Analysis of the effects of micronized purified flavonoid fraction versus placebo on symptoms and quality of life in patients suffering from chronic venous disease: from a prospective randomized trial.

AIM: The aim was to investigate the effect of micronized purified flavonoid fraction (MPFF; Daflon® 500 mg, Laboratoires Servier, France) versus placebo, on pain and quality of life (QoL) in patients with symptomatic chronic venous disease (CVD). METHODS: A large randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate treatment effects on vesperal oedema using water displacement volumetry (WDV). Other criteria were leg pain\heaviness assessed by Visual Analog Scale (VAS) and Quality Of Life Questionnaire (CIVIQ-20). Study treatments were administered once a day for 4 months. The tolerance to the study treatments was assessed based on spontaneously reported adverse events, coded using the MedDRA dictionary. The present post-hoc analysis focuses on the subgroup of symptomatic patients having a baseline VAS>4 cm. RESULTS: The main study included 1137 patients classified C3 or C4 according to CEAP classification, with 592 in the symptomatic subgroup: 296 randomized to MPFF and 296 to placebo. Patient demographics and medical history were well-balanced at baseline. The main study was inconclusive on WDV for methodological reasons. In the symptomatic subgroup, MPFF treatment was associated with a greater reduction in VAS score than on placebo treatment (between-group difference =-0.5 cm; P=0.031) and greater improvement in CIVIQ score (between-group difference =3.1%; P=0.040). CONCLUSION: A 4-month treatment with MPFF significantly reduced leg pain/heaviness and improved QOL when compared to placebo and was well tolerated.

[Severe intermittent claudication: PGE1 treatment. A 40-week registry, efficacy and costs]. / Claudicatio intermittens severa: trattamento con PGE1. Registry, follow up (40 settimane), efficacia e costi.

AIM: Intermittent claudication (IC) in peripheral vascular disease is characterized by lower limb pain appearing on effort. Treatment with PGE1 has been successfully used to manage IC patients. This registry has evaluated safety and costs of PGE1 in the management of IC. METHODS: In this study a long-term treatment protocol (LTP), a short-term protocol (STP) and an outpatient (OP), "on-demand" treatment have been compared. A treadmill effort test has been used to evaluate walking distance. The follow up for these three protocols was 40 weeks. PGE1 treatment was associated to a risk reduction plan and to an exercise program. RESULTS: The final analysis has included 252 LTP patients, 223 STP patients and 284 OP patients (total 659 valid cases). A group of 171 comparable patients not treated with PGE1 was used for a parallel comparison. Cardiovascular mortality and morbidity has been evaluated in 731 PGE1 patients completing 24 months of follow up. All protocols have been well tolerated. No side effects were observed. The lower cost has been observed for OP patients. In the long term, mortality and morbidity were lower in patients treated with PGE1 in comparison with patients not treated with PGE1. CONCLUSION: Considering costs and results (increase in walking distance) and improvement in Karnofsky scale the STP plan appears to be better than LTP for IC patients. The OP, "on-demand" treatment offers further improvements. This last treatment plan is simpler; the plan allows better timing for exercise. The treatment can be used even in non-specialized centers.

Effects of elastic compression on hypomobility edema and fibrinolysis activation in multiple sclerosis.

AIM: In multiple sclerosis (MS) patients, loss of mobility leads to edema of the legs and raises their risk of thrombosis. They cannot use pharmacological prophylaxis over the long course of the disease. Elastic compression stockings are indicated to prevent venous thrombosis for hypomobile patients, and might therefore also limit edema. The aim of the study was to assess the feasibility of elastic compression with ATE stockings in severely disabled MS patients, and to make a preliminary assessment of their efficacy and safety. METHODS: We checked 201 MS patients, in a rehabilitation unit, by ultrasound for residues of thrombosis and recorded the duration of the MS, residual autonomy, and leg edema. Ninety-nine patients served as controls, and 102 were prescribed antithromboembolic stockings, to be worn 24h/day. RESULTS: The intervention group had higher baseline d-Dimer (471 ± 590 vs. 271 ± 183 mg/dL) and more had lower leg edema (80% vs. 40%). In all treated patients the edema disappeared. There were no cases of symptomatic deep venous thrombosis. D-Dimers dropped significantly in both groups, though more in the intervention group (to 363 ± 420 mg/dL, P=0.0001 and to 254 ± 180 mg/dL for controls, P=0.01). CONCLUSION: Antithromboembolic stockings can help eliminate edema of the legs in MS patients, and may also reduce the thrombotic risk: the lower d-Dimer values suggest an effect on the activation of inflammation and coagulation resulting from stasis-induced endothelial damage.

[Medical treatment of chronic venous disease: evolution or involution?]. / Trattamento medico della malattia venosa cronica: evoluzione o involuzione?

Chronic venous disease (CVD) is an important clinical condition with substantial epidemiological implications and socio-economic repercussions. In the Western world the consequences of its high prevalence, the costs of diagnosis and therapy, the significant loss of working hours and the repercussions on patients'quality of life are well known. Pharmacotherapy for CVD has greatly developed over the last 40 years and largely used in the symptomatic treatment of CVD together with compression therapy and to make patients more comfortable. The clinical efficacy on the symptoms (feeling of heaviness, pain, paresthesia, heat and burning sensations, night cramps, etc.) has long been confirmed by Level III, IV and V evidence, but there are now Level I and II trials on specific drugs. For the bioflavonoids double-blind, randomised trials have used micronized purified flavonoid fraction; rutosides; escin; anthocyanosides; and synthetic calcium dobesilate. It was therefore surprising some recent difficulties in the use of this important treatment in health national system in Italy. In this up-date we use the method on evidence-based medicine from the medical literature. We have started a governance and economic analysis of the problem in Italy. Particular consideration was given to the evidence set out in review, meta-analysis, guidelines and Consensus Statements in this field. The evidence for pharmacological agents in the treatment of CVD suggests today a wide use in all CEAP classes.

Nautilus survey on chronic venous diseases.

AIM: The large diffusion of venous disease (CVD) has been confirmed by several epidemiological studies in Europe and the USA. Since general practitioners (GPs) are the first segment of the population to evaluate for CVD, the Italian Project Nautilus (concerning vascular prevention) organized a monitoring campaign in 2009 with the aim of studying CVD using the CEAP classification criteria. METHODS: More than 1000 GPs were included in the survey. The study produced anamnestic and clinical data on more than 10,000 patients with CVD divided into three age segments: 60 years. Of these results, 83% were considered valid for a statistical evaluation. RESULTS: The prevalent population in CVD includes adult and aging subjects; four out of five are women. The number of pregnancies is the first risk or predisposing factor in the adult population, and prolonged standing is the first cause in younger subjects. Excess weight and previous thromboses, either superficial (SVT) or deep (DVT), become more significant factors with advancing age and included, respectively, 58% and 44% of the study's subjects over the age of 60. The most severe signs of CVD (edema, venous ulcers) show a significant progression in the aging segment of the population. Edema is present in 50% of the aging population, and inflammatory endothelial activation (swollen, heavy or painful legs) also increases with aging. Symptoms related to hemorrheological activation (including itching, nocturnal cramps) progress in parallel with increasing signs. A history of previous SVT or DVT episodes is the determining factor in more severe signs (CEAP: C4-C6) in more than 50% of the studied patients in comparison with only 20% of patients without a history for SVT or DVT. Diabetes is associated with more severe signs in 50% of patients. CONCLUSION: The Nautilus Survey of CVD indicates determining factors associated with the beginning and progression of CVD in three different age segments. These factors may be considered as clinically significant parameters for defining the clinical evolution of CVD. The observations are useful to evaluate the best preventive and treatment options on the basis of the most recent pathophysiological considerations.

Risk of deep venous thrombosis (DVT) in bedridden or wheelchair-bound multiple sclerosis patients: a prospective study.

BACKGROUND: Multiple sclerosis (MS) often causes progressive loss of mobility, leading to limb paralysis. Venous and lymphatic stasis is a risk condition for venous thromboembolism (VTE). There is, however, no data on the frequency of VTE complicating the progression of MS. The aim of this study was to assess the frequency of deep vein thrombosis (DVT) in patients with late-stage MS attending a neurology center for rehabilitation. PATIENTS AND METHODS: A total of 132 patients with MS were enrolled, 87 women and 45 men, mean age 58+/-11 years. The disease had started on average 18.7 years before; patients reported 9.6 hours bedridden per day or 14.3 hours wheelchair-bound. Only 25 patients reported a residual ability to walk alone or with help. Lower limb edema was present in 113 patients, bilateral in 41 cases. At admission all patients underwent extended compression ultrasonography. Their plasma D-dimer levels were measured. No antithrombotic prophylaxis was given. RESULTS: DVT was found in 58 patients (43.9%); 32 had a history of VTE. Forty of these patients (69%) had chronic lower limb edema, in 19 cases bilateral. D-dimer levels in the DVT patients were significantly higher than in patients without DVT (553+/-678 vs. 261+/-152 ng/mL, p=0.0112, Mann-Whitney Test). Nearly half the DVT patients (26, 45%) had high D-dimer levels (701+/-684 ng/mL). Of the 74 patients without DVT, 48 had normal D-dimer (193.37+/-67.28 ng/mL) and 26 high (387.61+/-187.42 ng/mL). CONCLUSIONS: The frequency of DVT in late-stage MS may be over 40%. The long history of the disease means the onset of each episode cannot be established with certainty. A number of patients with positive CUS findings had negative D-dimer values, suggesting a VTE event in the past. However, the level of DVT risk in this series should lead physicians to consider the systematic application of long-term preventive measures.

The first 1000 cases of Italian Endovenous-laser Working Group (IEWG). Rationale, and long-term outcomes for the 1999-2003 period.

AIM: The innovations for disease management need to be thoroughly evaluated so that their benefits and potential downsides can be compared with the already existing approaches. Endovascular laser (EVL) treatment for varicose veins offers today several advantages over surgical standard stripping. The Italian Endovenous-laser Working Group (IEWG) is a homogeneous group of surgeons and phlebologists who have been using EVL since 1999 and has undertaken to examine EVL in a multicenter study starting from a well defined rationale, with the benefit of a single protocol to use. METHODS: In a cooperative, multicenter, clinical study, 1076 limbs in 1050 patients, mean age of 54.5 years, 241 males and 809 females affected by chronic venous insufficiency (CVI) were considered eligible for surgery and stratified by CEAP classification in a four-year period (January 1999 December 2003). Inclusion criteria were insufficiency of the great and/or small saphenous vein at various levels, beyond those accessory saphenous trunks with incompetence in the saphenofemoral junction. In all cases truncular reflux apparead up on duplex scan examination, with or without associated varicosities. All the patients underwent a surgery on the basis of the clinical assessment. All the centres involved performed treatment in conformity with the Food and Drug Administration (FDA) validated procedure, using an endo-laser venous system kit with a 810-980 nm diode. Duplex scan was performed in all patients after 36 months with very few lost to follow-up cases. RESULTS: In the immediate postoperative period the results have been impressive, with a very effective closure of incompetent great saphenous vein and the other treated varicose veins (the early occlusion rate has been 99%). Major complications have not been detected: in particular, no deep venous thrombosis (DVT) evaluated duplex ultrasound. The patients' acceptability and satisfaction regarding the procedure, have been measured by means of a questionnaire on the quality of life, and the result was 96.7%. After 36 months, the total occusion rate of saphenous trunks has been 97%. CONCLUSIONS: The first important Italian experience with EVL based on preoperative, perioperative and postoperative duplex control and which is also based on the patients' satisfaction at mid/long-term has indicated some advantages over the standard treatment with the stripping method. In terms of reduced postoperative pain, shorter sick leave, a faster resumption of the normal activities, and, in particular, the total absence of DVT, we can conclude that EVL is a good solution for all patients with anatomic and hemodinamic patterns for saphenous vein surgery.

[Pararenal aortic aneurysms: definition, classification, directions for surgery]. / Gli aneurismi dell'aorta pararenale: definizione, classificazione, indicazione al trattamento chirurgico.

The formidable impact derived by the endovascular correction (Evar) of abdominal aorta aneurysms (AAA), has risen its classification aspects. The topographical criteria has assumed importance in decisional diagnostic-therapeutic strategy especially in cases of so called pararenal aneurysms (PRAA). DEFINITION: PRAA defines aneurysm being involved underenal juxtarenal aorta (JRA), or more rarely, suprarenal aorta with normal aortic diameter at level of celiac (JRA), or more rarely, suprarenal aorta with normal aortic diameter at level of celiac trunk. CLASSIFICATION: The morphologic-topographic aspect is considered in function of selection or eligibility of patients to Evar or standard open surgery, in the need of a suprarenal clamping for the tailoring of proximal anastomosis or anchorage of endoprotesis. Various specific classifications for these aneurysms have been proposed (Schumacher, 1997; Wolf, 2000; Ayari, 2001) that considers: 1. Aneurysm collar: short/long/tortuous, 2. Relations with renal arteries, 3. Relations with the left renal vein. DIRECTIONS FOR SURGICAL TREATMENT: The choice between the technical solution to prefer either open or endovascular surgery will have to consider a series of additional variables to the standard direction common to every AAA based on dimensions and morphology. Priority will have to be given to evaluating, using shared morphologic-topographical classification criteria, real incidence of PRAA-JRA (3%-20% in literature review); greater post opening mortality (1.3%-15.3%); dimensions (AAA with diameter > or = 5.5 cm in operating risk assessment of single patient, in clinical evolution and increase in the time of the lesion); in common occurrence in AAA of steno-obstructive lesions of renal arteries and involvement of same ones in the aneurysm collar in need of reconstruction and suprarenal aortic clamping.

Hemostatic efficacy and safety of TachoComb in surgery. Ready to use and rapid hemostatic agent.

TachoComb is a new, ready-to-use hemostatic agent consisting of a collagen sheet coated on one side with human fibrinogen, bovine thrombin, and bovine aprotinin. The product was used in 125 surgical operations (vascular, hepatic, urological and ENT) in which secondary hemostasis was required. It was placed over the cut surface or over the edges of the wound. The investigating surgeons expressed their opinion on the intra- and postoperative hemostatic efficacy, and routine laboratory tests were done postoperatively. TachoComb had good hemostatic efficacy in 67.2% of cases, and very good in 22.4%. No noteworthy systemic changes were observed. As an adjuvant to obtain complete hemostasis in surgery, TachoComb is effective, practical and quick to use, and is very well tolerated.

Optimal site for proximal and distal anastomoses in AAAs repair.

The replacement of straight graft for vascular aortic reconstruction, in the elective treatment of aortic and aorto-iliac aneurysms, is advisable and requires only two anastomoses and a low surgical risk. In our report we have tried to identify the simplest vascular reconstruction for juxtarenal involvement (15% in our experience), reducing the surgical time and the operative (or postoperative) injuries. The decision to employ the tube or the bifurcated reconstruction depends on the surgeon's assessment of the degree of common iliac dilatation, the presence of an iliac aneurysm or the concomitance of occlusive disease of the iliac-femoral district. Some authors extend the bifurcated repair to prevent the possible future occlusive events or iliac dilatation. We have much information about the natural history of aortic aneurysms but we have also to define the indications for a valuable surgical reconstruction. We have considered a consecutive series of 20 patients who underwent elective aortic and aorto-iliac aneurysm repair in S. Rita private hospital; in 13 patients (65%) the aneurysms were treated with tube grafts, the other patients received bifurcate grafts: 3 (15%) aorto-bisiliac, 2 (10%) aorto-bifemoral and 2 (10%) right aorto-iliac and left aortofemoral bypass procedure. We employed Crawford's inclusion in the juxtarenal involvements, generally without the reimplantation of renal arteries, extending the tube repair in the aorto-iliac dilatation, obtaining a simplification of the surgical procedures. The use of straight graft allows a sensible decrease of surgical operating time, a reduction of hematic loss and a very low incidence of postoperative injuries; this solution became possible also in some selected forms of aneurysmatic involvement of renal arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of early graft infection with rifampicin-bonded Gelseal grafts: a multicentre experimental study.

The possibility of increasing the resistance of a synthetic vascular graft to intraoperative or immediate postoperative bacterial contamination justifies the interest in methods such as antibiotic bonding or antibiotic soaking. On the basis of this experience and with the aim of testing the efficacy of such a graft, a multicentre experimental study on sheep to compare the susceptibility to infection of Dacron Gelseal grafts (control) versus rifampicin-bonded Dacron Gelseal grafts (treated) following the intravenous infusion of 10(7)-10(8) cells Staphylococcus aureus was conducted. The grafts were implanted in both common carotid arteries of sheep. In a group of 11 animals (group A), a treated and a control graft were implanted in the same animal. In a group of four sheep (group B), only treated or control grafts were implanted in each animal. In group A, 36% of (four of 11) the treated grafts became infected versus 54% (six of 11) of the control prostheses. In group B, none of the treated grafts was infected by the inoculated pathogen, which, by contrast, infected 75% (three of four) of the controls. These observations confirm the recent interest aroused by the possibility of pretreating gelatin-coated Dacron grafts with rifampicin in the prevention of early graft infection.

[Trapidil after one year]. / Trapidil un anno dopo.

Present knowledge about cerebral limb ischemia has pointed out the importance of a versatile pharmacological approach, which considers not only the hydraulic aspect of the problem through a vasodilating action, but also all the hemorheologic and hemocoagulative implications, which seem to characterize the pathology itself. For about one year Trapidil has been entering the therapeutic treatments for arterio-vascular diseases in Italy; this drug was already known and tested abroad. Trapidil has shown a more complete antithrombocytic activity than other antiaggregating drugs; as a matter of fact it inhibits the formation of TXA2 through a mechanism of receptorial antagonism and at the same time it favours an increase of prostacyclina from the arterial walls. Moreover this drug is provided with a selective inhibition of the mitogenic effects of PDGF, which occurs for the block of the receptorial binding of this factor at the level of the myointimal cells. In conclusion, in some experimental models Trapidil seems to be able to improve the hemoreologic properties of the blood. Some different clinical studies have demonstrated the therapeutic effectiveness of Trapidil. In the treating of claudication and of the pain during the rest in AOCP, we want to report two studies which have shown a general improving either of the free interval of run or a reduction of the pain. In particular the polycentric study of Bonavita has examined 200 patients afflicted with AOCP at II and III stage, who were divided into three treatment groups: Trapidil, ticlopidina and picotamide.

Double-blind comparison of nimesulide and diclofenac in the treatment of superficial thrombophlebitis with telethermographic assessment.

A total of 60 patients with acute varicophlebitis or acute superficial thrombophlebitis of the lower limbs were recruited to this randomised double-blind comparative study, which evaluated the efficacy and tolerability of oral nimesulide (100mg twice daily) with those of diclofenac (50 mg/kg twice daily) over a period of < or = 20 days (average duration 13.6 days for nimesulide and 12.6 days for diclofenac). The analgesic effect of both drugs was rapid. Spontaneous pain disappeared within 3 to 5 days of commencing therapy, and pain on palpation within 7 days. Reduced inflammation was observed after approximately 15 days, and total resolution of redness and swelling was observed by day 20. Telethermographic assessment showed a reduction in local temperature, either in absolute terms or in the extent of inflammation. Indeed, 93% of patients showed complete recovery while 7% of patients showed a partial reduction in hyperthermia. For these latter patients, medical treatment was extended, although the subjective symptoms of the disease were no longer present. The comparison between nimesulide and the reference drug, diclofenac sodium, showed no significant difference for any of the considered parameters. Both drugs were well tolerated and no patient reported an adverse event.

Thrombectomy for late graft limb occlusion: our experience in 182 consecutive cases.

Late occlusion of an aortofemoral bypass graft is usually caused by fibrointimal hyperplasia or progressive atherosclerosis. Several surgical approaches have been advocated in order to minimize the operative risk, to correct the impaired inflow and to provide a satisfactory outflow. In the last 16 years, in the Institute of Vascular Surgery and Angiology of the University of Milan, we have operated upon 182 consecutive thrombosed grafts. Inflow was restored by performing a graft limb thrombectomy using a Fogarty balloon catheter and simultaneously employing an endarterectomy ring stripper to dislodge tenaciously adherent fibrinous material and thrombotic plug. As the superficial femoral artery was generally occluded, usually a good outflow was achieved by profundaplasty in 101 cases (55.5%) or direct bypass (interposition graft), to a more distal segment of the profunda femoris artery in 55 cases (30.2%). Concomitant popliteal or tibial revascularization was done in the remaining 26 cases (14.3%) when pre-operative or intra-operative findings suggested an inadequate collateral network through the profunda femoris artery. Early re-occlusion, which occurred in 14 cases (7.6%), generally due to insufficient outflow, was corrected by additional intervention in 7 cases (3.8%), while 7 legs were amputated for extensive atherosclerotic disease. Six patients died giving a mortality rate of 3.3%. This low rate in a high risk population is probably related to our policy of operating under loco-regional anaesthesia. Long term results, with a patency rate of 62.0% at 3 years and 60.2% at 5 years (life table method), prove that this operation is a durable procedure for correction of graft limb thrombosis.