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International audience; Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening pulmonary embolism's (PE) complication whose incidence and predictors are not precisely determined.Objective: To determine the frequency and predictors for CTEPH after a first unprovoked PE.Patients/methods: In a randomized trial comparing an additional 18-month warfarin versus placebo in patients after a first unprovoked PE initially treated with vitamin K antagonist for 6 months, we applied recommended CTEPH screening strategies through 8-year follow-up to determine cumulative incidence of CTEPH. CTEPH predictors were estimated using Cox models. Pulmonary vascular obstruction (PVO) and systolic pulmonary arterial pressure (sPAP) at PE diagnosis and 6 months were studied by receiver operating curves analysis. All CTEPH cases and whether they were incident or prevalent were adjudicated.Results: During a median follow-up of 8.7 years, 9 CTEPH cases were diagnosed among 371 patients, with a cumulative incidence of 2.8% (95% confidence interval [CI], 0.95-4.64), and of 1.31% (95%CI, 0.01-2.60) after exclusion of 5 cases adjudicated as prevalent. At PE diagnosis, PVO>45% and sPAP>56mmHg were associated with CTEPH with a hazard ratio (HR) of 33.00 (95%CI 1.64-667.00, p=0.02) and 12.50 (95%CI 2.10-74.80, p65 years, lupus anticoagulant antibodies and non-O blood groups were also predictive of CTEPH. PVO>14% and sPAP>34mmHg at 6-month were associated with CTEPH (HRs 63.90 [95%CI, 3.11-1310.00, p

International audience; Background Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays.Objective To develop a pretest score for HIT.Design Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839).Setting Thirty-one tertiary hospitals in France, Switzerland, and Belgium.Patients Patients tested for HIT antibodies (2280 evaluable), randomly allocated to derivation and validation cohorts.Measurements Independent adjudicators diagnosed HIT based on the prospectively collected data and serotonin release assay results.Results Heparin-induced thrombocytopenia was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic-dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5- to 21-day interval from anticoagulation initiation to suspicion of HIT (4); >= 40% decrease in platelet count over

International audience

Background We aimed to identify risk factors for residual pulmonary vascular obstruction after a first unprovoked pulmonary embolism (PE). Methods Analyses were based on data from the double-blind randomized “PADIS-PE” trial that included 371 patients with a first unprovoked PE initially treated during 6 uninterrupted months; all patients underwent baseline ventilation–perfusion lung scanning at inclusion (i.e., after 6 months of anticoagulation). Each patient's pulmonary vascular obstruction indexes (PVOIs) at PE diagnosis and at inclusion were centrally assessed. Results Among the 371 included patients, residual PVOI was available in 356 patients, and 150 (42.1%) patients had PVOI ≥ 5%. At multivariable analysis, age > 65 years (odds ratio [OR], 2.81, 95% confidence interval [CI], 1.58–5.00), PVOI ≥ 25% at PE diagnosis (OR, 3.53, 95% CI, 1.94–6.41), elevated factor VIII (OR, 3.89, 95% CI, 1.41–10.8), and chronic respiratory disease (OR, 2.18, 95% CI, 1.11–4.26) were independent predictors for residual PVOI ≥ 5%. Patients with ≥ 1 of these factors represented 94.5% (123 patients) of all patients with residual PVOI ≥ 5%. Conclusion Six months after a first unprovoked PE, age > 65 years, PVOI ≥ 25% at PE diagnosis, elevated factor VIII, or chronic respiratory disease were found to be independent predictors for residual pulmonary vascular obstruction. Clinical Trials Registration URL: http://www.controlled-trials.com. Unique identifier: NCT00740883.

Introduction Two meta-analyses showed lower bone mineral density (BMD) in patients with haemophilia (haemophilia type and severity were often not specified) compared with healthy controls. This finding could be related to reduced mobility and sedentary lifestyle, and/or hepatitis C or HIV infection. The aim of this study is to determine osteoporosis prevalence in patients with haemophilia classified in function of the disease type (A or B) and severity, and to evaluate the potential role of regular prophylactic factor replacement (early vs delayed initiation) in preserving or restoring BMD. Methods and analysis The haemoPHILia and ostEoporOSis Study is a prospective, controlled, multicentre study that will include patients in France (13 haemophilia treatment centres), Belgium (1 centre) and Romania (1 centre). In total, 240 patients with haemophilia and 240 matched healthy controls will be recruited (1:1). The primary objective is to determine osteoporosis prevalence in patients with severe haemophilia A and B (HA and HB) without prophylaxis, compared with healthy controls. Secondary outcomes include: prevalence of osteoporosis and osteopenia in patients with mild, moderate and severe HA or HB with prophylaxis (grouped in function of their age at prophylaxis initiation), compared with healthy subjects; BMD in patients with HA and HB of comparable severity; correlation between BMD and basal factor VIII/IX levels and thrombin potential; and quantification of plasmatic markers of bone remodelling (formation and resorption) in patients with haemophilia. Ethics and dissemination The protocol was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2019-A03358-49). The results of this study will be actively disseminated through scientific publications and conference presentations. Trial registration number NCT04384341.

International audience; Background: Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients.Methods: In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin. The primary efficacy outcome of major venous thromboembolism was a composite of symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or venous thromboembolism-related death during the treatment period or asymptomatic proximal deep-vein thrombosis at the end of treatment. A test for superiority was planned if rivaroxaban proved to be noninferior to enoxaparin. For all outcomes, multiple imputation was used to account for missing data. Prespecified safety outcomes included major bleeding (fatal, critical, or clinically overt bleeding or bleeding at the surgical site leading to intervention) and nonmajor clinically relevant bleeding.Results: A total of 3604 patients underwent randomization; 1809 patients were assigned to receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembolism occurred in 4 of 1661 patients (0.2%) in the rivaroxaban group and in 18 of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval, 0.09 to 0.75; P

We aimed to validate the Men Continue and HERDOO2 (HERDOO2), D-dimer, age, sex, hormonal therapy (DASH), and updated Vienna recurrent venous thromboembolism prediction models in a population composed entirely of first unprovoked pulmonary embolism, and to analyze the impact of the addition of the pulmonary vascular obstruction index (PVOI) on score accuracy.Analyses were based on the double-blind, randomized PADIS-PE trial, which included 371 unprovoked pulmonary embolism patients initially treated for 6 months, successively randomized to receive an additional 18 months of warfarin or placebo, and subsequently followed-up for 2 years.The HERDOO2, DASH, and updated Vienna scores displayed C-statistics of 0.61 (95% CI 0.54-0.68), 0.60 (95% CI 0.53-0.66), and 0.58 (95% CI 0.51-0.66), respectively. Only the HERDOO2 score identified low recurrence risk patients (3%/year) after anticoagulation was stopped. When added to either of the prediction models, PVOI measured at pulmonary embolism diagnosis, after 6 months of anticoagulation, or both, improved scores' C-statistics between +0.06 and +0.11 points and consistently led to identifying at least 50% of patients who experienced recurrence but in whom the scores would have indicated against extended anticoagulation.In patients with a first unprovoked pulmonary embolism, the HERDOO2 score is able to identify patients with a low recurrence risk after treatment discontinuation. Addition of PVOI improves accuracy of all scores.URL: http://www.controlled-trials.com. Unique identifier: NCT00740883.

The need to accurately identify cancer outpatients at high risk of thrombotic complications is still unmet. In a prospective, multicenter cohort study (ONCOlogie et Chambres ImPlantables [ONCOCIP]), consecutive adult patients with a solid tumor and implanted port underwent 12-month follow-up. Our primary objective was to identify risk factors for (1) catheter-related thrombosis, defined as ipsilateral symptomatic upper-limb deep-vein thrombosis with or without pulmonary embolism, and (2) venous thromboembolism other than catheter-related, defined as any symptomatic superficial- or deep-vein thrombosis (other than catheter-related) or pulmonary embolism, and incidental pulmonary embolism. All events were objectively confirmed and centrally adjudicated. Rate assessments integrated competing risk of death. Overall, 3032 patients were included (median age: 63 years; women: 58%). The most frequent cancer locations were breast (33.7%), lung (18.5%), and colorectal (15.6%), cancer being metastatic in 43.2% of patients. Most patients (97.1%) received chemotherapy. By 12 months, 48 (1.6%) patients had been lost to follow-up and 656 (24.6%) had died; 3.8% (n = 111) of patients had experienced catheter-related thrombosis, and 9.6% (n = 276) venous thromboembolism other than catheter-related. By multivariate analysis, use of cephalic vein for catheter insertion predicted catheter-related thrombosis, whereas ongoing antiplatelet therapy was protective; risk factors for venous thromboembolism other than catheter-related were advanced age, previous venous thromboembolism, cancer site, and low hemoglobin level or increased leukocyte count before chemotherapy. In conclusion, this large prospective cohort study showed a high rate of venous thromboembolism in patients with a solid tumor and implanted port. Risk factors for catheter-related thrombosis differed from those for venous thromboembolism not catheter-related. This trial was registered at www.clinicaltrials.gov as #NCT02025894.

Introduction VTE-BLEED is a validated score for identification of patients at a 3 to 5-fold increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE; table 1). It is unknown whether VTE-BLEED high-risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score. Methods This was a post-hoc analysis of the randomised double-blind placebo-controlled PADIS-PE trial, in which patients with a first unprovoked pulmonary embolism (PE) initially treated for 6 months were randomised to receive an additional 18-month of warfarin versus placebo. Primary outcome of the current analysis was recurrent VTE during 2-year follow-up after anticoagulant discontinuation, i.e. after the initial 6-month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted on study treatment allocation, was compared between patients in the high- versus low-risk VTE-BLEED group. Results In complete case analysis (n=308; 82.4% of total population), 89 (28.9%) patients were classified as VTE-BLEED high risk. A total of 44 VTE events occurred after anticoagulant discontinuation during 668 patient-years. The cumulative incidence of recurrent VTE was 16.4% (95% CI 10.0–26.1%; 14 events) and 14.6% (95% CI 10.4–20.3%; 30 events) in the high-risk and low-risk VTE-BLEED groups, respectively, for an adjusted Hazard Ratio of 1.16 (95% CI 0.62–2.19; Figure 1). Figure 1 Conclusion In this study, patients with unprovoked PE classified at high risk of major bleeding by VTE-BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.

The optimal duration of anticoagulation after a first episode of unprovoked deep-vein thrombosis is uncertain. We aimed to assess the benefits and risks of an additional 18 months of treatment with warfarin versus placebo, after an initial 6 months of anticoagulation for a first unprovoked proximal deep-vein thrombosis. We conducted a multicenter, randomized, double-blind, controlled trial comparing an additional 18 months of warfarin with placebo in patients with a unprovoked proximal deep-vein thrombosis initially treated for 6 months (treatment period: 18 months; follow up after treatment period: 24 months). The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months. Secondary outcomes were the composite at 42 months, as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. All outcomes were centrally adjudicated. A total of 104 patients, enrolled between July 2007 and October 2013 were analyzed on an intention-to-treat basis; no patient was lost to follow-up. During the 18-month treatment period, the primary outcome occurred in none of the 50 patients in the warfarin group and in 16 out of 54 patients (cumulative risk, 29.6%) in the placebo group (hazard ratio, 0.03; 95% confidence interval: 0.01 to 0.09; P

Background: Diagnosis of heparin-induced thrombocytopenia (HIT) is based on a composite of clinical likelihood and laboratory testing. We aimed to develop a diagnostic score derived from multivariate analysis of clinical features, including platelet count changes, prospectively recorded in patients with suspected HIT. Methods: This multinational observational study (ClinicalTrials.gov no. NCT00748839) included 2280 adult patients with suspected HIT: 1597 (derivation cohort) formed the basis for developing the scoring system, subsequently validated in 683 additional randomly selected patients (validation cohort). HIT was diagnosed by two independent adjudicators based on clinical features, local laboratory data, and the results of a centrally performed serotonin release assay (SRA). Findings: Overall, 56.7% of the patients were treated in an intensive care unit of whom 57.4% received unfractionated heparin; thromboembolism occurred in 12.3%. In the derivation and validation cohorts, 234 (14.7%) and 99 (14.5%) patients, respectively, were diagnosed with HIT. Eight features were positively associated with HIT diagnosis in a multivariate model (in brackets the value assigned for score calculation): unfractionated heparin use (1); therapeutic-dose heparin use (1); cardiac surgery with cardiopulmonary bypass (2); major trauma (3); 5- to 21-day interval from anticoagulant treatment initiation to suspicion of HIT (4); ≥ 40% decrease in platelet count over ≤ 6 days during the last 10 days of anticoagulation exposure (3); thrombotic event, either arterial (3) or venous (3). The C statistic of the model was 0.791 [0.76; 0.82] (p-value 0.70, Hosmer-Lemeshow test). In the validation cohort, the area under the ROC curve was 0.77 [95% CI 0.74-0.80], and HIT prevalence was 2.6% for a score ≤2; 6% for a score of 3–8; and 28.8% for a score >8: Interpretation: This study distinguishes validated clinical features of HIT, permitting improved estimation of its likelihood. Trial Registration: (ClinicalTrials.gov no. NCT00748839) Funding Statement: Programme Hospitalier de Recherche Clinique (French Health Ministry), Sanofi, LFB, Organon SA. Declaration of Interests: Dr. Mullier reports personal fees from Aspen, personal fees from Stago, grants from Werfen, outside the submitted work; Dr. Gruel reports personal fees from Sanofi, personal fees from LFB, other from Stago, personal fees from Aspen, outside the submitted work; . All other authors declare no conflict of interests. Ethics Approval Statement: The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki, Good Clinical Practice, and relevant French, Swiss and Belgian legal and regulatory requirements regarding data protection. The protocol was approved by French, Swiss and Belgian independent ethics committees. All patients received written information about the study, emphasizing their right to refuse participation or to withdraw at any time. As no experimental interventions were induced from the protocol, no written informed consent was required for inclusion.

IntroductionTwo meta-analyses showed lower bone mineral density (BMD) in patients with haemophilia (haemophilia type and severity were often not specified) compared with healthy controls. This finding could be related to reduced mobility and sedentary lifestyle, and/or hepatitis C or HIV infection. The aim of this study is to determine osteoporosis prevalence in patients with haemophilia classified in function of the disease type (A or B) and severity, and to evaluate the potential role of regular prophylactic factor replacement (early vs delayed initiation) in preserving or restoring BMD.Methods and analysisThe haemoPHILia and ostEoporOSis Study is a prospective, controlled, multicentre study that will include patients in France (13 haemophilia treatment centres), Belgium (1 centre) and Romania (1 centre). In total, 240 patients with haemophilia and 240 matched healthy controls will be recruited (1:1). The primary objective is to determine osteoporosis prevalence in patients with severe haemophilia A and B (HA and HB) without prophylaxis, compared with healthy controls. Secondary outcomes include: prevalence of osteoporosis and osteopenia in patients with mild, moderate and severe HA or HB with prophylaxis (grouped in function of their age at prophylaxis initiation), compared with healthy subjects; BMD in patients with HA and HB of comparable severity; correlation between BMD and basal factor VIII/IX levels and thrombin potential; and quantification of plasmatic markers of bone remodelling (formation and resorption) in patients with haemophilia.Ethics and disseminationThe protocol was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2019-A03358-49). The results of this study will be actively disseminated through scientific publications and conference presentations.Trial registration numberNCT04384341.

We aimed to identify risk factors for recurrent venous thromboembolism (VTE) after unprovoked pulmonary embolism.Analyses were based on the double-blind randomised PADIS-PE trial, which included 371 patients with a first unprovoked pulmonary embolism initially treated during 6 months who were randomised to receive an additional 18 months of warfarin or placebo and followed up for 2 years after study treatment discontinuation. All patients had ventilation/perfusion lung scan at inclusion (i.e. at 6 months of anticoagulation).During a median follow-up of 41 months, recurrent VTE occurred in 67 out of 371 patients (6.8 events per 100 person-years). In main multivariate analysis, the hazard ratio for recurrence was 3.65 (95% CI 1.33–9.99) for age 50–65 years, 4.70 (95% CI 1.78–12.40) for age >65 years, 2.06 (95% CI 1.14–3.72) for patients with pulmonary vascular obstruction index (PVOI) ≥5% at 6 months and 2.38 (95% CI 1.15–4.89) for patients with antiphospholipid antibodies. When considering that PVOI at 6 months would not be available in practice, PVOI ≥40% at pulmonary embolism diagnosis (present in 40% of patients) was also associated with a 2-fold increased risk of recurrence.After a first unprovoked pulmonary embolism, age, PVOI at pulmonary embolism diagnosis or after 6 months of anticoagulation and antiphospholipid antibodies were found to be independent predictors for recurrence.

Objective Postoperative lymphopenia has been proposed as a risk factor for postoperative infections but has never been identified as such in a multivariate analysis. Postoperative pneumonia (POP) is one of the most common complications after lung cancer surgery and is associated with a worse outcome. We aimed to evaluate the association between postoperative lymphopenia and POP after lung cancer surgery. Methods Patients admitted for lung cancer surgery (lobectomy, bilobectomy, or pneumonectomy) aged ≥ 18 years and with no history of an immunosuppressive state were eligible for inclusion. Lymphocyte counts were determined in blood drawn on the day before surgery and at postoperative days 1, 3 and 7. POP diagnosis was based on clinical, biological and radiological data. A logistic regression model adjusted on currently described risk factors for POP was used to explain the onset of this condition. Results Two hundred patients were included, of whom 43 (21.5%) developed POP. Preoperative lymphocyte count was 1.8±0.6x10(9) cells/L and 2.0±0.7x10(9) cells/L in patients with and without POP, respectively (P = .091). In both groups, the lymphocyte count nadir occurred at postoperative day 1. In multivariate analysis, lymphopenia at postoperative day 1 was significantly associated with increased risk of POP (odds ratio: 2.63, 95% CI [1.03-5.40]). POP rate at postoperative day 7 was higher in patients presenting low lymphocyte counts (≤1.19x10(9) cells/L) at postoperative day 1 (P = .003). Conclusions Our study showed that lymphopenia following lung cancer surgery was maximal at postoperative day 1 and was associated with POP.

Objectives To evaluate the epileptic, academic, and developmental status at age 7 years in a large population of term-born children who sustained neonatal arterial ischemic stroke (NAIS), and to assess the co-occurrence of these outcomes. Study design A cohort study including 100 term newborns with NAIS was designed. Two infants died during the neonatal period, 13 families were lost to follow-up, and 5 families declined to participate in this evaluation. Thus, 80 families completed the 7-year clinical assessment. Epileptic status, schooling, motor abilities, global intellectual functioning, spoken language, and parental opinions were recorded. Principal component analysis was applied. Results Rates of impaired language, cerebral palsy, low academic skills, active epilepsy, and global intellectual deficiency were 49%, 32%, 28%, 11%, and 8%, respectively. All were highly correlated. Eventually, 59% of children were affected by at least 1 of the aforementioned conditions. In 30% of cases, the viewpoints of health practitioners and parents did not match. Conclusion The prevalence of severe disabilities at 7 years after NAIS is low, but most children exhibit some impairment in developmental profile. Trial registration ClinicalTrials.gov ( NCT02511249 ), Programme Hospitalier de Recherche Clinique Regional (0308052), Programme Hospitalier de Recherche Clinique Interregional (1008026), and EudraCT (2010-A00329-30).

We aimed to measure gastric antral cross-sectional area with ultrasound and estimate the gastric volume of 300 patients before unplanned surgery, fasted for at least six hours. Measurements were successfully recorded in 263 semi-recumbent patients. The median (IQR [range]) area was 333 (241-472 [28-1803]) mm2 and the mean (SD) estimated volume was 45.8 (34.0) ml. The area exceeded 410 mm2 in 92/263 (35%) measurements. Body mass index and morphine administration were associated with larger gastric areas on multivariable linear regression analysis, with beta coefficient (95%CI) 0.02 (0.01-0.04), p = 0.01, 0.23 (0.01-0.46), p = 0.04, respectively. Fasting time was not associated with gastric area and therefore could not substitute for ultrasound measurements in this cohort.

International audience; AIM:Neonatal arterial ischemic stroke (NAIS) results from a focal disruption of the blood flow in a cerebral artery by a not well understood mechanism. Our objective is to describe the acute MRangiography (MRA) findings in infants with an NAIS in the middle cerebral artery (MCA) territory and correlate them with early parenchymal infarcts and motor outcome.METHODS:Among one hundred prospectively followed neonates with NAIS, we studied thirty-seven patients with an MCA infarct explored with circle of Willis MRA. MCA flow characteristics were documented, along with infarct location/extent and motor outcome at age 7 years.RESULTS:Twenty-three (62%) of the children showed arterial changes, all ipsilateral to the NAIS, with occlusion in six, thrombus-type flow defect in nine, and unilateral increased flow in enlarged insular arteries in the remaining eight. There was a statistically significant correlation between parenchymal and arterial MR findings (p=0.0002). A normal MRA had a negative predictive value of 100% (95% CI: 76.8-100) in ruling out a main branch infarct. Patients with abnormal MRA tended to be at increased risk for cerebral palsy (OR=3.1). Occlusion was associated with a worse outcome (p=0.04).INTERPRETATION:MRangiography shows arterial abnormalities suggesting that embolism is a frequent cause of NAIS.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Summary. Background: The management strategies for symptomatic isolated superficial vein thrombosis (SVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) have yet to achieve widespread consensus. Concerns have been raised regarding the usefulness of prescribing anticoagulant treatments to all patients with isolated SVT. Determining the isolated SVT subgroups who have the highest risks of venous thromboembolism (VTE) recurrence (composite of DVT, PE, and new SVT) may facilitate the identification of patients who are likely to benefit from anticoagulant treatment. Design and methods: We performed a pooled analysis on individual data from two observational, multicenter, prospective studies, to determine predictors for VTE recurrence and their impact in an unselected population of symptomatic isolated SVT patients. Results: One thousand and seventy-four cases of symptomatic isolated SVT were followed up at 3 months. VTE recurrence was observed in 3.9% of the patients; 16.2% of the patients did not receive anticoagulants, and 0.6% experienced a VTE recurrence. Cancer, personal history of VTE and saphenofemoral/popliteal involvement significantly increased the risk of subsequent VTE or DVT/PE in univariate analyses. Only male sex significantly increased the risk of VTE or DVT/PE recurrence in multivariate analyses. Twelve per cent of the patients had cancer or saphenofemoral junction involvement, and were at higher risk of DVT/PE recurrence than patients without those characteristics (4.7% vs. 1.9%, P = 0.06). Conclusions: In patients with symptomatic SVT, only male sex significantly and independently increased the risk of VTE recurrence. Cancer or saphenofemoral junction involvement defined a population at high risk for deep VTE recurrence. Some SVTs might be safely managed without anticoagulants.

Background: Epidemiological data of paediatric moyamoya disease/syndrome (MMD/MMS) in non-Asian populations are scarce. Methods: A questionnaire was sent to every French neuropaediatric academic centre to estimate the prevalence, incidence, familial form rate and location of paediatric MMD/MMS cases. Specific paediatric data were also retrieved from the most recent nationwide Japanese study. Results: A 100% response rate was obtained. The prevalence of paediatric MMD/MMS was estimated at 0.39/100,000 children (95% CI: 0.28–0.49), and the incidence was estimated at 0.065/100,000 children/year (95% CI: 0.025–0.12), with 7.5% familial cases. The prevalence was homogenous within the different administrative areas. Conclusions: This comprehensive survey of MMD/MMS in academic neuropaediatric centres suggests that the prevalence of the disease in children in France is approximately 1/20th of that estimated in Asia.

Background: Elevated lipoprotein (Lp) (a) is the most common genetically determined risk factor found in babies with perinatal ischemic stroke. The influence of maternal Lp(a) has not been studied extensively to date. Objectives: To investigate the role of Lp(a) in our population of neonates with stroke. Methods: In a prospective uncontrolled cohort of term-born children with neonatal arterial ischemic stroke, Lp(a) levels were investigated in 69 mothers and 69 children. Paternal Lp(a) was not explored. Results: An increased Lp(a) level was found in 26 mothers [38%; 95% confidence interval (CI) 28–50%] and in 15 children (22%; 95% CI 13–33%). Both rates were higher than the reference range reported in the general Caucasian population (10% in adults and 5% in children). Additionally, there was a correlation between maternal and infantile Lp(a) levels (p < 0.0001) and between elevated maternal Lp(a) level and lower birth weight (p = 0.027). Conclusions: Elevated maternal Lp(a) is apparently a risk factor for neonatal arterial ischemic stroke. We speculate that the pathological mechanism of this relation may be mediated through a dysfunction of the placental vascularization.

Resume Nous avons realise une enquete nationale aupres de tous les centres de la douleur en France entre aout et septembre 2005. Cette enquete concerne les prises en charge non medicamenteuses de la douleur chronique et constitue un preliminaire a la realisation d’une evaluation de ces techniques demandee par la direction generale de la Sante (DGS) par des etudes cliniques multicentriques. Ce questionnaire, adresse aux 25 centres d’evaluation et de traitement de la douleur (CETD), concerne trois techniques non medicamenteuses : la neurostimulation transcutanee (NST), la relaxation et l’hypnose et leurs indications. Sur les 24 reponses, 19 centres pratiquent de maniere reguliere la NST et/ou la relaxation avec du personnel forme. Seuls 14 centres utilisent l’hypnose de maniere reguliere. Les indications les plus frequemment rapportees pour la pratique de ces techniques sont les suivantes : cephalees, douleurs neuropathiques, douleurs arthrosiques et fibromyalgie. La neurostimulation est une pratique la plus souvent proposee dans les douleurs neuropathiques et arthrosiques, la relaxation dans les cephalees. C’est a partir de ces donnees que deux etudes cliniques multicentriques ont ete proposees, la premiere pour une evaluation de la NST dans les lombalgies ou lomboradiculalgies chroniques, la seconde pour une evaluation de la relaxation dans les migraines severes. Ces etudes sont actuellement en cours et les resultats seront publies ulterieurement.

Introduction A seasonal variation of venous thromboembolic disease frequency is subject to discussion, and has been recently suggested for superficial vein thrombosis (SVT) in a small retrospective study. Our aim was to search for a seasonal variation of SVT frequency according to the data of larger studies. Materials and methods We analyzed the data of three French prospective multicenter studies with different designs which have included patients with SVT (STENOX, POST, and STEPH studies). Seasonal variation of SVT frequency was evaluated by comparing the observed seasonal frequency of SVT to a theoretical frequency of 25% for each season. Results The analysis included 1395 patients and 4.75 seasonal cycles. The difference to a theoretical frequency of 25% was statistically significant in one study (POST, p = 0.044). The higher risk difference was − 6.1% (95% CI − 11.7–−0.5) in summer in STENOX, + 7.1% (95% CI + 2.7–+11.5) in winter in POST and 4.2% (95% CI − 5.2–+13.7) in spring in STEPH, corresponding to a relative risk of 0.80, 1.40 and 1.20, respectively. Conclusions A seasonal variation was found in only one study which has the weakest methodology to warrant completeness. Variation pattern was different in each study. If this variation exists, it would probably be too low to have clinical consequences.

International audience; The optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain. To determine the benefits and harms of an additional 18-month treatment with warfarin vs placebo, after an initial 6-month nonrandomized treatment period on a vitamin K antagonist. Randomized, double-blind trial (treatment period, 18 months; median follow-up, 24 months); 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers. Warfarin or placebo for 18 months. The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization. Secondary outcomes were the composite at 42 months (treatment period plus 24-month follow-up), as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. After randomization, 4 patients were lost to follow-up, all after month 18, and 1 withdrew due to an adverse event. During the 18-month treatment period, the primary outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 (13.5%) in the placebo group (hazard ratio [HR], 0.22; 95% CI, 0.09-0.55; P = .001). Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group (HR, 0.15; 95% CI, 0.05-0.43); major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group (HR, 3.96; 95% CI, 0.44 to 35.89). During the 42-month entire study period (including the study treatment and follow-up periods), the composite outcome occurred in 33 patients (20.8%) in the warfarin group and in 42 (24.0%) in the placebo group (HR, 0.75; 95% CI, 0.47-1.18). Rates of recurrent venous thromboembolism, major bleeding, and unrelated death did not differ between groups. Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy. clinicaltrials.gov Identifier: NCT00740883.

International audience; BACKGROUND AND AIMS: The usefulness of anti-glycan antibodies alone or combined with anti-Saccharomyces cerevisiae [ASCA] or perinuclear antineutrophil cytoplasmic [pANCA] antibodies for diagnosis of inflammatory bowel disease [IBD], differentiation between Crohn's disease [CD] and ulcerative colitis [UC], disease stratification including IBD phenotype, and also for determination of the course of the disease, remain unclear. METHODS: A large panel of serological anti-glycan carbohydrate antibodies, including anti-mannobioside IgG antibodies [AMCA], anti-chitobioside IgA [ACCA], anti-laminaribioside IgG antibodies [ALCA], anti-laminarin [anti-L] and anti-chitine [anti-C] were measured in the serum from a cohort of 195 patients with IBD] [107 CD and 88 UC]. The respective accuracy of isolated or combined markers for diagnosis, disease differentiation, stratification disease phenotype, and severity of the disease course, defined by a wide panel of criteria obtained from the past medical history, was assessed. RESULTS: The positivity of at least one anti-glycan antibody was detected in a significant higher proportion of CD and UC compared with healthy controls [p \textless 0.0001 and p \textless 0.0007, respectively]. Whereas ASCA and ANCA antibody status had the highest efficacy to be associated with CD in comparison with UC (area under receiver operating characteristic curve [AUROC] = 0.70 for each], the adjunction of anti-laminarin antibody substantially improved the differentiation between CD and UC [AUROC = 0.77]. Titres of ACCA [\textgreater 51U/ml] and anti-laminarin [\textgreater 31U/ml] were significantly linked with a higher association with steroid dependency (odds ratio [OR] =2.0 [1.0-4.0], p = 0.03 and OR = 2.4 [1.1-5.2], p = 0.02, respectively]. We further defined the respective performance of anti-glycan antibodies to discriminate between patients with severe or not severe CD and UC course and determined the associated optimal cut-off values: severe CD course was significantly more likely in case of AMCA \textgreater 77U/ml [OR = 4.3; p = 0.002], ASCA \textgreater 63U/ml [OR = 3.5; p \textless 0.009] and at a lesser degree ACCA \textgreater 50U/ml [OR = 2.8; p \textless 0.02] and severe UC course was significantly associated with AMCA \textgreater 52U/ml [OR = 3.4; p = 0.04] and ACCA \textgreater 25U/ml [OR = 3.0; p \textless 0.04]. CONCLUSIONS: Anti-glycan antibodies are valuable serological markers, especially AMCA antibodies that may help clinicians to promptly classify patients into high risk for severe disease.

BACKGROUND Immunosuppressive therapies used for treating ulcerative colitis are known to favor chronic and latent viral diseases. This study aimed at evaluating prospectively the association between colonic cytomegalovirus (CMV) reactivation and anti-tumor necrosis factor (TNF) monoclonal antibodies (mabs) by comparison to azathioprine (AZA) in a series of flare-ups occurring in consecutive ulcerative colitis patients. METHODS A total of 109 flare-ups were recorded in 73 patients receiving a maintenance therapy by anti-TNF mabs (n = 69) or AZA (n = 40). The CMV DNA load in colonic tissue was determined by reverse transcription polymerase chain reaction on a pair of biopsies. RESULTS The number of CMV reactivation was of 35% and 38% in patients receiving anti-TNF mabs and AZA, respectively. The median of CMV DNA load was 378 [10-29,800] and 8300 [10-3,25,000] copies/mg of tissue in patients treated by anti-TNF mabs and AZA, respectively (P = 0.11 by Mann-Whitney U test). In a subgroup of 45 patients under anti-TNF mabs requiring an optimized treatment by infliximab, clinical remission (partial Mayo score

Importance Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. Objective To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. Design, Setting, and Participants Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. Interventions Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. Main Outcomes and Measures Primary efficacy outcome was symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. Results In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 [95% CI, 0.51-7.89]; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. Conclusions and Relevance Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. Trial Registration clinicaltrials.gov Identifier:NCT00457158

Introduction Lors de la realisation d’analyses multivariees, les donnees manquantes sur de potentiels facteurs explicatifs sont une veritable problematique clinique et statistique. Plusieurs solutions sont proposees pour gerer ces valeurs manquantes. La premiere est de construire le modele multivarie avec tous les facteurs potentiels, y compris ceux contenant des valeurs manquantes entrainant l’exclusion des patients de l’analyse, une perte de puissance et un biais possible si les donnees manquantes sont missing not at random (MNAR). La seconde approche consiste a ne pas inclure dans le modele multivarie les facteurs potentiels entaches de donnees manquantes, le risque etant alors de se priver d’un facteur potentiellement pertinent. La derniere possibilite est d’imputer les donnees manquantes, a l’aide notamment des methodes d’imputations multiples. Nous proposons ici une strategie d’imputation d’un facteur de risque potentiel qui s’exprime par une variable categorielle combinee construite a partir de deux autres variables quantitatives mesurees par l’echographie cardiaque. Methodes A partir d’une etude de 371 patients, nous souhaitions determiner les facteurs predictifs d’evenements thromboemboliques veineux a 42 mois. Le facteur de risque potentiel « retentissement cardiaque » etait manquant chez 223 patients. L’etude de la nature des donnees manquantes nous a permis de distinguer deux situations : des donnees manquantes car l’echographie cardiaque n’avait pas ete realisee, et des donnees manquantes car les donnees de l’echographie cardiaque n’avaient pas ete enregistrees. Pour la premiere situation, les 145 donnees manquantes ont ete considerees comme MNAR car les cliniciens ont precise que la prescription de l’echographie cardiaque etait liee a la probabilite de deceler un retentissement cardiaque et inversement. Pour la deuxieme situation, le facteur « retentissement cardiaque » etait manquant pour 78 patients et ces donnees ont ete considerees missing not at random (MAR). L’imputation de ces donnees a ete faite selon deux methodes d’imputation multiple par equations chainees (MICE) : soit en imputant les deux variables quantitatives permettant la construction de la variable de retentissement cardiaque (Markov Chain Monte-Carlo [MCMC]), soit en imputant directement la variable categorielle ( fully conditional specification [FCS]). Resultat Sans imputation (148 patients disponibles), le retentissement cardiaque etait associe au risque d’evenements thromboemboliques avec un hazard ratio (HR) de 0,93 [IC95 %, 0,36 ; 2,43]. Suite a l’imputation des donnees MNAR selon la demarche clinique (pas d’examen echographique signifie pas de retentissement cardiaque), l’analyse a porte sur 293 patients. L’estimation du HR pour le retentissement cardiaque etait alors de 1,73 [1,00 ; 2,96]. Les variables centre, âge, sexe, indice de masse corporelle, antecedent cardiaque et maladie respiratoire chronique ont ete prises en compte dans les modeles MICE pour imputer les donnees manquantes MAR restantes. A partir des donnees des 371 patients, l’estimation avec la methode d’imputation de chacune des variables quantitatives composant le critere combine « retentissement cardiaque » fournissait un HR de 1,56 [0,92 ; 2,63] et un HR de 1,62 [0,97 ; 2,71] en imputant le critere combine directement de facon categorielle. Conclusion Le resultat observe lors de l’imputation des donnees MNAR confirme bien la nature MNAR des donnees manquantes. Concernant les donnees MAR, l’imputation du retentissement cardiaque avec les deux variables quantitatives ou avec la variable combinee categorielle donnent un resultat identique. L’imputation selon un arbre decisionnel base sur le flow chart pourrait recommander pour realiser des imputations adaptees a la nature des donnees manquantes.

International audience; OBJECTIVE:Lymphedema treatment is based on Decongestive Lymphedema Therapy (DLT) with an intensive phase followed by a long-term maintenance phase. This study aimed to observe volume variation over the intensive phase and 6 months later.METHODS:Prospective multicentre observational study of patients with unilateral lymphedema. The primary objective was to assess lymphedema volume variation between baseline, the end of intensive phase and 6 months later. Secondary objectives were to assess the frequency of heaviness limiting limb function and treatments safety predictors for volume reduction.RESULTS:Three hundred and six patients (89.9% women; 59.9±14.3 years old) with upper/lower (n=184/122) limb lymphedema were included. At the end of the intensive phase, median excess lymphedema volume reduction was 31.0% (41.7-19.9) followed by a 16.5% (5.9-42.3) median increase over the 6-month maintenance period phase. Previous intensive treatment was the only significant predictor of this response. As compared to baseline, heaviness limiting limb use was much less frequently reported at the end of the reductive phase (75.5% versus 42.3% respectively), and was more frequent at the end of the maintenance phase (62.6%). The most frequent adverse events reported were skin redness and compression marks (18.4 and 15.7% of patients, respectively). Blisters requiring treatment stoppage were rare (1.4%).CONCLUSIONS:Intensive phase decreases lymphedema volume and heaviness limiting limb function. The benefit is partially abolished after the first 6 months of maintenance. There is a need to consider how to provide optimal patient care for the long-term control of lymphedema.

Summary Background The incidence of superficial vein thrombosis (SVT) in the general adult population remains unknown. Objectives To assess the annual diagnosis rate of symptomatic, objectively confirmed lower limb SVT, associated or not with concomitant deep vein thrombosis and/or symptomatic pulmonary embolism. Methods/patients We conducted, from November 14, 2011, to November 13, 2012, a multicenter, community-based study in the Saint-Etienne urban area, France, representing a population of 265 687 adult residents (according to the 2009 census). All 248 general practitioners located within the area were asked to refer any patient with clinically suspected lower limb acute SVT to a vascular physician for systematic compression ultrasonography. All 28 vascular physicians located within the area participated in the study. The annual diagnosis rate, with the corresponding 95% confidence interval (CI), was calculated as the number of patients with symptomatic, objectively confirmed SVT divided by the number of person-years at risk defined by population data of the area. All venous thromboembolic events were validated by an independent central adjudication committee. Results Overall, 171 patients with symptomatic, confirmed SVT were reported. The annual diagnosis rate was 0.64% (95% CI, 0.55%–0.74%), was higher in women, and increased with advancing age regardless of gender. Concomitant deep vein thrombosis (20 proximal) was observed in 42 patients (24.6% [95% CI, 18.3%–31.7%]), and concomitant symptomatic pulmonary embolism was observed in eight patients (4.7% [95% CI, 2.0%–9.0%]). Conclusions This first community-based study showed that symptomatic SVT with confirmed diagnosis is a relatively common disease frequently associated with thromboembolic events in the deep venous system.

Introduction Les methodes classiques d’estimation d’incidence cumulee consistent a censurer le delai d’observation lorsque l’evenement d’interet ne s’est pas produit, supposant l’independance entre la censure et l’evenement d’interet. En dehors des censures administratives, non-informatives, l’hypothese d’independance entre la censure et l’evenement d’interet est discutable notamment lorsque le delai d’observation est censure du fait de l’apparition d’un autre evenement appele evenement competitif. Des etudes par simulation ont montre que la prise en compte des risques competitifs permettait de limiter la surestimation de l’incidence observee avec la methode de Kaplan-Meier. Nous presentons ici les differentes methodes d’estimation dans une etude ou les censures du fait d’un evenement competitif sont superieures a 80 %. Methodes Nous avons conduit une cohorte prospective multicentrique francaise de patients hospitalises en soins palliatifs dont l’objectif principal etait d’estimer la frequence des hemorragies dans cette population (etude RHESO, NCT01056978 ). La difficulte en soins palliatifs est l’estimation de la frequence d’un evenement d’interet autre que la mortalite. Plusieurs methodes d’estimation ont ete envisagees : l’incidence brute a trois mois, l’incidence cumulee par la methode de Kaplan-Meier (KM), et l’incidence cumulee prenant en compte le risque competitif selon la methode de Kalbfleisch et Prentice. Les incidences ont ete calculees assorties de leur intervalle de confiance a 95 % (IC95 %). Resultats Au total, 1199 patients ont ete inclus dans l’etude. A trois mois, 116 patients ont presente une complication hemorragique majeure ou cliniquement pertinente, soit une incidence brute de 9,7 % (IC95 % 8,1 % ; 11,6 %). Pour l’estimation des incidences cumulees, 1083 patients ont ete censures, incluant 8 patients (0,6 %) perdus de vue et 980 (81,7 %) decedes sans avoir presente l’evenement d’interet. L’incidence cumulee des complications hemorragiques majeures ou cliniquement pertinentes estimee par KM est de 20,8 % (IC95 % 15,6 % ; 26,0 %). En prenant en compte le risque competitif, l’incidence cumulee est de 9,8 % (IC95 % 8,3 % ; 11,6 %). Conclusion En presence d’un evenement competitif, nous retrouvons une surestimation de l’incidence cumulee par la methode de KM. Lorsque les censures sont principalement dues a un evenement competitif, la methode d’estimation prenant en compte les risques competitifs fournit une incidence similaire a l’incidence brute. Pour la suite de ce travail quant a la determination des facteurs predictifs de l’hemorragie, les differentes methodes seront egalement comparees.

Background CXCR4 is a chemokine receptor with multiple effects on the immune system, upregulated in patients with SLE, and correlated with disease severity. Objective This study has investigated whether the levels of CXCR4 expressed on leucocyte subsets in lupus patients are correlated with the efficacy and the safety of the influenza vaccine. Methods Twenty-seven patients were vaccinated and vaccine immunogenicity and tolerance were evaluated. CXCR4 was assayed on leucocyte subsets and correlated with clinical and immunological signs of diseases activity. Results A significant increase in the titres of antibodies to the three viral strains was observed along with trends towards an increased vaccine efficacy in patients with quiescent disease vs patients with active disease. Recent flu vaccine history and, to a lesser extent, immunosuppressive treatment may influence vaccine immunogenicity. Influenza immunization was not associated with clinical side-effects or clinical lupus flare but with an increase in rheumatoid factor levels. Our study also confirms the correlation of CXCR4 expression with biological autoimmunity as shown by the correlation between the percentage of CXCR4-positive T cells and the ANA titres at D0, and the reverse correlation between CXCR4 expression and vaccine immunogenicity as demonstrated by the higher percentage of CXCR4-positive T cells at D0 and D30 in non-responders vs responders. Conclusion Altogether, our study confirms the efficacy and the safety of flu vaccine in SLE patients, highlights the role of CXCR4 as a surrogate marker for autoimmunity in lupus and shows that CXCR4 expression on T cells is predictive of vaccine efficacy in SLE patients.

Objective: We hypothesized that cryptogenic forms of arterial ischemic stroke (AIS) in children may present better outcomes than symptomatic ones. Methods: We conducted a single-centered retrospective cohort study using chart reviews of all inpatients aged 0.25–16 years and admitted for AIS or TIA between 1994 and 2007. Sixty-three consecutive children with AIS were divided into 2 stroke categories: first, AIS with an established cause, considered as symptomatic (S), and second, AIS only associated with risk factors, and considered as cryptogenic (C). AIS were further subclassified according to the CASCADE stroke classification system. We measured long-term outcome with 2 endpoints: recurrence rate and neurologic impairment score (NIS). We used univariate analysis to compare the clinical and radiologic characteristics of both groups. Results: AIS were cryptogenic in 28 patients (44%) and symptomatic in 35 (56%). Compared to patients in group S, patients in group C showed an absence of stroke recurrence under prolonged aspirin treatment (0% vs 30.3%; p p = 0.02), unilateral infarcts ( p = 0.01), M1 segment stenosis ( p = 0.02), and better stroke outcomes (mean NIS 2.7 vs 4.2; p = 0.04). Within group C, patients with post-varicella arteriopathy (PVA) had a profile comparable to that of patients with non-PVA strokes in terms of infarct topography, localization of vascular lesions, recurrence rate, and neurologic outcome. Conclusion: Cryptogenic AIS during childhood is a homogeneous clinical and radiologic entity, likely reflecting similar underlying pathophysiologic mechanisms. Under early and prolonged treatment with aspirin, cryptogenic AIS does not recur.

International audience; INTRODUCTION:The aim of this study was to correlate placental volumes deduced from three-dimensional ultrasound and virtual organ computer-aided analysis (VOCAL) software with systemic concentrations of D-dimer and soluble endothelial protein C receptor (sEPCR).METHODS:This was a monocentric experimental prospective study conducted from October 2008 to July 2009. Forty consecutive patients at risk of placental vascular pathology (PVP) recurrence or occurrence were included. Placental volumes were systematically measured three times (11-14, 16-18 and 20-22 weeks of gestation (WG)) by two independent sonographers. D-dimers and sEPCR plasma concentrations were measured using ELISA kits (Enzyme Linked ImmunoSorbent Assay).RESULTS:Eleven patients had a PVP. The plasma D-dimer level was positively correlated with placental volume (r = 0.45, p < 0.001). A smaller placental volume and placental quotient was evidenced in women who developed a PVP at the three gestational ages, and the difference was more pronounced during the third exam (20 WG). No obvious correlation could be demonstrated between the development of a PVP and the levels of D-dimer and sEPCR. There was no significant difference in the values of placental volumes measured by the two sonographers.CONCLUSION:The placenta growth could be a major determinant of the elevation of D-dimer during pregnancy. Consideration of placental volume could allow for modulation of the D-dimer concentrations for restoring their clinical interest.

Introduction Apres un premier episode d’embolie pulmonaire (EP) non provoquee, la persistance de defects perfusionnels pulmonaires pourrait etre associee a un risque accru de recidive thromboembolique apres l’arret du traitement anticoagulant. L’objectif est d’identifier les facteurs de risque de sequelles perfusionnelles scintigraphiques apres un premier episode d’EP non provoquee. Methodes Il s’agit d’une etude multicentrique, randomisee, controlee, en double insu. Apres 6 mois de traitement anticoagulant pour un premier episode d’EP non provoquee, 371 patients ont ete randomises a recevoir de la warfarine ou un placebo pendant 18 mois. A l’inclusion, une scintigraphie de ventilation/perfusion planaire a ete realisee chez tous les patients. Les sequelles perfusionnelles etaient definies par une absence de perfusion d’au moins 10 % du lit vasculaire pulmonaire. L’analyse des facteurs de risques biologiques, cliniques et morphologiques a ete realisee par une analyse univariee et multivariee. Resultats Apres 6 mois de traitement anticoagulant, 33 % des patients presentaient des sequelles perfusionnelles scintigraphiques. En analyse multivariee, l’âge de plus de 65 ans, une maladie respiratoire chronique, une pression arterielle pulmonaire systolique de plus de 50 mmHg et un rapport ventricule droit/ventricule gauche superieur a 0,9 etaient des facteurs independant de sequelles perfusionnelles pulmonaires (odds ratio : 3,4 [IC95 % : 2,0–6,0], 2,2 [IC95 % : 1,1–4,1] et 1,8 [IC95 % : 1,0–3,1], respectivement). Le traitement initial par une heparine de bas poids moleculaire (HBPM) etait en revanche associee a risque moindre de sequelles (odds ratio : 0,6 [IC95 % : 0,3–1,0]). Conclusion L’âge de plus de 65 ans, la presence d’une maladie respiratoire chronique, la dysfonction du ventricule droit sont significativement associees a un risque accru de sequelles perfusionnelles, alors que l’utilisation initiale d’HBPM en diminue le risque.

Introduction Apres l’arret du traitement anticoagulant lors d’un premier episode d’embolie pulmonaire (EP) non provoquee, le risque de recidive thromboembolique veineuse est eleve. L’objectif est d’identifier les facteurs de risque de recidive thromboembolique apres un premier episode d’EP non provoquee. Methodes Il s’agit d’une etude multicentrique, randomisee, controlee, en double insu. Apres 6 mois de traitement anticoagulant pour un premier episode d’EP non provoquee, 371 patients ont ete randomises a recevoir de la warfarine ou un placebo pendant 18 mois ; apres arret du traitement a l’etude, les patients ont ete suivis pendant 2 ans. A l’inclusion, une biobanque, une scintigraphie pulmonaire de ventilation/perfusion, une echographie trans-thoracique et un echo-Doppler veineux des membres inferieurs ont ete realises chez tous les patients. Les recidives thromboemboliques ont ete adjudiquees par un comite independant. L’analyse statistique a ete conduite en uni- puis multivariee. Resultats Sur une periode de suivi de 42 mois, 67 patients sur 371 (20 %) ont recidives. En analyse multivariee, le risque de recidive etait significativement augmente chez les patients âges de plus de 65 ans, ayant des sequelles de thrombose veineuse profonde (TVP) ou ayant des sequelles perfusionnelles pulmonaires (≥ 10 %) (odds ratio a 2,4 [IC95 % : 1,3–4,4], 2,0 [IC95 % : 1,1–3,9] et 2,2 [IC95 % : 1,2–4,0] respectivement). Les patients ayant au moins un de ces facteurs de risque representaient 76 % des recidives. Le sexe, une dysfonction du ventricule droit lors du diagnostic d’EP, un taux de D-Dimeres eleve a l’inclusion et la presence de thrombophilie n’etaient associes a un risque accru independant de recidive. Conclusion Chez les patients ayant un premier episode non provoque d’EP, l’âge de plus de 65 ans, les sequelles perfusionnelles pulmonaires ou les sequelles de TVP a 6 mois d’anticoagulation constituent des facteurs predictifs de recidive thromboembolique.

SummaryDespite the need for effective and safe thromboprophylactic drugs for patients with renal impairment, clinical trial data on anticoagulant agents are limited in this population. The study aim was to assess in the real-world setting the use of the once-daily 1.5 mg reduced dosage regimen of fondaparinux available for this context. In this prospective cohort study, patients with a creatinine clearance (CrCl) of 20–50 ml/ minute, undergoing total hip (THR) or knee (TKR) replacement or hip fracture surgery (HFS) received fondaparinux thromboprophylaxis. Main clinical outcomes were bleeding (major/clinically relevant nonmajor), symptomatic venous thromboembolism (VTE) and death. Overall, 442 patients (353 women; median age: 82 years; 39.4% in ASA class ≥3; mean ± SD CrCl: 39.0 ± 8.0 ml/minute; 78% with additional risk factors for bleeding), undergoing THR (43.7%), TKR (27.6%), or HFS (28.7%) received fondaparinux 1.5 mg for a mean ± SD duration of 16.0 ± 12.5 days. At postoperative day 10, the rates (95% confidence interval) of major bleeding, clinically relevant bleeding and symptomatic VTE were 4.5% (2.8–6.9), 0.5% (0.1–1.6) and 0.5% (0.05–1.62), respectively; no fatal bleeding, bleeding into a critical organ, pulmonary embolism or proximal deep-vein thrombosis occurred. Corresponding rates at one month were 5.2%, 0.7% and 0.7%. One-month mortality was 2.3% (0.9–3.6). This large clinical prospective study provides for the first time, under conditions reflecting “real-world” routine clinical practice, data on the bleeding and VTE risks of thromboprophylaxis with fondaparinux 1.5 mg after major orthopaedic surgery in renally impaired patients. It shows that these patients constitute a very elderly and fragile population.ClinicalTrials.gov number, NCT00555438

Recent data on lower-limb superficial-vein thrombosis (SVT) may substantially impact its clinical management. Thus, the clear confirmation that SVT is closely linked to deep-vein thrombosis (DVT) or pulmonary embolism (PE) highlights the potential severity of the disease. DVT or PE are diagnosed in 20-30% of SVT patients. Moreover, clinically relevant symptomatic thromboembolic events complicate isolated SVT (without concomitant DVT or PE at diagnosis) in 4-8% of patients. For the first time, an anticoagulant treatment, once-daily 2.5 mg fondaparinux for 45 days, was demonstrated to be effective and safe for preventing these symptomatic thromboembolic events in patients with lower-limb isolated SVT in the randomized placebo-controlled CALISTO study. Based on these recent findings, new recommendations on the management of SVT patients, including complete ultrasonography examination of the legs, and in patients with isolated SVT, prescription of once-daily 2.5 mg fondaparinux subcutaneously for 45 days on top of symptomatic treatments, may be proposed.

OBJECTIVE: We aimed to correlate early imaging data with motor outcomes in a large, homogeneous, cohort of infants with neonatal (diagnosed before 29 days of life) arterial ischemic stroke (AIS). METHODS: From a prospective cohort of 100 children with neonatal AIS, we analyzed the MRI studies performed within the 28 first days of life for 80 infants evaluated at 2 years of age. The relationships between infarction location and corticospinal tract (CST) involvement and motor outcomes were studied RESULTS: Seventy-three infarctions involved the middle cerebral artery (MCA) territory. Of those, 50 were superficial infarctions, 5 deep infarctions, and 18 mixed infarctions. The CST was involved in 24 cases. Nineteen patients with MCA infarctions (26% [95% confidence interval: 16%–34%]) developed hemiplegia. Mixed infarctions (P < .0001) and CST involvement (P < .0001) were highly predictive of hemiplegia. In contrast, 88% of children with isolated superficial MCA infarctions did not exhibit impairment. CONCLUSIONS: Accurate prediction of motor outcomes can be obtained from early MRI scans after neonatal AIS. The absence of involvement of the CST resulted in normal motor development in 94% of cases. CST involvement resulted in congenital hemiplegia in 66% of cases.

Summary We undertook a survey of French university hospital hematological laboratories to ascertain the clinical characteristics of patients with suspected HIT, the laboratory tests performed, and the therapeutic strategy adopted in current practice. Methods A standardized medical records database for patients with suspected HIT was sent to 19 laboratories. During two months, all consecutive patients for whom a biological test was performed were included. Results 169 patients were included, 27 (16%) patients having a final diagnosis of HIT. At the time HIT was suspected, the heparin duration and the level of thrombocytopenia were similar in HIT- positive and HIT-negative groups. The use of unfractionated heparin, a therapeutic heparin dose regimen and the presence of thrombotic complications were significantly more frequent in HIT-positive patients. When the heparin dose regimen was taken into account, only thrombotic complications under a therapeutic dose regimen were significantly increased in HIT-positive patients. Eighty-six percent of patients presented at least one alternative diagnosis of thrombocytopenia without significant difference between the two groups. Laboratory tests were performed after a mean of 0.3 days and mainly consisted of antigen assays. At the time HIT was suspected, heparin was stopped in 56 (33%) patients, being replaced mainly by danaparoid. Only three laboratories declared they usually received all the necessary clinical information to establish the likelihood of HIT. Conclusion In current practice in France, the clinical probability of HIT is rarely established, leading to systematic requests for laboratory HIT tests.