Clinical efficacy of once-daily micronized purified flavonoid fraction 1000 mg tablet in patients with symptomatic chronic venous disease.

AIM: To investigate the clinical efficacy of micronized purified flavonoid fraction (MPFF) 1000 mg given as a single 1000 mg tablet once daily in patients suffering from chronic venous disease (CVD) vs MPFF 500 mg twice daily. METHODS: In an international, randomized, double-blind, parallel-group study, patients classified C0s to C4 according to Clinical Etiological Anatomic Pathophysiologic [CEAP] classification and with leg pain graded as superior to 4 cm on a 10-cm visual analog scale (VAS), were treated for 8 weeks with either MPFF 1000 mg once daily or MPFF 500 mg twice daily. The present post-hoc analysis focuses on the effect of treatment over time in patients randomized to the MPFF 1000 mg group. Leg pain was assessed at each follow-up visit by VAS. VAS scores over time were compared between each visit using paired Student t-tests. RESULTS: In total, 87 patients out of 174 were randomized to the MPFF 1000 mg group. Mean age ± SD was 49.1 ± 12.2 years, most of the patients were female (81.6%), the main CEAP classes of the most affected leg were C1 (20.7%), C2 (39.1%), C3 (33.33%), and the mean duration of CVD was 14.6 ± 10.9 years. Patients with previous CVD treatment represent 27.6% of the patients. A MPFF 1000 mg tablet once daily was associated with a significant and continuous reduction in leg pain throughout the treatment period: -1.54 cm (±1.45) from baseline to week 2 (p < .01), -1.11 cm (±1.06) from week 2 to week 4 (p < .01), -1.57 cm (±1.05) from week 4 to week 8 (p < .01). CONCLUSIONS: The new MPFF 1000 mg dose regimen in once daily tablets was associated with a rapid and continuous reduction in leg pain throughout the 8-week treatment period.

Hypothesis related to the regulation of inducible nitric oxide synthase during carotid endarterectomy.

Sudden occlusion of an artery caused by a thrombus or emboli is the most frequent cause of acute brain ischemia (ABI). Carotid endarterectomy (CEA) represents the gold standard for preventing strokes of carotid origin. However, neuronal damage caused by ischemia and/or reperfusion may contribute to a poor clinical outcome after CEA. In response to shear stress caused by hypoxic-ischemic conditions in patients undergoing CEA, stimulation of the hypothalamic-pituitaryadrenal axis leads to biological responses known as hypermetabolic stress, characterized by hemodynamic, metabolic, inflammatory and immunological changes. These changes maintain homeostasis and assist recovery, but an unregulated inflammatory response could lead to further tissue damage and death of neurons. Nitric oxide (NO) is an important signaling molecule involved in several physiological and pathological processes, including ABI. However, an excess of NO could have detrimental effects. We hypothesized that the hypoxic-ischemic state induced by carotid clamping leads to overexpression of inducible NO synthase and that uncontrolled production of NO could adversely affect outcome after CEA.

Relationship Between Pain and CEAP C Categories of Chronic Venous Disease.

In this study, we investigated whether the occurrence and intensity of leg pain are related to C class of the clinical, etiological, anatomical, and pathophysiological (CEAP) classification for chronic venous disease (CVeD). This cross-sectional study, conducted in Serbia, included 2841 patients: 2027 (71.3%) women and 814 (28.7%) men with CVeD diagnosed by general practitioners. For the first time, the Numeric Rating Scale of 0 to 5 units was used to assess the intensity of pain. For the analysis, univariate and multivariate logistic and linear regressions were applied. Pain in the legs was reported by 90.5% of the patients. The occurrence of pain significantly (P < .001) increased with increasing C class. Of the patients who reported pain in the legs, 42.0% had moderate pain, 23.7% had moderate to severe pain, 22.8% had light pain, 11.2% had severe pain, and 0.3% had very severe pain. Severity of pain differed significantly (P < .001) according to C class. Light and moderate pain gradually decreased and severe pain gradually increased from C0 to C6 class. These associations remained significant after adjustment for age, body mass index, and family history of CVeD.

Iron concentrations in atherosclerotic plaque and serum in patients with carotid atherosclerosis.

The aim of this study was to investigate the iron concentrations in serum and carotid plaque in patients with different morphology of carotid atherosclerotic plaque and compared with other metal ions. Carotid endarterectomy due to the significant atherosclerotic stenosis was performed in 91 patients. Control group consisted of 27 patients, without carotid atherosclerosis. Atherosclerotic plaques were divided into four morphological groups, according to ultrasonic and intraoperative characteristics. Iron, copper and zinc concentration in plaque, carotid artery and serum were measured by spectrophotometry. Serum iron concentrations were higher in patients with hemorrhagic plaques in comparison to the control group (4.7 µmol/l ± 1.2 vs. 2.1 µmol/l ± 0.8, p < 0.05). Iron concentrations were higher in patients with hemorrhagic plaques in comparison to fibrolipid plaques (72.1 ± 14.3 µg/g vs. 39.3 ± 22.9 µg/g; p < 0.05). Negative significant correlation was found for zinc in serum and plaque iron concentration in patients (p < 0.05). We also demonstrated positive significant correlation for copper and iron in serum (p < 0.05). The data obtained in the current study are consistent with the hypothesis that high iron levels may contribute to atherosclerosis and its complications as factors in a multifactorial disease.

Copeptin level after carotid endarterectomy and perioperative stroke.

We evaluated the prognostic value of copeptin levels in a cohort of surgical patients after elective carotid endarterectomy (CEA). Twenty-one patients with perioperative stroke were prospectively recruited. The diagnosis of cerebrovascular event (CVE) was confirmed by computed tomography. Additionally, 21 patients with CEA without any complications (control patients) were enrolled. Blood samples were taken within 3 hours of the symptom onset. Circulating copeptin level was significantly higher in patients with CVE when compared to controls (P = .025), and significantly higher in nonsurvivors than in survivors (P = .030) after CVE. Plasma concentrations of interleukin 6 (IL-6) and C-reactive protein (CRP) were also elevated in patients with CVE (IL-6: P = .043; CRP: P = .002). We conclude that the activation of the stress axis in patients with CEA results with copeptin elevation, but more so in patients with perioperative stroke. Copeptin may be a helpful biomarker for stroke risk assessment in patients after CEA.

In situ revascularisation for femoropopliteal graft infection: ten years of experience with silver grafts.

PURPOSE: The purpose of this study was to analyze clinical outcome of patients for femoropopliteal graft infection who were treated by in situ reconstruction with a silver-coated prosthesis. BASIC METHODS: From December 2001 to December 2011, 27 patients were treated for femoropopliteal graft infection. Twenty patients (74%) were male and seven (26%) were female. Mean age was 65 years. The primary endpoint was recurrence of infection. Secondary endpoints were early and late mortality and morbidity, primary graft patency, major amputation rates and patient survival. PRINCIPAL FINDINGS: Early reinfection occurred in 11% and late in 8% of patients. Perioperative mortality was 7% and late was 4%. Above-knee amputation was performed in 4% of patients during early postoperative course and in 12% of patients during follow-up. Early and late graft patency was 96% and 72%, respectively. CONCLUSIONS: Results of in situ implantation of silver-coated grafts for femoropopliteal prosthesis infection are according to our opinion acceptable, but the risk of reinfection remains.

Anatomy and radiology of the variations of aortic arch branches in 1,266 patients.

BACKGROUND: The most reliable data about arterial variations, which are very important in surgery and radiology, can be obtained from a large series of patients. MATERIALS AND METHODS: We examined angiographic and multislice computerised tomography (MSCT) images in a group of 1,265 patients and in 1 dissected specimen. RESULTS: While in 946 (74.72%) of the patients a normal vascular pattern (type I) was noticed, in the remaining 320 (25.28%) patients variations of the branches of the aortic arch were found, which were classified into types II through VIII and a few subtypes. Type II (2.84%) comprised a common origin of the left commoncarotid and subclavian arteries. Type III (15.56%) was related to an origin of the left subclavian artery from the brachiocephalic trunk. Type IV (0.55%) included the aortic origin of both common carotid and subclavian arteries, with the right subclavian artery having a retroesophageal course. Type V (0.24%) included the same 4 supra-aortic branches, which, however, arose from a double or a right--sided aortic arch. Type VI (3.63%) comprised the aortic origin of the left vertebral artery, type VII (0.24%) the same origin of the right vertebral artery, and type VIII(2.22%) the aortic origin of the thyroideaima artery. A corresponding embryological background and clinical implications of the described aberrant vessels were presented. CONCLUSIONS: In more than one quarter of the cases, the branching pattern of the examined arteries did not follow the classical pattern. Detailed knowledge of aortic branch variations is of great significance in anatomy, embryology, and clinical medicine, especially in radiology and thoracic surgery.

Body mass index and primary chronic venous disease--a cross-sectional study.

OBJECTIVES: This study aims to investigate whether overweight and obesity are related to the clinical (C) category of clinical, etiologic, anatomic and pathophysiologic (CEAP) classification of chronic venous disease (CVD). DESIGN: A cross-sectional study. MATERIALS AND METHODS: The study was conducted in Serbia, in the year 2011. Men and women aged >18 years, consecutively coming to venous specialists because of venous problems in the legs, were included in the study. Patients demographic, anthropometric and clinical data were collected. For the analysis, univariate and multivariate logistic regressions were used. RESULTS: The study comprised 1116 subjects with primary CVD, 384 (34.4%) men and 732 (65.6%) women. Among them 464 (41.6%) were normal-weight patients (body mass index (BMI) < 25.0 kg m(-2)), 476 (42.7%) were overweight (BMI = 25.0-29.9 kg m(-2)) and 176 (15.8%) were obese (BMI ≥ 30.0 kg m(-2)). According to multivariate analysis, the CEAP C category of CVD was significantly more advanced in overweight and obese patients, the association being more pronounced in obese. Compared groups did not differ in the presence of venous reflux. In univariate analysis, venous obstruction was related to overweight and obesity but this association did not substantially affect the relationship between obesity and CEAP C categories of CVD. CONCLUSION: The CEAP C categories of CVD were significantly related to overweight and obesity, and this association was independent of age, sex and some other postulated risk factors.

Duplication of the superior vena cava associated with atrial termination of the left hepatic vein.

Duplication of the superior vena cava (SVC), associated with an aberrant left hepatic vein (LHV), was found in one of the 58 dissected specimens. The right SVC virtually showed a typical appearance. The persistent left SVC, which drained into the right atrium via the enlarged coronary sinus, was formed by the persistence of the left anterior cardinal vein. The LHV opened into the right atrium, due to the persistent left hepatocardiac channel. The left common carotid artery arose from the brachiocephalic trunk as a consequence of a regression of the embryonic aortic sac. The revealed venous and arterial variations seem to be the first reported vascular combination of this type.

Risk factors for chronic venous disease.

OBJECTIVE: Chronic venous disease (CVD) is a common problem in developing and developed countries. METHODS: A cross-sectional study, conducted in two major towns in Serbia, comprised 3225 subjects over 18 years old, enrolled in the survey consecutively by general practitioners (GPs) within their normal framework. Diagnosis of CVD was made by GPs on the basis of symptoms and visual examination. Data on potential risk factors were collected by the use of a questionnaire. RESULTS: The prevalence of CVD was significantly higher in women (73.7%) than in men (70.1%), although severe forms of CVD were significantly more frequent in men. Risk factors for CVD were age, body mass index ≥ 25.00 kg/m(2), family history of CVD, history of blood clots in veins and ever-smoking in both sexes, and menopause, increased number of child births and physical inactivity in women. CONCLUSION: The results obtained suggest the possibility of CVD prevention by modification of some behavioural risk factors.

Morphological and haemodynamic abnormalities in the jugular veins of patients with multiple sclerosis.

OBJECTIVES: Multiple areas of stenosis and different levels of obstruction of internal jugular and azygous veins (a condition known as cronic cerebrospinal venous insufficiency) recently emerged as an additional theory to the well-known autoimmune concept, explaining etiology of multiple sclerosis (MS). The aim of our study was to evaluate internal jugular vein (IJV) morphology and haemodynamic characteristics in patients with MS and compare it with well-matched healthy individuals and to evaluate the prevalence of venous flow abnormalities in both groups. METHODS: Sixty-four patients with clinically proven MS and 37 healthy individuals were included in our study. In all patients, IJV morphology and haemodynamic characteristics were evaluated by colour Doppler sonography as well as venous flow disorder. The patients were classified into four groups according to MS clinical form presentation. The prevalence of morphological and haemodynamic abnormalities in the IJV were assessed. RESULTS: The presence of stenosing lesion, mostly intraluminal defects like abnormal IJV valves, were observed in 28 patients (43%) in the MS group, and in 17 patients (45.9%) in the control group (P = NS). By adding haemodynamic Doppler information in the IJV venous outflow was significantly different in 42% of MS patients showing flow abnormalities (27/64), as compared with 8.1% of the controls (3/37), P < 0.001. CONCLUSION: In our group of patients, patients suffering from MS had significantly more IJV morphological changes and haemodynamic abnormalities when compared with healthy individuals not suffering from MS. These findings can be well demonstrated by non-invasive and cost-effective Doppler ultrasound.

Internal jugular vein duplication: a further truncular malformation in a patient with multiple sclerosis.

Different internal jugular vein (IJV) abnormalities can be found in patients with multiple sclerosis (MS): stenoses, complete occlusion, distortions and intraluminal structures, such as membranes, webs and inverted valves. IJV duplication is a very rare phenomenon. We report a case of right IJV duplication as an incidental finding during IJV morphological and haemodynamic assessment in a patient with MS. A 55-year-old female patient was admitted to our Institute for IJV and vertebral veins morphological and haemodynamic assessment. During the last seven years she had been treated for MS. Colour Doppler ultrasonography in our patient did not reveal IJV or vertebral veins stenoses or abnormal valves, but instead right IJV duplication. This finding was confirmed using multislice computed tomography angiography and by selective phlebography. In conclusion, to our knowledge, a case of IJV duplication in a patient with MS has not been described yet. This further venous malformation can be assessed by the means of Doppler ultrasounds.

Surgical reconstruction for unilateral iliac artery lesions in patients younger than 50 years.

BACKGROUND: To evaluate safety, short and long-term graft patency, clinical success rates, and factors associated with patency, limb salvage and mortality after surgical reconstruction in patients younger than 50 years of age who had undergone unilateral iliac artery bypass surgery. PATIENTS AND METHODS: From January 2000 to January 2010, 65 consecutive reconstructive vascular operations were performed in 22 women and 43 men of age < 50 years with unilateral iliac atherosclerotic lesions and claudication or chronic limb ischemia. All patients were followed at 1, 3, 6, and 12 months after surgery and every 6 months thereafter. RESULTS: There was in-hospital vascular graft thrombosis in four (6.1 %) patients. No in-hospital deaths occurred. Median follow-up was 49.6 ± 33 months. Primary patency rates at 1-, 3-, 5-, and 10-year were 92.2 %, 85.6 %, 73.6 %, and 56.5 %, respectively. Seven patients passed away during follow-up of which four patients due to coronary artery disease, two patients due to cerebrovascular disease and one patient due to malignancy. Limb salvage rate after 1-, 3-, 5-, and 10-year follow-up was 100 %, 100 %, 96.3 %, and 91.2 %, respectively. Cox regression analysis including age, sex, risk factors for vascular disease, indication for treatment, preoperative ABI, lesion length, graft diameter and type of pre-procedural lesion (stenosis/occlusion), showed that only age (beta - 0.281, expected beta 0.755, p = 0.007) and presence of diabetes mellitus during index surgery (beta - 1.292, expected beta 0.275, p = 0.026) were found to be significant predictors of diminishing graft patency during the follow-up. Presence of diabetes mellitus during index surgery (beta - 1.246, expected beta 0.291, p = 0.034) was the only variable predicting mortality. CONCLUSIONS: Surgical treatment for unilateral iliac lesions in patients with premature atherosclerosis is a safe procedure with a low operative risk and acceptable long-term results. Diabetes mellitus and age at index surgery are predictive for low graft patency. Presence of diabetes is associated with decreased long-term survival.

Relationship between education and atherosclerotic disease risk factors in patients with peripheral arterial disease.

AIM: The aim of the present study was to investigate whether different levels of education are associated with different atherosclerotic disease risk factors. METHODS: The cross-sectional study, involving 388 consecutive patients with verified peripheral arterial disease, was performed in Belgrade. Formal education level was used as a proxy for socioeconomic status. Anthropometric parameters and data on cardiovascular risk factors were analyzed in participants with different levels of education. In the analysis, univariate and multivariate logistic regressions were used. RESULTS: Multivariate analysis showed that low education was significantly positively related to alcohol consumption (Odds Ratio - OR, 4.67; 95% confidence interval - CI, 1.80-12.12), increased triglycerides (OR, 2.73; 95% CI, 1.13-6.61), and physical activity during work (OR, 43.10; 95% CI 14.37-129.28), and negatively related to former smoking (OR, 0.11; 95% CI, 0.03-0.46) and sports and leisure - time physical activity (OR, 0.13; 95% CI, 0.04-0.41 and OR, 0.25; 95% CI, 0.11-0.57). Medium education was significantly positively related to increased triglycerides (OR, 1.74; 95% CI 1.01-2.98) and increased LDL-cholesterol (OR 2.37; 95% CI, 1.35-4.18), and to physical activity during work (OR, 2.22; 95% CI, 1.34-3.67), and negatively related to age (OR, 0.95; 95% CI, 0.92-0.98) and leisure - time physical activity (OR, 0.47; 95% CI, 0.30-0.74). CONCLUSION: It can be concluded that if there are differences in the risk of the occurrence of peripheral arterial disease by education status, they could be only partly explained by differences in the observed atherosclerotic disease risk factors.

Dacron or ePTFE graft for above-knee femoropopliteal bypass reconstruction. A bi-centre randomised study.

BACKGROUND: The objective of this study was to compare polyester (Dacron) and expanded polytetrafluorethilene (ePTFE) grafts for above-knee femoropopliteal bypass. PATIENTS AND METHODS: Eighty five patients with disabling claudications or limb threatening ischemia suitable for above-knee femoropopliteal reconstruction were randomized into two groups. In the first group the surgery was performed using 8 mm Dacron graft, whereas the patients in the second group were operated using ePTFE grafts. RESULTS: The primary patency rates for Dacron and ePTFE were 100 %, and 88.37 % (p < 0.05), while secondary patency rates were 83.3 % and 75 % (p > 0.05) respectively. The early limb salvage rates for Dacron and ePTFE were 100 % and 97.7 % (p > 0.05). Early (30-day) complications (bleeding 2.38 % and 2.32 %; wound infection 11.9 % and 11.63 %) occurred in both groups with similar frequency (p > 0.05). The patients were followed up over a period of 6 to 12 months (mean 8.3 +/- 3.6 months). The overall mortality rate in the follow-up period was 2.38 % (one patient) for Dacron and 6.98 % (three patients) for ePTFE group (p > 0.05). Late graft infection was noted in three patients (7.1 %) in Dacron, and two patients (4.65 %) in ePTFE group (p > 0.05). Primary patency rates were not significantly influenced by obesity, diabetes, hypertension, hyperlipidemia, cigarette smoking, (p > 0.05). However, poor run-off (only one crural artery patent on preoperative angiography) significantly decreased patency of both grafts and favored the use of ePTFE graft (p < 0.05). CONCLUSIONS: This study confirms that both materials are suitable for above-knee femoropopliteal reconstructions. Above-knee femoropopliteal bypass does not have a good long-term prognosis in the presence of poor run-off.

Treatment of visceral artery aneurysms: retrospective study of 35 cases.

BACKGROUND: Visceral artery aneurysms (VAA) represent a rare clinical entity with possible life-threatening complications. The presentation, diagnosis and management vary accordingly to the artery involved and the underlying pathology. PATIENTS AND METHODS: During a 25-year period (1980-2005), 35 patients (25 males + 10 females, age range 36-73 years-median 59.2 years) with VAA were treated at two tertiary vascular surgery centers in Belgrade. All data were retrospectively collected from the patient's records. RESULTS: On presentation, 19/35 patients were symptomatic, and 3/35 had ruptured VAA. Surgery was performed in 28 cases; most commonly involved arteries were splenic (11), hepatic (5), celiac trunk (5), superior mesenteric (3), inferior mesenteric (3) and gastroduodenal (1). Fatal rupture occurred in two patients. In 5 patients abdominal aortic aneurysm was associated with VAA, and in 4 patients multiple aneurysms of the involved artery were noted. Successful embolization was performed in 3 patients. Overall, four patients were treated medically. In the surgically treated patients, perioperative mortality and morbidity were 11% (3/28) and 40% (10/25) respectively. Of 25 patients included in the long-term follow up, six died. CONCLUSION: Since VAA have considerable tendency to rupture, an active approach is necessary. Based on our experience, surgical treatment could be recommended for any VAA patient with symptoms. In addition, we believe that the choice of the therapeutic procedure should be made on an individual basis.

Single center experience on eversion versus standard carotid endarterectomy: a prospective non-randomized study.

BACKGROUND AND PURPOSE: The prospective studies that have compared the outcomes of eversion and standard longitudinal carotid endarcterectomy (CEA) have been few and small and available data to reach definitive conclusions are still scarce. This prospective, non-randomized study sought to compare eversion and standard CEA for early and late mortality and morbidity and the incidence of late restenosis. METHODS: Between 1992 and 1997, we performed 2806 CEAs in 2469 patients (2124 eversion CEAs in 1859 patients and 682 standard CEAs in 610 patients). All patients underwent preoperative neurological examination and cervical duplex scanning. Patients were followed up by neurological evaluation and duplex scanning at 1 and 6months after CEA, and yearly afterwards. RESULTS: Demographics and neurologic inidications for CEA were similar in both groups. Mean clamping time was shorter in the eversion CEA group (13.5+/-6.1 vs 19.9+/-19.1min, P<0.001). Early (30-day) postoperative mortality due to major stroke was lower after eversion CEA (10/2124 vs 9/682, P=0. 037), as well as total cardiovascular mortality (16/2124 vs 12/682, P=0.038). Early carotid occlusion was more frequent in standard CEA group (12/2124 vs 11/682, P=0.017), as well as total early morbidity (112/2124 vs 53/682, P<0.001). During follow-up (mean 56 months, range 6-92), restenosis rate was lower in the eversion CEA group (0. 5 vs 1.8%, P=0.006). CONCLUSIONS: Our data indicate that eversion CEA as compared to standard CEA technique is associated with lower total cardiovascular perioperative mortality and mortality due to major stroke, shorter clamping time, lower early occlusion rate, and lower late restenosis rate.