The risk of thrombosis in children with acute lymphoblastic leukemia (ALL) reportedly ranges between 1% and 37%. Epidemiologic studies have usually been hampered by small numbers, making accurate estimates of thrombosis risk in ALL patients very difficult. The aim of this study was to better estimate the frequency of this complication and to define how the disease, its treatment, and the host contribute to its occurrence. We made an attempt to combine and analyze all published data on the association between pediatric ALL and thrombosis, by using a meta-analytic method. The rate of thrombosis in 1752 children from 17 prospective studies was 5.2% (95% CI: 4.2-6.4). The risk varies depending on several factors. Most of the events occurred during the induction phase of therapy. Lower doses of asparaginase (ASP) for long periods were associated with the highest incidence of thrombosis, as were anthracyclines and prednisone (instead of dexamethasone). The presence of central lines and of thrombophilic genetic abnormalities also appeared to be frequently associated with thrombosis. In conclusion, the overall thrombotic risk in ALL children was significant, and the subgroup analysis was able to identify high-risk individuals, a finding that will hopefully guide future prospective studies aimed at decreasing this risk. IntroductionAcute lymphoblastic leukemia (ALL) is more frequent in children than in adults; indeed, two thirds of all cases occur at pediatric age. 1 The risk of thrombosis is increased in ALL patients, 2 and its occurrence may complicate the treatment course with a negative prognostic impact. Its frequency reportedly ranges between 1.1% and 36.7%, a quite large variation related to several factors, such as different definitions of thrombosis (symptomatic vs asymptomatic), diagnostic methods for its detection, study design (prospective vs retrospective), and differences in treatment protocols. 2 The pathogenesis of this increased thrombotic risk is not fully understood, but includes a combination of variables related to the disease itself, its treatment, and the host. [3][4][5] Although many clinical and epidemiologic studies were performed in this field, the majority were either retrospective or prospective observations on small numbers of subjects. Thus, the results are contradictory and inconclusive, mainly due to lack of statistical power. However, a careful assessment of risk factors would be useful to improve the quality of treatment and to identify subgroups in which prophylactic interventions would be beneficial.The objective of the present study was to quantitatively combine and analyze the available data, by a meta-analytic approach, to obtain accurate estimates of the thrombotic risk in pediatric patients with ALL.Several subgroup analyses were carried out to control for possible biases arising from heterogeneous pieces of information and to sort out subpopulations at higher risk of thrombosis. Materials and methods Meta-analysisIn the PubMed database, all available articles were searched usin...

BACKGROUND:Atrial fibrillation (AF) is a common cardiac disease in aging populations with high comorbidity and mortality. Sex differences in AF epidemiology are insufficiently understood. METHODS:In N=79 793 individuals without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1-97.6 years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA, Molisani Northern Sweden) of the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), we examined AF incidence, its association with mortality, common risk factors, biomarkers, and prevalent cardiovascular disease, and their attributable risk by sex. Median follow-up time was 12.6 (to a maximum of 28.2) years. RESULTS:Fewer AF cases were observed in women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor distribution and lipid profile at baseline were less beneficial in men than in women, and cardiovascular disease was more prevalent in men. Cumulative incidence increased markedly after the age of 50 years in men and after 60 years in women. The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF had a 3.5-fold risk of death in comparison with those without AF. Multivariable-adjusted models showed sex differences for the association of body mass index and AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval [CI], 1.12-1.23 in women versus 1.31; 95% CI 1.25-1.38 in men; interaction P value of 0.001). Total cholesterol was inversely associated with incident AF with a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81-0.90 versus 0.92; 95% CI, 0.88-0.97 in men; interaction P value of 0.023). No sex differences were seen for C-reactive protein and N-terminal pro B-type natriuretic peptide. The population-attributable risk of all risk factors combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed for body mass index. CONCLUSIONS:Lifetime risk of AF was high, and AF was strongly associated with increased mortality both in women and men. Body mass index explained the largest proportion of AF risk. Observed sex differences in the association of body mass index and total cholesterol with AF need to be evaluated for underlying pathophysiology and relevance to sexspecific prevention strategies. ORIGINAL RESEARCH ARTICLE A trial fibrillation (AF) is a common cardiac disease that increases the risk of morbidity and mortality in aging women and men. Sex Differences and Similarities in Atrial1-3 Considerable sex differences in prevalence, incidence, and mortality have been reported.2,4 AF prevalence in middle-aged and older community cohorts is almost twice as high in men as in women. [5][6][7] The increasing prevalence of AF and subsequent public health and economic burden require research efforts to understand sex differences in disease distribution and risk factor associations. 5 The onset of AF diminishes the survival advantage in women. 8 Risk of adverse outcomes in AF also appears to differ by sex, eg, st...

A B S T R A C T Bacterial infection is associated with disseminated intravascular coagulation and fibrin de-position in the microcirculation; the mechanism of these effects in humans is still unclear. We 28 March 1983. were observed in the absence of endothelial damage, as shown by phase-contrast mnicroscopy and lack of 51Cr release. These data coul(d contribute to elucidate the pathogenesis of vascular complications associated with endotoxemia in man.INTRODUCTIO'N Endotoxin-producing bacte ria cause disseminated intravascular coagulation (D[IC),' shock, and ultimate death of an estimated 25.% of patients with bloodstream infections (1,2). The mechanism of endotoxin action in man is still unclear and difficult to study. In animals endotoxin induce s injury of endothelial cells (EC) and this is thought to play an important role in blood clotting activation (3, 4).We describe here exp)eriments indicating that endotoxin induces the gelieration of tissue factor procoagulant by cultured inuman EC. This hitherto undescribed effect of endQtoxin could play a key role in the generation and deposition of fibrin in blood vessels.

Spousal pairs permit assessment of determinants of diseases related to environment, because they share the same lifestyle and environment. The authors reviewed spouses' concordance for the major coronary risk factors. A search of the MEDLINE, PubMed, and EMBASE databases was performed. Seventy-one papers were selected for a total of 207 cohorts of pairs and 424,613 correlations in more than 100,000 couples. The most strongly correlated within-pairs factors were smoking and body mass index, with overall correlations of 0.23 (95% confidence interval: 0.12, 0.36) and 0.15 (95% confidence interval: 0.05, 0.25), respectively. Statistically significant positive correlations were also found for diastolic blood pressure, triglycerides, total and low density lipoprotein cholesterol, weight, and the waist/hip ratio. The overall odds ratios for concordance in hypertension, smoking, diabetes, and obesity were all statistically significant, ranging from 1.16 to 3.25. Assortative mating influenced concordance for blood pressure, smoking, glucose, low density lipoprotein cholesterol, weight, body mass index, and waist circumference. This systematic review shows a statistically significant positive spousal concordance for the majority of main coronary risk factors. However, the strength of the concordance was markedly different among factors and appeared to be quite modest for all of them. Interventions to reduce cardiovascular risk factors should be addressed jointly to both members of a marital couple.