Literature review of transcutaneous electrical nerve stimulation in peripheral arterial occlusive disease of the lower limbs.

The therapeutic challenge in peripheral arterial occlusive disease (PAD) is often to increase walking distance, improve pain or heal a wound when PAD is symptomatic. Walking rehabilitation or surgical revascularization techniques are limited. Others strategies as alternatives and/or complementary treatments are needed. Among alternative options, Transcutaneous Electrical Nerve Stimulations (TENS) could be of interest, both for improved walking distance or pain reduction. The Transcutaneous Electrical Nerve Stimulation (TENS) is a non-pharmacological, mini-invasive technique involving transcutaneous electrical stimulation. However, there are other transcutaneous electrical nerve stimulation techniques based on the principle of vagus nerve stimulation with different mechanistics. Trans-auricular Vagus nerve stimulation (Ta-VNS) is another TENS technique (electrode on the external ear) which relies on the anti-inflammatory pathways of efferent and afferent vagal fibers. We propose here to review the literature of mini-invasive electrical stimulations, whatever the anatomical zone concerned, in PAD. METHOD: The aim was to evaluate the use of non-invasive transcutaneous electrical stimulation therapies (regardless of location) in PAD of the lower limbs, whatever the disease grade. A review of the literature was carried out via a search of the MEDLINE/PubMed database from 1975 to 2023. The articles were selected via abstracts by checking (1) medical indications: PAD patients with claudication were retained, excluding neurological or venous claudication, PAD whatever the disease grade (intermittent claudication or critical limb ischemia [CLI]) and (2) non invasive electrical stimulations were considered (neuromuscular electrical stimulation and spinal cord stimulation were excluded) whatever the anatomical site. Non-electrical stimuli such as acupuncture and reflexotherapy were excluded. RESULTS: Only 9 items were selected, including 7 studies with TENS treatment on the calf, one with trans-auricular vagus nerve stimulation and one with electro-acupuncture points of stimulation. CONCLUSION: Even if the mechanisms involved are different, TENS on the calves or in the external ears show an improvement of walking distance in PAD patients with intermittent claudication. The results of the studies show few positive effects in arteriopathy but we should keep vigilant in the technics used since mechanisms are different and not fully understood. Electro-stimulation of the calf and external ear appears to be an easy-to-use and accessible therapeutic option, especially since some PAD patients are still failing to be released from pain, despite the rise of endovascular interventional techniques.

Evaluation of patients' and practitionners' satisfaction with the use of hypnosis during a thermal endovenous procedure.

INTRODUCTION: In the field of vascular surgery, hypnosis has been used in the creation of venous approaches but also as a complement to local anesthesia during more extensive vascular surgery, including the insertion of abdominal aortic aneurysm stents. The practice of thermal endovenous procedures seems to us to be conducive to hypnotic support in particular to reinforce hypnoanalgesia. METHOD: We present a prospective and monocentric observational study at the University Hospital of Grenoble with consecutive inclusions whose objective was to evaluate the interest and the satisfaction of the patients and practionners about the practice of hypnosis during procedures of thermal endovenous treatments. RESULTS: Among the 31 patients treated with endovenous laser, 27 accepted the hypnosis proposal, 16 had hypnosis considered as formal and 13 conversational hypnosis and 10 conversation only. Among them, 29% of patients considered that the hypnoanalgesia technique had enormously relaxed them and 19% "very relaxed"; 42% of patients considered themselves "good", 32% "very good" and 19% "extremely good" at the end of the procedure. Concerning the practitioners performing the endovenous procedure, more than half (51, 51%) considered that hypnoanalgesia relaxed the patient "moderately and/or a lot". The results were as a whole point to a high level of satisfaction on the part of patients and practitioners with the practice of procedures with various levels of hypnosis induction. Despite many biases, this study has the merit of concluding that the patients were very satisfied with the apprehension of these gestures as well as the practitioners, and this without any additional time during the procedure.

Evaluation of socio-economic insecurity in peripheral artery disease patients.

The social and economic environment has become a major determinant of cardiovascular health. The objective of our study was to assess socio-economic insecurity in patients with symptomatic PAD. The PRECAR study was a non-interventional prospective cohort study. Patients were recruited from the Vascular Medicine and Surgery Departments of Grenoble-Alpes University Hospital or during a consultation as part of the therapeutic education program "On the move! Better understanding and better living with arterial disease". The analysis of socio-economic and environmental data was based on the EPICES score (a reliable index used to measure individual deprivation) and INSEE parameters (level of education and socio-professional category). Cardiovascular risk factors were also recorded. 150 patients with symptomatic PAD were included between November 2017 and June 2018. 84% were men. In our population 54% (CI95% 45.7 - 62.1) were in a precarious situation compared to 40% (CI95% 39.8 - 40.2) in the general population, according to the EPICES score (P<0.001). Levels of education were low and patients with a baccalaureate or higher education degree were under-represented. Executives, intellectuals and intermediate professions were also under-represented in the PAD population. This data opens new perspectives on the social characterisation of patients that may contribute to improving the outcomes of patients with peripheral vascular disease.

[Overt disseminated intravascular coagulation complicating a venous malformation]. / Une coagulopathie intravasculaire disséminée liée à une malformation veineuse.

INTRODUCTION: Coagulopathy related to venous malformations can be life threatening. This complication is little known and underestimated. CASE REPORT: We report the case of a 52-year-old female patient who presented with a left femoral fracture. She had a pre-existing muscular infiltrating venous malformation of the left hip. During surgery, she developed acute disseminated intravascular coagulation. The latter was probably a consequence of both surgery and localized intravascular coagulation that was unknown before the trauma. CONCLUSION: It is important to diagnose localized intravascular coagulation in venous malformations, since the risk of disseminated intravascular coagulation can be prevented by anticoagulant therapy.

Abnormal amplitude and kinetics of digital postocclusive reactive hyperemia in systemic sclerosis.

OBJECTIVES: Postocclusive reactive hyperemia is mediated by two major mediators: sensory nerves and endothelium-derived hyperpolarizing factors. We hypothesized that the skin microvascular response to 5 min ischemia would differ depending upon the hand location in patients with systemic sclerosis (SSc), primary Raynaud's phenomenon (PRP) and healthy controls. METHODS: Fifteen patients with SSc, 15 sex- and age-matched patients with PRP and healthy controls were enrolled. Their right hands were subjected to 5 min ischemia followed by a postocclusive hyperemia test, with local microcirculation monitoring by laser speckle contrast imaging on the dorsal face of the hand. RESULTS: Postocclusive reactive hyperemia was abnormal in terms of peak and area under the curve (AUC) on all fingers except the thumb in patients with SSc and PRP compared with controls. In contrast, the kinetics of the response was longer only in SSc patients, with mean (SD) time to peak on the index, middle and ring finger were respectively 72 (58), 73 (51) and 67 (47) s for SSc; 40 (20), 40 (20) and 36 (19) s for PRP; and 34 (30), 34 (30) and 29 (24) s for controls (P=0.009 for interaction). CONCLUSIONS: We observed decreased distal digital microvascular perfusion following 5 min of ischemia in patients presenting with PRP or SSc, while the kinetics was prolonged only in SSc. A dynamic assessment of digital skin blood flow using laser speckle contrast imaging following 5 min ischemia could be used as a tool to assess microvascular abnormalities in patients with Raynaud's phenomenon secondary to SSc.

The digital thermal hyperemia pattern is associated with the onset of digital ulcerations in systemic sclerosis during 3 years of follow-up.

OBJECTIVES: One of the most important skin complications in systemic sclerosis (SSc) is digital ulceration. Local thermal hyperemia (LTH) in the skin is a biphasic response to local heating involving both neurovascular and endothelial responses. Since LTH is abnormal in SSc patients, we aimed at testing whether LTH could be a prognostic tool for the onset of digital ulcers. METHODS: We prospectively enrolled 51 patients with SSc. Nailfold capillaroscopy and LTH were recorded at baseline, and patients were followed for 3 years. RESULTS: No patient with a LTH peak/plateau ratio ≥1 (n=19) developed digital ulcerations during the 3 year follow-up (100% negative predictive value), while 6 out of 32 patients with a LTH peak/plateau ratio <1 at enrolment presented with finger pad ulcerations within 3 years (p=0.05). In contrast, when lidocaine/prilocaine was applied to the finger pad, no relationship between thermal hyperemia and digital ulcerations was observed. CONCLUSIONS: A LTH peak/plateau ratio on the finger pad greater than 1, which can easily be determined in routine clinical practice, could be used to reassure patients, whatever the subtype of SSc, about the low probability of future digital ulceration. However, the prognostic value of this parameter should be confirmed in a larger cohort.

[Recurrent deep vein thrombosis and myeloproliferative syndrom: emergence of JAK2 mutation five years after the initial event]. / Thromboses veineuses à répétition et syndrome myéloprolifératif : positivité secondaire d'une mutation JAK2 cinq ans après l'événement initial.

JAK 2 mutation is the molecular event responsible for 95% of polycythemia cases and 50% of thrombocythemia vera and myelofibrosis cases. It can be used as a tool for the diagnosis of myeloproliferative disorders. We report a case illustrating the fact that a negative result does not definitively eliminate the diagnosis. A 40-year old woman, with a medical history of familial deep vein thrombosis, developed thrombosis of the inferior vena cava with extension to the suprahepatic veins and pulmonary embolism. No constitutional or acquired thrombophilia was diagnosed; search for JAK 2 mutation was negative. The patient was treated with fluindione. Five years later, she relapsed with popliteo-femoral and vena cava deep vein thrombosis. The etiological work-up included a PET scan which revealed diffuse uptake in bones and suspected neoplasic bone marrow invasion. Progenitor cell cultures were positive and JAK 2 mutation was confirmed. The bone marrow aspirate had the cytologic appearance of a myeloproliferative disorder. This case illustrates the fact that JAK 2 mutation can be identified several years after onset of a latent myeloproliferative disorder. Cases with a high clinical likelihood should lead to renewed search for this mutation. Secondary discovery of this mutation can be explained by a higher proportion of mutation expressing clones.

Cutaneous iontophoresis of treprostinil in systemic sclerosis: a proof-of-concept study.

Ischemic digital ulcer (DU) is a serious complication of systemic sclerosis (SSc). Intravenous prostanoids are the only approved treatment for active DUs, but they induce dose-limiting side effects and require hospitalization. Our objective was to evaluate the effect of iontophoresis (a noninvasive drug delivery method) of treprostinil in SSc patients. Three studies were conducted: a pharmacokinetic study in 12 healthy volunteers showed that peak dermal concentration was reached at 2 hours, whereas plasma treprostinil was undetected. Then, a placebo-controlled, double-blind incremental dose study assessed the effect of treprostinil on digital skin blood flow in 22 healthy subjects. The effect of the highest dose was then compared with that of placebo in 12 SSc patients. Treprostinil significantly increased skin blood flow in healthy subjects (P = 0.006) and in SSc patients (P = 0.023). In conclusion, digital iontophoresis of treprostinil is feasible, is well tolerated, and increases digital skin perfusion. It could be tested as a treatment for SSc-related DUs.

[Temporary vena caval filters: report on cohort of 72 patients in Grenoble, France]. / Filtres cave temporaires: suivi d'une cohorte de 72 patients au CHU de Grenoble.

Patients with a contra-indication for anticoagulation can benefit from temporary vena caval filters for protection against pulmonary embolism or recurrence. The filter can be removed secondarily, once the contra-indication is overcome, enabling better long-term outcome by reducing the risk of thrombotic and mechanic complications inherent in these devices. However, it has been shown in several studies that effective withdrawal rates were low and could be improved by the establishment of protocols and registries. We report a retrospective study of withdrawal in 72 patients in whom an ALN® vena caval filter was implanted at the Grenoble University Hospital over a period of three years with an intention for secondary retrieval. Seventy percent of the indications were related to the coexistence of thrombotic and hemorrhagic conditions. Fifty-five percent of filters were removed, the remaining 45% shared involved patients who died before retrieval (11%), those lost to follow-up (4%), technical failure of retrieval (6%), withdrawal technically unfeasible (3%), retrieval refused by patients (6%) and medical indications for continuing filtration (15%). Despite an effective follow-up of these patients and 91% success rate of withdrawal, nearly one out of two filters remains in place. A long-term follow-up of these patients is needed to learn more about the outcome of these filters.

[Identification of patients at high risk of cancer after a venous thromboembolic disease]. / Identification des patients à haut risque de cancer au décours d'une maladie thromboembolique veineuse.

OBJECTIVE: Assessment of cancer screening in the context of venous thromboembolic disease (VTE) remains controversial. We tried to characterize a population at high risk of developing cancer among patients suffering from VTE. METHOD: We conducted a retrospective ancillary case-control study among patients with VTE who later had a positive diagnosis of cancer. We assessed the association of cancer with characteristic features of VTE and with the results for four biological markers. RESULTS: Our population included 142 patients (53% men, median age 71 years). Two years after VTE, 24 patients (17%) had cancer. Median values for D-dimers, fibrin monomers and SP-selectin were significantly higher among patients who developed cancer. Logistic regression enabled us to identify two parameters targeting patients with a high risk of cancer: bilateral venous thrombosis (OR: 4.41, 95%CI: 1.41-13.78, P=0.01) and D-dimers superior to 3.8 µg/mL (OR: 3.68, 95%CI: 1.36-9.94, P=0.01). The information provided by these two characteristics was additive; 58% of patients in our population who had both factors developed cancer. CONCLUSION: Bilateral venous thrombosis and D-dimers superior to 3.8 µg/mL are highly associated with carcinoma. This result requires a prospective validation. It could be useful in limiting the screening process to the population most at risk.

Treatment of low-flow vascular malformations by ultrasound-guided sclerotherapy with polidocanol foam: 24 cases and literature review.

OBJECTIVES: Treatment by sclerotherapy has been suggested as a first-line treatment of low-flow vascular malformations. This study reports our experience in treating low-flow vascular malformations by ultrasound-guided sclerosis with polidocanol foam at the Vascular Medicine Department in Grenoble, France. DESIGN: Retrospective single-centre consecutive series. MATERIALS AND METHODS: Between January 2006 and December 2009, we analysed the complete records of patients with symptomatic low-flow vascular malformations of venous, lymphatic or complex type (Klippel-Trenaunay syndrome, KTS) treated by ultrasound-guided sclerosis. The therapeutic indication was always validated by the Consultative Committee for vascular malformations of the University Hospital of Grenoble. All vascular malformations were classified according to the Hamburg Classification. The sclerosing agent was polidocanol used as foam. RESULTS: A total of 24 patients between 7 and 78 years were treated (19 venous malformations, three KTSs and two venous-lymphatic malformations). The concentrations of polidocanol used ranged from 0.25% to 3%. The average number of sessions was 2.3 (1-16). After a median follow-up at 5 months after the last session, 23 out of 24 patients reported a decrease in pain; in nine cases (37.5%), over 50% reduction in size was observed, and in 14 cases (58.3%), a reduction of less than 50% of the original size was obtained. Two minor side effects were reported. CONCLUSIONS: Treatment by ultrasound-guided sclerosis using polidocanol foam seems to be well tolerated and can improve the symptoms of low-flow malformations without the risks of more aggressive sclerosing agents, such as ethanol.

[Evaluation of an education program for patients taking oral anticoagulants: Experience of the GRANTED network in Isère]. / Evaluation d'un programme d'éducation thérapeutique pour les traitements anticoagulants oraux : expérience du réseau Ville-Hôpital GRANTED du secteur Sud-Isère.

BACKGROUND: The guidelines for good clinical practices issued by the French Agency for Health and Drug Safety and the Superior Health Authority are designed to improve management of oral anticoagulants which can be an important source of iatrogenic morbidity. These guidelines have focused on the need for special education. The GRANTED network in Isère developed an education program for patients taking oral anticoagulants. OBJECTIVE: The purpose of this study was to evaluate quantitatively the therapeutic education of these patients taking oral anticoagulation, irrespective of their risk factor(s). PATIENTS AND METHODS: This was a retrospective analysis of 100 randomly selected patients taking oral anticoagulants for at least three months who participated in the GRANTED education program in 2007. The evaluation criterion was the number of hemorrhagic and/or thromboembolic events. RESULTS: Among the 97 patients contacted, 3.1% had a serious hemorrhagic event and 1.03% a recurrent thromboembolic event. CONCLUSIONS: The quality of a scientific study depends on the quality of the methodology, leading to a preference for prospective studies. It would nevertheless be pertinent to determine whether or not official management recommendations are applied correctly in real life conditions. We report a first evaluation of a therapeutic education program designed for patients taking oral anticoagulants. The education program within the GRANTED network has enabled a reduction in the iatrogenic morbidity related to oral anticoagulation despite the selection bias of the probably high-risk population enrolled in the GRANTED network.

[Circumscribed telangiectasic lesions of the upper limb: unilateral nevoid telangiectasia syndrome?]. / Lésions télangiectasiques circonscrites au membre supérieur: penser au syndrome des télangiectasies naevoïdes unilatérales.

Patients presenting skin disorders with a probably vascular origin are often addressed to the vascular medicine unit. In general, the diagnosis of telangiectasia is straightforward but in certain rare clinical forms may be misleading. We report the case of a female patient presenting unilateral circumscribed telangiectasia on the left arm. History taking revealed that these lesions were congenital and had become accentuated during a recent pregnancy. The unilateral localization was highly suggestive, following Blaschko's lines. We retained the diagnosis of congenital unilateral nevoid telangiectasia syndrome exaggerated by pregnancy and the consequent hyperestrogenism. While it may be rather easy to rule out medical emergencies such as purpura, identifying the etiology of telangiectasia may be quite difficult, implying a careful, precise and complete history taking. Unilateral nevoid telangiectasia is a rare entity to be recognized. The underlying pathogenic mechanism remains to be elucidated.

[Polidocanol induced cardiotoxicity: a case report and review of the literature]. / Toxicité cardiaque du polidocanol: rapport d'un cas et revue de la littérature.

OBJECTIVE: Polidocanol foam sclerotherapy is a treatment of symptomatic venous disease. This solution is highly valued by clinicians because of its high efficacy and excellent safety profile. Systemic adverse effects are rare. Some life-threatening reactions have been reported. We report a case of respiratory and cardiac arrest, and a literature review on the cardiac toxicity of polidocanol used within and outside their licensed indications. MAIN OUTCOME MEASURES: A 48-year-old woman, with a symptomatic venous disorder, CEAP grade C2, was treated by echosclerotherapy for a great saphenous vein. She developed a malaise and respiratory and cardiac arrest occurred within minutes after a 7 ml foam polidocanol injection. Cardiopulmonary resuscitation was immediately started before restoration of pulses. A literature search was done using the Medline database. RESULTS: Five cases of cardiac toxicity were reported with polidocanol, but four of them were used outside their licensed indications. Because of the very suggestive chronology and the lack of any other obvious etiology, this cardiac arrest was attributed to polidocanol. Initial ST-segment elevation and negativity of anaphylaxis markers suggest a direct myocardial toxicity. CONCLUSIONS: Clinicians should be aware of the possibility of little-known but potentially serious cardiac adverse reaction with polidacanol injection and be prepared to initiate cardiopulmonary resuscitation if needed.

[A rare cause of embolic ischemia of the hand: an isolated aneurism of a branch of the axillary artery]. / Une cause rare d'ischémie embolique de la main: un anévrisme isolé d'une branche de l'artère axillaire.

A 48-year-old man was admitted for subacute ischemia of the right hand of sudden onset. The patient, who participated in amateur sports, had an uneventful medical history. Duplex ultrasonography revealed thrombosis of the right radial and ulnar arteries. On heparin, the clinical course was favorable and investigations to search for an embolic source revealed an aneurism of the posterior circumflex artery (arteriography). The etiological work-up was negative as was the search for other aneurismal locations. Surgical excision was carried out. Pathology examination of the surgical specimen revealed a thrombosed aneurism that had developed on an atherosclerotic plaque. Aneurisms of the posterior circumflex artery have been described in professional baseball and volleyball players, but all sports that involve repetitive movements of the arm at extension, external rotation and forced abduction can complicate such damage. Compression of the aneurismal artery by the humeral head leads to extrusion of the thrombus under pressure and to retrograde embolisation towards the leg arteries. Thus, in the same way as for hypothenar hammer syndrome, signs of distal ischemia in an athlete should lead to a search for this type of injury.

[Vascular Ehlers-Danlos syndrome: a clinical syndrome to be known by every anaesthesiologist and intensive care physician]. / Syndrome d'Ehlers-Danlos de type vasculaire : une entité à connaître des anesthésistes-réanimateurs.

We report the case of a 29-year-old female who presented with a series of major vascular complications in rapid succession: haemothorax following rupture of a mammary artery aneurysm, pulmonary embolism, anterior myocardial infarction secondary to spontaneous dissection of the left anterior descending artery and rupture of a false aneurysm of the splenic artery. A diagnosis of Ehlers-Danlos syndrome (vascular variant) was considered the most likely in this context. Characterized by an extreme vascular fragility, this rare disease poses important clinical management issues for the anaesthetist and intensive care physician.

Non-conform diagnostic management of pulmonary embolism suspected patients is responsible for a higher risk of thrombotic event occurrence.

The aim of this 3-month follow-up prospective pragmatic study was to evaluate the implementation of a pulmonary embolism (PE) diagnostic strategy in clinical practice. One thousand and one hundred thirty-four consecutive in- and outpatients with clinically suspected PE were enrolled into a sequential diagnostic algorithm in which vascular medical unit plays a pivotal role in advising physicians and suggesting the most appropriate tests according to the diagnostic algorithm. In this observational study, patients that followed the proposed work-up were attributed to a so-called "conform group". Patients in whom diagnostic work-up was not according to protocol were attributed to a "non-conform group". Nine hundred and ninety-seven patients (87.9%) had a conform work-up, and 137 patients a non-conform work-up according to the proposed diagnostic algorithm. The non-conform work-up directly increased in relation to the age of the referred patients. PE was ruled out in 907 (80%) patients of whom 787 (86.8%) were in the conform group. Of the 797 patients who did not receive anticoagulant drugs, follow-up was obtained in 792 (99.4%). Among these patients, the incidence of acute thromboembolic events during the 3-month follow-up period was different in the group of patients that had a conform work-up (1%, [95% CI, 0.5-2.1%]) from the non-conform group patients (4.5%, [95% CI, 2-10.2%]. Therefore patients from the non-conform group have an independent increased risk to develop a thromboembolic event during the follow-up, adjusted odds ratio 3.3 [1.1-10, 95% CI]. Therefore we demonstrated that a non-conform diagnostic management strategy is associated with a higher risk of thrombotic event occurrence.