Consensus Document on Intermittent Claudication from the Central European Vascular Forum (C.E.V.F.)-3rd revision (2013) with the sharing of the Mediterranean League of Angiology and Vascular Surgery, and the North Africa and Middle East Chapter of International Union of Angiology.

This paper is the review of the Consensus Document on Intermittent Claudication of the Central European Vascular Forum (CEVF), published in 2008, and and shared with the North Africa and Middle East Chapter of International Union of Angiology and the Mediterranean League of Angiology and Vascular Surgery. The Document presents suggestions for general practitioners and vascular specialists for more precise and appropriate management of PAD, particularly of intermittent claudication, and underlines the investigations that should be required by GPs and what the GP should expect from the vascular specialist (angiologist, vascular surgeon). The idea of the Faculty is to produce a short document, which is an easy reference in daily clinical practice, both for the GPs and vascular specialists.

Role of sulodexide in the treatment of CVD.

Treatment of vascular diseases should be based on established pathophysiological concepts, and this also applies to chronic venous disease (CVD). On the basis of the latest research in this field, this paper summarizes the most advanced pathophysiological knowledge regarding the hemodynamics of the large veins and of the microcirculation, the endothelial function and inflammation, and the use of sulodexide in the treatment of CVD. The emerging theories on the pathophysiology of CVD consider inflammation, endothelial glycocalyx dysfunction, and the consequent changes in the extracellular matrix to play key roles in the development of CVD, and support a renewed interest in the research and application of sulodexide. As part of active approach to the treatment of CVD including edema and trophic venous alterations, sulodexide could help to alleviate progressive signs and symptoms of disease in any clinical CEAP class of CVD, from C1 to C6.

Propionyl l-carnitine: intermittent claudication and peripheral arterial disease.

Peripheral arterial disease (PAD) is a clinical manifestation of underlying aorto-iliac and leg atherosclerosis that is characterized by different stages of stenosis and obstruction. It affects approximately 12% of the adult population and about 20% of people over the age of 70 years, and is associated with increased cardiovascular (CV) and cerebrovascular morbidity. Intermittent claudication (IC) is the major symptom of PAD; it is defined as cramping leg pain (in the buttock, thigh, or calf) while/after clim bing one or two flights of stairs, or during walking. The goals of IC management are to: slow the progression of local and systemic atherosclerosis, prevent major fatal and nonfatal CV events (myocardial infarction and stroke), improve walking capacity, prevent and reduce resting pain and cutaneous lesions. Propionyl L-carnitine is an acyl derivative of levocarnitine (L-carnitine) and is indicated for patients with peripheral arterial occlusive disease. It corrects secondary muscle carnitine deficiency in patients with PAD, significantly improving the walking capacity; it is a free radical that produces positive effects on endothelial function; it protects from oxidative stress; and it enhances most measures of quality of life. The recent Trans-Atlantic Inter-Society Consensus II update recommends the use of propionyl L-carnitine in combination with physical training to improve the symptoms associated with PAD.

Unbalanced risk factors, could compromise the effectiveness of physical training in patients with intermittent claudication?

AIM: The correction of atherosclerotic risk factors is the unavoidable assumption to assure the maximal effectiveness and duration of the results of any therapeutic intervention (pharmacological and surgical) for the treatment of intermittent claudication. Aim of this study has been to verify if the presence/absence of risk factors and the degree of their correction could compromise the responsiveness of claudicant patients to the supervised physical training. METHODS: Initial (IDC), absolute (ACD) claudication distance, and recovery time (RT) have been measured by maximal treadmill exercise in 74 claudicants. The measurements have been repeated after 18 days of supervised physical training consisting of a daily walk reaching either a distance goal of 1-2 km or a time goal of at least 30 min. The working load of each single training session has been tailored at 60-70% of the ACD measured by a non-maximal treadmill exercise. The patients' cohort has been stratified in 7 groups and 18 sub-groups (no smokers, smokers in the past, still smokers, no-diabetics, well balanced and unbalanced diabetes, absent, well balanced and unbalanced hypercholesterolemia, normal weight, over weight and light obesity, hypertensive and no-hypertensive, with and without previous myocardial infarction and TIAs or stroke). The mean and standard error of ICD, ACD and RT before and after 18 days of physical training have been calculated and compared with Student's t test in each group and sub-group. On the data before and after training of ICD, ACD and RT of each group of risk factors the multivariate analysis of the variance has been carried out by analysis of variance (ANOVA). All the analyses were considered significant when the P value was less than 0.05. RESULTS: ICD values increased from 55.12 to 121.86 m, ACD from 103.16 to 191.58 m, RT reduced from 204.04 to 87.46 s, confirming the relevant (P<0.0001) effectiveness of supervised physical training on the walking capacity of claudicant patients. The comparison between the deltas (value after minus value before) of each sub-group did not show any significant difference. The multivariate ANOVA of before and after ICD ACD and RT of each risk factor groups showed values relevantly lesser than 0.05, indicating that risk factors did not influence the result of physical training. CONCLUSIONS: The supervised physical training is confirmed as an effective tool for the treatment of claudicant patient. We did not find any significant difference in the response to the programme related with the presence, absence or balance degree of risk factors, and we conclude that physical training effectiveness is independent from the their presence, absence or balance degree. This statement is very important because highlights the physical training as the only therapeutic tool for peripheral arterial disease (PAD) independent from the results of the risk factors' treatment.

Effectiveness and costs of a short-course supervised training program in claudicants: proposal for a shared protocol with aerobic working load.

AIM: The purpose of this study was to assess the costs and effectiveness of a short-course physical training program, consisting of an aerobic protocol with clearly defined working loads in each single training session, in patients with intermittent claudication (IC). METHODS: Initial (ICD), absolute (ACD) claudication distance, and recovery time (RT) have been measured by maximal treadmill exercise in 74 claudicants. Ankle brachial index (ABI) has been measured too. Measurements have been repeated after 18 days of supervised physical training consisting of a daily walk reaching either a distance goal of 1-2 km or a time goal of at least 30 min. The working load of each single training session has been tailored at 60-70% of the ACD measured by a non-maximal treadmill exercise. RESULTS: ICD increased from 56.2 (+/- standard deviation/+/- standard error: 35.3/4.1) to 123.9 (66.5/7.7); ACD increased from 104.8 (49.8/5.8) to 195.1 (81.7/9.5) and RT reduced from 201.2 (98.3/11.4) to 85.8 (43.6/5.1), with P<0.0001 for all parameters. We analyzed separately patients with moderate (M-CL) and severe (S-CL) claudication, and found significant improvements in both groups. The Ds (post-training value minus pretraining value) were: ICD 89.6 (59.9/10.9) in M-CL and 50.2 (29.9/4.6) in S-CL; ACD 102.8 (66.8/11.6) in M-CL and 80.1 (41.5/6.4) in S-CL; RT -98.7 (86.9/15.1) in M-CL and -128.5 (88.1/13.7) in S-CL, with P<0.0001 for all parameters. The differences between M-CL and S-CL were significant only for ICD (P=0.0003) and ACD (P<0.05). ABI showed an increasing trend, which was statistically significant (P<0.001), but clinically irrelevant. The protocol cost was 4179 Euro (average cost 46.30 Euro to walk one additional meter). CONCLUSION: Supervised physical training is confirmed to be an effective tool for the treatment of IC, and the proposed short-course protocol gave the same improvements as the longer ones while reducing the costs. The proposed procedure for tailoring the working load of a single session identifies clearly the working load, near maximal pain but avoiding the risk of inflammatory activation.

Occult atherosclerosis and physical vascular examination: a simple strategy to avoid inadequate cardiovascular prevention and under-use of diagnostic vascular guidelines in outpatients. A multicenter study by Angiology Care Units in North-Eastern Italy.

AIM: Recent studies show a high prevalence of inadequate secondary prevention in a subset of the US population at highest risk for stroke and acute myocardial infarction. METHODS: The present investigation evaluated subjects older than 50 years of age attending four Angiology Care Units in Northern Italy. The adequacy of risk factor (hypertension, body weight, cigarette smoking and hypercholesterolemia) control was in particular analyzed, and a search was made for occult atherosclerotic lesions during a thorough physical examination. Finally, adherence to diagnostic vascular guidelines was also evaluated. RESULTS: Twenty-two percent out of 483 patients enrolled in this study were found to have unexpected atherosclerotic lesions, 61.9% of the patients with a history of hypertension, 10.6% showed an inadequate control of blood pressure levels, 55% presented poor lipid control, 16.6% had not stopped smoking and 45.7% were overweight. The physical examination revealed that 13.8% of the patients had cervical bruits, 6.3% had aortic hyperpulsatility and 8.5% were lacking lower limb pulses, not previously diagnosed. It was found that in almost half of the participating patients diagnostic vascular guidelines were not being followed. CONCLUSION: This study shows a high prevalence of inadequate primary and secondary prevention and under-use of diagnostic vascular guidelines in the care of high-risk patients (older than 50 years with diabetes, smokers, etc.). Considerable efforts are required to effectively implement risk factor modification strategies and, with regard to Angiology Care Units, to correctly search for occult atherosclerotic lesions in high-risk patients.

Effectiveness of mesoglycan in patients with previous deep venous thrombosis and chronic venous insufficiency.

AIM: Retrospective analysis of mesoglycan therapeutic activity in venous disorders. The clinical data have been selected from the outpatient database of the Chair of Angiology of the University of Catania (from 1988 to 1997) through a cross survey between the prescription commercial name of mesoglycan and the key words varicose veins, deep venous thrombosis (DVT), chronic venous insufficiency (CVI), post-thrombotic syndrome (PTS), venous thrombosis, venous ulcer. METHODS: Patients have been selected on the basis of definite data relative to principal diagnosis, clinical history, clinical and instrumental objective phlebological picture, posology and duration of treatment, follow-up visits in the first three years following the first observation. Group 1: 56 patients with first episode DVT; Group 2: 27 patients with recurrent DVT; Group 3: 182 patients with CVI (107 with primitive CVI and 75 with secondary CVI). The selected patients data have been included in new databases. DVT patients were evaluated for recurrence prevalence during the follow-up period (6, 12, 18, 24, 30 and 36 months). In Group 2 the recurrence prevalence in the normal follow-up period was evaluated and, in addition, the clinical chronology of the recurrence previous to observation was drawn, in order to find out the recurrence prevalence of the thrombotic episode preceding our observation. The two prevalence trends ( mesoglycan treatment and episode preceding our observation) have been compared with the Student t test. CVI patients (Group 3) were classified according to CEAP classification criteria. The effectiveness of treatment was assessed according to the changes in the scores of venous dysfunction of CEAP classification (disability score; pain; oedema; skin color change; cutaneous ulcer). The mean and standard deviation of the considered scores have been evaluated with the Student t test comparing each series with the immediately previous series and with the T0 series. The mean dose of mesoglycan was 50 mg twice per day. RESULTS: Group 1 (1(st) episode DVT): the recurrence prevalence was 3.5% at 6 months, 9% at 12 months, 12.5% at 18 months, 14.28% at 24, 30 and 36 months. At the end of the 3 follow-up years the PTS diagnosis could be performed in 10 patients (17.85%). Group 2 (recurrent DVT): the recurrence prevalence was 3.7% at 6 months, 11.11% at 12 months, 14.81% at 24 months, 18.51% at 36 months during mesoglycan treatment. In the preceding period the prevalence was 11.11% at 6 months from the preceding episode, 16.66% at 12 months, 33.33% at 24 months and 37.03% at 36 months. In the remaining 62.96% the recurrence occurred at 36 and 48 months. The comparison between the two series showed a significant difference with P < 0.0004. PTS prevalence at the end of the 3 follow-up years was 17.85% in patients with a first episode of DVT and 81.41% in patients with recurrent DVT. Group 3 (CVI): all the venous dysfunction scores showed a significant improvement during the follow-up period, both in comparison with the beginning of treatment and with the immediately preceding control visit. CONCLUSION: The results obtained in groups 1 and 2 show that mesoglycan is effective in preventing thrombotic recurrence in patients with previous DVT. The recurrence prevalence in patients with DVT at 1(st) episode was lower than the prevalence reported by the literature data (17.5% within 2 years and 24.6% within 5 years). The positive trend was also confirmed in the recurrent DVT group, although with a major prevalence (18.51%) due to a higher thrombotic risk. However, the prevalence in the treatment period is significantly lower than the previous thrombotic episode. Mesoglycan was also effective in CVI patients, with a progressive and significant improvement of disability, pain and edema, which are the pathophysiologic elements responsible for the impairment of quality of life. At the various follow-up points the mean score value significantly reduced compared to T0 and to the values of the preceding control. In conclusion mesoglycan is a useful and effective medication in the treatment of venous disorders, both in the subacute phase of DVT and in the long-term therapy for CVI, and is worth more extensive documentation, in accordance with the criteria of evidence-based medicine.

Circulating levels of cytokines (IL-6 and IL-1beta) in patients with intermittent claudication, at rest, after maximal exercise treadmill test and during restore phase. Could they be progression markers of the disease?

AIM: Inflammation is considered to be one of the main mechanisms for the development and progression of peripheral arterial disease (PAD). Many studies have demonstrated that maximal exercise enhances the acute inflammatory response in claudicant patients, but no one has assessed the duration of this acute inflammatory activation. The aim of this study was to assess of the inflammatory pattern in claudicants and of the inflammatory response after maximal exercise and during the recovery from calf pain. METHODS: Eleven patients with moderate claudication (MC) (age: 60.5+/-5.8 years; body mass index [BMI]: 27.5+/-4.6; absolute claudication distance [ACD]: 165.4+/-38), 10 patients with severe claudication (SC) (age: 60.3+/-5 years; BMI: 27+/-4.5; ACD: 91+/-11.3) and 8 healthy subjects (age: 59.4+/-6.8; BMI: 28.7+/-4.16) underwent to maximal treadmill test (speed 2.5 km/h, slope 15%). At rest, just after stop of the exercise (appearance of calf pain in patients, and 6 min of treadmill in controls) the circulating levels of interleukin (IL)-1beta and IL-6 have been measured. STATISTICAL ANALYSIS: variance of mean values, Bonferroni t-test, split plot variance model, variance of d stop-before and stop-recovery have been utilized. P<0.05 has been considered the significant cut-off of the differences. RESULTS: The maximal exercise excited significant (P<0.01) inflammatory activation in all patients: MC (rest IL-1beta: 1.55, 3.3 at stop; rest IL-6: 5.97, 8.38 at the stop); SC (rest IL-1beta: 2.97, 5.72 at stop; rest IL-6: 6.98, 9.99 at the stop). During recovery, MC showed a reduction of the inflammatory activation, whilst SC showed further increase (IL-1beta: 7.55; IL-6: 11.94). CONCLUSION: The study confirms the higher inflammatory activation in claudicants and its enhancement after maximal exercise. During recovery, we found two kinds of response: type 1 (controls and MC), in which inflammation subsides, and type 2 (SC) characterized by further inflammatory increase. This trend is not univocal: 3 MC showed a type 2 response and 2 SC showed a type 1. In conclusion, inflammatory activation may depend not only on the degree of endothelial damage, but also on the individual inflammatory attitude, better assessed after maximal exercise than baseline values. This individual inflammatory responsiveness, considering the role of the rest measurement of markers of inflammation recently discussed, could be a useful marker for aggressive PAD.

Acute impairment of the endothelial function by maximal treadmill exercise in patients with intermittent claudication, and its improvement after supervised physical training.

AIM: The aim of this study was to determine the effects of maximal exercise and of physical training on endothelial function (EF) of patients with intermittent claudication (IC). METHODS: EF, assessed by ultrasonography of the brachial artery, has been measured in 22 male patients with IC before (pre-exercise EF) and after (postexercise EF) maximal treadmill test. Absolute claudication distance (ACD) and ankle brachial index (ABI) have been measured too. The measurements have been repeated after 18 days (3 times weekly, for 6 weeks) of supervised physical training. RESULTS: Before training, the pre-exercise EF was 7.6+/-2.94 and postexercise EF 5.28+/-3.3 (-33.2%) (P<0.01). After training, the pre-exercise EF was 10.3+/-4.04, whilst postexercise EF was 7.79+/-2.56 (-18.97%) (P<0.01). The differences between the pre-exercise value before and after training and between the postexercise value before and after training were significant (P<0.01). ACD and ABI after training increased respectively from 93.95 to 166.55 m and from 0.67 to 0.71 (P<0.001). CONCLUSIONS: Endothelial dysfunction takes a relevant part in the pathophysiology of IC, with 2/3 of the patients showing an EF lower than the pathological cut-off. Maximal exercise worsens the EF, according to the trend associated with the acute inflammatory response. All these features suggest that physical activity in IC should not utilize the maximal working load, in order to avoid the high inflammatory activation and the acute complications of atherosclerotic plaque. The supervised physical training, besides confirming itself as the most effective means to increase the walking ability, also proved to be able to improve the EF of these patients, as described about other diseases. It is probable that moderate hemodynamic stress reduces the levels of the inflammatory markers and increases the flow-mediated vasodilation through an ischemic preconditioning. The increased walking ability, associated with the improvement of EF could improve the heavy systemic outcome of claudicant patients, as it has been demonstrated in patients with coronary heart disease. Further prospective survival studies on cardiovascular outcomes of trained claudicant patients are needed.

Effects of elastic stocking on quality of life of patients with chronic venous insufficiency. An Italian pilot study on Triveneto Region.

AIM: Even though compression therapy is the most recommended treatment for chronic venous insufficiency (CVI) in the national and international guidelines, its application, at least in Italy, is lower than the estimated need from the prevalence of CVI in the epidemiological studies. Since we believe that the measurement of the impact of compression therapy on quality of life (QoL) could improve the compliance for this precious treatment, we carried out this study on 50 patients with CVI. METHODS: Fifty patients (23 CEAP C2 and 27 C(3-4-5), selected within a larger study on QoL in CVI), received a prescription for compression therapy. Before treatment and 4 months afterwards, the patients received the instrument for QoL assessment (MOS SF-36; CIVIQ-2; Euro-QoL 5D and a visual analogue scale). The score scales have been adjusted to poorest QoL as 0 and best QoL as 100. RESULTS: Baseline QoL of patients in class C2 did not show significant difference with the healthy Italian Population, except for the physical role item. The patients in class C(3-4-5) showed significant reduction of QoL. After 4 months all the items of the utilized instrument showed significant improvement (from P<0.01 to P<0.04 for SF-36; from P<0.099 to P<0.006 for other instruments) in all CEAP classes. CONCLUSIONS: The study unquestionably shows that the compression therapy improves the QoL of patients with CVI, and should be included in the CVI treatment covered by the Public National Health Insurance. Finally, the QoL measurement could be utilized as the scientific method to assess the effectiveness and efficacy of different therapeutic devices.

Quality of life in chronic venous insufficiency. An Italian pilot study of the Triveneto Region.

AIM: Chronic venous insufficiency (CVI) is a chronic disease, whose disability has not been appreciated clearly, and several treatment costs are not covered by Public Health Service, probably because its any social impact is not well known. The aim of the study was to assess the impact of CVI on quality of life (QoL), and to compare the sensitivity of more diffused instruments for QoL assessment. METHODS: One hundred and four patients with CVI received the Italian version of four QoL assessment instruments (MOS SF-36; CIVIQ-2; Euro-QoL 5D and a visual analogical scale). The poorest QoL was adjusted as 0, the best as 100. After filling the questionnaires, patients underwent a clinical and instrumental examination to assess the diagnosis according to the CEAP classification. RESULTS: The QoL is progressively impaired from CEAP class C1 to class C5-6. The SF-36 showed a normal QoL in patients of CEAP class C1 and C2. Class C3 showed a significant (P<0.0018) reduction of QoL (physical role and bodily pain), and the decline was more significant (P<0.0001) in class C4, involving all physical items and several mental ones. Class C5-6 showed very low scores of physical and social functioning, general health and vitality. Physical and emotional scores were better than C4 patients. CONCLUSIONS: QoL is progressively impaired in CVI, involving primarily the physical items and the emotional role, with worsening of mental items only in advanced stages. This early involvement of physical items underlines how CVI is not an esthetic problem, but, a disease. Its impact on the lifestyle and QoL is similar to that of other chronic diseases (diabetes, cancer, chronic pulmonary disease), reaching in the class C5-6 the poorest level, similar to heart failure.

Effects of defibrotide in patients with chronic deep insufficiency. The PROVEDIS study.

AIM: In the present study the effect of defibrotide, an antithrombotic and profibrinolytic agent, was investigated in patients with chronic venous insufficiency (CVI) due to deep vein obstruction and/or reflux (chronic deep vein insufficiency, CDVI). METHODS: The study was a multicenter, randomized, double blind placebo controlled trial in which only patients with CDVI confirmed by ultrasound were enrolled. All patients were treated with adequate elastic compression and randomized to receive either oral defibrotide (800 mg/die) or matching placebo for 1 year. Patients with active or previous leg ulcer were excluded. RESULTS: A total of 288 patients were randomized and 159 completed the study. At baseline ultrasound investigation, obstructive changes were found in 2/3 of all patients thus ascertaining a post-thrombotic syndrome (PTS). The primary endpoint, ankle circumference, was significantly reduced under defibrotide from day 120 throughout 360. Scores for pain and edema were improved. The number of episodes of superficial thrombophlebitis and deep vein thrombosis was significantly lower under defibrotide (n=2) than under placebo (n=10). The majority of these events occurred in the subset of patients with documented PTS. CONCLUSION: Treatment with defibrotide in addition to elastic compression in patients with objectively assessed CDVI, mostly due to PTS, resulted in clinical benefits and prevented thrombotic complications harmful to the limb conditions.

Spontaneous recanalization of internal carotid artery occlusion evaluated with color flow imaging and contrast arteriography.

AIM: In strokes of embolic origin a partial recanalization of the intracranial occluded vessel occurs with a high incidence (as high as 80%). In the literature, we find few cases of revascularization, detected with color flow imaging (CFI) or with arteriography (AGF), at carotid siphon or at the origin of an occluded internal carotid artery (ICA). Up to now there have been no reliable data on the incidence and clinical consequences of SR of an extracranial ICA occlusion. In this case-report we document 8 cases of SR of occluded ICA observed in the last 10 years in our Care Unit. METHODS: We observed 8 complete ICA occlusion at the origin, detected with CFI (8 of 8) and with AGF (7 of 8). All symptomatic patients and 2 of 5 asymptomatic patients underwent CT scan in the acute phase of stroke. All patients underwent CFI follow-up (every 6-12 monhts) to evaluate contralateral CCA and ICA and the presence of new focal neurological symptoms. All patients assumed BMT (antiplatelet or anticoagulant therapy). RESULTS: SR occurred in 6 patients between 24 and 96 months, in 1 patient within 8 months and 1 patient within 6 months from the diagnosis of ICA occlusion. Diagnosis of SR was based in all patients with CFI and in 4 patients confirmed with AGF. Five patients underwent CT scan that excluded haemorrhagic transformation of previous ischemic areas or new ischemic events (2 patients did CT scan only after SR). All patients underwent CFI follow-up in a 3-88 months period. There were no new focal neurological symptoms in 7 of 8 patients, 1 patient presented aspecific neurological symptoms. CONCLUSION: Diagnosing SR of occluded extracranical ICA seems to be more frequent than expected. SR is an event that has to be researched in follow-up of these patients; besides, it seems to have a relatively benign outcome with respect to the onset of new neurological symptoms.

[Evaluation of cutaneous necrosis risk in peripheral arterial diseases]. / La valutazione del rischio cutaneo di necrosi nelle arteriopatie periferiche.

BACKGROUND: In the last years the surgical and pharmacological treatment of critical limb ischaemia has been significantly modified, increasing the reduction of amputation and/or the increase of limbs recovery. However, neither survival nor incidence of amputations changed. This, probably has been related to an inadequate therapy after revascularization procedures or to an increase of complications. The assessment of cutaneous necrosis risk and of the recovery possibility of the ischemic limb can positively influence the therapeutic strategy, in these patients. The aim of this paper is to identify the reference parameters that can represent objectively the limit for cutaneous ischemic suffering, improving the physiological knowledges of critical limb ischemia. METHODS: In the first phase of our study 56 patients, in different stages of peripheral arterial disease have been, submitted to microcirculatory assessment measuring the pattern of TcPO2 and TcPCO2 in correlation with walking performance expressed as ACD at treadmill test (2.5 Km/h gradient 12.5%). The second phase assesses the clinical outcome after three months of 12 among 19 patients with critical limb ischemia, measuring the changes of TcPO2 and TcPCO2 with postural test and after infusion with prostanoids of two weeks. RESULTS: A reduction of the TcPO2 and an increase of the acidosis from stable to invalidant claudication have been observed, with a progressive loss of direct correlation between ACD and TcPO2, and an increase of the inverse correlation of the ACD with TcPCO2. In the CLI we found a very low TcPO2 levels with a TcPCO2 levels ( about 120 mmHg) with no correlation of ACD with TcPO2 and TcPCO2. The good clinical outcome was related to an increase of the TcPO2 and to a reduction of the TcPCO2 after postural stimulation and after therapy. In the patients with a bad response to the postural test, a possibility of recovery was observed only in those with a positive answer to therapeutic treatment. CONCLUSIONS: The invalidant claudication phase can be considered a point of physiopathological change from relative to absolute ischemia that is clinically equivalent to early sign of ischemia. The identification of recoverable patients seems to be related to postural test and pharmacological treatment with an increased values. Viceversa, it is still difficult to identify as non-responders, those patients with a bad postural test, or with a little improvement after pharmacological treatment, as those with an indication to primary amputation. More observations, evaluation data will contribute to a better definition of a negative trend.

Takayasu arteritis in a 66-year-old caucasian woman.

A 66 year-old Italian woman was admitted to the hospital for fatigue, malaise and fever. Radial pulses were absent. She underwent echo color Doppler examination and angiography, which pointed out tight stenosis of bilateral axillary arteries; particularly, the echo color Doppler showed diffuse arterial wall thickening in the left common carotid artery (1.7 mm). Clinical features and instrumental findings suggested active Takayasu is arteritis. Corticosteroid therapy was administered and bilateral radial pulse appeared again after two months of steroid therapy. This case demonstrates the presence of Takayasu's arteritis in Western Europe and showed how the disease onset can be observed also in geriatric patients.

The value of ultrasound screening for proximal vein thrombosis after total hip arthroplasty--a prospective cohort study.

The role of ultrasound screening for proximal deep-vein thrombosis (DVT) following major hip surgery is controversial. 202 consecutive patients, who had received warfarin prophylaxis after total hip arthroplasty underwent a bilateral ultrasound assessment of the proximal vein system (using the criterion of vein compressibility) before hospital discharge. In the 9 patients (4.5%; 95% CI, 2.1-8.3%) with positive test anticoagulant treatment was successfully continued for three months. In all the remaining 193 patients the warfarin treatment was withdrawn. A second ultrasound test was performed 15 days later, and showed a new (asymptomatic) abnormality compatible with proximal DVT in 2 patients (1.0%; 95% CI, 0.1-3.7%). All other 191 patients remained asymptomatic until the completion of a 3-month follow-up period (rate of symptomatic thromboembolism, 0/191, 0%; 95% CI, 0-1.9%). Because of the relatively high incidence of proximal DVT in patients undergoing major orthopaedic surgery under warfarin prophylaxis, screening for proximal DVT at hospital discharge in these patients is indicated. The negativity of this test has the potential of safely preventing the extension of anticoagulation beyond hospital stay. A larger controlled study in which the value of this strategy is tested against the prolongation of oral anticoagulation in patients with a negative ultrasound screening at discharge is indicated.

Tissue factor pathway inhibitor release induced by defibrotide and heparins.

We evaluated the release of tissue factor pathway inhibitor (TFPI) induced by defibrotide (DF), a single-stranded, negatively charged polydeoxyribonucleotide extracted from mammalian organ. Ten normal volunteers were injected with an intravenous bolus of 400 mg DF and 2,000 IU unfractionated heparin (UFH). In addition, three volunteers were also injected with an intravenous bolus of 2,000 anti-Xa U of two low-molecular-weight heparins (LMWHs), enoxaparin and nadroparin. UFH caused a 4-fold increase in plasma TFPI at 5 minutes, with a decrease that was parallel to the heparin level measured by the anti-Xa assay. However, at 80 minutes, although the plasma anti-Xa activity of UFH was almost undetectable, the level of TFPI remained 2-fold baseline. DF induced an increase of TFPI that was 2-fold higher than the baseline level, with a steady state achieved between 5 and 20 minutes. At 40 minutes, the TFPI levels returned to basal level. This pattern was not coincident with the clearance of DF and at 40 minutes, the concentration of DF was still one third of the levels at 5 minutes (25.4 +/- 4.04 microg/mL). Both of the LMWHs induced a similar TFPI peak level at 5 minutes (1.5-fold increase) and at 40 minutes the TFPI levels returned to the initial levels. At 5 minutes, both LMWHs showed a higher plasma anti-Xa activity than UFH, which was detectable even at 80 minutes. The current study demonstrated that one of the mechanisms of the antithrombotic activity of DF is mediated via TFPI. Furthermore, the release of TFPI by heparin is mediated by non-antithrombin III binding fragments. Thus, polyanionic electrolytes are capable of releasing TFPI irrespective of their antithrombin III effect.