Objective: To evaluate prospectively the diagnostic accuracy of the thyroid imaging reporting and data system (TI-RADS) and its interobserver agreement and to estimate the reduction of indications of fineneedle aspiration biopsies (FNABs). Design: A prospective comparative study was designed. Methods: In 2 years, 4550 nodules in 3543 patients were prospectively scored using a flowchart and a six-point scale and then submitted to US-FNAB. Results were read according to the Bethesda system. Histopathological results were available for 263 cases after surgery. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value, and accuracy were calculated for the gray-scale score, elastography, and a combination of both methods. Interobserver agreement was calculated using the kappa statistic. The reduction in the number of FNABs was estimated. Results: When compared with cytopathological results, sensitivity, specificity, NPV, and accuracy were 95.7, 61, 99.7, and 62% for the TI-RADS gray-scale score; 74.2, 91.1, 98, and 90% for elastography; and 98.5, 44.7, 99.8, and 48.3% for a combination of both methods respectively. When compared with histopathological results, the sensitivity of the gray-scale score, elastography, and a combination of both methods were 93.2, 41.9, and 96.7% respectively. Interobserver agreement for the six-point scale and the recommendation for biopsy were substantial (k valueZ0.72 and 0.76 respectively). The reduction in the number of FNABs was estimated to be 33.8%. Conclusion: The TI-RADS score has high sensitivity and NPV for the diagnosis of thyroid carcinoma. A hard nodule should always be considered as suspicious for malignancy but elastography cannot be used alone. Combination of elastography with gray-scale can be used to improve sensitivity or specificity. Interobserver agreement and decrease in unnecessary biopsies are significant.

Different macrophage depletion strategies have demonstrated a vital role of macrophages in bone healing, but the underlying molecular mechanisms are poorly understood. Here, with the use of a mouse model of tibia injury, we found that the cytokine oncostatin M [OSM or murine (m)OSM] was overexpressed during the initial inflammatory phase and that depletion of macrophages repressed mOSM expression. In Osm(-/-) mice, by micro-computed tomography and histology we observed a significant reduction in the amount of new intramedullar woven bone formed at the injured site, reduced number of Osterix(+) osteoblastic cells, and reduced expression of the osteoblast markers runt-related transcription factor 2 and alkaline phosphatase. In contrast, osteoclasts were normal throughout the healing period. One day after bone injury, Stat3, the main transcription factor activated by mOSM, was found phosphorylated/activated in endosteal osteoblastic cells located at the hedge of the hematoma. Interestingly, we observed reduced activation of Stat3 in Osm(-/-) mice. In addition, mice deficient in the mOSM receptor (Osmr(-/-)) also had reduced bone formation and osteoblast number within the injury site. These results suggest that mOSM, a product of macrophages, sustains intramembranous bone formation by signaling through Osmr and Stat3, acting on the recruitment, proliferation, and/or osteoblast differentiation of endosteal mesenchymal progenitor cells. Because bone resorption is largely unaltered, OSM could represent a new anabolic treatment for unconsolidated bone fractures.

Osteosarcomas are the most prevalent malignant primary bone tumors in children. Despite intensive efforts to improve both chemotherapeutics and surgical management, 40% of all osteosarcoma patients succumb to the disease. Specifically, the clinical outcome for metastatic osteosarcoma remains poor; less than 30% of patients who present metastases will survive five years after initial diagnosis. Treating metastatic osteosarcoma thus remains a challenge. One of the main characteristics of osteosarcomas is their ability to deregulate bone remodelling. The invasion of bone tissue by tumor cells indeed affects the balance between bone resorption and bone formation. This deregulation induces the release of cytokines or growth factors initially trapped in the bone matrix, such as transforming growth factor-β (TGF-β), which in turn promote tumor progression. Over the past years, there has been considerable interest in the TGF-β pathway within the cancer research community. This review discusses the involvement of the TGF-β signalling pathway in osteosarcoma development and in their metastatic progression.