Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism.

BACKGROUND: The Pulmonary Embolism Severity Index (PESI) estimates the risk of 30-day mortality in patients with acute pulmonary embolism (PE). We constructed a simplified version of the PESI. METHODS: The study retrospectively developed a simplified PESI clinical prediction rule for estimating the risk of 30-day mortality in a derivation cohort of Spanish outpatients. Simplified and original PESI performances were compared in the derivation cohort. The simplified PESI underwent retrospective external validation in an independent multinational cohort (Registro Informatizado de la Enfermedad Tromboembólica [RIETE] cohort) of outpatients. RESULTS: In the derivation data set, univariate logistic regression of the original 11 PESI variables led to the removal of variables that did not reach statistical significance and subsequently produced the simplified PESI that contained the variables of age, cancer, chronic cardiopulmonary disease, heart rate, systolic blood pressure, and oxyhemoglobin saturation levels. The prognostic accuracy of the original and simplified PESI scores did not differ (area under the curve, 0.75 [95% confidence interval (CI), 0.69-0.80]). The 305 of 995 patients (30.7%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.0% (95% CI, 0.0%-2.1%) compared with 10.9% (8.5%-13.2%) in the high-risk group. In the RIETE validation cohort, 2569 of 7106 patients (36.2%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.1% (95% CI, 0.7%-1.5%) compared with 8.9% (8.1%-9.8%) in the high-risk group. CONCLUSION: The simplified PESI has similar prognostic accuracy and clinical utility and greater ease of use compared with the original PESI.

A clinical prognostic model for the identification of low-risk patients with acute symptomatic pulmonary embolism and active cancer.

BACKGROUND: Physicians need a specific risk-stratification tool to facilitate safe and cost-effective approaches to the management of patients with cancer and acute pulmonary embolism (PE). The objective of this study was to develop a simple risk score for predicting 30-day mortality in patients with PE and cancer by using measures readily obtained at the time of PE diagnosis. METHODS: Investigators randomly allocated 1,556 consecutive patients with cancer and acute PE from the international multicenter Registro Informatizado de la Enfermedad TromboEmbólica to derivation (67%) and internal validation (33%) samples. The external validation cohort for this study consisted of 261 patients with cancer and acute PE. Investigators compared 30-day all-cause mortality and nonfatal adverse medical outcomes across the derivation and two validation samples. RESULTS: In the derivation sample, multivariable analyses produced the risk score, which contained six variables: age > 80 years, heart rate ≥ 110/min, systolic BP < 100 mm Hg, body weight < 60 kg, recent immobility, and presence of metastases. In the internal validation cohort (n = 508), the 22.2% of patients (113 of 508) classified as low risk by the prognostic model had a 30-day mortality of 4.4% (95% CI, 0.6%-8.2%) compared with 29.9% (95% CI, 25.4%-34.4%) in the high-risk group. In the external validation cohort, the 18% of patients (47 of 261) classified as low risk by the prognostic model had a 30-day mortality of 0%, compared with 19.6% (95% CI, 14.3%-25.0%) in the high-risk group. CONCLUSIONS: The developed clinical prediction rule accurately identifies low-risk patients with cancer and acute PE.

D'où viens-tu et où vas-tu? De la naissance impensable à la destinée impensée

(Résumé de l'ouvrage) Dans quelle mesure la sépulture est-elle un symbole privilégié pour penser le lien social aujourd'hui? Tel qu'il existe dans l'Antigone de Sophocle, le motif de la sépulture nous aiderait-il à penser - comme à panser - les traumatismes collectifs associés aux innombrables cadavres laissés sans sépulture au cours des siècles? Ce livre explore notamment ces questions sous l'angle archéologique, historique, anthropologique, philologique, théologique et psychanalytique.

Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis.

BACKGROUND: Controversy exists regarding the usefulness of troponin testing for the risk stratification of patients with acute pulmonary embolism (PE). We conducted an updated systematic review and a metaanalysis of troponin-based risk stratification of normotensive patients with acute symptomatic PE. The sources of our data were publications listed in Medline and Embase from 1980 through April 2008 and a review of cited references in those publications. METHODS: We included all studies that estimated the relation between troponin levels and the incidence of all-cause mortality in normotensive patients with acute symptomatic PE. Two reviewers independently abstracted data and assessed study quality. From the literature search, 596 publications were screened. Nine studies that consisted of 1,366 normotensive patients with acute symptomatic PE were deemed eligible. Pooled results showed that elevated troponin levels were associated with a 4.26-fold increased odds of overall mortality (95% CI, 2.13 to 8.50; heterogeneity chi(2) = 12.64; degrees of freedom = 8; p = 0.125). Summary receiver operating characteristic curve analysis showed a relationship between the sensitivity and specificity of troponin levels to predict overall mortality (Spearman rank correlation coefficient = 0.68; p = 0.046). Pooled likelihood ratios (LRs) were not extreme (negative LR, 0.59 [95% CI, 0.39 to 0.88]; positive LR, 2.26 [95% CI, 1.66 to 3.07]). The Begg rank correlation method did not detect evidence of publication bias. CONCLUSIONS: The results of this metaanalysis indicate that elevated troponin levels do not adequately discern normotensive patients with acute symptomatic PE who are at high risk for death from those who are at low risk for death.

Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations.

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2x10(-201)), ABCG2 (p = 3.1x10(-26)), SLC17A1 (p = 3.0x10(-14)), SLC22A11 (p = 6.7x10(-14)), SLC22A12 (p = 2.0x10(-9)), SLC16A9 (p = 1.1x10(-8)), GCKR (p = 1.4x10(-9)), LRRC16A (p = 8.5x10(-9)), and near PDZK1 (p = 2.7x10(-9)). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0x10(-26)) and propionyl-L-carnitine (p = 5.0x10(-8)) concentrations, which in turn were associated with serum UA levels (p = 1.4x10(-57) and p = 8.1x10(-54), respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.