BACKGROUND & AIMS: :Anthracyclines are anti-neoplastic drugs presenting cardiotoxicity as a side effect. Cardiac troponins (cTn) and echocardiography are currently used to assess cardiac damage and dysfunction, but early biomarkers identifying patients in need of preventive treatments remain a partially met need. Circulating microRNAs (miRNAs) represent good candidates, so we investigated their possible roles as predictors of troponin elevation upon anthracycline treatment. Eighty-eight female breast cancer patients administered with doxorubicin (DOX) or epirubicin (EPI) were divided into four groups basing on drug type and cTn positive (cTn+) or negative (cTn-) levels: DOX cTn-, DOX cTn+, EPI cTn- and EPI cTn+. Blood was collected at baseline, during treatment, and at follow-up. We identified plasma miRNAs of interest by OpenArray screening and single assay validation. Our results showed miR-122-5p, miR-499a-5p and miR-885-5p dysregulation in DOX patients at T0, identifying a signature separating, with good accuracy, DOX cTn- from DOX cTn+. No miRNAs showed differential expression in EPI subjects. Conversely, an anthracycline-mediated modulation (regardless of cTn) was observed for miR-34a-5p, -122-5p and -885-5p. Our study indicates specific circulating miRNAs as possible prediction markers for cardiac troponin perturbation upon anthracycline treatment. Indeed, our findings hint at the possible future use of plasma miRNAs to predict the cardiac responsiveness of patients to different anticancer agents.

背景与目标： : 蒽环类药物是抗肿瘤药物，具有心脏毒性作为副作用。心肌肌钙蛋白 (cTn) 和超声心动图目前用于评估心脏损伤和功能障碍，但早期识别需要预防性治疗的患者的生物标志物仍然是部分满足的需求。循环microrna (mirna) 代表了良好的候选者，因此我们研究了它们作为蒽环类药物治疗后肌钙蛋白升高的预测因子的可能作用。根据药物类型和cTn阳性 (cTn) 或阴性 (cTn-) 水平将88例接受阿霉素 (DOX) 或表柔比星 (EPI) 的女性乳腺癌患者分为四组: DOX cTn-，DOX cTn，EPI cTn-和EPI cTn。在基线，治疗期间和随访时收集血液。我们通过开放阵列筛选和单分析验证鉴定了目标血浆miRNAs。我们的结果显示，在T0时，DOX患者的miR-122-5p，miR-499a-5p和miR-885-5p失调，从而确定了将DOX cTn-与DOX cTn分离的准确性良好的特征。在EPI受试者中没有mirna显示差异表达。相反，对于miR-34a-5p，-122-5p和-885-5p观察到蒽环类药物介导的调节 (与cTn无关)。我们的研究表明，特定的循环mirna可能是蒽环类药物治疗后心肌肌钙蛋白扰动的预测标志物。实际上，我们的发现暗示了将来可能使用血浆mirna来预测患者对不同抗癌药物的心脏反应性。

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BACKGROUND & AIMS: :The original version of this article unfortunately contained a mistake. The given names and family names of all authors were interchanged.

背景与目标： : 这篇文章的原始版本不幸地包含了一个错误。所有作者的给定姓名和姓氏均已互换。

BACKGROUND & AIMS: INTRODUCTION:Post-operative cognitive dysfunction (POCD) is frequent in patients older than 60 years undergoing major non-cardiac surgery, and increases both morbidity and mortality. Anesthetic drugs may exert neurotoxic effects and contribute to the genesis of POCD. The hypothesis of the POCD-ELA trial was that closed-loop target-controlled infusion of propofol and remifentanil could reduce the occurrence of POCD by decreasing the risk of excessive depth of anesthesia and the dose of anesthetic drugs. METHODS AND ANALYSIS:We designed a single-center, single-blind, randomized, controlled, parallel trial and aim to include 204 patients aged >60 years undergoing elective major non-cardiac surgery. Patients will be randomized to receive closed-loop versus manual target-controlled infusion of propofol and remifentanil guided by bispectral index monitoring. Cognitive assessment will be performed the day before surgery (baseline) and within 72 hours after surgery, using a battery of validated neuropsychological tests. The primary outcome is the incidence of POCD within 72 hours after surgery. POCD is defined as a Z-score value > 1.96 for at least 2 different tests or a Z-score composite value >1.96. The calculation of the Z-score is based on data from an age-matched control population who did not undergo surgery or general anesthesia. ETHICS AND DISSEMINATION:This study was approved by the Ethics Committee (Comité de Protection des Personnes Est-II) and authorized by the French Health Products Agency (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. REGISTRATION:The trial is registered with ClinicalTrials.gov (Identifier: NCT02841423, principal investigator: Prof Emmanuel Samain, date of registration: July 22, 2016). Last amendment of protocol: version 8.0 April 2018.

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BACKGROUND & AIMS: BACKGROUND:There are a variety of techniques to handle missing data, such as removing observations with missing data from the analyses or estimating the missing values using various imputation algorithms. Dropping subjects from standard regression models and analyzing only completers, however, may bias results from the true value of reality. Likewise, 'last-observation-carried-forward' may not be an appropriate technique for studies measuring a particular variable over time. METHODS:This dataset was part of a larger prospective cohort study that examined postoperative cognitive decline (POCD) after surgery in older adults. Data collectors had provided the reasons for data being missing using adjectives including 'confused', 'incapable', 'stuporous', 'comatose', and 'intubated'. Data having these qualitative notations were re-coded as 'incapable' and trial scores of zero were recorded. This value of '0' indicated that the patient was cognitively incapable of performing the neuropsychological test. RESULTS:Missing data varied by cognitive test and postoperative day. Re-coding word list scores from missing to zero when a patient was too cognitively impaired to complete the tests improved sample size by 13.5% of postoperative day (POD) 1 and 12.8% on POD 2. Recoding missing data to zero for the digit symbol test resulted in 29.3% larger sample size on POD 1 and 22.7% on POD 2. Verbal fluency gained 15.7% sample size with re-coding for POD 1 and 13.7% for POD 2. Re-coding of each cognitive test reduced missing data sample size to 20-32% in all cognitive tests for each day. DISCUSSION:Our data suggest that using a scoring system that enters a value of '0' when patients are unable to perform cognitive testing did significantly increase the number of patients that met the diagnosis of postoperative cognitive decline using the criteria that were determined a priori and may lessen chances of type II error (failure to detect a difference).

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BACKGROUND & AIMS: Objectives:Clinical observation, as well as randomized controlled trials, indicated an increasing rate of postoperative cognitive dysfunction (POCD) with increasing depth of general anesthesia. However, the findings are subject to bias due to varying degree of analgesia. In this trial, we compared the rate of POCD between patients receiving light versus high anesthesia while holding analgesia comparable using nerve block. Methods:Elderly patients (≧60 years) receiving elective total knee replacement were randomized to receive the surgery under general anesthesia at BIS 40-50 (LOBIS group) or BIS 55-65 (HIBIS group). The femoral nerve and the sciatic nerve were blocked under ultrasonic guidance in all patients before induction. Cognitive performance was assessed with Montreal cognitive assessment (MoCA) at the baseline and 1d, 3d, and 7d after the surgery. POCD was defined by Z score of >1.96 using cross-reference. The extubation time and recovery time were also compared. Results:A total of 66 patients were randomized; 60 (n = 30 per group) completed trial as the protocol specified. POCD occurred in six patients (20%) in the LOBIS group vs. in one patient (3.3%) in the HIBIS group (Figure 3, p = .04). In all seven cases, the diagnosis of POCD was based on MoCA assessment on 1d after the surgery. Assessment in 3d and 7d after surgery did not reveal POCD in any case. Extubation time was longer in the LOBIS group (12.16 ± 2.58 vs. 5.77 ± 3.01 min in the HIBIS group (p < .001)). The time of comeback of directional ability was 13.47 ± 3.14 and 6.17 ± 3.23 min in the LOBIS and HIBIS groups, respectively (p < .001). Conclusions:In elderly patients receiving a total knee replacement, lighter anesthesia could reduce the rate of POCD with complete analgesia during surgery.

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BACKGROUND & AIMS: :POCD describes a decline in cognitive function after surgery with a predominance in the elderly patient. Although there is general agreement that POCD is likely to be multifactorial, whether its occurrence is a result of the effects of surgery or general anesthesia remains unclear. This review provides a synopsis of the available clinical and preclinical data and summarizes recent research relevant to the occurrence of POCD and possible pharmacologic algorithms for its prevention and treatment.

背景与目标： : POCD描述了老年患者手术后认知功能下降的趋势。尽管人们普遍认为POCD可能是多因素的，但尚不清楚POCD的发生是手术还是全身麻醉的结果。本文概述了现有的临床和临床前数据，并总结了与POCD发生有关的最新研究以及预防和治疗POCD的可能药理算法。

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BACKGROUND & AIMS: :We assessed the relationship between red blodd cell distribution width (RDW) and postoperative cognitive dysfunction (POCD) after coronary artery bypass grafting (CABG) in patients who usually had obvious hemodynamic changes. We enrolled 362 coronary heart disease patients who received CABG. POCD was assessed through neuropsychological examination at 21 days after operation. Demographics, history of diseases, blood biochemical parameters and perioperative data were collected. The receiver operating characteristic (ROC) curve was used to find the best cut-off value of RDW for diagnosis of POCD. Logistic regression was used to explore the relationship between RDW and POCD. The 21-day incidence of POCD in patients receiving CABG was 27.1% (98/362). The RDW of POCD patients was significantly higher than in the non-POCD patients (17.4 vs. 13.2). The sensitivity and specificity of RDW for predicting POCD were 82.7 and 64.8%, respectively. The POCD patients also tended to be older and had higher fasting plasma glucose, hypersensitive c-reactive protein, tumor necrosis factor-α, white blood cell levels and longer surgery time. No significant differences were found in other parameters. The 21-day neuropsychological test results were better in the POCD patients than the non-POCD patients. After adjustment of potential factors, the preoperative high RDW was still associated with an increased risk of POCD (odds ratio (OR) = 2.52, 95% confidence interval (CI): 1.28-4.31). Our study indicates that preoperative RDW is significantly elevated in POCD patients receiving CABG. The elevated preoperative RDW is associated with an increased risk of POCD and preoperative RDW can be an independent predictor of POCD.

背景与目标： : 我们评估了通常有明显血流动力学变化的患者在冠状动脉旁路移植术 (CABG) 后红色blodd细胞分布宽度 (RDW) 与术后认知功能障碍 (POCD) 之间的关系。我们招募了362例接受CABG的冠心病患者。术后21天通过神经心理学检查评估POCD。收集人口统计学、病史、血液生化指标和围手术期资料。使用接收器工作特性 (ROC) 曲线来找到RDW诊断POCD的最佳临界值。采用Logistic回归分析方法探讨RDW与POCD的关系。在接受CABG的患者中，POCD的21天发生率为27.1% (98/362)。POCD患者的RDW显著高于非POCD患者 (17.4对13.2)。RDW预测POCD的敏感性和特异性分别为82.7和64.8%。POCD患者的年龄也较大，空腹血糖，超敏c反应蛋白，肿瘤坏死因子-α，白细胞水平较高，手术时间较长。在其他参数中没有发现显着差异。POCD患者的21天神经心理测试结果优于非POCD患者。调整潜在因素后，术前高RDW仍与POCD风险增加相关 (比值比 (OR) = 2.52，95% 置信区间 (CI): 1.28-4.31)。我们的研究表明，接受CABG的POCD患者术前RDW显着升高。术前RDW升高与POCD风险增加相关，术前RDW可能是POCD的独立预测因子。

BACKGROUND & AIMS: INTRODUCTION:Postoperative cognitive dysfunction (POCD) and postoperative delirium (POD) are common postoperative complications in elderly patients. The effect of anesthesia depth on cognitive function remains unknown. We aimed to assess the correlations between anesthesia depth, cognitive function, and inflammation. EVIDENCE ACQUISITION:Literature searches were conducted on Web of Science, PubMed, EMBASE, and Cochrane libraries until August 2019. All studies were randomized controlled trials (RCTs). The STATA 15.0 and trial sequential analysis (TSA) version 0.9.5.10 beta software were used for data analysis. POD and POCD were calculated using a random-effects model. The combined effect estimates are expressed as risk ratios (RR) with 95% confidence intervals (CI). EVIDENCE SYNTHESIS:Ten RCTs involving 3142 patients met inclusion criteria. The meta-analysis indicated that the incidence of POCD in the light anesthesia group was significantly lower than the deep anesthesia group on days 1 (RR=0.14, 95% CI: 0.04 to 0.45; I²=0.00, P>0.10), and 90 (RR=0.72, 95% CI: 0.54 to 0.96; I²=0.00,P>0.10). Light anesthesia significantly reduced the risk of POD (RR=0.69, 95% CI: 0.58 to 0.82; I²=0.00, P>0.10). There was no statistical difference in the Mini-Mental State Examination score between the groups on postoperative day 1 (standardized mean difference (SMD)= 0.04, 95% CI: -0.25 to 0.33; I²=0.00, P>0.10).The TSA found that there was insufficient evidence on the effect of anesthesia depth on POCD, but that the conclusions on POD were reliable. CONCLUSIONS:Light anesthesia was associated with a decrease in POD and may promote better neurocognitive function postoperatively in comparison with deep anesthesia.

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