Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Prise en charge du syndrome coronarien aigu aux urgences du Centre Hospitalier de Vienne de 2002 à 2003

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF

Prise en charge du syndrome coronarien aigu aux urgences du Centre Hospitalier de Vienne de 2002 à 2003

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF

[Septic pulmonary embolism after removal of a venous access device for septic thrombophlebitis].

International audienceSeptic thrombophlebitis on a central venous access device (CVAD) is a rare and serious complication. According to current guidelines, the device should be removed and antibiotics be given. The risk of septic thrombophlebitis is related to the migration of septic emboli to the lung, a potentially fatal event, particularly in frail patients with lung cancer. We report a case observed in a 66-year-old man with multiple metastatic lung cancer who had a CVAD and who developed septic thrombophlebitis leading to coagulase-negative staphylococcal bacteriemia. After removal of the CVAD, the thrombophlebitis was complicated by pulmonary embolism affecting the entire network of the right lung

[Discovery of a yellow nail syndrome with major hypothyroidism].

International audienceThe yellow nail syndrome is rare. It associates the triad: yellow nails, lymphedema and thoracic events. We report two cases of this syndrome with major hypothyroidism. These observations suggest an association between these two diseases

[EGFR activating mutation in lung adenocarcinoma: risk factor of thromboembolic event?].

International audienceCancer is a known risk factor for the development of venous thromboembolism (VTE) and in particular, adenocarcinoma of the lung is known to be associated with a higher risk of thromboembolic event. EGFR activating mutations are more frequently found in this histological subtype than in other lung cancers. We report three cases of VTE in patients with adenocarcinoma of the lung and EGFR activating mutation. Our reported case series is atypical because the VTE event occurred early in the adenocarcinoma history: either leading to the diagnosis of cancer, or appearing very early in the management of the neoplasm

Targeting the MET-Signaling Pathway in Non- Small-Cell Lung Cancer: Evidence to Date

International audienceThe c-MET proto-oncogene (MET) plays an important role in lung oncogenesis, affecting cancer-cell survival, growth and invasiveness. The MET receptor in non-small–cell lung cancer (NSCLC) is a potential therapeutic target. The development of high-output next-generation sequencing techniques has enabled better identification of anomalies in the MET pathway, like the MET exon-14 (METex14) mutation. Moreover, analyses of epidermal growth factor-receptor (EGFR) and mechanisms of resistance to tyrosine-kinase inhibitors (TKIs) demonstrated the importance of MET amplification as an escape mechanism in patients with TKI-treated EGFR-mutated NSCLCs. This review summarizes the laboratory findings on MET and its anomalies, trial results on METex14 alterations and MET amplification in non-EGFR mutated NSCLCs, and acquired resistance to TKI in EGFR-mutated NSCLCs. The outcomes of the first trials with anti-MET agents on non-selected NSCLC patients or those selected for MET overexpression were disappointing. Two situations seem the most promising today for the use of anti-MET agents to treat these patients: tumors harboring METex14 and those EGFR-sensitive mutation mutated under TKI-EGFR with a MET-amplification mechanism of resistance or EGFR-resistance mutation

New PDL1 inhibitors for non-small cell lung cancer: focus on pembrolizumab

The advent of immune-checkpoint inhibitors during the past decade represents a major advancement in the treatment of non-small cell lung cancer (NSCLC) with personalized treatment. Platinum-based chemotherapy has reached its efficacy threshold, with its use remaining limited by its toxicity. For NSCLC, inhibitors of the PD1 protein and its ligand PDL1 show promising clinical activity and induce durable responses in patients with advanced disease. The US Food and Drug Administration has approved pembrolizumab for treatment-naïve metastatic NSCLC with $50$1% PDL1 expression after progression following first-line platinum-based doublet chemotherapy. In 2017, it also authorized the first-line combination of pembrolizumab and carboplatin-pemetrexed chemotherapy without selection based on PDL1 expression, but European health authorities are still waiting for the results of a Phase III trial. In this review, the clinical results of published and ongoing studies evaluating pembrolizumab for advanced NSCLC are analyzed and the potential role of PDL1 as a factor predictive of overall responses addressed