Culture and Use of Mesenchymal Stromal Cells in Phase I and II Clinical Trials

Present in numerous tissues, mesenchymal stem cells/multipotent stromal cells (MSCs) can differentiate into different cell types from a mesoderm origin. Their potential has been extended to pluripotency, by their possibility of differentiating into tissues and cells of nonmesodermic origin. Through the release of cytokines, growth factors and biologically active molecules, MSCs exert important paracrine effects during tissue repair and inflammation. Moreover, MSCs have immunosuppressive properties related to non-HLA restricted immunosuppressive capacities. All these features lead to an increasing range of possible applications of MSCs, from treating immunological diseases to tissue and organ repair, that should be tested in phase I and II clinical trials. The most widely used MSCs are cultured from bone marrow or adipose tissue. For clinical trial implementation, BM MSCs and ADSCs should be produced according to Good Manufacturing Practices. Safety remains the major concern and must be ensured during culture and validated with relevant controls. We describe some applications of MSCs in clinical trials

Exercise therapy for chronic symptomatic peripheral artery disease:A clinical consensus document of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases in collaboration with the European Society of Vascular Medicine and the European Society for Vascular Surgery

All guidelines worldwide strongly recommend exercise as a pillar in the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research.</p

Exercise therapy for chronic symptomatic peripheral artery disease:A clinical consensus document of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases in collaboration with the European Society of Vascular Medicine and the European Society for Vascular Surgery

All guidelines worldwide strongly recommend exercise as a pillar in the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research.</p

Exercise therapy for chronic symptomatic peripheral artery disease

Summary: All guidelines worldwide strongly recommend exercise as a pillar in the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research

Chronic kidney disease and the short-term risk of mortality and amputation in patients hospitalized for peripheral artery disease

International audienceObjective: The aim of the present study was to determine the prevalence of chronic kidney disease (CKD) and its prognostic value in patients hospitalized for lower extremity peripheral artery disease (PAD).Methods: Data from the COhorte des Patients ARTériopathes registry, a prospective multicenter, observational study of consecutive patients hospitalized for PAD in academic hospitals of southwestern France, were analyzed. All the subjects were in Rutherford grade ≥ 3, and 55.6% were in grade ≥ 5-6. Associations between CKD and 1-year mortality, as well as amputation rates, were evaluated by Cox analysis. Kaplan-Meier survival curves were analyzed according to estimated glomerular filtration rate (eGFR).Results: From May 2004 to January 2009, we enrolled 1010 patients. They were classified into four groups according to the eGFR: 21.7% were in group 1 (≥ 90 mL/min per 1.73 m(2)), 34% in group 2 (60-89 mL/min per 1.73 m(2)), 32.2% in group 3 (30-59 mL/min per 1.73 m(2)), and 12.1% in group 4 (<30 mL/min per 1.73 m(2) including dialysis). All-cause mortality was 25.1% at 1 year. The rate of major amputation was 26.3%. Mortality rates were, respectively, at 16%, 18%, 31.7%, and 44.3% (P < .0001) in groups 1 to 4. The major amputation rates were at 23.7%, 21.5%, 28%, and 40.2% (P = .0006), respectively. The presence of severe CKD (group 4) was associated with all-cause mortality (hazard ratio, 1.84; 95% confidence interval, 1.02-3.32; P = .044). In contrast, the risk of amputation was not associated with CKD after adjustments to risk factors.Conclusions: The prevalence of CKD in patients hospitalized for PAD is high. CKD is an independent predictor of 1-year mortality, but is not an independent predictor of limb amputation

Impact of angiotensin receptor blockers on mortality after hospitalization for symptomatic lower extremity artery disease

International audienceAims: The objective was to assess the association between angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) prescription at discharge in patients hospitalized for symptomatic lower extremity artery disease (LEAD) and 1-year mortality.Methods and results: The COPART registry is a multicentre, prospective, observational, cohort study which includes consecutive patients hospitalized for symptomatic LEAD in four French academic centres. All-cause mortality during a 1-year follow-up after hospital discharge was compared between patients with ARB, patients with ACEI and patients without ARB or ACEI. Analyses were performed using Cox models. As a sensitivity analysis, a propensity score (PS)-matching analysis was carried out. Among 1981 patients, 421 had ARB (21.3%), 766 ACEI (38.7%), and 794 no ACEI/ARB (40.1%) at discharge. During the 1-year follow-up, incidence rates for mortality were 12.6/100 person-years [95% confidence interval (CI) 9.7-16.1] for patients with ARB, 15.8/100 person-years (95% CI 13.4-18.6) for patients with ACEI and 19.8/100 person-years for patients without ACEI/ARB (95% CI 17.2-22.8). In a multivariate Cox model, ARB at discharge was associated with decreased mortality compared with no ACEI/ARB, hazard ratio (HR) 0.68 (95% CI 0.49-0.95), and with ACEI, HR 0.69 (95% CI 0.49-0.97). These results are consistent with those obtained by the Cox analyses in the PS-matched sample: HR 0.68 (95% CI 0.47-0.98) for patients with ARB compared with no ARB.Conclusion: Angiotensin receptor blockers at discharge after hospitalization for symptomatic LEAD is associated with a better survival compared with ACEI or no ACEI/ARB

Editor's Choice – External Applicability of the COMPASS and VOYAGER-PAD Trials on Patients with Symptomatic Lower Extremity Artery Disease in France: The COPART Registry

The COPART registry is supported by the French Vascular Medicine Society (SFMV) and received grants from Toulouse University Hospital, AstraZeneca France, Bayer France, Bristol-Myers Squibb (BMS) France, and Sanofi-Aventis France.International audienceObjective: The aim of this study was to examine the external applicability of the COMPASS and the VOYAGER-PAD trials in patients with lower extremity artery disease (LEAD) in the real world.Methods: This was a multicentre retrospective analysis of prospectively collected COPART data, a French multicentre registry of patients hospitalised for symptomatic LEAD. The proportion of patients eligible for the combination of rivaroxaban 2.5 mg twice daily plus aspirin based on either COMPASS or VOYAGER-PAD criteria is reported. The one year cumulative incidence of outcomes between eligible and non-eligible patients, as well as eligible patients vs. control arms of the COMPASS (LEAD patient subgroup) and the VOYAGER-PAD trials were compared. Analyses were performed using Cox models.Results: Of 2 259 evaluable patients, only 679 (30.1%) were eligible for a low dose rivaroxaban plus aspirin regimen. Others were not eligible because of the need for anticoagulant (48.5% and 38.9% of patients meeting COMPASS and VOYAGER-PAD exclusion criteria, respectively) or dual antiplatelet therapy use (15.7% and 16.5%, respectively), high bleeding risk (14.4% and 11.6%, respectively), malignancy (26.1% and 21.0%, respectively), history of ischaemic/haemorrhagic stroke (21.1% and 19.8%, respectively), and severe renal failure (13.2% and 10.5%, respectively). COMPASS and VOYAGER-PAD eligible and ineligible patients were at higher risk of ischaemic events than participants in these trials. The one year cumulative incidences were 6.0% (95% CI 4.3 - 8.1) in the COMPASS eligible subset vs. 3.5% (95% CI 2.9 - 4.3) in the COMPASS control arm for major adverse cardiovascular events, and 27.9% (95% CI 19.9 - 38.3) in the VOYAGER-PAD eligible subset vs. 6.0% (95% CI 5.3 - 6.9) in the VOYAGER-PAD control arm for major adverse limb events.Conclusion: Many patients hospitalised for symptomatic LEAD in France are not eligible for the low dose rivaroxaban plus aspirin combination. In turn, those eligible may potentially have greater absolute benefit because of higher risk than those enrolled in the trials

Systematic Screening for Deep Vein Thrombosis in Critically Ill Inpatients With COVID-19: Impact on the Incidence of Venous Thromboembolism

International audienceBackground: Several studies suggest an increased incidence of thrombosis in COVID-19 patients. However, evidence on how to prevent and even treat it is scarce. The aim of this study was to compare the cumulative incidence of venous thromboembolism (VTE) of two different methods for lower extremity deep vein thrombosis (LE-DVT) diagnosis: systematic vs. clinically guided complete compression venous ultrasonography (CCUS). We conducted a monocentric, prospective, open-label, non-randomized study. All consecutive patients admitted in three intensive care units (ICUs) of University Hospital of Toulouse for COVID-19 pneumonia were included: one performed systematic screening for LE-DVT, the others did not. The primary outcome was the 21-day cumulative incidence of VTE. The secondary end points were the 21-day cumulative incidences of major bleeding and death. Results: Among the 78 patients included, 27 (34.6%) underwent systematic screening for DVT 7 ± 2 days after ICU admission. Thirty-two patients (41.0%) were diagnosed with VTE, with a 21-day cumulative incidence of 42.3% (95% CI, 31.4-55.2), without difference between screened and non-screened patients (hazard ratio 1.45, 95% CI, 0.72-2.93). In the screened group, the frequency of isolated DVT was higher (25.9 vs. 5.9%, p-value = 0.027), but the frequency of pulmonary embolism was not reduced (25.9 vs. 29.4%, p-value = 0.745). The 21-day cumulative incidences of major bleeding and death were 9.6% (95% CI, 4.7-19.2) and 10.3% (95% CI, 5.0-20.8), respectively, without difference between the two groups. Conclusions: A systematic screening for DVT in patients hospitalized in ICU was not associated with a higher diagnosis of VTE or a reduced diagnosis of PE

Facteurs associés à la prescription d’anticoagulants oraux directs

Objectif. Décrire les facteurs associés à la prescription d’anticoagulants oraux directs (AOD). Méthode. Cohorte de patients de rythmologie du Centre Hospitalier Universitaire de Toulouse, traités par anticoagulants oraux dans le cadre d’une fibrillation atriale (FA). Une régression logistique a permis de décrire les facteurs associés à la prescription d’AOD et ceux associés à l’arrêt de l’anticoagulant. Résultats. Parmi les 140 patients inclus, 92 étaient traités par anti-vitamines K (AVK) et 48 par AOD. Les facteurs associés à la prescription d’AOD étaient un diagnostic de FA récent, la prise antérieure d’AVK et l’absence d’anti-agrégants plaquettaires (AAP). L’arrêt de l’anticoagulant (n = 24) était associé à la prise d’AOD. Conclusion. Les AOD sont moins prescrits que les AVK chez les patients sous AAP. L’international normalized ratio (INR) est équilibré chez la majorité des patients sous AVK étant passés aux AOD. Une étude plus puissante permettrait de confirmer le profil de prescription des AOD