Pycnogenol® supplementation to relieve symptoms after hemorrhoidectomy.

BACKGROUND: Hemorrhoids are a common problem associated with symptoms, like swelling, local thrombosis and generally with a decreased quality of life, often in otherwise healthy subjects. Hemorrhoids can be classified by grades (I to IV) according to their severity. In this registry study subjects treated with excisional hemorrhoidectomy (EH) for the first time, were included. After surgery, edema tends to complicate surgical areas causing relevant symptoms. Most hemorrhoids symptoms are related to alterations in bowel habits. Increase in diet fibers to avoid constipation, exercise, and limiting straining reduce recurrence after surgery. METHODS: The aim of the registry study was to evaluate the effects of Pycnogenol® (Horphag Research, Geneva, Switzerland) on relieving postoperative symptoms following hemorrhoidectomy. Pycnogenol® 150 mg/day was used between one month before surgery up to one month after surgery. The main postoperative symptoms were scored. RESULTS: Thirty-eight subjects completed the 60-day supplement registry study. Eighteen subjects were supplemented with Pycnogenol® in addition to the standard management (SM) and 20 subjects only received SM and were considered as controls. The two groups were comparable for age, sex and main symptoms distribution and for their clinical characteristics at inclusion. No other disease was present. The scores for pain, discomfort, and constipation were significantly lower with the supplement compared to controls (P<0.05) 10 and 30 days after surgery. In addition, the quality-of-life score was higher with Pycnogenol® (P<0.05) while bleeding (minimal, not clinically evaluable) and a possible residual anal stenosis (requiring a longer period of observation) were barely observed. A satisfactory return to activity was observed 30 days after surgery in the 18 subjects using Pycnogenol®, and in only 15 out of 20 patients (75%) in the control group (P<0.05). All Pycnogenol® subjects were able to drive and perform daily tasks in comparison with 14 out of 20 subjects in the control group. The proportion of patients that took pain medication from day 10 to 30 post-surgery was significantly lower in the Pycnogenol® group than in controls (P<0.05). CONCLUSIONS: In this post-surgical pilot, registry study, Pycnogenol® was effective in preventing and controlling postoperative symptoms after hemorrhoidectomy. To confirm the results, more cases are needed, including different surgical methods and clinical conditions. Mucosal and cutaneous edema and perianal swelling - generally seen after surgery - seem to be clearly reduced with Pycnogenol® and the supplement intake was associated with a more regular and pain-controlled convalescence and healing.

Pycnogenol® improves cognitive function in post-stroke patients: a 6 month-study.

BACKGROUND: This pilot study in post-stroke patients evaluated the effects of supplementation with Pycnogenol® on alterations in cognitive functions (COFU) over a period of 6 months, starting 4 weeks after the stroke. METHODS: The effects of supplementation - possibly acting on residual brain edema, on global cognitive function, attention and on mental performance - were studied. A control group used standard management (SM) and the other group added Pycnogenol®, 150 mg daily to SM. RESULTS: 38 post-stroke patients completed the 6-month-study, 20 in the Pycnogenol® group and 18 in the control group. No side effects were observed with the supplement. The tolerability was very good. The patients included into the two groups were comparable for age, sex and clinical distribution. There were 2 dropouts in the control group, due to non-medical problems. Main COFU parameters (assessed by a cognitive questionnaire) were significantly improved (all single items) with the supplement compared to controls (P<0.05). Additional observations indicate that Pycnogenol® patients experienced significantly less mini-accidents (including falls) than controls (P<0.05). The incidences of (minor) psychotic episodes or conflicts and distress and other problems including rare occurrence of minor hallucinations, were lower with the supplementation than in controls (P<0.05). Single observations concerning daily tasks indicated a better effect of Pycnogenol® compared to controls (P<0.05). Plasma free radicals also decreased significantly with the supplement in comparison to controls (P<0.05). Globally, supplemented subjects had a better recovery than controls. CONCLUSIONS: In post-stroke subjects, Pycnogenol® supplementation resulted in better recovery outcome and faster COFU 'normalization' after the stroke in comparison with SM; it can be considered a safe, manageable post-stroke, adjuvant management possibly reducing local brain edema. Nevertheless, more patients and a longer period of evaluation are needed to confirm these results.

Positive effects of Pycnogenol®-Centellicum® on venous elasticity: an ex-vivo concept study.

BACKGROUND: The aim of this ex-vivo study was to evaluate the efficacy of Pycnogenol®-Centellicum® oral supplementation on vein segments, retrieved from graft harvesting or from vein surgery. The parameters assessed were elasticity and recovery after dynamic tests: 1) an enlargement stress; 2) an elongation stress; and 3) elasticity after torsion. The tests were made in standardized conditions, less than 3 hours after explant, at 22 °C by the same operator with surgical and microsurgical experience. METHODS: Veins of 59 subjects were included in the study: 17 subjects with normal veins with a planned bypass graft and 42 subjects with varicose veins. Of the subjects with normal veins, 8 subjects followed standard management (group 1) and 9 took Pycnogenol®-Centellicum® for 4 weeks before surgery (group 2). In the group with varicose veins, 22 subjects served as controls (group 3) and 20 were supplemented with Pycnogenol®-Centellicum® for 4 weeks before surgery (group 4). No side effects or tolerability problems were observed in the supplementation period before surgery and veins harvesting. The full return to initial shape/sizes after dynamic stress was evaluated in 1 min after removing the stress. RESULTS: In group 1, 4 out of 8 vein segments recovered their size after forced enlargement vs. 7/9 in the Pycnogenol®-Centellicum® group 2 (P<0.05). In the elongation test, 3/8 normal control vein segments recovered their length (group 1) vs. 7/9 in the supplement group (group 2) (P<0.05). In the torsion test, 4/8 (group 1) veins recovered their shape after torsion vs. 9/9 veins in Pycnogenol®-Centellicum®-pretreated segments (group 2) (P<0.05). Only 45.8% of normal, control vein segments (group 1) recovered their shape/size in comparison with 85.2% of normal vein segments in the supplement group (group 2) (P<0.05). In group 3 and 4 (segments of varicose veins), the proportion of vein segments with enlargements, elongation and torsion were significantly lower at the end of the test (P<0.05) in the Pycnogenol®-Centellicum® group 4 with 51.7% of the vein segments recovering their shape in the Pycnogenol®-Centellicum® vs. 16.6% of the vein segments recovering their shape in control segments (P<0.05). Results show that Pycnogenol®-Centellicum® supplementation allows vein segments to better return to their original shape/size after a morphological alteration of shape (in different directions). This could be an expression of an improved wall tone and elasticity of the veins. No vein was teared or damaged during the 59 tests indicating that all stresses were well within the normal wall tensile characteristics of the veins. CONCLUSIONS: In this study, Pycnogenol®-Centellicum® improved vein elasticity in subjects with normal and varicose veins as vein segments were more elastic (able to recover length and shape) and less passively dilated by high pressure or dynamic stresses. This study indicates that the protective effects of Pycnogenol®-Centellicum® may partially stop passive dilatation of veins to varicose veins over time by improving vein elasticity. Pycnogenol®-Centellicum® managed vein segments return more rapidly back to the initial dimensions, shapes and diameters after a dynamic stress.

Pycnogenol® supplementation prevents inflammation and symptoms in recurrent, non-severe urinary infections.

BACKGROUND: The aim of this pilot, registry study was to evaluate the prophylactic effects of oral supplementation with Pycnogenol® (150 mg/day) in subjects with previous history of recurrent (urinary tract infections (UTI) in a 2-month open follow-up. METHODS: subjects with recurrent-UTIs, defined by: 1) at least three symptomatic UTIs over the past year; 2) two episodes of UTI's in the past six months; 3) symptoms of UTIs with urinalysis without bacterial presence, were included in the study. Pycnogenol® was supplemented at the dose of 150 mg/day for 2 months. RESULTS: The two groups of subjects (supplement and controls, each including 25 subjects) were demographically and clinically comparable at baseline. No side effects or tolerability problems were observed. The registry evaluated the number of recurrent UTIs in two months; there was a limited decrease in the rate of recurrent UTIs, in comparison with the period before inclusion of 9.93% in the standard management group in comparison with a more important decrease in the Pycnogenol® group (-50.1%; P<0.05). The number of episodes decreased from 3.22±0.4 to 2.9±0.3 in the control group in 2 months versus a decrease from 3.1±0.5 to 1.6±0.6 in the Pycnogenol® group. The number of infection-free subjects at the end of the two-month registry study was significantly higher with the supplement (P<0.05) than in controls. Oxidative stress measured as plasma free radicals at inclusion was 388±22 Carr units in the control group and resulted unchanged (not significant) at the end of the study (379±21 Carr units). In the supplement group, there was a significant decrease in oxidative stress from 389±24 to 227±14 Carr units at the end of the study (P<0.05). CONCLUSIONS: This pilot registry indicates that prophylaxis with Pycnogenol® decreases the occurrence of UTIs both in men and women without side effects and with a good tolerability. The effects of Pycnogenol® in these patients - including the control of oxidative stress - may be very important, particularly when a predominantly inflammatory component (UTI without infection or with a minimal bacterial component due to bacterial fragments) is present and maintains the inflammatory process.

Chronic venous insufficiency and venous microangiopathy: management with compression and Pycnogenol®.

BACKGROUND: The aim of this prospective supplement summer registry study was to evaluate the efficacy of Pycnogenol® in controlling symptoms of chronic venous insufficiency (CVI) and microcirculatory parameters: venous hypertension and microangiopathy. Pycnogenol® (Horphag Research) is the standardized extract of the bark of Pinus Pinaster. METHODS: During the summer period between June and August 142 patients were split into three groups: 1) Pycnogenol® 150 mg/day; 2) compression stockings; 3) and compression + Pycnogenol®. RESULTS: Venous pressure (ambulatory venous pressure, AVP) and refilling time (RT), microcirculatory and clinical measurements were comparable at inclusion. At 8 weeks variations in skin flux (RF), rate of ankle swelling (RAS), skin PO2-PCO2, Analogue Symptomatic Score (ASLS), Venous Disability and severity Scores and local oxidative stress (OS) indicated a statistically significant improvement by Pycnogenol® both as a single supplement and in association with compression in comparison with baseline. Pycnogenol® significantly improved the microcirculation in comparison with compression (P<0.05). The combined effects of Pycnogenol+compression produced the best results in most measurements. The summer study penalized compression - in a very hot summer - with many drops out. No side effects due to supplementation were observed; tolerability was optimal. The tolerability to stocking was less than optimal (70% of compression not correctly used). Pycnogenol® alone was more effective than compression alone. The increase (P<0.05) in skin O2 and the decrease in PCO2 were associated with the decrease in skin flux. The variations in capillary filtration (RAS) were the most important microcirculation changes. RAS is directly associated with swelling, the hallmark of CVI. Pycnogenol® in both Pycnogenol groups significantly improved RAS in comparison with compression only (P<0.05). The decrease in OS in both Pycnogenol® groups was significant in comparison with compression only (P<0.05). A lower OS is an important micro-metabolic indication of a better capillary bed with better nutritional, perfusional exchanges. The clinical measurements followed the patterns of the microcirculation with the supplement groups performing statistically better (P<0.002) than the compression-only. CONCLUSIONS: This "summer registry" study confirms the clinical and microcirculatory efficacy of Pycnogenol in CVI and venous microangiopathy. The study indicates the significant clinical role of Pycnogenol® (both as a single treatment and in association with compression) in the management, treatment and control of this common clinical problem.

Prevention of recurrent venous thrombosis and post-thrombotic syndrome.

BACKGROUND: This retrospective registry study evaluated different managements on the development of post-thrombotic syndrome (PTS) and recurrent deep venous thrombosis (R-DVT). The effects of aspirin (100 mg/day), added to the "standard management" (SM) (IUA consensus), were observed in patients after a proximal DVT. METHODS: The study started after the anticoagulant period. Comparable groups used the mild-antithrombotic agent Pycnogenol® (200 mg/day), ticlopidine (250 mg/day) or sulodexide (500 ULS/day). RESULTS: The groups were comparable for sex and age distribution and clinical pictures. In the SM group, 222 patients completed the follow-up (72 months). With SM, the percentage of patients with R-DVT (requiring anticoagulants) was 17.2%; 19.8% of SM patients had a PTS. In the aspirin group (202 subjects), R-DVT was observed in 14.8% of patients; 17.32% had a PTS. The reduction in R-DVT and PTS with aspirin was significant (P<0.05) vs. the SM. There was no tolerability problem in subjects using Pycnogenol® (137 patients); they had a much lower incidence of R-DVT (5.8%) and PTS (6.5%) vs. SM and aspirin (P<0.05). Ticlopidine (121 patients) reduced the incidence of R-DVT (12.4%) and PTS (19.8% of patients) (P<0.05 vs. SM). With sulodexide the incidence of R-DVT was 6.7% (P<0.05 vs. SM); the incidence of PTS was 16.6% (P<0.05 vs. SM). The combined R-DVT+PT syndrome was observed in 14.9% of subjects using SM and in 12.9% of subjects using aspirin (P<0.05 vs. SM), in 3.6% of subjects managed with Pycnogenol® (<0.05% vs. aspirin and all other managements). The incidence was 10.74% with ticlopidine and 6.7% with sulodexide (both significantly lower than SM). CONCLUSIONS: Interaction between PTS and R-DVT are complex; recurrences cause more PTSs, and a post-thrombotic limb is prone to R-DVT. Aspirin, for patients that can tolerate it, reduces the occurrence of PTS and R-DVT. In addition, ticlopidine and sulodexide are effective. Pycnogenol® is the most effective and safe for R-DVT and particularly PTS. Its full range of anti-thrombotic activity is now under evaluation.

Robuvit®: improvement of fatigue in medical convalescence.

BACKGROUND: The aim of this registry study was the evaluation of symptoms of fatigue following supplementation with an oak wood extract (Robuvit®) after disappearance of acute symptoms. Robuvit®, with established antioxidant-antifatigue activity, has been successfully used in hepatic failure and in chronic fatigue syndrome: these conditions are characterized by weakness and fatigue and are broadly comparable to convalescence that is associated to increased oxidative stress. METHODS: The registry study lasted 3 weeks. After a period (7-10 days) of flu, during the post-disease period (3 days without disease) subjects were included into the study. One group of subjects was supplemented with Robuvit® (300 mg/day) in addition to a standard management (SM) plan, another group of patients was treated with the standard management only. RESULTS: The SM and the supplement group were comparable in all convalescence parameters at inclusion. Weakness and heart rate were significantly reduced with Robuvit® in comparison with the controls (P<0.05) at 10 days and at 3 weeks; Attention and sleep patterns improved significantly at 3 weeks with Robuvit® (P<0.05) in comparison to controls. Recovery after efforts was normalized at 10 days in the supplement group, significantly better versus controls (P<0.05). O2 saturation increased significantly with Robuvit® at 10 days in comparison to controls (P<0.05). The alterations in working/concentration capacity were better improved with the supplement (P<0.05). Oxidative stress was significantly decreased (P<0.05) in comparison to controls. The improvement of health according to the Karrnofsky Scale was significantly more pronounced in the Robuvit® group (P<0.05). The supplement was well tolerated. CONCLUSIONS: The causative relations between Robuvit® supplementation, oxidative stress, vigor and fatigue in convalescence need more specific evaluations in a larger number of subjects. This preliminary study may indicate a possible supplementation in convalescence.

Centella asiatica (Centellicum®) facilitates the regular healing of surgical scars in subjects at high risk of keloids.

BACKGROUND: Formation of scars after surgical incisions requires the proper appositions of elements contributing to the scarring process. The structural rebuilding of damaged tissues is essential in producing a linear scar. The excess of blood, foreign particles, exuberant sutures, necrotic tissue, possible infective agents, as well as the ongoing inflammatory process may produce a non-linear, sometimes painful keloidal scar. Centella asiatica (CA) extracts have been used topically since ancient times for preventing keloids (i.e. after extensive burns) and for other applications including ulcer healing. The aim of this registry study was to evaluate the effect of supplementation with Centellicum® (Horphag Research Ltd.) on the healing of surgical wounds in subjects with previous hypertrophic or keloid scars, and to identify with ultrasound the collagen components of the scar in order to assess the quality (or linearity) of surgical wounds. METHODS: Subjects with history of hypertrophic scars or keloid following previous surgery were included in this registry. Short term antibiotic prophylaxis was used as per surgical standards with cephalosporins for three days maximum after surgery. Only patients receiving abdominal or knee surgery were included. A total of 129 patients were included: 64 in the control group treated only with standard management, and 65 in the active treatment group where CA supplementation with Centellicum® was used at the dose of two 225 mg capsules/day from the 2nd to 6th week after surgery. RESULTS: A total of 64 scars were analyzed within the control group and 65 in the supplement group. The tolerability to Centellicum® was overall good, and no side effects were reported. Compliance to treatment was optimal, with >98% of the CA capsules correctly used. The ultrasound-assessed scar tissue regularity was on average lower in controls than in supplemented subjects (P<0.05). Scars also appeared to be significantly more homogeneous in CA patients than in controls. CONCLUSIONS: Supplementation with Centellicum® is safe and does not interfere with other concomitant treatments. It is well tolerated and compliance to treatment is optimal.

Postpartum Varicose Veins: Supplementation with Pycnogenol or Elastic Compression-A 12-Month Follow-Up.

This open registry aimed to evaluate the clinical evolution of postpartum varicose veins (VVs), in healthy women after the second pregnancy, how these veins regain shape and competence, and possible treatments. The registry included two groups of women: (1) those who used elastic compression stockings, and (2) who used an oral venotonic agent (Pycnogenol, 100 mg/d). A total of 12 evaluation targets were established. Minor symptoms were scored in an analogue scale line. A visual analogue scale line evaluated the overall satisfaction relative to elastic compression or Pycnogenol. Overall 133 women completed the registry evaluation with at least 3 months of follow-up. The resulting two registry groups were comparable. At 3 and 6 months in the Pycnogenol group the number of veins and incompetent sites were lower. At 6 months there were 13.3% of patients with edema in controls versus 3.2% in the Pycnogenol group. Spider veins decreased in Pycnogenol patients. Cramps and other minor symptoms were less common in the Pycnogenol group. In both groups there was a significant improvement at 6 months with better results in the Pycnogenol group. The need for treatment was limited with a decreased need for sclerotherapy, surgery, and conservative treatments in the Pycnogenol group. The overall satisfaction was higher among Pycnogenol patients, and compliance was optimal. Re-evaluation at 12 months indicated that the variations in VVs and spider vein clusters and the associated symptoms did not change. Most remodeling appeared to happen within 6 months after the pregnancy. It was concluded that the use of Pycnogenol improves signs/symptoms of postpartum VVs, and venous function and shape seem to return faster to prepartum, physiological pattern with its use.

Pycnogenol® and Centella asiatica to prevent asymptomatic atherosclerosis progression in clinical events.

BACKGROUND: The aim of this study was to evaluate the effect of the nutritional supplements Pycnogenol® and Centella asiatica (CA) on atherosclerosis progression in low-risk, asymptomatic subjects with carotid or femoral stenosing plaques. METHODS: The study included subjects aged 45-60 with stenosing atherosclerotic plaques (50-60%) in at least one carotid or common femoral bifurcation. Subjects were allocated into 3 groups. In Group 1 (controls), management was based on education, exercise, diet and lifestyle changes. This same management plan was used in the other two groups: Group 2 used Pycnogenol® (100 mg/day), while Group 3 used Pycnogenol® 100 mg/day plus CA (100 mg/day). The follow-up lasted 4 years. Plaque progression was assessed using the ultrasonic arterial score based on arterial wall morphology, considering plaque characteristics and the number of subjects that had cardiovascular events. Oxidative stress was also measured. RESULTS: Of the 413 individuals that were admitted, 391 individuals completed 4 years. Group distribution was comparable. The rate of progression of ultrasound arterial score was significantly lower in the two supplement groups (P<0.05) in comparison with controls suggesting a beneficial effect of Pycnogenol® with a significant difference in favor of the combination (P<0.05). There was a reduction in plaques progression in the supplement groups with the best effects obtained by the combination, considering maximum plaque thickness and length and echogenicity (grey scale median) (P<0.05). Plaques became generally dense (more echogenic) achieving a mixed echogenicity. The occurrence of anginal events was less than 3% in the two supplement groups (in comparison with 6.25% in controls) (P<0.05) with the best results obtained by the combination (P<0.05). The occurrence in myocardial infarctions was significantly lower for the combination (P<0.05). Minor transient ischemic attacks were also less frequent with the supplements with the best results observed with the combination (P<0.05). Events in controls - requiring hospital admission - were globally seen in 16.4% of subjects (minor events) in comparison with 8.9% of subjects using Pycnogenol® and only 3.3% of patients using the combination. At 4 years, oxidative stress in the supplement groups was lower than in controls (P<0.05, with no significant difference between groups 2 and 3). CONCLUSIONS: Pycnogenol® and the combination of Pycnogenol® plus CA reduce the progression of arterial plaques and the progression to clinical stages. The reduction in plaques and clinical progression was associated with a reduction in oxidative stress. The results justify a larger study to define the efficacy of the combination of Pycnogenol® plus CA as a prophylaxis in preclinical atherosclerosis.

Carotid plaque stabilization induced by the supplement association Pycnogenol® and centella asiatica (Centellicum®).

BACKGROUND: Aim of this registry study was the evaluation of the stability of carotid plaques by ultrasound in asymptomatic subjects with high oxidative stress following supplementation with a combination of the extract from bark of Pinus pinaster, Pycnogenol®, with an extract from Centella asiatica leaves, Centellicum®. METHODS: 50 patients, mean age 61.5 years, with carotid plaques (<50% stenosis) and high oxidative stress were included in this 3 months registry study. 26 patients received the combination of Pycnogenol® and Centellicum® and standard management, a control group received standard management only. The 2 groups were comparable. RESULTS: The combination of Pycnogenol® and Centellicum® reduced significantly (p<0.05) plaque height and length as well as the number of plaques relative to controls. The plaque stability index, based on the echogenicity in the ultrasound picture of the "white" components of the plaque, increased significantly (p<0.01) in the verum group, no changes were observed in the controls. Plasma free radicals were significantly (p<0.05) decreased by the combination product, whereas the levels of plasma free radicals remained unchanged in the control group. No unwanted effects or abnormal laboratory tests were recorded. CONCLUSIONS: This registry study revealed a significant increase in stability of plaques, indicated by an enhanced density of the plaques, following supplementation with the combination of Pycnogenol® and Centellicum®. As size and number of plaques was simultaneously reduced, the combination of the two plant extracts could be a safe option for prevention of cardiovascular events for patients with carotid plaques.

Superficial venous incompetence: low-cost outpatient minisurgery, sclerotherapy and combined procedure as a management plan. Costs and efficacy. A 20-year, follow-up registry.

BACKGROUND: This registry study evaluated low-cost outpatient surgery (mini-S) for venous insufficiency as an alternative to stripping. METHODS: This 20-year follow-up is focused on the recurrence of varices and on the long-term efficacy of the mini-S (group 1) in comparison with controls (2, stripping), sclerotherapy (3) or a combination of mini-S+sclerotherapy (4). Costs were compared. RESULTS: At 20-years of follow-up, considering recurrence/development of new varicose veins, 24.05% of the limbs treated with mini-S developed new varices in comparison with 64.4% in group 2, 24.1% in group 3 and 15.4% in group 4 (P<0.05). New surgical procedures were needed in 18.9% of mini-S patients vs. 58.5% in group 2, 21.9% in group 3 and 19.7% in group 4 (P<0.05 between group 2 and the other groups). Sclerotherapy (in the years following the initial treatment) was used in 37.9% of mini-S patients in comparison with 67.7% of subjects in group 2 patients, 33.1% in group 3 and 22.8% in group 4 (P<0.05 between outpatient treatment and group 2). The superficial venous system was incompetent in 21% of mini-S patients in comparison with 38.8% in group 2 (P<0.05), 20.7% in group 3 and 17.9% of group 4. At 20 years edema was present in 10.5% of limbs in group 2 in comparison with a <3% (range 2.2-2.1%) in the other groups. Edema was more significant after stripping. Ambulatory venous pressure measurements in subgroups was lower in groups 1, 3 and 4 with a lower refilling time (P<0.05). The cost of in-hospital, daily surgical treatments were €1978 (covered by the heathcare provider). The cost of mini-S was on average €488 per limb (covered by patients). CONCLUSIONS: Outpatients procedures, in particular the mini-S management plan, were cheaper than stripping and more effective at 20-years follow-up. They could be a model for emerging contries with restricted budgets for vein surgery. Also being cheaper more people may have benefits from treatment when/where hospital procedures are not covered by an healthcare provider.

French Oak Wood (Quercus robur) Extract (Robuvit) in Primary Lymphedema: A Supplement, Pilot, Registry Evaluation.

The aim of this pilot supplement study was the evaluation of an oak wood extract (Robuvit, Quercus robur [QR], Horphag Research) in an 8-week registry study on lymphatic signs in primary lymphedema. Subjects with primary lymphedema confined to a single leg without skin changes or ulcerations were followed for at least 8 weeks. Lymphedema was mainly present distally (below the knee). Three groups were formed: one group used only the standard management for lymphedema; one used the same management plus 300 mg Robuvit; and one used the standard management plus 600 mg of Robuvit. The three groups were comparable. After 8 weeks the variation in leg volume was on average -6.2% with standard management, -15% in the QR 300 mg group, and -18.9% in the 600 mg group. The edema score was also significantly lower at 8 weeks in the two QR groups. The variation in proteins in the interstitial fluid in comparison with initial values was -14.8% in controls in comparison with -29.9% in QR 300 mg group and -36.9% in QR 600 mg group. Skin flux significantly improved (increased) in the two QR groups. Ultrasound pretibial skin thickness was decreased on average 6% in controls versus 10.3% in the low-dose QR group and 11.8% in the higher dose group. Perimalleolar thickness was decreased 7% in controls and more in the two QR groups. Ankle circumference was decreased 4.4% in controls and more in the two supplement groups. This pilot registry indicates that Robuvit can be effective in the management of primary lymphedema. More patients and longer evaluation periods are needed.

The efficacy of sulodexide in the prevention of postthrombotic syndrome.

AIM: The aim of this open, observational registry was to evaluate the effects of antithrombotic treatment on the development of postthrombotic syndrome (PTS): the effects of "standard management" (SM; according to International Union of Angiology guidelines) were compared to SM in association with sulodexide or aspirin. METHODS: Postthrombotic syndrome occurrence was observed in 3 nonparallel groups after deep venous thrombosis (DVT); the registry started after the end of the anticoagulation period. The target was to observe the occurrence of PTS in 5 years. Three possible options were suggested to the patients, and the patients and their caregivers defined the type of management. A group of 167 patients was involved in the SM with reevaluation every 6 months; the sulodexide group included 124 patients and the aspirin group included 48 patients. RESULTS: The 3 groups were clinically similar and comparable for age and sex distribution. Of the 167 patients in the SM group, 154 patients completed 60 months of follow-up. The percentage of patients with PTS in the SM group ranged from 14.9% (1 year after the end of anticoagulation) to 19.5% (60 months). In the nonparallel group using sulodexide (124 comparable patients at inclusion; 115 at 60 months), the percentage of PTS was variable from 8.8% (1 year after anticoagulants) to 12.17% at 60 months. These percentages are significantly lower than those observed with SM. In the nonparallel aspirin group (48 patients at inclusion and 34 at 54 months), there was a PTS incidence of 23.5% at 54 months (vs 12.17% in the sulodexide group and 18.23% in the SM group). The incidence of PTS was significantly higher in comparison with the other 2 groups. The incidence of PTS was lower in the sulodexide group in comparison with the 2 other groups. CONCLUSIONS: Sulodexide administration after DVT appears to be effective in preventing PTS in association with recommended management and a number of recurrent DVTs. Modalities of treatment, dosages, and timing of administration should be explored in more comprehensive and complete studies.

A controlled study of a lecithinized delivery system of curcumin (Meriva®) to alleviate the adverse effects of cancer treatment.

A proprietary lecithin delivery system of curcumin (Meriva) was evaluated in a controlled study to assess its efficacy in alleviating the side effects of cancer chemo- and radiotherapy in 160 patients undergoing these treatments. In both cases, a semi-quantitative evaluation of the side effects was carried out using a visual analogue scale, assessing also the plasma free radical status in all patients. Results showed that lecithinized curcumin might alleviate the burden of side effects associated to chemo- and radiotherapy, suggesting that the anecdotal use of various preparations of curcumin as a supportive agent for cancer treatment is well worth a systematic investigation in larger scale clinical trials. The capacity of curcumin to upregulate anti-oxidative responses and downregulate inflammatory pathways could explain its beneficial effect in tempering the prolonged and systemic oxidative and inflammatory effects of cancer treatment, and the beneficial effects observed in the plasma oxidative status in all patients of the treatment group support this view.

O-(beta-hydroxyethyl)-rutosides systemic and local treatment in chronic venous disease and microangiopathy: an independent prospective comparative study.

O-(beta-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 PO2, 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.

5-Year control and treatment of edema and increased capillary filtration in venous hypertension and diabetic microangiopathy using O-(beta-hydroxyethyl)-rutosides: a prospective comparative clinical registry.

This independent prospective controlled trial evaluates the efficacy of O-(beta-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.

Lymphatic tissue transplant in lymphedema--a minimally invasive, outpatient, surgical method: a 10-year follow-up pilot study.

Lymphedema is mainly characterized by swelling, fibrosis, and non-pitting edema. The aim of this study was evaluation of the long-term (10 years) effects of autologous lymphatic tissue implant in lymphedema. Lymphatic tissue from 9 patients (harvested form the same patient in areas not affected by lymphedema) was reimplanted into the affected limb, and these patients were followed for 10 years. Lymph nodes were harvested at the neck, axillary, or inguinal space (contralateral limb). Results showed that limb volume was decreased in the treatment group vs. controls. In ultrasound, black, low density, lymphatic spaces were visible in 100% of patients at inclusion but in only 23% of these subjects at 10 years. Thus, this early report proposes a new, minimally invasive method to improve lymphedema. Studies in progress will indicate the role of lymphatic transplant in the management of lymphedema and the best indications for this method.

Five-year treatment of chronic venous insufficiency with O-(ß-hydroxyethyl)-rutosides: safety aspects.

Chronic venous insufficiency (CVI), and related signs and symptoms of venous and diabetic microangiopathy, can be effectively treated with O-(ß-hydroxyethyl)-rutosides (HR). The aim of the present independent registry study was to evaluate HR in a long-term (five-year) period of administration that examined the tolerability and safety of HR. Patients with severe CVI and venous microangiopathy were included in the registry. Subjects who completed five years of treatment were considered in the analysis. Blood parameters, liver and renal function tests, microalbuminuria (in diabetic patients) and cholesterol levels were evaluated to assess the effects of HR treatment. Four groups were studied - group A (98 patients) received oral HR (1500 mg per day), group B (87 diabetic patients with CVI) was treated with 2 g of HR per day, group C (90 controls, including 42 diabetic patients) had no pharmacological treatment and group D (113 patients, including 48 diabetic patients) used elastic stockings. No significant negative changes in blood parameters were recorded at two and five years. Decreases in microalbuminuria and total cholesterol, and an increase in high-density lipoprotein cholesterol were observed in HR-treated patients, particularly in diabetic patients. Minimal (nonsignificant) variations were observed in the groups that did not use HR. In conclusion, HR treatment is safe, and some positive effects from HR on cholesterol levels and microalbuminuria (in diabetic patients) that were previously observed may suggest potential new clinical applications.