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OBJECTIVE: The effectiveness of starting systemic therapies after surgery for spinal metastases from renal cell carcinoma (RCC) has not been evaluated in randomized controlled trials. Agents that target tyrosine kinases, mammalian target of rapamycin signaling, and immune checkpoints are now commonly used. Variables like sarcopenia, nutritional status, and frailty may impact recovery from spine surgery and are considered when evaluating a patient's candidacy for such treatments. A better understanding of the significance of these variables may help improve patient selection for available treatment options after surgery. The authors used comparative effectiveness methods to study the treatment effect of postoperative systemic therapies (PSTs) on survival. METHODS: Univariable and multivariable Cox regression analyses were performed to determine factors associated with overall survival (OS) in a retrospective cohort of adult patients who underwent spine surgery for metastatic RCC between 2010 and 2019. Propensity score-matched (PSM) analysis and inverse probability weighting (IPW) were performed to determine the treatment effect of PST on OS. To address confounding and minimize bias in estimations, PSM and IPW were adjusted for covariates, including age, sex, frailty, sarcopenia, nutrition, visceral metastases, International Metastatic RCC Database Consortium (IMDC) risk score, and performance status. RESULTS: In total, 88 patients (73.9% male; median age 62 years, range 29-84 years) were identified; 49 patients (55.7%) had an intermediate IMDC risk, and 29 (33.0%) had a poor IMDC risk. The median follow-up was 17 months (range 1-104 months) during which 57 patients (64.7%) died. Poor IMDC risk (HR 3.2 [95% CI 1.08-9.3]), baseline performance status (Eastern Cooperative Oncology Group score 3 or 4; HR 2.7 [95% CI 1.5-4.7]), and nutrition (prognostic nutritional index [PNI] first tertile, PNI < 40.74; HR 2.69 [95% CI 1.42-5.1]) were associated with worse OS. Sarcopenia and frailty were not significantly associated with poor survival. PST was associated with prolonged OS, demonstrated by similar effects from multivariable Cox analysis (HR 0.55 [95% CI 0.30-1.00]), PSM (HR 0.53 [95% CI 0.29-0.93]), IPW (HR 0.47 [95% CI 0.24-0.94]), and comparable confidence intervals. The median survival for those receiving PST was 28 (95% CI 19-43) months versus 12 (95% CI 4-37) months for those who only had surgery (log-rank p = 0.027). CONCLUSIONS: This comparative analysis demonstrated that PST is associated with improved survival in specific cohorts with metastatic spinal RCC after adjusting for frailty, sarcopenia, and malnutrition. The marked differences in survival should be taken into consideration when planning for surgery.
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During the last 2 decades, evidence has accumulated that a high cholesterol level may increase the risk of developing Alzheimer disease (AD). With the global use of statins to treat hypercholesterolemia, this finding has led to the anticipation that statins could prove useful in treating or preventing AD. However, the results of work on this topic are inconsistent: some studies find beneficial effects, but other studies do not. In this first segment of a 2-part review, we examine the complex preclinical and clinical literature on cholesterol level and AD. First, we review epidemiological research on cholesterol level and the risk of AD and discuss the relevance of discrepancies among studies with regard to participants' age and clinical status. Second, we assess studies correlating cholesterol level with neuropathological AD type. The potential molecular mechanisms for the apparent adverse effects of cholesterol on the development of AD are then discussed. Third, we review preclinical studies of statin use and AD. Therefore, this first part of our review provides the background and rationale for investigating statins as potential therapeutic agents in patients with AD, the subject of the second part.