fixation failure, nonunion, deep infection, and SIR. Results: A total of 242 patients were included and stratified by construct type: TBW ( n = 106), plate ( n = 18), screws ( n = 39), TA ( n = 60), and multiple constructs ( n = 19). Patients treated with plates were significantly younger (37.1 vs. 45.8 years; p = 0.023) and more likely to have open fractures (50.0%; p = 0.025), comminuted fracture patterns (≥ 4 fragments: 83.3%; p < 0.001), and OTA 34C3 fractures (77.8%; p < 0.001). Plate fixation was associated with a higher rate of SIR compared to other groups (27.8%; p = 0.012), while no significant differences were observed in reoperation ( p = 0.142), nonunion ( p = 0.652), fixation failure ( p = 0.316), or infection ( p = 0.505). In subgroup analysis, suture cerclage augmentation in TBW was associated with significantly higher rates of reoperation (85.7% vs. 19.2%; p < 0.001), nonunion (57.1% vs. 8.1%; p = 0.003), and fixation failure (57.1% vs. 15.2%; p = 0.019). Conclusion: Plate fixation was associated with higher SIR, and suture cerclage in TBW constructs was associated with increased complications in patella fracture fixation.

DESeq2 results and DESEq2 size-factor normalize counts for TKO vs DKO bulk RNAseq samples

Pan-cancer TCGA analysis of macrophage infiltration correlation with SKP2 and survival via TIMER2.0