Indocyanine green lymphography as novel tool to assess lymphatics in patients with lipedema.

OBJECTIVE: Lipedema is a chronic and progressive disease associated with lymphatic impairment at later stages. The aim of our study was to describe the functional status and anatomy of lower limb superficial lymphatic system using indocyanine green (ICG) lymphography in patients with lipedema. METHODS: Following ICG injection at the dorsum of the foot, distance (cm) covered by the dye at 10 (T10') and 25 min (T25') was measured and normalized for limb length. If the dye did not reach the groin within 25 min, patients were classified as "drainage-needing" group (DNG). Values of fat and lean distribution assessed by dual-energy X-ray absorptiometry were extracted, and correlation analysis was performed. Furthermore, anatomical patterns of superficial lymphatics were assessed. RESULTS: Overall, 45 women were included, 25 (56%) of whom were classified as DNG. Symptoms duration was significantly associated with DNG status at multivariate analysis (odds ratio 1.07; 95% CI 1.01-1.14; p = 0.047). Moreover, Spearman's analysis showed a negative correlation between symptoms duration and T25' dye migration (r = -0.469; p = 0.037). Overall, no major anatomical lymphatic changes were found. CONCLUSIONS: Present study suggests that lymphatic functioning in patients with lipedema correlates with symptoms duration. Further research on larger cohorts should verify our findings and clarify their potential therapeutic implications. Overall, ICG lymphography may be promising technique to assess both lymphatic anatomy and functioning in patients with lipedema.

[Patient with lower extremity artery disease†: news in therapeutic approach]. / Artériopathie oblitérante des membres inférieurs†: nouveautés dans la thérapie médicamenteuse.

Prevalence of lower extremity artery disease (LEAD) is increasing with age, and there is a trend over the last decade towards an increase of LEAD patients. These patients are at increased risk of lower limb adverse event (MALE), but also at very high risk of major cardiovascular events (MACE). The best medical treatment, including medications, enable a reduction of this risk. Nevertheless, some patients will continue to develop MACE. New therapeutic molecules have been developed with randomized controlled trials, and showed a reduction of the -cardiovascular risk among these selected patients.

La prévalence de l'artériopathie oblitérante des membres inférieurs augmente avec l'âge, et, sur la dernière décennie, la tendance est à l'augmentation du nombre de patients atteints. Or ces patients sont à risque de développer des complications vasculaires locales, mais aussi des complications cardiovasculaires dans d'autres ­territoires. La prise en charge optimale, qui comporte un volet ­médicamenteux, permet de réduire le risque cardiovasculaire de ces patients. Chez certains, cependant, il persiste un risque résiduel. De nouvelles classes thérapeutiques ont été développées au travers d'essais cliniques contrôlés, randomisés, en double aveugle et ont permis de mettre en évidence une réduction complémentaire du risque cardiovasculaire chez ces patients.

[Should patients with type 2 diabetes be screened for lower extremity arterial disease?] / Faut-il dépister l'artériopathie oblitérante des membres inférieurs chez les patients avec diabète de type.

Lower extremity arterial disease (LEAD) is a serious and invalidating disease with a relatively high prevalence in the diabetic population. Patients suffering from both conditions have a less favourable prognosis of affected limbs compared to non-diabetic patients, with more frequent adverse limb events such as amputations. Nevertheless, awareness of LEAD remains sub-optimal in the diabetic population. Regular and appropriate screening for this condition is therefore recommended. Affected individuals should receive optimal medical treatment, including intensive management of the various cardiovascular risk factors and strict blood glucose control.

L'artériopathie oblitérante des membres inférieurs (AOMI) est une pathologie souvent sévère et invalidante, relativement fréquente dans la population diabétique. Les patients atteints des deux maladies ont un pronostic moins favorable au niveau des membres inférieurs par rapport aux patients non diabétiques, et souffrent plus fréquemment de complications graves comme des amputations. Néanmoins, la sensibilisation à l'AOMI chez les médecins prenant en charge les patients diabétiques reste sous-optimale. Un dépistage régulier et approprié de cette condition est donc recommandé. Les patients affectés doivent recevoir un traitement médical optimal, incluant une prise en charge intensive des différents facteurs de risque cardiovasculaire et un contrôle strict des glycémies.

Critical limb ischaemia and the response to bone marrow-derived cell therapy according to tcPO2 measurement.

BACKGROUND: Cell therapy is an emerging potential biotherapy for critical limb ischaemia (CLI) patients who are not eligible for revascularization. However, the findings on this technique's efficacy are inconsistent. Trials investigating this topic focused on the more severe CLI patients who were often beyond any therapy. Therefore, identifying those who may truly benefit from cell transplantation is now warranted. To this end, we studied the prognostic value of tcPO2 for major amputation after 1 year in patients treated with bone marrow-derived cells. PATIENTS AND METHODS: CLI patients ineligible for revascularization were included in a cell-therapy pilot study. On inclusion, patients underwent tcPO2 measurement in supine and sitting positions. For a tcPO2 < 10 mmHg in the supine position, the vascular reserve was defined by tcPO2 > 30 mmHg in the sitting position. Patients were administered intramuscular injections of mononuclear cells derived from aspirated bone marrow. RESULTS: In total, 25 patients (a lower limbs) were included for analysis. At inclusion, 11 lower limbs had tcPO2 at rest > 10 mmHg, and 16 lower limbs had a tcPO2 < 10 mmHg. The success probability for cell therapy was 0.79 (95 % CI 0.38-0.94) and 0.44 (95 % CI 0.18-0.67), respectively (p = 0.1). Of the 16 limbs with tcPO2 < 10 mmHg, the success rate was considerably higher in patients demonstrating a tcPO2 increase in a sitting position of over 30 mmHg (6/8, success probability 0.71, 95 % CI 0.26-0.92) compared to those without (2/8, success probability 0.15, 95 % CI 0.01-0.48, p = 0.03). CONCLUSIONS: For patients with chronic CLI for whom cellular therapy is a therapeutic option, a tcPO2 < 10 mmHg at rest, without vascular reserve (i. e. < 30 mmHg when sitting), is a prognostic indicator for poor outcome.
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Antithrombotic therapy after infrainguinal bypass.

OBJECTIVE: Bypass surgery is regularly performed for the treatment of critical limb ischemia, but the risk of occlusion remains significant. Antiplatelet therapy in patients with arterial disease is useful for secondary cardiovascular and bypass occlusion prevention. However, despite the common use of an antiplatelet agent, especially aspirin, which became the standard of care, the risk of graft occlusion persists. The best antithrombotic treatment for bypass patency therefore remains a matter of debate. METHODS: We conducted a systematic literature search to identify studies and consensus reporting the use of antithrombotic treatment to prevent bypass occlusion. We excluded case reports and clinical trials with a placebo arm. RESULTS: Aspirin remains the mainstay of treatment to improve infrainguinal bypass patency; however, the effect differs according to the bypass material used. The greatest beneficial effect of antiplatelet agents was observed with prosthetic bypasses. In such cases, the addition of clopidogrel to aspirin, for at least 1 year, in patients who benefited from a below-knee bypass graft significantly improved bypass patency (occlusion 32% vs 47% for aspirin alone; P = .02) and the amputation rate (9.4% vs 19.2% for aspirin alone; P = .03), without increasing the incidence of major hemorrhage. In contrast, antiplatelet regimens were less efficacious for autologous vein bypasses. The addition of a vitamin K antagonist (VKA) is not routinely proposed because of the increased incidence of associated major hemorrhage. The use of VKA alone, instead of aspirin, should probably be discussed in selected patients, and a combination of VKA and antiplatelet agents should be discussed in patients with venous infrainguinal bypasses considered to be at a high risk for occlusion. CONCLUSIONS: Although aspirin remains the first-line treatment to prevent infrainguinal bypass occlusion, future studies are needed to define stronger recommendations.

Update on the diagnosis of recurrence of lower limb deep vein thrombosis. A Consensus statement of the French Society for Vascular Medicine (SFMV).

An accurate diagnosis of lower limb deep vein thrombosis (DVT) recurrence is mandatory. The diagnosis is difficult and has not been well investigated. Our objective was to define the role of clinical probability assessment, D-dimer assay, venous ultrasound and other imaging methods in the diagnosis of this condition based on a review of published data. Our review did not find any clinical prediction rule (CPR) specific to the diagnosis of DVT recurrence. D-dimer assays have not been sufficiently validated or proved effective either alone or when combined with the assessment of clinical probability or with ultrasound. The only validated ultrasound criteria are a new non-compressible vein segment and a≥2mm or>4mm increase in diameter of the common femoral or popliteal vein under compression in the transverse plane between two examinations. Limitations of these criteria include poor inter-observer agreement, non-availability of previous ultrasound reports and measurements, a high percentage of non-diagnostic ultrasound results, lack of power in diagnostic accuracy and diagnostic management studies, and lack of external validation. The analysis of venous obstruction, thrombus appearance, vein diameter and blood flow based on colour Doppler ultrasound criteria has not yet been validated in studies. Magnetic resonance direct thrombus imaging (MRDTI) is a new promising diagnostic imaging method, but is hardly accessible, costly and needs large scale validation studies. Based on this review, an update of the guidance for clinical practice is proposed for the diagnostic management of patients with clinically suspected lower limb DVT recurrence.

25 mm Hg versus 35 mm Hg elastic compression stockings to prevent post-thrombotic syndrome after deep vein thrombosis (CELEST): a randomised, double-blind, non-inferiority trial.

BACKGROUND: The optimal strength of compression needed to prevent post-thrombotic syndrome (PTS) after a proximal deep vein thrombosis (DVT) is debated. We aimed to assess whether 25 mm Hg elastic compression stockings (ECS) are non-inferior to 35 mm Hg ECS in preventing PTS after a DVT. METHODS: In this multicentre, double-blind, non-inferiority, randomised controlled trial, we enrolled adults (≥18 years) with a first ipsilateral proximal DVT attending 46 French vascular medicine hospital departments or private practices. Participants were randomly allocated (1:1, stratified by centre, age, and sex; with varying block sizes of two and four) to wear 25 mm Hg or 35 mm Hg ECS for 2 years. The primary outcome was the cumulative rate of PTS 2 years after inclusion, defined by a Villalta scale (≥5). Efficacy was assessed by intention-to-treat and in eligible participants who had complete primary outcome data. A per-protocol analysis was also conducted among compliant patients as a secondary outcome measure. Safety was assessed in all participants who used ECS at least once, and for which we have at least some tolerance information during follow-up. The margin for non-inferiority was 12·5%. This study is registered with ClinicalTrials.gov, NCT01578122, and has been completed. FINDINGS: Between June 28, 2012, and July 21, 2017, we enrolled 341 eligible participants who consented to randomisation. 233 (68%) were men and median age was 59 years (IQR 45-70). Collection of ethnicity and race as a routine research variable is not authorised in France. Median follow-up was 735 days (IQR 721-760). 249 (73%) had complete data at 2 years. For the primary analysis, 40 (31%) of 129 participants with complete data in the 25 mm Hg ECS group and 40 (33%) of 120 in the 35 mm Hg group had PTS (absolute difference -2·3% [90% CI -12·1 to 7·4], pnon-inferiority=0·0062; relative risk 0·93, 95% CI 0·65 to 1·33). Results remained similar after imputation of missing data in patients we were authorised to do so: the cumulative proportion of PTS was 45 (29%) of 154 in the 25 mm Hg ECS group versus 52 (35%) of 148 in the 35 mm Hg ECS group (relative risk 0·83, 95% CI 0·60 to 1·16). Absolute difference was -5·9%, (90% CI -14·7 to 2·9), p=0·0003 for non-inferiority. Adherence was optimal (>80% and modified GIRERD score of 0-2) for 75 (51%) of 146 patients assigned to 25 mm Hg ECS and for 56 (42%) of 134 patients assigned to 35 mm Hg ECS (p=0·11). Regarding major adverse events related to ECS, there were no between-group differences in rates of deep vein thrombosis (0 vs 1 [0·6%]), ipsilateral leg ulcer (0 vs 1 [0·6%]), infection (0 vs 0), or death (0 vs 0) between the 169 patients evaluated in the 25 mm Hg ECS group and the 159 patients in the 35 mm Hg ECS group. Two (1%) of 328 patients who ever wore ESC developed ECS-related serious adverse events, one distal DVT and one leg ulcer (both in the 35 mm Hg ECS group). In the 25 mm Hg group, 6 patients died, 14 had a venous thromboembolic recurrence (proximal DVT or pulmonary embolism), and 7 had a major bleed. In the 35 mm Hg group, 5 patients died, 10 had a venous thromboembolic recurrence (proximal DVT or pulmonary embolism), and 6 had a major bleed. INTERPRETATION: Although we did not reach the prespecified sample size, our results suggest that 25 mm Hg ECS are non-inferior to 35 mm Hg ECS in preventing PTS. Larger more powerful studies are needed. FUNDING: Laboratoires Innothera, France.

Diagnosis of deep vein thrombosis recurrence: Ultrasound criteria.

INTRODUCTION: Recurrent deep vein thrombosis (DVT) is often suspected in patients after anticoagulant drug withdrawal. The clinical signs can be confused with the onset of post-thrombotic syndrome. For these reasons, diagnosis of DVT recurrence must rely on an accurate method. MATERIALS AND METHODS: In order to assess this challenging clinical issue, we performed an overview of the literature regarding ultrasound criteria for the diagnosis of recurrent DVT through a Medline search, which included articles published from January 1, 1980 to February 20, 2017. RESULTS: Eighty-eight publications were found based on the defined keywords, of which nine articles with a relevant abstract were selected. By searching the reference lists of these nine articles, we obtained another 27 relevant articles. A new non-compressible vein or an increase in the diameter of a previously thrombosed vein segment by >4mm are sufficient to confirm the diagnosis of DVT recurrence. In contrast, an increase in diameter of <2mm enables recurrence to be ruled out. An increase between 2 and 4mm is deemed equivocal. Criteria based on echogenicity and Doppler venous blood flow are not reproducible. Other diagnostic imaging methods, mainly direct thrombus magnetic resonance imaging, are currently under evaluation. CONCLUSIONS: Ultrasound remains the most useful test for the diagnosis of recurrent DVT. Further imaging tests need to be validated.