Arterial Blood-Flow Acceleration Time on Doppler Ultrasound Waveforms: What Are We Talking About?

In recent years, the assessment of systolic acceleration in lower-extremity peripheral artery disease (PAD) has been brought back into the spotlight, whatever measure is used: time (in s) or acceleration (in cm.s-2). Acceleration time (also called systolic rise time) and maximal acceleration are two different but very useful measurements of growing interest in PAD. A background of the historical development, physics rationale, semantics, and methods of measurement, as well as their strengths and weaknesses, are discussed herein. Acceleration time is a powerful tool for predicting significant arterial stenosis or for estimating the overall impact of PAD as it is highly correlated to the ankle or toe pressure indexes. It could even become a new diagnostic criterion for critical limb ischemia. Similarly, maximal systolic acceleration ratios are highly predictive of carotid or renal stenosis. However, the literature lacks reference standards or guidelines for the assessment of such variables, and their measurement techniques seem to differ between authors. We propose herein a semantic and measurement statement order to clarify and help standardize future research.

Skin Layer Thickness and Shear Wave Elastography Changes Induced by Intensive Decongestive Treatment of Lower Limb Lymphedema.

Background: A detailed quantitative evaluation would be beneficial for management of patients with limb lymphedema. Methods and Results: In 47 patients with lower limb lymphedema at International Society of Lymphology clinical stage 2A (18 limbs), 2B (41 limbs), and 3 (13 limbs), we measured the limb circumference and thickness of epidermis, dermis, and subcutis layers with B-mode ultrasonography and subcutis elastic modulus with ultrafast shear wave velocity (ultrasound elastography) at 5 anatomical levels (M1 to M5) before and after a 3- to 5-day intensive decongestive therapy (IDT) session. Limb circumference and thickness of the epidermis, dermis, and subcutis were greater in the 72 limbs with lymphedema than in the 22 unaffected limbs before and after IDT. The affected limb volume was 10,980 [8458-13,960] mL before and 9607 [7720-11,830] mL after IDT (p < 0.0001). The IDT-induced change in subcutis thickness was -9 [-25 to 13]% (NS), -11 [-26 to 3]% (p = 0.001), -18 [-40 to -1]% (p < 0.0001), -15 [-35 to 3]% (p = 0.0003), and -25 [-45 to -4]% (p < 0.0001) and significantly correlated with the change in elastic modulus, which was 13 [-21 to 90]% (p = 0.004), 33 [-27 to 115]% (p = 0.0002), 40[-13 to 169]% (p < 0.0001), 9 [-36 to 157]% (p = 0.024), and -13 [-40 to 97]% (NS), respectively, at the M1, M2, M3, M4, and M5 levels. Intraobserver reproducibility was satisfactory for skin thickness and fairly good for elastography, but interobserver reproducibility was poor or unacceptable. Conclusions: IDT reduced the circumference and subcutis thickness of lower limbs with lymphedema and increased their elastic modulus, implying greater tissue stiffness probably due to fluid evacuation. Although subcutis thickness measurement proved to be reliable, technological and methodological improvements are required before ultrasonographic elastography can be used in clinical practice.

SARS-CoV-2 Vaccine and Thrombosis: An Expert Consensus on Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Historically, the vaccination strategies developed in the second half of the 20th century have facilitated the eradication of infectious diseases. From the onset of COVID-19 pandemic to the end of April 2021, more than 150 million cases and 3 million deaths were documented worldwide with disruption of the economic and social activity, and with devastating material, physical, and psychological consequences. Reports of unusual and severe thrombotic events, including cerebral and splanchnic venous thrombosis and other autoimmune adverse reactions, such as immune thrombocytopenia or thrombotic microangiopathies in connection with some of the SARS-CoV-2 vaccines, have caused a great deal of concern within the population and the medical community. This report is intended to provide practical answers following an overview of our knowledge on these thrombotic events that are extremely rare but have serious consequences. Vaccine hesitancy threatens to reverse the progress made in controlling vaccine-preventable diseases. These adverse events must be put into perspective with an objective analysis of the facts and the issues of the vaccination strategy during this SARS-CoV-2 pandemic. Health care professionals remain the most pertinent advisors and influencers regarding vaccination decisions; they have to be supported to provide reliable and credible information on vaccines. We need to inform, reassure, and support our patients when the prescription is made. Facing these challenges and observations, a panel of experts express their insights and propose a tracking algorithm for vaccinated patients based on a 10-point guideline for decision-making on what to do and not to do.

Comparison of the clinical history of symptomatic isolated muscular calf vein thrombosis versus deep calf vein thrombosis.

BACKGROUND: Half of all lower limb deep vein thromboses (DVT) are distal DVT that are equally distributed between muscular calf vein thromboses (MCVT) and deep calf vein thromboses (DCVT). Despite their high prevalence, MCVT and DCVT have never been compared so far, which prevents possible modulation of distal DVT management according to the kind of distal DVT (MCVT or DCVT). METHODS: Using data from the French, multicenter, prospective observational OPTimisation de l'Interrogatoire dans l'évaluation du risque throMbo-Embolique Veineux (OPTIMEV) study, we compared the clinical presentation and risk factors of 268 symptomatic isolated DCVT and 457 symptomatic isolated MCVT and the 3-month outcomes of the 222 DCVT and 390 MCVT that were followed-up. RESULTS: During the entire follow-up, 86.5% of DCVT patients and 76.7% of MCVT patients were treated with anticoagulant drugs (P = .003). MCVT was significantly more associated with localized pain than DCVT (30.4% vs 22.4%, P = .02) and less associated with swelling (47.9% vs 62.7%, P < .001). MCVT and DCVT patients exhibited the same risk factors profile, except that recent surgery was slightly more associated with DCVT (odds ratio, 1.70%; confidence interval, 1.06-2.75), and had equivalent comorbidities as evaluated by the Charlson index. At 3 months, no statistically significant difference was noted between MCVT and DCVT in death (3.8% vs 4.1%), venous thromboembolism recurrence (1.5% vs 1.4%), and major bleeding (0% vs 0.5%). CONCLUSION: Isolated symptomatic MCVT and DCVT exhibit different clinical symptoms at presentation but affect the same patient population. Under anticoagulant treatment and in the short-term, isolated distal DVT constitutes a homogeneous entity. Therapeutic trials are needed to determine a consensual mode of care of MCVT and DCVT.

[Low-molecular-weight heparins for cancer-associated thromboembolism: What place in 2019?] / Héparines de bas poids moléculaires dans la maladie thromboembolique veineuse liée au cancer : quelle place en 2019 ?

According to international clinical practice guidelines, low-molecular-weight heparins are advocate for the treatment and the prevention of cancer associated thrombosis. Direct oral anticoagulants recently introduced represent an alternative to vitamin K antagonists and low-molecular-weight heparins since their use doesn't require coagulation monitoring or daily subcutaneous injections. Recent studies comparing direct oral anticoagulants and low-molecular-weight heparins have shown a trend towards a reduction of venous thromboembolism events of direct oral anticoagulants but an increased risk of major bleeding. Recent French inter-group recommendations on the treatment of venous thromboembolism in cancer patients, favor low molecular weight heparins over direct oral anticoagulants as curative agents. In the light of recent studies, the objective of this review is to re-evaluate the place of low-molecular-weight heparins in the management of patents with cancer-associated thrombosis and to focus on the recent updates of international guidelines.

A clinical prediction score for upper extremity deep venous thrombosis.

It was the objective of this study to design a clinical prediction score for the diagnosis of upper extremity deep venous thrombosis (UEDVT). A score was built by multivariate logistic regression in a sample of patients hospitalized for suspicion of UEDVT (derivation sample). It was validated in a second sample in the same university hospital, then in a sample from the multicenter OPTIMEV study that included both outpatients and inpatients. In these three samples, UEDVT diagnosis was objectively confirmed by ultrasound. The derivation sample included 140 patients among whom 50 had confirmed UEDVT, the validation sample included 103 patients among whom 46 had UEDVT, and the OPTIMEV sample included 214 patients among whom 65 had UEDVT. The clinical score identified a combination of four items (venous material, localized pain, unilateral pitting edema and other diagnosis as plausible). One point was attributed to each item (positive for the first 3 and negative for the other diagnosis). A score of -1 or 0 characterized low probability patients, a score of 1 identified intermediate probability patients, and a score of 2 or 3 identified patients with high probability. Low probability score identified a prevalence of UEDVT of 12, 9 and 13%, respectively, in the derivation, validation and OPTIMEV samples. High probability score identified a prevalence of UEDVT of 70, 64 and 69% respectively. In conclusion we propose a simple score to calculate clinical probability of UEDVT. This score might be a useful test in clinical trials as well as in clinical practice.

Clinical relevance of distal deep vein thrombosis. Review of literature data.

The standard diagnostic approach of suspected deep vein thrombosis (DVT) is serial lower limb compression ultrasound (CUS) of proximal veins. Although it only assesses the proximal veins, withholding anticoagulant treatment in patients with a negative CUS on day one and after one week has been proven to be safe. However, in many centres, distal DVT is systematically screened for and treated by anticoagulants. The objectives of the review were 1) to evaluate the rate of extension of distal DVTs to proximal veins 2) to compare the safety of proximal limited CUS versus single complete CUS. We performed a MEDLINE search covering the period from January 1983 to January 2005 by using the key-words "calf vein thrombosis", "distal thrombosis" and "compression ultrasonography". English, German and French language original studies were retrieved. Moreover, references of retrieved articles were screened in order to detect missed pertinent articles. We pooled data of management studies where proximal or complete (i.e. proximal and distal) CUS were used, respectively. Studies evaluating CUS limited to the proximal veins showed a good safety profile with a pooled estimate of the 3-month thromboembolic rate of 0.6% (95% CI: 0.4-0.9%) in patients in whom anticoagulation was withheld. Studies using proximal and distal CUS showed a similar pooled estimate of the 3-month thromboembolic rate (0.4%, 95% CI: 0.1-0.6%) but distal DVT accounted for as many as 50% of all diagnosed DVTs in those series. Therefore, searching for distal DVT potentially doubles the number of patients given anticoagulant therapy and entails a risk of over-treatment. Data suggesting that anticoagulation is indicated for distal DVT are limited, and realizing distal CUS entails a risk of over-treatment. There is an urgent need for randomised trials assessing the usefulness of anticoagulant treatment in distal DVT.

Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic deep vein thrombosis (DVT) of the calf. We aimed to assess whether therapeutic anticoagulation is superior to placebo in patients with symptomatic calf DVT. METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled low-risk outpatients (without active cancer or previous venous thromboembolic disease) with a first acute symptomatic DVT in the calf from 23 university medical centres or community medical clinics in Canada, France, and Switzerland. We randomly assigned (1:1) patients to receive either the low-molecular-weight heparin nadroparin (171 UI/kg, subcutaneously, once a day) or placebo (saline 0·9%, subcutaneously, once a day) for 6 weeks (42 days). Central randomisation was done using a computer-generated randomisation list, stratified by study centre. Random allocation sequences of variable block size were centrally determined by an independent research clinical centre. Study staff, patients, and outcome assessors (central adjudication committee) were masked to group assignment. Numbered boxes of active drug or placebo were provided to pharmacies in identical packaging. All patients were prescribed compression stockings and followed up for 90 days. The primary efficacy outcome was a composite measure of extension of calf DVT to proximal veins, contralateral proximal DVT, and symptomatic pulmonary embolism at day 42 in the modified intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding at day 42. The trial was registered with ClinicalTrials.gov, number NCT00421538. FINDINGS: Between Feb 1, 2008, and Nov 30, 2014, we screened 746 patients, enrolling 259 patients (50% of the prespecified sample size), before the trial steering committee terminated the trial because of expiry of study drug and slow recruitment. The intention-to-treat analysis population comprised 122 patients in the nadroparin group and 130 in the placebo group. There was no significant difference between the groups in the composite primary outcome, which occurred in four patients (3%) in the nadroparin group and in seven (5%) in the placebo group (risk difference -2·1%, 95% CI -7·8 to 3·5; p=0·54). Bleeding occurred in five patients (4%) in the nadroparin group and no patients in the placebo group (risk difference 4·1, 95% CI 0·4 to 9·2; p=0·0255). In the nadroparin group one patient died from metastatic pancreatic cancer and one patient was diagnosed with heparin-induced thrombocytopenia type 2. INTERPRETATION: Nadroparin was not superior to placebo in reducing the risk of proximal extension or venous thromboembolic events in low-risk outpatients with symptomatic calf DVT, but did increase the risk of bleeding. Avoidance of systematic anticoagulation for calf DVT could have a substantial impact on individual patients and from a public health perspective. FUNDING: Swiss National Science Foundation, the Programme Hospitalier de Recherche Clinique in France, and the Canadian Institutes of Health Research.

[Methods of development of recommendations for clinical practice (RCP) and of setting-up of a platform cancer heart vessels (PTF-CHV) in the inter3C Vaucluse-Arles]. / Méthodes d'élaboration des recommandations pour la pratique clinique (RPC) et fonctionnement de la plate forme cœur vaisseaux cancer (PTF-CVC) dans l'inter3C Vaucluse pays d'Arles.

Monitoring and prevention of cardiovascular complications of anti-neoplastic treatment are currently well known for anthracyclines and trastuzumab but remain poorly implemented. The management of cardiac and vascular side effects of targeted therapies is not codified. The purpose of the platform heart-vessel cancer is to optimize the management of such complications within a small area (Vaucluse region of Arles). The platform will offer prescribers an easily accessible database, doctors performing exams standardized monitoring forms and patients a uniform follow-up. We report here the methodology of the elaboration of recommendations for clinical practice and the ways to develop the platform. After a year of active process, an analysis of the will be performed to see opportunities for improvement and dissemination on a larger scale.

Wall mechanics of the stented extracranial carotid artery.

BACKGROUND AND PURPOSE: Abrupt compliance changes and concomitant nonlaminar flow patterns may contribute to endothelial dysfunction and subsequent neointimal thickening. The aim of this study was to test the feasibility of wall mechanics measurement using B-mode ultrasound image analysis by dedicated software in the stented human carotid artery. METHODS: Carotid Wallstents (Schneider) were placed in the extracranial carotid arteries of 15 patients. B-mode ultrasound examination was performed with a 7.5-MHz probe on the carotid artery upstream; at the proximal, mid, and distal stent levels; downstream from the stent; and on the contralateral internal and common carotid arteries. Carotid diameter (d) and systolic diameter changes (Deltad) were measured with a dedicated image processing system (IO version 3.1, IODP), while pulse blood pressure (DeltaP) was measured. Diameter compliance (Cd) and distensibility coefficient (DC) were calculated as Cd=2Deltad/DeltaP and DC=2Deltad/DeltaP/d and compared between measurement sites. RESULTS: The evaluation could be completed in 8 of 15 patients. Compliance was significantly lower at the proximal, mid, and distal stent levels (27.77+/-1.11, 27.38+/-1.08, 27.38+/-1.09x10(-3) mm x kPa(-1)) than upstream (103.3+/-36.7x10(-3) mm x kPa(-1)), downstream (91.5+/-41.3x10(-3) mm x kPa(-1)), or on the contralateral internal (87.6+/-28x10(-3) mm x kPa(-1)) and common (149.3+/-47.6x10(-3) mm x kPa(-1)) carotid arteries. CONCLUSIONS: Stenting of the extracranial carotid artery induces a compliance mismatch between the native and the stented artery.

Red blood cell methylfolate and plasma homocysteine as risk factors for venous thromboembolism: a matched case-control study.

BACKGROUND: Moderate hyperhomocysteinaemia is a risk factor for venous thromboembolism. We do not know whether this risk depends on homocysteine itself or on components of the homocysteine remethylation pathway, such as methylfolate. We did a case-control study to analyse the relation between the major components of the homocysteine remethylation pathway and risk of venous thromboembolism. METHODS: We measured concentrations of homocysteine, methionine, and folate in plasma, total folate and methylfolate in red-blood cells, and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotype and other known risk factors for venous thromboembolic disease in 243 patients with deep vein thrombosis or pulmonary embolism and controls matched for sex and age. FINDINGS: Concentrations in plasma of homocysteine differed significantly between cases and controls. We noted a strong concentration-dependent association between concentrations of methylfolate in red-blood cells and risk of venous thromboembolism. The adjusted conditional odds ratio ranged from 1.0 for methylfolate 249 microg/L or greater to 7.1 (3.2-15.8) for methylfolate 141 microg/L or less. Methionine concentrations below the median were also independently associated with raised risk of venous thromboembolic disease, as were established risk factors such as high body-mass index, history of cancer, family history of thromboembolism, oral contraceptive use, and factor V Leiden mutation. Furthermore, the association between concentrations of methylfolate in red-blood cells and risk of thromboembolism varied according to MTHFR C677T genotype. INTERPRETATION: Measurement of methylfolate concentrations in red-blood cells might help to identify people at risk of venous thromboembolism.