Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

新型冠状病毒肺炎中医诊疗方案用药规律数据挖掘＊

目的 基于中医传承辅助平台（V2.5），挖掘国家及省级卫生主管部门所公布的NCP中医诊疗方案的用药规律及新方挖掘。方法 收集国家及省级卫生主管部门公布的新型冠状病毒肺炎（Novel Coronavirus Pneumonia，NCP）中医诊疗方案，提取方案中四诊信息及处方用药信息，共收集到处方76首，录入中医传承辅助平台软件，建立数据库，采用软件集成的关联规则、复杂系统熵聚类核心组合分析及无监督的熵层次聚类新方分析等方法，分析NCP中医诊疗用药规律。结果 对入选的76首处方进行分析，得出本病治疗药物寒温并用，辛甘苦味为主，药物归经主要是肺、胃、脾经，常用药物有杏仁、甘草、生石膏、黄芩、麻黄、连翘、茯苓、苍术、大黄、法半夏等，并得到新处方7首。结论 NCP治疗以辛温解表、清热解毒、化湿健脾、清肺平喘为主。     

Quality of life in caregivers of a family member with serious mental illness: Evidence from China

Purpose

To evaluate the quality of life (QoL) and social support among family caregivers of a family member with a mental illness and to identify factors associated with the QoL.

部分调节性内斜视屈光状态与双眼单视功能的相关性研究

目的研究部分调节性内斜视患儿的屈光状态与双眼单视功能的相关性。 方法回顾性分析36例部分调节性内斜视患儿，对患儿裸眼视力、矫正视力、阿托品散瞳后的屈光度数、戴镜半年的远近残余斜视度及双眼单视功能等进行记录和统计学分析。左右眼等效球镜用配对秩和检验比较，右眼等效球镜与视力、斜视度和视功能的相关性采用Spearman分析。 结果36例部分调节性内斜视患儿年龄3~14岁，平均(79.39±31.21)个月，右眼等效球镜(+4.45±1.73)D，左眼等效球镜(+4.75±1.68)D；33 cm裸眼斜视度(+53.19±18.05)△，6 m裸眼斜视度(+47.50±19.00)△；33 cm残余斜视度(+30.36±12.03)△，6 m残余斜视度(+25.53±9.59)△。右眼等效球镜与同视机Ⅰ级、Ⅱ级和Ⅲ级视功能无相关性(r＝-0.012，-0.058，-0.016；P>0.05)。右眼等效球镜与33 cm裸眼斜视度呈正相关(r＝0.344，P<0.05)，与裸眼视力呈负相关(r＝-0.456，P<0.05)。33 cm裸眼斜视度与同视机Ⅰ级、Ⅱ级和Ⅲ级功能均呈负相关(r＝-0.378，-0.678，-0.482；P<0.05)，与Titmus立体图亦呈负相关(r＝-0.477，P<0.05)。6 m裸眼斜视度与同视机Ⅰ级、Ⅱ级和Ⅲ级功能均呈负相关(r＝-0.453，-0.610，-0.430；P<0.05)。33 cm残余斜视度与同视机Ⅱ和Ⅲ级功能均呈负相关(r＝-0.651，-0.600；P<0.05)，与Titmus立体图、立体动物和立体圆圈亦呈负相关(r＝-0.688，-0.625，-0.462；P<0.05)。6 m残余斜视度与同视机Ⅱ和Ⅲ级功能均呈负相关(r＝-0.587，-0.543；P<0.05)，与Titmus立体图、立体动物和立体圆圈亦呈负相关(r＝-0.644，-0.514，-0.492；P<0.05)。 结论部分调节性内斜视患儿的屈光状态与双眼单视功能不相关，与裸眼视力负相关。影响双眼单视功能的是残余斜视度。     

Frequency‐specific changes in the default mode network in patients with cingulate gyrus epilepsy

To identify abnormal functional connectivity of the default mode network in cingulate gyrus epilepsy, which may yield new information about the default mode network and suggest a new cingulate gyrus epilepsy biomarker. Fifteen patients with cingulate gyrus epilepsy (mean age = 21 years) and 15 healthy controls (mean age = 24 years) were studied in the resting state using magnetoencephalography. Twelve brain areas of interest in the default mode network were extracted and investigated with multifrequency signals that included alpha (α, 8–13 Hz), beta (β, 14–30 Hz), and gamma (γ, 31–80 Hz) band oscillations. Patients with cingulate gyrus epilepsy had significantly greater connectivity in all three frequency bands (α, β, γ). A frequency‐specific elevation of functional connectivity was found in patients compared to controls. The greater functional connectivity in the γ band was significantly more prominent than that of the α and β bands. Patients with cingulate gyrus epilepsy and controls differed significantly in functional connectivity between the left angular gyrus and left posterior cingulate cortex in the α, β, and γ bands. The results of the node degree analysis were similar to those of the functional connectivity analysis. Our findings reveal for the first time that brain activity in the γ band may play a key role in the default mode network in cingulate gyrus epilepsy. Altered functional connectivity of the left angular gyrus and left posterior cingulate cortex may be a new biomarker for cingulate gyrus epilepsy.     

Ethyl lactate as a potential green solvent to extract hydrophilic (polar) and lipophilic (non-polar) phytonutrients simultaneously from fruit and vegetable by-products

Phytonutrients extracted from natural resources are receiving much attention among researchers due to their highly antioxidative characteristics which prevent several degenerative diseases including cardiovascular diseases and cancers. These nutraceutical compounds can be used in food, pharmaceutical and cosmetic products as natural antioxidants, preservatives, colourants and functional foods. Huge volume of food wastes are generated from the processing industry and these low-value food residues are rich in various phytonutrients worth recovering. This approach of valorisation reduces the generation of food wastes and is cost-effective considering the cheap feedstock, reduced waste management expenses and high market value of extracted compounds. In light of the health and safety risks posed by commonly used organic extraction solvents derived from the petrochemical industry, there is a need to recover the phytonutrients using green, sustainable and efficient solvents that are safe for human consumption. This work discusses ethyl lactate as a safe, green, efficient and potentially cheap solvent to recover phytonutrients from fruit and vegetable by-products. Ethyl lactate is compared with other organic solvents commonly used from the aspects of safety, environmental impacts and efficiency. Current challenges when employing ethyl lactate are also discussed.     

Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Research question

Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone–oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone–oestradiol ratio?

A review of the safety and clinical utility of contrast echocardiography

There are limitations to the sensitivity and specificity of conventional two-dimensional echocardiograms in making an accurate diagnosis in certain patient populations. This led to the development of specific contrast-enhancing agents with the following characteristics: small enough to cross the pulmonary capillary bed, remain stable throughout the length of the procedure, do not dissolve in blood, and rapidly cleared from the body with low toxicity. Unfortunately, the use of contrast echocardiography has not taken off as expected. The low take-up rate among clinicians can largely be attributed to the black box warning by the United States Food and Drug Administration in 2007, after the coincidental occurrence of four patient deaths and about 190 severe cardiopulmonary reactions shortly after contrast agent administration. In this article, we address the clinical safety of contrast agents, share our institution’s experience in using it and elaborate on the clinical indications of contrast echocardiography.