Summaries of Recent Phlebological Abstracts

WA Marston, WJ Ennis, JC Lantis, et al.

J Vasc Surg: Venous and Lym Dis 2017; 5: 829–836

The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials. Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm² to 12 cm² in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm² and < 36 cm² with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure. This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < .10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < .05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134–1.690]), wound location on the leg (1.490 [1.187–1.871]), smaller wound area at baseline (0.907 [0.887–0.927]), and shorter wound duration at baseline (0.971 [0.955–0.987]). The authors concluded that factors associated with VLU lesions including location, area, and duration were important predictors of healing. Women were more likely than men to achieve wound closure. Factors including body mass index, the presence of diabetes mellitus, and higher concentrations of glycated hemoglobin were not significant independent predictors of wound closure in this analysis.

F Chassagne, C Helouin-Desenne, J Molimard, R Convert, P Badel, P Giraux

J Vasc Surg: Venous and Lym Dis 2017; 5: 851–858

Six different bandages, composed of one elastic bandage, one nonelastic bandage, or both, were applied in a spiral pattern on both legs of 25 patients at risk of venous thrombosis as a consequence of central or peripheral motor deficiency. Pressure was measured at four measurement points on the leg (B1 and C on the medial and lateral sides of the leg) and in three positions: supine, sitting, and standing. The two single bandages applied similar pressure in the supine position. Their superimposition showed different pressure levels (P < .05) but similar static stiffness index, depending on the order in which the bandage components were applied on the leg. The highest interface pressure was measured at point B1 on the medial side of the leg. This point also showed the highest pressure increase from supine to standing position. The pressure applied by the superimposition of two bandages was computed as a linear combination of the pressure applied by each single component (with a constant term set to 0). However, this linear combination did not properly fit the experimental pressure measurements. The investigators concluded that the order of bandage application showed a significant impact on interface pressure. However, the poor correlation between the pressure applied by each bandage component and the pressure resulting from their superimposition underlined the poor understanding of interface pressure generated by the superimposition of compression bandages and should lead to further investigations.

K Kulprachakarn, P Abkom, O Pongtam, et al.

Int J Low Extrem Wounds 2017 Epub ahead of print doi: 10.1177/1534734617740252

A 2-year cross-sectional study was conducted to ascertain if there was any correlation between food groups and varicose veins in an Asian population. The 558 eligible patients were divided into 2 groups: C0-C2 and C3-C6. 78.9% percent of the entire cohort was female and approximately 50% were greater than 50 years old. Seventeen out of 558 patients were diagnosed with high severity of venous disease. Remarkably, significantly higher body weight (73.8 ± 13.9 vs 58.4 ± 11.2 kg, P = .000) and body mass index (28.8 ± 4.4 vs 23.3 ± 3.9 kg/m², P = .000) was found in patients with severe types of venous disease compared with the mild group. Patients with severe venous disease showed lower frequency of chicken consumption (P = .022).

The authors concluded that the results suggested an association of chicken consumption with a reduced chance of developing varicose veins.

I Akar, I Ince, C Aslan, et al.

Vascular 2017 Epub ahead of print doi: 10.1177/1708538117741764

The aim of this study is to evaluate the oxidative stress at venous insufficiency and to provide preliminary knowledge about the role of prolidase enzyme in varicose vein formation. Ninety patients aged between 22 and 80 (47.35 ± 17.69) were included in the study and divided into 3 groups. Group1(n:30)(Serum control group): Patients without venous insufficiency. Group 2(n:30)(Tissue control group(healthy vein group): Patients underwent coronary artery bypass surgery (the remaining portion of great saphenous vein used as coronary artery bypass graft used as normal tissue). Group 3(n:30)(Varicose vein group): Patients underwent varicose vein surgery (varicose vein and serum of these patients were used for study). Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Oxidative Stress Index (OSI) and Prolidase enzyme levels were detected in tissue and serum samples. No significant changes were detected between three groups' serum samples in oxidative stress parameters and in the prolidase enzyme activity. The tissue TOS and OSI were higher in varicose vein group according to normal vein group and this was found statistically significant. And TAC levels in varicose vein group were significantly lower than normal vein group. Prolidase enzyme activity in varicose vein group was found higher according to normal vein group. The authors concluded that oxidative stress plays a role at the development of primary varicose veins at biochemical level. Prolidase enzyme related with oxidative stress may play an important role in the pathogenesis of primary varicose veins.

M Kanapathy, R Simpson, L Madden, et al.

Br J Surg 2017 Epub ahead of print doi: 10.1002/bjs.10653

The authors studied the relationship between connexin and varicose veins. Connexin, a gap junctional protein, is a marker for poor wound healing. Forty-eight paired biopsies were taken (12 each for CEAP class C0, C2, C4 and C6). In patients from C4-C6, the pathological skin showed progressive epithelial hyperthickening, an increase in the number and depth of rete ridges, increased inflammation, and loss of dermal architecture. The overall absolute connexin expression and mean connexin expression per cell in the pathological skin similarly increased across the CEAP classes from as early as C2. Connexin 43 expression showed the strongest positive correlation between pathological and control skin. Connexins were overexpressed in patients with simple varicose veins, with a stepwise increased expression through venous eczema to ulceration. This progressive finding suggests that varicose veins predispose skin to poor wound healing. The authors conclude that connexin could be a biomarker of venous disease progression, since connexin proteins were overexpressed in patients with uncomplicated varicose veins, before histological skin changes.

T Bai, W Jiang, Y Fan.

Dermatol Surg 2017 Epub ahead of print doi: 10.1097/DSS.0000000000001402

Five syringe types were used to prepare room temperature foam with various liquid-gas ratios. Foam decay process experiments were performed 5 times and recorded by video. The stability indices used include drainage time, half-life, bubble diameter, bubble surface density, and drainage rate. The 30 and 2-mL syringes, respectively, recorded the highest and lowest drainage speeds. Foam drainage time and half-life differences varied between 15 and 70 seconds, and 20 and 100 seconds, respectively. Foam bubble diameters were distributed over 0.1 to 2.0 mm with roughly 200 to 700 bubbles per square centimeter. The authors concluded that increased syringe volume causes the bubble diameter to increase. Thus, foam dispersion increases and foam half-life decreases suggesting that the practitioner use a small syringe several times to prepare foam in clinics using segmented injections.

H Robert-Ebadi, M Righini

Hematology Am Soc Hematol Educ Program 2017; 2017: 231–236.

Recent data arising from registries and nonrandomized studies have suggested that most distal DVTs do not extend to the proximal veins and have an uneventful follow-up when left untreated. These data had some impact on the international recommendations that recently stated that ultrasound surveillance instead of systematic therapeutic anticoagulation might be an option for selected low-risk patients. However, robust data from randomized studies are scarce. Only 5 randomized trials assessing the need for anticoagulation for calf DVT have been published. Many of these trials had an open-label design and were affected by methodological limitations. The only randomized placebo-controlled trial included low-risk patients (outpatients without cancer or previous venous thromboembolism [VTE]) and was hampered by limited statistical power. Nevertheless, data from this trial confirmed that the use of therapeutic anticoagulation in low-risk patients with symptomatic calf DVT is not superior to placebo in reducing VTE but is associated with a significantly higher risk of bleeding. Further randomized studies are needed to define the best therapy for high-risk patients (inpatients, patients with active cancer, or patients with previous VTE) and the optimal dose and duration of treatment.

SK Kakkos, M Timpilis, P Patrinos, et al.

Eur J Vasc Endovasc Surg 2017 Epub ahead of print doi: 10.1016/j.ejvs.2017.10.004

30 patients who never wore elastic stockings and presented with symptomatic primary varicose veins were randomized in a double blind placebo controlled trial to wear a graduated compression sock (GCS) (18–21 mmHg at the ankle level, n = 15) or a placebo stocking (0 mmHg, n = 15). Pain or aching of the index leg after 1 week was the primary outcome measure. All symptoms were scored on a visual analogue scale (VAS). At the completion of the study after 1 week, GCS were more effective than placebo stockings in reducing pain or aching (VAS score 1.7 ± 3.0 vs. 4.5 ± 2.8 for placebo, p = .02). Mean daily use of the placebo stockings and GCS was 8.0 hours and 10.2 hours, respectively (p = .13). Number needed to treat (95% CI) for a 50% or complete improvement of pain or aching in the index leg was 2 (95% CI 1.2–5.5) and 2 (95% CI 1.2–5.3), respectively. The authors concluded that among patients with varicose veins, GCS seem effective in improving symptoms, principally pain or aching, compared with placebo stockings.