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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.
We eagerly await the results of randomised controlled trials. Firm clinical outcome data are expected to emerge in the near future, though data on cost and radiation exposure will be needed before definitive conclusions can be made.
Background Escalating demand for specialist health care puts considerable demand on hospital services. Technology offers a means by which health care providers may increase the efficiency of health care delivery. Objective The aim of this study was to conduct a pilot study of the feasibility, benefits, and drawbacks of a virtual clinic (VC) in the general surgical service of a busy tertiary center. Methods Patient satisfaction with current care and attitudes to VC were surveyed prospectively in the general surgical outpatient department (OPD; n=223). A subset of patients who had undergone endoscopy and day surgery were recruited to follow-up in a VC and subsequently surveyed with regard to their satisfaction (20/243). Other outcomes measured included a comparison of consultation times in traditional and virtual outpatient settings and financial cost to both patients and the institution. Results Almost half of the patients reported barriers to prospective use of VCs. However, within the cohort who had been followed-up in the VC, satisfaction was higher than the traditional OPD (100% as compared with 187/223, 83.9%). Significant savings in both time (P=.003) and financial costs to patients and the institution were found. Conclusions For an appropriately selected group of patients, VCs offer a viable alternative to traditional OPD. This alternative can improve both patient satisfaction and efficiency of patient care.
Background and Purpose: Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window. Methods: Analyses were based on the SOLSTICE Consortium (Selection of Late-Window Stroke for Thrombectomy by Imaging Collateral Extent), which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, 90-day functional independence (modified Rankin Scale score ≤2), mortality, and symptomatic intracranial hemorrhage were compared between women and men. Effect of sex on the association of age and successful reperfusion (final Thrombolysis in Cerebral Infarction 2b–3) with outcomes was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, time from onset to puncture, occlusion location, intravenous thrombolysis, and successful reperfusion, with interaction terms. Results: Among 608 patients treated with endovascular treatment, 50.5% were women. Women were older than men (median age of 72 versus 68 years, P =0.02) and had a lower prevalence of tandem occlusions (14.0% versus 22.9%, P =0.005). Workflow times were similar between sexes. Adjusted outcomes did not differ between women and men. Functional independence at 90 days was achieved by 127 out of 292 women (43.5%) and 135 out of 291 men (46.4%). Mortality at 90 days (54 [18.5%] versus 48 [16.5%]) and symptomatic intracranial hemorrhage (37 [13.3%] versus 33 [11.6%]) were similar between women and men. There was no sex-by-age interaction on functional outcomes. However, men had higher likelihood of mortality ( P interaction =0.003) and symptomatic intracranial hemorrhage ( P interaction =0.017) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. Conclusions: In this multicenter analysis of late patients treated with endovascular treatment, sex was not associated with functional outcome. However, sex influenced the association between age and safety outcomes, with men experiencing worse outcomes with advancing age.
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