Effect of gender on the reliability of COVID-19 rapid antigen test among elderly

Defining con-founders that affect the reliability of diagnostic tests for coronavirus disease 2019 is vital to breaking the chain of infection. The elderly population is a higher risk group for the emerging virus. However, gender seems to exert a critical role in modifying the infection risk among women owing to hormonal changes. The menopause transition is an exceptional period for older women where the protective and immunomodulatory effects of the estrogen hormone are lost. Accordingly, attention should be given to postmenopausal women since they will have an increased risk compared to their pre-menopausal peers.     

伏立康唑一级预防急性白血病患者化疗期间并发真菌感染的临床疗效北大核心

目的:探讨初诊急性白血病患者化疗期间应用伏立康唑进行预防侵袭性真菌病(IFD)的临床疗效及安全性。方法:回顾性分析2016年02月至2018年03月期间我院血液科收治的初诊急性白血病行化疗的患者166例,按照是否使用抗真菌药进行预防性治疗分为观察组(应用伏立康唑进行预防治疗,n=103)和对照组(未应用抗真菌药物,n=63),比较两组患者IFD发生率差异,并分析抗真菌药物应用的不良反应。结果:观察组IFD发生率为10.7%,对照组为33.3%,两组患者的IFD发生率有明显差异(P<0.05);所有应用伏立康唑进行预防治疗的患者均未出现严重的不良反应。结论:伏立康唑可以有效减低急性白血病患者化疗期间IFD发生率,并且有着较好的安全性,值得在临床推广应用。     

Evaluation of unsupervised 30-second chair stand test performance assessed by wearable sensors to predict fall status in multiple sclerosis

BackgroundOne in two people with multiple sclerosis (PwMS) will fall in a three-month period. Predicting which patients will fall remains a challenge for clinicians. Standardized functional assessments provide insight into balance deficits and fall risk but their use has been limited to supervised visits.Research questionThe study aim was to characterize unsupervised 30-second chair stand test (30CST) performance using accelerometer-derived metrics and assess its ability to classify fall status in PwMS compared to supervised 30CST.MethodsThirty-seven PwMS (21 fallers) performed instrumented supervised and unsupervised 30CSTs with a single wearable sensor on the thigh. In unsupervised conditions, participants performed bi-hourly 30CSTs and rated their balance confidence and fatigue over 48-hours. ROC analysis was used to classify fall status for 30CST performance.ResultsNon-fallers (p = 0.02) but not fallers (p = 0.23) differed in their average unsupervised 30CST performance (repetitions) compared to their supervised performance. The unsupervised maximum number of 30CST repetitions performed optimized ROC classification AUC (0.79), accuracy (78.4%) and specificity (90.0%) for fall status with an optimal cutoff of 17 repetitions.SignificanceBrief durations of instrumented unsupervised monitoring as an adjunct to routine clinical assessments could improve the ability for predicting fall risk and fluctuations in functional mobility in PwMS.     

基于网络药理学和分子对接技术研究黄芪-赤芍治疗COPD的作用机制＊

目的 基于网络药理学和分子对接技术探究黄芪-赤芍配伍对治疗慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）的作用机制。方法 利用TCMSP，Pharmmaper数据库，筛选黄芪-赤芍治疗COPD的活性成分和潜在靶点；结合Genecards数据库挖掘的COPD相关靶点，对黄芪-赤芍药对与COPD靶点进行PPI网络构建，交互处理得到黄芪-赤芍药对治疗COPD的关键靶点，并进行GO分析和KEGG通路富集分析；并采用分子对接技术将主要活性成分与TNF-α（肿瘤坏死因子），IL-6（白细胞介素6）等进行分子对接；最后利用A549炎症细胞与人脐静脉内皮细胞缺氧损伤模型进行体外细胞实验对结果加以验证。结果 黄芪-赤芍药对中44个有效成分作用于COPD，核心成分为：槲皮素、山奈酚、丁子香萜、芍药苷、（2R，3R）-4-methoxyl-distylin、二氢异黄酮；黄芪-赤芍药对通过IL6、PTGS2、TNF等113个靶蛋白，调控Ras、PI3KAkt、IL-17等多条信号通路治疗COPD，且分子对接结果显示槲皮素、山奈酚、丁子香萜、芍药苷与IL-6、PTGS2、TNF大分子蛋白有良好的结合性，体外细胞试验证实，槲皮素与山奈酚均能减少IL-8，MMP-9炎症因子的分泌，具有不同程度的抗炎效果；芍药苷有明显的扩血管、抗血栓之效。结论 黄芪-赤芍药对治疗COPD具有多成分、多靶点、多通路、整体调节的作用特点。初步揭示了黄芪-赤芍药对通过抑制炎症反应、调节上皮细胞生长增强保护屏障等预测出黄芪-赤芍药对治疗COPD的潜在作用机制，以期为其活性成分的药效物质基础提供理论研究和思路。     

Living with the financial consequences of cancer: A life course perspective

Abstract

Purpose

Financial hardship can be a major cause of distress among persons with cancer, resulting in chronic stress and impacting physical and emotional health. This paper provides an analysis of the lived experience of cancer patients’ financial hardship from diagnosis to post-treatment.     

Inhibition of autophagy enhances apoptosis induced by bortezomib in AML cells

Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL.     

Differential Diagnosis of Acute Diarrhea

Acute diarrhea is a condition of increased water stool content, stool volume, and number of bowel movements that lasts less than 14 days. Mild diarrhea is usually self-limiting; however, undertreated moderate to severe diarrhea may cause severe dehydration and lead to hypovolemic shock. In order to prevent severe dehydration and treat patients appropriately, it is crucial for health care providers to determine the right diagnosis of patients with acute diarrhea. This article focuses on pathophysiology, general patient presentation, diagnostic tests and differential diagnosis lists of acute diarrhea to discuss which diagnosis should be made based on patient presentation and objective data.     

RESIRT: A Phase 1 Study of Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres in Patients With Primary Renal Cell Carcinoma

IntroductionSelective internal radiation therapy (SIRT) is a potential treatment of primary renal cell carcinoma (RCC) deemed unsuitable for conventional therapy. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.Patients and MethodsPatients with RCC, unsuitable for, or who declined conventional therapy, were eligible. A single transfemoral micro-catheter administration of yttrium-90 (Y-90) resin microspheres (SIR-Spheres) was delivered super selectively via the renal artery to the tumour at intended radiation doses of 75, 100, 150, 200, 300 Gy and a final cohort with a procedural endpoint of “imminent stasis,” in a dose-escalation design. Post-SIRT follow-up was 12 months. Study endpoints included safety and toxicity 30-days and 12-months post-SIRT and tumour response (RECIST v1.1).ResultsIn total, 21 patients were enrolled, mean (SD) age was 75 (9.3) years, WHO performance status was 0 in 81%, 12 (57%) had stage 3 chronic kidney disease, and 7 (33%) had prior contralateral nephrectomy. Overall, 71% of patients completed 12 months of follow-up. Intended doses were delivered without any dose-limiting toxicity. Seventeen out of 21 (81%) patients experienced an adverse event (AE) from any cause within 30 days post-SIRT; all SIRT-related AEs were grade 1 to 2. Best overall tumour responses were partial response 1/21 (4.8%), stable disease 19/21 (90.5%) and progressive disease 1/21 (4.8%).ConclusionThis study demonstrated good tolerability of SIRT at all dose levels including “imminent stasis” in treating primary tumours in RCC patients otherwise unsuitable for conventional therapy. SIRT with Y-90 resin microspheres may be a feasible treatment option for RCC.     

Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review

Background

Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury.

Methods

We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/ , http://www.clinicaltrials.gov/ , www.eudraCT.com , http://centerwatch.com/ , The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion

The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.