Arteriovenous fistula patency in the 3 years following vonapanitase and placebo treatment.

OBJECTIVE: This study explored the long-term outcomes of arteriovenous fistulas treated with vonapanitase (recombinant human elastase) at the time of surgical creation. METHODS: This was a randomized, double-blind, placebo-controlled trial of 151 patients undergoing radiocephalic or brachiocephalic arteriovenous fistula creation who were randomized equally to placebo, vonapanitase 10 µg, or vonapanitase 30 µg. The results after 1 year of follow-up were previously reported. The current analysis occurred when the last patient treated was observed for 3 years. For the current analysis, the primary end point was primary patency; the secondary end points included secondary patency, use of the fistula for hemodialysis, and rate of procedures to restore or to maintain patency. RESULTS: There was no significant difference in the risk of primary patency loss with vonapanitase 10 µg or 30 µg vs placebo. When seven initial patency loss events related to cephalic arch and central vein balloon angioplasty were excluded, the risk of patency loss was reduced with vonapanitase overall (hazard ratio [HR], 0.63; P = .049) and 30 µg (HR, 0.51; P = .03). In patients with radiocephalic fistulas (n = 67), the risks of primary and secondary patency loss were reduced with 30 µg (HR, 0.37 [P = .02] and 0.24 [P = .046], respectively). The rate of procedures to restore or to maintain fistula patency was reduced with 30 µg vs placebo (0.23 vs 0.72 procedure days/patient/year; P = .03) and also reduced in patients with radiocephalic fistulas with 30 µg vs placebo (0.17 vs 0.85 procedure days/patient/year; P = .048). CONCLUSIONS: In this study, vonapanitase did not significantly improve primary patency in the primary analysis but did significantly improve primary patency in an analysis that excluded patency loss due to cephalic arch and central vein balloon angioplasty. In patients with radiocephalic fistulas, 30 µg significantly improved primary and secondary patency. Vonapanitase 30 µg decreased the rate of procedures to restore or to maintain patency in the analysis that included all patients and in the subset with radiocephalic fistulas.

Complete robotic repair of a renal artery aneurysm.

Although the majority of renal artery aneurysms require only observation, those that require treatment have been addressed primarily surgically or endovascularly. We report a case of surgical resection of a large, symptomatic renal artery aneurysm from an entirely robotic approach.

Radiology Case of the Month: Rising Creatinine in an Elderly Woman.

To assess an elevated creatinine, a 67-year old woman underwent renal ultrasound which incidentally revealed an abdominal aortic aneurysm (AAA).

Endovascular stent-graft repair of ascending aortic dissection with a commercially available thoracic endograft.

We describe the endovascular treatment of a type A thoracic aortic dissection (TAAD) in a patient deemed unfit for surgical repair with a commercially available thoracic endograft. A patient with a symptomatic acute TAAD, multiple medical comorbidities, and ascending thoracic aortic and arch dilation underwent successful endovascular repair with the use of a commercially available stent graft, resulting in complete resolution of his symptoms despite slight but persistent perigraft false lumen perfusion. Although surgical repair remains the gold standard, endografting has promise and may have a positive impact on the current treatment algorithm for TAAD. Advances must occur in graft manufacturing, and further data will be required before wider application is appropriate.

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

BACKGROUND AND PURPOSE: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. METHODS: We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. RESULTS: Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, -$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. CONCLUSIONS: Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00004732.

Health-related quality of life after carotid stenting versus carotid endarterectomy: results from CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial).

OBJECTIVES: The purpose of this study was to compare health-related quality of life (HRQOL) outcomes in patients treated with carotid artery stenting (CAS) versus carotid endarterectomy (CEA). BACKGROUND: In CREST (Carotid Revascularization Endarterectomy versus Stenting Trial), the largest randomized trial of carotid revascularization to date, there was no significant difference in the primary composite endpoint, but rates of stroke and myocardial infarction (MI) differed between CAS and CEA. To help guide individualized clinical decision making, we compared HRQOL among patients enrolled in the CREST study. We also performed exploratory analyses to evaluate the association between periprocedural complications and HRQOL. METHODS: We measured HRQOL at baseline, and after 2 weeks, 1 month, and 1 year among 2,502 patients randomly assigned to either CAS or CEA in the CREST study. The HRQOL was assessed using the Medical Outcomes Study Short-Form 36 (SF-36) and 6 disease-specific scales designed to study HRQOL in patients undergoing carotid revascularization. RESULTS: At both 2 weeks and 1 month, CAS patients had better outcomes for multiple components of the SF-36, with large differences for role physical function, pain, and the physical component summary scale (all p < 0.01). On the disease-specific scales, CAS patients reported less difficulty with driving, eating/swallowing, neck pain, and headaches but more difficulty with walking and leg pain (all p < 0.05). However, by 1 year, there were no differences in any HRQOL measure between CAS and CEA. In the exploratory analyses, periprocedural stroke was associated with poorer 1-year HRQOL across all SF-36 domains, but periprocedural MI or cranial nerve palsy were not. CONCLUSIONS: Among patients undergoing carotid revascularization, CAS is associated with better HRQOL during the early recovery period as compared with CEA-particularly with regard to physical limitations and pain-but these differences diminish over time and are not evident after 1 year. Although CAS and CEA are associated with similar overall HRQOL at 1 year, event-specific analyses confirm that stroke has a greater and more sustained impact on HRQOL than MI. (Carotid Revascularization Endarterectomy versus Stenting Trial [CREST]; NCT00004732)

Influence of sex on outcomes of stenting versus endarterectomy: a subgroup analysis of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).

BACKGROUND: In the randomised Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the primary endpoint did not differ between carotid artery stenting and carotid endarterectomy in patients with symptomatic and asymptomatic stenosis. A prespecified secondary aim was to examine differences by sex. METHODS: Patients who were asymptomatic or had had a stroke or transient ischaemic attack within 180 days before random allocation were enrolled in CREST at 117 clinical centres in the USA and Canada. The primary outcome was the composite of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years. We used standard survival methods including Kaplan-Meier survival curves and sex-by-treatment interaction term to assess the relation between patient factors and risk of reaching the primary outcome. Analyses were by intention to treat. CREST is registered with ClinicalTrials.gov, NCT00004732. FINDINGS: Between Dec 21, 2000, and July 18, 2008, 2502 patients were randomly assigned to carotid endarterectomy (n=1240) or carotid artery stenting (n=1262), 872 (34.9%) of whom were women. Rates of the primary endpoint for carotid artery stenting compared with carotid endarterectomy were 6.2% versus 6.8% in men (hazard ratio [HR] 0.99, 95% CI 0.66-1.46) and 8.9% versus 6.7% in women (1.35, 0.82-2.23). There was no significant interaction in the primary endpoint between sexes (interaction p=0.34). Periprocedural events occurred in 35 (4.3%) of 807 men assigned to carotid artery stenting compared with 40 (4.9%) of 823 assigned to carotid endarterectomy (HR 0.90, 95% CI 0.57-1.41) and 31 (6.8%) of 455 women assigned to carotid artery stenting compared with 16 (3.8%) of 417 assigned to carotid endarterectomy (1.84, 1.01-3.37; interaction p=0.064). INTERPRETATION: Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy whereas there is little difference in men. Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women. FUNDING: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions (formerly Guidant).

Does sex matter? Thirty-day stroke and death rates after carotid artery stenting in women versus men: results from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) lead-in phase.

BACKGROUND AND PURPOSE: Several carotid endarterectomy randomized, controlled trials and series have reported higher perioperative stroke and death rates for women compared with men. The potential for this same relationship with carotid artery stenting was examined in the lead-in phase of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). METHODS: CREST compares efficacy of carotid endarterectomy and carotid artery stenting in preventing stroke, myocardial infarction, and death in the periprocedural period and ipsilateral stroke over the follow-up period. CREST included a "lead-in" phase of symptomatic (>or=50% stenosis) and asymptomatic (>or=70% stenosis) patients. Patients were examined by a neurologist preprocedure, at 24 hours, and at 30 days. Review of stroke and death was by an independent events committee. The association of sex with periprocedural stroke and death was examined in 1564 patients undergoing carotid artery stenting (26.5% symptomatic). RESULTS: Women comprised 37% of the lead-in cohort and did not differ from men by age, symptomatic status, or characteristics of the internal carotid artery. The 30-day stroke and death rate for women was 4.5% (26 of 579; 95% CI, 3.0% to 6.5%) compared with 4.2% (41 of 985; 95% CI, 3.0% to 5.6%) for men. The difference in stroke and death rate was not significant nor were there any significant differences by sex after adjustment for age, arterial characteristics, or cardiovascular risk factors. CONCLUSIONS: These results do not provide evidence that women have a higher carotid artery stenting stroke and death rate compared with men. The potential differential periprocedural risk by sex will be prospectively addressed in the randomized phase of CREST.

Aneurysm Outreach Inc., a nonprofit organization, offers community-based, ultrasonography screening for abdominal aortic aneurysms.

Aneurysm Outreach Inc. (AOI; http://www.alink.org) is a nonprofit volunteer organization founded in 1999 whose aim is to (a) raise public awareness about aneurysms; (b) stimulate and fund genetic research through donations; and (c) coordinate a support network for aneurysm patients and their families. Since abdominal ultrasonography examination of an asymptomatic individual is not presently reimbursed by health insurance in the United States, one of the initiatives supported by AOI is to have free ultrasonography screening for abdominal aortic aneurysm (AAA) for those most at risk. One of the initiatives supported by AOI is to have free ultrasonography screening for abdominal aortic aneurysm (AAA). To meet this goal, a free screening program was initiated in September 2001 and by November 2004 approximately 3,000 participants were screened and 61 (2.0%) participants were confirmed to have a dilated aorta and were referred to their primary care physicians or vascular surgeons for further follow-up and treatment, if indicated.

Community-based, nonprofit organization-sponsored ultrasonography screening program for abdominal aortic aneurysms is effective at identifying occult aneurysms.

Early diagnosis of abdominal aortic aneurysm (AAA), prior to rupture, is vital for optimizing patient survival. An abdominal ultrasonography examination of an asymptomatic individual to check for the presence of an AAA, however, is not presently reimbursed by health insurance in the United States. This article reports the results of one nonprofit, community-based screening program, run by Aneurysm Outreach, Inc. (AOI; www.alink.org). AOI offered free screening for AAA to anyone who met the criteria of being (1) over 60 years old; (2) over 50 years old, male, and with positive family history for AAA; or (3) over 55 years old, female, and with positive family history for AAA. AOI organized 21 ultrasonographic screening events between September 2001 and November 2004, and the number of participants per event varied from 24 to 240. Altogether 3,088 individuals met the screening criteria and 22 of them were already known to have AAAs. Thirty-six (1.2%) individuals were excluded from the final analysis due to poor quality of the ultrasonographic images. Among the remaining 3,030 individuals, a dilatation of the aorta was detected and confirmed in 61 (2.0%) individuals, in 4.3% of the screened males and in 0.6% of the screened females. Thirteen individuals had their AAAs repaired surgically. The frequencies of males and current smokers were significantly higher in the AAA group than in the group with normal-size aorta (male AAA 83.6% vs. normal 42.0%, p < 0.0001; smoker AAA 54.9% vs. normal 18.1%, p < 0.0001). The mean age was significantly higher in the AAA group than in the group with normal-size aorta (AAA 71.0 +/- 6.2 vs. normal 68.4 +/- 7.0, p = 0.005). In conclusion, the results of this community-based free ultrasonographic screening program are in agreement with randomized controlled screening programs and emphasize the need for systematic screening programs and the importance of finding individuals harboring AAAs before their rupture.

Repair of a blunt traumatic inferior vena cava laceration with commercially available endografts.

Endografts have recently been used in the trauma setting for arterial injuries in surgically inaccessible areas or in medically unstable patients. There have been considerably fewer reports on the use of endografts for treatment of traumatic venous injuries. We present the case of an endograft repair of a blunt, traumatic inferior vena cava injury in a patient deemed at high risk for surgical repair.

Upper gastrointestinal bleeding caused by a "hypophrenic" diverticulum of the distal esophagus.

Distal esophageal diverticula are uncommon acquired anomalies of the distal thoracic esophagus. We report a case of an elderly man presenting with a history of upper gastrointestinal bleeding secondary to a distal esophageal diverticulum arising from the intra-abdominal portion of the esophagus. To our knowledge, this is the first report of upper gastrointestinal bleeding from a subdiaphragmatic esophageal diverticulum. We propose the term "hypophrenic diverticulum of the esophagus" for this disease entity, and we would like to bring it to the attention of readers of The American Surgeon.

Early results with use of gracilis muscle flap coverage of infected groin wounds after vascular surgery.

INTRODUCTION: Management of a nonhealing femoral wound after vascular surgery can pose a challenging problem, particularly when there is prosthetic material involved. We prefer to use pedicled gracilis muscle flaps (PGMFs) to cover problematic groin wounds when more conventional management is not possible. METHODS: We describe the technique for using PGMFs to provide groin coverage, report a summary of our short-term and long-term results, and describe why we prefer this reconstructive technique. RESULTS: Twenty PGMFs were placed in 18 patients to treat nonhealing and infected groin wounds. Exposed prosthetic vascular reconstructions were covered with the PGMF in 14 wounds, and in situ autogenous vascular reconstructions were covered in four. Seven wound infections were polymicrobial, 10 had a single gram-positive organism, and one had a single gram-negative organism. Pseudomonas cultured out in four wounds, and Candida in one wound. Two patients had a virulent combination of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus. Complete healing was initially achieved in all wounds, and no patient died within 30 days of surgery. Two PGMFs failed, at 2 weeks and 2 months, respectively, one from tension on the flap pedicle and one from acute inflow occlusion. Underlying prosthetic reconstruction was salvaged in 12 of 14 wounds; the remaining wounds with autogenous reconstructions or exposed femoral vessels all closed successfully. At a mean follow-up of 40 +/- 10 months there were no recurrent groin infections. Seven patients died, at 2.5, 3, 8, 12, 14, 22, and 28 months, respectively. CONCLUSION: PGMF transposition is an effective option to cover infected or exposed femoral vessels or salvage prosthetic graft material in the groin. In appropriately selected patients, when complete graft removal and extra-anatomic bypass is not an acceptable option, gracilis muscle flap coverage is a viable alternative. The technique is relatively simple, and morbidity from PGMF harvest is minimal.

Safety of gadolinium contrast angiography in patients with chronic renal insufficiency.

OBJECTIVE: To prevent iodinated contrast medium-induced nephrotoxicity, gadolinium has been used increasingly for magnetic resonance angiography (MRA) or conventional digital subtraction angiography (DSA) to visualize arterial anatomy in patients undergoing vascular surgery who are considered at high risk because of chronic renal insufficiency. We assessed the safety of gadolinium-based contrast medium as a substitute for iodinated contrast medium-enhanced examinations. We determined the incidence of gadolinium-induced nephrotoxicity in a clinical setting and searched for contributing risk factors. Patients and methods In a single-center retrospective study from December 1999 to January 2001, 218 inpatients underwent MRA and 42 inpatients underwent DSA, with gadolinium as the sole contrast agent. Patient comorbid conditions, indications for vascular imaging, contrast dose, urine output, baseline and post-procedure serum creatinine concentration (SCr), and outcome were recorded for all patients in whom gadolinium-induced renal failure developed. RESULTS: Of 260 patients who received gadolinium-based contrast agents, at a dose of 0.25 mmol/kg or more, 195 patients (75%) had pre-test baseline chronic renal insufficiency. In 7 of 195 patients (3.5%) acute renal failure developed after gadolinium-based contrast medium administration, for MRA (n = 153) in 3 patients (1.9%) and DSA (n = 42) in 4 patients (9.5%). Average baseline SCr in the 195 patients with chronic renal insufficiency was 38.2 +/- 1.6 mL/min/1.73 m(2), and in the 7 patients in whom acute renal failure developed, baseline SCr was 32.5 +/- 7.8 mL/min/1.73 m(2) (P =.33). Respective intravenous and intra-arterial gadolinium doses in these 7 patients ranged from 0.31 to 0.41 mmol/kg for MRA and 0.27 to 0.42 mmol/kg for DSA. Acute renal failure did not develop in any of 65 patients with normal baseline SCr. CONCLUSION: Despite reports of negligible nephrotoxicity, rarely gadolinium-based contrast agents can cause acute renal failure in patients with underlying chronic renal insufficiency. Estimation of creatinine clearance alone does not enable prediction of which patients are likely to have acute renal failure. Patients at high-risk should be identified, and prophylactic measures should be taken to reduce the risk for nephrotoxicity.

Inferior vena cava thrombus removal using hypothermic circulatory arrest in two patients with osteosarcoma.

In this case report, the technique of deep hypothermia and circulatory arrest (DHCA) is used to successfully extract extensive symptomatic tumor thrombus from the inferior vena cava (IVC) in two patients with osteosarcoma. This is the first description of the use of this modality for treatment of osteosarcoma involving the IVC. Osteosarcoma and the use of DHCA are discussed.

Inhibiting adenosine deaminase modulates the systemic inflammatory response syndrome in endotoxemia and sepsis.

By pharmacological manipulation of endogenous adenosine, using chemically distinct methods, we tested the hypothesis that endogenous adenosine tempers proinflammatory cytokine responses and oxyradical-mediated tissue damage during endotoxemia and sepsis. Rats were pretreated with varying doses of pentostatin (PNT; adenosine deaminase inhibitor) or 8-sulfophenyltheophylline (8-SPT; adenosine receptor antagonist) and then received either E. coli endotoxin (lipopolysaccharide; 0.01 or 2.0 mg/kg) or a slurry of cecal matter in 5% dextrose in water (200 mg/kg). Resultant levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-10 were measured in serum and in liver and spleen. Untreated, 2 mg/kg lipopolysaccharide elevated serum TNF-alpha, IL-1beta, and IL-10. PNT dose dependently attenuated, without ablating, the elevation in serum TNF-alpha and IL-1beta and raised liver and spleen IL-10. PNT also attenuated elevation of TNF-alpha in serum, liver, and spleen at 4 and 24 h after sepsis induction, and 8-SPT resulted in higher proinflammatory cytokines. Modulating endogenous adenosine was also effective in exacerbated (8-SPT) or diminished (PNT) tissue peroxidation. Survival from sepsis was also improved when PNT was used as a posttreatment. These data indicate that endogenous adenosine is an important modulatory component of systemic inflammatory response syndromes. These data also indicate that inhibition of adenosine deaminase may be a novel and viable therapeutic approach to managing the systemic inflammatory response syndrome without ablating important physiological functions.

Induction of peritoneal sepsis increases the susceptibility of isolated hearts to a calcium paradox-mediated injury.

The present study was designed to test the hypothesis that induction of chronic peritoneal sepsis in rats would produce a more severe calcium paradox-mediated myocardial injury in isolated heart preparation than is seen in normal hearts, and that this would be inhibited by sucrose as in normal hearts. Male Sprague-Dawley rats were made septic using 200 mg of cecal material (obtained from a donor rat) suspended in 5 mL of 5% dextrose in sterile water D5 W/kg. In septic animals, the cecal material was injected in the peritoneum, while sham-septic animals received only D5 W/kg (5 mL/kg). A third group consisting of normal rats (no surgery) group was also included. Hearts were harvested from all three groups and were subjected to a calcium paradox-mediated injury in an isolated heart preparation. Hearts were perfused with Krebs-Henseleit (KH) medium and were allowed to stabilize, followed by a perfusion with Ca2+-free KH for 10 min. After this 10-min Ca2+-free KH perfusion, rats were reperfused with KH medium for 60 min. Ca2+-free KH medium was used in control experiments, while sucrose experiments were conducted with the same medium except that 150 mM sucrose replaced 75 mM NaCl. A marked decrease in ATP and phosphocreatine occurred during Ca2+ reperfusion in all hearts in absence of sucrose. In the presence of the disaccharide, no change in high-energy phosphate (HEP) levels was observed in normal hearts, while lower ATP concentrations were seen in sham and septic hearts. Thus, sucrose did not inhibit cellular injury in sham and septic hearts as it did in normal hearts, and this might be due to a smaller HEP availability. Control studies with normal, sham, and septic hearts exhibited cessation of contractions in the absence of Ca2+, and appearance of large amounts of cytosolic protein in the effluent perfusate during Ca2+ reperfusion. With normal hearts, perfusion with sucrose caused a 96% inhibition of the total creatine kinase (CK) release observed in control experiments. With sham hearts, 32% of CK release was inhibited by sucrose, while 68% of the CK release was attributed to stress associated with surgery performed in the sham-septic group. In septic hearts, only 8% of the CK release was inhibited by sucrose, suggesting that more severe myocardial injury occurs when septic hearts are subjected to a calcium paradox as compared to other groups. It is evident that sucrose can inhibit a small fraction of the CK release from septic hearts during the calcium paradox as compared to the large CK loss associated with sham sepsis. We have concluded that induction of sepsis made the heart more susceptible to a calcium paradox-mediated myocardial injury.