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International audience; The benefit of early admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) as soon as they develop organ injury is unknown. We performed a retrospective study on 92 patients admitted to the ICU to determine the impact of time from organ injury to ICU admission on outcome. The number of organ injuries prior to ICU admission was associated with an increased in-hospital mortality (OR 1.7, 95% CI 1–2.7, p = 0.04). Time between first organ injury and ICU admission was also associated with an increased in-hospital survival (OR 1.4, 95% CI 1.1–1.8, p = 0.02). A score combining these two covariates—the number of organ injuries/day (sum of days spent with each individual organ injury)—further improved the prediction of hospital survival. Patients with more organ injuries/day had significantly higher in-hospital mortality rate even after adjustment for refractory acute GVHD and the SOFA (OR 1.3, 95% CI 1–1.7, p = 0.02). Early ICU admission of allogeneic SCT recipients to the ICU as soon as they develop organ injury is associated with decreased in-hospital mortality.

Summary Background The ability of the pulmonary embolism rule-out criteria (PERC) to exclude pulmonary embolism without further testing remains debated outside the USA, especially in the population with suspected pulmonary embolism who have a high prevalence of the condition. Our main objective was to prospectively assess the predictive value of negative PERC to rule out pulmonary embolism among European patients with low implicit clinical probability. Methods We did a multicentre, prospective, observational study in 12 emergency departments in France and Belgium. We included consecutive patients aged 18 years or older with suspected pulmonary embolism. Patients were excluded if they had already been hospitalised for more than 2 days, had curative anticoagulant therapy in progress for more than 48 h, or had a diagnosis of thromboembolic disease documented before admission to emergency department. Physicians completed a standardised case report form comprising implicit clinical probability assessment (low, moderate, or high) and a list of risk factors including criteria of the PERC rule. They were asked to follow international recommendations for diagnostic strategy, masked to PERC assessment. The primary endpoint was the proportion of patients with low implicit clinical probability and negative PERC who had venous thromboembolic events, diagnosed during initial diagnostic work-up or during 3-month follow-up, as externally adjudicated by an independent committee masked to the PERC and clinical probability assessment. The upper limit of the 95% CI around the 3-month thromboembolic risk was set at 3%. We did all analyses by intention to treat, including all patients with complete follow-up. This trial is registered with ClinicalTrials.gov, number NCT02360540. Findings Between May 1, 2015, and April 30, 2016, 1773 consecutive patients with suspected pulmonary embolism were prospectively assessed for inclusion, of whom 1757 were included. 1052 (60%) patients were classed as having low clinical probability, 49 (4·7%, 95% CI 3·5–6·1) of whom had a venous thromboembolic event. In patients with a low implicit clinical probability, 337 (32%) patients had negative PERC, of whom four (1·2%; 95% CI 0·4–2·9) went on to have a pulmonary embolism. Interpretation In European patients with low implicit clinical probability, PERC can exclude pulmonary embolism with a low percentage of false-negative results. The results of our prospective, observational study allow and justify an implementation study of the PERC rule in Europe. Funding French Ministry of Health.

International audience; Background. Admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) remains controversial , especially when graft-versus-host disease (GVHD) is present. Methods. We performed a retrospective study to assess prognostic factors of survival in all allogeneic SCT recipients admitted to the ICU between 2002 and 2013 in our center which has flexible admission criteria, especially regarding GVHD. Results. Of 349 patients who underwent allogeneic SCT during the study period, 92 patients (26%) were admitted to the ICU. Intensive care unit and hospital discharge rates were 66% and 46%, respectively , whereas 1 year survival was 24%. Acute GVHD, either grade III to IV (30 patients, 33%) or refractory (12 patients, 13%) had a nonsignificant impact on hospital mortality (odds ratio [OR], 2.1; P = 0.1; OR, 5, P = 0.05, respectively). Fifty percent of patients required invasive mechanical ventilation, 30% required vasopressors, 17% required renal replacement therapy, and 28% had liver impairment (bilirubin >34 μmol/L), each of these parameters defining organ failure. Mortality was closely associated with the number of organ failures as hospital discharge rates were 69%, 50%, 42%, and 0% among patients with 0 (26 patients), 1 (26 patients), 2 (26 patients), and 3 to 4 (14 patients) organ failures, respectively (OR, 2.7; 95% confidence interval, 1.6-4.6; P < 0.001 according to the number of organ failures). Conclusions. Early mortality of allogeneic SCT recipients admitted to the ICU is especially influenced by the number of organ failures and therefore patients with 0 to 2 organ failures should be considered if required. Refractory GVHD affects survival but not within the confined ICU admission.

18F-Fluorodesoxyglucose Positron-Emission-Tomography combined with Computed-Tomography (FDG PET/CT) might be an attractive tool for cancer screening in patients with venous thromboembolism (VTE), allowing non-invasive whole-body imaging. One of the frequent criticisms to the use of FDG PET/CT for screening is the potential for false positive results leading to unnecessary/invasive investigations. Our aim was to compare the frequency and invasiveness of additional testing following extensive and limited screening strategies for occult malignancy in patients with unprovoked VTE. We analysed patients included in the MVTEP study, a randomized trial that compared a screening strategy based on FDG-PET/CT with a limited screening strategy for occult malignancy diagnosis in patients with unprovoked VTE. All additional diagnostic procedures following screening were recorded and classified as invasive or non-invasive. A total of 394 patients were analysed. Additional diagnostic procedures realized in patients of each group consisted of 59 tests in patients of the FDG PET/CT group versus 53 tests among the patients from the limited screening group (p=0.65). Overall, 45 (22.8%) patients in the FDG PET/CT group underwent additional diagnostic tests, versus 32 (16.2%) in the limited screening group (absolute risk difference+6.6%, 95% CI -1.3 to +14.4%, p=0.13). Sixteen (8.1%) patients in the FDG PET/CT group underwent invasive procedures, versus 6 (3%) in the limited screening group (absolute risk difference+5.1%, 95% CI +0.5 to +10.0%, p=0.03). We found no statistical difference in the number of additional procedures following each screening strategy. However, a higher number of invasive tests were performed in the FDG PET/CT group.

International audience; BACKGROUND: Multislice CT (MSCT) combined with D-dimer measurement can safely exclude pulmonary embolism in patients with a low or intermediate clinical probability of this disease. We compared this combination with a strategy in which both a negative venous ultrasonography of the leg and MSCT were needed to exclude pulmonary embolism. METHODS: We included 1819 consecutive outpatients with clinically suspected pulmonary embolism in a multicentre non-inferiority randomised controlled trial comparing two strategies: clinical probability assessment and either D-dimer measurement and MSCT (DD-CT strategy [n=903]) or D-dimer measurement, venous compression ultrasonography of the leg, and MSCT (DD-US-CT strategy [n=916]). Randomisation was by computer-generated blocks with stratification according to centre. Patients with a high clinical probability according to the revised Geneva score and a negative work-up for pulmonary embolism were further investigated in both groups. The primary outcome was the 3-month thromboembolic risk in patients who were left untreated on the basis of the exclusion of pulmonary embolism by diagnostic strategy. Clinicians assessing outcome were blinded to group assignment. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00117169. FINDINGS: The prevalence of pulmonary embolism was 20.6% in both groups (189 cases in DD-US-CT group and 186 in DD-CT group). We analysed 855 patients in the DD-US-CT group and 838 in the DD-CT group per protocol. The 3-month thromboembolic risk was 0.3% (95% CI 0.1-1.1) in the DD-US-CT group and 0.3% (0.1-1.2) in the DD-CT group (difference 0.0% [-0.9 to 0.8]). In the DD-US-CT group, ultrasonography showed a deep-venous thrombosis in 53 (9% [7-12]) of 574 patients, and thus MSCT was not undertaken. INTERPRETATION: The strategy combining D-dimer and MSCT is as safe as the strategy using D-dimer followed by venous compression ultrasonography of the leg and MSCT for exclusion of pulmonary embolism. An ultrasound could be of use in patients with a contraindication to CT.

Objectives In older patients, the the D-dimer test for pulmonary embolism has reduced specificity and is therefore less useful. In this study a new, age dependent cut-off value for the test was devised and its usefulness with older patients assessed. Design Retrospective multicentre cohort study. Setting General and teaching hospitals in Belgium, France, the Netherlands, and Switzerland. Patients 5132 consecutive patients with clinically suspected pulmonary embolism. Intervention Development of a new D-dimer cut-off point in patients aged >50 years in a derivation set (data from two multicentre cohort studies), based on receiver operating characteristics (ROC) curves. This cut-off value was then validated with two independent validation datasets. Main outcome measures The proportion of patients in the validation cohorts with a negative D-dimer test, the proportion in whom pulmonary embolism could be excluded, and the false negative rates. Results The new D-dimer cut-off value was defined as (patient's age x 10) mu g/l in patients aged >50. In 1331 patients in the derivation set with an "unlikely" score from clinical probability assessment, pulmonary embolism could be excluded in 42% with the new cut-off value versus 36% with the old cut-off value (70 years, ranging from 13% to 16% in the three datasets. The failure rates (all ages) were 0.2% (95% CI 0% to 1.0%) in the derivation set and 0.6% (0.3% to 1.3%) and 0.3% (0.1% to 1.1%) in the two validation sets. Conclusions The age adjusted D-dimer cut-off point, combined with clinical probability, greatly increased the proportion of older patients in whom pulmonary embolism could be safely excluded.

SummaryPractice guidelines recommend outpatient care for selected patients with non-massive pulmonary embolism (PE), but fail to specify how these low-risk patients should be identified. Using data from U.S. patients, we previously derived the Pulmonary Embolism Severity Index (PESI), a prediction rule that risk stratifies patients with PE. We sought to validate the PESI in a European patient cohort. We prospectively validated the PESI in patients with PE diagnosed at six emergency departments in three European countries. We used baseline data for the rule’s 11 prognostic variables to stratify patients into five risk classes (I-V) of increasing probability of mortality. The outcome was overall mortality at 90 days after presentation.To assess the accuracy of the PESI to predict mortality, we estimated the sensitivity, specificity, and predictive values for low- (risk classes I/II) versus higher- risk patients (risk classes III-V), and the discriminatory power using the area under the receiver operating characteristic (ROC) curve. Among 357 patients with PE, overall mortality was 5.9%, ranging from 0% in class I to 17.9% in class V. The 186 (52%) low-risk patients had an overall mortality of 1.1% (95% confidence interval [CI]: 0.1–3.8%) compared to 11.1% (95% CI: 6.8–16.8%) in the 171 (48%) higher- risk patients. The PESI had a high sensitivity (91%,95% CI: 71–97%) and a negative predictive value (99%, 95% CI: 96–100%) for predicting mortality. The area under the ROC curve was 0.78 (95% CI:0.70–0.86). The PESI reliably identifies patients with PE who are at low risk of death and who are potential candidates for outpatient care. The PESI may help physicians make more rational decisions about hospitalization for patients with PE.

SummaryThe presence of a clot – even asymptomatic – in the proximal lower limb veins of a patient with clinically suspected pulmonary embolism (PE) provides evidence for venous thromboembolism and indicates anticoagulant therapy in such patients. We aimed at assessing the diagnostic performance of compression ultrasonography as compared to multi-slice computed tomography (MSCT) for the diagnosis of PE. We analyzed data from a large outcome management study that included consecutive outpatients referred to the emergency ward with clinically suspected PE. All high clinical probability patients, and all non-high clinical probability patients with a positive D-dimer test underwent both MSCT and CUS. Of the 756 included patients, 232 had PE ruled out on the basis of a negative D-dimer test, and 524 patients underwent both MSCT and CUS. PE was found in 187 out of the 511 patients witha conclusive MSCT. The sensitivity of CUS for the presence of PE on MSCT was 39% (95% confidence interval: 32 to 46%), and its specificity was 99% (95% CI:97 to 100%). Positive and negative likelihood ratios were 42.2 (95% CI: 13.5 to 131.9) and 0.6 (95% CI: 0.5 to 0.7), respectively. We conclude from that large study of unselected patients that CUS has high specificity but low sensitivity, for the diagnosis of PE at MSCT in suspected patients. It allows ruling in the diagnosis of PE without further invasive and/or expensive testing in suspected patients.

International audience; BACKGROUND: D-dimer levels remain elevated in many patients after completion of a 6-month anticoagulant drug course for a first episode of venous thromboembolism (VTE), which may limit the clinical usefulness of D-dimer testing for ruling out a possible recurrence. METHODS: We assessed the safety and usefulness of D-dimer testing in patients with suspected pulmonary embolism (PE) who had experienced a previous VTE. We analyzed data from 2 outcome studies that enrolled 1721 consecutive emergency department patients with clinically suspected PE. Information on the existence of a previous episode of VTE was abstracted from the database. All the patients underwent a sequential diagnostic workup, including an enzyme-linked immunosorbent assay D-dimer test and a 3-month follow-up. RESULTS: The proportion of confirmed PE was 24.1% (415/1719); PE was ruled out by a negative D-dimer test result in 32.7% (462/1411) of the patients without previous VTE but in only 15.9% (49/308) of the patients with previous VTE (P

SummaryLimited data are available about the diagnostic value of D-dimer testing in cancer patients with clinically suspected pulmonary embolism (PE).Therefore, we evaluated i) the safety and clinical usefulness of an ELISA D-dimer test to rule out PE in cancer patients compared with non-cancer patients and ii) whether adopting a higher D-dimer cut-off value might increase the usefulness of D-dimer in cancer patients. We analysed data from two outcome studies which enrolled 1,721 consecutive patients presenting in the emergency department with clinically suspected PE. Presence of an active malignancy was abstracted from the database. All patients underwent a sequential diagnostic work-up including an ELISA D-dimer test and a 3-month followup. Sensitivity and predictive value (NPV) were 100% in both cancer and non-cancer patients. PE was ruled out by a negative D-dimer test in 494/1,554 (32%) patients without cancer, and in 18/164 (11%) patients witha malignancy. At cut-off values varying from 500 to 900 µg/l, the sensitivity was unchanged (100%, 95% CI: 93% to 100%) and the specificity increased from 16% (95% CI:11% to 24%) to 30% (95% CI:22% to 39%).The 3-month thromboembolic risk was 0% (95 % CI: 0% to 18%) in cancer patients witha negative D-dimer test. ELISA D-dimer appears safe to rule out pulmonary embolism in cancer patients but it is negative in only one of ten patients at the usual cut-off value. Increasing the cut-off value of D-dimer in cancer patients might increase the test’s clinical usefulness.

International audience; BACKGROUND: Single-detector-row computed tomography (CT) has a low sensitivity for pulmonary embolism and must be combined with venous-compression ultrasonography of the lower limbs. We evaluated whether the use of D-dimer measurement and multidetector-row CT, without lower-limb ultrasonography, might safely rule out pulmonary embolism. METHODS: We included 756 consecutive patients with clinically suspected pulmonary embolism from the emergency departments of three teaching hospitals and managed their cases according to a standardized sequential diagnostic strategy. All patients were followed for three months. RESULTS: Pulmonary embolism was detected in 194 of the 756 patients (26 percent). Among the 82 patients with a high clinical probability of pulmonary embolism, multidetector-row CT showed pulmonary embolism in 78, and 1 patient had proximal deep venous thrombosis and a CT scan that was negative for pulmonary embolism. Of the 674 patients without a high probability of pulmonary embolism, 232 (34 percent) had a negative D-dimer assay and an uneventful follow-up; CT showed pulmonary embolism in 109 patients. CT and ultrasonography were negative in 318 patients, of whom 3 had a definite thromboembolic event and 2 died of possible pulmonary embolism during follow-up (three-month risk of thromboembolism, 1.7 percent; 95 percent confidence interval, 0.7 to 3.9). Two patients had proximal deep venous thrombosis and a negative CT scan (risk, 0.6 percent; 95 percent confidence interval, 0.2 to 2.2). The overall three-month risk of thromboembolism in patients without pulmonary embolism would have been 1.5 percent (95 percent confidence interval, 0.8 to 3.0) if the D-dimer assay and multidetector-row CT had been the only tests used to rule out pulmonary embolism and ultrasonography had not been performed. CONCLUSIONS: Our data indicate the potential clinical use of a diagnostic strategy for ruling out pulmonary embolism on the basis of D-dimer testing and multidetector-row CT without lower-limb ultrasonography. A larger outcome study is needed before this approach can be adopted.