Prognostic impact of acute kidney injury in patients with acute pulmonary embolism data from the RIETE registry.

Risk stratification is recommended for patients with pulmonary embolism (PE), and usually starts with the assessment of the hemodynamic status and the simplified Pulmonary Embolism Severity Index (sPESI). The influence of acute kidney injury (AKI) on the prognostic stratification has not been evaluated according to the "Kidney Disease: Improving Global Outcomes" (KDIGO). AKI was computed according to the KDIGO definition in patients with acute PE in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Patients with hemodynamic instability were considered high-risk. Normotensive patients were stratified according to the sPESI score (low-risk: sPESI = 0; intermediate-risk: sPESI > 0). The primary outcome was all-cause 30-day mortality. Secondary outcomes were major bleeding and VTE recurrences during the same period. Among 30,532 patients with PE, 1108 (3.6%) were classified to be at high-risk, 10,577 (34.6%) at low-risk, and the remaining 18,847 (61.8%) at intermediate-risk of adverse events. At baseline, 7879 (26%) had AKI. Overall, 1543 of 30,532 patients (5.1%) died within the first 30 days. The presence of AKI was associated with increased mortality rates in all subgroups of patients: in those at low-risk it increased from 0.46 to 3%, in intermediate-risk from 5.4 to 10%, and in high-risk patients from 9.4 to 18%. The presence of AKI was also associated with an increased risk of major bleeding in all subgroups. The addition of the AKI status to the sPESI score improved the prediction of the 30-day mortality and may be particularly helpful for decisions such as identification of low-risk patient for home discharge.

In patients with unprovoked VTE, does the addition of FDG PET/CT to a limited occult cancer screening strategy offer good value for money? A cost-effectiveness analysis from the publicly funded health care systems.

INTRODUCTION: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an undiagnosed cancer. We assessed the cost-effectiveness of 18F-Fluorodesoxyglucose Positron Emission/Computed Tomography (FDG PET/CT) plus limited screening and limited screening strategies in patients with unprovoked VTE from the perspectives of the Ontario (Canada) and French health care systems. METHODS: We conducted a cost-effectiveness analysis based on a published randomized controlled trial of 394 patients aged 18 years or older who were diagnosed with unprovoked VTE. We obtained data with respect to efficacy and health care utilization from the published trial. The primary measure of effectiveness was the number of avoided cases of delayed cancer diagnosis and the secondary measure of effectiveness was the quality adjusted life year (QALY) at the end of the study in each group. We used generalized linear models to estimate incremental cost-effectiveness ratios (ICER) while controlling for patient demographic and clinical characteristics. Results were presented as the incremental cost to avoid one case of delayed cancer diagnosis and the incremental cost per QALY gained. The 95% confidence intervals (CIs) were estimated using bootstrap re-sampling procedures with 5000 iterations. RESULTS: Compared to a limited screening strategy, the ICER of limited strategy plus FDG PET/CT scan was C$ 26,840.19 (95% CI: C$ 24,046.51; C$ 34,581.53) per one avoided case of delayed cancer diagnosis from the Ontario health system perspective and €16,370.45 (95% CI: € 9904.48; € 39,578.91) per one avoided case of delayed cancer diagnosis from the French health system perspective. The probabilities that addition of FDG PET/CT to limited screening is cost-effective rose with increasing willingness to pay values. Compared with the limited screening, the extensive screening was associated with C$ 3412.85 per QALY gained (95% CI: 1463.89; -13,935.88) from the Ontario health system perspective and €2162.83 per QALY gained (95% CI 958.78; -10,544.42) from the French health system perspective. CONCLUSION: Addition of a FDG PET/CT for occult cancer diagnosis was associated with better health outcomes (fewer cases of delayed cancer diagnosis and greater QALYs) and a higher cost from the perspective of publicly funded health care systems; the cost-effectiveness results are however highly uncertain.

Cancer-associated thrombosis in patients with implanted ports: a prospective multicenter French cohort study (ONCOCIP).

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.

Anticoagulant therapy for venous thromboembolism in patients with inflammatory bowel disease.

BACKGROUND: There is lack of evidence to guide the type, intensity, and the duration of anticoagulation following venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Registro Informatizado Enfermedad Trombo Embólica (RIETE) is an ongoing, multicenter, observational registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We used the RIETE database to compare the rate of VTE recurrences and major bleeding during the course of anticoagulation in noncancer patients with or without IBD. RESULTS: As of October 2014, 41 927 patients without active cancer have been recruited in RIETE. Of these, 265 (0.63%) had IBD and 85 (32%) had the VTE during an acute flare. The duration of anticoagulation was similar in patients with VTE during an acute flare (8.3±8.8 months), in remission (9.4±11.5 months), or without IBD (10.0±12.8 months). The rate of VTE recurrences [7.25, 95% confidence interval (CI): 1.46-21.2; 8.84, 95% CI: 3.23-19.2; and 5.85, 95% CI: 5.46-6.26 per 100 patient-years, respectively] and major bleeding (7.25, 95% CI: 1.46-21.2; 2.95, 95% CI: 0.33-10.6; and 4.79, 95% CI: 4.44-5.15, respectively) were similar in all three subgroups. Propensity score matching analysis confirmed the absence of differences in the rate of VTE recurrences (rate ratio: 1.16, 95% CI: 0.54-2.47) or major bleeding (rate ratio: 0.84, 95% CI: 0.31-2.23) between patients with or without IBD. CONCLUSION: Therapeutic anticoagulation for patients with IBD and VTE is as safe and effective as for those with VTE without IBD.

Predictors of Early Mortality in Cancer-Associated Thrombosis: Analysis of the RIETE Database.

Cancer-associated thrombosis (CT) carries a high, heterogeneous, and poorly predicted likelihood of mortality. Thus, we aimed to define predictors of 30-day mortality in 10,025 patients with CT. In a randomly selected derivation cohort, we used recursive partitioning analysis to detect variables that select for a risk of mortality within 30 days. In a validation cohort, we evaluated our results using Cochran-Armitage test. The most common types of cancer were lung (16%), breast (14%), and colorectal (14%); median age was 69 years (range, 14-101); most had metastatic disease (63%); 13% of patients died within 30 days. In the derivation cohort ( n = 6,660), a white blood cell (WBC) count in the highest quartile predicted early mortality (odds ratio, 7.8; 95% confidence interval [CI], 4.6-13.1); and the presence of metastatic disease, pulmonary embolism (PE), and immobility defined the risk of those with normal WBC count. We defined death risk according four sequential questions: (1) Does the patient have an elevated WBC count? (Yes, group D). (2) If no, does the patient have metastasis? (No, group A). (3) If yes, is the patient immobile? (Yes, group D). (4) If no, does the patient have a PE? (Yes, group C; no, group B). In the validation cohort ( n = 3,365), the 30-day risk of death was 2.9% in group A (95% CI, 1.9-4.3), compared with 25% in group D (95% CI, 22.5-27.5), and there was a rate escalation between groups ( p for trend < 0.01). In conclusion, with four sequential questions, the risk of death in CT can be easily stratified. An elevated WBC count at baseline predicted 30-day mortality better than metastases, PE, or immobility.

Risk factors of occult malignancy in patients with unprovoked venous thromboembolism.

Venous thromboembolism (VTE) can occur as the first manifestation of an underlying occult malignancy. It remains unclear whether or not a better selection of high risk patients might lead to more efficient occult cancer screening strategies. Our aim was to assess the predictors of occult malignancy diagnosis in patients with unprovoked VTE. Univariate analyses were performed to assess the effect of candidate predictors on occult cancer detection in patients enrolled in a prospective, multicenter, randomized, controlled study (MVTEP study) whose primary aim was to compare a limited screening strategy with a strategy combining limited screening and FDG PET/CT in patients with unprovoked VTE. This trial is completed and registered with ClinicalTrials.gov, number NCT00964275. Between March 3, 2009, and August 18, 2012, 399 patients were included. Five patients withdrew consent and refused the use of their data, and no VTE was confirmed in 2 patients who were excluded from this analysis. A total of 25 (6.4%) out of the 392 analysed patients received a new diagnosis of malignancyduring the 2-years follow-up. Age≥50years (p=0.01), male gender (p=0.04), leukocytes count (p=0.01), and platelets count (p=0.03) were associated with occult cancer detection. Patients with leukocytosis or thrombocytosis had a risk of cancer way above 10%. Previous VTE and smoker status (combining previous and current smokers) were not associated with occult cancer diagnosis (p>0.05). Demographic characteristics (age and sex), and laboratory tests (high platelets and leukocytes counts) may be associated with cancer detection in patients withunprovoked VTE.

Performance of 18F-fluorodesoxyglucose positron-emission tomography combined with low-dose computed tomography for cancer screening in patients with unprovoked venous thromboembolism.

PURPOSE: Small series have suggested that Fluorodesoxyglucose Positron-Emission-Tomography with Computed-Tomography (FDG-PET/CT) is feasible to screen for cancer in patients with unprovoked venous thromboembolism (VTE), but without validation in a large population. The aim was to assess diagnostic accuracy indices of FDG-PET/CT for occult cancer diagnosis in patients with unprovoked VTE. MATERIALS AND METHODS: We analysed patients from the FDG-PET/CT group of a randomized trial that compared a screening strategy based on FDG-PET/CT with a limited screening strategy for occult malignancy detection in patients with unprovoked VTE. FDG-PET/CT was interpreted as positive for cancer, as negative or as equivocal. Patients were considered as having cancer on the basis of screening results, or of any test performed during a two-years follow-up period. We ran two sets of analysis, considering patients with equivocal FDG-PET/CT as positive, then as negative for malignancy. RESULTS: Between March 2009, and August 2012, 172 patients were included. FDG-PET/CT was interpreted as positive for malignancy in 10 patients (5.8%), as equivocal in 23 patients (13.4%) and as negative in 139 patients (80.8%). Malignancy was diagnosed in 7/10 (70.0%), 2/23 (8.7%) and 1/139 (0.7%) patients, respectively. Grouping positive and equivocal results, sensitivity and specificity were 90% (95%CI 60% to 98%) and 85% (95%CI 79% to 90%), respectively. Grouping negative and equivocal results, sensitivity and specificity were 70% (95%CI 40% to 89%) and 98% (95%CI 95% to 99%), respectively. CONCLUSION: FDG-PET/CT showed good accuracy for occult cancer screening in patients with unprovoked VTE. Remaining challenges include the need to define specific interpretation criteria in this dedicated population.

Additional testing following screening strategies for occult malignancy diagnosis in patients with unprovoked venous thromboembolism.

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.

Prior thromboprophylaxis and outcome in patients experiencing acute venous thromboembolism after an acute medical illness.

BACKGROUND: Even despite the use of thromboprophylaxis, some patients with an acute medical illness develop symptomatic venous thromboembolism (VTE). It is unclear whether the outcome in these patients is different in those in whom prophylaxis was not prescribed. PATIENTS AND METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to compare the 3-month outcome (death, fatal pulmonary embolism, VTE recurrences, major bleeding) of patients with acute VTE after immobilization for an acute medical disease, according to the use of prophylaxis. RESULTS: Thromboprophylaxis was prescribed in 1313 (37%) of the 3527 patients included in August 2014. Acute infection was the most frequent cause of immobilization. Patients who received prophylaxis were more frequently immobilized in hospital than at home (70% vs. 22%), and fewer patients were immobilized for cancer (13% vs. 22%). During the first 3months of treatment, the rates of all-cause death (23 vs. 21%), fatal PE (2.6 vs. 3.1%), VTE recurrences (2.4% vs. 2.8%), and major bleeding (4.2% for both) did not differ between the two groups. Thromboprophylaxis was not associated with each outcome in multivariate analysis. CONCLUSIONS: The outcome in patients with VTE provoked by medical immobilization was not influenced by the use of thromboprophylaxis during the period of immobility.

Seasonal variation in the superficial vein thrombosis frequency.

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

[Pulmonary hypertension in the elderly]. / Hypertension pulmonaire chez la personne âgée.

In the past decade, a significant improvement has been done in the management of pulmonary arterial hypertension, a devastating disease. Beside the aging population, one of the next challenges is to develop a specific management of a pulmonary hypertension's suspicion, in the aged patients. In fact, recent data have shown that if pulmonary hypertension were mostly related to chronic heart or lung failure, or pulmonary embolism, some elderly may in fact develop a real pulmonary arterial hypertension. Because of the potential therapies which may be proposed, the evaluation of a pulmonary hypertension's suspicion in the elderly needs a stringent evaluation by trained physicians, in collaboration with geriatricians.

[Thromboprophylaxis in medical patients: Which modifications with the new oral anticoagulants?]. / Thromboprophylaxie en médecine : quelles modifications avec les nouveaux anticoagulants oraux ?

Thromboprophylaxis with low molecular weight heparin or fondaparinux is associated with a 50% reduction in the risk of venous thrombo-embolism (VTE) in medical patients. Thromboprophylaxis is indicated in the prevention of VTE in medical patients at risk of VTE. Extended thromboprophylaxis with apixaban is associated with a greater reduction in VTE events but also with an increase in bleeding events when compared to standard therapy with enoxaparine. Extended thromboprophylaxis with rivaroxaban is associated with a greater reduction in VTE events but also with an increase in bleeding events, when compared to standard therapy with enoxaparine. Rivaroxaban and apixaban are currently not indicated in medical prophylaxis.

[Venous thromboembolism medical thromboprophylaxis in patients admitted to palliative units]. / Prophylaxie médicamenteuse de la maladie veineuse thromboembolique en soins palliatifs.

Venous thromboembolism incidence as identification of bleeding risk factors is not well defined in patients admitted to palliative units. There is no randomized controlled trial evaluating medical thromboprophylaxis in patients admitted to palliative units. Medical thromboprophylaxis seems to be inappropriate in patients admitted to palliative units. Medical thromboprophylaxis prescription should be discussed individually in patients admitted to palliative units. Conversely, cancer patients admitted for an acute medical disease should receive medical thromboprophylaxis, if their prognosis exceeds several months.

Epidemiology, diagnosis, treatment and management of superficial-vein thrombosis of the legs.

Recent data on lower-limb superficial-vein thrombosis (SVT) may substantially impact its clinical management. Particularly, 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 is 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. More recent data from another randomized trial support these 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, wherever the cost of fondaparinux is acceptable. Superficial-vein thrombosis (SVT) of the lower limbs has long been regarded as a benign, self-limiting disease, expected to resolve spontaneously and rapidly, and requiring only symptomatic treatments [1,2]. However, the perception of this disease is now changing with the recent publication of data indicating its potential severity [3] and showing for the first time the benefit of a therapeutic strategy based on the administration of an anticoagulant treatment [4]. The overall management of this frequent disease therefore needs to be reconsidered.