Effects of iloprost in patients with critical limb ischemia: Results of a cohort study from the COPART registry.

BACKGROUND: Iloprost has been proposed as an alternative to amputation in Critical Limb Ischemia (CLI) patients when revascularization was unsuccessful or not possible. Nonetheless, there is limited evidence of its benefit. The main objective was to evaluate the effectiveness of iloprost and the secondary objective was to evaluate its safety. METHODS: In this cohort study including CLI patients from the COPART registry from 2006/10 to 2021/01, patients exposed to iloprost were matched with up to three unexposed patients according to age, sex, and Propensity Score (PS) for exposure to iloprost. The main outcome combined the occurrence of all-cause death and major amputations; survival was assessed over one-year using Kaplan-Meier estimates and Cox model analyses. Major Adverse Cardiovascular Events (MACE) were chosen as the safety outcome; the association with iloprost was estimated using a logistic regression model. RESULTS: Among 1850 CLI patients, 201 were exposed to iloprost (71.6% men; median age: 72 years vs. 72.1%; 75 years for unexposed). In 134 exposed patients matched to 375 unexposed patients, 14 major amputations and 24 deaths occurred in exposed patients (28.4%) vs. 33 and 46 respectively in the unexposed patients (20.9%). The hazard ratio (HR) was of 1.49 (95% Confidence Interval: 1.01-2.20). The association remained in the subgroup of "no option" patients (HR: 1.74; [1.01-2.20]). Regarding safety, 21/201 (10.7%) exposed patients experienced MACE vs. 146/1649 (9.41%) unexposed patients (unadjusted Odds Ratio [OR]: 1.17 [0.72-1.90]; adjusted OR: 1.23 [0.72-2.11]). CONCLUSION: The study did not find any benefit of iloprost in CLI patients and even suggested a deleterious effect.

[Lower-limb peripheral arterial disease]. / Artériopathie oblitérante des membres inférieurs.

Peripheral arterial disease is a result of atheroma. This disease is frequent in subjects with vascular risk factors. This disease is also frequent in low income countries. The detection and the diagnosis of peripheral arterial disease is obtained by calculating the ankle brachial index. Patients with peripheral arterial disease are not always symptomatic thus explaining how this disease is under diagnosed. The symptoms can be absent, and especially in case of diabetes or in women. In case of peripheral arterial disease, atheroma often involves other arterial vascular networks especially the coronaries. An adapted treatment reduces the morbi-mortality linked to this disease. This treatment is based on the correction of the vascular risk factors and especially tobacco cessation, walking rehabilitation and drugs (antiplatelet agent, statin, renin angiotensin system blocker). In case of rest or critic ischemia, the first-line treatment is a revascularisation. In peripheral arterial disease, management of patients is often non optimal and therapeutic targets fairly often obtained.

[College of the French Vascular Medicine Teachers (CEMV) statement: Arterial Doppler waveforms analysis (simplified Saint-Bonnet classification)]. / Recommandations du Collège des enseignants de médecine vasculaire (CEMV) : analyse des flux artériels Doppler (classification de Saint-Bonnet simplifiée).

Lower extremity peripheral artery disease is a frequent disease. Arterial Doppler waveforms analysis is a key element in vascular medicine, especially to diagnose lower peripheral artery disease. Although Doppler waveforms are often used, descriptions are highly heterogeneous. This review presents the simplified Saint-Bonnet classification that is tought to vascular medicine residents in order to homogenize arterial flow description.

[Cerebral vasoreactivity: Concordance of breath holding test and acetazolamide injection in current practice: 20 cases of asymptomatic carotid artery stenosis]. / Étude de la vasoréactivité cérébrale en Doppler transcrânien : évaluation du test d'apnée comparé à l'injection d'acetazolamide en soins courants. Exploration de 20 sténoses carotidiennes asymptomatiques.

INTRODUCTION: Cerebral vasoreactivity (CVR) is the ability of the brain's vascular system to keep cerebral blood inflow stable. Impaired CVR is a risk marker of stroke in patients with asymptomatic carotid stenosis. The gold standard to assess CVR with transcranial ultrasound is acetazolamide (ACTZ) injection. The breath holding test (BHT) might be easier to perform. CVR proved to be efficient in laboratory conditions but not in routine practice. OBJECTIVES: To study the validity of BHT versus ACTZ in routine practice in a vascular exploration unit in patients with asymptomatic carotid stenosis. METHODS: Study of concordance of BHT and ACTZ, to assess CVR in patients consecutively explored on the same day. RESULTS: Eighteen patients with 20 carotid stenosis were included. The temporal window was missing in 20% of cases. Only 11 out of the 20 procedures were analyzed. Concordance was low between BHT and ACTZ to assess CVR (k=0.3714). CONCLUSION: BHT cannot replace ACTZ injection. It might be a first-step test so that ACTZ injection might be avoided if CVR is normal. Our present results must be confirmed by further study enrolling many more patients.

Long-term outcomes of cancer-related isolated distal deep vein thrombosis: the OPTIMEV study.

Essentials Clinical significance of cancer-related isolated distal deep vein thrombosis (iDDVT) is unknown. We studied patients with iDDVT, with and without cancer, and proximal DVT with cancer. Cancer-related iDDVT patients have a much poorer prognosis than iDDVT patients without cancer. Cancer-related iDDVT patients have a similar prognosis to cancer-related proximal DVT patients. SUMMARY: Background Isolated distal deep vein thrombosis (iDDVT) (infra-popliteal DVT without pulmonary embolism [PE]) is a frequent event and, in the absence of cancer, is usually considered to be a minor form of venous thromboembolism (VTE). However, the clinical significance of cancer-related iDDVT is unknown. Methods Using data from the observational, prospective multicenter OPTIMEV cohort, we compared, at 3 years, the incidences of death, VTE recurrence and major bleeding in patients with cancer-related iDDVT with those in cancer patients with isolated proximal DVT (matched 1:1 on age and sex) and patients with iDDVT without cancer (matched 1:2 on age and sex). Results As compared with patients with cancer-related isolated proximal DVT (n = 92), those with cancer-related iDDVT (n = 92) had a similar risk of death (40.8% per patient-year (PY) vs. 38.3% per PY; aHR = 1.0, 95% CI[0.7-1.4]) and of major bleeding (3.8% per PY vs. 3.6% per PY, aCHR = 0.9 [0.3-3.2]) and a higher risk of VTE recurrence (5.4% per PY vs. 11.5% per PY; aCHR = 1.8 [0.7-4.5]). As compared with patients with iDDVT without cancer (n = 184), those with cancer-related iDDVT had a nine times higher risk of death (3.5% per PY vs. 38.3% per PY; aHR = 9.3 [5.5-15.9]), a higher risk of major bleeding (1.8% per PY vs. 3.6% per PY; aCHR = 2.0 [0.6-6.1]) and a higher risk of VTE recurrence (5.0% per PY vs. 11.5% per PY; aCHR = 2.0 [1.0-3.7]). The results remained similar in the subgroup of patients without history of VTE. Conclusion Patients with cancer-related iDDVT seem to have a prognosis that is similar to that of patients with cancer-related isolated proximal DVT and a dramatically poorer prognosis than patients with iDDVT without cancer. This underlines the high clinical significance of cancer-related iDDVT and the need for additional studies.

[Macrovascular complications of systemic sclerosis: Prospective descriptive Doppler ultrasound study in 20 patients]. / Atteinte macrovasculaire de la sclérodermie systémique : étude descriptive prospective de 20 patients en échodoppler.

PURPOSE: Systemic sclerosis is characterized by cutaneous sclerosis, vascular disease and immunological dysfunction. The prevalence of macrovascular disease remains controversial. PATIENTS AND METHODS: This was a descriptive prospective single-center study conducted in the vascular medicine department of the University Hospital of Bordeaux from July 1 to September 1, 2015. All inpatients followed for systemic scleroderma were included. Each patient had a Doppler ultrasound of the supra-aortic, upper and lower limb, and digital arteries as well as the aorta. The main objective of the study was to describe the presence and location of arterial lesions in patients with systemic sclerosis. RESULTS: Of the twenty patients included, there were 13 women and 7 men; mean age was 58±16years. Patients exhibited wall thickening (n=16, 80%), calcified plaques (n=10, 50%), hemodynamically significant stenoses (n=3, 15%) and arterial occlusions (n=12, 60%). Ankle brachial pressure index (ABPI) was 0.98±0.16 on the right and 0.99±0.21 on the left. Two patients had ABPI<0.8. The mean brachial systolic blood pressure was 113±14mmHg. Arterial mapping (860 arterial sites) found wall thickening (n=93 arteries, 10%), calcified plaques (n=47, 5%), hemodynamically significant stenoses (n=7) and occlusions (n=22). Arterial occlusions were located in the ulnar arteries (n=2), the digital arteries (n=18), the posterior tibial artery (n=1) and the dorsalis pedis artery (n=1). CONCLUSION: The data of our study correlate with macrovascular disease described in the literature. This finding raises two questions: how does this concept integrate with the severity of Raynaud's phenomenon and the risk of digital ulcers and changes in patients' capillaroscopic landscape during follow-up? What is the cause of these vascular anomalies, some of which are very different from what is observed in atherosclerosis?

[Paroxysmal nocturnal hemoglobinuria: An unknown cause of thrombosis?]. / L'hémoglobinurie paroxystique nocturne : une cause méconnue de thrombose ?

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cells. Somatic mutation in the phosphatidylinositol glycan class A (PIG-A), X-linked gene, is responsible for a deficiency in glycosphosphatidylinositol-anchored proteins (GPI-AP). The lack of one of the GPI-AP complement regulatory proteins (CD55, CD59) leads to hemolysis. The disease is diagnosed with hemolytic anemia, marrow failure and thrombosis. Thromboembolic complication occurs in 30% of patient after 10 years of follow-up and is the first event in one out of 10 patients. The two most common sites are hepatic and cerebral veins. These locations are correlated with high risk of death. Currently, these data are balanced with the use of a monoclonal antibody (Eculizumab), which has significantly improved the prognosis with a survival similar to general population after 36 months of follow-up. Anticoagulant treatment is recommended after a thromboembolic event but has no place in primary prophylaxis.

[Detection of micro-embolic signals: a review of the literature]. / Détection de signaux micro-emboliques: revue de la littérature.

BACKGROUND: The detection of micro-embolic signals (MES), by transcranial Doppler sonography might be useful for risk stratification in patients with symptomatic and asymptomatic carotid or cerebral artery stenosis, dissections, aortic atheroma, interventional procedures, and right to left cardiac shunts. AIM: Review of the technique and clinical situations of MES detection. METHODS: PubMed search from 1990 to 2012. RESULTS: MES were found in 0,19, 48% versus 0,3, and 12% of patients with symptomatic and asymptomatic inferior than 30, 30 to 69, and 70 to 99% carotid stenosis, respectively. MES were related to the risk of recurrent stroke or transient ischemic attack (TIA). In the ACES study, the absolute annual risk of stroke or TIA after 2 years was 7% with vs 3% without MES. In patients with intracranial stenosis, the risk of stroke recurrence was 48% with vs 7% without MES at 13.6 months follow-up. MES were reported in 25% of the symptomatic versus none of the asymptomatic patients with intracranial stenosis. CONCLUSION: Detection of MES is feasible and reproducible for multicenter studies, using rigourous methodology and long lasting recordings. It may contribute to risk stratification, especially in patients with extra- or intracranial stenosis.

[How to quantify limb edema?]. / Comment quantifier un oedème des membres?

Edema of venous or lymphatic origin is frequently encountered in vasculopathies. Clinical diagnosis is readily made but precise quantification of edema is difficult. Various procedures have been proposed to quantify edema volume or analyze its composition. Water volumetry remains the gold standard but volumetry calculated with formulas from circumferential measurements for a cylinder or frustum methods are reproducible with high interrater and intrarater reliability. Automated measurement systems are expensive and reserved for research. Ideally, volume measurements for a given patient during the follow-up should be made by the same practitioner using the same method because the different methods are not interchangeable. Notably, edema composition can be evaluated by high frequency ultrasound, CT-scan, MRI or bioimpedance. Edema quantification is essential during patient follow-up and the method to be used depends on the objectives to be met.

[Digital ischemia in two patients treated with gemcitabine]. / Ischémie digitale sous gemcitabine, à propos de deux cas.

A 73-year-old man with an urothelial carcinoma treated with gemcitabine and carboplatinium and an 84-year-old man with a mesothelioma treated with gemcitabine alone developed digital ischemia. In the first patient, the ischemia involved all fingers except the thumbs during the second cycle of treatment. The ischemia developed during the first cycle in the second patient and involved the right major and ring fingers. In the literature, gemcitabine vascular toxicity is probably potentialized by platinium salts. Several nosological entities occur simultaneously. The most widely described involve isolated digital ischemia for doses to the order of 3000mg, and a hemolytic and uremic thrombotic microangiopathy for gemcitabine doses above 10,000mg. The vascular toxicity of platinium salts is not dose-dependent. In these two patients, the clinical course was favorable with interruption of the chemotherapy, treatment by iloprost and aspirin.

[Therapeutic consequences of thrombophilic testing]. / Conséquences thérapeutiques de la mise en évidence d'une thrombophilie.

OBJECTIVE: The objectives of this article are to review the data about the consequences of thrombophilia testing and to think about its indications. CURRENT KNOWLEDGE AND KEY POINTS: The indications of congenital thrombophilic testing have extended since the discovery of prevalent abnormalities, such as mutations of factor V or II genes. However, thrombophilia does not result in a significant increase in the risk of recurrence unlike the spontaneous occurrence of thrombotic events. The factor V Leiden mutation is associated with a moderate increase in recurrence rate, while the G20210A mutation of factor II is not associated with a significant increase in recurrence. Regarding the decrease in natural anticoagulants is concerned, there is no definite conclusion, although the decrease in antithrombin is suspected of being associated with an increase in recurrence. FUTURE PROSPECTS AND PROJECTS: Finally, identification of a constitutional thrombophilia most often do not influence the therapeutic decisions unless some rare abnormalities are found, such as a decrease in antithrombin, homozygous mutations in factors V or II genes or associations of thrombophilia. One must remember that antiphospholipid antibodies must be searched because their impact on recurrences is well-known. Diagnostic work-up for thrombophilia is not useful after a distal or a superficial venous thrombosis (except for antiphospholipid antibodies in case of distal venous thrombosis).