Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism.

BACKGROUND: Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with suspected pulmonary embolism undergo computed tomographic (CT) pulmonary angiography or ventilation-perfusion scanning, both of which involve radiation exposure to the mother and fetus. Whether a pregnancy-adapted algorithm could be used to safely avoid diagnostic imaging in pregnant women with suspected pulmonary embolism is unknown. METHODS: In a prospective study involving pregnant women with suspected pulmonary embolism, we assessed three criteria from the YEARS algorithm (clinical signs of deep-vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the d-dimer level. Pulmonary embolism was ruled out if none of the three criteria were met and the d-dimer level was less than 1000 ng per milliliter or if one or more of the three criteria were met and the d-dimer level was less than 500 ng per milliliter. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep-vein thrombosis; if the results were positive (i.e., a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism. RESULTS: A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep-vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval [CI], 0.04 to 1.2); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% CI, 35 to 44). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester. CONCLUSIONS: Pulmonary embolism was safely ruled out by the pregnancy-adapted YEARS diagnostic algorithm across all trimesters of pregnancy. CT pulmonary angiography was avoided in 32 to 65% of patients. (Funded by Leiden University Medical Center and 17 other participating hospitals; Artemis Netherlands Trial Register number, NL5726.).

Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial.

AIMS: The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment. METHODS AND RESULTS: Normotensive patients with PE of 26 hospitals from France, Belgium, the Netherlands, and Switzerland were randomized to either triaging with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician-in-charge, taking into account the patient's opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent venous thrombo-embolism, major bleeding or all-cause death (non-inferiority analysis with 2.5% absolute risk difference as margin), and the rate of patients discharged home within 24 h after randomization (NCT02811237). From January 2017 through July 2019, 1975 patients were included. In the per-protocol population, the primary outcome occurred in 3.82% (34/891) in the Hestia arm and 3.57% (32/896) in the sPESI arm (P = 0.004 for non-inferiority). In the intention-to-treat population, 38.4% of the Hestia patients (378/984) were treated at home vs. 36.6% (361/986) of the sPESI patients (P = 0.41 for superiority), with a 30-day composite outcome rate of 1.33% (5/375) and 1.11% (4/359), respectively. No recurrent or fatal PE occurred in either home treatment arm. CONCLUSIONS: For triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI had similar safety and effectiveness. With either tool complemented by the overruling of the physician-in-charge, more than a third of patients were treated at home with a low incidence of complications.

Outcomes and Prognosis Factors in Patients With Vena Cava Filters in a Quaternary Medical Center: A 5-Year Retrospective Analysis.

BACKGROUND: Indications for inferior vena cava filter (IVCF) placement are controversial. This study assesses the proportion of different indications for IVCF placement and the associated 30-day event rates and predictors for all-cause mortality, deep vein thrombosis (DVT), pulmonary embolism, and bleeding after IVCF placement. METHOD: In this 5-year retrospective cohort observational study in a quaternary care center, consecutive patients with IVCF placement were identified through cross-matching of 3 database sets and classified into 3 indication groups defined as "standard" in patients with venous thromboembolism (VTE) and contraindication to anticoagulants, "extended" in patients with VTE but no contraindication to anticoagulants, and "prophylactic" in patients without VTE. RESULTS: We identified 1248 IVCF placements, that is, 238 (19.1%) IVCF placements for standard indications, 583 (46.7%) IVCF placements for extended indications, and 427 (34.2%) IVCF placements for prophylactic indications. Deep vein thrombosis rates [95% confidence interval] were higher in the extended (8.06% [5.98-10.58]) and prophylactic (7.73% [5.38-10.68]) groups than in the standard group (3.36% [1.46-6.52]). Mortality rates were higher in the standard group (12.18% [8.31-17.03]) than in the extended group (7.55% [5.54-9.99]) and the prophylactic (5.85% [3.82-8.52]) group. Bleeding rates were higher in the standard group (4.62% [2.33-8.12]) than in the prophylactic group (2.11% [0.97-3.96]). Best predictors for VTE were acute medical conditions; best predictors for mortality were age, acute medical conditions, cancer, and Medicare health insurance. CONCLUSIONS: Prophylactic and extended indications account for the majority of IVCF placements. The standard indication is associated with the lowest VTE rate that may be explained by the competing risk of mortality higher in this group and related to the underlying medical conditions and bleeding risk. In the prophylactic group (no VTE at baseline), the exceedingly high DVT rate may be related to the IVCF placement.

Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective Management Outcome Study.

Background: Data on the optimal diagnostic management of pregnant women with suspected pulmonary embolism (PE) are limited, and guidelines provide inconsistent recommendations on use of diagnostic tests. Objective: To prospectively validate a diagnostic strategy in pregnant women with suspected PE. Design: Multicenter, multinational, prospective diagnostic management outcome study involving pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb compression ultrasonography (CUS), and computed tomography pulmonary angiography (CTPA). (ClinicalTrials.gov: NCT00740454). Setting: 11 centers in France and Switzerland between August 2008 and July 2016. Patients: Pregnant women with clinically suspected PE in emergency departments. Intervention: Pulmonary embolism was excluded in patients with a low or intermediate pretest clinical probability and a negative D-dimer result. All others underwent lower limb CUS and, if results were negative, CTPA. A ventilation-perfusion (V/Q) scan was done if CTPA results were inconclusive. Pulmonary embolism was excluded if results of the diagnostic work-up were negative, and untreated pregnant women had clinical follow-up at 3 months. Measurements: The primary outcome was the rate of adjudicated venous thromboembolic events during the 3-month follow-up. Results: 441 women were assessed for eligibility, and 395 were included in the study. Among these, PE was diagnosed in 28 (7.1%) (proximal deep venous thrombosis found on ultrasonography [n = 7], positive CTPA result [n = 19], and high-probability V/Q scan [n = 2]) and excluded in 367 (clinical probability and negative D-dimer result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received extended anticoagulation during follow-up, mainly for previous venous thromboembolic disease. The rate of symptomatic venous thromboembolic events was 0.0% (95% CI, 0.0% to 1.0%) among untreated women after exclusion of PE on the basis of negative results on the diagnostic work-up. Limitation: There were several protocol deviations, reflecting the difficulty of performing studies in pregnant women with suspected PE. Conclusion: A diagnostic strategy based on assessment of clinical probability, D-dimer measurement, CUS, and CTPA can safely rule out PE in pregnant women. Primary Funding Source: Swiss National Foundation for Scientific Research, Groupe d'Etude de la Thrombose de Bretagne Occidentale, and International Society on Thrombosis and Haemostasis.

Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial.

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.

Recurrent venous thromboembolism in anticoagulated cancer patients: Diagnosis and treatment.

Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression.

Central venous catheter associated upper extremity deep vein thrombosis in cancer patients: Diagnosis and therapeutic management.

Catheter-related thrombosis (CRT) is a relatively frequent and potentially fatal complication arising in patients with cancer who require a central catheter placement for intravenous treatment. In everyday practice, CRT remains a challenge for management; despite its frequency and its negative clinical impact, few data are available concerning diagnosis and treatment of CRT. In particular, no diagnostic studies or clinical trials have been published that included exclusively patients with cancer and a central venous catheter (CVC). For this reason, many questions regarding optimal management of CRT remain unanswered. Due to the paucity of high-grade evidence regarding CRT in cancer patients, guidelines are derived from upper extremity DVT studies for diagnosis, and from those for lower limb DVT for treatment. This article addresses the issues of diagnosis and management of CRT through a review of the available literature and makes a number of proposals based on the available evidence. In symptomatic patients, venous ultrasound is the most appropriate choice for first-line diagnostic imaging of CRT because it is noninvasive, and its diagnostic performance is high (which is not the case in asymptomatic patients). In the absence of direct comparative clinical trials, we suggest treating patients with CRT with a therapeutic dose of either a LMWH or a direct oral factor Xa inhibitor, with or without a loading dose. These anticoagulants should be given for a total of at least three months, including at least one month after catheter removal following initiation of therapy.

Home treatment for patients with cancer-associated venous thromboembolism.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

[Translation into French and republication of: "Home treatment for patients with cancer-associated venous thromboembolism"]. / Traduction et republication de : « Traitement à domicile des patients atteints de maladie veineuse thromboembolique associée au cancer ¼.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

Evaluation of Elastic Venous Compression Device dispensation in pregnant and post-partum women using the French National Health Insurance Claims Database: The ProFIL retrospective cohort study.

OBJECTIVES: To describe the real-world use of Elastic Venous Compression Devices (EVCDs) during pregnancy and post-partum using data from a representative subset of the French National Health Insurance Claims Database (the Echantillon Généraliste des Bénéficiaires, EGB). STUDY DESIGN: Women aged 15-49 who were pregnant between 1st July 2017 and 15th June 2018 were identified in the EGB using pregnancy-specific acts (certain prenatal examinations or deliveries). Subgroups were defined by age, presence of Venous Thrombo-Embolism (VTE) risk factors, history of VTE, delivery type and time period. EVCD dispensations (format, prescriber, and date) were identified among those for "standard orthotics" using their unique reimbursement tariffs. Dispensation rates were computed for all subgroups, overall and by format and were compared. RESULTS: 15,528 pregnant women were included: 7,252 [46.7 %] deliveries (5,796 vaginal [79.9 %], 482 planned cesarean sections (C-sections) [6.7 %] and 974 unplanned C-Sections [13.4 %]), 2,734 (17.6 %) terminations and 5,542 (35.7 %) unknown outcomes. Overall, 4,919 (31.7 %) women were dispensed at least one EVCD. Ante-partum dispensation occurred in 43.1 % (n = 3,122) of women whose pregnancy led to a delivery. Dispensation rates were 17.3 % (n = 1,005), 46.7 % (n = 225) and 44.1 % (n = 430) after vaginal delivery, planned C-sections or unplanned C-sections, respectively. Overall, dispensation rates significantly increased with age, the presence of VTE risk factors, and a history of VTE (p < 0.01). EVCD dispensation was most frequent (17.0 %) during the 5th month of pregnancy. Among pregnant women who were dispensed at least one EVCD during ante- or post-partum, 69.0 % had one or two units of compression (27.1 % [one unit], 41.9 % [two units]). Stockings (48.6 %, n = 6,038) were dispensed significantly more frequently than socks (36.9 %, n = 4,586) and tights (14.5 %, n = 1,806) (p < 0.01). The main contributors to mechanical VTE prophylaxis were gynecologists (26.3 % of dispensations, n = 2,280), general practitioners (20.2 %, n = 1,749) and midwives (15.1 %, n = 1,314). CONCLUSIONS: Low observed dispensation rates highlight a discrepancy between the French National Authority for Health (Haute Autorité de Santé, HAS), recommending EVCDs use during pregnancy and after delivery, and the real-life use of EVCD. Prescription sensitization combined with targeted information campaigns for pregnant women would be beneficial to contribute to the prevention of VTE, a health problem for pregnant women.

Systematic review of the use of ultrasound for venous assessment and venous thrombosis screening in spaceflight.

The validity of venous ultrasound (V-US) for the diagnosis of deep vein thrombosis (DVT) during spaceflight is unknown and difficult to establish in diagnostic accuracy and diagnostic management studies in this context. We performed a systematic review of the use of V-US in the upper-body venous system in spaceflight to identify microgravity-related changes and the effect of venous interventions to reverse them, and to assess appropriateness of spaceflight V-US with terrestrial standards. An appropriateness tool was developed following expert panel discussions and review of terrestrial diagnostic studies, including criteria relevant to crew experience, in-flight equipment, assessment sites, ultrasound modalities, and DVT diagnosis. Microgravity-related findings reported as an increase in internal jugular vein (IJV) cross-sectional area and pressure were associated with reduced, stagnant, and retrograde flow. Changes were on average responsive to venous interventions using lower body negative pressure, Bracelets, Valsalva and Mueller manoeuvres, and contralateral IJV compression. In comparison with terrestrial standards, spaceflight V-US did not meet all appropriateness criteria. In DVT studies (n = 3), a single thrombosis was reported and only ultrasound modality criterion met the standards. In the other studies (n = 15), all the criteria were appropriate except crew experience criterion, which was appropriate in only four studies. Future practice and research should account for microgravity-related changes, evaluate individual effect of venous interventions, and adopt Earth-based V-US standards.

Outpatient management of cancer-associated pulmonary embolism: A post-hoc analysis from the HOME-PE trial.

INTRODUCTION: Cancer-related pulmonary embolism (PE) is associated with poor prognosis. Some decision rules identifying patients eligible for home treatment categorize cancer patients at high risk of complications, precluding home treatment. We sought to assess the effectiveness and the safety of outpatient management of patients with low-risk cancer-associated PE. METHODS: In the HOME-PE trial, hemodynamically stable patients with symptomatic PE were randomized to either triaging with Hestia criteria or sPESI score. We analyzed 3 groups of low-risk PE patients: 47 with active cancer treated at home (group 1), 691 without active cancer treated at home (group 2), and 33 with active cancer as the only sPESI criterion qualifying them for hospitalization (group 3). The main outcome was the composite of recurrent venous thromboembolism, major bleeding, and all-cause death within 30 days after randomization. RESULTS: Patients treated at home had composite outcome rates of 4.3 % (2/47) for those with cancer vs. 1.0 % (7/691) for those without (odds ratio (OR) 4.98, 95%CI 1.15-21.49). Patients with cancer had rates of complications of 4.3 % when treated at home vs. 3.0 % (1/33) when hospitalized (OR 1.19, 95%CI 0.15-9.47). In multivariable analysis, active cancer was associated with an increased risk of complications for patients treated at home (OR 7.95; 95%CI 1.48-42.82). For patients with active cancer, home treatment was not associated with the primary outcome (OR 1.19, 95%CI 0.15-9.74). CONCLUSIONS: Among patients treated at home, active cancer was a risk factor for complications, but among patients with active cancer, home treatment was not associated with adverse outcomes.

Effects of whole-body vibration or resistive-vibration exercise on blood clotting and related biomarkers: a systematic review.

Whole-body vibration (WBV) and resistive vibration exercise (RVE) are utilized as countermeasures against bone loss, muscle wasting, and physical deconditioning. The safety of the interventions, in terms of the risk of inducing undesired blood clotting and venous thrombosis, is not clear. We therefore performed the present systematic review of the available scientific literature on the issue. The review was conducted following the guidelines by the Space Biomedicine Systematic Review Group, based on Cochrane review guidelines. The relevant context or environment of the studies was "ground-based environment"; space analogs or diseased conditions were not included. The search retrieved 801 studies; 77 articles were selected for further consideration after an initial screening. Thirty-three studies met the inclusion criteria. The main variables related to blood markers involved angiogenic and endothelial factors, fibrinolysis and coagulation markers, cytokine levels, inflammatory and plasma oxidative stress markers. Functional and hemodynamic markers involved blood pressure measurements, systemic vascular resistance, blood flow and microvascular and endothelial functions. The available evidence suggests neutral or potentially positive effects of short- and long-term interventions with WBV and RVE on variables related to blood coagulation, fibrinolysis, inflammatory status, oxidative stress, cardiovascular, microvascular and endothelial functions. No significant warning signs towards an increased risk of undesired clotting and venous thrombosis were identified. If confirmed by further studies, WBV and RVE could be part of the countermeasures aimed at preventing or attenuating the muscular and cardiovascular deconditioning associated with spaceflights, permanence on planetary habitats and ground-based simulations of microgravity.

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk.

Noninvasive diagnostic work-up for suspected acute pulmonary embolism during pregnancy: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women. OBJECTIVES: The aim of this study was to establish the safety and efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis. METHODS: We performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided. RESULTS: We identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0·37%-1·4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2·3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0·79%; number needed to test 127). CONCLUSION: This study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis.

Search for Venous Endothelial Biomarkers Heralding Venous Thromboembolism in Space: A Qualitative Systematic Review of Terrestrial Studies.

Background: The recent discovery of a venous thrombosis in the internal jugular vein of an astronaut has highlighted the need to predict the risk of venous thromboembolism in otherwise healthy individuals (VTE) in space. Virchow's triad defines the three classic risk factors for VTE: blood stasis, hypercoagulability, and endothelial disruption/dysfunction. Among these risk factors, venous endothelial disruption/dysfunction remains incompletely understood, making it difficult to accurately predict risk, set up relevant prophylactic measures and initiate timely treatment of VTE, especially in an extreme environment. Methods: A qualitative systematic review focused on endothelial disruption/dysfunction was conducted following the guidelines produced by the Space Biomedicine Systematic Review Group, which are based on Cochrane review guidelines. We aimed to assess the venous endothelial biochemical and imaging markers that may predict increased risk of VTE during spaceflight by surveying the existing knowledge base surrounding these markers in analogous populations to astronauts on the ground. Results: Limited imaging markers related to endothelial dysfunction that were outside the bounds of routine clinical practice were identified. While multiple potential biomarkers were identified that may provide insight into the etiology of endothelial dysfunction and its link to future VTE, insufficient prospective evidence is available to formally recommend screening potential astronauts or healthy patients with any currently available novel biomarker. Conclusion: Our review highlights a critical knowledge gap regarding the role biomarkers of venous endothelial disruption have in predicting and identifying VTE. Future population-based prospective studies are required to link potential risk factors and biomarkers for venous endothelial dysfunction to occurrence of VTE.

Risk of neonatal hypothyroidism in newborns from mothers exposed to CTPA during pregnancy: Ancillary data from a prospective outcome study.

BACKGROUND: Neonatal hypothyroidism is often raised as a potential concern for the use of computed tomography pulmonary angiography (CTPA) in pregnant women with suspected pulmonary embolism (PE). OBJECTIVES: To assess the incidence of neonatal hypothyroidism among newborns from mothers exposed to CTPA. PATIENTS/METHODS: Pregnant women with clinically suspected PE were included in a multicenter, multinational prospective diagnostic management outcome study, based on pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb venous compression ultrasonography, and CTPA. Results of Guthrie tests were systematically collected for newborns of all women who required CTPA as part of the diagnostic strategy. A thyroid-stimulating hormone (TSH) level above 15 U/ml was used to define hypothyroidism. RESULTS: Out of the 166 women included in the Swiss participating centers, 149 underwent a CTPA including 14 with twin pregnancies. Eight women suffered a pregnancy loss and results of the Guthrie test could not be retrieved for four newborns. All TSH levels were reported as being below 15 U/ml. The incidence of neonatal hypothyroidism was 0/151 (0.0%, 95% confidence interval: 0.0%-2.5%). CONCLUSIONS: We did not identify any cases of neonatal hypothyroidism in our cohort of 149 pregnant women investigated for suspected PE using a CTPA. Along with previous literature data, this provides further reassuring data regarding the use of CTPA in this indication.

Rivaroxaban vs Dalteparin in Cancer-Associated Thromboembolism: A Randomized Trial.

BACKGROUND: Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE. RESEARCH QUESTION: Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE? STUDY DESIGN AND METHODS: In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months. RESULTS: Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio [SHR], 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97). INTERPRETATION: In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02746185; URL: www. CLINICALTRIALS: gov.

Acute ischaemia of the lower limb due to non-bacterial thrombotic endocarditis with recent venous thrombo-embolic disease as the initial manifestation of lung adenocarcinoma: a case report.

BACKGROUND: Non-bacterial thrombotic endocarditis is a rare condition. Optimal management is based on early diagnosis which remains difficult. CASE SUMMARY: A 75-year-old male patient was admitted to the hospital with acute ischaemia of the left lower limb due to popliteal artery occlusion despite anticoagulation with rivaroxaban for pulmonary embolism diagnosed 2 weeks earlier. Transoesophageal echocardiography (TOE) showed a mobile vegetation with mild mitral valve regurgitation. Positron emission tomography (PET) scan did not show hyperfixation at the mitral valve but rather lymphadenopathy hyperfixation at different sites. Biopsy of a lymph node from Barety's space identified a bronchopulmonary adenocarcinoma. The outcome was favourable after popliteal artery thrombectomy and low-molecular-weight heparin treatment. The patient was referred to the department of onco-pneumology for further care. DISCUSSION: Upon clinical presentation, the combination of an arterial and prior venous thrombotic event suggested that the origin could be either a patent foramen ovale (PFO) or a thrombosis from an underlying cancer. A transthoracic echocardiography and TOE excluded a PFO and demonstrated a mobile echogenic mass at the mitral valve site together with a mild regurgitation. The diagnosis of non-bacterial thrombotic endocarditis was suggested given the absence of clinical and biological infectious signs, negative blood cultures and serology for endocarditis, the presence of both arterial and venous thrombosis, as well as the presence of intra-thoracic lymphadenopathy hyperfixation on the PET scan for which a biopsy demonstrated lung adenocarcinoma.