Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC

Background:

We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis.

Methods:

We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers.

Results:

Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45–0.65) and MST 6.3 (95% CI 4.2–8.3) years. The overall overdiagnosis was 42% (95% CI 37–52) of the screen-detected cancers, with 58% (95% CI 54–65) in men with the lower and 37% (95% CI 31–47) in those with higher polygenic risk.

Conclusion:

Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.     

Arterial remodelling in Fabry disease

Aim : The enzymatic defect in Fabry disease results in the slow systemic deposition of uncleaved glycosphingolipids in the lysosomes of vascular endothelium and smooth muscle cells, leading to ischaemic strokes, cardiomyopathy and renal failure. Whereas it is known that Fabry disease affects small blood vessels, little is known about its effects on peripheral large arteries. We therefore set out to compare parameters of arterial wall structure and function in a cohort of patients with Fabry disease and an age-matched control group. Methods : Large artery phenotype was non-invasively investigated in 21 hemizygous patients with Fabry disease and 24 age-matched male controls. Common carotid and radial artery diameter, intima-media thickness (IMT) and distensibility were determined with high-definition echotracking systems and aplanation tonometry. Results : Patients with Fabry disease had a significant twofold increase in radial artery IMT and distensibility, independent of body surface area, age and mean blood pressure. In both groups, older age at the time of examination was significantly associated with larger radial artery IMT. The relationship between age and radial IMT was 2.3-fold higher in patients with Fabry disease than in controls ( p > 0.01). Carotid IMT was mildly but significantly increased in patients with Fabry disease (+18%), whereas distensibility was unchanged.
Conclusion : This study presents evidence of a major increase in arterial wall thickness and distensibility, measurable at the site of a medium-sized artery, in a cohort of patients with classic Fabry disease.     

Adhesion of Pseudomonas aeruginosa ocular isolates to mucin

The purpose of this study was to compare the adhesion of Pseudomonas aeruginosa ocular isolates to mucin. An adhesion assay was developed using biotin‐labelled P. aeruginosa strains (two corneal ulcer, two acute red eye, one asymptomatic and one standard strains) incubated with porcine gastric mucin immobilized on a nitrocellulose membrane. The adhesion was semiquantified using densitometry. The results showed that all P. aeruginosa strains tested were able to adhere to mucin to various extents with three strains (one corneal ulcer, one acute red eye, one asymptomatic) binding significantly greater than the negative control (P < 0.1). Results suggest that ocular strains of P. aeruginosa strains differ in their adhesion to mucin but this did not correlate with the pathogenic origin of the strain. It is concluded that the adhesion of P. aeruginosa strains to mucin alone may not be a principal determinant of pathogenesis but may be a contributing factor along with other bacterial virulence traits.     

不同孔径纳米羟基磷灰石人工骨修复兔桡骨缺损效果比较

目的:纳米级的羟基磷灰石材料与人体内组织成分更为相似,具有更佳的生物性能。评价不同孔径的多孔纳米羟基磷灰石人工骨的骨缺损修复能力,从而筛选出适合的孔径以达到骨传导功能与生物力学性能的良好统一。方法:实验于2005-10/2006-10在深圳市第二人民医院中心实验室完成。①实验材料:纳米羟基磷灰石人工骨以硝酸钙和磷酸二氢铵为原料,采用溶胶-絮凝法制备粉体,运用压力成型、木模成型和浸渍成型分别制得孔隙分布均匀的孔径分别为50～150μm、100～250μm和300～500μm的多孔纳米羟基磷灰石人工骨。②实验动物:雄性新西兰大白兔60只随机分为植入50～150μm孔径材料组、植入100～250μm孔径材料组、植入300～500μm孔径材料组、空白对照组,每组15只。实验过程中对动物处置符合动物伦理学要求。③实验方法:制备双侧桡骨骨缺损动物模型,然后用3种不同孔径的纳米羟基磷灰石人工骨材料植入骨缺损处进行修复,空白对照组不植入任何材料。④实验评估:术后4,8和12周分别行大体标本观察、X射线片观察、扫描电镜观察及生物力学测试,比较各组材料修复骨缺损的能力。结果:实验动物均进入结果分析。①X射线片检查结果:术后4周、8周、12周,植入100～250μm孔径材料组X射线评分高于植入50～150μm,300～500μm孔径材料组,差异有显著性意义(P<0.05)。②生物力学检测结果:术后4周、8周、12周,植入100～250μm孔径材料组生物力学强度高于植入50～150μm,300～500μm孔径材料组,差异有显著性意义(P<0.05)。③扫描电镜观察结果:植入100～250μm孔径材料组成骨效果明显优于植入50～150μm,300～500μm孔径材料组和空白对照组。结论:纳米羟基磷灰石人工骨具有良好的成骨能力,但其骨修复能力受孔径因素的影响,孔径100～250μm的纳米羟基磷灰石人工骨材料成骨能力较好。     

Inhaled corticosteroid use in HIV‐positive individuals taking protease inhibitors: a review of pharmacokinetics,case reports and clinical management

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug?drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug?drug interaction in order to suggest options for the clinical management of HIV‐positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.     

日本血吸虫重组22kD表膜蛋白免疫水牛的效果观察

目的 用重组日本血吸虫22kD表膜蛋白（rSj22)免疫水牛,检测特异性IgG抗体的应答水平,并观察抗血吸虫的保护效果。方法 用抗原（rSj22)加佐剂（Quil-A)肌肉注射免疫水牛,以1000条日本血吸虫尾蚴攻击感染,感染后55d剖杀,计算减虫和减卵率,用免疫印斑和ELISA方法测定抗体反应。结果 免疫组每头牛血清均能特异地识别Quil-A对照组相比,减虫率仅8.5%肝卵EPG减少12.3%,粪卵EPG减少26.8%,但均无统计学意义,结论 用rSj22kD抗原免疫水牛诱导的特异性IgG抗体不能发挥免疫保护作用。