Treatment Of Chronic Venous Insufficiency Research Articles

The Neuroprotective Effect of Micronized Purified Flavonoid Fraction in an Experimental Parkinson’s Disease Model

Micronized purified flavonoid fraction (MPFF; Daflon®) containing 90% diosmin and 10% hesperidin is a vasoactive drug used for the treatment of chronic venous insufficiency and hemorrhoids. The aim of this study was to examine the effect of MPFF on the development of brain oxidative stress and neuronal damage induced in the rat by systemic rotenone injection. Rats received subcutaneous injections of rotenone (1.5 mg/kg) every other day for two weeks and were orally treated with MPFF (9 or 18 mg/kg). Results indicated that rotenone caused a significantly elevated oxidative stress in the cerebral cortex, striatum, and the rest of the brain tissue. Malondialdehyde (MDA) and nitric oxide concentrations were increased. In contrast, the level of reduced glutathione (GSH) and the activity of paraoxonase-1 (PON-1) were decreased in the above brain regions. Moreover, the concentration of the antiapoptotic protein B cell/lymphoma-2 (Bcl-2) in the striatum decreased after rotenone injection. Rotenone caused neuronal vacuolation and apoptotic neurons in the striatum, cortex, and hippocampus. Treatment with MPFF reduced, in a dose-dependent manner, the rotenone-induced increase in brain lipid peroxidation and nitric oxide and restored GSH level and PON-1 activity to vehicle control values. Moreover, MPFF was found to attenuate the decrease in Bcl-2 and the histopathological changes in the brain of rotenone-treated animals. These results suggest that MPFF could be a potential therapeutic “add on” for the pharmacological treatment of Parkinson’s disease.

Динамика состояния кожи нижних конечностей у пациентов с хронической венозной недостаточностью на фоне применения негормонального противовоспалительного и увлажняющего средства на основе нафталанской нефти

Background: chronic venous insufficiency with venous hypertension results in skin trophic changes as well as the proliferation and keratinization of epidermal cells that leads to multiple microinjuries. These microinjuries are a portal of entry for secondary infections. A group of medicines, skin protectors, aims to normalize these processes. Medications that improve skin regeneration and also demonstrate anti-inflammatory and antibacterial effects are of particular interest. Aim: to assess the effect of 3% naphthalan cream Losterin on the skin of the lower extremities in patients with chronic venous insufficiency. Patients and Methods: 15 patients (5 men and 10 women, mean age 67.27±1.03 years) were examined. All participants applied Losterin® on the right tibial and foot skin while the left lower limb was the control. Optical coherence tomography (OCT) of symmetrical tibial and foot skin areas was performed before and after one week of the treatment to evaluate its efficacy. The brightness, height, and border sharpness of skin layers as well as blood vessels were assessed. Results: all patients reported on the improvement of dryness, itching, desquamation, and skin elasticity after the topical treatment versus no-treatment. OCT performed after one week of the treatment with Losterin demonstrated less edema, lower height and brightness of the 1st and 2nd optical layers thus illustrating reduced hyperkeratosis. Additionally, reduced stratum corneum thickness was revealed after the topical treatment. Conclusions: Losterin allows for higher efficacy of the complex treatment for chronic venous insufficiency by reducing the risk of skin microinjuries, regenerating the hydrolipid mantle of the skin, and improving physiological desquamation. Moreover, subjective perceptions are fully in line with OCT findings. KEYWORDS: Losterin, skin protectors, optical coherence tomography, trophic ulcers, venous hypertension. FOR CITATION: Petrova K.S., Nemirova S.V., Islamov R.A., Karpenko A.A. Dynamics of skin lesions of the lower leg in patients with chronic venous insufficiency after the applications of a non-hormonal anti-inflammatory moisturizer based on naphthalan oil. Russian Medical Inquiry. 2020;4(10):632–636. DOI: 10.32364/2587-6821-2020-4-10-632-636.

Impacts of endovenous laser ablation on neovascularization in treatment of chronic venous insufficiency (CVI)

Objectives: The aim of this experimental study is to contribute to the elucidation of the etiopathogenesis of recurrence and to investigate the effect of thermal energy on neovascularization in Sapheno-Femoral Junction (SFJ) divisions. Methods: Seven adult wistar rats have been used for each group. The left legs of the same rats without any attemp were accepted as the control group. The other groups were named surgical and Endovascular laser ablasyon (EVLA) group respectively, after right femoral venous binding, with scissor divide and directly with cotter divide. After routine light microscopic tissue processing; tissue samples were stained by Hemotoxylin-Eosin and VEGF. In light microscopic sections, capillaries were counted with 10 different field x20 lens magnification, and the average was taken and H-Scores were determined. For the statistical analysis, the Spousal T Test was applied and the groups were compared according to the result. Kolmogorov-Simirnov Test was applied to individual distributions of each group. Results: In statistical analysis; the Kolmogorov-Simirnov test was normally distributed separately (p>0,05). In VEGF immunostaining; while there was statistically significant difference between Control and Surgery group (p: 0,001), between Surgery and EVLA group (p: 0,039) and there was no statistically significant difference between Control and EVLA group (P: 0,199). Conclusions: In our study, it was observed that the use of thermal ablation in EVLA application of varicose vein surgery in SFJ reduced neovascularization emerging in varicose vein recurrence. EVLA may be an easily applicable, minimally invasive and alternative way of preventing varicose venous recurrences.

Use of Detravenol in treatment of chronic venous insufficiency of lower limbs

The purpose of this study was to prove that Detravenol is not inferior by clinical efficacy to Detralex® in the course administration in patients presenting with chronic venous insufficiency of the lower extremities caused by lower limb varicose veins. Ours was a prospective randomized open-liable comparative trial aimed at determining efficacy and safety of the two drugs in parallel groups with active control. The trial enrolled a total of 106 patients with chronic venous insufficiency of the lower extremities secondary to lower limb varicose veins. The patients took the drug during 60 days twice daily. The primary outcome measure of efficacy was reduction of the malleolar circumference upon completion of treatment as compared with the baseline values, with the secondary outcome measures being the dynamics of parameters according to the Venous Clinical Severity Score (VCSS), CIVIQ-2 quality of life questionnaire, and the findings of ultrasonographic duplex scanning. The obtained findings demonstrated efficacy of therapy with the use of Detravenol in treatment of patients with chronic venous insufficiency of the lower limbs. The 60-day therapy with the study drug resulted in decreased oedema of the lower extremities: the malleolar circumference reduced averagely by 4%, the composite index of the venous clinical severity score diminished averagely by 50%, and the subjective measure of quality of life increased. Patients taking the study drug demonstrated positive dynamics according to the findings of ultrasonographic duplex scanning, with no serious adverse events during the trial observed. By the primary outcome measure of efficacy (reduction of the malleolar circumference) therapy using the investigational drug proved to be not inferior to therapy with the comparator drug. By the secondary outcome measures the compared therapies appeared equally effective. The study drug and the comparator were found to have a similar safety profile.

Differential diagnosis and treatment of edema of lower extremities

The article gives a definition, classification and mechanisms for the development of edema (increased hydrostatic pressure, increased capillary permeability, decreased colloidal osmotic pressure). The main diseases accompanied by edematous syndrome are considered, diagnostic search algorithms are given. The clinic and treatment of edema of the lower extremities due to lymphatic and venous insufficiency are separately discussed. The data of a clinical study of the effectiveness of drugs based on diosmin and hesperidin in the treatment of chronic venous insufficiency are presented.

Studies of physico-chemical and pharmaco-technological parameters of bioflavonoids diosmin and hesperidin

The use of medicinal substances of herbal origin are perspective direction for the development sector of the pharmaceutical industry of healthcare in Ukraine, even though increased demand for synthetic medicines. The natural substances that have a wide range of therapeutic effects, low toxicity and can be used in therapy of anorectal diseases is diosmin and hesperidin. In the pharmaceutical market of Ukraine the substances of diosmin and hesperidin are presented as solid dosage forms, which can be used for treatment of chronic venous insufficiency. It is appropriate to development composition and technology of new combination dosage form, which can purposefully release active substances in the places of progressing pathological process. The definition of substance properties is based on a comprehensive research, which results will have a significant impact on the technology of obtaining a new drug.The aim of the work was physic-chemical and pharmaco-technological researches of substances diosmin and hesperidin.Results. The result of our work were carrying out a microscopic research, which is confirming results a differential curve of particle distribution, studied derivatographic characteristics of the substances, moisture absorption and solubility. Based on the research it can be concluded about insufficient solubility of diosmin and hesperidin, their high hygroscopicity and high critical degradation of substances. According to the results of microscopic analysis, diosmin has a few fractions with different distributions of particles and hesperidin has capable of agglomeration.Conclusions. On the basis of research it can be concluded for the feasibility of further research, which can improve properties of the substances diosmin and hesperidin. The results of research can be concluded, that conducted results will have impact on development of the composition and technology of the new dosage form with diosmin and hesperidin

Development of a Minimum Data Set Registry for Chronic Venous Insufficiency of the Lower Limbs.

The purpose of this study was to develop a minimum data set (MDS) registry for the prevention, diagnosis and treatment of chronic venous insufficiency (CVI) of the lower limbs. We designed the instrument in two phases, comprising a literature review and an e-Delphi study to validate the content. We obtained a total of 39 documents that we used to develop a registry with 125 items grouped in 7 categories, as follows: Patient examination, venous disease assessment methods, diagnostic tests to confirm the disease, ulcer assessment, treatments to manage the disease at all its stages, patient quality of life, and patient health education. The instrument content was validated by 25 experts, 88% of whom were primary healthcare and hospital nurses and 84% had more than 10 years’ experience in wound care. Using a two-round Delphi approach, we reduced the number of items in the MDS-CVI to 106 items. The categories remained unchanged. We developed an MDS for CVI with seven categories to assist healthcare professionals in the prevention, early detection, and treatment history of CVI. This tool will allow the creation of a registry in the primary care setting to monitor the venous health state of the population.

Effectiveness and safety of sulodexide in the treatment of venous diseases

This article presents a review of the literature assessing the effectiveness and safety of sulodexide in the prophylaxis of deep vein thrombosis and treatment of chronic venous disease. It was demonstrated that sulodexide is effective and safe in the prophylaxis of deep vein thrombosis and treatment of chronic venous insufficiency with ulcers. Sulodexide is characterized by low frequency of bleeding complications.

Endovenous Deep Vein Valve Creation for the Treatment of Chronic Venous Insufficiency

Endovenous Deep Vein Valve Creation for the Treatment of Chronic Venous Insufficiency

Mechano-Chemical Endo-Venous Ablation of Varicose Veins with Flebogrif Occlusion Catheter

AbstractBackground: Varicose veins may present a major health problem nowadays, as it has been detected in about 70% of population worldwide. This created a sense of urgency to develop less invasive techniques to manage such a condition.Aim of Study: The aim of this study was to evaluate the effectiveness and safety of mechano-chemical ablation tech-nique in management of varicose veins using the flebogrif endo-venous occlusion catheter.Patients and Methods: A total of 30 patients (35 lower limbs) had mechan-ochemical ablation for their varicose veins using the flebogrif endo-venous catheter; 22 for great saphe-nous vein (GSV) incompetence, 9 bilateral GSV, 3 shorts saphenous vein (SSV), one bilateral SSV and 2 combined unilateral great saphenous vein and SSV. Patients came back for follow-up one week, one month and 3 months post proce-dure having ultrasound duplex done. Recanalization, pigmen-tation, intra and post procedural pain were recorded, as post-operative complications.Results: All 35 procedures were under local anaesthesia. Complete occlusion of the treated vein was initially achieved in all the patients, but at 3 months' follow-up, there was only partial recanalization in 2 from 35 (6%) of the veins. Those two were successfully treated with additional complementary ultrasound guided foam sclerotherapy. No significant compli-cations were reported.Conclusions: Flebogrif is an effective treatment for chronic venous insufficiency of the long and short saphenous veins. Bilateral procedures can be successfully performed and toler-ated as can multiple veins in the same setting and same leg.

Scientific Papers and Patents on Substances with Unproven Effects. Part 2.

Several examples are discussed in this review, where substances without proven effects were proposed for practical use within the scope of evidence-based medicines. The following is discussed here: generalizations of the hormesis concept and its use in support of homeopathy; phytoestrogens and soy products potentially having feminizing effects; glycosaminoglycans for the treatment of osteoarthritis and possibilities of their replacement by diet modifications; flavonoids recommended for the treatment of chronic venous insufficiency and varicose veins; acetylcysteine as a mucolytic agent and its questionable efficiency especially by an oral intake; stem cells and cell therapies. In conclusion, placebo therapies can be beneficial and ethically justifiable but it is not a sufficient reason to publish biased information. Importantly, placebo must be devoid of adverse effects, otherwise, it is named pseudo-placebo. Therapeutic methods with unproven effects should be tested in high-quality research shielded from the funding bias. Some issues discussed in this review are not entirely clear, and the arguments provided here can initiate a constructive discussion.

Treatment of chronic venous insufficiency of the lower extremities

The article discusses up-to-date concepts of the prevalence, pathogenesis and clinical manifestations of chronic venous diseases and chronic venous insufficiency of the lower extremities. It discusses the current views on the mechanism of action of various phlebotrophic drugs used in the symptomatic treatment of chronic venous diseases of the lower extremities and chronic venous insufficiency, updates data on the advantages of micronized purified flavonoid fraction for the treatment of all clinical classes of chronic venous diseases.

Balneotherapy for chronic venous insufficiency.

Balneotherapy for chronic venous insufficiency.

Therapeutic compression materials and wound dressings for chronic venous insufficiency: A comprehensive review.

Chronic venous insufficiency (CVI) is a common disorder worldwide. Related pathophysiological mechanisms reportedly involve venous pooling and reduced venous return, leading to heaviness, aching, itchiness, tiredness, varicosities, pigmentation, and even lower limb ulceration. Approaches adopted to manage CVI at various stages of clinical-etiology-anatomy-pathophysiology include compression therapy, pharmacological treatment, ultrasound treatment, surgery, electrical or wireless microcurrent stimulation, and pulsed electromagnetic treatment. Among these, polymer-based therapeutic compression materials and wound dressings play increasingly key roles in treating all stages of CVI because of their unique physical, mechanical, chemical, and biological functions. However, the characteristics, working mechanisms, and effectiveness of these CVI treatment materials are not comprehensively understood. The present systematic review examines the structures, properties, types, and applications of various polymer-based compression materials and wound dressings used in prophylaxis and treatment of CVI. Existing problems, limitations, and future trends of CVI treatment materials are also discussed. This review could contribute to the design and application of new functional polymer materials and dressings to enhance the efficiency of CVI treatments, thereby facilitating patients' self-care ability and long-term health improvement.

A critical review on the three-dimensional finite element modelling of the compression therapy for chronic venous insufficiency

Compression therapy is an adjuvant physical intervention providing the benefits of calibrated compression and controlled stretch and consequently is increasingly applied for the treatment of chronic venous insufficiency. However, the mechanism of the compression therapy for chronic venous insufficiency is still unclear. To elaborate the mechanism of compression therapy, in recent years, the computational modelling technique, especially the finite element modelling method, has been widely used. However, there are still many unclear issues regarding the finite element modelling of compression therapy, for example, the selection of appropriate material models, the validation of the finite element predictions, the post-processing of the results. To shed light on these unclear issues, this study provides a state-of-the-art review on the application of finite element modelling technique in the compression therapy for chronic venous insufficiency. The aims of the present study are as follows: (1) to provide guidance on the application of the finite element technique in healthcare and relevant fields, (2) to enhance the understanding of the mechanism of compression therapy and (3) to foster the collaborations among different disciplines. To achieve these aims, the following parts are reviewed: (1) the background on chronic venous insufficiency and the computational modelling approach, (2) the acquisition of medical images and the procedure for generating the finite element model, (3) the definition of material models in the finite element model, (4) the methods for validating the finite element predictions, (5) the post-processing of the finite element results and (6) future challenges in the finite element modelling of compression therapy.

Biological necrectomy and vacuum-therapy in complex treatment of decompensated chronic venous insufficiency of the lower extremities

Objective. To improve the results of treatment in patients, suffering decompensated forms of chronic venous insufficiency (CHVI) of the lower extremities, using introduction of biological necrectomy and vacuum-therapy in combination with complex of optimal surgical interventions, depending on state of venous hemodynamics of the lower extremities.
 Materials and methods. In 2015-2018 yrs in Surgical Clinic of the Zakarpattya Regional Clinical Hospital named after Andriy Novak 147 patients, ageing 40 yrs old and older, suffering CHVI Category C6 in accordance to the CEAP Classification, were treated. All the patients were divided into two groups: the Group I consisted of 76 patients, suffering CHVI in decompensated stage on background of varicose disease, and the Group II - 71 patients, suffering trophic ulcers (TU) on background of postthrombophlebitic syndrome (PTHPHS).
 Results. There was established, that the TU clearance under the action of maggot-therapy in patients, suffering decompensated course of CHVI, is significantly more effective, than under the impact of vacuum-therapy. Autodermoplasty must be performed in all the patients, having TU with 4 cm in diameter,
 Good and satisfactory results were observed in 75 (98.7%) patients of Group I and in 63 (88.7%) patients of Group II, while poor results - in 8 (11.3%) patients of Group II. The working capacity of patients, suffering CHVI in decompensated stage of varicose genesis, have enhanced in 16.5 times, while in the patients, suffering TU on background of PTHPHS – in 1.25 times.
 Conclusion. Combined treatment of CHVI in decompensated stage, occurring on background of varicose disease includes the TU clearance, using vacuum-therapy or biological necrectomy with subsequent elimination of vertical reflux. In the patients, suffering TU on the PTHPHS background the biologic necrectomy with elimination of horizontal reflux is advantageous. The working capacity in patients with CHVI in decompensated stage of varicose genesis have enhanced in 16.5 times, while in the patients with TU on the PTHPHS background - in 1.25 times.

2nd Mexican Consensus of Endovenous Chemical Ablation (Scleorotherapy) 2018

Abstract Background Sclerotherapy has been carried out since 1516 and is accepted and performed worldwide according to many references from books and journals. Mexican doctors participated in other consensuses in order to obtain various agreements, references, methods and procedures that are universally accepted to establish this document, including the European consensus of sclerotherapy 2003 and its last revision in 2006, the Clinical practice guidelines for prevention, diagnosis and treatment of chronic venous insufficiency in 2009 in México, the Argentine and Latin American consensus for sclerotherapy in 2012, European sclerotherapy guidelines in chronic venous diseases of 2013,and various literature sources as well. The first Mexican consensus on sclerotherapy published in January 2014 which was reviewed and updated in this document. Objective Review and update the general bases of Endovenous Chemical Ablation (ECA) also known as Sclerotherapy, according to evidence-based medicine updating the previously published consensus. Method General questions about Endovenous Chemical Ablation (ECA) were established concerning: indications, contraindications, types of sclerosing agents and the concentrations used, patient position, methods of application, way to prepare and preserve the sclerosants, necessary equipment, injection volumes, differents administration ways, compressive therapy and special comments. To answer these questions the existing literature and the topics in which the reports showed uniformity were consulted. A panel of experts was constituted who provided their personal experience, the answers were formulated in the form of clinical guidelines or general recommendations to provide concrete answers to the specific questions, in some issues we include possible accepted variations.

The cytotoxic properties and apoptotic potential of N-butyl and 2-octyl cyanoacrylates used in surgical treatment of chronic venous insufficiency.

This study aims to investigate the cytotoxic effects and apoptotic potential of N-butyl cyanoacrylate and 2-octyl cyanoacrylate used in surgical treatment of chronic venous insufficiency. N-butyl cyanoacrylate and 2-octyl cyanoacrylate were cultured in cell-culture using human umbilical endothelial cell-line. Cytotoxicity and viability were assessed at 24 and 72 hours with lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, respectively. Apoptotic potential was documented at 24 and 72 hours with relative caspase-3 activity. The mean cytotoxicity at 24 and 72 hours were: N-butyl cyanoacrylate with an area of dot/line: 37.0±3.9%/29.3±2.7% and 46.4±1.6%/45.1±7.1%, 2-octyl cyanoacrylate with an area of dot/line: 39.0±7.0%/37.3±4.6% and 47.0±2.3%/40.7±7.5%. Cytotoxicity increased by time in each group (p<0.05). The mean viability at 24 and 72 hours were: N-butyl cyanoacrylate with an area of dot/line: 53.4±7.7%/72.0±5.7% and 35.7±1.9%/37.8±3.7%, 2-octyl cyanoacrylate with an area of dot/line: 54.3±4.4%/73.5±19.9% and 33.6±2.8%/30.7±4.5%. The mean viability decreased by time in each group (p<0.05). The mean relative caspase-3 activity at 24 and 72 hours were: control group: 0.084±0.006 and 0.065±0.002, N-butyl cyanoacrylate with an area of dot/line: 0.940±0.037/0.924±0.053 and 0.999±0.072/1.056±0.015, 2-octyl cyanoacrylate with an area of dot/line: 0.900±0.044/0.928±0.018 and 0.989±0.084/0.999±0.072. The mean relative caspase-3 activity was higher than control group in each group at each time interval (p<0.05) and activity increased by time in N-butyl cyanoacrylate line and in 2-octyl cyanoacrylate line groups (p<0.05). Our findings indicate that N-butyl cyanoacrylate and 2-octyl cyanoacrylate cause cytotoxicity in cell-culture media. We may also postulate that they induce apoptosis in cell-culture media.

Escin suppresses HMGB1-induced overexpression of aquaporin-1 and increased permeability in endothelial cells.

Escin, a natural triterpene saponin mixture obtained from the horse chestnut tree (Aesculus hippocastanum), has been used for the treatment of chronic venous insufficiency (CVI), hemorrhoids, and edema. However, it is unclear how escin protects against endothelial barrier dysfunction induced by pro‐inflammatory high mobility group protein 1 (HMGB1). Here, we report that escin can suppress (a) HMGB1‐induced overexpression of the aquaporin‐1 (AQP1) water channel in endothelial cells and (b) HMGB1‐induced increases in endothelial cell permeability. This is the first report that escin inhibits AQP1 and alleviates barrier dysfunction in HMGB1‐induced inflammatory response.

Initial Results of a Clinical Feasibility Study for Endovenous Deep Venous Valve Formation to Treat Chronic Venous Insufficiency

Chronic venous insufficiency (CVI), due to superficial and deep venous reflux (DVR) and venous obstruction, is widespread and associated with significant morbidity. DVR correlates with increased symptoms. Historically, therapeutic approaches to DVR involved difficult and morbid surgical procedures or unsuccessful attempts to implant valves. The study objective was to assess the safety and effectiveness of endovenous formation of autogenous deep vein valves in patients with DVR and significant associated symptoms. The study is ongoing, and results are presented for the first 10 treated patients. Patients with DVR and correlating symptoms of CVI (Clinical, Etiology, Anatomy, and Pathophysiology [CEAP] class C4-C6) were treated with an endovenous autogenous valve formation system in four centers in New Zealand and Australia. Patients with outflow obstruction were excluded. Retrograde percutaneous access was obtained through the common femoral vein, and contrast venography and intravascular ultrasound were used to assess reflux and to identify potential treatment sites. If the patient was deemed eligible, the 16F study device was introduced and used to form monocuspid valves in femoropopliteal vein segments spanning 7 to 11 mm in diameter. Intravascular ultrasound and venography were used to assess valve functionality. Postprocedurally, patients were prescribed 7 days of low-molecular-weight heparin injections, followed by 6 months of anticoagulation. Follow-up included duplex ultrasound scan, physical examination, and questionnaires. Deep venous thrombosis (DVT) was defined as a treated vein found to be noncompressible with visible echogenic thrombus or dilated with decreased flow by ultrasound. Mural thrombus was a deposition that did not fit the DVT criteria. The patients were clinical class C4 (n = 3), C5 (n = 2), and C6 (n = 5) and of both primary (n = 8) and secondary (n = 2) etiology. One or more monocuspid valves were successfully formed in 9 of 10 patients. One valve formation was completed in four patients, two formations in four patients, and three formations in one patient; the anatomy did not accommodate successful valve formation in one patient. Follow-up ranged from 30 to 210 days with a median of 30 days. During this time, no occlusive DVTs were reported, and adverse events related to the device or procedure included access site-related events (n = 7) and mural thrombus (n = 3). All mural thrombi resolved by 90 days. At 30 days, there was a median change in reflux time (seconds) in the proximal femoral vein of 0.3 (−1.9 to 4.3), in the distal femoral vein of 0.4 (−1.4 to 5.6), and in the mid popliteal vein of 0.2 (−3.3 to 6.7). Seven of 10 patients had a ≥4-point improvement in the Venous Clinical Severity Score. Endovenous valve formation in the deep venous system is feasible. Initial experience suggests that it may be safe and effective for treatment of CVI.