Biomedical analysis of four fixation systems in treatment of type II traumatic spondylolisthesis of the axis: a finite element analysis.

This study aimed to compare the properties and safety of self-designed plates in type II traumatic spondylolisthesis of the axis with those of traditional devices via finite element (FE) analysis. We constructed a hangman's fracture FE model from the occipital bone (C0) level to the C3 level. Then, FE models were constructed for the following four fixation systems: an anterior cervical L-shaped plate with four vertebral screws (4-ACLP), or six screws (6-ACLP), an anterior cervical orion plate (ACOP), and a posterior fixation system. A preloaded compressive force of 50 N and a moment of 1.5 N·m were applied to each model under six working conditions. The mobility of the C2/3 segment decreased significantly in four fixation models. In the Mises stress cloud diagram, 4-ACLP showed a better stress distribution in both the bone graft and fixation system than 6-ACLP and ACOP. The resultant force of 4-ACLP was lower but higher than ACOP in axial force. Additionally, the cage in the 4-ACLP configuration experienced the highest stress in the six working conditions. Hence, this novel self-designed plate has the potential to mitigate the operational difficulties, provide sufficient stability, reduce the risk of plate or screw fractures, and improve bone fusion.

A Novel Free-hand Technique of Pedicle Screw Placement in the Lumbar Spine: Accuracy Evaluation and Preliminary Clinical Results.

OBJECTIVE: Pedicle screw implantation is the most common technique to achieve stability during spinal surgeries. Current methods for locating the entry point do not have a quantified criteria and highly rely on the surgeons' experience. Therefore, we aim to propose a quantified pedicle screw placement technique in the lumbar spine and to investigate its accuracy and safety in clinical practice. METHODS: We conducted a retrospective study involving 110 patients who received spinal surgery in our hospital from August 2018 to August 2021. All patients included had herniation of a single lumbar disc and were consistently treated with posterior discectomy, inter-body fusion, and transpedicular internal fixation. For 54 patients in the observation group, the pedicle screws were placed with our technique, which is located at 4 mm below the superior edge of the transverse process in line with the lateral margin of the superior articular process. For 56 patients in the control group, pedicle screws were placed according to the traditional crista lambdoidalis method. Comparisons were made in terms of the operation time, blood loss, time for exposure, the accuracy of placement, and postoperative complications. Furthermore, we applied our method to 64 patients with indistinguishable crista lambdoidalis and evaluated the accuracy of screw placement and clinical outcomes according to the visual analogue scale (VAS) and the Japanese Orthopaedic Association (JOA) score. RESULTS: There was no significant difference in intraoperative bleeding, accuracy of placement, and postoperative complications between our technique and the traditional crista lambdoidalis method (P > 0.05). However, the exposure time before screw placement (12.8 ± 0.3 vs. 17.4 ± 0.3, P = 0.001) and the total surgery time (97.2 ± 1.9 vs 102.3 ± 0.9, P = 0.020) were significantly shortened with our method. Additionally, in cases with indistinguishable crista lambdoidalis, our technique showed satisfying accuracy, with 97.6% screws placed in appropriate trajectory on the first attempt and all screws eventually positioned in the safe zone according to the Gertzbein-Robbins grading. All patients experienced steady improvement after surgery. CONCLUSION: Placing pedicle screws at 4 mm below the superior edge of the transverse process in line with the lateral margin of the superior articular process is a viable pedicle screw placement method. With this method, we observed a higher success rate and shorter operation time. In addition, this method can be applied in cases with indistinguishable crista lambdoidalis, and have satisfied success rate and clinical outcome.

Reconstructing avascular necrotic femoral head through a bioactive ß-TCP system: From design to application.

A variety of techniques have been used for treating avascular necrosis of the femoral head (ANFH), but have frequently failed. In this study, we proposed a ß-TCP system for the treatment of ANFH by boosting revascularization and bone regeneration. The angio-conductive properties and concurrent osteogenesis of the highly interconnected porous ß-TCP scaffold were revealed and quantified through an in vivo model that simulated the ischemic environment of ANFH. Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation, and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone, along with continuous material degradation and bone regeneration. For translational application, we further conducted a multi-center open-label clinical trial to assess the efficacy of the ß-TCP system in treating ANFH. Two hundred fourteen patients with 246 hips were enrolled for evaluation, and 82.1% of the operated hips survived at a 42.79-month median follow-up. The imaging results, hip function, and pain scores were dramatically improved compared to preoperative levels. ARCO stage Ⅱ disease outperformed stage Ⅲ in terms of clinical effectiveness. Thus, bio-adaptive reconstruction using the ß-TCP system is a promising hip-preserving strategy for the treatment of ANFH.

Predicting chemosensitivity based on mini patient-derived xenografts in osteosarcoma patients: A retrospective study.

Context: The survival of patients diagnosed with osteosarcoma has not improved in the past three decades because of chemoresistance. Aim: This study aimed to improve the prognosis of patients with osteosarcoma. Settings and Design: From January 1, 2018, to June 30, 2019, a total of 14 patients with osteosarcoma were enrolled who underwent mini patient-derived xenograft (mini-PDX) assay in our hospital. Methods and Materials: We recruited 14 patients with osteosarcoma having acquirable lesions to establish PDX models and examine the sensitivity of nine drugs, including methotrexate (MTX), ifosfamide (IFO), epirubicin, and etoposide. Drug sensitivity was evaluated using the tumor relative proliferation rate (TRPR), and the patients' responses were assessed according to the RECIST 1.1 guidelines. Statistical Analysis Used: The difference in TRPR was analyzed using a paired t-test, while progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Results: The mini-PDX results revealed that IFO had a lower tumor proliferation rate than MTX, indicating that IFO was more sensitive in patients with osteosarcoma (38.3% vs. 84.3%, P = 0.031). Thus, the regimen where IFO alternates with doxorubicin and cisplatin was recommended as adjuvant chemotherapy. MTX could replace IFO if the TRPR was better. Finally, 11 patients received adjuvant chemotherapy. A comparison of PFS revealed that sensitive patients with TRPR of <40% had a better prognosis (9.4 months vs. 3.7 months, P = 0.0324). Conclusions: Chemotherapy based on mini-PDX can improve the survival of patients with osteosarcoma whose TRPR was <40%, and that chemotherapy without MTX could be an alternative for osteosarcoma.

Evaluation of Anlotinib Combined with Adriamycin and Ifosfamide as Conversion Therapy for Unresectable Soft Tissue Sarcomas.

(1) Background: This study investigated the safety and efficiency of adriamycin and ifosfamide combined with anlotinib (AI/AN) as a neoadjuvant conversion therapy in uSTS. (2) Methods: Patients with uSTS were eligible to receive AI/An, including adriamycin (20 mg/m2/d) and ifosfamide (3 g/m2/d) for the first to the third day combined with anlotinib (12 mg/d) for 2 weeks on/1 week off, all of which combine to comprise one cycle. Surgery was recommended after four cycles of treatment. (3) Results: A total of 28 patients were enrolled from June 2018 to December 2020. The best tumor responses included eight patients with partial responses and 20 with a stable disease. Patients with synovial sarcoma and liposarcoma had a significant decrease in the number of tumors compared with fibrosarcoma (p = 0.012; p = 0.042). The overall response rate and disease control rate were 28.57% and 100%, respectively. In total, 24 patients received surgery, while the rates of limb salvage and R0 resection were 91.67% (n = 22/24) and 87.50% (n = 21/24), respectively. Until the last follow-up visit, the mean PFS and RFS were 21.70 and 23.97 months, respectively. During drug administration, 67.87% of patients had grade ≥3 AEs. No treatment-related death occurred. (4) Conclusions: AI/AN followed by surgery showed favorable efficiency and manageable safety in patients with uSTS. A randomized controlled study with a large cohort should be performed for further investigations.

Lateral Malleolus Reconstruction After Tumor Resection in Children: A Case Report and Literature Review.

BACKGROUND: Pediatric reconstruction of lateral malleolus was necessary and challengeable. Up to now, vascularized fibular was the optimal graft to reconstruct epiphyseal defection. However, the sophisticated microvascular operation has limited the wide application of this technique. CASE PRESENTATION: We present the case of a 9-year-old boy with Ewing sarcoma in left distal fibula. In order to restore the growth capacity, we used reverse-flow vascularized fibular epiphyseal graft with tibialis anterior artery to reconstruct the bone defect after tumor resection with no microvascular anastomosis. More than 4 years after the operation and adjuvant chemotherapy, the patient was free of pain and recurrence, and the function and stability of ankle joint was perfect. Radiology examination revealed satisfied bony union of fibula and normal growth of the fibular head transplant. CONCLUSIONS: The advantage of reverse-flow vascularized fibular epiphyseal graft is requiring no microvascular anastomosis which could not only shorten operating time, but also reduce factitious damage of vessels. This report presented that this technique might be an available option for reconstruction of lateral malleolus in children.

Establishment of a rabbit's model for modified Capanna technique.

BACKGROUND: Massive bone allograft with an intramedullary vascularized fibula (Capanna technique) represents one of the most widely used methods for the reconstruction of massive bone defect. However, the mechanisms, healing process, and underlying influential factors were poorly understood due to the lack of suitable experimental animal models. METHODS: Critical-sized defects (CSD) in bone were constructed in the proximal tibia of 24 rabbits and randomly divided into two groups. Allogeneic bone segments of the same size as CSDs were obtained from another 12 rabbits and then inactivated. In group Ⅰ, an ipsilateral pedicled vascularized fibula was dissociated and transferred into the intramedullary cavity of allograft to assemble a composite for CSD reconstruction (Capanna technique), while group Ⅱ received a reconstruction with allogeneic bone alone. Radiographic evaluation was performed every week after the operation to assess union status. All animals were sacrificed at 16th week, and the specimens were histologically analyzed. RESULTS: All animals survived without severe intraoperative complications. There was one rabbit (8.33%) in group Ⅰ developed a postoperative infection and died, while three rabbits (25%) had postoperative complications in group Ⅱ (two died of infection and one died of internal fixation fracture). Radiographically, the mean time to union at the allograft-host junction in group Ⅰ was 12.8 ± 1.80 weeks, significantly shorter than in group II (>15.18±1.12 weeks; p<0.001). The grade of graft union of group Ⅰ was significantly higher than that of group Ⅱ both at 8th and 16th week (8th week: p = 0.035; 16th week: p = 0.033). Fully bone union at the junctions was histologically confirmed in all specimens in group Ⅰ and 66.67% (8/12) in group Ⅱ. CONCLUSION: Combined allograft and intramedullary vascularized fibula transfer in rabbit's tibia represent an ideal model that accurately simulates the Capanna technique for CSD reconstruction.

Three-dimensional finite element analysis of a novel interzygapophyseal fusion device for lower cervical spine.

PURPOSE: A three-dimensional finite element model of the lower cervical spine was established to evaluate the biomechanical stability and stress distribution of the new lower cervical interzygapophyseal fusion device (IZFD) developed by ourselves under different construct. The aim of this study was to provide theoretical basis for further clinical application. METHODS: A normal fresh cadaveric specimen (male, 35 years old) was used to establish an intact three-dimensional finite element model of C3-C6. On this basis, the comparative finite element models of the lateral mass screw rod (LMSR) system and LMSR+IZFD were established. Only C4-C5 is fixed in the lateral mass. The range of motion (ROM) and stress distribution in the flexion,extension, lateral bending and rotation of the C4-C5 segment under the three constructs were analyzed. RESULTS: The ROM and stress distribution of the three-dimensional finite element model under load construct were within a reasonable range, which proved the validity and reliability of the model. The ROM and stress distribution of C4-C5 segment was significantly decreased in both LMSR and LMSR+IZFD constructs than those in the intact construct. The ROM and stresss distribution were even smaller in LMSR+IZFD construct than in LMSR construct. CONCLUSIONS: The IZFD combined with LMSR system can provide satisfactory stability for the lower cervical spine, and the IZFD can further improve the fixation effect of the LMSR system.

Assessment of Efficiency and Safety of Apatinib in Advanced Bone and Soft Tissue Sarcomas: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies, both in vitro and in vivo, have established that apatinib has anti-tumor properties. However, insufficient empirical evidence of the efficacy and safety of apatinib has been published for bone and soft tissue sarcoma, the reported results differing widely. Here, we conducted a meta-analysis to assess the efficacy and toxicity of apatinib for the treatment of bone and soft tissue sarcoma. METHODS: Pubmed, Medline, Web of Science, ScienceDirect, Ovid, Embase, Cochrane Library, Scopus, Vip (China), Cnki (China), Wanfang (China), and CBM (China) databases and literature from conferences were searched for studies of apatinib for the treatment of bone and soft tissue sarcomas, published from the inception of each database to Sep 1, 2020, without language restrictions. Primary outcomes were efficacy and toxicity of apatinib for the treatment of bone and soft tissue sarcoma, including treatment response, progression-free survival (PFS), and the incidence of adverse events. After extraction of data and methodological quality evaluation, random or fixed-effects models, as appropriate, were selected to calculate pooled effect estimates using R software (Version 3.4.1). RESULTS: A total of 21 studies with 827 participants were included in the present meta-analysis. The mean MINORS score was 10.48 ± 1.75 (range: 7-13), indicating evidence of moderate quality. Pooled outcomes indicated that overall response rate (ORR) and disease control rate (DCR) were 23.85% (95% CI: 18.47%-30.21%) and 79.16% (95% CI: 73.78%-83.68%), respectively. Median PFS ranged from 3.5 to 13.1 months, with a mean of 7.08 ± 2.98 months. Furthermore, the rates of PFS (PFR) after 1, 6, and 12 months were 99.31%, 44.90%, and 14.31%, respectively. Drug-related toxicity appears to be common in patients administered apatinib, for which hand-foot syndrome (41.13%), hypertension (36.15%), and fatigue (20.52%) ranked the top three most common adverse events. However, the incidence of grade 3-4 adverse events was relatively low and manageable. CONCLUSIONS: Based on the best evidence currently available, apatinib demonstrates promising clinical efficacy and an acceptable safety profile for the treatment of advanced bone and soft tissue sarcoma, although additional high-quality clinical studies are required to further define its properties and toxicity.

Effective treatment of anlotinib in giant delayed pulmonary metastasis of osteosarcoma: a case report and literature review.

Tumor relapse and pulmonary metastasis, especially unresectable lesions, are the major cause of poor prognosis of patients with osteosarcoma. Anlotinib, a novel small-molecule tyrosine kinase inhibitor (TKI), has been proved to have desirable anti-tumor effects via blocking VEGFR2 and PDGFRß phosphorylation in several tumors, including non-small cell lung cancer and soft tissue sarcoma. In this study, we presented a case of giant delayed pulmonary metastasis of osteosarcoma which was effectively treated by anlotinib. CT scan of this patient showed a giant neoplasm with the size of 1,366 cm3 in the left lung, clinically diagnosed as pulmonary metastasis of osteosarcoma. Due to refusing to chemotherapy and not eligible for surgery of the giant neoplasm, anlotinib was recommended. As a result, the tumor volume decreased more than 82% during 24-week anlotinib administration, from 1,366 to 247 cm3. Unfortunately, disease progression was observed at 27-week. Although argon-helium cryoablation (AHC) was performed followed by apatinib administration, the patient was dead in 16 weeks after disease progression. The progression-free survival (PFS) and overall survival since anlotinib administration of this patient was 27 weeks and 43 weeks, respectively. The toxicity included hypertension, fatigue and hand-foot skin syndrome in grade 1-2, which were controllable and well tolerated. Meanwhile, immunohistochemical staining showed that the expression of VEGFR2 and PDGFRß was decreased significantly and the whole exon sequencing revealed that c-MYC was duplicated, which was potentially associated with anlotinib resistance. Anlotinib had promising anti-tumor efficiency in the treatment of delayed pulmonary metastatic osteosarcoma. However, the potential mechanism of anlotinib resistance and the subsequent therapy after resistance were still challengeable and needed further investigation.

Novel 3D-printed prosthetic composite for reconstruction of massive bone defects in lower extremities after malignant tumor resection.

OBJECTIVE: To introduce a novel 3D-printed prosthetic composite for reconstruction of massive bone defects after resection for bone malignancy of lower extremities. The design concept, surgical technique, and the preliminary outcomes were elaborated. METHODS: Patients with primary malignant tumors of lower extremities requiring tumor resection and reconstruction were recruited between Jun 2015 and Nov 2018. Patient-specific 3D-printed prostheses were designed according to preoperative imaging data. After tumor resection, reconstruction was performed with composites consisting of 3D- printed prosthesis, beta-tricalcium phosphate (ß-TCP) bioceramics and/or vascularized fibula. All patients underwent regular follow-up postoperatively. The functional outcomes were assessed by the Musculoskeletal Tumor Society score (MSTS). Oncological outcomes, imaging results, and complications were recorded and analyzed. RESULTS: Ten cases averaging 12.90 years of age participated in this study. There were five femur and five tibia reconstructions. The mean follow-up period was 16.90 months. At last follow-up, all patients were alive without tumor recurrence. Average MSTS functional score was 80.33 ± 11.05%. All prostheses were intact and stable without failure or systemic breakage. No serious complications occurred after the operation. Postoperative X-ray, computed tomography (CT) and single-photon emission computed tomography (SPECT) showed an ideal integration between the bone and the prosthetic composite. Moreover, vascularized fibula and implanted ß-TCP bioceramics indicated relatively high metabolic activity in vivo. CONCLUSIONS: Patient-specific 3D-printed prostheses combined with ß-TCP bioceramics and/or vascularized fibula provide an excellent option for reconstruction of massive bone defects after lower extremity malignant tumor extirpation. Short-term follow up showed promising clinical results in recovering lower limb function, promoting osseointegration and reducing complications.

Collagen/ß-TCP composite as a bone-graft substitute for posterior spinal fusion in rabbit model: a comparison study.

ß-TCP bioceramic, as a kind of biocompatible and biodegradable artificial bone scaffolds, is increasingly used to supplement lamina autografts when performing instrumented or non-instrumented spinal fusion, clinically, although solid fusion is not always achieved. The addition of collagen to ß-TCP appears to be a potential strategy to improve bone regeneration, thereby enhancing the rate of spinal fusion. This study aimed to compare the fusion in collagen/ß-TCP composite, ß-TCP and autologous bone in a posterior spinal fusion model. The fusion grade evaluated radiography was greater in the collagen/ß-TCP group than in the ß-TCP group (p < 0.05). Stiffness and yield strength of the fused segments in collagen/ß-TCP group were comparable to that in autogenous bone group. Histological analysis revealed that the proportion of new bone formation in collagen/ß-TCP group were significantly greater than in ß-TCP group (p < 0.05). In addition, bone deposition rate in the collagen/ß-TCP group was greater than in the ß-TCP group (p < 0.05) and comparable to that in the autogenous bone group. We therefore concluded that collagen/ß-TCP is superior to ß-TCP alone in facilitating posterior spinal fusion. The addition of collagen to ß-TCP represents a simple strategy that couples the osteogenic effect, providing a promising alternative to autologous bone in the clinical treatment of spinal disorders.

Prognostic and clinicopathological significance of circulating tumor cells in osteosarcoma.

Osteosarcoma is the most common form of primary malignant bone tumor, with metastasis playing an essential role in determining a patient's prospects for survival. It is essential that new and better molecular targets that respond effectively to therapies and are predictive of the risk of tumor metastasis are identified. We have therefore undertaken the present prospective study to ascertain the clinical significance of circulating tumor cells (CTCs) in osteosarcoma patients. Peripheral blood was obtained from patients both pre- and post-surgery then processed using a CanPatrol™ system, an enrichment technique allowing isolation of CTCs by virtue of their size at baseline. Multiplex RNA in situ hybridization (RNA-ISH) was subsequently conducted to characterize the CTCs based on various molecular markers including MTA1, CD45, EpCAM, CK8, CK19, Vimentin and Twist. MTA1 expression was further validated by immunohistochemistry of the tumor tissue. Besides defining a diagnosis and prognosis for osteosarcoma patients, the correlation between CTC count and their molecular and clinicopathological characteristics was found to assist in the analysis of the response of patients to neoadjuvant chemotherapy. Our results revealed that the number of CTCs was significantly higher at baseline in metastatic patients than in those whose osteosarcomas were localized. The variation was attributed to the neoadjuvant chemotherapy treatment. A cut-off value of 7 CTCs/5 mL was found to effectively distinguish patients who had either a favorable or unfavorable prognosis. Notably, the ratio of mesenchymal CTCs at baseline was found to be higher in metastatic vs. localized osteosarcoma patients. In addition, the expression of MTA1 was higher in mesenchymal CTCs than the other CTC phenotypes. Furthermore, immunohistochemical analysis demonstrated a higher expression of MTA1 in tumor tissues from metastatic osteosarcoma patients. Taken together, our findings conclusively establish that the number and molecular phenotype of CTCs are predictive of tumor metastasis and the response of patients to neoadjuvant chemotherapy.