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.

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.

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.

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.

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.

Chronic venous disease - Part II: Proteolytic biomarkers in wound healing.

Venous leg ulcers (VLU) are characterized by sustained proteolytic microenvironment impairing the healing process. Wound fluid (WF) reflect the biomolecular activities occurring within the wound area; however, it is unclear if WF from different healing phases have different proteolytic profiles and how VLU microenvironment affects the wound healing mechanisms. We investigated the proteolytic network of WF from distinct VLU phases, and in WF- and LPS-stimulated THP-1 monocytes treated with glycosaminoglycan sulodexide, a well known therapeutic approach for VLU healing. WF were collected from patients with VLU during inflammatory (Infl) and granulating (Gran) phases. WF and THP-1 supernatants were analyzed for nine matrix metalloproteinases (MMP) and four tissue inhibitors of metalloproteinases (TIMP) by multiplex immunoassays. Our results demonstrated that: 1) WF from Infl VLU contained significantly increased concentrations of MMP-2, MMP-9, MMP-12, TIMP-1, and TIMP-2 compared to Gran WF; 2) WF from Gran VLU showed significantly increased levels of MMP-1, MMP-7, MMP-13, and TIMP-4 compared to Infl WF; 3) LPS- and WF-stimulation of THP-1 cells significantly increased the expression of several MMP compared to untreated cells; 4) Sulodexide treatment of both LPS- and WF-stimulated THP-1 significantly down-regulated the release of several MMPs. Our study provides evidence-based medicine during treatment of patients with VLU. WF from Infl and Gran VLU have different MMP and TIMP signatures, consistent with their clinical state. The modulation of proteolytic pathways in wound microenvironment by glycosaminoglycan sulodexide, provide insights for translating research into clinical practice during VLU therapy.

Chronic venous disease - Part I: Inflammatory biomarkers in wound healing.

Venous leg ulcers (VLUs) produce wound fluid (WF), as a result of inflammatory processes within the wound. It is unclear if WF from different healing phases of VLU has a peculiar biochemical profile and how VLU microenvironment affects the wound healing mechanisms. This study was conducted to evaluate the cytokine/chemokine profiles in WF from distinct VLU phases, in WF- and LPS-stimulated monocytes and treated with glycosaminoglycan Sulodexide, a therapeutic option for VLU healing. WF and plasma were collected from patients with VLU during active inflammatory (Infl) and granulating (Gran) phases. Demographics, clinical characteristics and pain measurements were evaluated. WF, plasma, and THP-1 supernatants were analyzed for 27 inflammatory mediators by multiplex immunoassay. Our results demonstrated that: 1) pain was significantly increased in patients with Infl compared to Gran VLU; 2) cytokine profile of Infl WF was found to be statistically different from that Gran WF, as well significantly increased respect to plasma; 3) LPS- and WF-stimulation of THP-1 cells significantly increased the expression of several cytokines compared to untreated cells; 4) Sulodexide treatment of both LPS- and WF-stimulated THP-1 monocytes was able to significantly down-regulate the release of peculiar inflammatory mediators. Our study highlighted the importance to understand biomolecular processes underlying CVI when providing treatment for chronic VLU. Identification of inflammatory biomarkers in leg ulcer microenvironment, may provide useful tools for predicting healing outcome and developing targeted therapies.

Rupture of a True Profunda Femoris Artery Aneurysm: Two Case Reports and Review of the English Language Literature.

Profunda femoris artery aneurysms (PFAAs) are very rare and easily overlooked because they are located deeply within thigh muscle. PFAAs have a high rate of rupture in comparison with other peripheral arterial aneurysms, resulting in emergency surgical procedures with significant morbidity. PFAA is diagnosed with color arterial Doppler ultrasound, although computed tomography angiography remains the best imaging method to precisely define the exact site and length of arterial involvement. PFAAs should be treated surgically once diagnosed, even if they are asymptomatic due to the high incidence of complications. Currently, around 28 patients with PFAA rupture, including the 2 cases from this report, have been described in the English language literature. In this report, we describe the diagnosis and treatment of 2 true ruptured aneurysms of the profunda femoris artery with 2 different approaches, and will review the relevant literature.

Chronic Venous Insufficiency: Transforming Growth Factor-ß Isoforms and Soluble Endoglin Concentration in Different States of Wound Healing.

Venous leg ulcer (VLU) is a huge healthcare problem with poorly understood pathophysiology. Transforming growth factor-ß (TGF-ß) and endoglin (Eng), are inflammatory and wound healing mediators. Eng, co-receptor for TGF-ß type-II receptors, may be cleaved forming soluble Eng (sEng), antagonizing TGF-ß signaling, a crucial process in vascular pathologies. We evaluated the accumulation in wound fluid (WF) of TGF-ß isoforms and sEng in healing stages, showing the effects of sulodexide treatments, a glycosaminoglycan with clinical efficacy in VLU healing. Patients with inflammatory (Infl) and granulating (Gran) VLU were recruited. WFs and THP-1 monocytes exposed to Infl and Gran WF (treated/untreated with sulodexide) were analyzed for TGF-ß isoforms and sEng by multiplex immunoassay. In both Infl and Gran WF, TGF-ß1 and ß2 were similar; TGF-ß3 was significantly increased in Infl compared to Gran WFs (p = 0.033). sEng was significantly elevated in Gran compared to Infl WFs (p = 0.002). In THP-1 monocytes there was a significant increase in sEng after co-treatment of WF and sulodexide. The increase in TGF-ß3 found in Infl WF highlights its negative effect on wound healing, while the increased levels of sEng in Gran WF affects the leukocyte adhesion/transmigration through the endothelium, reducing the inflammatory response and favoring the wound healing. Glycosaminoglycan sulodexide potentiates the effects of sEng release from monocyte, representing an important therapeutic option for wound healing.

Impact of coexisting aneurysms on open revascularization for aortoiliac occlusive disease.

OBJECTIVE: National data evaluating outcomes for occlusive abdominal aortic reconstructions are well described. The relative effect of operative indication as well as the presence of concomitant abdominal aortic aneurysm (AAA) on in-hospital mortality is not well defined. METHODS: The Nationwide Inpatient Sample was queried to identify patients who underwent open aortic surgery (2003-2010). Indication for surgery was classified by International Classification of Diseases, Ninth Revision diagnostic codes to identify isolated occlusive indications as well as combined occlusive disease and AAA. Primary outcome was in-hospital mortality. Secondary outcomes were complications and discharge disposition. RESULTS: Overall, 56,374 underwent aortic reconstruction, 48,591 for occlusive disease (86.2%) and 7783 for combined occlusive disease with AAA (13.8%). Intermittent claudication was the most common indication for intervention (60.9%), whereas 39.7% underwent intervention for critical limb ischemia (22.2% rest pain, 17.6% gangrene). Patients with intermittent claudication had more concomitant AAAs (17.3%) than did patients with critical limb ischemia (8.4%). The baseline characteristics for those with occlusive disease and combined occlusive with AAA disease were similar in terms of obesity (4.8% vs 4.2%; P = .27) and congestive heart failure (6.6% vs 6.3%; P = .65) but differed by age (62.2 years vs 68.4 years; P < .0001) and hypertension (65.4% vs 69.1%; P = .005). Patients with combined occlusive and AAA disease had higher mortality than those with occlusive disease alone (3.9% vs 2.7%; P = .01). On multivariable regression, factors associated with in-hospital mortality included gangrene with AAA compared with gangrene alone (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.6-4.7; P < .0002), age >65 years age (OR, 3.1; 95% CI, 2.4-4.1; P < .0001), renal failure (OR, 2.7; 95% CI, 1.9-3.8; P < .0001), and concurrent lower extremity revascularization (OR, 1.3; 95% CI, 1.1-1.7; P < .02). CONCLUSIONS: Intermittent claudication or critical limb ischemia with concomitant AAA carries a higher mortality than intermittent claudication or critical limb ischemia alone, especially in older patients with gangrene requiring revascularization and renal insufficiency. Preoperative risk stratification strategies should focus on the indication for surgery as well as the presence of concomitant AAA.

Venous leg ulceration pathophysiology and evidence based treatment.

Venous leg ulceration (VLU) is one of the most predominate medical disorders worldwide and in the western hemisphere it affects around 1.5% of the general population and up to 5% of the elderly population. Unfortunately, this trend will only increase given the growth of an aging population worldwide. Understanding its pathophysiology that begins with venous hemodynamic abnormalities and leads to inflammatory alterations with microcirculatory changes is critical to delivering effective curative therapy. As such, the main component to treatment is reversing the underlying venous hypertension and pro-inflammatory milieu using compression treatment along with various adjuvant therapies. Given its impact, a comprehensive multi-pronged approach to care, treatment and prevention is required to reverse the increasing trend that is observed worldwide.

Congenital Absence of Inferior Vena Cava in a Young Patient with Iliofemoral Deep Venous Thrombosis Treated with Ultrasound-accelerated Catheter-directed Thrombolysis: Case Report and Review of the Literature.

Absence of the inferior vena cava (AIVC) is a rare congenital anomaly and result from aberrant development during embryogenesis. Deep vein thrombosis (DVT) is a frequent finding in healthy young adults who are diagnosed with congenital AIVC. This condition is best diagnosed with color venous Doppler ultrasound and computed tomography angiography or magnetic resonance imaging, and managed using anticoagulation, mechanical catheter-directed thrombectomy, and thrombolysis. Catheter-directed thrombolysis (CDT) followed by systemic anticoagulation and use of compression stockings appears safe and effective in the treatment of patients who present with acute DVT and AIVC. We present a case report of DVT with underlying AIVC treated successfully with CDT and will review the relevant English literature.

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 CVD patient, reducing severity of the CVD related symptoms and swelling but also reducting inflammation and protecting endothelial cells. In this research, the effects of the serum obtained from CVD patients before and after sulodexide treatment was evaluated for in vivo and in vitro inflammatory markers and endothelial cell function. MATERIAL AND METHODS: Inflammatory markers (IL-6, MMP-9, VCAM-1, vWF) from the incompetent great saphenous (GSV) veins and from the systemic venous circulation were studied in 10 CVD C2s patients before and after 2 months of sulodexide (2 x 500 LSU/day) therapy. Serum from pretreatment and following sulodexide treated patients was evaluated for in vitro cultured human umbilical vein endothelial cells (HUVEC) function. RESULTS: Serum collected from lower leg incompetent GSVs had significantly elevated levels of VCAM-1 (+ 29%, p<0.001) than 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<0.01), as well as increased markers of senescence (prolongation of PDT, ß-galactosidase activity, 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 serum collected from incompetent GSV was stronger as compared to 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 CVD patients there are significant differences between circulating inflammatory markers analyzed from the lower leg incompetent GSV segments compared to the systemic circulation, indicating a higher inflammatory condition in CVD. Treatment with sulodexide reduces the proinflammatory and endothelial cell activation proprieties of the serum from CVD patients.

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.

Endothelium-dependent nitric oxide and hyperpolarization-mediated venous relaxation pathways in rat inferior vena cava.

INTRODUCTION: The vascular endothelium plays a major role in the control of arterial tone; however, its role in venous tissues is less clear. The purpose of this study was to determine the role of endothelium in the control of venous function and the relaxation pathways involved. METHODS: Circular segments of inferior vena cava (IVC) from male Sprague-Dawley rats were suspended between two wires and isometric contraction to phenylephrine (Phe; 10(-5)M) and 96 mM KCl was measured. Acetylcholine (Ach; 10(-10) to 10(-5)M) was added and the percentage of venous relaxation was measured. To determine the role of nitric oxide (NO) and prostacyclin (PGI(2)), vein relaxation was measured in the presence of the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME; 3 × 10(-4) M) and the cyclooxygenase inhibitor indomethacin (10(-5) M). To measure the role of hyperpolarization, vein relaxation was measured in the presence of K(+) channel activator cromakalim (10(-11) to 10(-6) M), and the nonselective K(+) channel blocker tetraethylammonium (TEA; 10(-3) M). To test for the contribution of a specific K(+) channel, the effects of K(+) channel blockers: glibenclamide (adenosine triphosphate [ATP]-sensitive K(ATP), 10(-5) M), 4-aminopyridine (4-AP; voltage-dependent K(v), 10(-3) M), apamin (small conductance Ca(2+)-dependent SK(Ca), 10(-7) M), and iberiotoxin (large conductance Ca(2+)-dependent BK(Ca), 10(-8) M) on Ach-induced relaxation were tested. RESULTS: Ach caused concentration-dependent relaxation of Phe contraction (maximum 49.9 ± 4.9%). Removal of endothelium abolished Ach-induced relaxation. IVC treatment with L-NAME partially reduced Ach relaxation (32.8 ± 4.9%). In IVC treated with L-NAME plus indomethacin, significant Ach-induced relaxation (33.6 ± 3.2%) could still be observed, suggesting a role of endothelium-derived hyperpolarizing factor (EDHF). In IVC treated with L-NAME, indomethacin and TEA, Ach relaxation was abolished, supporting a role of EDHF. In veins stimulated with high KCl, Ach caused relaxation (maximum 59.5 ± 3.5%) that was abolished in the presence of L-NAME and indomethacin suggesting that any Ach-induced EDHF is blocked in the presence of high KCl depolarizing solution, which does not favor outward movement of K(+) ion and membrane hyperpolarization. Cromakalim, an activator of K(ATP), caused significant IVC relaxation when applied alone or on top of maximal Ach-induced relaxation, suggesting that the Ach response may not involve K(ATP). Ach-induced relaxation was not inhibited by glibenclamide, 4-AP, or apamin, suggesting little role of K(ATP), K(v) or SK(Ca), respectively. In contrast, iberiotoxin significantly inhibited Ach-induced relaxation, suggesting a role of BK(Ca). CONCLUSIONS: Thus, endothelium-dependent venous relaxation plays a major role in the control of venous function. In addition to NO, an EDHF pathway involving BK(Ca) may play a role in endothelium-dependent venous relaxation.

Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum.

BACKGROUND: The anticoagulant treatment of acute deep venous thrombosis (DVT) has been historically directed toward the prevention of recurrent venous thromboembolism. However, such treatment imperfectly protects against late manifestations of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, early thrombus removal strategies can potentially decrease postthrombotic morbidity. OBJECTIVE: A committee of experts in venous disease was charged by the Society for Vascular Surgery and the American Venous Forum to develop evidence-based practice guidelines for early thrombus removal strategies, including catheter-directed pharmacologic thrombolysis, pharmacomechanical thrombolysis, and surgical thrombectomy. METHODS: Evidence-based recommendations are based on a systematic review and meta-analysis of the relevant literature, supplemented when necessary by less rigorous data. Recommendations are made according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, incorporating the strength of the recommendation (strong: 1; weak: 2) and an evaluation of the level of the evidence (A to C). RESULTS: On the basis of the best evidence currently available, we recommend against routine use of the term "proximal venous thrombosis" in favor of more precise characterization of thrombi as involving the iliofemoral or femoropopliteal venous segments (Grade 1A). We further suggest the use of early thrombus removal strategies in ambulatory patients with good functional capacity and a first episode of iliofemoral DVT of <14 days in duration (Grade 2C) and strongly recommend their use in patients with limb-threatening ischemia due to iliofemoral venous outflow obstruction (Grade 1A). We suggest pharmacomechanical strategies over catheter-directed pharmacologic thrombolysis alone if resources are available and that surgical thrombectomy be considered if thrombolytic therapy is contraindicated (Grade 2C). CONCLUSIONS: Most data regarding early thrombus removal strategies are of low quality but do suggest patient-important benefits with respect to reducing postthrombotic morbidity. We anticipate revision of these guidelines as additional evidence becomes available.

Acute expansion of a hospital-acquired methicillin-resistant Staphylococcus aureus-infected abdominal aortic aneurysm.

Infected aortic aneurysms (IAAs) are rare but can have devastating outcomes, particularly if diagnosis and treatment are delayed. The incidence of IAA is between 0.65% and 2% of all aortic aneurysms. The disease has a poor prognosis because these aneurysms have an increased tendency to grow rapidly and to rupture, and patients often have severe comorbidities and coexisting sepsis. Typical microorganisms associated with IAA are Salmonella, Streptococci, and Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus (MRSA) continues to emerge as a cause of serious infections, but its association with IAA is extremely rare. We present a rare case of infected abdominal aortic aneurysm caused by hospital-acquired (HA) MRSA. This case adds another presentation to the clinical spectrum of HA MRSA infections, and it highlights the problems encountered in the choice of the therapy of serious HA or health care-acquired infections in an era of increasing MRSA infections. We will discuss the clinical spectrum of HA MRSA infections as well as the problems encountered in the management of IAA, and will review the relevant literature.