This article summarizes recent evidence on the cortical bone trajectory (CBT) obtained from published anatomical, biomechanical, and clinical studies. CBT was proposed by Santoni in 2009 as a new trajectory that can improve the fixation of pedicle screws in response to screw loosening in osteoporotic patients. Recently, research interest has been growing with increasing numbers of published series and frequent reports of new applications. We performed an online database search using the terms “cortical bone trajectory,” “pedicle screw,” “CBT spine,” “CBT fixation,” “MISS CBT,” and “traditional trajectory.” The search included the PubMed, Ovid MEDLINE, Cochrane, and Google Scholar databases, resulting in an analysis of 42 articles in total. These covered three aspects of CBT research: anatomical studies, biomechanical parameters, and clinical cases or series. Compared to the traditional trajectory, CBT improves pullout strength, provides greater stiffness in cephalocaudal and mediolateral loading, and shows superior resistance to flexion/extension; however, it is inferior in lateral bending and axial rotation. CBT seems to provide better immediate implant stability. In clinical studies, CBT has shown better perioperative results for blood loss, length of stay in hospital, and surgery time; similar or better clinical postoperative scores; and similar comorbidity, without any major fixation system complications due to instrumentation failure or screw misplacement. In addition, advantages such as less lateral exposure allow it to be used as a minimally invasive technique. However, most of the clinical studies were retrospective case series or case-control studies; prospective evidence on this technique is scarce, making a definitive comparison with the traditional trajectory difficult. Nevertheless, we can conclude that CBT is a safe technique that offers good clinical results with similar biomechanical and perioperative parameters to those of the traditional trajectory. In addition, new applications can improve its results and make it useful for additional pathologies.
Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9–RAGE–NF-κB–JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.
BACKGROUND AND IMPORTANCE Deep brain stimulation of the posteromedial hypothalamus (PMH DBS) appears to be an effective treatment for drug-resistant aggressiveness. Weaver syndrome (WS) is a rare genetic disorder in which patients develop some degree of intellectual disability and rarely severe behavioral alterations that may benefit from this procedure. CLINICAL PRESENTATION We present the case of a 26-yr-old man diagnosed with WS presenting with uncontrollable self and heteroaggressiveness and disruptive behavior refractory to pharmacological treatment and under severe physical and mechanical restraining measures. The patient was successfully treated with bilateral PMH DBS resulting in affective improvement, greater tolerance for signs of affection, regularization in his sleep pattern and appetite disturbances at 12-mo follow-up. A detailed description and video of the procedure are presented, and a review of the clinical characteristics of WS and the utility and benefits of PMH DBS for refractory aggressiveness are reviewed. CONCLUSION To our knowledge, this is the first case of refractory aggressiveness described in WS as well as the first patient with WS successfully treated with PMH DBS.
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