Patients Experience Significant Long-Term Social and Health Challenges After Major Lower Extremity Amputation.

BACKGROUND: Major lower extremity amputation is a significant life-changing event that can have long-term implications. The goal of this study was to assess long-term medical outcomes and social determinants of health (SDH) challenges in this population. METHODS: A retrospective review of major lower extremity (previously mentioned ankle) amputations (2018-2022) was performed at a safety-net tertiary care center. Patients who participated in an SDH survey between 6 months and 1.5 years postoperatively were included for survey analysis. Patient demographics, comorbidities, and perioperative and long-term outcomes were analyzed. RESULTS: There were 100 patients included. Mean age was 61.5 years and 23% were of female gender. The majority (57%) were Black race, 20% White race, and 21% Hispanic ethnicity. Comorbidities included diabetes (78%), chronic kidney disease (51%), coronary artery disease (31%), congestive heart failure (23%), previous cerebrovascular events (19%), and 37% used opioids preadmission. At baseline, the majority (62%) lived at home. Guillotine amputation was performed in 24%, with definitive amputation in the following and previously mentioned knee in 67% and 33%, respectively. Median length of stay was 7 days. Readmission at 30 days, 90 days, and 1 year was 13%, 30%, and 43% respectively. The average follow up was 839 days. At long-term follow up, 55% lived at home, 25% used opioids, and only 25% were independently ambulatory. In the SDH survey at follow up, 32% identified at least one SDH challenge, with younger patients more often affected (58 vs. 63 years, P = 0.031). SDH challenges consisted of food insecurity (17%), housing insecurity (13%), transportation challenges (13%), seeking employment (8%), difficulty paying for utilities (5%) and medications (4%), seeking further education (5%), and difficulty caring for family/friends (4%). On multivariable analysis, having at least one SDH challenge was independently associated with 1-year readmission (odds ratio 6.7, 95% confidence interval 1.3-35.8, P < 0.001). Older age was associated with lower long-term independent ambulation (odds ratio 0.92, 95% confidence interval 0.85-0.99, P = 0.025). CONCLUSIONS: After major lower extremity amputation, patients have significant medical and social challenges with fewer living at home, the majority were not independently ambulatory, and one-third having at least one SDH challenge. Improvements in long-term support including medical, social, and rehabilitation services are required for this vulnerable population.

Assessing Time to Removal of Tunneled Dialysis Catheters after Arteriovenous Access Creation.

BACKGROUND: Tunneled dialysis catheters (TDCs) are a temporary bridge until definitive arteriovenous (AV) access is established. Our objective was to evaluate the time to TDC removal in patients who underwent AV access creations with TDCs already in place. METHODS: A single-center analysis of all AV access creations in patients with TDCs was performed (2014-2020). Primary outcome was time to TDC removal after access creation. RESULTS: There were 364 AV access creations with TDCs in place. The average age was 58 years, 44% of patients were female, and 64% were Black. The median time to TDC removal was 113 days (range, 22-931 days) with 71.4% having a TDC >90 days after access creation. Patients with TDC >90 days were often older (60 vs. 54.7), had hypertension (98.1% vs. 93.3%), were diabetic (65.4% vs. 47.1%), and had longer average time to maturation (107.1 vs. 55.4 days, P < 0.001) and first access (114 vs. 59.4 days, P < 0.001). Multivariable analysis showed that older age was associated with prolonged TDC placement (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, P = 0.005) and prosthetic graft use was associated with shorter TDC indwelling time (OR 0.09, 95% CI 0.04-0.23, P ≤ 0.001). Kaplan-Meier analysis showed that 87% of TDCs were removed at 1 year. CONCLUSIONS: The majority of patients with TDCs who underwent AV access creation had prolonged TDC placement. Prosthetic graft use was associated with shorter catheter times. Close follow-up after access placement, improving maturation times, and access type selection should be considered to shortened TDC times.

Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation.

Primary cilia are hairlike extensions of the plasma membrane of most mammalian cells that serve specialized signaling functions. To traffic properly to cilia, multiple cilia proteins rely on palmitoylation, the post-translational attachment of a saturated 16-carbon lipid. However, details regarding the mechanism of how palmitoylation affects cilia protein localization and function are unknown. Herein, we investigated the protein ADP-ribosylation factor-like GTPase 13b (ARL13b) as a model palmitoylated ciliary protein. Using biochemical, cellular, and in vivo studies, we found that ARL13b palmitoylation occurs in vivo in mouse kidneys and that it is required for trafficking to and function within cilia. Myristoylation, a 14-carbon lipid, is shown to largely substitute for palmitoylation with regard to cilia localization of ARL13b, but not with regard to its function within cilia. The functional importance of palmitoylation results in part from a dramatic increase in ARL13b stability, which is not observed with myristoylation. Additional results show that blockade of depalmitoylation slows the degradation of ARL13b that occurs during cilia resorption, raising the possibility that the sensitivity of ARL13b stability to palmitoylation may be exploited by the cell to accelerate degradation of ARL13b by depalmitoylating it. Together, the results show that palmitoylation plays a unique and critical role in controlling the localization, stability, abundance, and thus function of ARL13b. Pharmacological manipulation of protein palmitoylation may be a strategy to alter cilia function.

A sensitivity metric and software to guide the analysis of soft films measured by a quartz crystal microbalance.

This article introduces a set of mathematical and computational tools for use with a quartz crystal microbalance (QCM) to aid in experimental planning and data interpretation. The optimisation tools are based on a metric we term the total parameter matrix sensitivity (TPM-sensitivity). TPM-sensitivity is defined mathematically as the Jacobian determinant of a QCM's responses (e.g., frequency change or dissipation/bandwidth change for a given harmonic) with respect to changes in the physical properties of a soft film and surrounding solution (e.g., density or viscosity). Large TPM-sensitivity values denote conditions where the sensor responses are not only large but also allow the selected unknown physical properties to be mathematically decoupled. In some cases, the viscoelastic properties of an adlayer can be determined using only frequency responses. We validated this method using experimentally obtained data of an ageing adlayer of the enzyme bilirubin oxidase from Myrothecium verrucaria. Fits to these measurements produced more realistic film parameters when responses, including frequency-only combinations, were selected to maximise TPM sensitivity. We provide documented MATLAB code with a graphical user interface to enable other QCM users to employ this analysis. The current software can be applied to any single, homogeneous adlayer that obeys a Kelvin-Voigt viscoelastic model and sits under a semi-infinite Newtonian fluid. Only initial estimates of the film values are required, with the analysis providing guidance and predictions, allowing users to create testable hypothesis and determine the physical changes on the surface rather than have pre-existing values for them.

A Susceptibility Locus on Chromosome 13 Profoundly Impacts the Stability of Genomic Imprinting in Mouse Pluripotent Stem Cells.

Cultured pluripotent cells accumulate detrimental chromatin alterations, including DNA methylation changes at imprinted genes known as loss of imprinting (LOI). Although the occurrence of LOI is considered a stochastic phenomenon, here we document a genetic determinant that segregates mouse pluripotent cells into stable and unstable cell lines. Unstable lines exhibit hypermethylation at Dlk1-Dio3 and other imprinted loci, in addition to impaired developmental potential. Stimulation of demethylases by ascorbic acid prevents LOI and loss of developmental potential. Susceptibility to LOI greatly differs between commonly used mouse strains, which we use to map a causal region on chromosome 13 with quantitative trait locus (QTL) analysis. Our observations identify a strong genetic determinant of locus-specific chromatin abnormalities in pluripotent cells and provide a non-invasive way to suppress them. This highlights the importance of considering genetics in conjunction with culture conditions for assuring the quality of pluripotent cells for biomedical applications.

A versatile route to edge-specific modifications to pristine graphene by electrophilic aromatic substitution.

Electrophilic aromatic substitution produces edge-specific modifications to CVD graphene and graphene nanoplatelets that are suitable for specific attachment of biomolecules.

High-spatial-resolution contrast-enhanced MR angiography of abdominal arteries with parallel acquisition at 3.0 T: initial experience in 32 patients.

OBJECTIVE: The objective of our study was to evaluate an isotropic high-spatial-resolution 3D contrast-enhanced MR angiography (CE-MRA) protocol with high acceleration parallel acquisition at 3.0 T for the display of the abdominal vasculature. SUBJECTS AND METHODS: Thirty-two consecutive patients (13 men, 19 women; age range, 28-88 years) with suspected abdominal arterial disease underwent abdominal 3D CE-MRA on a 3.0-T MR system, using a high-spatial-resolution (0.7 x 0.82 x 0.8 mm3) 3D gradient-refocused echo (GRE) sequence, integrated with a generalized autocalibrating partially parallel acquisitions (GRAPPA) technique with an acceleration factor of 3. Two vascular radiologists evaluated image quality and the presence and degree of arterial stenoses. Interobserver variability was calculated, using the kappa coefficient. The sensitivity and specificity of the technique were calculated and comparative analysis was performed with those of conventional catheter angiography (in eight patients) as the standard of reference. RESULTS: The abdominal arterial vasculature was visualized with diagnostic image quality in all subjects. Arterial stenoses were detected in 148 and 142 arterial segments by observer 1 and observer 2, respectively, with good interobserver agreement (kappa = 0.75; 95% confidence interval [CI]: 0.69-0.81). The sensitivity and specificity values for CE-MRA for the detection of significant (> 50%) arterial stenoses were 100% and 96% for observer 1 and 100% and 92% for observer 2, respectively. There was a significant correlation between CE-MRA and conventional angiography (R = 0.96 and 0.93 for observers 1 and 2, respectively) for the assessment of the degree of stenosis. CONCLUSION: The outlined MR angiography protocol at 3.0 T combined with parallel acquisition technique renders highly reliable and isotropic high-spatial-resolution imaging of the abdominal vasculature.

Optimizing the Mass-Specific Activity of Bilirubin Oxidase Adlayers through Combined Electrochemical Quartz Crystal Microbalance and Dual Polarization Interferometry Analyses.

Two surface analysis techniques, dual polarization interferometry (DPI) and analysis by an electrochemical quartz crystal microbalance with dissipation capability (E-QCM-D), were paired to find the deposition conditions that give the highest and most stable electrocatalytic activity per adsorbed mass of enzyme. Layers were formed by adsorption from buffered solutions of bilirubin oxidase from Myrothecium verrucaria at pH 6.0 to planar surfaces, under high enzyme loading (≥1 mg mL(-1)) for contact periods of up to 2 min. Both unmodified and carboxylate-functionalized gold-coated sensors showed that a deposition solution concentration of 10-25 mg mL(-1) gave the highest activity per mass of adsorbed enzyme with an effective catalytic rate constant (k(cat)) of about 60 s(-1). The densification of adsorbed layers observed by DPI correlated with reduced bioactivity observed by parallel E-QCM-D measurements. Postadsorption changes in thickness and density observed by DPI were incorporated into Kelvin-Voigt models of the QCM-D response. The modeled response matched experimental observations when the adlayer viscosity tripled after adsorption.

Bilirubin oxidase from Myrothecium verrucaria: X-ray determination of the complete crystal structure and a rational surface modification for enhanced electrocatalytic O2 reduction.

The blue multi-copper oxidase bilirubin oxidase (BOx) from the ascomycete plant pathogen Myrothecium verrucaria (Mv) efficiently catalyses the oxidation of bilirubin to biliverdin, with the concomitant reduction of O(2) to water, a reaction of considerable interest for low-temperature bio-fuel cell applications. We have solved the complete X-ray determined structure of Mv BOx at 2.4 Å resolution, using molecular replacement with the Spore Coat Protein A (CotA) enzyme from Bacillus subtilis (PDB code 1GSK) as a template. The structure reveals an unusual environment around the blue type 1 copper (T1 Cu) that includes two non-coordinating hydrophilic amino acids, asparagine and threonine. The presence of a long, narrow and hydrophilic pocket near the T1 Cu suggests that structure of the substrate-binding site is dynamically determined in vivo. We show that the interaction between the binding pocket of Mv BOx and its highly conjugated natural organic substrate, bilirubin, can be used to stabilise the enzyme on a pyrolytic graphite electrode, more than doubling its electrocatalytic activity relative to the current obtained by simple adsorption of the protein to the carbon surface.

Primary cryoplasty therapy provides durable support for limb salvage in critical limb ischemia patients with infrapopliteal lesions: 12-month follow-up results from the BTK Chill Trial.

PURPOSE: To report the 12-month follow-up data from the prospective 16-center Below-the-Knee (BTK) Chill Trial, which examined the use of primary cryoplasty for BTK occlusive disease in patients with critical limb ischemia (CLI). METHODS: The trial included 108 patients (77 men; mean age 73 +/- 11 years, range 41-101) with CLI (Rutherford categories 4-6) involving 111 limbs with 115 target infrapopliteal lesions. Angiographic inclusion criteria were reference vessel diameter > or = 2.5 mm and < or = 5.0 mm and target lesion stenosis > or = 50%. The primary study endpoints were acute technical success (the ability to achieve < or = 50% residual stenosis and continuous inline flow to the foot) and absence of major amputation of the target limb at 6 months. Secondary endpoints were serious adverse events specifically related to use of primary cryoplasty and absence of major amputation of the target limb at 1, 3, and 12 months. RESULTS: Acute technical success was achieved in 108 (97.3%) of treated limbs, with only 1 clinically significant dissection (> or = type C) and 2 residual stenoses >50%; stent placement was required following cryoplasty in only 3 (2.7%) procedures. At 6 months and 1 year, major amputation was avoided in 93.4% (85/91) and 85.2% (69/81) of patients, respectively. Through 1 year, 21% (17/81) of patients underwent target limb revascularization. Rates of major amputation and death at 1 year were 0% for limbs of patients with initial Rutherford category 4; 11.4% and 0%, respectively, for initial category 5; and 40.0% and 31.8% for initial category 6. One-year rates of major amputation and death were 20.4% and 8.8%, respectively, for diabetics, versus 4.0% and 10.7% for non-diabetics. At 1 year, major amputation occurred in 16.7% (2/12) of limbs that were expected to be amputated at the time of treatment. CONCLUSION: Cryoplasty therapy is a safe and effective method of treating infrapopliteal disease, providing excellent results and a high rate of limb salvage in patients with CLI. Study outcomes through 1 year support the use of cryoplasty as a primary treatment option for patients with CLI secondary to BTK occlusive disease.

Ultrasound-accelerated thrombolysis for the treatment of deep vein thrombosis: initial clinical experience.

PURPOSE: To evaluate the success of lysis and clinical outcomes in patients treated with ultrasound (US)-accelerated thrombolysis for deep vein thrombosis (DVT). MATERIALS AND METHODS: Forty-seven patients with 53 cases of DVT were treated with US-accelerated thrombolysis at eight centers in the United States. Sixty percent of the occlusions were in the lower extremity, 36% were in the upper extremity, and 4% were hepatic. The clot was acute (< or =14 days) in 47% of cases, subacute (15-28 d) in 8%, chronic (>28 d) in 17%, acute-on-chronic in 17%, and not specified in 11%. Patients were treated with urokinase (UK), tissue plasminogen activator (tPA), recombinant plasminogen activator (rPA), or tenecteplase. RESULTS: Complete lysis (> or =90%) was seen in 37 of 53 cases (70%) and overall lysis (complete plus partial) was seen in 48 (91%). No lysis occurred in five cases (9%), four of which were chronic. The median thrombolysis infusion time was 22.0 hours. Major complications (hematoma at site of earlier surgery) occurred in only two patients (3.8%), with no incidence of intracranial or retroperitoneal hemorrhage. US-accelerated thrombolysis exhibited comparable or better lysis with a lower average drug dose and shorter median treatment times than reported in the National Venous Registry and a more recently published study of standard catheter-directed thrombolysis. CONCLUSIONS: US-accelerated thrombolysis was shown to be a safe and efficacious treatment for DVT in this multicenter experience. The addition of US reduces total infusion time and provides a greater incidence of complete lysis with a reduction in bleeding rates.

Supraaortic arteries: contrast-enhanced MR angiography at 3.0 T--highly accelerated parallel acquisition for improved spatial resolution over an extended field of view.

PURPOSE: To prospectively use 3.0-T breath-hold high-spatial-resolution contrast material-enhanced magnetic resonance (MR) angiography with highly accelerated parallel acquisition to image the supraaortic arteries of patients suspected of having arterial occlusive disease. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained for this HIPAA-compliant study. Eighty patients (44 men, 36 women; age range, 44-90 years) underwent contrast-enhanced MR angiography of the head and neck at 3.0 T with an eight-channel neurovascular array coil. By applying a generalized autocalibrating partially parallel acquisition algorithm with an acceleration factor of four, high-spatial-resolution (0.7 x 0.7 x 0.9 mm = 0.44-mm(3) voxels) three-dimensional contrast-enhanced MR angiography was performed during a 20-second breath hold. Two neuroradiologists evaluated vascular image quality and arterial stenoses. Interobserver variability was tested with the kappa coefficient. Quantitation of stenosis at MR angiography was compared with that at digital subtraction angiography (DSA) (n = 13) and computed tomographic (CT) angiography (n = 12) with Spearman rank correlation coefficient (R(s)). RESULTS: Arterial stenoses were detected with contrast-enhanced MR angiography in 208 (reader 1) and 218 (reader 2) segments, with excellent interobserver agreement (kappa = 0.80). There was a significant correlation between contrast-enhanced MR angiography and CT angiography (R(s) = 0.95, reader 1; R(s) = 0.87, reader 2) and between contrast-enhanced MR angiography and DSA (R(s) = 0.94, reader 1; R(s) = 0.92, reader 2) for the degree of stenosis. Sensitivity and specificity of contrast-enhanced MR angiography for detection of arterial stenoses greater than 50% were 94% and 98% for reader 1 and 100% and 98% for reader 2, with DSA as the standard of reference. Vascular image quality was sufficient for diagnosis or excellent for 97% of arterial segments evaluated. CONCLUSION: By using highly accelerated parallel acquisition, the described 3.0-T contrast-enhanced MR angiographic protocol enabled visualization and characterization of the majority of supraaortic arteries, with diagnostic or excellent image quality (97% of arterial segments) and diagnostic values comparable with those obtained by using CT angiography and DSA for detection of arterial stenoses.

Cryoplasty therapy for limb salvage in patients with critical limb ischemia.

PURPOSE: To report the 6-month outcomes from a prospective multicenter study investigating the use of cryoplasty (cold balloon angioplasty) to treat below-knee occlusive disease in patients with critical limb ischemia (CLI). METHODS: Between August 2004 and October 2005, 108 patients (77 men; mean age 73+/-12 years, range 41-101) with CLI involving 111 limbs were enrolled in a prospective multicenter trial (Below-the-Knee Chill Study), which was conducted at 16 institutions. The primary study endpoints were acute technical success, defined as the ability to achieve < or =50% residual stenosis and continuous inline flow to the foot, and absence of major (above or below-knee) amputation of the target limb 180 days post procedure. RESULTS: Acute technical success was achieved in 108 (97.3%) of the 111 limbs treated, with only 1 (0.9%) clinically significant dissection (> or =type C) and 2 residual stenoses >50%. During the 180-day follow-up, 15 (13.9%) of the initial 108 patients either withdrew or were lost to follow-up. Five (4.6%) deaths occurred, leaving 88 (81.5%) patients with 91 (82.0%) treated limbs available for 180-day assessment. The rate of freedom from major amputation at 180 days was 93.4%. Amputation-free survival was 89.3% at 180 days (5 deaths, 6 major amputations). Stratifying data by diabetics (n=71) versus non-diabetics (n=34), the 180-day death and amputation rates were 4.9% and 10.0%, respectively, for diabetics versus 6.7% and 0.0%, respectively, for non-diabetics. CONCLUSION: Cryoplasty therapy is a safe and effective method of treating infrapopliteal disease, providing excellent acute outcomes and a high rate of limb salvage in patients with CLI. Study outcomes support the use of cryoplasty therapy as a primary treatment option for patients with CLI secondary to below- knee disease.

Adjunctive parenteral therapy with lipo-ecraprost, a prostaglandin E1 analog, in patients with critical limb ischemia undergoing distal revascularization does not improve 6-month outcomes.

PURPOSE: In patients with critical limb ischemia (CLI), distal revascularization remains the procedure of choice for preventing limb loss, but long-term outcomes for pain relief, wound healing, and prevention of amputation remain suboptimal. Prostaglandin drug therapy as an adjuvant to revascularization may improve these outcomes. The current trial was designed to test the hypothesis that the use of lipo-ecraprost, a lipid encapsulated prostaglandin E(1) prodrug, as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI. METHODS: The study was randomized, multicenter, double blind, and placebo controlled. Patients meeting clinical and hemodynamic criteria for CLI who were undergoing either bypass or endovascular revascularization of the below knee popliteal or more distal arteries were randomized to receive placebo or a 60-microg dose of lipo-ecraprost administered intravenously starting

Cryoplasty for the treatment of femoropopliteal arterial disease: extended follow-up results.

PURPOSE: To report the findings from a multicenter study of patients treated with cryoplasty who were then followed for an average of > 2 years post-treatment. METHODS: Extended clinical follow-up was obtained for 70 patients (45 men; mean age 70.5 +/- 8.8 years) who originally received cryoplasty therapy to treat symptoms of intermittent claudication as part of a multicenter investigational device exemption (IDE) study. For all subjects, cryoplasty was used to treat stenoses or occlusions < or = 10 cm in the femoropopliteal arteries. The original IDE study protocol enrolled 102 patients with a primary endpoint of target lesion patency at 9 months post-treatment. This collection of additional longer term follow-up data was initiated 2.5 years after the onset of study enrollment. RESULTS: Extended clinical follow-up ranged from 11 to 41 months (mean 31). The clinical patency rate (freedom from target lesion revascularization) calculated by the Kaplan-Meier method was 83.2% after the original follow-up period of 300 days. After > 3 years (1253 days), the clinical patency rate was well maintained at 75.0%. CONCLUSIONS: Long-term data indicate that cryoplasty is a durable therapy, with relatively low long-term restenosis rates compared to other endovascular treatment approaches.

Parenteral therapy with lipo-ecraprost, a lipid-based formulation of a PGE1 analog, does not alter six-month outcomes in patients with critical leg ischemia.

PURPOSE: Eicosanoids with vasodilating and angiogenic properties have been postulated to be effective therapies for critical leg ischemia (CLI) secondary to atherosclerotic peripheral arterial disease. The ability to deliver active drug to the site of action at adequate doses for sufficient duration has been a major limitation in the clinical development of such therapies. Lipo-ecraprost is a lipid-encapsulated prostaglandin E1 prodrug with the potential to deliver active prostaglandin to the site of critical arterial ischemia. The current trial was designed to test the hypothesis that lipo-ecraprost would improve amputation-free survival in patients with CLI who had no revascularization options. METHODS: The study was randomized, multicenter, double blind, and placebo controlled. Patients who met clinical and hemodynamic criteria were randomized to receive placebo or lipo-ecraprost (60 microg) administered intravenously on each of 5 days per week, for a total of 8 weeks. The study's primary endpoint was the rate of a composite end point of death or amputation above the level of the ankle at 180 days (6 months). RESULTS: The study was terminated on a recommendation from the Data and Safety Monitoring Board after the completion of a protocol-specified interim analysis for futility. At the time of termination, 383 of the planned 560 patients had been randomized, of which 379 received at least one dose of study medication and thus were included in the intention-to-treat population. Twenty-three patients were lost to follow-up and were not available for 6-month assessments. At 6 months of follow-up, there were 23 amputations in the 177 patients who received placebo, and 29 amputations in the 179 patients randomized to lipo-ecraprost. At 6 months, 10 deaths had occurred in the placebo group and 18 deaths had occurred in the lipo-ecraprost arm. Changes in lower-extremity hemodynamics over the 6-month study period did not differ between the placebo and lipo-ecraprost treatment arms. CONCLUSION: Intensive treatment with lipo-ecraprost failed to modify the 6-month amputation rate in patients with CLI who were not candidates for revascularization.

Cryoplasty for the treatment of femoropopliteal arterial disease: results of a prospective, multicenter registry.

PURPOSE: Despite suboptimal results, angioplasty of femoropopliteal arterial lesions has been a mainstay of endovascular therapy for many years. The recent introduction of cryoplasty marks a potential advance in the ability to effectively treat peripheral arterial atherosclerotic stenoses. This article presents the results of a prospective, multicenter trial that evaluated the efficacy of cryoplasty for femoropopliteal disease. MATERIALS AND METHODS: One hundred two patients with claudication and lesions of the superficial femoral and popliteal arteries of no greater than 10 cm were studied. All patients were treated with a primary strategy of stand-alone cryoplasty with use of the PolarCath cryoplasty system. The primary endpoints of the study were acute technical success and clinical patency at 9 months. Technical success was defined as the ability to achieve residual angiographic stenosis no greater than 30% and residual stenosis less than 50% by duplex ultrasound (US) imaging. Clinical patency was defined as freedom from target lesion revascularization within 9 months. Primary patency was defined by a duplex US systolic velocity ratio no greater than 2.0. RESULTS: A total of 102 patients were enrolled at 16 centers. Of those treated, 31% had diabetes and 31% were active cigarette smokers. The majority of the lesions were confined to the superficial femoral artery (84.3%) and 14.7% presented with total occlusions. The mean vessel diameter treated was 5.5 mm +/- 0.5, the mean stenosis diameter was 87% +/- 10%, and the mean lesion length was 4.7 cm +/- 2.6. The technical success rate was 85.3% with a mean residual stenosis after cryoplasty of 11.2% +/- 11.2% (P < .05 vs baseline). Clinical patency in this group was 82.2%, as only 16 patients required target lesion revascularization during the 9-month surveillance period. Primary patency determined by duplex US was 70.1%. CONCLUSIONS: Cryoplasty demonstrated a high degree of acute angiographic success and a low frequency of target lesion revascularization. The patency rate observed compares favorably to that previously documented with conventional angioplasty.

Reteplase monotherapy and reteplase/abciximab combination therapy in peripheral arterial occlusive disease: results from the RELAX trial.

PURPOSE: The safety and efficacy of increasing doses of intraarterial reteplase monotherapy and reteplase/abciximab combination therapy were examined in patients with acute peripheral arterial occlusive disease (PAOD). The primary endpoint of this analysis was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) investigators. MATERIALS AND METHODS: The RELAX trial was a prospective, dose-escalating safety trial of reteplase monotherapy (0.1, 0.2, 0.5, or 1.0 U/h) and reteplase/abciximab combination therapy (0.25-mg/kg bolus and 0.125 micro g/kg/min abciximab in addition to each reteplase regimen) for patients with acute or subacute clinical deterioration of PAOD. Reteplase was administered intraarterially to 74 patients; 38 patients were also administered intravenous abciximab for the duration of reteplase infusion. Protocol-specified angiograms were obtained at 6 and 20 hours or for clinical need. Each angiogram was assessed for volume of thrombus dissolved and for arterial patency. The primary safety endpoint (TIMI major bleeding) was assessed at discharge and at day 7. Clinical endpoints were assessed at discharge and at days 30 and 90. RESULTS: Major bleeding occurred with similar frequency in patients treated with and without abciximab (15% of the pooled patients receiving reteplase monotherapy and 20% of patients receiving reteplase/abciximab combination therapy). There were no intracranial hemorrhagic events in the 74 patients. Reteplase doses of at least 0.2 U/hour were effective at dissolving thrombus and restoring patency. There was no clear dose-response relationship for reteplase. However, the addition of abciximab reduced the occurrence of distal embolic events requiring intervention (5% vs. 31%; P =.014). CONCLUSIONS: Over the range of reteplase doses studied for peripheral arterial thrombolysis, there were no significant differences in safety or efficacy. However, the addition of intravenous abciximab to reteplase was associated with a decreased rate of distal embolic events without a significant increase in the risk of hemorrhagic complications. Further investigation is needed to define the role of abciximab in catheter-directed thrombolysis with reteplase for PAOD.

Rheolytic thrombectomy in the management of limb ischemia: 30-day results from a multicenter registry.

PURPOSE: To evaluate the use of rheolytic thrombectomy (RT) with the AngioJet catheter for treatment of lower extremity ischemia due to arterial/graft thrombotic occlusion. METHODS: A retrospective multicenter review was performed of 99 consecutive patients (52 men; mean age 67 +/- 13 years, range 30-90) who underwent RT for thrombotic occlusions in native arteries (n=80) or bypass grafts (n=19). Pre- and postprocedural limb ischemia and in-hospital events were evaluated. Amputation and mortality rates at 30 days were determined. RESULTS: The majority of patients (78.8%) presented within 14 days of symptom onset. RT resulted in substantial to complete thrombus removal in 70 (70.7%) patients and partial in 22 (22.2%); there was no angiographic change in 7 (7.1%). Adjunctive post RT thrombolysis was used in 37 patients. Underlying stenoses found in 81 limbs were treated with one or more of the following procedures: balloon angioplasty (n=62), stenting (n=35), or nonemergent surgical revision (n=5). In-hospital complications included 2 major amputations, 5 cases of minor tissue loss, 7 rethromboses, and 3 cases of transient renal insufficiency. Four (4.0% patients died in-hospital; the 95 surviving patients all had viable limbs at discharge. Mortality and amputation rates at 30 days were 7.1% and 4.0%, respectively. CONCLUSIONS: Percutaneous treatment of thrombotic occlusions with RT, followed by definitive treatment of the underlying stenosis, is a promising therapeutic option for patients with limb-threatening ischemia.