The Prediction of Survival after Surgical Management of Bone Metastases of the Extremities-A Comparison of Prognostic Models.

Individualized survival prognostic models for symptomatic patients with appendicular metastatic bone disease are key to guiding clinical decision-making for the orthopedic surgeon. Several prognostic models have been developed in recent years; however, most orthopedic surgeons have not incorporated these models into routine practice. This is possibly due to uncertainty concerning their accuracy and the lack of comparison publications and recommendations. Our aim was to conduct a review and quality assessment of these models. A computerized literature search in MEDLINE, EMBASE and PubMed up to February 2022 was done, using keywords: "Bone metastasis", "survival", "extremity" and "prognosis". We evaluated each model's performance, assessing the estimated discriminative power and calibration accuracy for the analyzed patients. We included 11 studies out of the 1779 citations initially retrieved. The 11 studies included seven different models for estimating survival. Among externally validated survival prediction scores, PATHFx 3.0, 2013-SPRING and potentially Optimodel were found to be the best models in terms of performance. Currently, it is still a challenge to recommend any of the models as the standard for predicting survival for these patients. However, some models show better performance status and other quality characteristics. We recommend future, large, multicenter, prospective studies to compare between PATHfx 3.0, SPRING 2013 and OptiModel using the same external validation dataset.

Potential neurotoxicity of titanium implants: Prospective, in-vivo and in-vitro study.

Titanium dioxide (TiO2) is a frequently used biomaterial, particularly in orthopedic and dental implants, and it is considered an inert and benign compound. This has resulted in toxicological scrutiny for TiO2 in the past decade, with numerus studies showing potential pathologic downstream effects. Herein we describe case report of a 77-year-old male with subacute CNS dysfunction, secondary to breakdown of a titanium-based carotid stent and leading to blood levels 1000 times higher (3 ppm) than the reported normal. We prospectively collected tissues adjacent to orthopedic implants and found a positive correlation between titanium concentration and time of implant in the body (r = 0.67, p < 0.02). Rats bearing titanium implants or intravascularly treated with TiO2 nanoparticles (TiNP) exhibited memory impairments. A human blood-brain barrier (BBB) in-vitro model exposed to TiNP showed paracellular leakiness, which was corroborated in-vivo with the decrease of key BBB transcripts in isolated blood vessels from hippocampi harvested from TiNP-treated mice. Titanium particles rapidly internalized into brain-like endothelial cells via caveolae-mediated endocytosis and macropinocytosis and induced pro-inflammatory reaction with increased expression of pro-inflammatory genes and proteins. Immune reaction was mediated partially by IL-1R and IL-6. In summary, we show that high levels of titanium accumulate in humans adjacent to orthopedic implants, and our in-vivo and in-vitro studies suggest it may be neurotoxic.