A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

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。     

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

流动人口基层医疗卫生机构首诊现状及影响因素分析

目的:了解流动人口基层首诊现状及其影响因素,为推进流动人口分级诊疗提供实证参考依据。方法:基于2017年全国流动人口动态监测调查数据中82734名最近1次患病(负伤)流动人口数据,利用SPSS 25.0统计软件分析其基层首诊情况及影响因素。结果:82734名最近1次患病(负伤)流动人口中首选到基层医疗卫生机构就诊15936人,基层首诊率仅为19.3%;二分类logistic回归分析结果显示:年龄≥65岁、农业户口、流动时间0~5年、患慢性病、至少参加1项医疗保险,居住地到最近医疗服务机构所需时间≤15 min的流动人口患病后更愿意选择到基层首诊。学历大专及以上、家庭月均收入>10000元、市跨县、东北地区、不愿意落户、自评健康状况为不健康的流动人口患病后更不愿意选择到基层首诊。结论:流动人口患病(负伤)后选择到基层首诊率较低,年龄、受教育程度、户口类型、家庭月均总收入、流动时间、流动范围、流入地区域、落户意愿、自评健康状况、是否患慢性病、有无参加医疗保险、居住地到最近医疗服务机构所需时间是影响流动人口患病(负伤)后选择到基层首诊的主要因素。     

Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Effects of anteriorly-loaded treadmill walking on dynamic gait stability in young adults

BackgroundAnteriorly-loaded walking is common in many occupations and may increase fall risk. Dynamic gait stability, defined by the Feasible Stability Region (FSR) theory, quantifies the kinematic relationship between the body’s center of mass (COM) and base of support (BOS). FSR-based dynamic gait stability has been used to evaluate the fall risk.Research questionHow does front load carriage affect dynamic gait stability, step length, and trunk angle among young adults during treadmill walking?MethodsIn this between-subject design study, 30 healthy young adults were evenly randomized into three load groups (0%, 10%, or 20% of body weight). Participants carried their assigned load while walking on a treadmill at a speed of 1.2 m/s. Body kinematics were collected during treadmill walking. Dynamic gait stability (the primary variable) was calculated for two gait events: touchdown and liftoff. Step length and trunk angle were measured as secondary variables. One-way analysis of variance was conducted to detect any group-related differences for all variables. Post-hoc analysis with Bonferroni correction was performed when main group differences were found.ResultsNo significant differences but medium to large effect sizes were found between groups for dynamic gait stability at touchdown (p = 0.194, η² = 0.114) and liftoff (p = 0.122, η² = 0.139). Trunk angle significantly increased (indicating backward lean) with the front load at touchdown (p < 0.001, η² = 0.648) and liftoff (p < 0.001, η² = 0.543). No significant between-group difference was found related to the step length (p = 0.344, η² = 0.076).SignificanceCarrying a front load during walking significantly alters the trunk orientation and may change the COM-BOS kinematic relationship and, therefore, fall risk. The findings could inform the design of future studies focusing on the impact of anterior load carriage on fall risk during different locomotion.