15-Lipoxygenase promotes resolution of inflammation in lymphedema by controlling Treg cell function through IFN-ß.

Lymphedema (LD) is characterized by the accumulation of interstitial fluid, lipids and inflammatory cell infiltrate in the limb. Here, we find that LD tissues from women who developed LD after breast cancer exhibit an inflamed gene expression profile. Lipidomic analysis reveals decrease in specialized pro-resolving mediators (SPM) generated by the 15-lipoxygenase (15-LO) in LD. In mice, the loss of SPM is associated with an increase in apoptotic regulatory T (Treg) cell number. In addition, the selective depletion of 15-LO in the lymphatic endothelium induces an aggravation of LD that can be rescued by Treg cell adoptive transfer or ALOX15-expressing lentivector injections. Mechanistically, exogenous injections of the pro-resolving cytokine IFN-ß restores both 15-LO expression and Treg cell number in a mouse model of LD. These results provide evidence that lymphatic 15-LO may represent a therapeutic target for LD by serving as a mediator of Treg cell populations to resolve inflammation.

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.

Duration of anticoagulation for upper extremity deep vein thrombosis associated with cancer and central venous catheter: Outcome of a cohort study.

INTRODUCTION: In cancer patients with catheter-associated upper extremity deep vein thrombosis, 3 months of anticoagulation is recommended. The main objective of this study was to compare the incidence of thrombosis recurrence in these patients in case of continuation or discontinuation of anticoagulation, at the end of 3 months and after catheter has been removed. The secondary objectives were the incidence of major bleeding and death. MATERIAL AND METHODS: We conducted a retrospective cohort study including patients with a cancer and a catheter-associated upper extremity deep vein thrombosis. RESULTS: About 60 patients included, 44 stopped anticoagulation after the first 3 months and 16 continued it. The median time between catheter insertion and deep vein thrombosis was 26±83 days. Three recurrences occurred during the one-year follow-up: 2 in the group who stopped anticoagulation, with a cumulative incidence at 1 year of 4,8% (95%IC 1.2-18.1) and 1 in the group who continued anticoagulation, with a cumulative incidence at 1 year of 14.3% (95%IC 2.1-66.6). No major bleeding event occurred in anticoagulation discontinued group. The group who stopped anticoagulation was significantly associated with a lower risk of death (HR 0.21-95%IC 0.09-0.48, P<0.001). CONCLUSION: The risk of recurrence in cancer patients with a catheter-associated upper extremity deep vein thrombosis was low and statistically comparable between the group who stopped anticoagulation and the group who continued it. These results suggest that anticoagulation after the first 3 months deserves to be considered when catheter is removed.

Management of upper extremity deep vein thrombosis in Occitanie: practice assessment.

BACKGROUND: The incidence of upper extremity deep vein thrombosis (UEDVT) is increasing. Its management is sometimes complex and difficult due to its complications and the lack of strong recommendations. The aim was to describe the practice of vascular physicians in Occitanie region in the management of upper extremity deep vein thrombosis. MATERIAL AND METHODS: We used a descriptive observational study in the form of a declarative survey by means of a questionnaire from April to May 2019 among vascular physicians. RESULTS: Of the 142 physicians contacted, 84 responded, with a reply rate of 59.1%. The majority of physicians introduced low-molecular-weight heparin treatment (60.71%) and 29.76% direct oral anticoagulation after a diagnosis of UEDVT. Three months of anticoagulation was chosen by 69% of physicians against 27.4% for a duration of 6 months. Diagnostic work-up included biological risk factors, chest and/or cervical radiography and ultrasonography with dynamic maneuvers. Three quarters of doctors recommended venous compression. A control ultrasonography was performed for 67.86% of patients at one month and at the end of treatment. After the acute phase, 63% of physicians introduced direct oral anticoagulation and 11% recommended venous revascularization. DISCUSSION AND CONCLUSIONS: The mobilization of vascular physicians reflects their interest for this pathology. The management of UEDVT requires specific studies to address therapeutic modalities, the duration of anticoagulation or the place of venous compression in the acute phase.

D-dimer levels and risk of recurrence following provoked venous thromboembolism: findings from the RIETE registry.

BACKGROUND: Patients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at-risk patients could help to guide the duration of therapy. METHODS: We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel). RESULTS: In December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d-dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19-9.57) events per 100 patient-years in those with raised d-dimer levels and 2.68 (95% CI: 1.45-4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71-10.4) and 3.34 (95% CI: 2.39-4.53), respectively. Patients with major risk factors and raised d-dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio [HR]: 2.14; 95% CI: 0.96-4.79) than those with normal levels. Patients with minor risk factors and raised d-dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51-3.63) than those with normal levels. On multivariate analysis, raised d-dimers (HR: 1.74; 95% CI: 1.09-2.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors. CONCLUSIONS: Patients with raised d-dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences.

[Medical residents and wound healing: A French national survey]. / Internes en médecine et cicatrisation des plaies : une étude descriptive multicentrique entre février et avril 2018.

OBJECTIVES: Around 2.5 million wounds are recorded in France, representing, in terms of cost and quality of life, a real problem of public health issue. In France, residents are among the first line personnel having to manage wounds and their complications: this study is carried out to identify the view and feelings of residents concerning their preparation and training in this field. MATERIALS AND METHODS: A questionnaire was distributed to residents throughout France. Residents' characteristics, interests and training in wound healing, training courses and opinions concerning their training were recorded. RESULTS: Seven hundred and eleven French residents answered the questionnaire, the majority of whom (79 %) had not experienced training in wound healing. The majority of residents (69 %) believe that all physicians are concerned. Training in wound management and wound healing is considered insufficient (94 %) and most (79 %) had never received any training in wound management and wound healing. Ninety-eight percent stated they needed additional training courses in wound management. CONCLUSIONS: Wound management and healing is a topic of interest to residents. Residents need more training in wound management in their curriculum to improve their practice.

[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.

[Blood pressure target in 2017]. / Objectif tensionnel en 2017.

OBJECTIVE: The issue of how far blood pressure (BP) should be lowered under antihypertensive treatment is still an important matter of scientific debate. The aim of the present review is to consider the clinical relevance of individualized BP goal under treatment in hypertensive patients according to their age, comorbidities or established cardio-vascular (CV) disease. DATA FROM THE LITERATURE: The French and European recommendations propose a systolic BP target between 130 and 139mmHg (<150mmHg after 80 years) and diastolic BP target <90mmHg in hypertensive patients whatever their level of risk. The results of the recent SPRINT study suggest that a more ambitious systolic BP target, <120mmHg, significantly reduces CV morbidity and mortality, but with an increased iatrogenic risk. Several questions in everyday practice have to be considered. An important issue concerns BP measurement methods in this clinical trial (Dinamap) versus in routine clinical practice and the implications on BP treatment targets. In addition, close monitoring of participants in clinical trials and active orthostatic hypotension research limit the incidence of adverse events related to intensive treatement. Finally, in the presence of an established CV disease, an intensive therapeutic approach could be associated with a J-curve relationship between BP level and CV events. CONCLUSION: An early and strict BP control in young or middle-aged hypertensive patients in primary prevention should be a priority. In this hypertensive population with low to moderate CV risk, without established CV or renal diseases, more stringent than recommended BP-lowering treatment could potentially prevent hypertensive arterial damage and thus correct the increased residual CV risk later in life. The tolerance of an intensive therapeutic approach should remain a concern in elderly patients and in patients with established CV disease.

[Venous thromboembolic disease: Comparison of management practices in France, Italy and Spain]. / Comparaison en France, en Italie et en Espagne des modalités de prise en charge de la maladie thromboembolique veineuse.

BACKGROUND: Many national and international guidelines have been established for venous thromboembolic disease (VTE). Homogeneous management practices could be expected in the different European countries. To verify this hypothesis, we compared practices in France, Italy and Spain. METHOD: We used data from the international RIETE registry to compare VTE management between France, Italy and Spain. RESULTS: From 2001 January to 2011 January, patients were consecutively included in France (n=1548), Italy (n=2083) and Spain (29,824). All patients received anticoagulant treatment. Low molecular-weight heparin (LMWH) was the most frequently used drug as initial therapy in all three countries, but unfractionated heparin (UFH) was more frequently used in France and Italy than in Spain. In France, the proportion of patients receiving LMWH was lower than the proportion of patients with active cancer (cancer 22.5 %, long-term treatment with LMWH 17.4 %). A vena cava filter was significantly more frequently used in France (5.5 % in France, 3.2 % in Italy and 2 % in Spain, P<0.0001). High bleeding risk because of surgery with recent thromboembolic disease was the most frequent indication in France and Italy for vena cava filter placement (36.4 %, and 31.3 %, respectively). CONCLUSION: Despite the publication of national and international guidelines, VTE management differs among the three major European countries included in the RIETE registry, France, Italy and Spain.

Improved Fetal Hemoglobin With mTOR Inhibitor-Based Immunosuppression in a Kidney Transplant Recipient With Sickle Cell Disease.

Fetal hemoglobin induction is a key point in the management of sickle cell disease (SCD). We report the case of a kidney transplant recipient with SCD who was treated with everolimus, a mammalian target of rapamycin inhibitor. At 10 months after initiating therapy, the patient's fetal hemoglobin level was dramatically increased (from 4.8% to 15%) and there was excellent tolerance to treatment.

[Prevalence and prognosis of aspirin resistance in critical limb ischemia patients]. / Prévalence et valeur pronostique de la résistance à l'aspirine chez les patients en ischémie critique chronique des membres inférieurs.

OBJECTIVES: To assess the prevalence and the association between aspirin resistance in critical limb ischemia patients using the VerifyNow® bed-side platelet test, and occurrence of cardiovascular morbidity and/or death at one year. MATERIALS AND METHODS: National multicenter prospective observational study related to COPART II centers. From 2010 through 2014, 64 subjects hospitalized for critical limb ischemia and already treated by aspirin before the VerifyNow® test were included. A VerifyNow® test>550 ARU was defined as aspirin resistance. Critical limb ischemia was defined according to the TASC I criteria. The primary outcome was a composite including death, acute coronary syndrome, stroke and major amputation during the one-year follow-up period. RESULTS: In all, 9/64 patients were aspirin resistant, the status was confirmed in one case. The prevalence of aspirin resistance was 14.06%. There was no significant difference between aspirin resistant and aspirin non-resistant groups in terms of cardiovascular history and glycemia status. Neither was there significant difference between the two groups in terms of survival. CONCLUSION: Aspirin resistance was not predictive of poorer survival in critical limb ischemia patients. However, our population was limited. Considering that a clear definition of aspirin resistance and standardized diagnostic tests are lacking, complementary studies might be useful.

[Ultrasound screening of abdominal aortic aneurysm: Lessons from Vesale 2013]. / Dépistage échographique de l'anévrisme de l'aorte abdominale - les enseignements de Vésale 2013.

Although aneurysm of the abdominal infra-renal aorta (AAA) meets criteria warranting B mode ultrasound screening, the advantages of mass screening versus selective targeted opportunistic screening remain a subject of debate. In France, the French Society of Vascular Medicine (SFMV) and the Health Authority (HAS) published recommendations for targeted opportunistic screening in 2006 and 2013 respectively. The SFMV held a mainstream communication day on November 21, 2013 in France involving participants from metropolitan France and overseas departments that led to a proposal for free AAA ultrasound screening: the Vesalius operation. Being a consumer operation, the selection criteria were limited to age (men and women between 60 and 75 years); the age limit was lowered to 50 years in case of direct family history of AAA. More than 7000 people (as many women as men) were screened in 83 centers with a 1.70% prevalence of AAA in the age-based target population (3.12% for men, 0.27% for women). The median diameter of detected AAA was 33 mm (range 20 to 74 mm). The prevalence of AAA was 1.7% in this population. Vesalius data are consistent with those of the literature both in terms of prevalence and for cardiovascular risk factors with the important role of smoking. Lessons from Vesalius to take into consideration are: screening is warranted in men 60 years and over, especially smokers, and in female smokers. Screening beyond 75 years should be discussed. Given the importance of screening, the SFMV set up a year of national screening for AAA (Vesalius operation 2014/2015) in order to increase public and physician awareness about AAA detection, therapeutic management, and monitoring. AAA is a serious, common, disease that kills 6000 people each year. The goal of screening is cost-effective reduction in the death toll.

[Prevalence and risk factors of peripheral arterial disease in an outpatient screening campaign]. / Évaluation de la prévalence et des facteurs de risque de l'artériopathie oblitérante des membres inférieurs dans le cadre d'une campagne de dépistage ambulatoire.

BACKGROUND: Peripheral arterial disease (PAD) is an important predictor of cardiovascular disease with major medico-economic consequences. However, systematic screening of asymptomatic patients free from history of cardiovascular disease is debated. OBJECTIVE: Determining the prevalence, risk factors for PAD in a population of outpatients at intermediate or high-risk of cardiovascular disease, free from history of cardiovascular disease to assess the potential impact of PAD screening in such groups of patients. METHODS: Multicenter 1-day screening program of PAD conducted from 2008 to 2010 in a population defined by diabetes plus age greater than 50 years, positive active smoking status, or age greater than 70 years. PAD was defined as an ankle-brachial index (ABI) less than 0.9 measured as follows: lowest systolic ankle pressure divided by highest systolic arm pressure. RESULTS: Ten thousand six hundred and fourteen patients fulfilled study inclusion criteria: 16.7% (n = 1774) exhibited an ABI less than 0.9 and 3.8% (n = 407) an ABI less than 0.7. ABI greater than 1.3 was found in 7.7% of patients (n = 818). Age greater than 70 years, male gender, active smoking status, hypertension and diabetes (treated) were independent risk factors for PAD. CONCLUSION: Primary prevention outpatient screening of a population with intermediate or high cardiovascular risk can identify numerous patients with PAD. The medical impact in terms of cardiovascular mortality and morbidity of such a screening needs to be assessed.

[Prolongation of anti vitamin K treatment for 18 months versus placebo after 6 months treatment of a first episode of ideopathic pulmonary embolism: a mutlicentre, randomised double blind trail. The PADIS-EP Trial]. / Prolongation d'un traitement par antivitamine K pendant dix-huit mois versus placebo au décours d'un premier épisode d'embolie pulmonaire idiopathique traité six mois: un essai randomisé multicentrique en double aveugle. Essai "PADIS-EP".

BACKGROUND: After stopping a 3 to 6 months course of oral anticoagulation for a first episode of idiopathic venous thromboembolism (VTE), the risk of recurrent VTE is high (10% per year). In this setting, international guidelines recommend at least 6 months treatment. However, this recommendation is not satisfactory for the following reasons: (1) no randomized trial has compared 6 months to extended duration (2 years) anticoagulation; and (2), even though the frequency of recurrent VTE is similar after pulmonary embolism (PE) and deep vein thrombosis (DVT), the fatality rate of recurrent VTE after PE is higher than that after DVT. METHODS: A French multicentre double blind randomized trial. The main objective is to demonstrate, after a first episode of symptomatic idiopathic PE treated for 6 months using a vitamin K antagonist, that extended anticoagulation for 18 months (INR between 2 and 3) is associated with an increased benefit / risk ratio (recurrent VTE and severe anticoagulant-related bleeding) compared to placebo. The double blind evaluation is ensured using by active warfarin and placebo, and blinded INR. The protocol was approved by the ethics board of the Brest Hospital on the 7th of March 2006. For an alpha risk of 5% and a beta risk of 20%, the estimated sample size is 374 patients. EXPECTED RESULTS: This study has the potential to: (1) demonstrate that the benefit / risk ratio of extended anticoagulation for 18 months is higher than that observed with placebo in patients with a first episode of idiopathic PE initially treated for 6 months, during and after the treatment period; and (2) to validate or invalidate the contribution of isotope lung scans, lower limb Doppler ultrasound and D-Dimer at 6 months of treatment as predictors of recurrent VTE (medico-economic analysis included).