[Complement inhibitors: A global point of view]. / Les inhibiteurs du complément : une vue d'ensemble.

Innate immunity, and more specifically the complement system, has arised renewed interest in the medical field in recent years. Many innovative complement-inhibiting drugs have appeared, acting at various levels of the complement cascade. These drugs have made it possible to transform poor prognosis of certain diseases. Many of them are currently being tested in clinical trials for various indications. Many questions appear about their optimal use and their future indications. This article recalls the fundamental role of the complement system in the human organism. It then discusses the diseases in which the complement is involved on the pathophysiological level. The third part details the different classes of complement inhibitors and briefly recalls the indications for which these treatments seem the most promising. Finally, we end with a discussion that highlights the different aspects and questions induced by these new treatments.

[Place of internal medicine specialists in inpatient unprogrammed care of adult patients in France: A survey of in training and senior internal medicine specialists]. / Place des internistes dans la prise en charge hospitalière de la médecine adulte non programmée : enquête auprès des internistes en formation et en exercice.

INTRODUCTION: French internal medicine specialists are trained in clinical immunology and rare diseases as well as frequent ones. The latest activity is rarely highlighted by practitioners themselves and their representative authorities. Frequent diseases care in French hospitals are also the tasks of physicians without internal medicine specialty, mostly trained in general medicine, who practice in departments carrying various names. METHODS: We conducted a survey to estimate the part of frequent diseases' care and unplanned hospital medicine in the practice of specialists and residents in internal medicine in France, and its designation, through two surveys released by the "Collège National Professionnel de Médecine Interne" (for the internal medicine specialists), and the "Amicale des Jeunes Internists" (for the internal medicine residents). RESULTS: A total of 180 and 247 responses were obtained among the residents and the specialists, respectively, representing 31.3% and 24.8% of the internal medicine specialist's workforce. The most suitable qualifier for frequent diseases' care and unplanned hospital medicine, primarily post-emergency, was "general hospital medicine" for 48.9% of the residents and "general internal medicine" for 35.6% of the specialists. Unplanned hospital medicine was considered to represent a large part of the internal medicine activity by 66.7% and 64.7% of residents and specialists, respectively. A 50% and more hourly part of the activity devoted to it was reported by 71.4% of the residents and 76.1% of the specialists. General hospital medicine was reported to be distinct from internal medicine-clinical immunology by 46.1% of the residents and 47.4% of the specialists. CONCLUSION: French internists devote a large part of their activities to frequent diseases' care and unscheduled medicine, the name of which was not consensual. However, their work could not be summarized to it, often involving a specific activity named internal medicine - clinical immunology.

Outcomes in patients with acute pulmonary embolism and patent foramen ovale: Findings from the RIETE registry.

INTRODUCTION: An increased risk of ischemic stroke in patients with acute pulmonary embolism (PE) and patent foramen ovale (PFO) was reported but few data exist regarding prognostic outcomes of those patients. MATERIAL AND METHODS: Using data in the RIETE registry, we compared the characteristics, therapeutic approaches and outcomes of patients with PE according to the presence or absence of PFO. RESULTS: From August 2016 to January 2020, 4148 patients with acute PE were enrolled. Of these, 2775 (67%) had no transthoracic echocardiogram (TTE), 993 (24%) underwent TTE but had no reported results on PFO. Among the remaining 380 patients, 287 (74%) did not have PFO and 93 (26%) had PFO. Patients with PFO were more likely to have chronic heart failure, prior myocardial infarction or ischemic stroke than those without PFO. Patients with PFO had a higher rate of subsequent ischemic stroke than those without PFO (hazard ratio (HR): 9.28; 95% CI: 1.83-69.1), than those with TTE but no data on PFO (HR: 10.1; 95% CI: 2.56-42.4) or without TTE (HR: 9.78; 95% CI: 3.02-28.4). On multivariable analysis, patients with PFO were at increased risk for subsequent ischemic stroke than those without PFO (HR: 8.96; 95% CI: 1.68-47.7). CONCLUSIONS: PFO was searched in a minority of patients with an acute PE in real life setting. Subject to possible selection and measurement biases, our results confirmed a higher risk of ischemic stroke in PE patients with PFO compared to those without PFO. This association warrants further investigation before determining the best therapeutic option in patients with acute PE and concomitant PFO.

[Pre-eclampsia prevention in 2018 in general population and in lupic women: At the dawn of a personalized medicine?] / Prévention de la pré-éclampsie en 2018 en population générale et chez la femme lupique : à l'aube d'une médecine personnalisée ?

Pre-eclampsia prevention represents a major public health issue, as this vasculo-placental disorder generates a great burden of foeto-maternal morbi-mortality. Aspirin has proved its efficacy in primary and secondary pre-eclampsia prevention, especially when it is given at 150mg per day bedtime before 15 weeks of gestation to high-risk women. In the English trial ASPRE, high-risk women were identified by an algorithm taking into account angiogenic biomarkers ascertained at the end of first trimester of pregnancy. This article focuses on physiopathological mechanisms and risk factors of pre-eclampsia and on the interest of early angiogenic biomarkers dosing during pregnancy, for the assessment of pre-eclampsia risk. Unlike Great Britain or Israel, cost-effectiveness of this algorithm in general population has not been assessed in France. Finally, systemic lupus erythematous is at high risk of vasculo-placental disorders. Although few studies of angiogenic biomarkers dosing during lupus pregnancies identified a correlation between high sFlt1 levels at the end of first trimester and subsequent onset of severe vasculo-placental disorders, with a very good negative predictive value of sFtl1. Angiogenic biomarkers ascertainment for screening of vasculo-placental disorders in pregnant women with systemic lupus erythematous could allow targeting at best women needing an aspirin treatment and a closer monitoring.

Antipsychotic drugs and the risk of recurrent venous thromboembolism: A prospective cohort study.

BACKGROUND: Numerous studies have suggested that antipsychotic drugs are associated with an increased risk for a first episode of venous thromboembolism (VTE). However, after anticoagulation discontinuation, the impact of antipsychotic drugs on the risk of recurrent VTE (rVTE) remains unknown. OBJECTIVE: To estimate the risk of rVTE in association with antipsychotic drugs. METHODS: Between May 2000 and December 2012, we included all consecutive patients with a first unprovoked symptomatic VTE and who discontinued anticoagulation. During follow-up, exposure to antipsychotic drugs was systematically assessed. RESULTS: A total of 736 patients with a first unprovoked symptomatic VTE were followed-up during a median period of 27.0 months (interquartile range (IQR) 6.2-60.0). Patients' median age was 66.0 years (IQR 49.0-76.0), 404 (54.9%) were men, and 61 (8.3%) were exposed to antipsychotics during follow-up. The incidence rate of r VTE was 12.1% person-year (95% CI 7.2-20.5) in antipsychotics users compared with 8.3% person-year (95% CI 7.1-9.8) in non-users (p = 0.20). Multivariate analysis showed a significant increased risk of recurrence associated with antipsychotic exposure (adjusted hazard ratio 1.9, 95% CI 1.1-3.3). CONCLUSIONS: In this cohort study, exposure to antipsychotic drugs was found to be associated with an increased risk of rVTE among patients with a previous first unprovoked symptomatic VTE and who discontinued anticoagulation. Larger studies are needed to confirm and further explore this association.

Body mass index, a major confounder to insulin resistance association with unprovoked venous thromboembolism. Results from the EDITH case-control study.

Shared risk factors help explain the association between venous thromboembolism (VTE) and atherothrombosis. The potential association between insulin resistance and VTE has been poorly evaluated. Thus, we aimed to assess the association between insulin resistance and VTE in the EDITH hospital-based case-control study. Between May 2000 and December 2004, 677 patients with unprovoked VTE and their age- and sex-matched controls were included. Fasting glycaemia and insulinaemia were measured and insulin resistance was estimated with the homeostasis model assessment of insulin resistance (HOMA-IR) equation. The association between HOMA-IR and VTE was determined in non-diabetic patients in a quintile-based analysis. A total of 590 non-diabetic cases (median age 73.0 years, 255 men) and 581 non-diabetic controls (median age 72.0 years, 247 men) were analysed. There was a trend for a higher median level of HOMA-IR index in cases than in controls (1.21 [interquartile range 0.84-2.10] vs1.19 [interquartile range 0.72-2.02], p=0.08). The unadjusted analysis showed an increased risk of unprovoked VTE associated with increasing HOMA-IR (odds ratio [OR] 1.53; 95% confidence interval [CI] 1.00-2.34 for the highest quintile of HOMA-IR compared with the first quintile). Adjustment for lipid lowering drugs and antiplatelet agents use slightly modified the association (OR 1.51; 95% CI 0.97-2.34). When body mass index was added in the adjusted model, HOMA-IR was no longer associated with VTE (OR 1.08; 95% CI 0.67-1.73). Our results highlight the role of body mass index in the association between cardiovascular risk factors and VTE.

Assessment of activated protein C resistance using a new and rapid venom-based test: STA Staclot APC-R.

Activated protein C (APC) resistance is related to a single point mutation in the factor V gene (FV:Q506) and appears to be the most common inherited risk factor for venous thromboembolism. A reliable screening test is therefore useful. We aimed to evaluate a new APC resistance test, on the basis of the procoagulant activity present in one snake venom of a crotalidae family: STA Staclot APC-R. We studied 36 consecutive patients with an acute deep venous thrombosis (DVT) confirmed by compression ultrasonography and carrying the FV:Q506 allele, assessed by DNA analysis, 103 of their family members and 35 consecutive patients with a proven DVT but who did not carry the FV:Q506 allele. Blood samples were collected within 24 h of admission for the DVT cases and on the day of medical registration for the family members. Tests were performed blind. The STA Staclot APC-R test, using a cut-off value of 0.80, had an overall sensitivity of 100% (95% CI, 95-100) and a specificity of 98.8% (95% CI, 92.0-99.6). An acute thrombosis process did not influence the performance of the test. We conclude that this test is easy and rapid to perform in every day practice and fulfills the criteria for a screening test.

Evaluation of a new, rapid, and quantitative D-Dimer test in patients with suspected pulmonary embolism.

Previous studies have suggested the utility of D-Dimer ELISA assays in eliminating a diagnosis of pulmonary embolism (PE). Our objectives were to evaluate the performance of a new, rapid, quantitative, and automated Liatest D-Dimer Assay in patients with suspected PE. Three hundred eighty-six consecutive patients referred to our institution between March 1992 and December 1996 for clinically suspected PE, with recent clinical signs not exceeding 1 wk, were included in this study. Diagnosis of PE was based on clinical evaluation, radionuclide lung imaging, lower limb examination, and, when required, pulmonary angiography. D-Dimer performances, for both Liatest D-Dimer and standard D-Dimer ELISA (Asserachrom DDi), assays, were assessed at the end of the study. Among the 386 patients tested, 146 (37.8%) were classified as PE-positive. Liatest D-Dimer assay had a 100% sensitivity (95% confidence interval, 97 to 100%) and a negative predictive value of 100% (95% confidence interval, 94 to 100%). A normal result, below the cutoff of 500 ng/ml, occurred in 83 of the 386 (21%) patients. There was a strong agreement between Liatest D-Dimer and Asserachrom DDi analyses. These findings suggest that this rapid, quantitative, and automated D-Dimer assay provides a useful diagnostic tool for the clinician with regard to exclusion of PE.

Evaluation of a new rapid D-dimer assay for clinically suspected deep venous thrombosis (Liatest D-dimer).

In previous studies, enzyme-linked immunosorbent assays (ELISA) for plasma D-dimer analysis have demonstrated high sensitivity, suggesting their potential usefulness in excluding deep venous thrombosis (DVT). We evaluated the usefulness of a new D-dimer test (Liatest D-dimer) for suspected DVT in a prospective study of patients admitted to the hospital because of recent (not exceeding 1 week before admission) clinical signs. Contrast venography or compression ultrasonography or both were performed within 24 hours of admission. A new quantitative determination of D-dimer concentration using a suspension of microlatex particles coated with specific antibodies was tested. A standard plasma D-dimer ELISA measurement was also performed. Of 464 patients, 276 had a proven DVT (distal, 74; proximal, 202). For a cutoff level of 400 ng/mL, sensitivity of the Liatest method in the diagnosis of overall DVT was 94.6% (95% confidence interval, 92.0%-97.0%), and the specificity was 35% (95% confidence interval, 28%-42%). The sensitivity and negative predictive value were 98.5% and 95.6%, respectively, in the diagnosis of proximal DVT, but only 83.8% and 84.6%, respectively, in the diagnosis of distal DVT. This new rapid Liatest D-dimer assay seems to be highly sensitive and could replace the ELISA method in excluding patients with proximal DVT. Both methods provide lower sensitivity for distal DVT.

[Pulmonary embolism and unusual deep venous thrombosis. Report of two cases]. / Embolies pulmonaires et thromboses veineuses profondes inhabituelles. A propos de deux observations.

Contrast venography is the gold standard for the diagnosis of deep vein thrombosis in the lower limb extremities, but it fails to visualize deep veins like deep femoral vein and internal iliac vein. The internal iliac can be examined with duplex scanning if the technique and the examination conditions are correct. As reported in these two cases, thrombosis of these deep veins may lead to pulmonary embolism. The first case is a young female with venous thromboembolic disease in whom internal iliac vein thrombosis was documented only at the second examination. In the second case, deep femoral vein thrombosis appeared early in a comatose young male. This thrombosis may be classified as proximal muscular vein thrombosis. These two cases emphasize the importance of a duplex scanning examination performed with rigorous technique, whose the main limitation being examination conditions.

Diagnostic value of a new sensitive membrane based technique for instantaneous D-dimer evaluation in patients with clinically suspected deep venous thrombosis.

BACKGROUND: Plasma D-Dimer analysis, using ELISA assays, has demonstrated in previous studies a high sensitivity, suggesting its utility in excluding deep venous thrombosis (DVT). AIM: To assess the performance of a new rapid plasma D-Dimer ELISA measurement in suspected DVT patients with recent clinical signs, not exceeding one week. METHODS: A prospective study of patients admitted for a suspected recent DVT. Contrast venography or compression ultrasonography were performed within 24 h of admission. A new membrane based ELISA technique, which uses an immunofiltration and two complementary monoclonal antibodies was tested. Results were expressed as positive or negative. A standard plasma D-Dimer ELISA measurement was also performed. D-Dimer performances were assessed at the end of the study. RESULTS: 265/448 patients had a proven DVT (72 distal, 193 proximal). The sensitivity of the instantaneous method in the diagnosis of overall DVT is 92 +/- 3.4% (95% CI), and specificity is 36.6 +/- 6.9%. Positive predictive value is 67.7 +/- 4.8% and negative predictive value is 76.1 +/- 8.9%. Sensitivity and negative predictive values reach 97.9 and 94.3% in the diagnosis of proximal DVT, but only 76.3 and 79.7% in the diagnosis of distal DVT. Similar results are observed with the standard ELISA method. CONCLUSION: This new rapid plasma D-Dimer measurement appears highly sensitive, and could substitute the older ELISA methods. Both methods provide lower sensitivity in the case of a distal DVT location.

Association between IgM anticardiolipin antibodies and deep venous thrombosis in patients without systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) are at risk of developing deep venous thrombosis (DVT). Should anticardiolipin antibodies (aCL) be detectable, this risk is significantly raised, particularly when these autoanti-bodies are cofactor-dependent. We conducted a cross-sectional study of consecutive unselected outpatients referred for clinical suspicion of DVT, as an attempt to address the following questions: firstly, were aCL antibodies associated with DVT in non-SLE patients? Secondly, was this association related to the cofactor dependence? From March 1992 to February 1994, 208 patients were enrolled in the study. Venography was positive in 110 patients (DVT patients), while the diagnosis of DVT could not be confirmed in the remaining 98 (referred to as disease controls). ACL was measured by ELISA, for IgG and IgM isotypes in two ways: fetal calf serum or bovine serum albumin were used as blocking agents to distinguish between cofactor-dependent and cofactor-independent antibodies. Positive aCL was defined as optical density (OD) values greater than the 95th percentile of OD distribution of 60 healthy controls. We found a high frequency of positive IgG aCL antibodies in both DVT patients and in disease controls (25.5 vs 23.5%). We suggest an association between IgM aCL and DVT. This association was, however, not dependent on the cofactor requirement.

The value of a risk factor analysis in clinically suspected deep venous thrombosis.

BACKGROUND: The value of a risk factor analysis in the presence of a clinically suspected deep venous thrombosis (DVT) has been assessed mainly in inpatient populations. The aim of this prospective study was to evaluate the potential association between DVT and acquired circumstances suspected as risk factors, in a cohort of outpatients with a clinically suspected DVT. METHODS: Consecutive outpatients referred for a clinically suspected DVT, with recent clinical signs, not exceeding 1 week, were included. Before venography, all patients were interviewed by a trained physician to detect the presence of risk factors. RESULTS: From March 1992 to February 1994, 277 patients were included; venography was positive in 162 (58.4%). Five independent variables were significantly associated with the occurrence of DVT; in a multivariate analysis, 64.7% of patients were correctly classified; odds ratios for having DVT in the presence of these underlying conditions were respectively: 1.75 for age over 65 years, 1.68 for prior history of venous thromboembolism, 1.69 for high risk circumstances (any type of surgery or leg trauma within the past 3 months), 5.59 for malignancy, and 2.56 for varicose veins. CONCLUSIONS: In outpatients referred for a clinically suspected DVT, recognition of associated conditions might increase the certainty of the diagnosis.

[Prevention of deep venous thrombosis in medical care]. / Prévention de la thrombose veineuse profonde en milieu médical.

Venous thromboembolism is a frequent and potentially severe ailment in medical patients; the clinical signs are unreliable and as early detection of the thrombosis process by non-invasive techniques is not available, prevention appears to be an alternative. Careful definition of the medical situations at risk from venous thromboembolism is necessary. Age, prior history of venous thromboembolism, and immobilization constitute high risk circumstances. Analysis of the published studies advocates prevention in three circumstances: myocardial infarction, stroke and intensive care. In other cases, further controlled studies, randomized versus placebo, are needed.