Prognostic Implications of Mitral Annular Plane Systolic Excursion in Patients with Hypertension and a Clinical Indication for Cardiac Magnetic Resonance Imaging: A Multicenter Study

ObjectivesThis study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived mitral annular plane systolic excursion (MAPSE) in a large multicenter population of patients with hypertension.BackgroundIn patients with hypertension, cardiac abnormalities are powerful predictors of adverse outcomes. Long-axis mitral annular movement plays a fundamental role in cardiac mechanics and is an early marker for a number of pathological processes. Given the adverse consequences of cardiac involvement in hypertension, the authors hypothesized that lateral MAPSE may provide incremental prognostic information in these patients.MethodsConsecutive patients with hypertension and a clinical indication for CMR at 4 U.S. medical centers were included in this study (n = 1,735). Lateral MAPSE was measured in the 4-chamber cine view. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the association between lateral MAPSE and death. The incremental prognostic value of lateral MAPSE was assessed in nested models.ResultsOver a median follow-up period of 5.1 years, 235 patients died. By Kaplan-Meier analysis, risk of death was significantly higher in patients with a lateral MAPSE < median (10 mm) (log-rank; p < 0.0001). Lateral MAPSE was associated with risk of death after adjustment for clinical and imaging risk factors (hazard ratio [HR]: 1.402-per-millimeter decrease; p < 0.001). Addition of lateral MAPSE in this model resulted in significant improvement in the C-statistic (0.735 to 0.815; p < 0.0001). Continuous net reclassification improvement was 0.739 (95% confidence interval: 0.601 to 0.902). Lateral MAPSE remained significantly associated with death even after adjustment for feature tracking global longitudinal strain (HR: 1.192-per-millimeter decrease; p < 0.001). Lateral MAPSE was independently associated with death among the subgroups of patients with preserved ejection fraction (HR = 1.339; p < 0.001) and in those without history of myocardial infarction (HR: 1.390; p < 0.001).ConclusionsCMR-derived lateral MAPSE is a powerful, independent predictor of mortality in patients with hypertension and a clinical indication for CMR, incremental to common clinical and CMR risk factors. These findings may suggest a role for CMR-derived lateral MAPSE in identifying hypertensive patients at highest risk of death.     

Spouse's subjective social status predicts older adults’ prospective cognitive functioning

Objectives: The current study aims to investigate the association between subjective social status (SSS) and prospective cognitive functioning of older adults and their spouses, and to explore the potential mediating roles of health habits and physical activities in this association.

Method: Using the longitudinal data of 512 pairs of community-dwelling older couples aged 65–91 years (M = 72.2 ± 4.6), we tested the effects of SSS in cognitive functioning using an Actor-Partner Interdependence Model. SSS was measured by a self-anchoring social ladder, and cognitive functioning was measured by the Mini-Mental State Examination at baseline and 4-year follow-up. Socioeconomic status (i.e. education) was tested as a moderator, and physical activity (measured by the Physical Activity Scale for the Elderly) as well as health habits (i.e. tobacco and alcohol consumption) were included as potential mediators.

Results: A partner effect of SSS was found only in the low-education group, in which the wife's higher level of SSS in the community was associated with the husband's better cognitive functioning in the follow-up. A small proportion of this effect was found to be partially mediated by participation in housework, such that the wife's higher SSS was associated with the husband's increased housework activity, which was related to higher prospective cognitive functioning.

Conclusion: By examining the dyadic effects of SSS with a longitudinal design, our findings extended the understanding on how subjective social status influenced older couples’ cognitive health, and provided evidence-based insights for future studies on cognitive health in later life.     

How does measurement of platelet P-selectin compare with other methods of measuring platelet function as a means of determining the effectiveness of antiplatelet therapy?

Measurement of P-selectin on activated platelets as a means of measuring platelet function utilizing the technology described here has the advantage of not requiring immediate access to specialist equipment and expertise. Blood samples are activated, fixed, stored, and transported to a central laboratory for flow cytometric analysis. Here we have compared P-selectin with other more traditional approaches to measuring platelet function in blood and/or platelet-rich plasma (PRP) from patients with acute coronary syndromes on treatment for at least 1 month with either aspirin and clopidogrel or aspirin with prasugrel. The comparators were light transmission aggregometry (LTA), VerifyNow and Multiplate aggregometry (for determining the effects of aspirin) and LTA, VerifyNow and Multiplate together with the BioCytex VASP phosphorylation assay (for the P2Y₁₂ antagonists). The P-selectin Aspirin Test revealed substantial inhibition of platelet function in all but three of 96 patients receiving aspirin with clopidogrel and in none of 51 patients receiving aspirin and prasugrel. The results were very similar to those obtained using LTA. There was only one patient with high residual platelet aggregation and low P-selectin expression. The same patients identified as “non-responders” to aspirin also presented with the highest residual platelet activity as measured using the VerifyNow system, although not quite as well separated from the other values. With the Multiplate test only one of these patients clearly stood out from the others. The results obtained using the P-selectin P2Y₁₂ Test in 102 patients taking aspirin and clopidogrel were similar to the more traditional approaches in that a wide scatter of results was obtained. Generally, high values seen with the P-selectin P2Y₁₂ Test were also high with the LTA, VerifyNow, Multiplate, and BioCytex VASP P2Y₁₂ Tests. Similarly, low residual platelet function using the P2Y₁₂ test was seen irrespective of the testing procedure used. However, there were differences in some patients. Prasugrel was always more effective than clopidogrel in inhibiting platelet function with none of 56 patients (P-selectin and VerifyNow), only 2 of 56 patients (Multiplate) and only 3 of 56 patients (Biocytex VASP) demonstrating high on-treatment residual platelet reactivity (HRPR) defined using previously published cut-off values. The exception was LTA where there were 11 of 56 patients with HRPR. It remains to be seen which experimental approach provides the most useful information regarding outcomes after adjusting therapies in treated patients.     

儿童免疫性血小板减少症发病机制研究进展

免疫性血小板减少症(immune thrombocytopenia,ITP)是一种由自身免疫介导的出血性疾病,其特点为血小板破坏增多和生成不足。ITP发病机制复杂多样,具有异质性,至今尚未完全明确,在儿童中尤其突出。现有研究表明,免疫失耐受引起各种免疫细胞或分子异常,进而导致血小板破坏增多或生成不足,是ITP的核心发病机制。随着研究的不断深入,越来越多的机制被报道。该文就儿童ITP的发病机制及其研究进展进行介绍。     

The role of dark adaptation in understanding early AMD

The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD.Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time.Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD.     

Cut Points of Chair Stand Test for Poor Physical Function and Its Association With Adverse Health Outcomes in Community-Dwelling Older Adults: A Cross-Sectional and Longitudinal Study

ObjectivesTo identify the optimal cutoff points for poor physical function [measured by a 5-times sit-to-stand (5-STS) test] associated with slowness in community-dwelling older adults and to validate the 5-STS cut points by determining whether they predicted future slowness and clinically relevant health outcomes over a 2-year-follow-up period.DesignCross-sectional and longitudinal analyses of a cohort study.Setting and ParticipantsWe conducted cross-sectional (n = 2977) and prospective 2-year follow-up analyses (n = 2515) among participants aged 70-84 years enrolled in the nationwide Korean Frailty and Aging Cohort Study (KFACS).MethodsClassification and regression tree (CART) analysis was used to identify the 5-STS cut points for poor performance in terms of slowness (eg, gait speed ≥1.0 m/s, gait speed >0.8 m/s and <1.0 m/s, gait speed ≤0.8 m/s) at baseline. Multinomial logistic regression models were used to evaluate the prevalence and incidence of slowness and clinical outcomes according to the three 5-STS categories (normal, intermediate, and poor) in the cross-sectional and longitudinal analyses.ResultsThe overall prevalence of slowness in our study sample was 9.0% for a gait speed of ≤0.8 m/s and 32.1% for a gait speed of <1.0 m/s. The CART model identified 5-STS cut points of 10.8 seconds and 12.8 seconds for intermediate and poor physical function, respectively. In the adjusted model, the cut point of 12.8 seconds had a significantly increased likelihood of incident slowness and clinically relevant health outcomes (ie, mobility limitation, disability, frailty, sarcopenia risk, and falls) over the 2-year-follow-up period (all, P < .05).Conclusions and ImplicationsOur study established 5-STS test cutoff points for poor physical function. Thresholds of 10.8 and 12.8 seconds (intermediate and poor physical function, respectively) for a 5-STS test might help identify individuals at risk of physical function impairments and, thus, help design preventive interventions in community health care settings.     

基于突触可塑性探讨电针改善大脑中动脉闭塞大鼠运动障碍的作用机制

目的：基于突触可塑性观察电针曲池、足三里对大脑中动脉闭塞（MCAO）大鼠运动障碍的改善。方法：将60只雄性SD大鼠随机分为假手术组、模型组、穴位组、非穴组，每组15只。采用Zea Longa线拴法制备MCAO大鼠模型，电针曲池、足三里，干预14 d。通过神经功能评分判断大鼠的神经功能缺损情况；CatWalk步态分析比较各组大鼠运动功能，TTC染色观察脑梗死体积，透射电镜观察突触超微结构和数量，免疫荧光检测缺血侧运动皮层突触相关因子突触后致密物-95（PSD-95)、突触蛋白的表达情况。结果：干预14 d后，与模型组比较，穴位组大鼠神经功能评分降低(P<0.05)；步行速度提高、双足支撑时间缩短(P<0.05)；脑梗死体积减少(P<0.05)；突触超微结构改善明显，突触数量增加(P<0.05)，突触相关因子突触蛋白、PSD-95表达上调(P<0.05)。Catwalk步态参数、脑梗死体积与突触超微结构改善有一致性。结论：电针曲池、足三里穴可改善MCAO大鼠运动障碍，其机制可能与上调突触相关因子的表达，改善突触可塑性有关。