Andrea Di Renzo

Prevention of edema, flight microangiopathy and venous thrombosis in long flights with elastic stockings. A randomized trial: The LONFLIT 4 Concorde Edema-SSL Study.

The LONFLIT1/2 studies have established that in high-risk subjects after long (> 10 hours) flights the incidence of deep venous thrombosis (DVT) is between 4% and 6%. The LONFLIT4 study has been planned to evaluate the control of edema and DVT in low-medium-risk subjects. The aim of this study was to evaluate edema and its control with specific flight stockings, in long-haul flights. In the first part of the study 400 subjects at low-medium risk for DVT were contacted; 28 were excluded for several nonmedical problems; 372 were randomized into 2 groups to evaluate prophylaxis with stockings in 7-8-hour flights; the control group had no prophylaxis. Below-knee, Scholl, Flight Socks, producing 14-17 mm Hg of pressure at the ankle, were used in the treatment group. The occurrence of DVT was evaluated with high-resolution ultrasound scanning (femoral, popliteal, and tibial veins). Edema was assessed with a composite score based on parametric and nonparametric measurements. Part II: In this part of the study 285 subjects at low-medium risk for DVT were included and randomized into 2 groups to evaluate edema prophylaxis in 11-12-hour flights; the controls had no prophylaxis while the prevention group had below-knee, Scholl, Flight Socks (comparable to part I). Results. Part I: DVT evaluation. Of the 184 included subjects in the stockings group and 188 in the control group, 358 (96.2%) completed the study. Dropouts were due to compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 179 subjects (mean age 49; SD 7; M:F = 101:78), none had DVT or superficial thromboses. Control Group: of 179 subjects (mean age 48.4; SD 7.3; M:F = 98:81), 4 (2.2%) had a DVT. There were also 2 superficial thromboses. In total, 3.35% (6) subjects had a thrombotic event. The difference (p < 0.002) is significant. Intention-to-treat analysis detects 15 failures in the control group (9 lost + 6 thromboses) out of 188 subjects (7.9%) versus 5 subjects (2.7%) in the stockings group (p < 0.05). All thrombotic events were observed in passengers sitting in nonaisle seats. The tolerability of the stockings was very good and there were no complaints or side effects. Thrombotic events were asymptomatic. No difference was observed in the distribution of events between men and women. The 3 women who had a thrombotic event were taking low-dose, oral contraceptives. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 6.7 (3.1) in controls; in the stockings group the score was 2.9 times lower (p < 0.05). The control of edema with stockings was clear considering both parametric (circumference, volume) and nonparametric (analogue scale lines) data. Part II: DVT evaluation. Of the 285 included subjects, 271 (95%) completed the study. Dropouts were due to low compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 142 subjects (mean age 48; SD 8; M:F = 89:53), none had DVT or superficial thromboses. Control Group: of 143 subjects (mean age 47; SD 8; M:F = 87:56), 3 had a popliteal DVT and 3 a superficial thrombosis. In total, 4.2% (6) subjects had a thrombotic event. The difference (p < 0.02) between groups is significant. Intention-to-treat analysis detects 14 failures in the control group (8 lost + 6 thromboses = 9.7%) versus 6 (all lost = 4.2% in the stockings group) (p < 0.05). Four of 6 events (3 DVT + 1 SVT) were observed in non-aisle seats. The tolerability of the stockings was very good. No difference was observed in the distribution of events between men and women. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 8.08 (2.9) in controls while in the stockings group the score was 2.56 (1.5) (p < 0.005). In conclusion. Scholl Flight Socks are very effective in controlling edema. Also this type of compression is effective in significantly reducing the incidence of DVT and thrombotic events in low-medium-risk subjects, in long-haul flights. Conclusions: Considering these observations, Flight Socks are effective in controlling edema and in reducing the incidence of DVT in low-medium-risk subjects, in long-haul flights (7-11 hours).

Pycnogenol® Improves Microcirculation, Retinal Edema, and Visual Acuity in Early Diabetic Retinopathy

PURPOSE The growing numbers of diabetes cases in the developed world are followed by increasing numbers of people diagnosed with diabetic complications. Diabetic microangiopathies in the eye lead to the development of retinopathy involving gradual loss of vision. Previous studies with Pycnogenol showed effectiveness for stopping progression of preproliferative stages of retinopathy. The aim of our study was to show protective effects of Pycnogenol in early stages of retinopathy, characterized by mild to moderate retinal edema in the absence of hemorrhages or hard exudates in the macula center. METHODS Following treatment with Pycnogenol (24 patients) for 3 months, retinal edema score (dilated ophthalmology) and retinal thickness (high resolution ultrasound) showed statistically significant improvement as compared to the placebo group (22 patients), which showed negligible changes to baseline. Laser Doppler flow velocity measurements at the central retinal artery showed a statistically significant increase from 34 to 44 cm/s in the Pycnogenol group as compared to marginal effects in the control group. RESULTS The major positive observation of this study is the visual improvement, which was subjectively perceived by 18 out of 24 patients in the Pycnogenol group. Testing of visual acuity using the Snellen chart showed a significant improvement from baseline 14/20 to 17/20 already, after 2 months treatment, whereas no change was found in the control group. CONCLUSIONS Pycnogenol taken at this early stage of retinopathy may enhance retinal blood circulation accompanied by regression of edema, which favorably improves vision of patients.

Prevention of Influenza Episodes With Colostrum Compared With Vaccination in Healthy and High-Risk Cardiovascular Subjects The Epidemiologic Study in San Valentino

The efficacy of a 2-month treatment with oral colostrum in the prevention of flu episodes compared with antiinfluenza vaccination was evaluated. Groups included healthy subjects without prophylaxis and those receiving both vaccination and colostrum. After 3 months of follow-up, the number of days with flu was 3 times higher in the non-colostrum subjects. The colostrum group had 13 episodes versus 14 in the colostrum + vaccination group, 41 in the group without prophylaxis, and 57 in nontreated subjects. Part 2 of the study had a similar protocol with 65 very high-risk cardiovascular subjects, all of whom had prophylaxis. The incidence of complications and hospital admission was higher in the group that received only a vaccination compared with the colostrum groups. Colostrum, both in healthy subjects and high-risk cardiovascular patients, is at least 3 times more effective than vaccination to prevent flu and is very cost-effective.

Circulating endothelial cells in venous blood as a marker of endothelial damage in chronic venous insufficiency: improvement with venoruton.

Damage to endothelial cells is common in vascular disorders and in reactions associated with transplantation. An elevated number of circulating endothelial cells indicates the extent of endothelial damage in a variety of disorders. In chronic venous insufficiency (CVI), the number of endothelial cells is abnormally increased, and this can be considered an important indication of endothelial damage. A group of 23 subjects with two levels of CVI (severe and very severe with previous ulcerations) with an increased endothelial cell count (seen by microscopy) was studied and treated for 4 weeks with oral Venoruton (0-[beta-hydroxyethyl]-rutosides) (1 g/day) to evaluate the effects of treatment on the circulating endothelial cells in blood taken from a peripheral leg vein. The controls comprised two groups with comparable age and sex distribution, one of healthy individuals and one of CVI subjects. After 4 weeks, a significant decrease was noted in endothelial cells both in subjects with CVI and in those with very severe CVI with previous ulcerations. This study suggests that endothelial cells may play a significant role in venous disease, being both an indication of severe disease and a further problem in itself. The use of Venoruton appears to decrease the number of circulating endothelial cells. This suggests an important role of this compound in protecting the endothelium and offers new potentially important therapeutic options that are not limited only to venous disease.

5-Year Control and Treatment of Edema and Increased Capillary Filtration in Venous Hypertension and Diabetic Microangiopathy Using O-(β-Hydroxyethyl)-Rutosides: A Prospective Comparative Clinical Registry

This independent prospective controlled trial evaluates the efficacy of O-(β-hydroxyethyl)-rutosides (HR) during 5 years of administration against signs and symptoms and further degeneration of microcirculatory disturbances. The protective effect of HR in preventing end-point complications such as venous ulceration is evaluated. This study is based on evaluation of edema and the capillary filtration rate (CFR) in association with a clinical score scale. Patients having a severe degree of chronic venous insufficiency (CVI) and venous microangiopathy and completing at least 5 years of treatment are included. The following 4 groups are considered: group A (patients with CVI but without diabetes mellitus, receiving 1500 mg/d of HR), group B (patients with CVI and diabetes mellitus, receiving 2 g/d of HR), group C (control subjects receiving no pharmacologic or compression treatment), and group D (patients using elastic compression stockings only). All patients received the “best” available treatment. No adverse effects or intolerance is noted, with good compliance (>85%). In group A, there is a statistically significant decrease in the CFR during 5 years of follow-up. In group B, the decrease in the CFR is greater than that in group A. Reductions in edema, swelling, and the CFR during 5 years are notable, and values approach normal levels. During 5 years, HR is effective in treating venous edema and hypertension and in preventing deterioration of the distal venous system. The prevention of ulcerations with HR is another important observation. The effects of HR seem to be partially dose related, and tolerability and compliance are good.

O-(β-Hydroxyethyl)-Rutosides Systemic and Local Treatment in Chronic Venous Disease and Microangiopathy: An Independent Prospective Comparative Study

O-(β-hydroxyethyl)-rutosides (HR) is used to treat chronic venous disease and signs and symptoms of chronic venous insufficiency (CVI), varicose veins, and deep venous disease. This independent prospective controlled trial (a registry study) evaluates how the efficacy of HR at the local level (perimalleolar region) can be increased by the administration of a topical HR gel. The study is based on evaluation of microcirculatory variables in patients with severe CVI (ambulatory venous pressure, >56 mm Hg) and venous microangiopathy. Patients are treated using 1 of the following 3 regimens: oral treatment with 1-g sachets of HR (2 g/d total) plus topical HR 2% gel applied 3 times daily at the internal perimalleolar region; oral treatment only (same dosage), or light elastic compression stockings. Laser Doppler skin flux at rest, skin flux at the perimalleolar region, and transcutaneous PO2 and PCO2 are measured at baseline and at the end of the treatment period. A comparable group of healthy individuals without treatment is observed for 8 weeks. In the treatment groups, flux is increased, PO2 is decreased, and PCO2 is increased compared with normal skin. At 4 and 8 weeks, the improvement in skin flux (which is decreased by all measurements), the increase in PO 2, and the decrease in PCO2 (indicating microcirculatory improvement) are statistically significantly greater in the combined oral plus topical treatment group (P < .05). No adverse effects, tolerability problems, or compliance issues are noted. These results indicate an important role of HR in the treatment and control of CVI and venous microangiopathy.

Control of Edema in Hypertensive Subjects Treated With Calcium Antagonist (Nifedipine) or Angiotensin-Converting Enzyme Inhibitors With Pycnogenol

The presence of edema in different phases and stages of essential hypertension may be due to antihypertensive treatment. Some drugs may cause edema by inducing vasodilatation, increasing the capillary exchange surface and capillary filtration. Pycnogenol has an important anti-edema effect in diabetic microangiopathy and chronic venous insufficiency. This 8-week study evaluated capillary filtration in 2 comparable treatment groups with hypertension treated with a calcium antagonist (nifedipine) or angiotensin-converting enzyme inhibitor to define its efficacy in preventing edema caused by antihypertensives. A significant decrease in filtration was observed in the Pycnogenol groups. Pycnogenol controls this type of edema, it helps to prevent and limit long-term damage in the microcirculation in hypertensive patients, and allows the dose of anti-hypertensive drugs to be reduced in most patients.

The LONFLIT4-Venoruton Study: a randomized trial--prophylaxis of flight-edema in venous patients.

The aim of this independent study was to evaluate the protective effects, on the development of flight edema, of Venoruton. The study included patients with venous disease traveling in economy in long-haul flights (9 hours). Edema is a relevant aspect of long-haul flights affecting both patients with venous disease and normal subjects. Microcirculatory variations during flights cause a microangiopathy and biochemical and coagulation alterations. This condition may be defined as flight microangiopathy. A group of 203 subjects with chronic venous disease (uncomplicated varicose veins) at low-medium risk for DVT were contacted; 43 subjects were excluded for several nonmedical, travel-related problems or inconvenient eval uation time; the remaining 160 were randomized, after informed consent, into 2 groups to evaluate 2 prophylaxes in 7-8-hour, long-haul flights: The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. The edema score was based on the edema tester, ankle circumference, volume measurements, subjective swelling, and discomfort score. Items 1, 4, and 5 are based on an analogue scale line (1 to 10) directly defined by the subjects before and after the flights. Of the 160 included subjects 139 completed the study. Dropouts (21) were due to poor compliance, traveling, and/or connection problems (11 in the control group, 10 in the treatment group). Age and sex distribution were comparable in the 2 groups as were risk factors distributions. The level of edema at inclusion was comparable in the 2 groups of subjects. After the flight there was an average score of 7.2 (sd 2) in the control group, while in the Venoruton group the score was on average 3.2. (sd 1.1) (p < 0.05), 2.25 times lower than in the control group (p < 0.05). In the control group 89% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspec tion and associated with discomfort. In the Venoruton group edema was clearly present in 12% of subjects (associated with discomfort between 5 and 7 on the analogue scale line) and it was mild-moderate, not associated with symptoms (pain, discomfort between 2 and 4 on the analogue scale line). Therefore, the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and nonparametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for patients treated with Venoruton. No deep vein thrombosis or superficial vein thrombosis was observed in this study.

Kidney Flow and Function in Hypertension: Protective Effects of Pycnogenol in Hypertensive Participants—A Controlled Study

This study evaluated the effects of Pycnogenol as an adjunct to angiotensin-converting enzyme (ACE)-inhibitor ramipril treatment of hypertensive patients presenting with early signs of renal function problems. One group of 26 patients was medicated with 10 mg ramipril per day only; a second group of 29 patients took Pycnogenol in addition to the ACE inhibitor over a period of 6 months. At trial end, a lowered systolic and diastolic blood pressure was found in both groups, with a significant further reduction of diastolic pressure in the group given Pycnogenol in addition to ramipril. The major aim of this study was the investigation of kidney-protective effects of Pycnogenol. Urinary albumin decreased from 87 ± 23 to 64 ± 16 mg/d with ramipril only. Additional Pycnogenol lowered albumin significantly better from 91 ± 25 to 39 ± 13 mg/day (P < .05). In both groups, serum creatinine was lowered; however, only in the combination treatment group did the effect reached statistical significance. In both groups, CRP levels decreased from 2.1 to 1.8 with ramipril and from 2.2 to 1.1 with the ramipril—Pycnogenol combination; the latter reached statistical significance. Kidney cortical flow velocity was investigated by Doppler color duplex ultrasonography. Both systolic and diastolic flow velocities increased significantly after 6 months medication with ramipril. The addition of Pycnogenol to the regimen statistically significantly further enhanced kidney cortical flow velocities, by 8% for diastolic flow and 12% for systolic flow, relative to values found for the group taking ramipril only. The protective effects of Pycnogenol for initial kidney damage found in this study warrant further research with a larger number of patients and over a longer period of time.

The LONFLIT4-VENORUTON Study A Randomized Trial Prophylaxis of Flight-Edema in Normal Subjects

This study evaluated the protective effects of Venoruton on the development of flight edema in normal subjects travelling in economy in long-haul flights (8-9 hours). Edema is a relevant aspect of long-haul flights affecting both venous patients and normal subjects. Edema and flight microangiopathy were studied in a group of 164 subjects randomized (after informed consent) into two groups to evaluate prophylaxis in 8 to 9-hour flights. The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. Edema was evaluated with a composite edema score based on the edema tester, on the measurements of ankle circumference, volume measurements, subjective swelling, and on a discomfort score. Items 1, 4, and 5 are based on an analogue scale line (I to 10) directly defined by the subjects before and after the flights. Of the included subjects, 151 completed the study. Dropouts were due to poor compliance, travelling, or connection problems. Age and gender distribution were comparable in the two groups as were risk factor distributions. The level of edema at inclusion was comparable in the two groups of subjects. After the flight there was an average score of 6.7 (SD 1.7) in the control group, while in the Venoruton group the score was on average 3 (SD 1.1) (p < 0.05). In the control group 77% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspection and associated with discomfort. In the Venoruton group, edema was clearly present only in 8% of subjects (associated with discomfort rated between 3 and 6 on the analogue scale line) and it was mild, not associated with symptoms. Therefore the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and non-parametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for subjects under prophylaxis with Venoruton.