Endothelial vascular cell adhesion molecule 1 is a marker for high-risk carotid plaques and target for ultrasound molecular imaging.

BACKGROUND: Molecular imaging of carotid plaque vulnerability to atheroembolic events is likely to lead to improvements in selection of patients for carotid endarterectomy (CEA). The aims of this study were to assess the relative value of endothelial inflammatory markers for this application and to develop molecular ultrasound contrast agents for their imaging. METHODS: Human CEA specimens were obtained prospectively from asymptomatic (30) and symptomatic (30) patients. Plaques were assessed by semiquantitative immunohistochemistry for vascular cell adhesion molecule 1 (VCAM-1), lectin-like oxidized low-density lipoprotein receptor 1, P-selectin, and von Willebrand factor. Established small peptide ligands to each of these targets were then synthesized and covalently conjugated to the surface of lipid-shelled microbubble ultrasound contrast agents, which were then evaluated in a flow chamber for binding kinetics to activated human aortic endothelial cells under variable shear conditions. RESULTS: Expression of VCAM-1 on the endothelium of CEA specimens from symptomatic patients was 2.4-fold greater than that from asymptomatic patients (P < .01). Expression was not significantly different between groups for P-selectin (P = .43), von Willebrand factor (P = .59), or lectin-like oxidized low-density lipoprotein receptor 1 (P = .99). Although most plaques from asymptomatic patients displayed low VCAM-1 expression, approximately one in five expressed high VCAM-1 similar to plaques from symptomatic patients. In vitro flow chamber experiments demonstrated that VCAM-1-targeted microbubbles bind cells that express VCAM-1, even under high-shear conditions that approximate those found in human carotid arteries, whereas binding efficiency was lower for the other agents. CONCLUSIONS: VCAM-1 displays significantly higher expression on high-risk (symptomatic) vs low-risk (asymptomatic) carotid plaques. Ultrasound contrast agents bearing ligands for VCAM-1 can sustain high-shear attachment and may be useful for identifying patients in whom more aggressive treatment is warranted.

The influence of do-not-resuscitate status on the outcomes of patients undergoing emergency vascular operations.

BACKGROUND: Do-not-resuscitate (DNR) orders allow patients to communicate their wishes regarding cardiopulmonary resuscitation. Although DNR status may influence physician decision making regarding resuscitation, the effect of DNR status on outcomes of patients undergoing emergency vascular operation remains unknown. The aim of this study was to analyze the effect of DNR status on the outcomes of emergency vascular surgery. METHODS: The National Surgical Quality Improvement Program database was queried to identify all patients requiring emergency vascular surgical interventions between 2005 and 2010. Demographics, clinical data, and outcomes were extracted. Patients were compared according to DNR status. The primary outcome measure was 30-day mortality. RESULTS: During the study period, 16,678 patients underwent emergency vascular operations (10.8% of the total vascular surgery population). Of those, 548 patients (3.3%) had a DNR status. The differences in rates of open or endovascular repair or of intraoperative blood requirement between the two groups were not significant. After adjusting for differences in demographics and clinical data, DNR patients were more likely to have higher rates of graft failure (8.7% vs 2.4%; adjusted P < .01) and failure to wean from mechanical ventilation (14.9 % vs 9.9%; adjusted P < .001). DNR status was associated with a 2.5-fold rise in 30-day mortality (35.0% vs 14.0%; 95% confidence interval, 1.7-2.9; adjusted P < .001). CONCLUSIONS: The presence of a DNR order was independently associated with mortality. Patient and family counseling on surgical expectations before emergency vascular operations is warranted because the risks of perioperative events are significantly elevated when a DNR order exists.

Outcomes of endovascular management of acute thoracic aortic emergencies in an academic level 1 trauma center.

BACKGROUND: Thoracic aortic emergencies account for 10% of thoracic-related admissions in the United States and remain associated with high morbidity and mortality rates. Open repair has declined owing to the emergence of thoracic endovascular aortic repair (TEVAR), but data on emergency TEVAR use for acute aortic pathology remain limited. We therefore reviewed our experience. METHODS: We retrospectively evaluated emergency descending thoracic aortic endovascular interventions performed at a single academic level 1 trauma center between January 2005 and August 2013 including all cases of traumatic aortic injury, ruptured descending thoracic aneurysm, penetrating atherosclerotic ulcer, aortoenteric fistula, and acute complicated type B dissection. Demographics, clinical data, and outcomes were extracted. Stepwise logistic regression was used to identify independent risk factors for death. RESULTS: During the study period, 51 patients underwent TEVAR; 22 cases (43.1%) were performed emergently (11 patients [50.0%] traumatic aortic injury; 4 [18.2%] ruptured descending thoracic aneurysm; 4 [18.2%] complicated type B dissection; 2 [9.1%] penetrating aortic ulcer; and 1 [4.5%] aortoenteric fistula). Overall, 72.7% (n = 16) were male with a mean age of 54.8 ± 15.9 years. Nineteen patients (86.4%) required only a single TEVAR procedure, whereas 2 (9.1%) required additional endovascular therapy, and 1 (4.5%) open thoracotomy. Four traumatic aortic injury patients required exploratory laparotomy for concomitant intra-abdominal injuries. During a mean hospital length of stay of 18.9 days (range, 1 to 76 days), 3 patients (13.6%) developed major complications. In-hospital mortality was 27.2%, consisting of 6 deaths from traumatic brain injury (1); exsanguination in the operating room before repair could be achieved (2); bowel ischemia (1) and multisystem organ failure (1); and family withdrawal of care (1). A stepwise logistic regression model identified 24-hour packed red blood cell requirements ≥4 units, admission mean arterial pressure <60 mm Hg, and 24-hour fresh frozen plasma to packed red blood cell (pRBC) ratio <1:1.5 as independent risk factors for death in this cohort. During a mean follow-up of 369 days (range, 35 to 957 days), no subsequent major complications or deaths occurred. All patients underwent serial computed tomographic angiography surveillance, and no device-related problems were identified during intermediate follow-up. CONCLUSIONS: Thoracic aortic emergencies remain challenging. Our experience in a moderate-volume center supports the utilization of TEVAR in the acute setting. Twenty-four-hour pRBC requirements ≥4 units, admission mean arterial pressure <60 mm Hg, and 24 hour fresh frozen plasma to pRBC ratio <1:1.5 were independently associated with death.

Trends and outcomes of endovascular therapy in the management of civilian vascular injuries.

OBJECTIVE: The rapid evolution of endovascular surgery has greatly expanded management options for a wide variety of vascular diseases. Endovascular therapy provides a less invasive alternative to open surgery for critically ill patients who have sustained arterial injuries. The purpose of this study was to evaluate recent trends in the management of arterial injuries in the United States with specific reference to the use of endovascular strategies and to examine the outcomes of endovascular vs open therapy for the treatment of civilian arterial traumatic injuries. METHODS: A 9-year analysis of the National Trauma Data Bank was performed to identify all patients who sustained arterial injuries. Demographics, clinical data, interventions, and outcomes were extracted. Propensity scores were used to match endovascular patients to those undergoing open operation. Patient outcomes were compared according to treatment approach. RESULTS: A total of 23,105 patients were available for analysis. Overall, there was a significant increase in the use of endovascular procedures during 9 years (from 0.3% in 2002 to 9.0% in 2010; P < .001), particularly among blunt trauma patients (from 0.4% in 2002 to 13.2% in 2010; P < .001). This increase was noteworthy and dramatic for injuries of the internal iliac artery (from 8.0% in 2002 to 40.3% in 2010; P < .001), thoracic aorta (from 0.5% in 2002 to 21.9% in 2010; P < .001), and common/external iliac arteries (from 0.4% in 2002 to 20.4% in 2010; P < .001). A significant decrease was noted for open procedures (49.1% in 2002 to 45.6%; P < .001), especially for blunt trauma (42.9% in 2002 to 35.8% in 2010; P < .001). There was a stepwise increase in the proportion of patients managed by endovascular therapy as the Injury Severity Score increased (highest in the spectrum Injury Severity Score 31-50). When outcomes were compared between matched patients who underwent endovascular and open procedures, patients who underwent endovascular procedures had significantly lower in-hospital mortality (12.9% vs 22.4%; odds ratio, 0.5; 95% confidence interval, 0.4-0.6; P < .001). Endovascular patients also had decreased rates of sepsis (7.5% vs 5.4%; odds ratio, 0.7; 95% confidence interval, 0.5-0.9; P = .025). CONCLUSIONS: The use of endovascular therapy in the United States has increased dramatically during the last decade, in particular among severely injured blunt trauma patients. Endovascular therapy was associated with improved in-hospital mortality and lower rates of sepsis.