Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at... Show moreIntermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure <= 110mm Hg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations. Show less
Mahe, I.; Agnelli, G.; Ay, C.; Bamias, A.; Becattini, C.; Carrier, M.; ... ; Laporte, S. 2021
Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them... Show moreCancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed >= 6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (beta=80%; alpha one-sided=0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding. Show less
Background: We previously described that adenoid tissue in children with chronic otitis media (COM) contained more mucosal biofilms than adenoid tissue removed for hypertrophy.Aims/objectives: The... Show moreBackground: We previously described that adenoid tissue in children with chronic otitis media (COM) contained more mucosal biofilms than adenoid tissue removed for hypertrophy.Aims/objectives: The aim of the second part was to characterize nasopharyngeal microbiota and explore virulence of the most common middle ear pathogens.Material and methods: Bacteriological analysis was performed following a culture-based approach on the samples recovered from 30 patients of COM group (15 biofilm-positive and 15 biofilm-negative) and from 30 patients of a control group (15 biofilm-positive and 15 biofilm-negative). Virulence factors of Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae were investigated.Results: The most frequent species were Firmicutes followed by Proteobacteria and Actinobacteria. The presence of biofilm was statistically associated with an increase of the number of bacterial species and Firmicutes phylum regardless of the condition (case/control). No virulence factors associated with invasive isolates were found for the most common middle ear pathogens.Conclusions and significance: This case-control study demonstrated that the presence of COM plus biofilm was associated with a given microbiota which contained more Firmicutes. Our study allows a better understanding of physiopathological mechanisms involved in chronic otitis media and paves the way for further investigations. Show less
IntroductionSymptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which... Show moreIntroductionSymptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined.MethodsIn a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) post-PE impairment' (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II-IV.ResultsConfirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up.ConclusionsCTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae. Show less
Kania, R.; Vironneau, P.; Dang, H.; Bercot, B.; Cambau, E.; Verillaud, B.; ... ; Abbeele, T. van den 2019
BACKGROUND\nMATERIAL AND METHODS\nRESULTS\nCONCLUSIONS AND SIGNIFICANCE\nBiofilms are communities of bacteria embedded in a self-produced glycocalyx matrix. Adenoids have been shown to harbor... Show moreBACKGROUND\nMATERIAL AND METHODS\nRESULTS\nCONCLUSIONS AND SIGNIFICANCE\nBiofilms are communities of bacteria embedded in a self-produced glycocalyx matrix. Adenoids have been shown to harbor bacterial biofilms. Aim/objectives: To compare the prevalence of biofilms in adenoid of children with chronic otitis media (COM) (group1) versus a control group without any COM (group 2) having adenoids removed because of hypertrophy.\nOne hundred and three children were prospectively enrolled in this case-control study, group 1 (n = 52) and group 2 (n = 51). The main outcome measurement was the prevalence of biofilm in adenoidectomy specimens analyzed using confocal laser scanning microscopy. Children in group 1 who had middle ear (ME) effusion and requiring the insertion of a tympanostomy tube underwent biopsy of the ME mucosa and effusion sampling.\nBiofilms were found in adenoids' specimens of both groups and in the ME biopsy and effusion. The biofilm prevalence in adenoids was 63.5% (33/52) in group 1 and 47.1% (24/51) in group 2. Day nursery and previous antibiotics intake were significantly more frequent in group 1 than in group 2.\nThis case-control study demonstrates that adenoid tissue in children with COM contains more mucosal biofilms than adenoid tissue removed for hypertrophy. Biofilm was seen in ME biopsies and effusion. Show less
