This study aimed to evaluate the clinical outcomes and complications of reconstruction with a composite free fibula inside other biological grafts. We retrospectively reviewed 26 patients who underwent reconstruction after bone tumor resection of the diaphysis of the long bone. Surgical data, time to bony union, functional outcomes, and complications were evaluated in all cases. The median follow-up was 72.5 months. The limb salvage rate was 100%. Primary osseous union was achieved in 90.4% of the junctions. The union rates at the metaphyseal and diaphyseal junctions were 100% and 85.7%, respectively (p = 0.255). The mean time of bony union in the upper (87.5%) and lower (91.7%) extremity was 4.6 ± 1.6 months and 6.9 ± 2 months, respectively. The mean MSTS score was 27.2 ± 3.2, with a mean MSTS rating of 90.7%. Complications occurred in 15.4% of the cases. The administration of vascularized or non-vascularized grafts did not significantly influence the union time (p = 0.875), functional outcome (p = 0.501), or blood loss (p = 0.189), but showed differences in operation time (p = 0.012) in lower extremity reconstruction. A composite free fibula inside other biological grafts provides a reasonable and durable option for osseous oncologic reconstruction of the long bone diaphysis of the extremities with an acceptable rate of complications. A higher union rate was achieved after secondary bone grafting. In lower-extremity reconstruction, two plates may be considered a better option for internal fixation. Vascularizing the fibula did not significantly affect the union time.

Obesity is increasingly recognized as a negative prognostic factor for cancers, including osteosarcoma. However, the mechanisms linking obesity to chemoresistance in osteosarcoma remain unclear. This study found obesity is significantly associated with poor responses to cisplatin‐based chemotherapy in osteosarcoma patients. In vitro, adipocyte‐conditioned medium (Adi‐CM) induced cisplatin resistance, while peritumoral adipocytes and diet‐induced obesity (DIO) reduce the cisplatin efficacy in vivo. Mechanistically, Adi‐CM enhanced DNA repair by the PARP1/ATM pathway activation. Proteomic analysis identified A1BG, a secreted protein upregulated in adipocytes from chemoresistant patients, as a key mediator of this effect. A1BG depletion in adipocytes restored cisplatin sensitivity, whereas recombinant A1BG enhanced resistance and promoted DNA repair. Further investigation revealed a direct interaction between A1BG and NAMPT, leading to the stabilization of NAMPT and an increased NAD⁺ production. This enhanced PARP1 activity and subsequent DNA repair. Importantly, pharmacological inhibition of NAMPT and PARP1 using FK886 and Olaparib, respectively, reversed Adi‐CM‐induced cisplatin resistance and restored cisplatin sensitivity in osteosarcoma cells, DIO mouse models, and patient‐derived organoids. A novel link between obesity and cisplatin resistance in osteosarcoma is established, highlighting the A1BG/NAMPT/PARP1 axis as a critical driver. Targeting this axis may represent a promising therapeutic strategy for overcoming obesity‐associated chemoresistance in osteosarcoma.

Aims: The reconstruction of proximal humeral defects resulting from tumor resection is challenging. The purpose of this work was to retrospectively study the functional outcomes in patients with large bone defects after the resection of proximal humeral tumors. Methods: We performed a retrospective analysis of 49 patients with malignant or aggressive benign tumors in the proximal humerus at our institution between 2010 and 2021. Forty-nine patients were included in the study (prosthetic replacement, n = 27; shoulder arthrodesis, n = 22). The mean follow-up was 52.8 months (range, 14–129 months). The factors evaluated included the Musculoskeletal Tumor Society (MSTS) functional score, Constant Murley Score (CMS), and complications. Results: Of the 49 patients enrolled in the study, 35 were disease-free by the time of the latest follow-up, and 14 died because of the disease. Adjuvant therapies and medical comorbidities were similar between the two groups. Osteosarcoma was the most common abnormality among all the patients. The mean MSTS scores for surviving patients in the prosthesis and arthrodesis groups were 57.4% and 80.9%, respectively. The mean CMS score for the surviving patients in the prosthesis group was 43.47, and it was 61.44 for arthrodesis cases. Patients with shoulder arthrodesis demonstrated evidence of bony union at a mean of 4.5 months. Conclusions: Shoulder arthrodesis is a reliable reconstructive procedure in patients with large bone defects after the resection of proximal humeral tumors for pediatric osteosarcoma patients. Moreover, prosthetic replacement with anatomical implants results in poor function in older metastasis patients with large bone defects and resection of the deltoid muscle.

Generative artificial intelligence (AI) is increasingly used in postgraduate medical education and research, but the relationship between self-efficacy and