Newly diagnosed versus relapsed idiopathic thrombotic thrombocytopenic purpura: a comparison of presenting clinical characteristics and response to treatment

The remission rate with plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) exceeds 80%, but the disease relapses in up to 20–30% of the cases. Clinical characteristics and response to treatment of relapsed TTP are not well defined. The objective of the present study was to compare the clinical and biological characteristics at presentation and the response to treatment between de novo and relapsed TTP. For such purpose, a total of 102 episodes of idiopathic TTP (70 de novo and 32 relapses) included in a recent multicentric prospective cohort study were analysed. All patients were homogeneously treated with daily PE and costicosteroids. In comparison with de novo TTP, episodes of relapsed TTP showed a higher Hb level (median, 122 g/l versus 91 g/l, p < 0.001) and lower serum lactate dehydrogenase (2.2- versus 4.5-fold above the upper limit of normality, p < 0.001). Neurological symptoms and fever were less frequently observed in patients with relapsed TTP than in patients with de novo TTP. Patients with relapsed TTP needed fewer PE sessions (five versus ten, p = 0.02) and a smaller volume of plasma (221 ml/kg versus 468 ml/kg, p = 0.004) to achieve remission than those with de novo TTP. There was no significant difference in the rate of recrudescence under treatment, the need of complementary treatments or the frequency of refractoriness to PE therapy. In conclusion, relapsed TTP has a milder clinical profile and responds more easily to PE than de novo TTP. Alberto Alvarez-Larrán and Julio del Río-Garma contributed equally to this article. Grant support: This work was supported in part by a grant awarded by the Ministry of Health of the Government of Spain (FIS 05/2189).     

The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage

STUDY QUESTION: Is there any effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage? SUMMARY ANSWER: There was no significant difference in the chromosome abnormality rate between sporadic and recurrent miscarriage but the chromosome abnormality rate increased significantly with maternal age. WHAT IS KNOWN ALREADY: About 50-70% of non-recurrent miscarriages occur because of a chromosomal anomaly, but no agreement about the effect of either maternal age or the number of previous miscarriages on the chromosomal anomaly rate has been reached. STUDY DESIGN, SIZE, DURATION: A retrospective cohort of 353 miscarriages successfully karyotyped in the same center between 2002 and 2011, grouped according to the number of miscarriages and maternal age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 353 women, 153 were below 35 years (73 with sporadic, 48 with two and 32 with recurrent miscarriage) and 200 were 35 years or more (81 with sporadic, 55 with two and 64 with recurrent miscarriage). The chromosomal anomaly rate and the anomaly spectrum were compared between sporadic and recurrent miscarriage, within the two maternal age groups, using the chi-square test and the Bonferroni correction for all the P-values. Risk of chromosomal anomaly was estimated for maternal age, number of miscarriages and previous live births by multivariate binary logistic regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Sporadic and recurrent miscarriage did not show significantly different chromosomal anomaly rates (68 versus 60%) and maternal age was the only statistically significant predictor of the chromosomal anomaly risk we identified. Some trends were observed in the chromosomal anomaly spectrum when sporadic was compared with recurrent miscarriage: recurrent miscarriage exhibited a decrease in viable trisomies (37 versus 11%) and an increase in non-viable trisomies (38 versus 57%) in women >35 years, together with an increase in unbalanced structural anomalies (4.9 versus 29%) in younger women. LIMITATION, REASONS FOR CAUTION: The mixed origin of our study population, and the limited number of recurrent miscarriages, particularly in the younger group, limits statistical power to detect differences. WIDER IMPLICATIONS OF THE FINDINGS: The most commonly observed chromosomal anomaly type in recurrent miscarriage depends on maternal age: non-viable autosomal trisomies in older women and unbalanced structural anomalies in younger women. When a chromosomal anomaly is identified as the cause of miscarriage, additional maternal evaluation may be avoided. STUDY FUNDING/COMPETING INTERESTS: No competing interests declared.     

Cell-Autonomous Inactivation of the Reelin Pathway Impairs Adult Neurogenesis in the Hippocampus

Adult hippocampal neurogenesis is thought to be essential for learning and memory, and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an extracellular matrix protein that is vital for neuronal development. Activation of the Reelin cascade leads to phosphorylation of Disabled-1, an adaptor protein required for Reelin signaling. Here we used transgenic mouse and retroviral reporters along with Reelin signaling gain-of-function and loss-of-function studies to show that the Reelin pathway regulates migration and dendritic development of adult-generated hippocampal neurons. Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprogenitor cells resulted in aberrant migration, decreased dendrite development, formation of ectopic dendrites in the hilus, and the establishment of aberrant circuits. Our findings support a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and the integration of adult-generated granule cells and point to this pathway as a key regulator of adult neurogenesis. Moreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential implications for the pathogenesis of several neurological and psychiatric disorders.     

Social inequalities in the association between partner/marital status and health among workers in Spain

The objectives of this study are to examine the association between partner/marital status and several health outcomes among workers and to assess whether it depends on gender and occupational social class. The sample was composed of all workers aged 21-64 years interviewed in the 2006 Spanish National Health Survey (8563 men and 5881 women). Partner/marital status had seven categories: married and living with the spouse (reference category), married and not living with the spouse, cohabiting, single and living with parents, single and not living with parents, separated/divorced and widowed. Four health outcomes were analysed: self-perceived health status, mental health, psychiatric drugs consumption and hypertension. Multiple logistic regression models stratified by sex and social class were fitted. Female manual workers who were cohabiting were more likely to report poor self-perceived health status, poor mental health status, psychiatric medication consumption and hypertension than their married and living with the spouse counterparts. In that group the prevalence of poor health outcomes was even higher when compared with single people. Among male non-manual workers, being married and not living with the spouse was associated with poor self-perceived health status, poor mental health status and hypertension. There were almost no differences in health between being married and the rest of partner/marital status categories for different combinations of gender and social class and, even, some groups of single people reported better health outcomes than people who were married. Our results show no evidence that being married and living with the spouse is unequivocally linked to better health status among Spanish workers. They emphasize the importance of not only considering marital status, but also partner status, as well as the role of gender, social class and the sociocultural context in the analysis of the association between family characteristics and health.     

Racial/ethnic residential segregation: framing the context of health risk and health disparities

An increasing body of public health literature links patterns of racial/ethnic residential segregation to health status and health disparities. Despite substantial new empirical work, meaningful understanding of the pathways through which segregation operates to influence health remains elusive. The literature on segregation and health was appraised with an emphasis on select conceptual, methodological, and analytical issues. Recommendations for advancing the next generation of racial/ethnic residential segregation and health research will require closer attention to sharpening the methodology of measuring segregation, testing mediating pathways and effect modification, incorporating stronger test of causality, exploring factors of resilience in segregated areas, applying a life-course perspective, broadening the scope of the investigation of segregation to include nativity status in blacks and other racial/ethnic groups, and linking segregation measures with biological data.     

Behavioral, neuroendocrine, and immunological outcomes of escapable or inescapable shocks.

The present study was designed to evaluate the effects of repeated exposure to escapable or inescapable shocks on subsequent behavior in an activity cage, and on the reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the immune system. We also studied the possible influence of behavioral factors on the behavioral and physiological impact of stress. Although exposure to different stressful situations pointed out marked differential effects in subsequent behavior, it failed to elicit differences in the neuroendocrine and immunological parameters studied. However, interesting results were found in analyzing the influence of behavioral factors. The degree of control exerted over the shock was inversely related to ACTH and corticosterone levels. In addition, individual differences in the exploratory activity to novelty were correlated with poststress lymphoproliferation and antibody formation. These data indicate that the behavioral and physiological outcomes of stress depend on the interrelations between environmental and individual factors (including both preexisting individual differences and the coping responses during stress).