Vascular complications secondary to resuscitative endovascular balloon occlusion of the aorta placement at a Level 1 Trauma Center.

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is designed to manage severe hemorrhagic shock. Popularized in medical care during military conflicts, the concept has emerged as a lifesaving technique that is utilized around the United States. Literature on risks of REBOA placement, especially vascular injuries, are not well-reported. Our goal was to assess the incidence of vascular injury from REBOA placement and the risk factors associated with injury and death among these patients at our institution. METHODS: We performed a retrospective cohort study of all patients who underwent REBOA placement between September 2017 and June 2022 at our Level 1 Trauma Center. The primary outcome variable was the presence of an injury related to REBOA insertion or use. Secondary outcomes studied were limb loss, the need for dialysis, and mortality. Data were analyzed using descriptive statistics, χ2, and t-tests as appropriate for the variable type. RESULTS: We identified 99 patients who underwent REBOA placement during the study period. The mean age of patients was 43.1 ± 17.2 years, and 67.7% (67/99) were males. The majority of injuries were from blunt trauma (79.8%; 79/99). Twelve of the patients (12.1%; 12/99) had a vascular injury related to REBOA placement. All but one required intervention. The complications included local vessel injury (58.3%; 7/12), distal embolization (16.7%; 2/12), excessive bleeding requiring vascular consult (8.3%; 1/12), pseudoaneurysm requiring intervention (8.3%; 1/12), and one incident of inability to remove the REBOA device (8.3%; 1/12). The repairs were performed by vascular surgery (75%; 9/12), interventional radiology (16.7%; 2/12), and trauma surgery (8.3%; 1/12). There was no association of age, gender, race, and blunt vs penetrating injury to REBOA-related complications. Mortality in this patient population was high (40.4%), but there was no association with REBOA-related complications. Ipsilateral limb loss occurred in two patients with REBOA-related injuries, but both were due to their injuries and not to REBOA-related ischemia. CONCLUSIONS: Although vascular complications are not unusual in REBOA placement, there does not appear to be an association with limb loss, dialysis, or mortality if they are addressed promptly. Close coordination between vascular surgeons and trauma surgeons is essential in patients undergoing REBOA placement.

Transradial approach for percutaneous intervention of malfunctioning arteriovenous accesses.

OBJECTIVE: Interventions on arteriovenous (AV) access are typically performed with a direct puncture into the fistula. An alternative is the transradial approach (TRA), which offers the advantage of visualizing both the arterial and venous limbs as well as any juxta-anastomotic stenosis, all through one access. METHODS: From September 2010 to 2013, 511 fistulograms were performed on 322 patients, 55 of which were TRA procedures in 40 patients (50% male; mean age, 60.4 ± 16.5 years). Of these, 37 of 40 accesses (92.5%) were AV fistulas, and 54 of 55 interventions (98%) were performed for stenotic lesion(s). There were 37 initial interventions, 13 secondary inventions, and five diagnostic fistulograms through the TRA. Stenotic lesions were juxta-anastomotic in 28, venous in 11, or both in 11. Mean follow-up was 14.3 months in 37 of 40 patients. Outcomes included technical and clinical success, complications, functional patency, and flow rate changes. RESULTS: All TRA punctures were successful, with no radial artery thromboses or hand ischemia. Technical success was 88% (44 of 50). Functional patency rates were 88.5% (23 of 26), 84.2% (16 of 19), and 83% (10 of 12) at 1, 6, and 12 months, respectively. The complication rate was 1.8% (one of 55), consisting of AV fistula rupture after angioplasty. The average flow rate in the 20 juxta-anastomotic stenosis increased from 637 mL/min to 1094 mL/min (P = .01) after the procedure. CONCLUSIONS: The TRA is a practical option with functional patency rates that are comparable to traditional approaches when intervening on a malfunctioning dialysis access in the appropriately selected patient. No hand ischemia was noted. This approach may be particularly attractive for treatment of juxta-anastomotic stenoses in a variety of AV accesses and offers unique practical advantages for the maintenance of AV accesses.

Retrograde pedal access for patients with critical limb ischemia.

OBJECTIVE: Retrograde pedal access may allow the treatment of tibial occlusive lesions when standard endovascular techniques fail. We aimed to analyze the outcomes in patients with chronic limb ischemia (Rutherford class IV and V) who were not surgical candidates for a tibial bypass and had undergone an unsuccessful attempt at revascularization through an antegrade access. METHODS: During a 3-year period, a retrograde pedal access was selectively chosen when a popliteal or tibial lesion could not be crossed through an antegrade approach. Retrograde pedal access was performed under ultrasound guidance using a 4F micropuncture coaxial sheath. All interventions were performed in a sheathless fashion using a 0.014- or 0.018-inch "bareback" wire as support for a 2- or 2.5-mm balloon angioplasty catheter to cross and treat tibial chronic total occlusions that could not be treated through an antegrade approach. Routine anticoagulation and dual-antiplatelet therapy were used periprocedurally. Antegrade access was used to treat any lesion that required a stent placement after the retrograde wire was snared and brought through the antegrade guidecatheter. Patient indications and comorbidities were recorded. Outcomes analyzed were limb salvage rate, periprocedural complications, and mortality. Mean and standard deviations were calculated. The Kaplan-Meier method was used to calculate limb salvage rates. RESULTS: A review of the 681 lower extremity angiograms in which a patient had an intervention from July 2010 through December 2013 identified 13 patients (nine men) in whom a retrograde pedal access was performed (mean age, 71.4 ± 12.4 years). Among these, diabetes was present in 10 of 13 (77%) and chronic renal insufficiency (stages II-V) in nine (69%). Five (38%) had undergone contralateral amputation. Indications for a retrograde pedal revascularization were Rutherford chronic limb ischemia class IV in two (15%) and class V in 11 (85%). Technical success rate was 69% (nine of 13). A variety of popliteal (two of 13) and tibial (13 of 13) vessels were treated with angioplasty alone (10 of 13) or angioplasty/stent placement (three of 13) through a retrograde approach. The technical failures were due to inability to cross the occlusion(s). Periprocedurally, there was one myocardial infarction but no local complications, worsening renal insufficiency, or deaths. At a mean follow-up of 17.1 ± 10.3 months, the limb salvage rate was 77% (10 of 13). There was a high mortality rate of 23% (three of 13) on follow-up in this cohort, occurring at median 6 ± 4 months. CONCLUSIONS: Retrograde pedal access for limb salvage in high-risk patients is feasible and safe, with acceptable limb salvage rates at intermediate follow-up. Appropriate candidates are those who have failed an antegrade intervention and are poor candidates for a tibial bypass. Future studies should test whether this mode of revascularization has favorable limb salvage rates in larger patient populations and seek to identify specific patient populations who will benefit from this technique.

Hospital reimbursement for carotid stenting and endarterectomy.

PURPOSE: To investigate the cost-effectiveness of carotid endarterectomy (CEA) vs. carotid artery stenting (CAS) in terms of hospital reimbursement. METHODS: A retrospective analysis was conducted of hospital reimbursement for patients undergoing CEA and CAS from 1 January 2008 through 30 September 2010 at a single tertiary referral institution. Hospital cost and reimbursement were assessed using patient-specific data gathered by the institution's cost accounting system. Professional fees were excluded. RESULTS: Hospital reimbursement data were extracted for a total of 301 cases (169 CEA and 132 CAS). Mean hospital reimbursement was 16% higher for CAS ($12,000±$7372) vs. CEA ($10,160±$6840, p=0.02). However, because of the significantly higher cost of materials necessary to perform CAS, the net revenue for the hospital was 29% greater in patients undergoing CEA ($3487) vs. CAS ($2603). The differences in hospital reimbursement and net revenue were consistent in asymptomatic (n=183), symptomatic (n=123), and urgent (n=36) subgroups. When focusing on cases by diagnosis-related group (DRG) codes vs. current procedural terminology (CPT) codes, the data shifted. Several patients were coded as an outpatient procedure (DRG 0): 28 (21%) of the 132 CAS patients and 7 (4%) of the 169 CEA patients, reducing their mean reimbursement to $4046 and $2513, respectively. If these patients were excluded, the mean hospital reimbursement differential widened between and CEA ($10,515) and CAS ($13,825). CONCLUSION: Hospital reimbursement for CAS is significantly higher than that for CEA. While both procedures created net positive income for the hospital, CEA was associated with a 29% higher net revenue due to the 40% cost premium of CAS when looking at all carotid procedures. However, proper DRG coding of CAS cases would have likely resulted in similar net revenue. Asymptomatic patients had the lowest cost and highest net revenue of all the subgroups. Per capita, significantly more healthcare resources were expended with CAS when compared to CEA. Given the lack of improved clinical outcome in most cases, CAS cannot be considered cost-effective for most patients.

Array comparative genome hybridization for tumor classification and gene discovery in mouse models of malignant melanoma.

Chromosomal numerical aberrations (CNAs), particularly regional amplifications and deletions, are a hallmark of solid tumor genomes. These genomic alterations carry the potential to convey etiologic and clinical significance by virtue of their clonality within a tumor cell population, their distinctive patterns in relation to tumor staging, and their recurrence across different tumor types. In this study, we showed that array-based comparative genomic hybridization (CGH) analysis of genome-wide CNAs can classify tumors on the basis of differing etiologies and provide mechanistic insights to specific biological processes. In a RAS-induced p19(Arf-/-) mouse model that experienced accelerated melanoma formation after UV exposure, array-CGH analysis was effective in distinguishing phenotypically identical melanomas that differed solely by previous UV exposure. Moreover, classification by array-CGH identified key CNAs unique to each class, including amplification of cyclin-dependent kinase 6 in UV-treated cohort, a finding consistent with our recent report that UVB targets components of the p16(INK4a)-cyclin-dependent kinase-RB pathway in melanoma genesis (K. Kannan, et al., Proc. Natl. Acad. Sci. USA, 21: 2003). These results are the first to establish the utility of array-CGH as a means of etiology-based tumor classification in genetically defined cancer-prone models.

Future management of carotid stenosis: role of urgent carotid interventions in the acutely symptomatic carotid patient and best medical therapy for asymptomatic carotid disease.

BACKGROUND: Stroke is the fourth leading cause of death in the United States, leading to devastating disability. Most strokes are ischemic, and nearly one-third of these are caused by carotid disease. The primary mechanism of carotid-related stroke is an atheroembolic event from an unstable atherosclerotic plaque rupture. In the 1990s, randomized trials demonstrated the benefit of carotid endarterectomy (CEA) in reducing the risk of stroke in both symptomatic and asymptomatic carotid disease. METHODS: We review best medical therapy (BMT) for asymptomatic carotid disease and recent randomized trials comparing CEA and carotid angioplasty stenting (CAS), and we discuss the role of urgent carotid interventions in patients with acute neurologic symptoms. RESULTS: In 2010, 2 large trials demonstrated the efficacy of CAS in select patients, although CAS was associated with an increased procedural stroke risk compared to CEA. An age effect was observed; patients >75 years do worse with CAS compared to CEA. As BMT has evolved in the past decade, a future trial (CREST-2) will address whether BMT is equal to intervention (CEA or CAS) in asymptomatic carotid disease. In a subgroup of patients with asymptomatic carotid disease, CEA plus BMT will likely remain the mainstay therapy for carotid disease compared to BMT alone. CEA and CAS will continue to play complementary roles in the future, as CAS will be done in select patients in whom CEA cannot be undertaken because of high-risk anatomical or medical conditions. Finally, a role for urgent carotid interventions in a select group of patients who present with acute neurologic symptoms is developing as a way to prevent recurrent stroke after an initial carotid plaque rupture event. CONCLUSION: CAS has an increasingly higher risk of stroke with advancing age. Patients treated with CAS have a 1.76-fold increased risk of stroke (95% CI, 1.35-2.31) with each 10-year increase in age. No such age effect is seen in patients treated with CEA. Age is a critical variable in making informed choices regarding treatment of severe carotid artery stenosis.

Chronic activation of wild-type epidermal growth factor receptor and loss of Cdkn2a cause mouse glioblastoma formation.

Glioblastoma multiforme (GBM) is characterized by overexpression of epidermal growth factor receptor (EGFR) and loss of the tumor suppressors Ink4a/Arf. Efforts at modeling GBM using wild-type EGFR in mice have proven unsuccessful. Here, we present a unique mouse model of wild-type EGFR-driven gliomagenesis. We used a combination of somatic conditional overexpression and ligand-mediated chronic activation of EGFR in cooperation with Ink4a/Arf loss in the central nervous system of adult mice to generate tumors with the histopathologic and molecular characteristics of human GBMs. Sustained, ligand-mediated activation of EGFR was necessary for gliomagenesis, functionally substantiating the clinical observation that EGFR-positive GBMs from patients express EGFR ligands. To gain a better understanding of the clinically disappointing EGFR-targeted therapies for GBM, we investigated the molecular responses to EGFR tyrosine kinase inhibitor (TKI) treatment in this model. Gefitinib treatment of primary GBM cells resulted in a robust apoptotic response, partially conveyed by mitogen-activated protein kinase (MAPK) signaling attenuation and accompanied by BIM(EL) expression. In human GBMs, loss-of-function mutations in the tumor suppressor PTEN are a common occurrence. Elimination of PTEN expression in GBM cells posttumor formation did not confer resistance to TKI treatment, showing that PTEN status in our model is not predictive. Together, these findings offer important mechanistic insights into the genetic determinants of EGFR gliomagenesis and sensitivity to TKIs and provide a robust discovery platform to better understand the molecular events that are associated with predictive markers of TKI therapy.

Inframesocolic Abdominal Aortic Injury and Lumbar Vertebral Body Fracture Secondary to Hyperextension with Blunt Trauma.

This case study describes an abdominal aortic injury and lumbar vertebral body fracture after blunt trauma. Abdominal aortic pseudoaneurysm is a rare complication of blunt abdominal trauma. Recent data reveal seven other reports in the literature. We describe a case of an inframesocolic abdominal aortic injury and lumbar vertebral body fracture from blunt trauma in a 16-year-old male after a hyperextension injury while body board surfing.

Response of motor complications in Cockayne syndrome to carbidopa-levodopa.

BACKGROUND: Gait difficulties, tremors, and coordination difficulties are common features of Cockayne syndrome that are consequences of leukodystrophy, cerebellar atrophy, and demyelinating neuropathy, but no pharmacotherapy for these disabling symptoms is available. OBJECTIVE: To determine whether carbidopa-levodopa relieves tremors and other motor complications of Cockayne syndrome. DESIGN: Mutation analysis and case report study. SETTING: Hospital clinic and genetics research laboratory. Patients We studied 3 patients with Cockayne syndrome, a rare autosomal recessive neurodegenerative disorder for which no known treatments are available. Intervention Carbidopa-levodopa therapy. MAIN OUTCOME MEASURES: Status of tremors, ability to perform daily tasks, serial physical examinations, and results of handwriting samples. RESULTS: All 3 patients had a clear reduction in tremors and improvements in handwriting and manipulation of utensils and cups. CONCLUSIONS: Patients with Cockayne syndrome should be evaluated carefully for movement disorders. A clinical trial should be considered to evaluate this therapy further.