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RATIONALE: The short-term prognosis of pulmonary embolism (PE) depends on hemodynamic status and underlying disease. The prognostic value of right ventricular dysfunction and injury is less well established. Objectives: To evaluate prognostic factors of PE in a multicenter prospective cohort study. METHODS: Echocardiography, brain natriuretic peptide (BNP), N-terminal-proBNP and cardiac troponin I measurements were done on admission of 570 consecutive patients with an acute PE. A predictive model was based on independent predictors of 30-day adverse events defined as death, secondary cardiogenic shock, or recurrent venous thromboembolism. MEASUREMENTS AND MAIN RESULTS: At 30 days, 42 patients (7.4%; 95% confidence interval [CI], 5.5-9.8%) had adverse events. On multivariate analysis, altered mental state (odds ratio [OR] 6.8; 95% confidence interval [CI], 2.0-23.3), shock on admission (OR 2.8; 95% CI, 1.1-7.5), cancer (OR 2.9; 95% CI, 1.2-6.9), BNP (OR 1.3 for an increase of 250 ng/L; 95% CI, 1.1-1.6) and right to left ventricle diameter ratio (OR 1.2 for an increase of 0.1; 95% CI, 1.1-1.4) were associated with 30-days of adverse events. The predictive performance of the model was good (area under receiver operating characteristics curve 0.84 [95% CI, 0.78-0.90]), making it possible to develop a bedside prognostic score. CONCLUSIONS: BNP and echocardiography may be useful determinants of the short-term outcome for patients with PE, together with clinical findings. Patients with PE can be stratified according to the initial risk of adverse outcome, using a simple score based on clinical, echocardiographic, and biochemical variables. [ABSTRACT FROM AUTHOR]

Cohort studies suggest that exposure to antipsychotic agents may be associated with an increased risk of venous thromboembolism (VTE). Few data concerning antidepressant drugs are available. Using a different methodological approach, the aim of this study was to estimate the association between neuroleptic and antidepressant drug use and the risk of VTE. We report the results of a case–control study designed to evaluate interactions between acquired and inherited risk factors of VTE. We included 677 cases hospitalized with deep vein thrombosis and or pulmonary embolism with no major acquired risk factor for VTE, and 677 controls matched for gender and age. Drug exposure was defined as current use of drugs at admission. Neuroleptic exposure was associated with an increased risk of VTE (OR = 2.1, 95% CI 1.4–3.2). Among neuroleptics, antipsychotic agent use was associated with a 3.5-fold increased risk of VTE (OR = 3.5, 95% CI 2.0–6.2). No association was found between antidepressant drug exposure and the risk of VTE (OR = 1.1, 95% CI 0.9–1.5). In this hospital-based case–control study, exposure to antipsychotic drugs was associated with an increased risk of VTE. These results, added to previous results, suggest that clinicians should consider antipsychotic drug exposure as a potential risk factor of VTE. More studies are needed in order to further elucidate this adverse effect, and to determine the possible predisposing factors and the biological mechanisms involved. [ABSTRACT FROM AUTHOR]

Current guidelines recommend extended anticoagulation in patients with unprovoked venous thromboembolism (VTE). However, a precise description of these patients from the "real-world" is lacking. The EPI-GETBO study is a prospective epidemiologic study of VTE in the geographically well-defined Brest district area. All cases of symptomatic VTE between March 2013 and February 2015 were recorded, adjudicated, and included in the study. During the study period, 555 patients with unprovoked symptomatic VTE were included in EPI-GETBO. Patients' median age was 72.0 years (IQR 57.0;83.0), 45.2% were male, 64.7% had a pulmonary embolism (PE) associated or not with a deep vein thrombosis (DVT) and 29.2% had a previous history of VTE. 5.6% of the patients had atrial fibrillation at the time of VTE diagnosis, 5.9% had a history of coronary artery disease, and 17.3% received antiplatelet medications. A total of 283 (51.0%) patients discontinued anticoagulation during the observation period. In these patients, the median duration of treatment was 183 days (range 0 to 853 days). Patients with PE associated or not with DVT were treated for a longer time than patients with isolated DVT (P = 0.01). A total of 40 recurrences (14.1%) were observed during follow-up (up to 2 years after initial VTE event) after anticoagulation discontinuation. Based on indirect standardization, we expect an annual 50,054 cases of unprovoked VTE in France, including 32,346 PEs. The 14,1% recurrence rate of VTE after anticoagulation discontinuation confirms the need for extended duration of treatment in this patient population. Attention should be made for the significant number of patients with concomitant arterial disease who may need aspirin if low-dose DOAC is chosen for extended therapy or who may not be eligible for a low-dose DOAC in case of presence of atrial fibrillation. [ABSTRACT FROM AUTHOR]

There are a number of pathophysiological mechanisms that can lead to the development of pulmonary aspergillosis and the manifestations of this condition are diverse. The diversity of the clinical manifestations depends on the virulence of the microbe, the status of the host’s immune system and local anatomical conditions. Aspergilloma, allergic bronchopulmonary aspergillosis and invasive pulmonary aspergillosis are the three main entities, but intermediate forms have been described. As therapy differs for each of these entities, a precise diagnosis should be attempted. Accordingly, a precise diagnosis is now even more important because of the availability of promising new anti-fungal drugs that are more effective and tolerated better relative to drugs that are currently available for the treatment of severe forms of pulmonary aspergillosis. [Copyright &y& Elsevier]

Venous thromboembolism (VTE) afflicts 117 people per 100,000 each year and is an important cause of morbidity and mortality. VTE can lead to: – death through pulmonary embolism; – the post-thrombotic syndrome, or; – chronic pulmonary hypertension resulting in significant chronic respiratory compromise. Inflammatory pathways are intricately involved in venous thromboembolism mechanisms. In pathological conditions, adenosine triphosphate (ATP) is released in the extracellular compartment and is recognized as a danger signal. Recent data indicated that the CD39/CD73 system involved in the metabolism of ATP into AMP might protect against thrombosis by downregulating the pro-inflammatory pathway of the inflammasome. ATP can also interact with the P2X7 receptor involved in inflammation causing a wide range of responses. Determine how the endothelial P2X7 receptor contribute to venous thromboembolism. HUVEC were incubated with BzATP, thrombin or both. In some experiment, HUVEC were primed with TNFa prior to stimulation. We used immunofluorescence, western blot and real-time quantitative PCR analyses to assess P2X7 expression by endothelial cells, activation of p38 and NFkB activation and expression of pro-inflammatory and procoagulant genes. We confirmed that endothelial cells expressed P2X7 in vitro in HUVECs and in vivo after induction of venous thrombosis by ligation of the inferior vena cava. Treatment of endothelial cells with BzATP and thrombin induced the activation of p38 and NFkB signaling pathways. This was associated with an increased expression of IL-1b and tissue factor and downregulation of thrombomodulin expression. Our data suggest that ATP released in the extracellular space following cell damage or activation induced the inflammasome in endothelial through P2X7 activation. P2X7 might have a pro-thrombotic role exacerbating venous thromboembolism. [ABSTRACT FROM AUTHOR]

However, women younger than 50 years accounted for 11% of MI admitted in hospital and their incidence is increasing. The main objective of this study is to systematically collect and describe clinical, morphological and biological characteristics, in hospital mortality and 12 months outcomes. We performed a clinical prospective observational multicenter study including all female patients admitted for MI under the age of 50. Three hundred and fourteen patients were included in twenty-eight participating centers. Mean age was 42.9 (±5.7) years old. One hundred and ninety two presented with ST elevation MI and One hundred and twenty two with non ST elevation MI. A total of 75% were active smokers, 14.6% had diabetes, 26.4% high blood pressure but only 15.3% with antihypertensive therapy, 35% had a family history of cardiovascular disease. Their specific risk factor included 33% of prior complication of pregnancy, 45.5% were under hormonal contraception 15.6% were already menopaused. Among STEMI patient 90.6% presented with typical chest pain and 58.9% reported also associated symptoms (nausea, vomiting, asthenia, sweats, dizziness or palpitation). A total of 10.4% reported prior symptoms for more than 1 week before. At admission, 13% presented with cardiac arrest. Interestingly, for STEMI patients, pre-hospital antiplatelet drugs were not systematically administered. At angiography, normal coronary angiogram was found in 6.8% of STEMI and 10.7% of NSTEMI. 29.6% of the patients included had significant multivessel disease despite their young age. Spontaneous coronary artery dissection was reported in 14.6% of STEMI and 20.5% of NSTEMI. No death, but 3 strokes, 3 recurrences of MI and 1 serious bleeding occurred during the hospitalization. A comprehensive and systematized analysis of MI in young woman would improve our understanding and enable physician to offer patients a more appropriate therapeutic and monitoring. [ABSTRACT FROM AUTHOR]

Bien que tous les patients atteints de thrombose associée au cancer (TAC) présentent un risque élevé de morbidité et de mortalité, certains groupes de patients sont particulièrement vulnérables. Cela peut exposer le patient à un risque accru de récidive thrombotique ou d'hémorragie (ou les deux), car le rapport bénéfice/risque du traitement anticoagulant peut être modifié. Le traitement doit donc être choisi avec soin. Ces groupes vulnérables comprennent les patients âgés, les patients souffrant d'insuffisance rénale ou de thrombopénie, ainsi que les patients obèses ou en sous-poids. Cependant, ces groupes de patients sont peu représentés dans les essais cliniques, ce qui limite les données disponibles sur lesquelles les décisions thérapeutiques peuvent être basées. Une méta-analyse des données issues d'essais cliniques randomisés suggère que l'impact relatif des inhibiteurs directs du facteur Xa par voie orale (DXI) et des héparines de bas poids moléculaire (HBPM) en ce qui concerne les hémorragies majeures pourrait être influencé par l'âge avancé. Aucune preuve n'a été obtenue quant à une modification du balance bénéficie risque relatif des DXI par rapport aux HBPM, chez les patients souffrant d'insuffisance rénale ou de faible poids corporel. Les données disponibles, bien que limitées, ne permettent pas de restreindre l'utilisation des DXI chez les patients de faible poids corporel ou souffrant d'insuffisance rénale. Chez les patients plus âgés, l'âge n'est pas en soi un facteur déterminant pour le choix du traitement, contrairement à la fragilité. La fragilité des patients âgés de plus de 70 ans ayant une TAC mérite d'être évaluée avant de choisir un traitement. Les facteurs de risque hémorragique modifiables devraient également être pris en compte. Chez les patients souffrant d'insuffisance rénale, la clairance de la créatine doit être évaluée et surveillée régulièrement par la suite. Chez les patients dont le DFGe est inférieur à 30 mL/min/1,72 m2, il peut être nécessaire d'adapter le traitement anticoagulant. De même, la numération plaquettaire doit être évaluée avant le traitement et surveillée régulièrement. Chez les patients ayant une thrombopénie de grade 3–4 (moins de 50 000 plaquettes/L), un traitement par HBPM à dose réduite doit être envisagé. Pour les patients de faible poids corporel, les recommandations de traitement anticoagulant standard sont appropriées, tandis que pour les patients obèses, l'apixaban peut être préféré. Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with TAC on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR less than 30 mL/min/1.72 m2, the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3–4, thrombocytopenia (less than 50,000 platelets/μL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred. [ABSTRACT FROM AUTHOR]

Factor V serves an important role in the regulation of blood coagulation. The rs6025 (R534Q) and rs4524 (K858R) polymorphisms in the F5 gene, are known to influence the risk of venous thrombosis. While the rare Q534 (factor V Leiden) allele is associated with an increased risk of venous thrombosis, the minor R858 allele is associated with a lower risk of disease. However, no study has deeply examined the cumulative impact of these two variations on venous thrombosis risk. We study the association of these polymorphisms with the risk of venous thrombosis in 4 French case-control populations comprising 3719 patients and 4086 controls. We demonstrate that the Q534 allele has a dominant effect over R858. Besides, we show that in individuals not carrying the Q534 allele, the protective effect of the R858 allele acts in a dominant mode. Thrombin generation-based normalized activated protein C sensitivity ratio was lower in the 858R/R homozygotes than in the 858K/K homozygotes (1.92 ± 1.61 vs 2.81 ± 1.57, p = 0.025). We demonstrate that the R858 allele of the F5 rs4524 variant protects from venous thrombosis only in non-carriers of the Q534 allele of the F5 rs6025. Its protective effect is mediated by reduced factor VIII levels and reduced activated protein C resistance. [ABSTRACT FROM AUTHOR]