The role of genomic data in the discovery, annotation and evolutionary interpretation of the interferon-lambda family.

BACKGROUND: Type-I interferons, type-II interferons, and the IL-10 family are helical cytokines with similar three-dimensional folds. However, their homologous relationship is difficult to detect on the basis of sequence alone. We have previously described the discovery of the human type-III interferons (IFN lambda-1, -2, -3 or IL-29, IL-28A, IL-28B), which required a combination of manual and computational techniques applied to predicted protein sequences. PRINCIPAL FINDINGS: Here we describe how the use of gene structure analysis and comparative genomics enabled a more extensive understanding of these genes early in the discovery process. More recently, additional mammalian genome sequences have shown that there are between one and potentially nine copies of interferon lambda genes in each genome, and that several species have single exon versions of the interferon lambda gene. SIGNIFICANCE: The variable number of single exon type-I interferons in mammals, along with recently identified genes in zebrafish homologous to interferons allows a story of interferon evolution to be proposed. This model suggests that the gene duplications and single exon retrotransposons of mammalian type-III interferons are positively selected for within a genome. These characteristics are also shared with the fish interferons and could be responsible for the generation of the IL10 family and also the single exon type-I interferons.

The management of severe aortoiliac occlusive disease: endovascular therapy rivals open reconstruction.

OBJECTIVE: Aortobifemoral bypass (ABF) grafting has been the traditional treatment for extensive aortoiliac occlusive disease (AIOD). This retrospective study compared the outcomes and durability of recanalization, percutaneous transluminal angioplasty, and stenting (R/PTAS) vs ABF for severe AIOD. METHODS: Between 1998 and 2004, 86 patients (161 limbs) underwent ABF (n = 75) or iliofemoral bypass (n = 11), and 83 patients (127 limbs) underwent R/PTAS. All patients had severe symptomatic AIOD (claudication, 53%; rest pain, 28%; tissue loss, 12%; acute limb ischemia, 7%). The analyses excluded patients treated for aneurysms, extra-anatomic procedures, and endovascular treatment of iliac stenoses. Original angiographic imaging, medical records, and noninvasive testing were reviewed. Kaplan-Meier estimates for patency and survival were calculated and univariate analyses performed. Mortality was verified by the Social Security database. RESULTS: The ABF patients were younger than the R/PTAS patients (60 vs 65 years; P = .003) and had higher rates of hyperlipidemia (P = .009) and smoking (P < .001). All other clinical variables, including cardiac status, diabetes, symptoms at presentation, TransAtlantic Inter-Society Consensus stratification, and presence of poor outflow were similar between the two groups. Patients underwent ABF with general anesthesia (96%), often with concomitant treatment of femoral or infrainguinal disease (61% endarterectomy, profundaplasty, or distal bypass). Technical success was universal, with marked improvement in ankle-brachial indices (0.48 to 0.84, P < .001). Patients underwent R/PTAS with local anesthesia/sedation (78%), with a 96% technical success rate and similar hemodynamic improvement (0.36 to 0.82, P < .001). At the time of R/PTAS, 21% of patients underwent femoral endarterectomy/profundaplasty or bypass (n = 5) for concomitant infrainguinal disease. Limb-based primary patency at 3 years was significantly higher for ABF than for R/PTAS (93% vs 74%, P = .002). Secondary patency rates (97% vs 95%), limb salvage (98% vs. 98%), and long-term survival (80% vs 80%) were similar. Diabetes mellitus and the requirement of distal bypass were associated with decreased patency (P < .001). Critical limb ischemia at presentation (tissue loss, hazard ratio [HR], 8.1; P < .001), poor outflow (HR, 2; P = .023), and renal failure (HR, 2.5; P = .02) were associated with decreased survival. CONCLUSION: R/PTAS is a suitable, less invasive alternative to ABF for the treatment of severe AIOD. Repair of the concomitant femoral occlusive disease is often needed regardless of open or endovascular treatment. Infrainguinal disease negatively affects the durability of the procedure and patient survival.

Endovascular management of iliac artery occlusions: extending treatment to TransAtlantic Inter-Society Consensus class C and D patients.

OBJECTIVE: The preferential use of endovascular techniques to treat complex aortoiliac disease has increased in recent years. The purpose of this study was to review the outcomes and durability of recanalization, percutaneous transluminal angioplasty, and stenting for iliac occlusions based on the patient's TransAtlantic Inter-Society Consensus (TASC) stratification. METHODS: Between 1998 and 2004, more than 628 patients with a clinical diagnosis of aortoiliac atherosclerotic disease underwent arteriography. The endovascular treatment of 89 consecutive patients (mean age, 66 years; 58% male) with symptomatic iliac occlusions (TASC-B, -C, and -D) was the basis for this study. Original angiographic imaging was evaluated for lesion grade and runoff. Electronic and hard copy medical records were reviewed for demographic data, clinical variables, and noninvasive vascular laboratory testing. Kaplan-Meier estimators were used to determine patency rates according to Society for Vascular Surgery criteria. Univariate and multivariate analyses were performed. P values of <.05 were considered significant. RESULTS: Recanalization and percutaneous transluminal angioplasty/stenting (total, 178 stents) of occluded iliac arteries was technically successful in 84 (91%) of 92 procedures. Patients in the TASC-C and -D groups often required multiple access sites (50%) and femoral artery endarterectomy/patch angioplasty for diffuse disease (24%). The mean ankle-brachial index increased from 0.45 to 0.83. Distal embolization led to major amputation and eventual death in one patient. Two other deaths occurred in the perioperative period secondary to cardiorespiratory causes. Three-year primary patency, secondary patency, and limb salvage rates were 76%, 90%, and 97%, respectively, and progression of infrainguinal disease led to late limb loss in two patients. Diabetes as a risk factor was significantly associated with decreased primary patency (57% vs 83%; P = .049). Critical ischemia at presentation was associated with decreased patency rates as well (P = .002), but TASC classification did not significantly alter patency rates. CONCLUSIONS: Complex long-segment and bilateral iliac occlusions can be safely treated via endovascular means with high rates of symptom resolution. Initial technical success, low morbidity, and mid-term durability are comparable to results with open reconstruction. A liberal posture to open femoral artery reconstruction extends the ability to treat diffuse TASC-C and -D lesions via endovascular means.

Initial management and outcome of aortic endograft limb occlusion.

OBJECTIVE: The purpose of this study was to determine the differences in outcome related to initial management of aortic endograft limb occlusion (ELO). METHODS: During a 7-year period, 823 endovascular aneurysm repairs (EVARs) resulted in 25 ELOs in 22 patients. The initial management and outcome of these ELOs were reviewed. Median follow-up after ELO was 24.2 +/- 16.8 months. RESULTS: Initial EVARs included both unsupported unibody (n = 5) and supported modular (n = 17) devices. ELO was significantly more common in the unsupported unibody graft design (P <.024) and with extension of the graft limb to the external iliac artery (P <.001). ELO was managed with an endovascular approach (EVA), including some combination of mechanical thrombectomy (n = 8), angioplasty with or without stenting (n = 8), and thrombolysis (n = 2) in 12 patients and bypass procedures (femoral-femoral bypass, n = 11; axillofemoral bypass, n = 1; and aortofemoral bypass, n = 1) in 13. At 12-month follow-up, freedom from secondary procedures with EVA was 80.2 +/- 17.7% versus 53.2 +/-17.1% with extra-anatomic bypass (EB) (P = NS). Secondary patency was 100% with EVA and 80.6 +/- 14.4% with EB (P = NS). Of the 12 EVAs, there was 1 (8.3%) perioperative mortality with EVA and none with EB. EB failure was directly attributed to donor limb occlusion in 4 of 6 EVAs (67%), and when this occurred it resulted in bilateral lower extremity ischemia. Amputation was required in 2 of 12 (16.7%) EBs versus none of the 12 EVAs (P = NS). EVA never resulted in graft dislodgement or endoleak but did identify an underlying treatable cause in 8 of 12 (67%). CONCLUSION: Both EVA and EB are acceptable management strategies for ELO. The potential risk of graft dislodgement was not observed with an EVA. If EB is employed, assessment of the donor limb and treatment of any underlying lesions is advisable in an attempt to minimize future donor limb occlusion.

Stent-graft migration: a reappraisal of analysis methods and proposed revised definition.

PURPOSE: To demonstrate the need for a radiographic definition of migration that accurately describes a specific failure mode of an aortic stent-graft. METHODS: The diagnosis of endograft migration, as defined by the Society for Vascular Surgery/American Association for Vascular Surgery (SVS/AAVS) standards, requires a synthesis of clinical and/or radiographic observations. Radiographic studies and clinical reports of 704 consecutive patients treated over a 6-year period with abdominal aortic endografts were retrospectively reviewed. According to the current SVS/AAVS standards, 25 patients were identified as having endograft migration. Follow-up computed tomographic scans and radiographs available for 24 of these patients were scrutinized from discharge to the time of any observed proximal or distal fixation system movement based upon the discharge or 30-day CT scan. Proximal migration was defined with respect to the origin of the superior mesenteric artery (SMA) as movement in a caudal or cranial direction of >/=10 mm or >2 times the reconstructed resolution of the imaging study (whichever measurement was less). Distal migration was similarly defined using the aortic bifurcation and respective hypogastric artery origin as reference points. In an effort to assess the scan-to-scan variation, the distance between the SMA and lowest renal artery, which was expected to remain consistent, was measured. RESULTS: Film analysis with application of the revised migration definition confirmed fixation system failure with respect to the native arterial system in 12 (50%) of the 24 patients. Subjects judged to have endograft migration according to the reporting standards but not to have radiographic evidence of migration based on the modified criteria included 2 proximal endoleaks without evidence of device movement treated with proximal extensions, 1 procedure-related migration, 2 type III endoleaks treated with a second prosthesis implanted within the first, 1 distal endoleak treated with a limb extension, 1 rupture with presumed distal limb migration, and 2 cases of component separation. Three limb extensions were placed in the absence of leak or migration. These 12 patients all had radiographic evidence that the proximal and distal aspects of the originally implanted device did not move with respect to the native arterial vasculature, thus confirming stability of the respective fixation system. CONCLUSIONS: Adherence to this comprehensive definition of device migration, which differs from the published reporting standards, allows differentiation of the specific mechanisms of device failure. Data viewed in this context will aid in the understanding of device strengths and weaknesses, potentially improve patient assessment, and encourage design modifications to address specific aspects relating to fixation failure.

Endovascular aneurysm repair: gender-specific results.

OBJECTIVES: The outcome for a wide variety of diseases and treatment methods varies by gender. In an effort to determine whether gender has a role in the outcome of endovascular aortic aneurysm repair, we analyzed data from consecutive patients treated at a single institution over 6 years. METHODS: Over 6 years ending in March 2002, 704 patients underwent endovascular repair of an infrarenal abdominal aortic aneurysm at The Cleveland Clinic. Six hundred six patients (86.1%) were men and 98 patients (13.9%) were women. Preprocedure and postprocedure imaging studies were evaluated to determine the frequency of aneurysm sac shrinkage or growth, defined as diameter change equal to or greater than 5 mm. Presence and type of endoleak was assessed with non-contrast material-enhanced, post-contrast-enhanced, and delayed post-contrast-enhanced computed tomography scans. These and other clinical variables were assessed with the Kaplan-Meier method and the Cox-Mantel log-rank test, and values were expressed as mean +/- SE. RESULTS: Male and female patients were comparable with respect to baseline comorbid conditions. Women, however, were slightly older (76.7 +/- 0.7 years vs 74.4 +/- 0.3 years; P =.009), and had slightly smaller aneurysms (5.2 +/- 0.1 cm vs 5.4 +/- 0.04 cm; P =.033). There were no gender-specific differences in perioperative mortality (men, 1.3%; women, 3.1%; P =.197) or mid-term (24 months) survival (men, 80% +/- 2.6%; women, 78% +/- 8.1%). Similarly, there were no differences at 24 months in risk for graft migration (7.5% +/- 2.0% vs 5.4% +/- 3.2%), need for secondary remedial procedures (24% +/- 2.9% vs 21% +/- 6.3%), conversion to open surgery (3.9% +/- 1.5% vs 3.8% +/-2.7%), or post-repair aneurysm rupture (1.1% +/- 0.9% vs 2.2% +/-2.2%) in male and female patients, respectively. In contrast, risk for graft limb occlusion at 24 months was significantly higher in women than in men (11% +/- 5.2% vs 3.3% +/- 1.1%; P =.022). While frequency of endoleak of any type did not differ among male and female patients, aneurysm sac shrinkage at 24 months was more rapid in women (76% +/- 8.1% vs 57% +/- 3.5%; P =.019). CONCLUSIONS: With the exception of slightly older age and somewhat smaller aneurysm, female patients are similar to male patients undergoing endovascular aneurysm repair. A greater frequency of graft limb occlusion was observed in female patients, but no statistically significant differences were detected in survival, rupture risk, or need for secondary procedures. Moreover, a more rapid rate of aneurysm sac shrinkage was detected in women. These observations suggest that endovascular aneurysm repair should be offered to suitable candidates irrespective of gender.

Nature, frequency, and predictors of secondary procedures after endovascular repair of abdominal aortic aneurysm.

OBJECTIVES: Endovascular stent grafting offers a potentially less invasive option for treatment of abdominal aortic aneurysm. Clinical benefit has been demonstrated with respect to early parameters such as blood transfusion, return of gastrointestinal function, and length of hospital stay. Endovascular repair, however, has been criticized on the basis of inferior long-term outcome. Secondary procedures may be necessary to address durability issues such as migration, high-pressure endoleak, graft limb thrombosis, and degeneration of the stent-fabric structure itself, issues that may compromise the primary goal of aneurysm repair, protection from rupture. METHODS: Between 1996 and 2002, 703 patients underwent endovascular treatment of infrarenal abdominal aortic aneurysm at The Cleveland Clinic Foundation. During this time, five devices were used: Ancure, AneuRx, Excluder, Talent, and Zenith. Outcome was assessed with physical examination, lower extremity arterial studies, plain abdominal radiography, and computed tomography at discharge, at 1, 6, and 12 months postoperatively, and annually thereafter. Secondary procedures were defined as any procedure, exclusive of diagnostic angiography, performed after stent graft implantation, directed at treatment of aneurysm-related events. Multivariable statistical techniques for censored data (Cox proportional hazards modeling) were used to determine baseline parameters associated with need for secondary procedures over follow-up, with calculation of hazards ratio (HR) and 95% confidence interval (CI). RESULTS: Patient follow-up averaged 12.2 +/- 11.7 months. Patient survival was 90% +/- 1.4% at 1 year, 78% +/- 2.6% at 2 years, and 70% +/- 3.8% at 3 years. Aneurysm rupture occurred in 3 patients (0.4%), accounting for rupture risk of 1.4% over the first 2 years of follow-up (Kaplan-Meier method). Overall, 128 secondary procedures were required in 104 patients (15%), with a cumulative risk of 12% +/- 1.5% at 1 year, 24% +/- 2.8% at 2 years, and 35% +/- 4.4% at 3 years after stent graft implantation. Among the secondary procedures, new stent grafts and extensions were placed in 34 patients (27%), embolization of endoleak was performed in 33 patients (26%), and open surgical conversion was undertaken in 11 patients (9%). Periprocedural mortality of secondary procedures was 8% overall, but was 18% for patients undergoing open surgical conversion. Multivariable modeling identified the date the procedure was performed (HR, 1.53 per 3-month period of study; CI, 1.22-1.92; P <.001) and aneurysm size (HR, 1.35 per centimeter of minor axis; CI, 1.13-1.60; P <.001) as independent predictors of need for secondary procedures. CONCLUSIONS: Current endovascular devices are associated with a relatively high rate of complications over mid-term follow-up, culminating in frequent need for secondary remedial procedures. With strict follow-up imaging compliance, however, risk for rupture and aneurysm-related death remain exceedingly low. Newer technology may achieve improved durability and a lower requirement for secondary procedures, while maintaining the minimally invasive nature of presently available devices.

Endovascular repair of abdominal aortic aneurysms: device-specific outcome.

OBJECTIVES: Endovascular repair of abdominal aortic aneurysms, while advantageous because of its minimally invasive nature, falls short of achieving the long-term durability of traditional open surgical repair. Problems such as device migration, continued sac pressurization from endoleak, and graft limb thrombosis culminate in a high rate of secondary procedures and failure to protect against aneurysm rupture. While prior studies hint at a correlation between these postprocedural events and specific device design, a single comparative analysis that correlates device attributes with clinical outcome has not been performed. METHODS: Over 6 years ending in 2002, 703 patients underwent endovascular treatment of infrarenal abdominal aortic aneurysms. During this time, five devices were used, ie, Ancure, AneuRx, Excluder, Talent, and Zenith, and six device-specific groups were analyzed; the Zenith group was subdivided into those placed as part of the multicenter trial (Zenith-MCT) and those under a sponsor-investigator investigational device exemption trial (Zenith-SIT). Results were assessed with the Kaplan-Meier method for censored data, and the log-rank test was used to ascertain differences between device groups. RESULTS: While overall survival was diminished in the Zenith-SIT group (P =.046), risk for aneurysm-related death was similar in all groups (P =.336), averaging 2% or less at 12 months. Among the total cohort of patients, freedom from rupture was 98.7% +/- 0.9% at 24 months, without demonstrable differences between groups (P =.533). There were no statistically significant differences in rate of secondary procedures, conversion to open repair, or migration. There were, however, significant differences in risk for graft limb occlusion and rate of endoleak between groups. Limb occlusion occurred most often with Ancure devices (11% +/- 4.6% at 12 months, P =.009). Endoleak of any type was most common with Excluder devices (64% +/- 11% at 12 months, P =.003), a finding directly related to increased frequency of type II leaks in that group (58% +/- 11% at 12 months, P =.001). While there were no differences in frequency of type I or type III endoleak, a trend toward increased risk for microleak was observed with AneuRx devices (4.0% +/- 1.3%, P =.054), and more modular separations were observed with Zenith devices (3.5% +/- 2.3%, P =.032). Shrinkage at 12 months correlated with frequency of endoleak in the device groups, and was most common in the two Zenith groups (54% +/- 7.3% in the Zenith-MCT group and 56% +/- 7.8% in the Zenith-SIT group) and the Talent group (52% +/- 9.7%) and was least in the Excluder group (15% +/- 7.9% at 12 months, P <.001). By contrast, sac growth occurred most often in the Zenith-SIT group (13% +/- 4.5% at 12 months, P =.034), possibly as a result of the challenging aortoiliac anatomy frequently present in these patients. CONCLUSIONS: There are significant differences in frequency of limb occlusion and endoleak between groups with different endovascular devices. Knowledge of these and other differences is instructional in development of next-generation endovascular devices, incorporating design features linked to satisfactory outcome while abandoning those associated with device failure.

Disparate outcome after endovascular treatment of small versus large abdominal aortic aneurysm.

OBJECTIVES: The size of an abdominal aortic aneurysm is the most important parameter for determining whether repair is appropriate. This decision, however, must be considered in the context of long-term outcome of treatment, balancing risk for rupture with mortality from the initial procedure and all subsequent secondary procedures necessary when durability is not ideal. Information on the results of endovascular repair of small versus large aneurysms has not been available. METHODS: Preoperative imaging studies and postoperative outcome were assessed in 700 patients who underwent endovascular repair of abdominal aortic aneurysm over 6 years at a single institution. Patients were divided into two groups: 416 patients (59.4%) with aneurysms smaller than 5.5 cm in diameter and 284 patients (40.6%) with aneurysms 5.5 cm or larger in diameter. Outcome variables were assessed with the Kaplan-Meier method and the log-rank test. RESULTS: Patients with small and large aneurysms were comparable with regard to all baseline parameters assessed, with the single exception of a small increase in age (2.3 years) in patients with large aneurysms (P =.031). While there were no differences in rate of type II endoleaks, mid-term changes in sac diameter, or aneurysm rupture between the two groups, at 24 months patients with large aneurysms had more type I leaks (6.4% +/- 2.3% vs 1.4% +/- 0.6%; P =.011), device migration (13% +/- 4.0% vs 4.4% +/- 1.8%; P =.006), and conversion to open surgical repair (8.2% +/- 3.2% vs 1.4% +/- 1.1%; P =.031). Of greatest importance, at 24 months patient survival was diminished (71% +/- 4.6% vs 86% +/- 2.8%; P <.001) and risk for aneurysm-related death was increased (6.1% +/- 2.6% vs 1.5% +/- 1.0%; P =.011) in the group with large aneurysms. CONCLUSIONS: Outcome after endovascular repair of abdominal aortic aneurysm depends on size; results appear inferior in patients with larger aneurysms. These differences attain importance when choosing between observation and repair, balancing risk for rupture against size-dependent outcome.

Contemporary results of juxtarenal aneurysm repair.

OBJECTIVE: The increasing use of aortic endografts predictably will add to the complexity of open abdominal aortic aneurysm (AAA) repair and, therefore, the proportion of surgically treated infrarenal AAAs that are juxtarenal in location (JRA) will grow. This study reviews a single-center experience with JRAs. METHODS: Between June 1994 and December 2000, 138 patients underwent elective repair of a JRA, comprising 16.1% of 859 consecutive asymptomatic and intact symptomatic nonruptured infrarenal AAAs repaired over the same period. All patients with JRA needed proximal suprarenal clamping (SRC) or supravisceral (SVC) clamping. Patient demographics, selected risk factors, and operative details were recorded. Univariate analyses of selected risk factors for an adverse perioperative event were assessed, and multivariate analyses were performed with linear and logistic regression with backwards selection. RESULTS: SRC was used in 95 patients (69%), and 43 patients (31%) underwent SVC. The mortality rate was 5.1% (7/138) for JRA repair, and 2.8% (20/720) for infrarenal AAA repair (P =.03). The mortality rate was significantly greater for those patients who received SVC compared with SRC (11.6% versus 2.1%; P =.02). Multivariate analysis identified SVC position as the only independent predictor of mortality (odds ratio [OR], 6.1; 95% CI, 1.1 to 32.9; P =.035). Transient renal insufficiency occurred in 39 patients (28.3%), but only eight patients (5.8%) needed dialysis. Patients who had SVC had a significantly greater rate of renal insufficiency than those who received SRC (41.9% versus 22.1%; P =.02). Multivariate analysis showed SVC position (OR, 3.3; 95% CI, 1.4 to 7.8; P =.008), diabetes (OR, 3.7; 95% CI, 1.1 to 12.9; P =.04), and preoperative renal insufficiency (OR, 5.8; 95% CI, 2.2 to 15.4; P <.001) were independent predictors of postoperative renal insufficiency. Renal ischemia during proximal clamping cannot alone explain renal complications because clamp time was shorter in patients with SVC (24.9 +/- 2.4 minutes versus 32.2 +/- 1.5 minutes; P =.009). CONCLUSION: JRA repair can be accomplished with a low mortality rate, but a more proximal clamp position may adversely affect outcome in these patients. Postoperative renal insufficiency is related to diabetes, preoperative renal insufficiency, and SVC position. These results suggest SRC is safer than SVC for proximal aortic clamp control of JRAs. Although clamp level must be tailored to patient anatomy, outcome may be improved if the clamp level can be kept distal to the superior mesenteric artery origin.

Broadening the applicability of endovascular aneurysm repair: the use of iliac conduits.

OBJECTIVE: Suboptimal iliac anatomy has sometimes precluded endovascular repair of abdominal aortic aneurysm (AAA). In an effort to increase the applicability of endovascular repair, a limited retroperitoneal approach and iliac conduit was used in some patients with unsuitable iliac anatomy at high risk for open repair. METHODS: Charts and imaging studies of 312 patients who underwent endovascular (AAA) repair at the Cleveland Clinic Foundation between June 1999 and November 2000 were reviewed. Among these, 22 patients with complex iliac anatomy had an iliac conduit placed. Seventeen of these procedures were planned, but five were unplanned and placed after an iliac artery injury. A group of 17 patients who underwent a standard endovascular repair without conduits was selected and matched to the 17 patients in the planned conduit group by baseline comorbidities. The conduits were 8-mm or 10-mm polyester grafts sewn proximally to the common iliac artery and provided unobstructed access to the aneurysm. After insertion of the endograft device through the conduit, the distal end of the conduit was anastomosed to the external iliac or common femoral vessels. RESULTS: Operative time and estimated blood loss were higher among patients in whom conduits were performed, especially when performed urgently as an unplanned procedure. Although operative time and intensive care unit and hospital stays were longer for the group of patients with iliac conduits, the cardiac pulmonary and renal complication rates were similar for the conduit and the standard endovascular repair group. CONCLUSION: The use of a limited retroperitoneal approach and iliac conduit for patients with difficult iliac anatomy increases the applicability of the endovascular repair of AAA. This technique should be considered when an open surgical approach is inadvisable on the basis of medical comorbidities.

Open infrarenal abdominal aortic aneurysm repair: the Cleveland Clinic experience from 1989 to 1998.

PURPOSE: The purpose of this study was to determine the safety and durability of traditional surgical treatment for asymptomatic infrarenal abdominal aortic aneurysms (AAAs) in a large series of patients who underwent open operations during the decade preceding the commercial availability of stent graft devices for endovascular AAA repair. METHODS: From 1989 to 1998, 1135 consecutive patients (985 men [87%], 150 women; mean age, 70 +/- 7 years) underwent elective graft replacement of infrarenal AAA. Computerized perioperative data have been supplemented with a retrospective review of hospital charts/outpatient records and a telephone canvass to calculate survival rates and the incidence rate of subsequent graft-related complications. Seventy-four patients (6.5%) were lost during a median follow-up period of 57 months for the entire series. RESULTS: The 30-day mortality rate was 1.2%. The hospital course was completely uneventful for 939 patients (83%), and the median length of stay for all patients was 8 days. A total of 196 patients had single (n = 150; 13%) or multiple (n = 46; 4%) postoperative complications, which were more likely to occur in men (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.1 to 5.2) and in patients with a history of congestive heart failure (OR, 3.7; 95% CI, 1.7 to 7.8), chronic pulmonary disease (OR, 1.9; 95% CI, 1.2 to 2.9), or renal insufficiency (OR, 2.5; 95% CI, 1.3 to 4.7). Kaplan-Meier method survival rate estimates were 75% at 5 years and 49% at 10 years. As was the case with early complications, the long-term mortality rate primarily was influenced by age of more than 75 years (risk ratio [RR], 2.2; 95% CI, 1.7 to 2.8) or previous history of congestive heart failure (RR, 2.1; 95% CI, 1.3 to 3.4), chronic pulmonary disease (RR, 1.5; 95% CI, 1.2 to 2.0), or renal insufficiency (RR, 3.2; 95% CI, 2.2 to 4.6). Of the 1047 patients who survived their operations and remained available for follow-up study, only four (0.4%) have had late complications that were related to their aortic replacement grafts. CONCLUSION: These results reconfirm the exemplary success of open infrarenal AAA repair. The future of endovascular AAA repair is exceedingly bright, but until the long-term outcome of the current generation of stent grafts is adequately documented, their use should be justified by the presence of serious surgical risk factors.

Gender as a primary predictor of outcome after carotid endarterectomy.

OBJECTIVE: Post hoc analysis results of the North American Symptomatic Carotid Endarterectomy Trial and the Asymptomatic Carotid Atherosclerosis Study suggest that carotid endarterectomy (CEA) may not be as efficacious in women as it is in men. This study was undertaken for the evaluation of whether there is a difference between men and women in early postoperative outcome after CEA and whether such a difference is consistent across other predictors. METHODS: We conducted a retrospective review of all CEAs entered into our departmental registry between January 1, 1989, and November 30, 2000. A total of 3422 CEAs was performed in 3077 consecutive patients. The ratio of men to women was 2:1, and the ratio of patients who were asymptomatic to patients who were symptomatic was 2.3:1. The following in-hospital outcome data were analyzed: transient ischemic attack (TIA), stroke, mortality, combined TIA or stroke, and combined stroke or mortality. Univariate and multivariate analysis results of selected risk factors for an adverse perioperative event were assessed with generalized estimating equation analysis with backwards selection. The following risk factors were considered: gender, preoperative neurologic status, urgency of operation, type of arteriotomy repair, reoperative CEA for recurrent stenosis, history of cardiopulmonary disease, previous coronary artery intervention, simultaneous CEA and coronary bypass grafting surgery, renal failure, and diabetes. RESULTS: Univariate analysis results of gender differences revealed that women were at higher risk for a postoperative TIA or stroke (3.3% for women versus 2.1% for men; odds ratio [OR], 1.6; confidence interval [CI], 1.04 to 2.5; P =.03) and for postoperative stroke or mortality (3.1% for women versus 2.1% for men; OR, 1.6; CI, 1.04 to 2.5; P =.03). Multivariate analysis results showed that female gender was an independent predictor for a postoperative TIA or stroke (OR, 1.7; CI, 1.1 to 2.6; P =.03). Further analysis disclosed that women who were asymptomatic were at greater risk than were men for postoperative stroke or mortality (OR, 2.3; CI, 1.3 to 3.9; P =.003). Conversely, there was no gender association for postoperative stroke or mortality in the consideration of only patients who were symptomatic (OR, 1.0; CI, 0.45 to 2.1; P =.95). The interaction between women and preoperative symptoms approached significance (P =.07) with respect to postoperative stroke and mortality rate, which suggests that the gender effect could be influenced by the clinical presentation. CONCLUSION: The combined TIA or stroke and stroke or mortality rates are higher in women as compared with men in the postoperative period, but these risks remain acceptable when CEA is performed for appropriate indications. The interaction between symptoms and gender suggests that, in patients who are asymptomatic, women are more likely than are men to have early complications. However, there is no gender difference in patients who are symptomatic. Therefore, despite a low postoperative complication rate, CEA is appropriate in both women who are asymptomatic and women who are symptomatic only if the postoperative TIA, stroke, and mortality rates are appreciably lower than in the natural history of medical management of these patients.

The use of bovine hemoglobin glutamer-250 (Hemopure) in surgical patients: results of a multicenter, randomized, single-blinded trial.

UNLABELLED: Hemoglobin-based oxygen carrier-201 (HBOC-201, hemoglobin glutamer-250 [bovine], Hemopure; Biopure Corporation, Cambridge, MA) is polymerized hemoglobin of bovine origin being developed as an oxygen therapeutic. In this study, we evaluated the tolerability of a single intraoperative dose of HBOC-201 in surgical patients. In a single-blinded, multicenter study, 81 patients were randomized to receive either a single infusion of HBOC-201 (55 patients) or an equivalent volume of lactated Ringer's solution (26 patients). Forty-two patients originally assigned to the HBOC-201 group received the entire planned treatment of only one of the following doses: 0.6, 0.9, 1.2, 1.5, 2.0, or 2.5 g/kg of body weight. Thirteen of the 55 patients in the HBOC-201-assigned group did not reach the trigger point for transfusion administration, and they were not included in the analysis. We studied clinical outcomes and compared hematologic findings, blood chemistry values, and blood use in the two treatment groups. There were no patient deaths in this study. No pattern of clinically significant laboratory abnormalities could be attributed to exposure to HBOC-201. In the HBOC-201 group, 2 patients had a transient increased concentration of serum transaminases and 6 had transient skin discoloration. One patient in the HBOC-201 group had mast cell degranulation with hypotension. Postoperatively, methemoglobin plasma concentrations increased in the HBOC-201 group in a dose-dependent manner, reaching maximal values of 3.7% +/- 3.2% (average of all doses given) on postoperative day 3. There was no difference in the mean number of allogeneic blood units transfused in the 2 groups (3.3 +/- 1.8 and 3.7 +/- 4.1 for the lactated Ringer's solution and HBOC-201 groups, respectively) over the course of hospitalization. The intraoperative administration of HBOC-201, up to a maximum of 245 g, was generally well tolerated. There was no relationship between HBOC-201 use and the number of allogeneic blood units transfused over the entire hospitalization course. The administration of HBOC-201 was associated with a delayed (third postoperative day) dose-dependent increase in the plasma methemoglobin concentration. We conclude that the intraoperative use of HBOC-201 was generally well tolerated. IMPLICATIONS: The intraoperative use of hemoglobin glutamer-250 (bovine) (HBOC-201, Hemopure was generally well tolerated. The administration of HBOC-201 was associated with a delayed increase in the plasma methemoglobin concentrations.

A prospective, randomized study of saphenous vein patching versus synthetic patching during carotid endarterectomy.

OBJECTIVE: The objective of this study was the determination of whether the choice of either autogenous saphenous vein (ASV) or synthetic material for patch angioplasty significantly influences the results after carotid endarterectomy (CEA). METHODS: With Institutional Review Board approval, 195 patients (145 men and 50 women; mean age, 69 years) who underwent 207 CEAs were prospectively randomized to arteriotomy closure with ASV or synthetic patches from July 1996 to January 2000. One hundred and one patients (52%) were randomized to the ASV cohort, and 94 (48%) were randomized to the synthetic cohort. Aside from a slight gender imbalance (70% versus 79% male in the ASV versus the synthetic group), there were no clinically important differences in baseline demographic variables, risk factors, or surgical indications between the ASV and synthetic groups. RESULTS: With all 207 randomized procedures on an intent-to-treat basis, there were two early (<30 days) postoperative deaths (1%). There were three perioperative strokes in the ASV cohort (3.0%) and two in the synthetic cohort (2.1%; P =.99). Two of these early strokes occurred in a subset of nine patients who received neither patch material, all after randomization but before CEA. Two patients in each group had late strokes. The cumulative freedom from stroke rate at 1 year (ASV, 94%; synthetic, 95%) was virtually identical for both cohorts. With the 125 patients who had at least one postoperative duplex scan, the incidence rate of recurrent (>or=60%) carotid stenosis was 4.8% (three of 62) for the ASV group and 6.3% (four of 63) for the synthetic group (P =.99). CONCLUSION: No significant differences in the stroke, mortality, or restenosis rates were shown between the ASV and the synthetic cohorts. While conceding the power limitations inherent in this study, we conclude that CEA may be safely performed with similar early results with ASV or synthetic patches.