Chronic thromboembolic pulmonary hypertension suspicion after pulmonary embolism in cancer patients.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe condition which should be screened in patient with persistent dyspnea after pulmonary embolism (PE). After PE, CTEPH incidence was estimated between 0.1 and 9.1% in overall patients. Although cancer is associated with an increased risk of CTEPH, CTEPH incidence is still unknown in cancer patients with PE. We aimed to estimate the frequency CTEPH-likely patients after PE, in cancer patients. MATERIALS: We individualized cancer patients of a monocentric prospective registry including consecutive patients with symptomatic PE. The primary outcome was the frequency of "CTEPH-likely" patients defined by the European Respiratory Society (ERS) guidelines (an accelerated tricuspid regurgitation more than 2.8m/s and at least 1-2 segmental or larger-sized defects, after more than 3 months of therapeutic anticoagulation). RESULTS: We included 129 cancer patients with PE. Colorectal cancer (19%), breast cancer (17%) and prostate cancer (15%) were the most frequent cancers. PE occurred after surgery or medical immobilization in 17% of patients, while 26% of patients had history of venous thromboembolism. During the follow-up, 2 patients (1.5%) had a clinical suspicion of CTEPH and only 1 patient with ovarian cancer (0.75% 95%CI [0.0%-2.2%]) was classified as "CTEPH-likely", 6 months after PE. CONCLUSION: The frequency of screening for CTEPH seems negligible in PE patients with cancer. Concomitant cancer may affect the clinical suspicion of CTEPH.

Assessment of clinically relevant bleeding as a surrogate outcome for major bleeding: validation by meta-analysis of randomized controlled trials.

Essentials Surrogacy of clinically relevant bleeding (CRB) for major bleeding has never been validated. Our meta-analysis evaluated CRB surrogacy in trials of new versus traditional anticoagulants. Surrogacy was not validated in orthopedic surgery, venous thromboembolism or atrial fibrillation The difficulty in demonstrating the surrogacy may reflect a lack of homogeneity in its definition SUMMARY: Background Clinically relevant bleeding (CRB), comprising major bleeding and clinically relevant non-major bleeding, has been used as a surrogate for major bleeding in most anticoagulant trials. The validity of this surrogate to estimate trade-off between thrombotic and bleeding events in clinical trials was never assessed. Methods We systematically reviewed randomized phase III trials comparing new anticoagulants with the standard of care for venous thromboembolism prevention following major orthopedic surgery, venous thromboembolism (VTE) treatment, or stroke and systemic embolism prevention in atrial fibrillation (AF), and reporting both major bleeding and CRB rates. The validity of CRB as a surrogate for major bleeding was assessed according to the strength of the association between the relative risks of major bleeding and CRB, measured by the use of R2trial and its 95% confidence interval (CI). Results In the postoperative prophylactic setting (13 studies), major bleeding and CRB rates were 1.12% and 3.56%, respectively, and R2trial was 0.69 (95% CI 0.34-0.93). For acute VTE studies (n = 12), major bleeding and CRB rates were 1.87% and 9.07%; the corresponding R2trial values were 0.28 (95% CI 0.01-0.80) and 0.68 (95% CI 0.09-1.00) when only double-blind studies were considered (n = 7). For AF studies (n = 7; 22 strata), major bleeding and CRB rates were 4.82% and 15.3%, and R2trial was 0.59 (95% CI 0.15-0.82). Conclusion Despite an apparent correlation between CRB and major bleeding in major orthopedic surgery, AF, and double-blind acute VTE studies, the wide CIs suggest that CRB might not be an acceptable surrogate outcome in any of these settings.

Bleeding risk of terminally ill patients hospitalized in palliative care units: the RHESO study.

Essentials Bleeding incidence as hemorrhagic risk factors are unknown in palliative care inpatients. We conducted a multicenter observational study (22 Palliative Care Units, 1199 patients). At three months, the cumulative incidence of clinically relevant bleeding was 9.8%. Cancer, recent bleeding, thromboprophylaxis and antiplatelet therapy were independent risk factors. SUMMARY: Background The value of primary thromboprophylaxis in patients admitted to palliative care units is debatable. Moreover, the risk of bleeding in these patients is unknown. Objectives Our primary aim was to assess the bleeding risk of patients in a real-world practice setting of hospital palliative care. Our secondary aim was to determine the incidence of symptomatic deep vein thrombosis and to identify risk factors for bleeding. Patients/Methods In this prospective, observational study in 22 French palliative care units, 1199 patients (median age, 71 years; male, 45.5%), admitted for the first time to a palliative care unit for advanced cancer or pulmonary, cardiac or neurologic disease were included. The primary outcome was adjudicated clinically relevant bleeding (i.e. a composite of major and clinically relevant non-major bleeding) at 3 months. The secondary outcome was symptomatic deep vein thrombosis. Results The most common reason for palliative care was cancer (90.7%). By 3 months, 1087 patients (91.3%) had died and 116 patients had presented at least one episode of clinically relevant bleeding (fatal in 23 patients). Taking into account the competing risk of death, the cumulative incidence of clinically relevant bleeding was 9.8% (95% confidence interval [CI], 8.3-11.6). Deep vein thrombosis occurred in six patients (cumulative incidence, 0.5%; 95% CI, 0.2-1.1). Cancer, recent bleeding, antithrombotic prophylaxis and antiplatelet therapy were independently associated with clinically relevant bleeding at 3 months. Conclusions Decisions regarding the use of thromboprophylaxis in palliative care patients should take into account the high risk of bleeding in these patients.

Frequency and prognostic value of cutaneous molecular residual disease in mycosis fungoides: a prospective multicentre trial of the Cutaneous Lymphoma French Study Group.

BACKGROUND: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. OBJECTIVES: To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. METHODS: Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. The results were compared with the clinical status each year for 4 years. RESULTS: We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61·8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46·6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50·5%) still being followed up were in CR and 44 of 109 (40·4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1·0; positive predictive value 36·4%; negative predictive value 67·6%). CONCLUSIONS: T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years.

Annual diagnosis rate of superficial vein thrombosis of the lower limbs: the STEPH community-based study.

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 [corrected]. 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.