Pregnancy-associated venous insufficiency course with placental and systemic oxidative stress.

The development of lower extremity venous insufficiency (VI) during pregnancy has been associated with placental damage. VI is associated with increased oxidative stress in venous wall. We have investigated potential disturbance/dysregulation of the production of reactive oxygen species (ROS) in placenta and its eventual systemic effects through the measurement of malondialdehyde (MDA) plasma levels in women with VI. A total of 62 women with VI and 52 healthy controls (HCs) were studied. Levels of nicotinamide adenine dinucleotide phosphate-oxidase 1 (NOX1), 2 (NOX2), inducible nitric oxide synthase (iNOS), endothelial (eNOS), poly(ADP-ribose) polymerase PARP (PARP) and ERK were measured in placental tissue with immunohistochemistry and RT-qPCR. Plasma and placental levels of MDA were determined by colorimetry at the two study times of 32 weeks of gestation and post-partum. Protein and gene expression levels of NOX1, NOX2, iNOS, PARP and ERK were significantly increased in placentas of VI. eNOS activity was low in both study groups, and there were no significant differences in gene or protein expression levels. Women with VI showed a significant elevation of plasma MDA levels at 32 weeks of gestation, and these levels remained elevated at 32 weeks post-partum. The MDA levels were significantly higher in placentas of women with VI. Placental damage that was found in the women with VI was characterized by overexpression of oxidative stress markers NOX1, NOX2, and iNOS, as well as PARP and ERK. Pregnant women with VI showed systemic increases in oxidative stress markers such as plasma MDA levels. The foetuses of women with VI had a significant decrease in their venous pH as compared to those from HC women. The situation of oxidative stress and cellular damage created in the placenta is in coexpression with the production of a pH acidification.

Virchow's triad in "silent" deep vein thrombosis.

OBJECTIVE: While determining the incidence of chronic deep vein thrombosis (DVT) and the hypercoagulation profiles of patients who underwent venous stenting for symptomatic venous insufficiency, we assessed the significance of Virchow's triad in the setting of proximal venous outflow obstruction and DVT. METHODS: Within our registry of 500 patients who underwent venous stenting for proximal venous outflow obstruction between 2013 and 2016, we selected the first 152 consecutive patients who had routine hypercoagulation profile testing performed preoperatively. Statistical analysis was performed using independent t-tests, χ2 tests, and multiple logistic regressions. RESULTS: By history or intraoperative chronic postphlebitic changes (CPPCs), 77 patients (50.7%) were positive for remote DVT; 51 (33.6%) had intraoperative findings of CPPCs without a history of DVT, 20 (13.2%) had intraoperative CPPCs with a history of DVT, and 6 (3.9%) had a history of DVT without intraoperative findings. The χ2 tests were significant for increased findings of CPPCs among patients with a history of DVT (81% vs 38%; P < .01). The χ2 tests were also significant for increased rates of intraoperative findings of CPPCs in patients with one or more positive hypercoagulation markers (67% vs 42%; P < .01). The most significant predictor for findings of CPPCs or DVT history was the presence of at least one hypercoagulation marker (n = 148; odds ratio, 2.41; P = .022). CONCLUSIONS: Remote history of DVT and intraoperative findings of CPPCs were prevalent. CPPC findings were found in many patients with no history of DVT. Hypercoagulation markers conferred significant predictive value for DVT. This information may influence our understanding of Virchow's triad and DVT etiology.

Sulodexide in venous disease.

Sulodexide is a glycosaminoglycan extracted from porcine intestinal mucosa. The purpose of this review is to discuss sulodexide's complex pharmacological profile and its clinical applications for venous disease. Sulodexide has wide-ranging biological effects on the vascular system, including antithrombotic, profibrinolytic, anti-inflammatory, endothelial protective and vasoregulatory effects. Sulodexide has emerged as a potential therapeutic option for the management of chronic venous insufficiency, including venous ulceration, and the prevention of recurrent venous thromboembolism, with a low rate of major bleeding complications. Sulodexide's pleiotropic vascular effects may facilitate the management of common venous disorders.

Influence of Diosmin Treatment on the Level of Oxidative Stress Markers in Patients with Chronic Venous Insufficiency.

Oxidative stress plays an important role in the pathophysiology of many human disorders, while antioxidants prevent the development of various adverse symptoms. Diosmin is a natural flavonoid applied in vascular system disorders, especially in chronic venous insufficiency (CVI), and it plays a significant part in the alleviation of CVI symptoms. Due to antioxidant activity, it also has the ability to scavenge the oxygen free radicals and hence decreases the level of oxidative stress biomarkers, such as prostaglandins and their precursors-isoprostanes. In the study, the influence of diosmin treatment on the level of isoprostanes in plasma samples of patients suffering from CVI was examined. The qualitative analysis was performed using high-performance liquid chromatography with spectrometry detection (LC-MS). The statistically significant decrease of isoprostane content after 3 months of treatment was observed within the studied group; however, the most significant changes were observed in patients who smoke.

Validation of a Gravitational Model to Study Local Endogenous Biomarkers in Chronic Venous Insufficiency.

OBJECTIVE/BACKGROUND: Unlike most systemic chronic diseases, chronic venous insufficiency (CVI) is ideal to study using endogenous biomarkers. The stimulus causing damage can be turned on and off with gravitational positioning and venous blood samples can be taken locally. Annexin V (apoptosis) and microparticles (cell membrane debris) were used as markers of cell destruction, with matrix metalloproteinases (MMPs) as markers of tissue remodelling. The aim of this proof of concept study was to validate a gravitational model by investigating whether standing induced biochemical stress and whether recovery occurs on lying and after compression. METHODS: Fourteen patients (C4a-b) and 14 volunteers (C0-1) were tested under three supervised laboratory conditions for 1 h on separate days: (i) stationary standing on a small paper square; (ii) lying with both legs elevated 20°; (iii) compression standing using a 23-32 mmHg below knee stocking. Immediately after each condition, venous blood was withdrawn from the ankle. Commercial enzyme linked immunosorbent assay kits were used for batch analysis of the plasma samples. RESULTS: Median (interquartile range [IQR]) values of annexin V (AU/mL) and microparticles (nM) standing were as follows: volunteers 2.9 (2 - 3.4) and 10.2 (8.8 - 13.8), and patients 2.2 (1.3 - 6) and 11.3 (7.7 - 20), respectively. Significant reductions were observed lying: volunteers 2.1 (1.5 - 2.7; p = .019) and 8.5 (7.4 - 9.4; p = .041), patients 1.7 (1.2 - 2.7; p = .004) and 8.5 (7.0 - 11.4; p = .041), respectively. Globally, all median MMP values in the patients reduced with lying and with compression versus standing (p = .004). Individually, significant reductions occurred in MMPs 2 and 13 with compression and MMPs 3, 7, 8, 9, 10, and 12 on lying. Lying was more effective at reducing MMP levels than compression. CONCLUSION: Annexin V and microparticle concentrations are responsive to elevation and compression after 1 h. In the patients, all the tested MMPs decreased after lying and with compression versus standing. This model provides evidence supporting gravitational protection in the treatment of CVI.

Suppressed networks of inflammatory mediators characterize chronic venous insufficiency.

OBJECTIVE: Chronic venous insufficiency (CVI) affects 25 million adults in the United States. Little emphasis has been placed on inflammatory changes associated with CVI. We hypothesize that in patients with early to mid-stage benign varicose vein disease, differences in circulating inflammatory mediators will be manifested in blood draining the involved area vs circulating blood in control subjects. METHODS: Patients undergoing either endovenous ablation or sclerotherapy for Clinical, Etiology, Anatomy, and Pathophysiology clinical class 3 to 5 disease underwent phlebotomy from regional veins at the time of the procedure. The patient's age, gender, clinical class, duration of symptoms, presence of superficial truncal reflux by duplex ultrasound, and treatment modality were recorded. Plasma from patients and banked blood samples from healthy volunteers (HVs) were subjected to Luminex (EMD Millipore, Billerica, Mass) to evaluate the expression of an established panel of 20 inflammatory mediators. Mediator concentrations were compared between patients and HVs using Mann-Whitney U tests. Importantly, computational analysis allowed us to compare not only the panel of inflammatory mediators but also the inflammatory networks connecting these mediators to one another. Principal components were analyzed to assess network robustness in each group. RESULTS: CVI venous blood revealed significantly lower levels of monokine induced by γ interferon, soluble interleukin (IL) 2 receptor α chain, IL-4, IL-6, IL-7, tumor necrosis factor α, eotaxin, and granulocyte-macrophage colony-stimulating factor than blood from controls. Inflammatory networks were significantly less complex and less robust in the CVI patients compared with HVs. Based on principal component analysis, responses among HVs were more varied than those of CVI patients. CONCLUSIONS: We demonstrate that patients with CVI have significant differences not only in blood-borne inflammatory mediators but also in the interconnectedness of these mediators with one another and in their principal inflammatory characteristics. Results suggest hypoinflammation in chronic nonhealing changes in CVI. These novel findings, if validated in larger cohorts, may help predict the risk of disease progression or response to therapy in the future and may guide mechanistic studies on tissue responses to CVI.

The Outcome of Anticoagulation on Endovenous Laser Therapy for Superficial Venous Incompetence.

OBJECTIVES: The purpose of this study was to evaluate whether anticoagulation (warfarin or direct oral inhibitors) affected the success of endovenous treatment. METHODS: Patients taking anticoagulation (warfarin or direct oral inhibitors) undergoing endovenous treatment in the form of endovenous laser ablation (EVLA) were matched against controls for sex, age, leg, and vein. Data were collected prospectively between January 2012 and March 2017. The primary endpoint was failure of treatment at 6-week postoperative duplex scan. The rates of major bleeding, hematoma, endothermal heat-induced thrombosis, venous thromboembolism, or pulmonary embolism were also compared between groups. RESULTS: Two hundred eighty-four limbs underwent EVLA during the study period. Of this, 23/284 (8.1%) procedures were done in patients on anticoagulation. 21/23 (91.3%) limbs had venous occlusion at follow-up compared with 23/23 (100%) of controls ( P = .49). The patient who failed treatment in the anticoagulation group had undergone small saphenous vein (SSV) ablation. There was no difference in the complication rates between groups. DISCUSSION: This study demonstrates that anticoagulation does not affect success rates of EVLA though there was higher recanalization rate in patients undergoing SSV ablation. Anticoagulation can be continued safely in patients undergoing this procedure.

Plasma concentration of selected biochemical markers of endothelial dysfunction in women with various severity of chronic venous insufficiency (CVI)-A pilot study.

BACKGROUND: Although the endothelial dysfunction is considered to be implicated in the pathogenesis of chronic venous insufficiency (CVI) the endothelial status in patients with venous disorders is still not fully evaluated. Therefore the aim of the study was to measure the concentration of selected markers of endothelial dysfunction: von Willebrand factor (vWf), soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM) and soluble VE-cadherin (sVE-cadherin) in CVI women who constitute the most numerous group of patients suffering from venous disease. MATERIALS AND METHODS: Forty four women with CVI were involved in the study and divided into subgroups based on CEAP classification. Concentration of vWf, sP-selectin, sTM and sVE-cadherin were measured and compared with those obtained in 25 healthy age and sex-matched women. RESULTS: It was found that the concentration of sTM increased and sVEcadherin decreased along with disease severity in CVI women. A significant rise of sTM was observed especially in CVI women, with the highest inflammation status reflected by hsCRP or elastase concentration, and in CVI women with a high oxidative stress manifested by an increased plasma MDA. A significant fall of circulating sVE-cadherin was reported in CVI women with moderate to highest intensity of inflammation and oxidative stress. There was no change in vWF and sP-selectin concentration at any stage of CVI severity. CONCLUSIONS: The results of the present study demonstrate the presence of endothelial dysfunction in women suffering from CVI which seems to progress with the disease severity and may be associated with inflammation and enhanced oxidative stress.

Alcohol Consumption, High-Density Lipoprotein Cholesterol, Antithrombin III, and Body Mass Index Are Associated with Great Saphenous Vein Reflux in the Thigh.

BACKGROUND: Venous valvular reflux is the main cause of chronic venous dysfunction. However, the etiology of valvular reflux is not completely understood. We conducted this study to investigate new risk factors for venous reflux of the great saphenous vein (GSV) in the thigh. METHODS: We studied 139 consecutive patients (278 legs) who underwent Doppler ultrasonography at our hospital between March 2015 and February 2016 for leg discomfort with visible varicosities, edema, skin changes, or venous ulcer in the legs. Continuous variables included age, body mass index (BMI), hematological and blood chemistry parameters, smoking (pack-years), and alcohol consumption (days). Nominal variables included sex, comorbidities, smoking status, alcohol drinking status, and specific antibodies. The relationship of GSV reflux with pregnancy and number of children was investigated in 184 legs of 92 patients among 96 female patients. RESULTS: On logistic regression analysis, independent factors determining GSV reflux were BMI (B = 0.126, P = 0.012), high-density lipoprotein (HDL) cholesterol level (B = 0.029, P = 0.025), duration of alcohol consumption (B = 1.237 E-4, P = 0.016), and antithrombin III level (B = -0.036, P = 0.011). CONCLUSIONS: In this study, the factors determining GSV reflux were higher HDL cholesterol level, longer duration of alcohol consumption, lower antithrombin III level, and higher BMI.

Evaluation of inflammatory cell biomarkers in chronic venous insufficiency.

Objective Inflammation has been implicated as a factor that may contribute to chronic venous insufficiency. The purpose of this study is to compare readily available inflammatory cell biomarkers, with an emphasis on neutrophil count, lymphocyte count, and neutrophil lymphocyte ratio, in patients with chronic venous insufficiency. We hypothesized that circulating leukocyte counts would be higher in the peripheral blood of patients with severe compared to mild chronic venous insufficiency. Methods We performed a retrospective medical record review of patients discharged from Ruby Memorial Hospital (Morgantown, WV, USA) with a primary diagnosis of chronic venous insufficiency. Patients were organized into two groups-mild and severe chronic venous insufficiency-based on the Clinical, Etiologic, Anatomic, and Pathophysiological classification system, and inflammatory cell counts were compared between groups. Results We observed a significantly higher neutrophil count ( p = .002) and neutrophil-lymphocyte ratio ( p = .005) in patients with severe chronic venous insufficiency compared to mild. Further, the neutrophil-lymphocyte ratio may be a useful predictor of chronic venous insufficiency severity. Conclusions We reported significant differences in inflammatory cell biomarkers between mild and severe chronic venous insufficiency, as well as provided support for the use of the neutrophil-lymphocyte ratio as a predictor of chronic venous insufficiency severity. These results may provide clinicians with additional insight to manage chronic venous insufficiency in patients and provide a framework for the development of novel treatment options targeting the immune system in chronic venous insufficiency.

The Diagnosis and Management of Early Deep Vein Thrombosis.

The diagnosis and management of an acute DVT is difficult and mistakes are often made. The cost to the National Health Service (NHS) of litigation arising from failure to diagnose and treat DVT early is substantial. Clinical diagnosis alone is often unreliable and a large proportion of DVT occurring in hospital are asymptomatic. In the United Kingdom, clinical scoring systems, D-dimer and ultrasound (US) imaging have all been adopted to aid diagnosis via DVT pathways. These pathways aim to exclude DVT only and often fail to actually address the cause of the symptoms once DVT is eventually cleared.

[Concentration of matrix metalloproteinases and magnesium ions in patients with varicose veins of lower limbs]. / Kontsentratsiya matriksnykh metalloproteinaz i ionov magniya pri varikoznoi bolezni ven nizhnikh konechnostei.

The study was aimed at investigating alterations in the concentration of matrix metalloproteinases (MMP-1, MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as the level of magnesium ions (Mg2+) as an indicator of connective tissue dysplasia (CTD) in patients presenting with lower limb varicose veins. The study included a total of 110 people. Of these, the Study Group comprised 90 patients with lower limb varicose veins of clinical class C2-C6 (according to the CEAP classification) and the Control Group was composed of 20 apparently healthy volunteers. Samples of peripheral blood were examined. The content of MMP-9, MMP-1 and TIMP-1 in blood serum was determined by means of the quantitative solid-phase immunoenzymatic assay. The concentration of Mg2+ was determined by the colorimetric method. We revealed a statistically significant interrelationship between the concentrations of matrix metalloproteinases and severity of varicose transformation of lower-limb veins, with the highest level of matrix metalloproteinases being observed in patients with cutaneous alterations and trophic ulcers. Determination of the level of matrix metalloproteinases and magnesium ions, characterizing connective tissue dysplasia, makes it possible to predict the development of lower limb chronic venous insufficiency and to evaluate the degree of its severity.

Are Inflammatory Biomarkers Increased in Varicose Vein Blood?

OBJECTIVES: To test for the presence of inflammatory biomarkers in blood taken from varicose veins versus antecubital blood of the same patient and compare this to levels in healthy controls. METHODS: Using a multiplex biochip array method (Randox, United Kingdom), the interleukins (ILs) IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10; vascular endothelial growth factor; interferon γ, tumor necrosis factor α ; monocyte chemotactic protein 1 (MCP-1); and epidermal growth factor were measured in citrated plasma samples drawn from the arms and legs of 24 patients with varicose veins and 24 controls. RESULTS: Expressed as median (interquartile range) in pg/mL, leg samples from patients with varicose veins had significantly higher levels of IL-8 and MCP-1 compared to their own arm samples (IL-8: local 2.3 [1.71-3.3] vs systemic 2.3 [1.62-2.98], P = .023; MCP-1: local 114.42 [84.29-139.05] vs systemic 103.56 [79.75-126.42], P < .0005). This was not observed in the control group. Leg samples from both patients with varicose vein and controls had higher levels of IL-6 compared to their own arm samples (patients: local 1.67 [0.82-4.48] vs systemic 1.24 [0.58-3.26], P = .002; controls: local 1.23 [0.83-1.7] vs systemic 1.03 [1.7-1.52], P = .005). No significant differences were detected with the other biomarkers. CONCLUSIONS: Blood drawn from the site of varicose veins appears to have significantly increased concentrations of IL-6, IL-8, and MCP-1 when compared to the same patient's arm blood. This supports the hypothesis that inflammation is activated from the tissues drained by the varicose veins.

Estudio de la insuficiencia venosa crónica mediante ecografía Doppler y realización de cartografía venosa / Doppler ultrasound study and venous mapping in chronic venous insufficiency

La insuficiencia venosa crónica (IVC) de las extremidades inferiores es una enfermedad muy prevalente. La ecografía Doppler se ha establecido en las últimas décadas como el método de elección en el estudio de esta patología, por lo que resulta imprescindible ante una eventual indicación quirúrgica. El objetivo de este trabajo es establecer una metodología en la exploración, incluyendo la realización de cartografía y el marcaje prequirúrgico. Para ello revisaremos la anatomía venosa de los miembros inferiores y la fisiopatología de la IVC explicando los conceptos hemodinámicos básicos y la terminología necesarios para la realización de un informe radiológico que permita una adecuada planificación terapéutica y comunicación con otros especialistas. Explicaremos brevemente la estrategia CHIVA (cura hemodinámica de la insuficiencia venosa ambulatoria), método quirúrgico mínimamente invasivo que tiene como objetivo restaurar la hemodinámica venosa sin extirpar la vena safena (AU)

Chronic venous insufficiency of the lower limbs is very prevalent. In recent decades, Doppler ultrasound has become the method of choice to study this condition, and it is considered essential when surgery is indicated. This article aims to establish a method for the examination, including venous mapping and preoperative marking. To this end, we review the venous anatomy of the lower limbs and the pathophysiology of chronic venous insufficiency and explain the basic hemodynamic concepts and the terminology required to elaborate a radiological report that will enable appropriate treatment planning and communication with other specialists. We briefly explain the CHIVA (the acronym for the French term "cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire" = conservative hemodynamic treatment for chronic venous insufficiency) strategy, a minimally invasive surgical strategy that aims to restore correct venous hemodynamics without resecting the saphenous vein (AU)

Neuroendocrine Responses to Transvascular Autonomic Modulation: A Modified Balloon Angioplasty in Multiple Sclerosis Patients.

Balloon angioplasty (BA) is a treatment modality to correct vascular lesions in multiple sclerosis (MS) patients, who present with chronic cerebrospinal venous insufficiency (CCSVI). We hypothesized that BA clinical benefits stems in part from improvement in cardiovascular autonomic nervous system (ANS) function. We adopted the Transvascular Autonomic Modulation (TVAM), as a modified BA technique, with the objective of further enhancing ANS functional activities. TVAM involved dilation of multiple vascular beds, including IJVs, azygos and renal veins, and application of manual compression. Since the ANS regulates the function of the hypothalamus pituitary (HPA) axis, we examined TVAM effects on HPA axis in MS patients, and determined the relationship between ANS function and HPA activity. The adrenocorticotropic hormone (ACTH) and cortisol serum levels, systolic and diastolic blood pressure (BP), and heart rate variability (HRV) parameters were measured before and 24 h after TVAM procedure in 72 MS patients. Baseline ACTH and cortisol serum levels were lower than normal ranges in 18% and 25% MS patients respectively. The intervention resulted in significant reductions in both ACTH and cortisol (p<0.001), with a more marked ACTH reduction in males compared to females (p<0.001). Post-TVAM BP increased in patients who presented with baseline BP within lower limits of normal ranges, but decreased in patients with baseline BP above the normal ranges. In a univariate analysis, the changes (Δ) in ACTH serum levels correlated weakly, although significantly, with Δ in diastolic BP (r=-0.265, p=0.03), and Δ in cortisol serum levels correlated weakly, but significantly, with Δ in systolic BP (r=-0.283, p=0.01). The observed ACTH and cortisol reductions are counter to the stress-mediated increases in serum levels of these hormones, which are expected following an invasive procedure. The clinical implications of this unexpected response warrant further investigations.

Assessment of arterial stiffness in patients with chronic lower extremity venous disease: An observational study.

OBJECTIVES: Arterial stiffness is associated with major adverse cardiovascular events. Chronic venous insufficiency (CVI) is severe form of chronic venous disease (CVD). The aim of this study is to investigate arterial stiffness by cardio-ankle vascular index (CAVI) in patients with CVI. METHODS: This observational and cross-sectional study involved 87 subjects with CVI and 86 healthy subjects. All subjects underwent ultrasonography examination. CAVI was measured by VaSera-1000 CAVI instrument. RESULTS: High density lipoprotein cholesterol (HDL) was significantly lower in patients with CVI than controls (46.83 ± 9.25 mg/dl vs 51.33 ± 11.13 mg/dl, p = 0.004). Body mass index (BMI) was significantly higher in CVI patients than controls (28.53 ± 4.10 kg/m(2) vs 26.37 ± 5.16 kg/m(2), p = 0.003). Ankle brachial index (ABI) was significantly lower in patients with CVI compared to controls (1.08 ± 0.08 vs 1.14 ± 0.11, p < 0.001). CAVI was significantly higher in patients with CVI than controls (7.94 ± 1.37 vs 6.73 ± 1.16, p < 0.001). Mean arterial pressure (MAP) was significantly higher in patients with CVI than control group (105.41 ± 10.77 mmHg vs 99.70 ± 11.17 mmHg, p = 0.001). CAVI (p < 0.001, Odds ratio (OR) = 2.033, 95% Confidence interval (CI) = 1.493-2.768), ABI (p = 0.003, OR = 0.003, 95% CI = 0.001-0.137), female sex (p < 0.001, OR = 3.949, 95% CI = 1.613-9.663), and HDL (p < 0.001, OR = 0.923, 95% CI = 0.883-0.964) were the independent predictors of CVI. A CAVI value > 7.9 had a sensitivity 64.4% and a specificity of 94.7% for predicting the presence of CVI in ROC analysis (area under curve = 0.791, 95% CI = 0.723-0.849, p < 0.001). CONCLUSION: CAVI is independently increased in CVI patients. Therefore CVI may be accepted a form of vascular sclerosis and vascular system should be evaluated in continuum not isolated.

Simple blood tests as predictive markers of disease severity and clinical condition in patients with venous insufficiency.

Chronic venous insufficiency (CVI) is a progressive inflammatory disease. Because of its inflammatory nature, several circulating markers were investigated for predicting disease progression. We aimed to investigate simple inflammatory blood markers as predictors of clinical class and disease severity in patients with CVI. Eighty patients with CVI were divided into three groups according to clinical class (grade 1, 2 and 3) and score of disease severity (mild, moderate and severe). The basic inflammatory blood markers [neutrophil, lymphocyte, mean platelet volume (MPV), white blood cell (WBC), platelet, albumin, D-dimer, fibrinogen, fibrinogen to albumin ratio, and neutrophil to lymphocyte ratio] were investigated in each group. Serum neutrophil, lymphocyte, MPV, platelet count, D-dimer and neutrophil to lymphocyte ratio levels were similar among the groups (P > 0.05). Although the serum WBC levels were significant in the clinical severity groups (P < 0.05), it was useless to separate each severity class. However, albumin, fibrinogen and the fibrinogen to albumin ratio were significant predictors of clinical class and disease severity. Especially, the fibrinogen to albumin ratio was detected as an independent indicator for a clinical class and disease severity with high sensitivity and specificity (75% sensitivity and 87.5% specificity for clinical class and 90% sensitivity and 88.3% specificity for disease severity). Serum fibrinogen and albumin levels can be useful parameters to determine clinical class and disease severity in patients with CVI. Moreover, the fibrinogen to albumin ratio is a more sensitive and specific predictor of the progression of CVI.

Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

Modulation of circulating cytokine-chemokine profile in patients affected by chronic venous insufficiency undergoing surgical hemodynamic correction.

The expression of proinflammatory cytokines/chemokines has been reported in in vitro/ex vivo settings of chronic venous insufficiency (CVI), but the identification of circulating mediators that might be associated with altered hemodynamic forces or might represent innovative biomarkers is still missing. In this study, the circulating levels of 31 cytokines/chemokines involved in inflammatory/angiogenic processes were analysed in (i) CVI patients at baseline before surgical hemody namic correction, (ii) healthy subjects, and (iii) CVI patients after surgery. In a subgroup of CVI patients, in whom the baseline levels of cytokines/chemokines were analyzed in paired blood samples obtained from varicose vein and forearm vein, EGF, PDGF, and RANTES were increased at the varicose vein site as compared to the general circulation. Moreover, while at baseline, CVI patients showed increased levels of 14 cytokines/chemokines as compared to healthy subjects, 6 months after surgery, 11 cytokines/chemokines levels were significantly reduced in the treated CVI patients as compared to the CVI patients before surgery. Of note, a patient who exhibited recurrence of the disease 6 months after surgery, showed higher levels of EGF, PDGF, and RANTES compared to nonrecurrent patients, highlighting the potential role of the EGF/PDGF/RANTES triad as sensitive biomarkers in the context of CVI.