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.

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.

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.

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.

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.

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.

Design of the PReferences for Open Versus Endovascular Repair of Abdominal Aortic Aneurysm (PROVE-AAA) Trial.

For patients with abdominal aortic aneurysm (AAA), randomized trials have found endovascular AAA repair (EVAR) is associated with lower perioperative morbidity and mortality than open surgical repair (OSR). However, OSR has fewer long-term aneurysm-related complications, such as endoleak or late rupture. Patients treated with EVAR and OSR have similar survival rates within two years after surgery, and OSR does not require intensive surveillance. Few have examined if patient preferences are aligned with the type of treatment they receive for their AAA. Although many assume that patients may universally prefer the less-invasive nature of EVAR, our preliminary work suggests that patients who value the lower risk of late complications may prefer OSR. In this study, called The PReferences for Open Versus Endovascular Repair of Abdominal Aortic Aneurysm (PROVE-AAA) trial, we describe a cluster-randomized trial to test if a decision aid can better align patients' preferences and their treatment type for AAA. Patients enrolled in the study are candidates for either endovascular or open repair and are followed up at VA hospitals by vascular surgery teams who regularly perform both types of repair. In Aim 1, we will determine patients' preferences for endovascular or open repair and identify domains associated with each repair type. In Aim 2, we will assess alignment between patients' preferences and the repair type elected and then compare the impact of a decision aid on this alignment between the intervention and control groups. This study will help us to accomplish two goals. First, we will better understand the factors that affect patient preference when choosing between EVAR and OSR. Second, we will better understand if a decision aid can help patients be more likely to receive the treatment strategy they prefer for their AAA. Study enrollment began on June 1, 2017. Between June 1, 2017 and November 1, 2018, we have enrolled 178 of a total goal of 240 veterans from 20 VA medical centers and their vascular surgery teams across the country. We anticipate completing enrollment in PROVE-AAA in June 2019, and study analyses will be performed thereafter.

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.

Sulodexide Improves Contraction and Decreases Matrix Metalloproteinase-2 and -9 in Veins Under Prolonged Stretch.

High pressure in the lower-limb veins is often associated with chronic venous insufficiency and varicose veins (VVs), making it important to search for the mechanisms and agents that control venous function. We have shown that protracted increases in venous stretch/wall tension reduce vein contraction and augment matrix metalloproteinase (MMP)-2 and -9. Also, MMP-2 and MMP-9 promote venodilation, a hallmark of VVs. Sulodexide (SDX) is a blend of glycosaminoglycans with efficient profibrinolysis and antithrombosis activities, but its actions on vein function and the mechanisms involved are unclear. We tested the hypothesis that SDX enhances venous contractile response by decreasing MMP expression/activity in veins subjected to protracted stretch. Rat inferior vena cava (IVC) rings were treated with SDX (0.001-1 mg/mL) or vehicle, equilibrated under control 0.5-g resting tension or protracted 2-g stretch for 18 hours, and the contractile response to 96-mM KCl and phenylephrine (Phe) in SDX-treated and nontreated veins was recorded. In IVC rings under control 0.5-g resting tension, SDX caused dose-dependent contraction, 96-mM KCl caused marked contraction (176-mg/mg tissue), and Phe caused dose-dependent contraction with a maximum (56-mg/mg tissue) at 10 M. In IVC subjected to protracted 2-g stretch, 96-mM KCl-induced contraction was reduced to 112 mg/mg and maximal Phe-induced contraction was decreased to 23 mg/mg. In IVC subjected to protracted 2-g stretch plus SDX, 96-mM KCl-induced contraction was restored to 228 mg/mg and maximal Phe-induced contraction was improved to 115 mg/mg. Gelatin zymography and Western blots revealed increases in MMP-2 and MMP-9 levels/gelatinolytic activity in veins subjected to protracted 2-g stretch and reversal to control levels in veins subjected to 2-g stretch plus SDX. Thus, SDX improves vein function and augments the contractile response in veins subjected to protracted stretch. The SDX-induced improvement of contraction and restoration of vein function appear to involve decreases in MMP-2 and MMP-9 and may contribute to the benefits of SDX in chronic venous insufficiency and VVs.

Risk prediction of 30-day mortality after lower extremity major amputation.

OBJECTIVE: Universal risk calculators may underestimate mortality risk, whereas purely observational administrative data may lack appropriate granularity to individualize risk. The purpose of this study was to create a simple risk prediction model to identify the factors associated with 30-day morality after lower extremity major amputation for ischemic vascular disease. METHODS: The Veterans Affairs Surgical Quality Improvement Program national data set was queried from 2005 to 2015 to identify 14,890 patients undergoing elective above-knee or below-knee amputation for rest pain, tissue loss, or gangrene. The data set was divided into a two-thirds derivation set and one-third validation set for the purpose of creating a risk prediction model. The primary end point was 30-day mortality. Eight independent risk factors for mortality 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 (8-10), and very high (>10). RESULTS: Mortality in the derivation data set was 4.6% (n = 453). By multivariable backward elimination, predictors of 30-day mortality (odds ratio [95% confidence limits]) included preoperative do not resuscitate order (3.1 [2.3-4.0]), congestive heart failure (2.8 [2.1-3.6]), age >80 years (1.8 [1.4-2.2]), chronic renal insufficiency (2.1 [1.7-2.5]), above-knee amputation (1.8 [1.4-2.2]), dependent functional status (2.0 [1.6-2.5]), coronary artery disease (1.3 [1.1-1.6]), and chronic obstructive pulmonary disease (1.3 [1.0-1.6]); the final model held a C statistic of 0.74. In both the derivation and validation sets, 30-day mortality correlated with risk category. Among the defined categories in the derivation set, 30-day mortality rates were 2.3% for low-risk patients, 4.3% for moderate-risk patients, 7.5% for high-risk patients, and 17.5% for very-high-risk patients, with similar results for the validation data set. CONCLUSIONS: This risk prediction model uses eight easily obtainable clinical metrics that allow early assessment of 30-day mortality risk of patients undergoing major lower extremity amputation for ischemic indications. The internal validation of the risk score demonstrates the increased mortality with increasing risk category. Reliable expected mortality prediction is critically important for surgeons to make recommendations in accordance with a patient's or family's goals of care. These data may also be used to set realistic expectations for hospital-based quality initiatives and to provide guidance in preoperative medical optimization.

Sulodexide promotes arterial relaxation via endothelium-dependent nitric oxide-mediated pathway.

Sulodexide (SDX) is a highly purified glycosaminoglycan with antithrombotic and profibrinolytic properties and reported benefits in thrombotic and atherosclerotic vascular disorders. However, the effects of SDX on vascular function are unclear. We tested whether SDX affects vascular relaxation and examined the potential underlying mechanisms. Isolated segments of male rat abdominal aorta and mesenteric artery were suspended in a tissue bath, and the changes in arterial contraction/relaxation were measured. The α-adrenergic receptor agonist phenylephrine (Phe) (10-9-10-5 M) caused concentration-dependent aortic and mesenteric artery contraction that was reduced in tissues pretreated with SDX (1 mg/ml). In aortic and mesenteric arterial segments precontracted with submaximal concentration of Phe (3 × 10-7-6 × 10-7 M), SDX (0.001-1 mg/ml) caused concentration-dependent relaxation. To test the role of endothelium, SDX-induced relaxation was compared with that of acetylcholine (ACh), a known activator of endothelium-dependent relaxation. In Phe precontracted aorta, ACh relaxation was abolished and SDX relaxation was significantly inhibited by endothelium removal or the nitric oxide synthase (NOS) inhibitor Nω-nitro-l-arginine methyl ester (L-NAME), suggesting a role of NO. In mesenteric artery, ACh relaxation was abolished by endothelium removal, partially blocked by L-NAME, and completely blocked by a mixture of indomethacin, a cyclooxygenase inhibitor and blocker of the PGI2-cAMP pathway, and tetraethylammonium, a blocker of K+ channels and EDHF-dependent hyperpolarization pathway. In comparison, SDX relaxation of mesenteric artery was almost completely inhibited by endothelium removal or NOS inhibitor L-NAME. SDX enhanced vascular relaxation and increased nitrate/nitrite production in response to all ACh concentrations in the aorta, but only to low ACh concentrations (<10-7 M) in mesenteric artery. SDX did not affect aortic or mesenteric artery endothelium-independent relaxation to the NO donor sodium nitroprusside. Thus, SDX promotes arterial relaxation via a mechanism involving endothelium-dependent NO production; an effect that could enhance vasodilation and decrease vasoconstriction in vascular disorders.

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.