Black holes in compression therapy: A quest for data.

OBJECTIVE: Although compression therapy (CT) is considered a crucial conservative treatment in chronic venous disease, strong evidence is missing for many clinical indications. This literature review aims to point out what strong evidence we have for CT and all the clinical scenarios where strong evidence still needs to be included. METHODS: The research was conducted on MEDLINE with PubMed, Scopus and Web of Science. The time range was set between January 1980 and October 2022. Only articles in English were included. RESULTS: The main problem with CT is the low scientific quality of many studies on compression. Consequently, we have robust data on the effectiveness of CT only for advanced venous insufficiency (C3-C6), deep vein thrombosis and lymphedema. We have data on the efficacy of compression for venous symptoms control and in sports recovery, but the low quality of studies cannot result in a strong recommendation. For compression in postvenous procedures, superficial venous thrombosis, thromboprophylaxis, post-thrombotic syndrome prevention and treatment, and sports performance, we have either no data or very debated data not allowing any recommendation. CONCLUSIONS: We need high-level scientific studies to assess if CT can be effective or definitely ineffective in the clinical indications where we still have a paucity of or contrasting data.

Rationale and current evidence of aquatic exercise therapy in venous disease: A narrative review.

Chronic venous disorders (CVD) of the lower limbs can be treated with different strategies. Typically, conservative management is based on compression therapy, anticoagulants and venoactive drugs. Endovenous treatments remain the gold standard to treat saphenous insufficiency, with sclerotherapy and surgery maintaining a role in selected cases. In addition, several 'unconventional' approaches have been proposed to prevent CVD progression and complications, minimize symptoms and improve the quality of life and postoperative outcomes. Among these, balneotherapy and aquatic exercises are proving as valid and effective supporting treatments, as mentioned in a growing number of scientific publications. Moreover, aquatic protocols have been studied for both venous and lymphatic insufficiency. For these reasons, they were mentioned in the last CVD guidelines provided by the European Society for Vascular Surgery. The aim of this narrative review is to overview and summarize current literature evidences on the role and effectiveness of aquatic rehabilitative protocols in CVD, reviewing old and current literature. Furthermore, the physical basis of the effects of water immersion on lower limb venous and tissues modifications are also described.

Subcutaneous calcifications in legs with chronic venous diseases.

BACKGROUND: Calcifications in the subcutaneous layer (SCL) have been described by radiographic studies of legs with advanced chronic venous disease (CVD). However, SCL calcifications have rarely been included among the CVD-related changes. The aim of the present study was to evaluate the prevalence and morphology of SCL calcifications in legs with CVD of all grades of severity determined by ultrasound. METHODS: A total of 500 legs in 250 patients (148 women and 102 men; mean age, 51 years; range, 18-87 years) referred to our vascular clinic for symptoms and signs of CVD were included. After duplex ultrasound evaluation of the deep, superficial, and perforating veins, the skin and SCL were investigated using duplex ultrasound. Those patients with other possible causes of SCL calcification were excluded. RESULTS: Using the C component of the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification, 43 legs were classified as C1, 189 as C2, 34 as C3, 16 as C4A, 45 as C4B or C, 18 as C5, and 16 as C6. Varicose veins were reported in 273 legs, and lipodermatosclerosis in 79 legs. Subcutaneous calcifications were demonstrated in 35 of 361 legs with CVD in two different locations: the wall of superficial varicose veins and in subcutaneous tissue unrelated to the path of the superficial veins. Superficial veins calcifications were found in 12 of 273 legs with varicose veins (4.4%) and were found in older patients with severe varicose vein disease (grade 3 using the venous clinical severity score and disease duration >30 years). Subcutaneous tissue calcifications (STCs) were found in 24 of 95 legs with a more advanced CVD stage (C4A-C6). No STCs were found in legs with a C1, C2, or C3 class. CONCLUSIONS: Superficial veins calcifications were found only in the legs with severe and long-lasting varicose veins and seemed to be related to chronic severe inflammation of the venous wall. STCs were independent of the vein wall and were found only in the damaged areas of legs with severe CVD (C4-C6). STCs are possibly related to chronic inflammation of the subcutaneous tissue. Their avulsion from the ulcer bed has been recommended to facilitate ulcer healing and prevent recurrence.

Effectiveness of Blue light photobiomodulation therapy in the treatment of chronic wounds. Results of the Blue Light for Ulcer Reduction (B.L.U.R.) Study.

BACKGROUND: Lower limb ulcers not responding to standard treatments after 8 weeks are defined as chronic wounds, and they are a significant medical problem. Blue light (410-430 nm) proved to be effective in treating wounds, but there is a lack of data on chronic wounds in clinical practice. The aim of the study was to determine if blue light photobiomodulation with EmoLED (Emoled Srl, Sesto Fiorentino, Florence, Italy) medical device in addition to standard of care is more effective compared to standard of care alone in promoting re-epithelialization of chronic wounds of lower limbs in 10 weeks. METHODS: Ninety patients affected by multiple or large area ulcers were enrolled. To minimize all variabilities, each patient has been used as control of himself. Primary endpoint was the comparison of the re-epithelialization rate expressed as a percentage of the difference between the initial and final area. Secondary endpoints were: treatment safety, pain reduction, wound area reduction trend over time, healing rate. RESULTS: At week 10, the wounds treated with EmoLED in addition to standard care showed a smaller residual wound area compared to the wounds treated with standard of care alone: 42.1% vs. 63.4% (P=0.029). The difference is particularly evident in venous leg ulcers, 33.3% vs. 60.1% (P=0.007). 17 treated wounds and 12 controls showed complete healing at week 10. Patients showed a significant reduction in pain (P=2×10-7). CONCLUSIONS: Blue light treatment in addition to standard of care accelerates consistently the re-epithelialization rate of chronic wounds, especially venous leg ulcers and increases the chances of total wound healing in 10 weeks.

Compression Stocking With 100% Donning and Doffing Success: An Open Label Randomised Controlled Trial.

OBJECTIVE: The aim of this study was to test whether an investigational two layer stocking exerting 27-29 mmHg pressure at the medial supramalleolar level, but without compression in the foot and heel, is easier to put on and take off than a standard stocking of the same compression class (23-32 mmHg), and also to assess the prevention of diurnal oedema with both types of stocking. METHODS: This was an open label randomised controlled trial, which included 47 patients. All participants were at least 65 years of age and suffered from chronic venous disease class C3 - C6 in one leg. The primary end point was donning success; secondary endpoints were doffing success, prevention of diurnal oedema over one day, and the comfort of wearing the stocking. Patients were randomly allocated to one of two groups. Both types of compression stocking were compared in each group for ease of donning and doffing in the manner of a crossover study. Subsequently, patients wore the stocking type assigned to their group for a whole day to evaluate comfort and the effect on diurnal leg volume. RESULTS: All participants were able to don the investigational stocking unaided, compared with 75% for the standard stocking (p < .001). Unaided removal success was 100% with the investigational stocking vs. 66% for the standard stocking (p < .001). There was no significant difference in leg volume reduction between the study groups after a day of wear. The investigational stocking was also rated as being more comfortable than the standard stocking (p < .001). CONCLUSION: The investigational stocking, which has no compression in the foot or heel area, is significantly easier to don and doff, with no inferiority in oedema prevention, compared with a standard stocking of the same compression class.

Volume control of the lower limb with graduated compression during different muscle pump activation conditions and the relation to limb circumference variation.

BACKGROUND: The literature supports the use of graduated compression stockings (GCS) for leg edema. Nevertheless, there is a paucity of data on the GCS effect on limb edema related to sitting, standing, and walking. Data of different limb shapes and their impact on GCS-exerted pressure are lacking. This investigation provides evidence-based information on the effect of GCS on edema reduction and the impact of limb circumference gradients on GCS pressure. METHODS: Thirty healthy individuals (15 men and 15 women; mean age, 32 ± 5 years) were included. All the participants underwent lower limb volume (Kuhnke formula) measurement, before and after sitting for 30 minutes, wearing below-ankle noncompressive socks. The same assessment was repeated 7 days later, in the same participants, but with wearing of below-knee 16 to 20 mm Hg GCS. At 7-day intervals, 1 week with below-ankle noncompressive socks and 1 week with below-knee 16 to 20 mm Hg GCS, all the participants repeated the same protocol including standing and walking. Ten participants underwent bioimpedance assessment (Biody Xpert II; eBIODY, La Ciotat, France) before and after sitting, standing, and walking. In the same group, B and B1 interface pressure values were measured. RESULTS: Data collection was completed in all 60 limbs. Sitting or walking without GCS led to no significant volume changes, whereas volume was decreased by the use of GCS (-4.8% [P < .00001] and -4.4% [P < .00001], respectively). Standing up without GCS led to an increase in volume (2.7%; P < .0001), whereas limb volume was decreased (4.6%; P < .0001) by use of GCS. Bioimpedance showed extracellular water reduction only while walking with GCS (from 40.55% ± 1.66% to 40.45% ± 1.71%; P < .017). Mean interface pressure was 19 ± 5 mm Hg (B) and 16 ± 5 mm Hg (B1). The interface pressure variation from B to B1 was not homogeneous among participants (mean percentage variation of -13% ± 25%, ranging from -54% to 16%). A negative linear trend between pressure variation and circumference percentage increase was found; the subanalysis excluding the two outliers showed a strong negative linear correlation (Pearson coefficient r = -0.96). CONCLUSIONS: GCS led to a significant limb volume reduction irrespective of limb position and muscle pump function. However, extracellular fluid is mobilized only during muscle contraction while walking with GCS. Interestingly, different lower limb circumference variations influence the interface pressure gradient, indicating the importance of proper fitting of both B and B1 during prescription. These data provide a foundation to future investigations dealing with GCS effect on fluid mobilization and with limb geometry impact on compression performance.

Cadaveric Skin Grafts May Greatly Increase the Healing Rate of Recalcitrant Ulcers When Used Both Alone and in Combination With Split-Thickness Skin Grafts.

BACKGROUND: Leg ulcers that do not heal despite appropriate treatment are defined as recalcitrant ulcers. Large surface area, depth, and long duration represent some of most important factors impeding ulcer healing. After sharp debridement, dermal substitutes including skin from cadaver donors may increase the healing rate of recalcitrant ulcers reducing the risk of scar formation and recurrence. OBJECTIVE: Assessing if, after sharp debridement, dermal substitutes including skin from cadaver donors may increase the healing rate of recalcitrant ulcers reducing the risk of scar formation and recurrence. PATIENTS AND METHODS: Among patients admitted to our hospital for all types of chronic leg ulcers, we retrospectively reviewed the records of patients affected by recalcitrant ulcers (surface greater than 100 cm, tissue loss involving epidermis, dermis, and subcutaneous tissue, duration longer than 1 year, and showing no healing tendency). After sharp debridement, the ulcers were covered by allografts with strict follow-up after discharge. Multiple allografts were performed when necessary, and a final autograft was applied in case of incomplete healing. RESULTS: The records of 414 patients were analyzed. Forty-three patients were lost at follow-up, and the remaining 371 healed after 765 grafting procedures. In 163 patients, the ulcers healed by means of a final autograft. In all the remaining cases, allograft led to ulcer healing. CONCLUSION: Allografts represent an effective treatment option in case of recalcitrant, large, deep and long-lasting leg ulcers.

A Wearable Compression Device to Normalise Calf Muscle Pump Function in Chronic Venous Insufficiency for Each Postural Position.

BACKGROUND: For the currently used compression therapy, the applied compression pressure is usually inadequate to exert an effective impact on the veins in different body positions. The aim was to assess the venous ejection fraction achieved by a new compression device which automatically adjusts the interface pressure to body position in an acute experimental setting. METHODS: A new portable, battery driven compression device providing pressure adjusted to allow for body position, and connected to a less or very stiff calf cuff wrap was tested. In patients with superficial venous incompetence, the ejection fraction (EF) of the calf pump was measured by strain gauge plethysmography. Applied in a random sequence, values achieved without compression, with the two cuffs, and with compression stockings exerting 23-32 mmHg, were compared. The applied compression pressures were simultaneously recorded in the supine and standing positions, and during walking. Comfort was assessed by a visual analogue scale (VAS) with 0 corresponding to very low comfort and 10 to very comfortable. RESULTS: In 16 patients with CEAP clinical stage C3-C6, EF without compression was 37%, increasing to 46.9% with stockings, to 64.8% (p < .001) by less stiff and to 75.5% (p < .001) by stiffer wraps. The median interface pressure (supine/standing) was 31/56 mmHg for the less stiff device, 32/68 mmHg for the stiffer device, and 23/26 mmHg for the stockings. The static stiffness index and the walking pressure amplitudes were significantly higher than those generated by the stocking, and the highest values were found with the stiffer wrap material. The device comfort was high both in the supine and standing positions (VAS 8 ± 2). CONCLUSIONS: The tested devices were comfortable at rest and haemodynamically effective during walking by automatically adjusting compression pressures to body position. They are significantly more effective than elastic stockings in improving EF. The system is able to overcome the problems of fast pressure loss by continuously re-adjusting the compression pressure.

Lower limb volume in healthy individuals after walking with compression stockings.

OBJECTIVE: Despite the modern appeal of wearing compressive garments during physical activities, the literature is lacking in quality data and controversial in the investigations dealing with the pathophysiologic mechanism by which graduated compression stockings (GCS) affect the calf pump activation in healthy individuals. The aim of the investigation was to provide insight into the clinical effects of GCS use during a standardized walking exercise. METHODS: Twenty physically active healthy volunteers (mean age, 34 ± 5 years; body mass index, 22 ± 2 kg/m2) underwent lower limb ultrasound scanning to exclude vascular impairment. All individuals performed continuous aerobic exercise, walking for 30 minutes on a treadmill, under cardiac monitoring, at 70% of individual estimated maximal heart rate according to the Tanaka equation. The study population performed the standardized walk without GCS (baseline) and at 1 week performed the same standardized walk wearing knee-length 20 to 30 mm Hg GCS (compression). All individuals underwent a lower limb volume assessment by truncated cone formula before and after the walk and a perceived exertion assessment by means of the validated Borg scale at the end of the exercise protocol. RESULTS: All individuals had normal venous and arterial ultrasound examination findings. No significant postural defects were reported. Both legs were assessed in all 20 individuals for a total of 40 cases with and 40 cases without GCS. In the baseline group, the median (interquartile range) lower limb volume changed from 2496 (770) mL before exercise to 2512 (805) mL (P = .2597) after exercise. The compression group reported a significant lower limb volume change from 2466 (670) mL before exercise to 2276 (567) mL (P = .0001) after exercise. Mean perceived exertion was 13 (11) and 11 (1) in the baseline and compression groups, respectively (P = .0001). The interface pressure exerted by the GCS was 24 (2) mm Hg. No complaints in terms of discomfort were reported after use of GCS. CONCLUSIONS: In healthy individuals, GCS (24 [2] mm Hg) use during a continuous standardized walk of 30 minutes is associated with a significant decrease in lower limb volume and a decrease in perceived exertion. The mechanism by which GCS impart their effect during physical activity may involve improved muscle pump function and reductions in inflammatory pathways. Further study will need to validate the mechanisms of the function of GCS used during physical exercise.

Compression therapy after invasive treatment of superficial veins of the lower extremities: Clinical practice guidelines of the American Venous Forum, Society for Vascular Surgery, American College of Phlebology, Society for Vascular Medicine, and International Union of Phlebology.

Guideline 1.1: Compression after thermal ablation or stripping of the saphenous veins. When possible, we suggest compression (elastic stockings or wraps) should be used after surgical or thermal procedures to eliminate varicose veins. [GRADE - 2; LEVEL OF EVIDENCE - C] Guideline 1.2: Dose of compression after thermal ablation or stripping of the varicose veins. If compression dressings are to be used postprocedurally in patients undergoing ablation or surgical procedures on the saphenous veins, those providing pressures >20 mm Hg together with eccentric pads placed directly over the vein ablated or operated on provide the greatest reduction in postoperative pain.[GRADE - 2; LEVEL OF EVIDENCE - B] Guideline 2.1: Duration of compression therapy after thermal ablation or stripping of the saphenous veins. In the absence of convincing evidence, we recommend best clinical judgment to determine the duration of compression therapy after treatment. [BEST PRACTICE] Guideline 3.1: Compression therapy after sclerotherapy. We suggest compression therapy immediately after treatment of superficial veins with sclerotherapy to improve outcomes of sclerotherapy. [GRADE - 2; LEVEL OF EVIDENCE - C] Guideline 3.2: Duration of compression therapy after sclerotherapy. In the absence of convincing evidence, we recommend best clinical judgment to determine the duration of compression therapy after sclerotherapy. [BEST PRACTICE] Guideline 4.1: Compression after superficial vein treatment in patients with a venous leg ulcer. In a patient with a venous leg ulcer, we recommend compression therapy over no compression therapy to increase venous leg ulcer healing rate and to decrease the risk of ulcer recurrence. [GRADE - 1; LEVEL OF EVIDENCE - B] Guideline 4.2: Compression after superficial vein treatment in patients with a mixed arterial and venous leg ulcer. In a patient with a venous leg ulcer and underlying arterial disease, we suggest limiting the use of compression to patients with ankle-brachial index exceeding 0.5 or if absolute ankle pressure is >60 mm Hg. [GRADE - 2; LEVEL OF EVIDENCE - C].

Photodynamic therapy in infected venous and mixed leg ulcers: a pilot experience.

OBJECTIVE: To assess the tolerability and efficacy of photodynamic therapy (PDT) with RLP068, a novel phthalocyanine-derived photosensitiser, in controlling the bacterial load in different leg ulcers, due to vascular pathophysiology. METHOD: An observational study of patients with infected leg ulcers of different pathophysiology, admitted to the hospital for a skin grafting procedure, were included. All patients underwent two sessions of PDT at time zero and after 72 hours. A semi-quantitative swab was taken before and 30 minutes after both sessions of PTD. During the time interval between the two treatments the ulcer was covered with foam dressing and compression therapy was applied to all patients. No systemic or topical antibiotics were administered. Statistical analysis of results was performed. RESULTS: A total of 36 patients (13 males, 23 females; aged 72.4±8.6 years, range: 55-85 years) were recruited; two had ulcers on both legs. PDT was shown to be effective in reducing bacterial load after the first treatment. Before the second PDT treatment (72 hours after first PDT treatment), a slight increase of the bacterial load was observed in all ulcers. However, after the second PDT session, bacterial swab results were negative in all but two ulcers. The procedure was well tolerated in all but four patients, who reported a very severe pain at baseline, which increased during treatment. CONCLUSION: In this study, PDT was effective in reducing bacterial load in patients with infected vascular leg ulcers, and allowed successful skin grafting to take place in all patients. The treatment was generally well tolerated. Studies with a greater number of patients and a control group are planned to confirm these results.

A Polyphenol-Based Multicomponent Nutraceutical in Dysmetabolism and Oxidative Stress: Results from a Pilot Study.

To assess short-term efficacy and safety of a multicomponent nutraceutical (MCN) on dysmetabolism and oxidative stress, a pilot prospective observational study was performed on 21 individuals (12 men and 9 women) who took, for 60 days, 2 tablets per day of an MCN based on antioxidants and metabolism regulators: hydroxytyrosol (15 mg), maqui (300 mg), amla (200 mg), monacolin K (10 mg), berberine (245 mg), astaxanthin (0.5 mg), coenzyme Q10 (100 mg), and folic acid (200 mcg). On day 0 (T0) and day 60 (T60), all participants underwent laboratory tests related to lipid profile, carbohydrate metabolism, oxidative stress, and cellular inflammation. Statistical analysis was applied to the resulting data. A significant improvement of most atherogenesis and oxidative stress biomarkers was recorded (mean figure at T0 and T60, p value): total cholesterol 243.50/194.83 mg/dl, p =.0002; low-density lipoproteins 174.50/124.58 mg/dl, p =.0001; glycemia 96.25/88.50 mg/dl, p =.035; total free radicals 306.44/280.93 U.Carr., p =.036; serum antioxidant capacity 2103.00/2246.06 umol/l, p =.0042; oxidized cholesterol 680.33/597.25 uEq/l, p =.0511. Insulinemia, microalbuminuria, high-density lipoproteins, C-reactive protein, and triglycerides had no statistically significant variation. Body weight and systo-diastolic pressure showed no significant change from T0 to T60. No relevant side effects were reported. The investigated MCN (Eonlipid), based on polyphenols, significantly improved the oxidative stress parameters and decreased the majority of atherogenesis parameters at short term. No significant side effects were reported. Further placebo-controlled studies should possibly corroborate the promising results of this pilot study.

A New Two Component Compression System Turning an Elastic Bandage into an Inelastic Compression Device: Interface Pressure, Stiffness, and Haemodynamic Effectiveness.

INTRODUCTION: Bandage application does not exert consistent compression pressure, leading to extremely variable compression when applied to patients. A new elastic bandage can exert a predefined pressure independently of healthcare providers and the size of the wrapped limb. The bandage system includes a series of non-stretchable patches that when applied to the bandage make it stiff. The aim of this work was to assess, in an experimental setting, the venous ejection fraction (EF) from the lower leg and the tolerability of this new bandage in a group of patients affected by superficial venous incompetence. METHODS: EF was measured using strain gauge plethysmography under baseline conditions and the bandage was applied with a supine pressure of 20 and 30 mmHg, with and without the stiff patches, in 25 patients with severe venous reflux in the great saphenous vein. The interface pressure of the bandages was measured simultaneously in the medial gaiter area. RESULTS: All patients showed EF values that were significantly reduced compared with normal individuals. Elastic bandages with an average pressure of 20 and 30 mmHg in the supine position achieved a slight improvement in EF, and, after applying non-stretchable patches on the same bandage with similar resting pressure, EF was restored to its normal range (p < .001). Improvement in EF correlates with the pressure differences between standing and lying pressure and between muscle systole and diastole during exercise. CONCLUSION: This study confirms that inelastic is much more effective than elastic compression for improving impaired venous haemodynamics. The test material can be applied with a predetermined pressure, which considerably enhances the consistency of application, and it is easily transformed into an inelastic system just by applying stiff patches without any stretch and without significantly increasing the comfortable supine pressure.