[Human immunodeficiency virus and venous thromboembolism: Role of direct oral anticoagulants]. / Modalités du traitement de la maladie veineuse thromboembolique du patient VIH par les anticoagulants oraux directs.

Nowadays, thanks to highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV) infection is transforming into a chronic disease. The life expectancy of people living with HIV (PWH) has increased, as well as their risk of developing several co-morbidities, in particular cardiovascular diseases. In addition, the incidence of venous thromboembolism (VTE) is increased in PWH with a 2 to 10 times higher incidence when compared to the general population. Over the last decade, direct oral anticoagulants (DOACs) have been widely used in the treatment and prevention of VTE and non-valvular atrial fibrillation. DOACs are characterized by a rapid onset of activity, a predictable response and a relatively wide therapeutic window. Nevertheless, drug interactions exist between HAART and DOACs, exposing PWH to a theoretically increased bleeding or thrombotic risk. DOACs are substrates of the transport protein P-glycoprotein and/or of isoforms of cytochromes P450 pathway, which can be affected by some antiretroviral drugs. Limited guidelines are available to assist physicians with the complexity of those drug-drug interactions. The aim of this paper is to provide an updated review on the evidence of the high risk of VTE in PWH and the place of DOAC therapy in this population.

Subarachnoid-pleural fistula: To drain or not to drain.

Subarachnoid-pleural fistula (SPF) is a rare complication of spine surgery with a transthoracic approach. The outcome of such an injury is affected by not only the pulmonary status due to the pleural effusion but also the neurological one, secondary to the intracranial hypotension. After reviewing the few published cases of SPF, the journey to diagnosis seams heterogenous and the management plan non-uniform. We report the case of a 48-year old women who underwent a right transthoracic discectomy that was complicated by an SPF. The diagnosis, although suspected perioperatively, was established with the gathering of an abundant post-operative pleural effusion, a subdural hematoma on head Computerized Tomography after drainage and Cerebro-Spinal Fluid markers present in the pleural fluid. The defect was effectively corrected with a radiological procedure. We compare our clinical and paraclinical findings and management plans to those reported in the few other published cases of SPF.

[Evaluation of the use of a simulation software in the learning of cardiopulmonary auscultation in undergraduate medical students]. / Evaluation de l'utilisation d'un logiciel de simulation dans l'apprentissage de l'auscultation cardio-pulmonaire chez les étudiants en premier cycle d'études médicales.

INTRODUCTION: Medsounds™ software allows to create an auscultation learning platform, by providing real pre-recorded cardiopulmonary sounds on virtual chests. The study aimed at comparing the skills in cardiopulmonary auscultation between students who benefited from this platform and students who did not have access to it. METHODS: A controlled trial was conducted with 2nd year medical students randomised into three groups. Groups A, B and C received 10 h of cardiopulmonary clinical training. In addition, group B benefited from an online access to the educative platform, and group C had a demonstration of the platform during their clinical training, then an online access. The main outcome was a 3-point multiple-choice questionnaire based on 2 original case vignettes about the description of cardiopulmonary sounds. The secondary outcome was the faculty exam on high-fidelity cardiopulmonary simulator. RESULTS: Groups A and B included 127 students, and group C 117. Students in group C had a significantly higher score than those in group A (1.72/3 versus 1.48/3; p = 0.02), without difference between the groups B and C. Students who actually had a demonstration of the platform and used it at home had a higher score than those who did not use it (1.87 versus 1.51; p = 0.01). Students who had a demonstration of the platform before using it performed a better pulmonary examination on high-fidelity simulators. CONCLUSION: The supervised use of an online auscultation simulation software in addition to the traditional clinical training seems to improve the auscultation performances of undergraduated medical students.

Safety of multidetector computed tomography pulmonary angiography to exclude pulmonary embolism in patients with a likely pretest clinical probability.

Essentials Safety of computed tomography (CTPA) to exclude pulmonary embolism (PE) in all patients is debated. We analysed the outcome of PE-likely outpatients left untreated after negative CTPA alone. The 3-month venous thromboembolic risk in these patients was very low (0.6%; 95% CI 0.2-2.3). Multidetector CTPA alone safely excludes PE in patients with likely clinical probability. SUMMARY: Background In patients with suspected pulmonary embolism (PE) classified as having a likely or high pretest clinical probability, the need to perform additional testing after a negative multidetector computed tomography pulmonary angiography (CTPA) finding remains a matter of debate. Objectives To assess the safety of excluding PE by CTPA without additional imaging in patients with a likely pretest probability of PE. Patients/Methods We retrospectively analyzed patients included in two multicenter management outcome studies that assessed diagnostic algorithms for PE diagnosis. Results Two thousand five hundred and twenty-two outpatients with suspected PE were available for analysis. Of these 2522 patients, 845 had a likely clinical probability as assessed by use of the simplified revised Geneva score. Of all of these patients, 314 had the diagnosis of PE excluded by a negative CTPA finding alone without additional testing, and were left without anticoagulant treatment and followed up for 3 months. Two patients presented with a venous thromboembolism (VTE) during follow-up. Therefore, the 3-month VTE risk in likely-probability patients after a negative CTPA finding alone was 2/314 (0.6%; 95% confidence interval [CI] 0.2-2.3%). Conclusions In outpatients with suspected PE and a likely clinical probability as assessed by use of the simplified revised Geneva score, CTPA alone seems to be able to safely exclude PE, with a low 3-month VTE rate, which is similar to the VTE rate following the gold standard, i.e. pulmonary angiography.

Performance of the age-adjusted cut-off for D-dimer in patients with cancer and suspected pulmonary embolism.

BACKGROUND: Cancer patients frequently present with suspected pulmonary embolism (PE). The D-dimer (DD) test is less useful in excluding PE in cancer patients due to the lower specificity. In the general population, the age-adjusted cutoff for DD combined with a clinical decision rule (CDR) improved specificity in the diagnosis of PE. OBJECTIVES: To evaluate the safety and efficacy of the age-adjusted cutoff (defined as age∗10µg/L in patients >50years) combined with a CDR for the exclusion of PE in cancer patients. METHODS: We conducted a prospective study to evaluate the age-adjusted cutoff in patients with suspected PE. Here we report a post-hoc analysis on the performance of the age-adjusted cutoff in patients with and without cancer. The primary outcome was the rate of venous thromboembolic events (VTE) during three-month follow-up. RESULTS: Of 3324 patients with suspected PE, 429 (12.9%) patients had cancer. The prevalence of PE was 25.2% in cancer patients and 18% in patients without cancer (p<0.001). Among cancer patients with an unlikely CDR, 9.9% had a DD <500µg/L as compared with 19.7% using the age-adjusted cutoff. In patients without cancer, these rates were 30.1% and 41.9%. The proportion of cancer patients in whom PE could be excluded by CDR and DD doubled from 6.3% to 12.6%. No VTE occurred during three-month follow-up (failure rate 0.0% (95% CI 0.0-6.9%)). CONCLUSION: Compared with the conventional cutoff, the age-adjusted D-dimer cutoff doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and DD without imaging.

PO-29 - Age-adjusted D-dimer cutoff level increases the number of cancer patients in who pulmonary embolism can be safely excluded without CT-PA imaging: The ADJUST-PE cancer substudy.

INTRODUCTION: Patients with cancer frequently present with suspected pulmonary embolism (PE). The D-dimer test is less useful to rule out PE in cancer patients due to a lower specificity, whereas the safety of the combination of a clinical decision rule (CDR) and D-dimer test to rule out PE in these patients is unclear. In the general population, use of an age-adjusted cutoff for D-dimer in combination with a CDR has been shown to improve specificity in the diagnosis of PE. AIM: We prospectively analysed the safety and efficacy of the age-adjusted D-dimer (defined as age×10 in patients >50 years) combined with CDR for the exclusion of PE in patients with cancer. MATERIALS AND METHODS: We conducted a multicenter multinational prospective management outcome study in 19 centers in Belgium, France, The Netherlands and Switzerland, the ADJUST-PE study, to validate an age-adjusted D-dimer cut-off in patients with suspected PE. The performance of the age-adjusted D-dimer cut-off and CDR was compared between patients with and without cancer. The primary outcome was the rate of adjudicated thromboembolic events during three-month follow-up. RESULTS: Of the 3,324 patients with suspected PE, 429 (12.9%) patients had cancer. Cancer patients were older and more often had surgery or immobilisation. The prevalence of PE was 108/429 (25.2%) in cancer patients and 522/2894 (18%) in patients without cancer, p<0.001. Among cancer patients with an unlikely CDR, 27/274 (9.9%) had a D-Dimer <500 µg/L as compared with 19.7% using the age-adjusted D-dimer cut-off; in patients without cancer, these rates were 30.1% and 41.9%, respectively. The percentage of cancer patients in whom PE could be excluded based on CDR and age-adjusted D-dimer doubled from 6.3% to 12.6%. None of these cancer patients had a venous thromboembolic event during three-month follow-up, thus the failure rate was 0.0% (95% CI 0.0-6.9%). CONCLUSIONS: Compared with the usual cut-off, the age-adjusted D-dimer cut-off doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and D-dimer without need for CTPA imaging.

Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients.

UNLABELLED: ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE. BACKGROUND: Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. METHODS: Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed. RESULTS: In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4). CONCLUSION: These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.

Pulmonary embolism: whom to discharge and whom to thrombolyze?

Patients with pulmonary embolism can be divided in two groups according to their risk of death or major complication: a small group of high-risk patients defined by the presence of systemic hypotension or cardiogenic shock and a large group of normotensive patients. Among normotensive patients, further risk stratification, based on clinical grounds alone or on the combination of clinical data, biomarkers, and imaging tests, allows selection of low-risk patients and intermediate-risk patients. The safety of outpatient treatment for low-risk patients has been established mainly on the basis of retrospective and prospective cohorts using different selection tools. In most studies, about 50% of the patients have been safely treated at home. Although thrombolytic therapy has a favorable benefit to risk profile in patients with high-risk pulmonary embolism, the risk of major and especially intracranial bleeding outweighs the benefits in terms of hemodynamic decompensation in patients with intermediate-risk pulmonary embolism.

Knowledge of the diagnostic algorithm for pulmonary embolism in primary care.

BACKGROUND: Diagnostic algorithms for pulmonary embolism (PE) have been validated in patients attending hospital emergency departments. However, general practitioners (GPs) are often the professionals of first resort for the majority of non-critical cases of PE. AIM: To evaluate the knowledge of the diagnostic algorithm for PE among GPs in France. DESIGN AND SETTING: Questionnaire-based survey of GPs with a private practice. METHOD: All GPs in the study area were sent a questionnaire including several questions on the diagnosis of PE and two clinical cases scenario with suspected PE. Factors associated with knowledge of the diagnostic algorithm were analysed by univariate and multivariate analyses. RESULTS: Five-hundred and eight questionnaires were distributed and 155 (30.5%) were available for analysis. Only 55% of the GPs did know about clinical scores for the assessment of clinical probability of PE and 42% of the GPs were aware that clinical probability is needed to interpret the result of D-dimer testing. Forty GPs (26%) gave valid responses to both clinical cases, 54 GPs (35%) had one valid case out of the two and 61 (39%) gave invalid responses to both clinical cases. Participation in specific training on PE was significantly associated with valid responses to the two clinical cases in multivariate analysis (p<0.017). CONCLUSION: The majority of GPs were unaware of the diagnostic algorithm for PE. Clinical probability was rarely assessed and knowledge about D-dimers was poor. Specific training on PE and greater awareness of clinical probability scores may promote knowledge of PE algorithm diagnosis.

Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Prevalence of CTEPH after pulmonary embolism.

Chronic thromboembolic pulmonary hypertension (CTEPH) has been estimated to occur in 0.1-0.5% of patients who survive a pulmonary embolism (PE), but more recent prospective studies suggest that its incidence may be much higher. The absence of initial haemodynamic evaluation at the time of PE should explain this discrepancy. We performed a prospective multicentre study including patients with PE in order to assess the prevalence and to describe risk factors of CTEPH. Follow-up every year included an evaluation of dyspnea and echocardiography using a predefined algorithm. In case of suspected CTEPH, the diagnosis was confirmed using right heart catheterisation (RHC). Signs of CTEPH were searched on the multidetector computed tomography (CT) and echocardiography performed at the time of PE. Of the 146 patients analysed, eight patients (5.4%) had suspected CTEPH during a median follow-up of 26 months. CTEPH was confirmed using RHC in seven cases (4.8%; 95%CI, 2.3 - 9.6) and ruled-out in one. Patients with CTEPH were older, had more frequently previous venous thromboembolic events and more proximal PE than those without CTEPH. At the time of PE diagnosis, patients with CTEPH had a higher systolic pulmonary artery pressure and at least two signs of CTEPH on the initial CT. After acute PE, the prevalence of CTEPH appears high. However, initial echocardiography and CT data at the time of the index PE suggest that a majority of patients with CTEPH had previously unknown pulmonary hypertension, indicating that a first clinical presentation of CTEPH may mimic acute PE.

[The role of atypical microorganisms and viruses in severe acute community-acquired pneumonia]. / Place des micro-organismes atypiques et des virus dans les pneumonies aiguës communautaires sévères.

Usually, intensivists do not focus on atypical bacteria and viruses in severe community-acquired pneumonia (CAP). Only Legionella pneumophila and influenza virus, following the recent H1N1 influenza pandemic, are routinely suggested as responsible agents. However, CAP due to atypical bacteria may represent up to 44% of all CAP. Viral CAP is considered less severe than the usual bacterial ones, although 25% of them warrant hospitalization and 15% result in severe sepsis. Even though L. pneumophila is the most frequently atypical pathogen involved in severe cases, Mycoplasma pneumoniae may be responsible for multiorgan failure. To date, tools including detection of Legionella antigen in urine and Mycoplasma using polymerase chain reaction (PCR) allow rapid and accurate diagnosis. The treatment is based on macrolides and fluoroquinolones that can be associated in severe Legionnaire diseases. The presence of virus in CAP, either alone or in association with bacteria, has been demonstrated using molecular biology tests. These techniques also allowed the identification of several new viruses in CAP. However, the exact role of these detected viruses in CAP as well as the efficiency of antiviral therapy still represent major unsolved concerns.

Risk factors and clinical outcome of unsuspected pulmonary embolism in cancer patients: a case-control study.

BACKGROUND: Little is known about the risk factors and outcome of unsuspected pulmonary embolism (UPE) in cancer patients. OBJECTIVES: To assess the risk factors and outcome of UPE in cancer patients. METHODS: The charts of 66 patients diagnosed with UPE were reviewed. Two control groups were selected: 132 cancer patients without pulmonary embolism (PE) and 65 cancer patients with clinically suspected PE. Variables associated with UPE were identified by multivariable analysis. Six-month survival and recurrent venous thromboembolism were compared by use of Cox proportional analysis. RESULTS: Twenty-seven (40.9%) patients with UPE had symptoms suggesting PE. Adenocarcinoma (odds ratio [OR] 4.45; 95% confidence interval [CI] 1.98-9.97), advanced age (OR 1.18; 95% CI 1.02-1.38), recent chemotherapy (OR 4.62; 95% CI 2.26-9.44), performance status > 2 (OR 7.31; 95% CI 1.90-28.15) and previous venous thromboembolism (OR 4.47; 95% CI 1.16-17.13) were associated with UPE. When adjusted for tumor stage and performance status, 6-month mortality did not differ between patients with UPE and patients without PE (hazard ratio 1.40; 95% CI 0.53-3.66; P = 0.50). Patients with UPE were more likely to have central venous catheters and chemotherapy and less likely to have proximal clots than patients with clinically suspected PE. Recurrent venous thromboembolism occurred in 6.1% and 7.7% of patients with UPE and symptomatic PE, respectively. CONCLUSION: UPE is not associated with an increased risk of death. Patients with clinically suspected PE and those with UPE have similar risks of recurrent venous thromboembolism.

Diagnostic accuracy of magnetic resonance imaging for an acute pulmonary embolism: results of the 'IRM-EP' study.

BACKGROUND: Magnetic resonance imaging (MRI) has not been validated as an alternative diagnostic test to computed tomography angiography (CTA) in patients with suspicion of a pulmonary embolism (PE). OBJECTIVES: To evaluate performance of current MRI technology in diagnosing PE, in reference to a 64-detector CTA. PATIENTS/METHODS: Prospective investigation including 300 patients with a suspected PE, referred for CTA after assessment of clinical probability and D-dimer testing. MRI protocol included unenhanced, perfusion and angiographic sequences. MRI results were interpreted by two independent readers, to evaluate inter-reader agreement. Sensitivity and specificity were evaluated globally and according to PE location and to clinical probability category. RESULTS: Of 300 enrolled patients, 274 were analyzed and 103 (37.5%) had a PE diagnosed by CTA. For patients with conclusive MRI results (72% for reader 1, 70% for reader 2), sensitivity and specificity were 84.5% (95% confidence interval [CI], 74.9-91.4%) and 99.1% (95% CI, 95.1-100.0%), respectively, for reader 1, and 78.7% (95% CI, 68.2-87.1%) and 100% (95% CI, 96.7-100.0%) for reader 2. After exclusion of inconclusive MRI results for both readers, inter-reader agreement was excellent (kappa value: 0.93, 95% CI: 0.88-0.99). Sensitivity was better for proximal (97.7-100%) than for segmental (68.0-91.7%) and sub-segmental (21.4-33.3%) PE (P < 0.0001). Sensitivity was similar for both readers within each clinical probability category. CONCLUSIONS: Current MRI technology demonstrates high specificity and high sensitivity for proximal PE, but still limited sensitivity for distal PE and 30% of inconclusive results. Although a positive result can aid in clinical decision making, MRI cannot be used as a stand-alone test to exclude PE.

[Update on diagnosis and treatment of high-risk pulmonary embolism]. / Prise en charge diagnostique et thérapeutique de l'embolie pulmonaire grave.

INTRODUCTION: High-risk pulmonary embolism (PE) is associated with a significant early mortality, approaching 25%, and is defined by the presence of cardiogenic shock. STATE OF THE ART: The high early mortality rate for patients with shock requires a rapid diagnostic approach with bedside tests. Right ventricular dilatation assessed by echocardiography in patients with a high clinical probability for PE confirms the diagnosis without the need for additional testing. Spiral CT pulmonary angiography remains the first line investigation for patients without shock. Anticoagulant treatment should be started as soon as pulmonary embolism is suspected. Fibrinolytic therapy is recommended for patients with high-risk pulmonary embolism. The prognostic value of cardiac biomarkers, such as B natriuretic peptide, troponins and right ventricular dilatation for early mortality has been demonstrated. These markers permit the identification of an intermediate risk group of patients with normotensive pulmonary embolism and prognostic scores have been developed. PERSPECTIVES: It remains to be established whether fibrinolysis can have a clinical benefit or reduce mortality in patients with intermediate risk pulmonary embolism. A large randomised placebo-controlled study is currently under way to answer this question. Further studies will more clearly define the role of various predictive rules to identify patients requiring hospital care or those who should be considered for outpatient management.

[Sensory-nerves and airway inflammation: interaction with beta-2-adrenoceptor agonists]. / Le système neurosensoriel et l'inflammation bronchique: interaction avec les agonistes des récepteurs beta-2-adrénergiques.

beta-2-adrenoceptor agonists are used as bronchodilatators in asthma and chronic obstructive pulmonary disease (COPD) treatment. However, regular single use of these molecules may enhance bronchial hyperresponsiveness, a component of asthma and COPD. Indeed, pathophysiologic mechanisms underlying bronchial hyperresponsiveness remain unclear. Sensory nerves have been recently found in the respiratory tract and they play an important role in the regulation of bronchial responsiveness through the release of tachykinins and activation of vanilloid TRPV1 (Transient Receptor Potential Vanilloid 1) receptors. The purpose of this review is to highlight the most recent findings concerning the interactions between beta-2-adrenoceptor agonists and bronchial sensory nerves.