Changes of the serum properties and its effect on the endothelial cells restoration in patients with chronic disease treated with sulodexide.

OBJECTIVE: Inflammation and endothelial dysfunction are important venous changes in patients with chronic venous disease (CVD). The use of the venoactive drugs remains an important treatment modality for patients with CVD, reducing the severity of the CVD-related symptoms and swelling but also reducing inflammation and protecting endothelial cells. In this research, the effects of the serum obtained from patients with CVD before and after sulodexide treatment were evaluated for in vivo and in vitro inflammatory markers and endothelial cell function. METHODS: Inflammatory markers (IL-6, matrix metalloproteinase-9 [MMP-9], vascular cell adhesion molecule-1 [VCAM-1], and von Willebrand factor [vWF]) from the incompetent great saphenous veins (GSVs) and from the systemic venous circulation were studied in 10 patients with CVD (C2s) before and after 2 months of sulodexide (2 × 500 LSU/d) therapy. Serum from pretreatment and following sulodexide treated patients was evaluated for in vitro cultured human umbilical vein endothelial cell function. RESULTS: The serum collected from lower leg incompetent GSVs had significantly elevated levels of VCAM-1 (+29%, P < .001) compared with the serum from the systemic circulation. Endothelial cells exposed to the serum from the incompetent lower leg veins of the untreated CVD patients demonstrated higher stimulated synthesis of MMP-9 (+17%, P < .01), as well as increased markers of senescence (prolongation of population doubling time, ß-galactosidase activity, and expression of p21 and p53 genes). CVD serum-induced senescent endothelial cells had a higher expression of genes regulating IL-6, MMP-9, VCAM-1, and vWF synthesis. The overall proinflammatory effect on endothelial cells by the serum collected from the incompetent GSVs was stronger as compared with the serum from the systemic circulation. Serum collected from the veins after sulodexide treatment caused lower levels of endothelial cell inflammatory markers as well as respective gene expression than serum obtained at the beginning of the study (before sulodexide treatment). Sulodexide application also reduced the inflammatory secretory activity of the senescent endothelial cells. Sulodexide treatment resulted in the decrease of the majority of the studied inflammatory parameters in both lower limb incompetent vein and systemic blood. CONCLUSIONS: In patients with CVD, there are significant differences between circulating inflammatory markers analyzed from the lower leg incompetent GSV segments compared with the systemic circulation, indicating a higher inflammatory condition in CVD. Treatment with sulodexide reduces the proinflammatory and endothelial cell activation properties of the serum from patients with CVD. CLINICAL RELEVANCE: The study documented the significant proinflammatory human vascular endothelial cell activation when exposed to the serum collected from the varicose veins as compared with the serum from the systemic circulation in patients with chronic venous disease (CVD). The inflammatory marker expression, endothelial dysfunction, and endothelial cell senescence transformation can be successfully controlled and downregulated by patients' exposure to the glycosaminoglycan (sulodexide) treatment. Further studies are needed to confirm if glycosaminoglycan application can prevent further CVD clinical progression due to potential CVD-related pathological processes' modulation and their downregulation.

Predicting wound complications following lower extremity revascularization.

OBJECTIVE: The aim of this study was to create a simple risk score to identify factors associated with wound complications after infrainguinal revascularization. METHODS: The Veterans Affairs Surgical Quality Improvement Program national data set was queried from 2005 to 2021 to identify 22,114 patients undergoing elective open revascularization for peripheral arterial disease (claudication, rest pain, tissue loss) or peripheral aneurysm. Emergency and trauma cases were excluded. The data set was divided into a two-thirds derivation set and one-third validation set to create a risk prediction model. The primary end point was wound complication (wound dehiscence, superficial/deep wound surgical site infection). Eight independent risk factors for wound complications resulted from the model and were assigned whole number integer risk scores. Summary risk scores were collapsed into categories and defined as low (0-3 points), moderate (4-7 points), high (8-11 points), and very high (>12 points). RESULTS: The wound complication rate in the derivation data set was 9.7% (n = 1428). Predictors of wound complication included age ≤73 (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.08-1.46), body mass index ≥35 kg/m2 (OR, 1.99; 95% CI, 1.68-2.36), non-Hispanic White (vs others: OR, 1.48; 95% CI, 1.30-1.69), diabetes (OR, 1.23; 95% CI, 1.10-1.37), white blood cell count >9900/mm3 (OR, 1.18; 95% CI, 1.03-1.35), absence of coronary artery disease (OR, 1.27; 95% CI, 1.03-1.35), operative time >6 hours (OR, 1.20; 95% CI, 1.05-1.37), and undergoing a femoral endarterectomy in conjunction with bypass (OR, 1.34; 95% CI, 1.14-1.57). In both the derivation and validation sets, wound complications correlated with risk category. Among the defined categories in the derivation set, wound complication rates were 4.5% for low-risk patients, 8.5% for moderate-risk patients, 13.8% for high-risk patients, and 23.8% for very high-risk patients, with similar results for the internal validation data set. Operative indication did not independently associate with wound complications. Patients with wound complications had higher rates of reoperation and graft failure. CONCLUSIONS: This risk prediction model uses easily obtainable clinical metrics that allow for informed discussion of wound complication risk for patients undergoing open infrainguinal revascularization.

Venous compression syndromes in females: A descriptive review.

Venous compression syndromes have been described, yet the role of sex is poorly understood. Although iliac vein compression has been discussed more often with the advent of newer technologies, research has fallen short on defining epidemiology, best practices for evaluation and treatment, and differences in responses to treatment between men and females. The authors report on iliac vein compression, nonthrombotic renal vein compression, and other venous compression syndromes in females. Literature searches of PubMed were performed using the following keywords: females/females and May Thurner, venous stenting, venous outcomes, deep venous disease, deep venous compression, venous stenting, renal vein compression, renal vein surgery/stent, popliteal vein entrapment, venous thoracic vein entrapment, and popliteal vein entrapment. The articles prompted the authors to research further as the referenced articles were reviewed. Sex representation has not been addressed adequately in the research of venous compression syndromes, making the discussion of best treatment options and long-term outcomes difficult. More specific understanding of epidemiology and response to interventions will only come from research that addresses these issues directly, understanding that some of these syndromes occur rarely.

Fake-news-free evidence-based communication for proper vein-lymphatic disease management.

Published scientific evidence demonstrate the current spread of healthcare misinformation in the most popular social networks and unofficial communication channels. Up to 40% of the medical websites were identified reporting inappropriate information, moreover being shared more than 450,000 times in a 5-year-time frame. The phenomenon is particularly spread in infective diseases medicine, oncology and cardiovascular medicine. The present document is the result of a scientific and educational endeavor by a worldwide group of top experts who selected and analyzed the major issues and related evidence-based facts on vein and lymphatic management. A section of this work is entirely dedicated to the patients and therefore written in layman terms, with the aim of improving public vein-lymphatic awareness. The part dedicated to the medical professionals includes a revision of the current literature, summing up the statements that are fully evidence-based in venous and lymphatic disease management, and suggesting future lines of research to fulfill the still unmet needs. The document has been written following an intense digital interaction among dedicated working groups, leading to an institutional project presentation during the Universal Expo in Dubai, in the occasion of the v-WINter 2022 meeting.

Effect of a Decision Aid on Agreement Between Patient Preferences and Repair Type for Abdominal Aortic Aneurysm: A Randomized Clinical Trial.

Importance: Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair. Objective: To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive. Design, Setting, and Participants: In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021. Interventions: Presurgical consultation using a decision aid vs usual care. Main Outcomes and Measures: The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios. Results: Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70). Conclusions and Relevance: Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT03115346.

Factors associated with preference of choice of aortic aneurysm repair in the PReference for Open Versus Endovascular repair of AAA (PROVE-AAA) study.

OBJECTIVE: Patients can choose between open repair and endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). However, the factors associated with patient preference for one repair type over another are not well-characterized. Here we assess the factors associated with preference of choice for open or endovascular AAA repair among veterans exposed to a decision aid to help with choosing surgical treatment. METHODS: Across 12 Veterans Affairs hospitals, veterans received a decision aid covering domains including patient information sources and understanding preference. Veterans were then given a series of surveys at different timepoints examining their preferences for open versus endovascular AAA repair. Questions from the preference survey were used in analyses of patient preference. Results were analyzed using χ2 tests. A logistic regression analysis was performed to assess factors associated with preference for open repair or preference for EVAR. RESULTS: A total of 126 veterans received a decision aid informing them of their treatment choices, after which 121 completed all preference survey questions; five veterans completed only part of the instruments. Overall, veterans who preferred open repair were typically younger (70 years vs 73 years; P = .02), with similar rates of common comorbidities (coronary disease 16% vs 28%; P = .21), and similar aneurysms compared with those who preferred EVAR (6.0 cm vs 5.7 cm; P = .50). Veterans in both preference categories (28% of veterans preferring EVAR, 48% of veterans preferring open repair) reported taking their doctor's advice as the top box response for the single most important factor influencing their decision. When comparing the tradeoff between less invasive surgery and higher risk of long-term complications, more than one-half of veterans preferring EVAR reported invasiveness as more important compared with approximately 1 in 10 of those preferring open repair (53% vs 12%; P < .001). Shorter recovery was an important factor for the EVAR group (74%) and not important in the open repair group (76%) (P = .5). In multivariable analyses, valuing a short hospital stay (odds ratio, 12.4; 95% confidence interval, 1.13-135.70) and valuing a shorter recovery (odds ratio, 15.72; 95% confidence interval, 1.03-240.20) were associated with a greater odds of preference for EVAR, whereas finding these characteristics not important was associated with a greater odds of preference for open repair. CONCLUSIONS: When faced with the decision of open repair versus EVAR, veterans who valued a shorter hospital stay and a shorter recovery were more likely to prefer EVAR, whereas those more concerned about long-term complications preferred an open repair. Veterans typically value the advice of their surgeon over their own beliefs and preferences. These findings need to be considered by surgeons as they guide their patients to a shared decision.

Peri-Procedural Management of Hemodynamic Instability in Patients Undergoing Carotid Revascularization.

Acute perioperative changes in arterial pressure occur frequently, particularly in patients with cardiovascular disease or those receiving vasoactive medications, or in relation to certain cardiovascular surgical procedures. Hemodynamic Instability (HI) is common in patients undergoing carotid revascularization because of unique patho-physiological and surgical factors. The operation, by necessity, disrupts the afferent pathway of the baroreflex, which can lead to postendarterectomy HI. Poor arterial pressure control is associated with increased morbidity and mortality after carotid revascularization, but good control of arterial pressure is often difficult to achieve in practice. The incidence, implications, and etiology of HI associated with carotid surgery are reviewed, and some recommendations made for its management. Close monitoring and titration of therapy are probably the most important considerations rather than specific choice of agents.

Late type III endoleaks are common in early generation Endologix AFX stent grafts.

OBJECTIVE: Early generation Endologix AFX endovascular abdominal aortic aneurysm (AAA) stent graft devices are at risk of developing type IIIa (intercomponent/overlap-related) as well as type IIIb (fabric tear) endoleaks over time. Current follow-up studies are limited to short (<24 months) and midterm (24-48 months) reports. The purpose of this study was to identify the incidence of type III endoleaks associated with these endografts over a long-term follow-up (>4 years) period and discuss current management strategies. METHODS: A retrospective, single-institution cohort analysis of all Endologix AFX endografts implanted from October 2011 to October 2016 was performed. Patient characteristics, imaging, and follow-up were obtained via chart review. Type III endoleaks were characterized based on computed tomography angiogram/operative findings and confirmed by two surgeons. Statistical analysis was performed with SAS v9.4. RESULTS: Sixty-three patients underwent AFX stent graft implantation for aneurysmal disease. Forty-seven patients comprised the final cohort for analysis after exclusions were made for primary iliac aneurysms as well as off-label use of the device (eg, hypogastric snorkel) or primary occlusive indications. The average age was 73.3 years, with the longest follow-up being 8.7 years (median, 5.2 years). Most AAAs (89.2%) were fusiform, with initial median diameter 5.5 cm. Initial 30-day mortality was 0%. Of the initial cohort, 10 (21.3%) type III endoleaks were treated, of which six (60%) were type IIIa and four (40%) were type IIIb. By time-to-event analysis at latest follow-up, freedom from type III intervention was 48% at 8 years. The median time to type III endoleak discovery was 4.7 years (range, 1.1-7.2 years), an interval that was similar for type IIIa and type IIIb leak types (P = .73). Patients with type III endoleaks had average sac growth of 1.3 cm over the follow-up interval compared with a net decrease for patients without type III endoleaks (P < .0001). Of the 10 patients treated for type III leaks, seven (70%) underwent complete endovascular re-lining, one (10%) had partial re-lining, and two (20.0%) underwent open endograft explant with aortic graft reconstruction. Reintervention 30-day mortality was 0% for all approaches. CONCLUSIONS: Early generation Endologix AFX stent grafts have a high rate of type III endoleaks, with freedom from type III leak <50% at 8-year follow-up. Most of these are not detected until several years (>4.5 years) after initial implantation, beyond the range of the follow-up interval of most published reports. Long-term imaging surveillance is critical, and a low threshold for complete relining should be considered with any sign of sac enlargement, even if endoleak is not clearly demonstrated in patients with early generation Endologix AFX grafts.

The American Venous Forum, American Vein and Lymphatic Society and the Society for Vascular Medicine expert opinion consensus on lymphedema diagnosis and treatment.

BACKGROUND: Lymphedema imposes a significant economic and social burden in modern societies. Controversies about its risk factors, diagnosis, and treatment permeate the literature. The goal of this study was to assess experts' opinions on the available literature on lymphedema while following the Delphi methodology. METHODS: In December of 2019, the American Venous Forum created a working group tasked to develop a consensus statement regarding current practices for the diagnosis and treatment of lymphedema. A panel of experts was identified by the working group. The working group then compiled a list of clinical questions, risk factors, diagnosis and evaluation, and treatment of lymphedema. Fifteen questions that met the criteria for consensus were included in the list. Using a modified Delphi methodology, six questions that received between 60% and 80% of the votes were included in the list for the second round of analysis. Consensus was reached whenever >70% agreement was achieved. RESULTS: The panel of experts reached consensus that cancer, infection, chronic venous disease, and surgery are risk factors for secondary lymphedema. Consensus was also reached that clinical examination is adequate for diagnosing lymphedema and that all patients with chronic venous insufficiency (C3-C6) should be treated as lymphedema patients. No consensus was reached regarding routine clinical practice use of radionuclide lymphoscintigraphy as a mandatory diagnostic tool. However, the panel came to consensus regarding the importance of quantifying edema in all patients (93.6% in favor). In terms of treatment, consensus was reached favoring the regular use of compression garments to reduce lymphedema progression (89.4% in favor, 10.6% against; mean score of 79), but the use of Velcro devices as the first line of compression therapy did not reach consensus (59.6% in favor vs 40.4% against; total score of 15). There was agreement that sequential pneumatic compression should be considered as adjuvant therapy in the maintenance phase of treatment (91.5% in favor vs. 8.5% against; mean score of 85), but less so in its initial phases (61.7% in favor vs. 38.3% against; mean score of 27). Most of the panel agreed that manual lymphatic drainage should be a mandatory treatment modality (70.2% in favor), but the panel was split in half regarding the proposal that reductive surgery should be considered for patients with failed conservative treatment. CONCLUSION: This consensus process demonstrated that lymphedema experts agree on the majority of the statements related to risk factors for lymphedema, and the diagnostic workup for lymphedema patients. Less agreement was demonstrated on statements related to treatment of lymphedema. This consensus suggests that variability in lymphedema care is high even among the experts. Developers of future practice guidelines for lymphedema should consider this information, especially in cases of low-level evidence that supports practice patterns with which the majority of experts disagree.

Review of the current evidence for topical treatment for venous leg ulcers.

OBJECTIVE: The development of a venous leg ulcer (VLU) represents the most severe clinical manifestation of a chronic venous disease. Despite major progress, our understanding of the VLU pathogenesis and wound healing biology has remained limited. Treatment of VLUs remains a serious challenge for physicians of different specialties. In the present review, we focused on describing the rationale and scientific basis for topical wound care in the management of VLUs. METHODS: A literature review was performed to summarize the methods with proven efficacy in VLU management. A systematic search was also performed to identify new evidence from the randomized controlled trials reported from 2014 to 2021. The scientific challenges, clinical practice concerns, economic obstacles, and possible directions for further research have been discussed. RESULTS: Hundreds of topical products have been advertised for the treatment of VLUs. However, the reported data on the topical treatment of venous ulcers are insufficient, scattered, and weak, with significant methodologic flaws. A total of 43 randomized controlled trials on the topical treatment of VLUs were reported from 2014 to 2021. Thus, the clinical practice guidelines require updating. We identified major gaps in knowledge and have provided suggestions for future research directions. CONCLUSIONS: The American Venous Forum Research Committee would like to bring attention to the use of topical wound care for VLUs as a critical gap in knowledge and to encourage scientists, practitioners, and industry to collaborate to fill this gap.

Mechanisms of Lower Extremity Vein Dysfunction in Chronic Venous Disease and Implications in Management of Varicose Veins.

Chronic venous disease (CVD) is a common venous disorder of the lower extremities. CVD can be manifested as varicose veins (VVs), with dilated and tortuous veins, dysfunctional valves and venous reflux. If not adequately treated, VVs could progress to chronic venous insufficiency (CVI) and lead to venous leg ulcer (VLU). Predisposing familial and genetic factors have been implicated in CVD. Additional environmental, behavioral and dietary factors including sedentary lifestyle and obesity may also contribute to CVD. Alterations in the mRNA expression, protein levels and proteolytic activity of matrix metalloproteinases (MMPs) have been detected in VVs and VLU. MMP expression/activity can be modulated by venous hydrostatic pressure, hypoxia, tissue metabolites, and inflammation. MMPs in turn increase proteolysis of different protein substrates in the extracellular matrix particularly collagen and elastin, leading to weakening of the vein wall. MMPs could also promote venous dilation by increasing the release of endothelium-derived vasodilators and activating potassium channels, leading to smooth muscle hyperpolarization and relaxation. Depending on VVs severity, management usually includes compression stockings, sclerotherapy and surgical removal. Venotonics have also been promoted to decrease the progression of VVs. Sulodexide has also shown benefits in VLU and CVI, and recent data suggest that it could improve venous smooth muscle contraction. Other lines of treatment including induction of endogenous tissue inhibitors of metalloproteinases (TIMPs) and administration of exogenous synthetic inhibitors of MMPs are being explored, and could provide alternative strategies in the treatment of CVD.

A Unique Case of Acute Coronary Syndrome in a Patient With COVID-19 Infection.

The coronavirus pandemic has caused significant mortality and morbidity in just over a year of its course since the first case was identified in Wuhan, China in December 2019. The varied presenting symptoms of this enveloped positive-sense single-stranded RNA virus infection and the unknown surrounding the pathophysiology of the disease process have been extensively reported in the literature. In this case report, we present a coronavirus disease 2019 (COVID-19) positive patient who presented with chest pain, diagnosed with acute coronary syndrome. Interestingly, the patient was noted to have non-ST elevation myocardial infarction with cardiac catheterization showing coronary microthrombi rather than typical acute coronary thrombotic occlusive disease.

Sulodexide in the Treatment of Patients with Early Stages of COVID-19: A Randomized Controlled Trial.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce several vascular endothelial-dependent systemic complications, and sulodexide has pleiotropic actions on the vascular endothelium, which may prove beneficial. We aimed to assess the effect of sulodexide when used within 3 days of coronavirus disease 2019 (COVID-19) clinical onset. We conducted a randomized placebo-controlled outpatient trial. To be included, patients must have been at high risk for severe clinical progression. Participants received sulodexide (oral 1,000 LRU/d) or placebo for 21 days. The primary endpoint was the need for hospital care. Also assessed were patients' need for supplemental oxygen as well as D-dimer and C-reactive protein (CRP) levels, thromboembolic events, major bleeding, and mortality. A total of 243 patients were included in the per-protocol analysis from June 5 to August 30, 2020. Of these, 124 received sulodexide and 119 received a placebo. Only 17.7% of the patients in the sulodexide group required hospitalization, compared with 29.4% in the placebo group (p = 0.03). This benefit persisted in the intention-to-treat analysis (15% in sulodexide group vs. 24% with placebo [p = 0.04]). With sulodexide, fewer patients required supplemental oxygen (30 vs. 42% [p = 0.05]). After 2 weeks, fewer patients had D-dimer levels >500 ng/dL (22 vs. 47% [p < 0.01]), and patients also had lower mean CRP levels (12.5 vs. 17.8 mg/dL [p < 0.01]). There were no between-group differences in thromboembolic events, major bleeding, or mortality. Treatment of COVID-19 patients with sulodexide, when provided within 3 days of clinical onset, improved their clinical outcomes. Although the results should be confirmed, sulodexide could be valuable in an outpatient setting.

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment.

Venous leg ulcers (VLUs) are one of the most common ulcers of the lower extremity. VLU affects many individuals worldwide, could pose a significant socioeconomic burden to the healthcare system, and has major psychological and physical impacts on the affected individual. VLU often occurs in association with post-thrombotic syndrome, advanced chronic venous disease, varicose veins, and venous hypertension. Several demographic, genetic, and environmental factors could trigger chronic venous disease with venous dilation, incompetent valves, venous reflux, and venous hypertension. Endothelial cell injury and changes in the glycocalyx, venous shear-stress, and adhesion molecules could be initiating events in VLU. Increased endothelial cell permeability and leukocyte infiltration, and increases in inflammatory cytokines, matrix metalloproteinases (MMPs), reactive oxygen and nitrogen species, iron deposition, and tissue metabolites also contribute to the pathogenesis of VLU. Treatment of VLU includes compression therapy and endovenous ablation to occlude the axial reflux. Other interventional approaches such as subfascial endoscopic perforator surgery and iliac venous stent have shown mixed results. With good wound care and compression therapy, VLU usually heals within 6 months. VLU healing involves orchestrated processes including hemostasis, inflammation, proliferation, and remodeling and the contribution of different cells including leukocytes, platelets, fibroblasts, vascular smooth muscle cells, endothelial cells, and keratinocytes as well as the release of various biomolecules including transforming growth factor-ß, cytokines, chemokines, MMPs, tissue inhibitors of MMPs (TIMPs), elastase, urokinase plasminogen activator, fibrin, collagen, and albumin. Alterations in any of these physiological wound closure processes could delay VLU healing. Also, these histological and soluble biomarkers can be used for VLU diagnosis and assessment of its progression, responsiveness to healing, and prognosis. If not treated adequately, VLU could progress to non-healed or granulating VLU, causing physical immobility, reduced quality of life, cellulitis, severe infections, osteomyelitis, and neoplastic transformation. Recalcitrant VLU shows prolonged healing time with advanced age, obesity, nutritional deficiencies, colder temperature, preexisting venous disease, deep venous thrombosis, and larger wound area. VLU also has a high, 50-70% recurrence rate, likely due to noncompliance with compression therapy, failure of surgical procedures, incorrect ulcer diagnosis, progression of venous disease, and poorly understood pathophysiology. Understanding the molecular pathways underlying VLU has led to new lines of therapy with significant promise including biologics such as bilayer living skin construct, fibroblast derivatives, and extracellular matrices and non-biologic products such as poly-N-acetyl glucosamine, human placental membranes amnion/chorion allografts, ACT1 peptide inhibitor of connexin 43, sulodexide, growth factors, silver dressings, MMP inhibitors, and modulators of reactive oxygen and nitrogen species, the immune response and tissue metabolites. Preventive measures including compression therapy and venotonics could also reduce the risk of progression to chronic venous insufficiency and VLU in susceptible individuals.

Comparative Efficacy and Safety of Sulodexide and Other Extended Anticoagulation Treatments for Prevention of Recurrent Venous Thromboembolism: A Bayesian Network Meta-analysis.

Objective This network meta-analysis (NMA) assesses the clinical comparative efficacy and safety of sulodexide versus direct-acting oral anticoagulants (DOACs), vitamin K antagonist (VKA), and aspirin in patients with an unprovoked venous thromboembolism (VTE). Methods We conducted a literature search in MEDLINE, Embase, and Cochrane Library using both randomized controlled trials (RCTs) and observational studies. Reduction in recurrent deep venous thrombosis (r-DVT), pulmonary embolism (PE), major bleeding (MB), clinically relevant nonmajor bleeding (CRNMB) were the primary efficacy and safety outcomes. Other secondary end points were also included. We performed a fixed, random effects, and hierarchical models Bayesian NMA for each outcome. Results We identified 18 RCTs and seven observational studies. Random models showed sulodexide is the best treatment compared with DOACs, VKA, and aspirin at reducing the risk of CRNMB, for preventing death from any cause, and VTE/PE/myocardial infarction (MI)/stroke with 0.47, 0.81, and 0.65 probabilities, respectively. In the random model sulodexide was the best treatment for reducing the risk of MB with a 0.50 probability and hierarchical model that confirmed favorable results. Random and hierarchical models showed sulodexide and DOACs to be the best treatments for reducing PE risk. Sulodexide was more effective than aspirin for reducing r-DVT with 0.12 and less of 0.0001 probabilities, respectively. Conclusion Sulodexide is more effective for reducing MB and CRNMB, for preventing deaths from any cause, and from VTE/PE/MI/stroke, than other treatments, for both random and hierarchical models. Sulodexide showed to be more effective than aspirin in reducing the risk of r-DVT and PE. Sulodexide's reduction in bleeding while protecting from recurrent DVT risk makes this therapeutic option an important alternative for extended anticoagulation treatment.

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.

Patient information sources when facing repair of abdominal aortic aneurysm.

OBJECTIVE: Shared medical decision making is most important when there are competing options for repair such as in treatment of abdominal aortic aneurysm (AAA). We sought to understand the sources of patients' pre-existing knowledge about AAA to better inform treating physicians about patients' needs for preoperative counseling. METHODS: We performed a multicenter survey of patients facing AAA repair at 20 Veterans Affairs hospitals across the United States as part of the Preferences for Open Versus Endovascular Repair of AAA study. A validated survey instrument was administered to examine the sources of information available and commonly used by patients to learn about their repair options. The survey was administered by study personnel before the patient had any interaction with the vascular surgeon because survey data were collected before the vascular clinic visit. RESULTS: Preliminary analysis of data from 99 patients showed that our cohort was primarily male (99%) and elderly (mean age 73 years). Patients commonly had a history of hypertension (86%), prior myocardial infarction (32%), diabetes (32%), and were overweight (58%). Patients arrived at their surgeon's office appointment with limited information. A majority of patients (52%) reported that they had not talked to their primary care physician at all about their options for AAA repair, and one-half (50%) reported that their view of the different surgical options had not been influenced by anyone. Slightly less than one-half of patients reported that they did not receive any information about open surgical aneurysm repair and endovascular aortic aneurysm repair (41% and 37%, respectively). Few patients indicated using the internet as their main source of information about open surgical aneurysm repair and endovascular aortic aneurysm repair (10% and 11%, respectively). CONCLUSIONS: Patients are commonly referred for AAA repair having little to no information regarding AAA pathology or repair options. Fewer than one in five patients searched the internet or had accessed other sources of information on their own. Most vascular surgeons should assume that patients will present to their first vascular surgery appointment with minimal understanding of the treatment options available to them.