Laser Atherectomy for the Treatment of Peripheral Arterial Disease.

BACKGROUND: The aim of the study was to investigate the clinical results of laser atherectomy in the treatment of peripheral arterial disease. METHODS: Retrospective analysis of consecutive patients underwent laser atherectomy at a single institution during a 7-year period by vascular surgeons and interventional cardiologists in a tertiary university-affiliated hospital. Clinical data were retrieved from patient charts and hospital electronic medical records along with the associated arteriograms. RESULTS: A total of 461 lesions in 343 limbs were treated in 300 patients with a mean age of 70 years. The indication was critical limb ischemia (CLI) with rest pain or tissue loss in 227 (66%) of interventions and claudication in 116 (34%). All procedures included an associated balloon angioplasty, while stenting was performed in 33%. Technical success was achieved in 99% with only 2 (<1%) cases with an acute procedure-related complication requiring surgical intervention. At a mean follow-up of 28 months (range, 1-87 months; median 24 months), 156 patients (45%) became asymptomatic or achieved significant clinical improvement (resolution of tissue loss or rest pain), 60 (17%) remained with CLI, 30 (9%) had a major proximal amputation, and 18 (5%) had a minor amputation. Freedom from major amputation was 90% at 5 years by life-table analysis. Univariate statistical analysis demonstrated the risk of a major amputation to be associated with diabetes, hemodialysis, and tissue loss (P < 0.05 to P < 0.005), while multivariate logistic regression analysis indicated diabetes to be overwhelmingly important (RR: 4.84; 95% confidence interval [CI]: 1.1-21.3; P < 0.05). In a similar manner, multivariate analysis indicated dialysis (RR: 2.46; 95% CI: 1.01-5.98; P < 0.05) and CLI (RR: 2.27; 95% CI: 1.42-3.65; P < 0.01) were associated with higher likelihood for lack of clinical improvement. There was no difference in major amputation rates between surgeons and interventional cardiologists (RR: 1.5; 95% CI: 0.7-2.1; P < 0.1) although it was 3 times more likely for the patients treated by surgeons to suffer from CLI (odds ratio: 3.2; 95% CI: 1.9-5.4; P < 0.0001). CONCLUSIONS: Laser atherectomy is a safe and useful adjunct in limb salvage. Diabetics have much higher probability of requiring a proximal amputation, while those on dialysis and with CLI are least likely to gain clinical benefit.

Perception of Chemical Venous Thromboprophylaxis for Oncologic Lung Resections among Thoracic Surgeons.

BACKGROUND: Controversies on chemical venous thromboembolic (VTE) prophylaxis in patients undergoing lung resection for malignancy exist. The available guidelines on VTE do not specifically address its prophylaxis in patients undergoing oncologic lung resections. The goal of this survey was to evaluate the perception of VTE prophylaxis among thoracic surgeons performing these operations. METHODS: A self-reported online survey was distributed to 267 active members of the General Thoracic Surgical Club between July and September 2015. The survey consisted of 22 questions related to the use of chemical venous thromboprophylaxis in patients undergoing oncologic lung resection and their impact on outcomes. RESULTS: Fifty-six thoracic surgeons replied to the survey. The majority of these surgeons (57%) perform both open and thoracoscopic surgery for lung cancer. All respondents stated that treatment modality and extent of surgical resection have no influence on their decision to use chemical VTE prophylaxis. Twenty-two (39%) respondents do not use chemical VTE prophylaxis prior to their oncologic lung resections, while the remaining 34 (61%) reported use of anticoagulants prior to them. None of the respondents prescribe extended 30-day VTE prophylaxis to these patients. Forty-nine (87%) respondents believe that chemical VTE prophylaxis is not related to major postoperative bleeding episodes. Forty-five (81%) respondents reported that none of their reoperations for bleeding were secondary to VTE prophylaxis or if it was, that isolated event could be successfully managed nonoperatively. CONCLUSIONS: The majority of thoracic surgeons surveyed believe that chemical VTE prophylaxis is safe and should be used regardless of the magnitude of oncologic lung resections whenever possible. Extended 30-day VTE prophylaxis is not yet used by the survey respondents.

Endovascular treatment of stenoses in a pediatric patient with incomplete aortic duplication, mesenteric ischemia, and renovascular hypertension.

Variations in abdominal aortic anatomy may have significant implications in various surgical procedures. We report here a pediatric patient with symptoms of chronic mesenteric ischemia, labile hypertension, and lower extremity claudication. Angiography revealed a partially duplicated aorta with the anterior aorta containing the splanchnic and renal arteries and the posterior segment perfusing the lower extremities. She was successfully treated with balloon angioplasty of two focal stenoses and is normotensive without abdominal symptoms at 1-year follow-up. To our knowledge, this is the first report of a successful endovascular intervention in a partially duplicated aorta.

Glucose metabolism during the early "flow phase" after burn injury.

BACKGROUND: Burn injury (BI) is associated with insulin resistance (IR) and hyperglycemia which complicate clinical management. We investigated the impact of BI on glucose metabolism in a rabbit model of BI using a combination of positron emission tomography (PET) and stable isotope studies under euglycemic insulin clamp (EIC) conditions. MATERIALS AND METHODS: Twelve male rabbits were subjected to either full-thickness BI (B) or sham burn. An EIC condition was established by constant infusion of insulin, concomitantly with a variable rate of dextrose infusion 3 d after treatment. PET imaging of the hind limbs was conducted to determine the rates of peripheral O(2) and glucose utilization. Each animal also received a primed constant infusion of [6,6-(2)H(2)] glucose to determine endogenous glucose production. RESULTS: The fasting blood glucose in the burned rabbits was higher than that in the sham group. Under EIC conditions, the sham burn group required more exogenous dextrose than the B group to maintain blood glucose at physiological levels (22.2 ± 2.6 versus 13.3 ± 2.9 mg/min, P < 0.05), indicating a state of IR. PET imaging demonstrated that the rates of O(2) consumption and (18)F 2-fluoro-2-deoxy-D-glucose utilization by skeletal muscle remained at similar levels in both groups. Hepatic gluconeogenesis determined by the stable isotope tracer study was found significantly increased in the B group. CONCLUSIONS: These findings demonstrated that hyperglycemia and IR develop during the early "flow phase" after BI. Unsuppressed hepatic gluconeogenesis, but not peripheral skeletal muscular utilization of glucose, contributes to hyperglycemia at this stage.

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

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

Mechanisms of hepatocyte growth factor-mediated vascular smooth muscle cell migration.

The migration of vascular smooth muscle cells (SMCs) from the media into the neointima and their subsequent proliferation is important in the pathogenesis of atherosclerosis. This process is regulated by multiple factors, including growth factors, and involves changes in the interaction of SMCs with the extracellular matrix and in intracellular signaling cascades that regulate cell movement. We demonstrated previously that hepatocyte growth factor (HGF) is expressed in human atherosclerotic plaques. Although HGF has been shown to promote SMC migration, the mechanisms involved in this process have not been characterized fully. In this study, inhibitory antibodies were used to determine which integrins mediated HGF-induced SMC migration. Inhibition of beta1 or beta3 integrin resulted in a significant decrease in migration. Subsequent experiments were performed to characterize additional biochemical mechanisms involved in HGF-mediated migration. HGF induced the redistribution of focal adhesions, the activation of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) and their increased association with beta1 and beta3 integrins, and the production of pro-matrix metalloproteinase-2. Migration levels were significantly reduced by cotreatment of SMCs with the extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor, UO126, the p38 inhibitor, SB203580, or the phosphatidylinositol-3 kinase inhibitor, LY294002. In HGF-treated SMCs, focal adhesion redistribution and FAK and Pyk2 activation were decreased by ERK1/2 inhibition. Neither SB203580 nor LY294002 inhibited HGF-induced ERK1/2 activation. Thus, ERK1/2 signaling may play an important role in HGF-mediated SMC migration by contributing to focal adhesion redistribution and FAK and Pyk2 activation.

MCP-1-dependent signaling in CCR2(-/-) aortic smooth muscle cells.

Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a mediator of inflammation that has been implicated in the pathogenesis of a wide variety of human diseases. CCR2, a heterotrimeric G-coupled receptor, is the only known receptor that functions at physiologic concentrations of MCP-1. Despite the importance of CCR2 in mediating MCP-1 responses, several recent studies have suggested that there may be another functional MCP-1 receptor. Using arterial smooth muscle cells (SMC) from CCR2(-/-) mice, we demonstrate that MCP-1 induces tissue-factor activity at physiologic concentrations. The induction of tissue factor by MCP-1 is blocked by pertussis toxin and 1,2-bis(O-aminophenyl-ethane-ethan)-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, suggesting that signal transduction through the alternative receptor is G(alphai)-coupled and dependent on mobilization of intracellular Ca(2+). MCP-1 induces a time- and concentration-dependent phosphorylation of the mitogen-activated protein kinases p42/44. The induction of tissue factor activity by MCP-1 is blocked by PD98059, an inhibitor of p42/44 activation, but not by SB203580, a selective p38 inhibitor. These data establish that SMC possess an alternative MCP-1 receptor that signals at concentrations of MCP-1 that are similar to those that activate CCR2. This alternative receptor may be important in mediating some of the effects of MCP-1 in atherosclerotic arteries and in other inflammatory processes.

Variability in leg compression provided by gradient commercial stockings.

BACKGROUND: Compression stockings are commonly prescribed by physicians for lower extremity edema and venous insufficiency. However, no data are available for clinicians to assess the relative quality of various brands, particularly low-cost generics now available directly to consumers through the Internet. We examined the actual compression provided by gradient stockings from multiple manufacturers. METHODS: A total of 36 class 2 (20-30 mm Hg) men's medium-sized below-knee compression stockings from six different manufacturers (n = 6 of each brand) with approximately the same quality and materials were chosen to be studied. Identifying brand names were removed, and they were randomly and blindly tested by a technician in accordance with accepted industry standards. A calibrated constant rate of extension tensile instrument (Zwick Z010; Zwick Roell, Ulm, Germany) was used, and the tension generated by the stockings at the ankle and calf was measured using minimum, average, and maximum circumference sizes. All measurements were performed in duplicate. RESULTS: The compression pressures generated by the stockings were almost all within the stated range of 20 to 30 mm Hg at the ankle, but all except one were below 20 mm Hg at the calf. There were also significant differences between manufacturers at both the ankle and the calf (P < .0001). The expected pressure reduction between the two locations varied, but one stocking had only a minimal 2 mm Hg (8%) gradient, which was significantly less than all of the other tested brands and below the recommended 20% to 50% reduction. Cost analysis demonstrated that the discount brands were significantly lower in price but provided absolute compression and pressure gradients similar to those of the more expensive brands. CONCLUSIONS: There is significant variability among stockings, both in the absolute pressures and in the pressure gradients generated from the ankle to the calf, thought to be functionally important for venous flow. The cheaper stockings offered the same degree of compression and pressure gradient as the more expensive brands. These results suggest the need for manufacturing standards in the United States and a revision in labeling requirements to mandate more accurate and complete pressure disclosures.

Hepatocyte growth factor is a survival factor for endothelial cells and is expressed in human atherosclerotic plaques.

Hepatocyte growth factor (HGF) has multiple effects on target cells upon activation of its receptor, c-Met. In endothelial cells, HGF induces migration, proliferation, and angiogenesis. HGF can also act as an anti-apoptotic factor for several cell types. The signal transduction pathways involved in mediating its anti-apoptotic effects have not been fully clarified. We demonstrated that HGF is anti-apoptotic for human endothelial cells, and identified the signaling pathways by which it mediates its effects. Human umbilical vein endothelial cells (HUVEC) exhibited significant levels of apoptosis after serum deprivation. HGF inhibited apoptosis in a dose dependent manner in serum-deprived cultures. HGF induced the phosphorylation of Akt and Erk1/2, cell survival factors, in a time dependent manner in serum deprived HUVEC. Inhibition of Akt and Erk1/2 activation abolished the anti-apoptotic effects of HGF. The transcription factor, NF-kappaB, can also play a role in promoting cell survival. However, NF-kappaB does not appear to contribute to the anti-apoptotic properties of HGF, as nuclear translocation of NF-kappaB was not detected in HGF-treated cultures. Endothelial cell migration, proliferation, and apoptosis contribute to the pathogenesis of atherosclerosis, and HGF may play a role in the development and progression of vascular lesions. Immunohistochemical analysis of human carotid artery sections demonstrated HGF protein localization within atherosclerotic lesions but not in normal vessels, suggesting that HGF may participate in atherogenesis.

The real cost of treating venous ulcers in a contemporary vascular practice.

BACKGROUND: Venous leg ulcers (VLUs) are a prevalent and morbid disease that consumes considerable health care resources. Estimates place the total costs for treatment of VLU at 1% of health care budgets in many industrialized countries. Unfortunately, there is little contemporary information on the total cost of treating VLU in the United States, particularly in a wound center staffed by vascular specialists. The purpose of this study was to define the actual cost of treating VLU and to identify factors influencing costs. METHODS: A cohort of 84 patients with active VLU (Clinical, Etiologic, Anatomic, and Pathologic class 6 disease) who were treated in a wound center by five vascular surgeons with a minimum follow-up of 6 months (median, 368 days; range, 336-483 days) was retrospectively studied. Actual costs (not charges) were obtained for outpatient and inpatient facility, visiting nurse services, and our physician practice group to yield true cost. The proportion of healed VLUs and time to complete healing were determined to calculate time to healing as well as ulcer-free intervals. Calculations of cost/ulcer-free days and cost to complete healing for the entire follow-up period were carried out as well as univariate analysis of factors affecting cost. RESULTS: The mean total cost of treating VLU during this follow-up period was $15,732. A total of 50 patients (60%) healed their VLUs without recurrence in a mean time of 122 days (range, 6-379 days) at a cost of $10,563 (range, $430-$50,967). This translated to $86/day of treatment to heal an ulcer, resulting in a cost of $42/ulcer-free day. In comparison, the total cost was threefold higher at $33,907 (range, $390-$132,730) for the patients (n = 17; 20%) who did not heal their VLUs. Significant contributing factors included outpatient facility fees ($10,332) and visiting nurse services ($11,365) related to extended treatment of the open VLU. Patients who had a recurrence of their VLU (n = 17; 20%) during the follow-up period had a total cost of $12,760. Inpatient admission for wound-related issues increased total cost to $33,629. Nearly two thirds of admissions were for treatment of cellulitis with intravenous antibiotics. VLUs treated with surgical intervention did not significantly increase total cost ($12,304 vs $19,503; P > .05) but significantly reduced recurrence rates (34% vs 5%). There were three outliers who experienced complications after treatment of outflow obstruction that dramatically increased the total cost to $71,526. CONCLUSIONS: This economic analysis demonstrates the high true costs associated with modern treatment of VLU by aggressive medical and surgical techniques. Inpatient and outpatient facility fees, physician fees, and visiting nurse payments all contribute to the cumulative tally that results in these staggering direct costs for treatment of VLUs. The daily cost of treatment that accrues for the ongoing care of VLU patients until they are healed provides an economic rationale for initiatives that advance approaches seeking to provide more rapid wound healing. Our analysis also highlights the significant costs associated with treatment of infections and complications encountered in aggressive surgical interventions for patients with extensive chronic central venous occlusive disease. More aggressive early outpatient treatment of infections and refined criteria for selection of outflow stenting candidates may reduce total cost by preventing complications while improving outcomes.

Stem cells and burns: review and therapeutic implications.

Despite significant advances in burn resuscitation and wound care over the past 30 years, morbidity and mortality from thermal injury remain high. Limited donor skin in severely burned patients hinders effective wound excision and closure, leading to infectious complications and prolonged hospitalizations. Even with large-volume fluid resuscitation, the systemic inflammatory response syndrome compromises end-organ perfusion in burn patients, with resultant multiorgan failure. Stem cells, which enhance wound healing and counteract systemic inflammation, now offer potential therapies for these challenges. Through a review of the literature, this article seeks to illustrate applications of stem cell therapy to burn care and to highlight promising areas of research.