Daily Duration of Compression Treatment in Chronic Venous Disease Patients: A Systematic Review.

Background: There are no data on the daily regimen of compression therapy in patients with chronic venous disease. This systematic review aimed to establish the optimal daily duration of compression treatment. Methods: A systematic search of CENTRAL and MEDLINE was performed to identify RCTs, non-RCTs, reviews, systematic reviews, meta-analyses, and guidelines evaluating the use of compression regimens in the treatment of varicose veins. Results: Thirty-two RCTs, three non-RCTs, four observational studies, and two crossover trials reporting the duration and regimes of compression treatment fulfilled the inclusion criteria. The daily duration of compression was reported in patients after invasive treatment, for venous ulcer treatment, in patients with venous symptoms. The quality of the studies varied. We could not conduct a meta-analysis due to the heterogeneity of the research data and their quality. Twenty-three studies reported results of compression usage after invasive procedures. Eight studies reported daily duration regimens in patients with venous ulcers. Nine studies reported the impact of compression on venous symptoms and/or edema or limb volume change. One study was conducted to assess if compression improves QoL in venous patients. While there was a clear difference found in the daily duration depending on the clinical scenario, no data in support of exact regimens were found. Conclusions: There are no reliable data supporting exact daily regimens of compression treatment in various cohorts of CVD patients.

Low concentration of sodium tetradecyl sulfate and hypertonic glucose solution for the treatment of telangiectasia: A prospective randomized clinical trial.

OBJECTIVES: This study aimed to compare telangiectasias disappearance after sclerotherapy with hypertonic glucose (HG) and different concentrations of sodium tetradecyl sulfate (STS). METHODS: Women aged 18-70 years with telangiectasias were included. The primary efficacy endpoint was telangiectasia disappearance. The clearing of vessels was assessed using a six-point scale (from 0 to 5). RESULTS: A total of 116 women completed an 8-week follow-up: 31, 27, 25, and 33 were in the HG 75%, STS 0.05%, STS 0.1%, and STS 0.15% groups, respectively. The median score of vein disappearance was significantly lower in the STS 0.05% (3, 0.25-4), STS 0.1% (3, 1.25-4), and STS 0.15% (4, 2-4) groups than in the HG group (4, 3-5) after 56 days, p = .00002. CONCLUSION: Sclerotherapy of telangiectasias with 75% HG showed significantly better results than low concentrations of STS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04132323.

Monocyte chemoattractant protein 1 plasma concentration in blood from varicose veins decreases under venoactive drug treatment.

BACKGROUND: Vein-specific inflammation leads to vascular smooth muscle cells proliferation and extracellular matrix degradation of vein wall. This process is known as remodeling and is promoted by "trapped" leukocytes. Monocyte chemoattractant protein 1 (MCP-1) is a chemokine responsible for trafficking of leukocytes from blood to vein wall. The aim of this study was to measure the MCP-1 concentration in varicose veins blood before and after venoactive drug therapy and to compare it with a concentration of blood from varicose veins of subjects who did not receive drug treatment. METHODS: Non-randomized comparative study was conducted on 30 patients with primary varicose veins. 20 patients of the study group received diosmin 900 mg/hesperidin 100 mg once daily. 10 controls received no treatment. MCP-1 level was measured (pg/mL) in the blood from varicose veins twice, at the day of inclusion and after 60 days. Legs discomfort related to chronic venous disease (CVD) symptoms was measured with 10-cm Visual Analogue Scale (VAS) at inclusion and at completion of the study. RESULTS: Median (interquartile range, IQR) MCP-1 concentrations in treatment and control groups at inclusion were 171.9 (124.4-216.0) and 157.0 (120.1-163.1), resp., P=0.285. After 60 days of treatment MCP-1 level decreased, but non-significantly to 152.3 (124.1-178.3). In patients who did not receive treatment chemokine level slightly increased to 163.0 (134.0-172.9). Median changes over time were -6.6 (-30.9-7.4) and 10.6 (-3.7-19.2) in the study and control groups, resp. (P=0.048). After 60 days in 12 of 19 and 2 of 9 patients of treatments and control groups MCP-1 decreased (P=0.103). Odds ratio for MCP-1 decreasing was 9.5 (95% CI 1.1-81.5, P=0.043) for those who received venoactive drug. Mean (± standard deviation [SD]) legs discomfort significantly dropped in the study group from 5.7 (±2.5) to 1.9 (±2.2) (P=0.0003), while in controls no changes were registered: 3.4 (±1.3) and 3.5 (± 1.4), resp., P=0.28). Mean difference of VAS at baseline and at follow-up was -3.5 (±2.6) and 0.9 (±2.1), resp. (P<0.0001). CONCLUSIONS: Plasma concentration of MCP-1 in varicose veins blood demonstrates a tendency to decrease under two months treatment with a venoactive drug. Future studies are needed to reveal a possible role of MCP-1 as a target considering its role in varicose veins pathogenesis.

Complications and Adverse Events of Gonadal Vein Embolization with Coils.

Background: The efficacy and safety of gonadal vein embolization (GVE) with coils in the treatment of pelvic venous disease (PeVD) has not been fully investigated, and the outcomes after GVE do not always meet expectations of both doctors and patients. The study was aimed at assessing the incidence and causes of the complications after GVE with coils in patients with PeVD. Methods: This retrospective cohort study included 150 female patients with PeVD who underwent GVE with coils in 2000-2020. A total of 4975 patients with chronic pelvic pain (CPP) were examined, of which 1107 patients had the PeVD-related CPP and 305 underwent surgical or endovascular interventions on the gonadal veins. Complication rates were evaluated 30 days after GVE and classified according to the Society for Interventional Radiology (SIR) adverse event classification system. The pain severity before and after GVE was assessed using a visual analogue scale (VAS). All patients underwent duplex ultrasound after GVE, while patients with persisting pain syndrome and suspected perforation of the gonadal vein were also evaluated using computed tomographic venography. Results: At 30 days after GVE, the CPP was decreased in 109 (72.6%) patients (from 8.2 ± 1.5 at baseline to 1.7 ± 0.8 scores, p = 0.0001) and persisted in 41 (27.4%) patients (mean change from 8.1 ± 0.7 at baseline to 7.8 ± 0.4 scores; p = 0.71). Post-embolic syndrome (PES) occurred in 22% of patients and was completely resolved in 1 month after GVE. The efficacy of GVE in the CPP relief after resolving PES was 94.6%. The GVE complications were identified in 52 (34.6%) patients. Minor complications included access-site hematoma (4%) and allergic reactions (1.3%), and major complications included protrusion of coils (5.3%), thrombosis of the parametrial/uterine veins (21.3%) and deep veins of the calf (2.7%). Conclusions: Gonadal vein embolization with coils in the treatment of PeVD is associated with the development of specific complications and adverse events. The most common complication was pelvic vein thrombosis. Post-embolization syndrome should be considered as an adverse event of this procedure.

Relationships of Pelvic Vein Diameter and Reflux with Clinical Manifestations of Pelvic Venous Disorder.

The causes of chronic pelvic pain (CPP) in patients with pelvic venous disorder (PeVD) are not completely understood. Various authors consider dilation of pelvic veins (PeVs) and pelvic venous reflux (PVR) as the main mechanisms underlying symptomatic forms of PeVD. The aim of this study was to assess relationships of pelvic vein dilation and PVR with clinical manifestations of PeVD. This non-randomized comparative cohort study included 80 female patients with PeVD who were allocated into two groups with symptomatic (n = 42) and asymptomatic (n = 38) forms of the disease. All patients underwent duplex scanning and single-photon emission computed tomography (SPECT) of PeVs with in vivo labeled red blood cells (RBCs). The PeV diameters, the presence, duration and pattern of PVR in the pelvic veins, as well as the coefficient of pelvic venous congestion (CPVC) were assessed. Two groups did not differ significantly in pelvic vein diameters (gonadal veins (GVs): 7.7 ± 1.3 vs. 8.5 ± 0.5 mm; parametrial veins (PVs): 9.8 ± 0.9 vs. 9.5 ± 0.9 mm; and uterine veins (UVs): 5.6 ± 0.2 vs. 5.5 ± 0.6 mm). Despite this, CPVC was significantly higher in symptomatic versus asymptomatic patients (1.9 ± 0.4 vs. 0.7 ± 0.2, respectively; p = 0.008). Symptomatic patients had type II or III PVR, while asymptomatic patients had type I PVR. The reflux duration was found to be significantly greater in symptomatic versus asymptomatic patients (median and interquartile range: 4.0 [3.0; 5.0] vs. 1.0 [0; 2.0] s for GVs, p = 0.008; 4.0 [3.0; 5.0] vs. 1.1 [1.0; 2.0] s for PVs, p = 0.007; and 2.0 [2.0; 3.0] vs. 1.0 [1.0; 2.0] s for UVs, p = 0.04). Linear correlation analysis revealed a strong positive relationship (Pearson's r = 0.78; p = 0.007) of CPP with the PVR duration but not with vein diameter. The grade of PeV dilation may not be a determining factor in CPP development in patients with PeVD. The presence and duration of reflux in the pelvic veins were found to be predictors of the development of symptomatic PeVD.

The Effect of Venoactive Drug Therapy on the Development and Severity of Post-Embolization Syndrome in Endovascular Interventions on the Gonadal Veins.

Objective. To evaluate the incidence of post-embolization syndrome (PES) and the effect of venoactive therapy on its development, severity, and duration after endovascular embolization of gonadal veins (EEGV) with coils in patients with pelvic congestion syndrome (PCS). Materials and Methods. We analyzed the outcomes of EEGV with coils in 70 female patients who received (n = 38; group 1) or did not receive (n = 32; group 2) treatment with a venoactive drug (VAD) before and after the procedure. Assessments of the EEGV efficacy and for possible signs of PES were done on days 1, 5, 10, 15, 20, and 30 after the intervention. All patients underwent transvaginal and transabdominal duplex ultrasound scanning (DUS) after EEGV. In addition, patients with PES were examined using the computed tomography of the pelvic veins in the postprocedural period. Results. Technical success of EEGV was achieved in 100% of patients. Pelvic venous pain (PVP) reduction after EEGV was observed in 77.1% of patients. The PES was diagnosed in 18.6% of cases (10.5% in group 1 vs. 28.1% in group 2, p > 0.05). In three patients of group 1, the protrusion of coils was suspected and eventually verified during the resection of the left gonadal vein with coils. The group 1 patients had less severe post-embolization pain (6.2 ± 0.4 vs. 7.8 ± 0.3 scores in group 2; p = 0.009) and three times shorter duration of PES (5.0 ± 1.2 vs. 16.2 ± 2.7 days; p = 0.003). No significant differences in the diameters of gonadal veins, side of embolization, and number of coils were revealed between patients with and without PES. The rate of parametrium vein thrombosis was found to be significantly higher in patients with PES than in those without PES (30.7% vs. 18.5%, respectively; p < 0.05). Conclusion. The PES is a frequent complication of EEGV with coils and occurs in 18.6% of patients. Venoactive treatment does not effect the incidence of this complication but reduces the PES severity and duration.

Stratification of pelvic venous reflux in patients with pelvic varicose veins.

OBJECTIVE: We investigated the association between the pattern and duration of pelvic venous reflux (PVR) and pelvic pain severity in patients with pelvic varicose veins (PVVs). METHODS: The present retrospective study included 600 female patients with PVVs. Of the 600 patients, 453 had had PVVs and pelvic congestion syndrome (group 1) and 147 had had an asymptomatic disease course (group 2). Pelvic venous pain (PVP) was assessed using a visual analog scale. All the patients had undergone duplex ultrasound of the left and right renal veins, external, internal, and common iliac veins, and parametrial, uterine, gonadal, and vulvar veins (PV, UV, GV, and VV, respectively), with an assessment of their patency and diameter and the presence and duration of reflux. Reflux in the pelvic veins was considered pathologic if it lasted for >1 second. RESULTS: In group 1, PVR type I (1-2 seconds), II (3-5 seconds), and III (>5 seconds or spontaneous reflux in the absence of a loading test) was found in 31%, 58%, and 11% of the patients, respectively. Moderate and severe reflux (types II and III) was associated with severe PVP (mean score, 8.3 ± 0.5) in 69% of the group 1 patients. A combination of reflux in the GV, PV, UV, and internal iliac vein was associated with severe PVP (mean score, 8.1 ± 0.3) in 51% of these patients. A combination of reflux in the PVs, UVs, and VVs was associated with moderate pain (mean score, 5.3 ± 0.2) in 49.2% of group 1. In group 2, PVR type I, II, and III was present in 95%, 4%, and 1% of the patients, respectively, and was observed in the PV only in patients with type I; in the GVs, PVs, UVs, and internal iliac veins in those with type II; and in the PVs and GVs in the patients with type III reflux. Reflux in the GVs and UVs was significantly more prevalent in group 1 than in group 2 (GVs, 51% vs 6%; P = .0001; UVs, 57% vs 7%; P = .0001). A combination of reflux in the GVs and UVs was a predictor of severe PVVs (odds ratio, 19.7; 95% confidence interval, 11.3-34.6). CONCLUSIONS: In patients with PVVs, the presence and severity of pelvic pain will be determined by the type of PVR and its distribution in the pelvic veins. The combination of moderate to severe reflux (types II and III) in the PVs, UVs, and GVs was a predictor of severe PVP. Patients with asymptomatic PVVs were characterized by mild reflux (type I) in the PVs, with rare involvement of the GVs and UVs.

A randomized trial of class II compression sleeves for full legs versus stockings after thermal ablation with phlebectomy.

OBJECTIVE: Compression stockings and bandages are widely used after invasive treatment of varicose veins. The goals of compression after venous interventions are to reduce pain, bruising, and ecchymosis. Nevertheless, patients often report discomfort with the compression. To make postprocedural compression more tolerable, foot-sparing bandages were tested in a randomized clinical trial of noninferiority. METHODS: A total of 187 patients were randomized to use class II foot-sparing compression sleeves for the full leg or class II stockings after radiofrequency ablation with concomitant phlebectomy. The primary endpoint was the quality of life, measured using the Chronic Venous Disease Quality of Life Questionnaire 20-item scale 30 days after intervention. The secondary endpoints were pain in the leg and discomfort related to the compression garment, which were assessed using the visual analog scale (VAS) at 2, 7, 14, and 30 days. RESULTS: The global index score of the questionnaire was 66.1 and 70.6 and 83.8 and 87.7 for the sleeve and stocking groups before and 30 days after intervention, respectively (P = .542 and P = .150, respectively). The VAS for pain score in the operated leg was slightly higher in the sleeve group the day after the intervention (score, 2.1 vs 1.6; P = .03). At 7, 14, and 30 days, the VAS for pain scores did not differ significantly (score, 0.7 vs 0.5; 0.5 vs 0.3; and 0.1 vs 0.1, respectively; P = NS for all). The VAS for discomfort score was not significantly different statistically in the study group at 2 days (sleeve, 1.9; vs stocking, 1.4; P = .08) but was higher after 7 days (sleeve, 0.9; vs stocking, 0.6; P = .008). No difference in discomfort was found between the study and control groups at 14 or 30 days (sleeve, 0.6; vs stocking, 0.4; and sleeve, 0.4; vs stocking, 0.4, respectively; P = NS for both). CONCLUSIONS: Quality of life after thermal ablation with phlebectomy improved equivalently in patients who had used class II compression sleeves for full legs and those who had used class II compression stockings. Pain and discomfort were slightly higher in the sleeve group.

Inferior vena cava filters utilization in patients with venous thromboembolism: Analysis of a database of a tertiary hospital.

PURPOSE: The aim of the study was to assess the inferior vena cava filter (IVCF) utilization in patients with venous thromboembolism (VTE) in tertiary care. METHODS: We performed a retrospective analysis of database of a tertiary hospital in 2016-2017. All the records of patients admitted for VTE or diagnosed with VTE being hospitalized for other reasons were extracted. The data collected were number of patients, who received IVCF, indications to filter insertion, PE and death rate after procedure, frequency of IVCF occlusion. RESULTS: 2399 patients with VTE were admitted to hospital. 442 (18,4%) of them received IVCF (239 in 2016 and 203 in 2017). Retrievable models were used in most cases (98,8%). In 119 (5,0%) patients cava filters were used due to contraindications for anticoagulation, while in 184 (7,7%) patients' anticoagulation was not effective and thrombosis progression was registered. 101 (4,2%) patients received IVCF due to high PE risk (length of floating thrombus ≥7 cm, in proximal location), high pulmonary hypertension was indication to IVCF insertion in 38 (1,6%) patients with deep vein thrombosis (DVT) in combination with pulmonary embolism (PE). Overall mortality rate after IVCF insertion was 5 (0,2%). No fatal PE was registered. IVCF occlusion during hospitalization occurred in 116 (4,8%) cases. Only 29 (1,2%) of patients were admitted back for IVCF removal. CONCLUSIONS: Every one in five patients with proximal DVT and/or PE receives IVCF in a routine practice in tertiary hospital. The most common indications for IVCF implantation were inability for anticoagulation or anticoagulation failure. Removal rate of retrievable cava filters is low.

Cancer Stem Cells: Emergent Nature of Tumor Emergency.

A functional analysis of 167 genes overexpressed in Krebs-2 tumor initiating cells was performed. In the first part of the study, the genes were analyzed for their belonging to one or more of the three groups, which represent the three major phenotypic manifestation of malignancy of cancer cells, namely (1) proliferative self-sufficiency, (2) invasive growth and metastasis, and (3) multiple drug resistance. 96 genes out of 167 were identified as possible contributors to at least one of these fundamental properties. It was also found that substantial part of these genes are also known as genes responsible for formation and/or maintenance of the stemness of normal pluri-/multipotent stem cells. These results suggest that the malignancy is simply the ability to maintain the stem cell specific genes expression profile, and, as a consequence, the stemness itself regardless of the controlling effect of stem niches. In the second part of the study, three stress factors combined into the single concept of "generalized cellular stress," which are assumed to activate the expression of these genes, were defined. In addition, possible mechanisms for such activation were identified. The data obtained suggest the existence of a mechanism for the de novo formation of a pluripotent/stem phenotype in the subpopulation of "committed" tumor cells.

Clinical significance of the UGT1A1*28 allele detection in HIV-infected patients.

INTRODUCTION: The UGT1A1*28 (rs8175347) polymorphism is associated with hyperbilirubinemia. The presence of 6 TA-repeats in the UGT1A1 gene promoter region corresponds to normal UGT1TA1 activity. A detection of 7 TA-repeats in hetero- or homozygous individuals [(TA)6/(TA)7 and (TA)7/(TA)7] is associated with lower UGT1TA1 activity, which may eventually result in the development of Gilbert syndrome and/or modified individual response to drugs metabolized by this enzyme. ATV contributes to the decreased levels of UGT1A1, which may lead to elevations of indirect bilirubin, jaundice and even to therapy discontinuation. We evaluated the prevalence of the UGT1A1*28 among HIV-infected patients and the dependence of the frequency and severity of AE during ATV treatment on individual genetic characteristics. MATERIALS AND METHODS: 47 HIV-infected patients was screen for UGT1A1 genotype and the presence of UGT1A1*28. All patients received ATV in the HAART regimen for 48 weeks. Changes in the total, direct and indirect bilirubin, ALT, AST, GGT and jaundice were evaluated. Statistical analysis was performed using Microsoft Office Excel for Windows XP Professional 2007 and Biostat. RESULTS: All patients were followed up in the AIDS Center (males 72.3%, median age 33 years, median CD4+ count-282 cells/µl (19.5%)). HBV/HCV was in 36.2% patients. Ten patients had risk factors that could affect bilirubin turnover (chronic cholecystitis, biliary dyskinesia, etc.). Genotype (TA)6/(TA)6 was found in 42.6% patients, (TA)6/(TA)7-42.6% and (TA)7/(TA)7-14.9%. Overall prevalence of UGT1A1*28 was 57.4%, and homozygous allele frequency was 14.9%. G3/4 of indirect bilirubin were detected in 36.2% patients [(TA)6/(TA)6 in 10-20%, (TA)6/(TA)7-25-40%, (TA)7/(TA)7-72-86%], and significant jaundice in 10.6% [80% with (TA)7/(TA)7]. The OR for hyperbilirubinemia>40 µmol/L in patients with heterozygous UGT1A1*28 was increased 3 times over patients without this allele (OR 3.07, 95% CI 1.54-4.6) and 34 times as compared with homozygotes (OR 33.9, 95% CI 31.45-36.35). The presence of additional risk factors increased the probability of G3/4 hyperbilirubinemia. No significant changes in the ALT, AST, and GGT levels were observed. CONCLUSIONS: The risk of severe hyperbilirubinemia during ATV treatment is minimal for patients without UGT1A1*28 and no more than one additional risk factor and for patients with UGT1A1*28 and no additional risk factors; patients with homozygous genotype UGT1A1*28 are at the highest risk.