Blockade of CD47 function attenuates restenosis by promoting smooth muscle cell efferocytosis and inhibiting their migration and proliferation.

Cluster of differentiation 47 (CD47) plays an important role in the pathophysiology of various diseases including atherosclerosis but its role in neointimal hyperplasia which contributes to restenosis has not been studied. Using molecular approaches in combination with a mouse vascular endothelial denudation model, we studied the role of CD47 in injury-induced neointimal hyperplasia. We determined that thrombin-induced CD47 expression both in human aortic smooth muscle cells (HASMCs) and mouse aortic smooth muscle cells. In exploring the mechanisms, we found that the protease-activated receptor 1-Gα protein q/11 (Gαq/11)-phospholipase Cß3-nuclear factor of activated T cells c1 signaling axis regulates thrombin-induced CD47 expression in HASMCs. Depletion of CD47 levels using its siRNA or interference of its function by its blocking antibody (bAb) blunted thrombin-induced migration and proliferation of HASMCs and mouse aortic smooth muscle cells. In addition, we found that thrombin-induced HASMC migration requires CD47 interaction with integrin ß3. On the other hand, thrombin-induced HASMC proliferation was dependent on CD47's role in nuclear export and degradation of cyclin-dependent kinase-interacting protein 1. In addition, suppression of CD47 function by its bAb rescued HASMC efferocytosis from inhibition by thrombin. We also found that vascular injury induces CD47 expression in intimal SMCs and that inhibition of CD47 function by its bAb, while alleviating injury-induced inhibition of SMC efferocytosis, attenuated SMC migration, and proliferation resulting in reduced neointima formation. Thus, these findings reveal a pathological role for CD47 in neointimal hyperplasia.

Long-term outcomes of autologous vein bypass for repair of upper and lower extremity major arterial trauma.

OBJECTIVE: Autologous vein is the preferred bypass conduit for extremity arterial injuries owing to superior patency and low infection risk; however, long-term data on outcomes in civilians are limited. Our goal was to assess short- and long-term outcomes of autologous vein bypass for upper and lower extremity arterial trauma. METHODS: A retrospective review was performed of patients with major extremity arterial injuries (2001-2019) at a level I trauma center. Demographics, injury and intervention details, and outcomes were recorded. Primary outcomes were primary patency at 1 year and 3 years. Secondary outcomes were limb function at 6 months, major amputation, and mortality. Multivariable analysis determined risk factors for functional impairment. RESULTS: There were 107 extremity arterial injuries (31.8% upper and 68.2% lower) treated with autologous vein bypass. Mechanism was penetrating in 77% of cases, of which 79.3% were due to firearms. The most frequently injured vessels were the common and superficial femoral (38%), popliteal (30%), and brachial arteries (29%). For upper extremity trauma, concomitant nerve and orthopedic injuries were found in 15 (44.1%) and 11 (32.4%) cases, respectively. For lower extremities, concomitant nerve injuries were found in 10 (13.7%) cases, and orthopedic injuries in 31 (42.5%). Great saphenous vein was the conduit in 96% of cases. Immediate intraoperative bypass revision occurred in 9.3% of patients, most commonly for graft thrombosis. The in-hospital return to operating room rate was 15.9%, with graft thrombosis (47.1%) and wound infections (23.5%) being the most common reasons. The median follow-up was 3.6 years. Kaplan-Meier analysis showed 92% primary patency at 1 year and 90% at 3 years. At 6 months, 36.1% of patients had functional impairment. Of patients with functional impairment at 6 months, 62.9% had concomitant nerve and 60% concomitant orthopedic injuries. Of those with nerve injury, 91.7% had functional impairment, compared with 17.8% without nerve injury (P < .001). Of patients with orthopedic injuries, 51.2% had functional impairment, vs 25% of those without orthopedic injuries (P = .01). On multivariable analysis, concomitant nerve injury (odds ratio, 127.4; 95% confidence interval, 17-957; P <. 001) and immediate intraoperative revision (odds ratio, 11.03; 95% confidence interval, 1.27-95.55; P = .029) were associated with functional impairment. CONCLUSIONS: Autologous vein bypass for major extremity arterial trauma is durable; however, many patients have long-term limb dysfunction associated with concomitant nerve injury and immediate intraoperative bypass revision. These factors may allow clinicians to identify patients at higher risk for functional impairment, to outline patient expectations and direct rehabilitation efforts toward improving functional outcomes.

Outcomes of thoracic endovascular aortic repair in patients with concomitant blunt thoracic aortic injury and traumatic brain injury from the Aortic Trauma Foundation global registry.

BACKGROUND: Traumatic brain injury (TBI) and blunt thoracic aortic injury (BTAI) are the top two leading causes of death after blunt force trauma. Patients presenting with concomitant BTAI and TBI pose a specific challenge with respect to management strategy, because the optimal hemodynamic parameters are conflicting between the two pathologies. Early thoracic endovascular aortic repair (TEVAR) is often performed, even for minimal aortic injuries, to allow for the higher blood pressure parameters required for TBI management. However, the optimal timing of TEVAR for the treatment of BTAI in patients with concomitant TBI remains an active matter of controversy. METHODS: The Aortic Trauma Foundation international prospective multicenter registry was used to identify all patients who had undergone TEVAR for BTAI in the setting of TBI from 2015 to 2020. The primary outcomes included delayed ischemic or hemorrhagic stroke, in-hospital mortality, and aortic-related mortality. The outcomes were examined among patients who had undergone TEVAR at emergent (<6 vs ≥6 hours) or urgent (<24 vs ≥24 hours) intervals. RESULTS: A total of 100 patients (median age, 43 years; 79% men; median injury severity score, 41) with BTAI (Society for Vascular Surgery BTAI grade 1, 3%; grade 2, 10%; grade 3, 78%; grade 4, 9%) and concomitant TBI who had undergone TEVAR were identified. Emergent repair was performed for 51 patients (51%). Comparing emergent repair (<6 hours) to urgent repair (≥6 hours), no difference was found in delayed cerebral ischemic events (2.0% vs 4.1%; P = .614), in-hospital mortality (15.7% vs 22.4%; P = .389), or aortic-related mortality (2.0% vs 2.0%; P = .996) and no patient had experienced delayed hemorrhagic stroke. Likewise, repairs conducted in an urgent (<24 hours) setting showed no differences compared with those completed in an emergent (≥24 hours) setting regarding delayed ischemic stroke (2.6% vs 4.3%; P = .548), in-hospital mortality (18.2% vs 21.7%; P = .764), or aortic-related mortality (1.3% vs 4.3%; P = .654), and no patient had experienced delayed hemorrhagic stroke. CONCLUSIONS: In contrast to prior retrospective efforts, results from the Aortic Trauma Foundation international prospective multicenter registry have demonstrated that neither emergent nor urgent TEVAR for patients with concomitant BTAI and TBI was associated with delayed stroke, in-hospital mortality, or aortic-related mortality. In these patients, the timing of TEVAR did not have an effect on the outcomes. Therefore, the decision to intervene should be guided by individual patient factors rather than surgical timing.

Analysis of Traumatic Axillo-Subclavian Vessel Injuries: Endovascular Management is a Viable Option to Open Surgical Reconstruction.

BACKGROUND: In traumatic axillo-subclavian vessel injuries, endovascular repair has been increasingly described, despite ongoing questions regarding infection risk and long-term durability. We sought to compare the clinical and safety outcomes between endovascular and surgical treatment of traumatic axillo-subclavian vessel injuries. METHOD: A search query of the prospectively maintained PROOVIT registry for patients older than 18 years of age with a diagnosis of axillary or subclavian vessel injury between 2014-2019 was performed at a Level 1 Trauma Center. Patient demographics, severity of injury, Mangled Extremity Severity Score (MESS), Injury Severity Score (ISS), procedural interventions, complications, and patency outcomes were collected and analyzed. RESULTS: Twenty-three patients with traumatic axillo-subclavian vessel injuries were included. There were similar rates of penetrating and blunt injuries (48% vs. 52%, respectively). Eighteen patients (78%) underwent intervention: 11 underwent endovascular stenting or diagnostic angiography; 7 underwent open surgical repair. There was similar severity of arterial injuries between the endovascular and open surgical groups: transection (30% vs. 40%, respectively), occlusion (30% vs. 40%, respectively). The open surgical group had worse initial clinical comorbidities: higher ISS scores (17.0 vs 13.5, p = 0.034), higher median MESS scores (6 vs. 3.5, P = 0.001). The technical success for the endovascular group was 100%. The endovascular group had a lower estimated procedural blood loss (27.5 mL vs. 624 mL, P = 0.03). The endovascular arterial group trended toward a shorter length of hospital stay (5.6 days vs. 27.6 days, P = 0.09) and slightly reduced procedural time (191.0 min vs. 223.5 min, P = 0.165). Regarding imaging follow up (average of 60 days post-discharge), 7 patients (54%) underwent surveillance imaging (5 with duplex ultrasound, 2 with computed tomography angiography CTA) that demonstrated 100% patency. Regardless of ISS or MESS scores, at long term clinical follow up (average of 214 days), there were no limb losses, graft infections or vascular complications in either the endovascular or open surgical group. CONCLUSIONS: Endovascular treatment is a viable option for axillo-subclavian vessel injuries. Preliminary results demonstrate that endovascular treatment, when compared to open surgical repair, can have similar rates of technical success and long-term outcomes in patency, infection and vascular complications.

Erythropoietin Receptor Signaling Supports Retinal Function after Vascular Injury.

The investigation of erythropoietin (EPO) has expanded to include potential nonhematopoietic roles in neural and retinal diseases, including diabetic retinopathy. However, it remains unclear how EPO functions to support the neural retina. Transgenic mice with hypoactive EPO receptor (EPOR) signaling (hWtEPOR) were compared with littermate control mice (WT) to test the role of EPOR signaling under normal conditions and after vascular injury and regrowth into the retina. Although retinal function tested with OptoMotry and electroretinography was comparable to adult (8-week-old) littermate WT mice, hWtEPOR mice had thinner inner and outer plexiform layers and a greater number of amacrine cells. Injury and repair caused by the oxygen-induced retinopathy model reduced visual acuity thresholds, reduced electroretinography amplitudes, and thinned the outer plexiform and inner nuclear layers of both WT and hWtEPOR 8-week-old mice. In hWtEPOR compared with WT mice, scotopic a-wave amplitudes were reduced by injury, despite no change in outer nuclear layer thickness; and peripheral rod, but not cone number, was reduced. Scotopic b-waves were reduced in injured hWtEPOR mice compared with WT, and rod bipolar cell ectopic neurites were increased in both genotypes after injury, suggesting a potential reparative process to preserve connectivity and the b-wave. Normal EPOR signaling appeared important because ectopic neurites and b-waves were lower in the hWtEPOR than WT injured mice.

Temporary intravascular shunt use improves early limb salvage after extremity vascular injury.

OBJECTIVE: The use of temporary intravascular shunts (TIVSs) allow for restoration of distal perfusion and reduce ischemic time in the setting of arterial injury. As a damage control method, adjunct shunts restore perfusion during treatment of life-threatening injuries, or when patients require evacuation to a higher level of care. Single-center reports and case series have demonstrate that TIVS use can extend the opportunity for limb salvage. However, few multi-institutional studies on the topic have been reported. The objective of the present study was to characterize TIVS use through a multi-institutional registry and define its effects on early limb salvage. METHODS: Data from the Prospective Observation Vascular Injury Treatment registry was analyzed. Civilian patients aged ≥18 years who had sustained an extremity vascular injury from September 2012 to November 2018 were included. Patients who had a TIVS used in the management of vascular injury were included in the TIVS group and those who had received treatment without a TIVS served as the control group. An unadjusted comparison of the groups was conducted to evaluate the differences in the baseline and outcome characteristics. Double robust estimation combining logistic regression with propensity score matching was used to evaluate the effect of TIVS usage on the primary end point of limb salvage. RESULTS: TIVS use was identified in 78 patients from 24 trauma centers. The control group included 613 patients. Unmatched analysis demonstrated that the TIVS group was more severely injured (mean ± standard deviation injury severity score, 18.83 ± 11.76 for TIVS vs 14.93 ± 10.46 for control; P = .002) and had more severely mangled extremities (mean ± standard deviation abbreviated injury scale, extremity, score 3.23 ± 0.80 for TIVS vs 2.95 ± 0.87 for control; P = .008). Logistic regression demonstrated that propensity-matched control patients had a three times greater likelihood of amputation compared with the TIVS patients (odds ratio, 3.6; 95% confidence interval, 1.2-11.1; P = .026). Concomitant nerve injury and orthopedic fracture were associated with a greater risk of amputation. The median follow-up for the TIVS group was 12 days (interquartile range, 4-25 days) compared with 9 days (interquartile range, 4-18 days) for the control group. CONCLUSIONS: To the best of our knowledge, the present study is the first multicenter, matched-cohort study to characterize early limb salvage as a function of TIVS use in the setting of extremity vascular injury. Shunts expedite limb perfusion and resulted in lower rates of amputation during the early phase of care. The use of TIVS should be one part of a more aggressive approach to restore perfusion in the most injured patients and ischemic limbs.

Four-year outcomes following endovascular repair in patients with traumatic isolated popliteal artery injuries.

OBJECTIVE: The effectiveness of endovascular treatment for popliteal arterial injury has not been well-documented. This study was aimed to investigate the midterm outcomes of endovascular repair of traumatic isolated popliteal arterial injury. METHODS: Medical records of the patients who underwent endovascular repair for traumatic popliteal arterial injuries from January 2012 to February 2020 were reviewed retrospectively. Clinical data including patient demographics, Injury Severity Score, type of injury, classification of acute limb ischemia, concomitant extremity fracture, runoff vessel status, complications, time of endovascular procedure, time interval from injury to blood flow restoration, length of hospital stay, reintervention, and follow-up were collected and analyzed. RESULTS: Endovascular repair was performed in 46 patients with traumatic popliteal arterial injuries. The mean Injury Severity Score was 15.8 ± 6.2. The overall limb salvage rate was 89.1%. There were 10 penetrating and 36 blunt injuries (78.3%). The initial angiographic findings revealed occlusion in 34 patients (73.9%), pseudoaneurysm in 2 (4.4%), active extravasation in 9 (19.5%), and arteriovenous fistulas in 1 (2.2%). Technical success was achieved in all 46 patients, via antegrade access in 24 patients (52.2%) and concurrent retrograde access in 22 (47.8%). The mean time interval from popliteal artery injury to blood flow restoration was 10.6 ± 4.9 hours and mean operative time was of 54.9 ± 10.0 minutes. The mean follow-up was 36.1 ± 14.5 months. The primary patency rate was 75.3% at 12 months, 61.9% at 24 months, and 55.7% at 48 months. The secondary patency rate was 92.2% at 12 and 24 months and 85.2% at 48 months. A Cox multivariate analysis revealed that single vessel runoff was an independent risk factor for primary patency loss. CONCLUSIONS: Endovascular repair of an isolated popliteal artery injury may be a safe and effective alternative treatment in select patients, with acceptable midterm outcomes. Single vessel runoff was an independent risk factor for primary patency loss.

Contemporary outcomes of traumatic popliteal artery injury repair from the popliteal scoring assessment for vascular extremity injury in trauma study.

OBJECTIVE: Traumatic popliteal artery injuries are associated with the greatest risk of limb loss of all peripheral vascular injuries, with amputation rates of 10% to 15%. The purpose of the present study was to examine the outcomes of patients who had undergone operative repair for traumatic popliteal arterial injuries and identify the factors independently associated with limb loss. METHODS: A multi-institutional retrospective review of all patients with traumatic popliteal artery injuries from 2007 to 2018 was performed. All the patients who had undergone operative repair of popliteal arterial injuries were included in the present analysis. The patients who had required a major lower extremity amputation (transtibial or transfemoral) were compared with those with successful limb salvage at the last follow-up. The significant predictors (P < .05) for amputation on univariate analysis were included in a multivariable analysis. RESULTS: A total of 302 patients from 11 institutions were included in the present analysis. The median age was 32 years (interquartile range, 21-40 years), and 79% were men. The median follow-up was 72 days (interquartile range, 20-366 days). The overall major amputation rate was 13%. Primary repair had been performed in 17% of patients, patch repair in 2%, and interposition or bypass in 81%. One patient had undergone endovascular repair with stenting. The overall 1-year primary patency was 89%. Of the patients who had lost primary patency, 46% ultimately required major amputation. Early loss (within 30 days postoperatively) of primary patency was five times more frequent for the patients who had subsequently required amputation. On multivariate regression, the significant perioperative factors independently associated with major amputation included the initial POPSAVEIT (popliteal scoring assessment for vascular extremity injury in trauma) score, loss of primary patency, absence of detectable immediate postoperative pedal Doppler signals, and lack of postoperative antiplatelet therapy. Concomitant popliteal vein injury, popliteal injury location (P1, P2, P3), injury severity score, and tibial vs popliteal distal bypass target were not independently associated with amputation. CONCLUSIONS: Traumatic popliteal artery injuries are associated with a significant rate of major amputation. The preoperative POPSAVEIT score remained independently associated with amputation after including the perioperative factors. The lack of postoperative pedal Doppler signals and loss of primary patency were highly associated with major amputation. The use of postoperative antiplatelet therapy was inversely associated with amputation, perhaps indicating a protective effect.

Popliteal scoring assessment for vascular extremity injuries in trauma study.

OBJECTIVE: Traumatic popliteal vascular injuries are associated with the highest risk of limb loss of all peripheral vascular injuries. A method to evaluate the predictors of amputation is needed because previous scores could not be validated. In the present study, we aimed to provide a simplified scoring system (POPSAVEIT [popliteal scoring assessment for vascular extremity injuries in trauma]) that could be used preoperatively to risk stratify patients with traumatic popliteal vascular injuries for amputation. METHODS: A review of patients sustaining traumatic popliteal artery injuries was performed. Patients requiring amputation were compared with those with limb salvage at the last follow-up. Of these patients, 80% were randomly assigned to a training group for score generation and 20% to a testing group for validation. Significant predictors of amputation (P < .1) on univariate analysis were included in a multivariable analysis. Those with P < .05 on multivariable analysis were assigned points according to the relative value of their odds ratios (ORs). Receiver operating characteristic curves were generated to determine low- vs high-risk scores. An area under the curve of >0.65 was considered adequate for validation. RESULTS: A total of 355 patients were included, with an overall amputation rate of 16%. On multivariate regression analysis, the risk factors independently associated with amputation in the final model were as follows: systolic blood pressure <90 mm Hg (OR, 3.2; P = .027; 1 point), associated orthopedic injury (OR, 4.9; P = .014; 2 points), and a lack of preoperative pedal Doppler signals (OR, 5.5; P = .002; 2 points [or 1 point for a lack of palpable pedal pulses if Doppler signal data were unavailable]). A score of ≥3 was found to maximize the sensitivity (85%) and specificity (49%) for a high risk of amputation. The receiver operating characteristic curve for the validation group had an area under the curve of 0.750, meeting the threshold for score validation. CONCLUSIONS: The POPSAVEIT score provides a simple and practical method to effectively stratify patients preoperatively into low- and high-risk major amputation categories.

Novel Paracrine Functions of Smooth Muscle Cells in Supporting Endothelial Regeneration Following Arterial Injury.

RATIONALE: Regeneration of denuded or injured endothelium is an important component of vascular injury response. Cell-cell communication between endothelial cells and smooth muscle cells (SMCs) plays a critical role not only in vascular homeostasis but also in disease. We have previously demonstrated that PKCδ (protein kinase C-delta) regulates multiple components of vascular injury response including apoptosis of SMCs and production of chemokines, thus is an attractive candidate for a role in SMC-endothelial cells communication. OBJECTIVE: To test whether PKCδ-mediated paracrine functions of SMCs influence reendothelialization in rodent models of arterial injury. METHODS AND RESULTS: Femoral artery wire injury was performed in SMC-conditional Prkcd knockout mice, and carotid angioplasty was conducted in rats receiving transient Prkcd knockdown or overexpression. SMC-specific knockout of Prkcd impaired reendothelialization, reflected by a smaller Evans blue-excluding area in the knockout compared with the wild-type controls. A similar impediment to reendothelialization was observed in rats with SMC-specific knockdown of Prkcd. In contrast, SMC-specific gene transfer of Prkcd accelerated reendothelialization. In vitro, medium conditioned by AdPKCδ-infected SMCs increased endothelial wound closure without affecting their proliferation. A polymerase chain reaction-based array analysis identified Cxcl1 and Cxcl7 among others as PKCδ-mediated chemokines produced by SMCs. Mechanistically, we postulated that PKCδ regulates Cxcl7 expression through STAT3 (signal transducer and activator of transcription 3) as knockdown of STAT3 abolished Cxcl7 expression. The role of CXCL7 in SMC-endothelial cells communication was demonstrated by blocking CXCL7 or its receptor CXCR2, both significantly inhibited endothelial wound closure. Furthermore, insertion of a Cxcl7 cDNA in the lentiviral vector that carries a Prkcd shRNA overcame the adverse effects of Prkcd knockdown on reendothelialization. CONCLUSIONS: SMCs promote reendothelialization in a PKCδ-dependent paracrine mechanism, likely through CXCL7-mediated recruitment of endothelial cells from uninjured endothelium.

Injury Length and Arteriole Constriction Shape Clot Growth and Blood-Flow Acceleration in a Mouse Model of Thrombosis.

OBJECTIVE: Quantitative relationships between the extent of injury and thrombus formation in vivo are not well understood. Moreover, it has not been investigated how increased injury severity translates to blood-flow modulation. Here, we investigated interconnections between injury length, clot growth, and blood flow in a mouse model of laser-induced thrombosis. Approach and Results: Using intravital microscopy, we analyzed 59 clotting events collected from the cremaster arteriole of 14 adult mice. We regarded injury length as a measure of injury severity. The injury caused transient constriction upstream and downstream of the injury site resulting in a 50% reduction in arteriole diameter. The amount of platelet accumulation and fibrin formation did not depend on arteriole diameter or deformation but displayed an exponentially increasing dependence on injury length. The height of the platelet clot depended linearly on injury length and the arteriole diameter. Upstream arteriolar constriction correlated with delayed upstream velocity increase, which, in turn, determined downstream velocity. Before clot formation, flow velocity positively correlated with the arteriole diameter. After the onset of thrombus growth, flow velocity at the injury site negatively correlated with the arteriole diameter and with the size of the above-clot lumen. CONCLUSIONS: Injury severity increased platelet accumulation and fibrin formation in a persistently steep fashion and, together with arteriole diameter, defined clot height. Arterial constriction and clot formation were characterized by a dynamic change in the blood flow, associated with increased flow velocity.

Macrophage (Drp1) Dynamin-Related Protein 1 Accelerates Intimal Thickening After Vascular Injury.

OBJECTIVE: Mitochondria consistently change their morphology in a process regulated by proteins, including Drp1 (dynamin-related protein 1), a protein promoting mitochondrial fission. Drp1 is involved in the mechanisms underlying various cardiovascular diseases, such as myocardial ischemia/reperfusion injury, heart failure, and pulmonary arterial hypertension. However, its role in macrophages, which promote various vascular diseases, is poorly understood. We therefore tested our hypothesis that macrophage Drp1 promotes vascular remodeling after injury. METHOD AND RESULTS: To explore the selective role of macrophage Drp1, we created macrophage-selective Drp1-deficient mice and performed femoral arterial wire injury. In these mice, intimal thickening and negative remodeling were attenuated at 4 weeks after injury when compared with control mice. Deletion of macrophage Drp1 also attenuated the macrophage accumulation and cell proliferation in the injured arteries. Gain- and loss-of-function experiments using cultured macrophages indicated that Drp1 induces the expression of molecules associated with inflammatory macrophages. Morphologically, mitochondrial fission was induced in inflammatory macrophages, whereas mitochondrial fusion was induced in less inflammatory/reparative macrophages. Pharmacological inhibition or knockdown of Drp1 decreased the mitochondrial reactive oxygen species and chemotactic activity in cultured macrophages. Co-culture experiments of macrophages with vascular smooth muscle cells indicated that deletion of macrophage Drp1 suppresses growth and migration of vascular smooth muscle cells induced by macrophage-derived soluble factors. CONCLUSIONS: Macrophage Drp1 accelerates intimal thickening after vascular injury by promoting macrophage-mediated inflammation. Macrophage Drp1 may be a potential therapeutic target of vascular diseases.

Assessing potential for aortoiliac vascular injury from venoarterial extracorporeal membrane oxygenation cannulae: An in vitro particle image velocimetry study.

Limb ischemia is a major complication associated with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). The high velocity jet from arterial cannulae can cause "sandblasting" injuries to the arterial endothelium, with the potential risk of distal embolization and end organ damage. The aim of this study was to identify, for a range of clinically relevant VA-ECMO cannulae and flow rates, any regions of peak flow velocity on the aortic wall which may predispose to vascular injury, and any regions of low-velocity flow which may predispose to thrombus formation. A silicone model of the aortic and iliac vessels was sourced and the right external iliac artery was cannulated. Cannulae ranged from 15 to 21 Fr in size. Simulated steady state ECMO flow rates were instituted using a magnetically levitated pump (CentriMag pump). Adaptive particle image velocimetry was performed for each cannula at 3, 3.5, 4, and 4.5 L/min. For all cannulae, in both horizontal and vertical side hole orientations, the peak velocity on the aortic wall ranged from 0.3 to 0.45 m/s, and the regions of lowest velocity flow were 0.05 m/s. The magnitude of peak velocity flow on the aortic wall was not different between a single pair versus multiple pairs of side holes. Maximum velocity flow on the aortic wall occurred earlier at a lower pump flow rate in the vertical orientation of distal side holes compared to a horizontal position. The presence of multiple paired side holes was associated with fewer low-velocity flow regions, and some retrograde flow, in the distal abdominal aorta compared to cannulae with a single pair of side holes. From this in vitro visualization study, the selection of a cannula design with multiple versus single pairs of side holes did not change the magnitude of peak velocity flow delivered to the vessel wall. Cannulae with multiple side holes were associated with fewer regions of low-velocity flow in the distal abdominal aorta. Further in vivo studies, and ideally clinical data would be required to assess any correlation of peak velocity flows with incidence of vascular injury, and any low-velocity flow regions with incidence of thrombosis.

A Systematic Review and Meta-Analysis of Ligation Versus Repair of Inferior Vena Cava Injuries.

OBJECTIVE: Inferior vena cava (IVC) injuries have a high mortality rate that may be related to the location of injury and type of repair. Previous studies have been either single center series or database studies lacking granular detail. These have reported conflicting results. We aimed to perform a systematic review and meta-analysis of published literature evaluating ligation versus repair. METHODS: Studies published in English on MEDLINE or EMBASE from 1946 through October 2018 were examined to evaluate mortality among patients treated with ligation versus repair of IVC injuries. Studies were included if they provided mortality associated with ligation versus repair and reported IVC injury by level. Risk of bias was assessed regarding incomplete and selective outcome reporting with Newcastle-Ottawa score of 7 or higher to evaluate study quality. We used a random-effects model with restricted maximum likelihood estimation method in R using the Metafor package to evaluate outcomes. RESULTS: Our systematic review identified 26 studies, of which 14 studies, including 855 patients, met our inclusion criteria for meta-analysis. IVC ligation was associated with higher mortality than IVC repair (OR: 3.12, P < 0.01, I2 = 49%). Ligation of infrarenal IVC injuries was not statistically associated with mortality (OR: 3.13, P = 0.09). Suprarenal injury location compared to infrarenal (OR 3.11, P < 0.01, I2 = 28%) and blunt mechanism compared to penetrating (OR: 1.91, P = 0.02, I2 = 0%) were also associated with higher mortality. CONCLUSIONS: In this meta-analysis, ligation of IVC injuries was associated with increased mortality compared to repair, but not specifically for infrarenal IVC injuries. Suprarenal IVC injury, and blunt mechanism was associated with increased mortality compared to infrarenal IVC injury and penetrating mechanism, respectively. Data are limited regarding acute renal injury and venous thromboembolic events after IVC ligation and may warrant multicenter studies. Standardized reporting of IVC injury data has not been well established and is needed in order to enable comparison of outcomes across institutions. In particular, reporting of injury location, severity, and repair type should be standardized. A contemporary prospective, multicenter study is needed in order to definitively compare surgical technique.

Splenic Vein as an Autologous Graft in Traumatic SMV Injuries: A Missed Valuable Alternative.

Traumatic superior mesenteric artery (SMA) and vein (SMV) injuries are rare but often lethal. The ideal management options of traumatic SMV injury are still controversial. Management options include venous repair and ligation. Splenic vein turndown procedure (SVTP) is a rare procedure that has been described in only 6 cases in the literature. Here, we reviewed the literature on the usage of the splenic vein turndown procedure (SVTP) as an alternative option in patients with traumatic SMV injury. METHODS: We performed a narrative review for the available literature on the usage of the splenic vein as an autologous graft in the management of the SMV injury. We included all studies of SVTP in traumatic SMV injuries only. RESULTS: We included only 5 studies. In total, 7 patients underwent SVTP. Five patients presented with a penetrating abdominal vascular trauma (AVT) and 2 patients with a blunt AVT. The advantages of the SVTP include no need for additional incisions to harvest potential autologous grafts, minimally increased operative time, and 1 less anastomotic site compared to other conduit options. CONCLUSIONS: In cases of traumatic SMV injuries with associated splenic or pancreatic injuries that need distal pancreatosplenectomy, surgeons may consider SVTP as an ideal management option rather than primary repair or ligation.

A Clampless Technique to Facilitate Successful End-to-End Anastomosis in Small Vessels With Spasm.

End-to-end anastomosis in small arteries can be challenging, especially when the stumps are in spasm after traumatic transection. We describe a novel technique to facilitate such anastomoses under local anesthesia, presenting a 24-year old patient who suffered complete traumatic transection of the left ulnar artery. After having found and prepared the proximal and distal stumps, a soft polyurethane feeding tube (La-med Healthcare, India) and a vein cannula were inserted in the proximal and distal stump, respectively, without using vascular clamps. The manipulation of the catheters offered excellent visualization and widening of the anastomotic line, enabling simultaneous infusion of heparinized saline or vasodilating agents. The anastomosis was completed with no stenosis and pulpable pulses were restored immediately postoperatively. At 1-month follow-up, the Allen test was normal with a normal regular flow of the ulnar artery at duplex ultrasound. The described technique ensures efficient sealing avoiding clamping, casts the small lumens, provides optimal visualization of the anastomotic aspects and prevents stenosis. We believe it should have a place in the surgeon's armamentarium.

Early Results of Supporting Free Flap Coverage of Mangled Lower Extremities with Long Saphenous Arteriovenous Loop Grafts.

BACKGROUND: The ability to salvage the mangled lower extremity is both technically challenging and time consuming. It requires the collaborative efforts among multiple surgical specialties in addition to comprehensive post-traumatic wound follow-up. Our institution has integrated a dynamic effort among these specialists in the planning and facilitating a successful limb salvage program with creation of a mangled extremity algorithm. An integral part in this process is the vascular inflow to prepare coverage for large tissue defects lacking adequate recipient targets. Utilization of long saphenous arteriovenous (AV) loop has been cited with minimal data available using larger inflow vessels in the acute trauma setting. We performed a retrospective review and describe our early experience using our protocol with AV loop creation with free flap reconstruction to salvage traumatic leg injuries. Using the data, we sought to develop a mangled extremity protocol for trauma centers to guide mangled limb salvage. METHODS: Since June 2016, 398 patients were admitted to our level II trauma facility with isolated traumatic wounds to the lower extremities. Thirty-one limbs were deemed mangled in which 21 received primary amputations due to multiple factors. Ten patients admitted from the trauma service with isolated mangled lower extremities injuries were identified for review. All 10 patients sustained severe crush injuries with large soft tissue defects and decreased perfusion for healing but deemed salvageable by multispecialty assessment. Mangled extremity severity scores were tabulated. Patients age ranged from 21-44 years, with 8 men and 2 women. Repeated debridements until successful sterilization of the wounds were accomplished. Ten long saphenous vein AV loops were anastomosed to the at or above knee popliteal vessels for free flap reconstruction. All patients were followed post-AV loop creation for vascular complications and wound assessments. RESULTS: All 10 patients had sterilization of the wounds with repair of the fracture site before vascular reconstruction. Mean debridement to surgical site sterilization was 4.3 washouts (range 2-7). Successful AV loop creation with long saphenous vein was completed in 100% of patients without vascular complications nor steal events. Free flap tissue transfers directly connected to the loop were completed using 6 rectus abdominis, 3 latissimus dorsi, and 1 anterior thigh graft within 10 days of its creation. Patency rates of the AV loop was 100% with 10 successful flap transfers and 90% amputation free survival. One flap did not survive due to recurrent bacterial infection of the hardware. The 9 patients with successful procedures reached preoperative ambulatory status within 3 months after their final surgery. At 24 months follow-up, 90% amputation free survival is still maintained. CONCLUSIONS: Although a small patient cohort, utilization of long saphenous vein AV loop is successful as a bridge to free flap transfer for isolated mangled lower extremities. Development and incorporation of our mangled extremity protocol to guide limb salvage has proven successful in our early experience. Long-term data need to be complied to assess patency of the free flap transfer and quality of life outcomes.

Relationship between Serum YKL-40 Level and Forearm Arterial Patency after Repair.

BACKGROUND: The study aimed to assess the effects of serum YKL-40 level on patency at the repair site in patients who underwent arterial repair at the level of the forearm. METHODS: The study included 58 subjects, including 29 patients (aged 18-50 years) who had ulnar or radial artery injury secondary to cut injury to wrist between June 2015 and November 2019 and no comorbid disease and 29 age- and sex-matched healthy controls. The vascular patency was assessed using Doppler sonography in patients who underwent arterial repair at the level of the forearm. The patients were defined as flow failure if the blood flow was ≤50%, and sufficient flow if the blood flow was >50% of those in the synonymous artery on the intact extremity. The YKL-40 level differences in the patient and control groups were compared to those in the sufficient and insufficient flow groups. RESULTS: The patients were stratified into 2 groups based on the presence of sufficient flow. The mean YKL level was 11.96 ± 8.87 in the sufficient flow groups, whereas it was 32.22 ± 15.43 in the insufficient flow groups (p= 0.038). Besides, it was found that each unit of increase in the YKL-40 level increased the likelihood of having flow failure by 1.128. CONCLUSION: Based on our results, it was observed that over-expression of the YKL-40 level has adverse effects on patency following arterial repair.

Thoracic Aortic Dilation after Endovascular Repair of Blunt Traumatic Aortic Injury.

BACKGROUND: Thoracic endovascular aneurysm repair (TEVAR) has become the current standard of care for emergent treatment of traumatic blunt thoracic aortic injuries (BTAI). Although aortic dilation (AD) of the infrarenal neck after EVAR for aortic aneurysms has been studied, changes in aortic diameter after TEVAR for BTAI is not well understood. This study aims to characterize changes in thoracic aortic diameter after stent-graft placement in the setting of nonaneurysmal traumatic aortic injury. METHODS: A single-center, retrospective review was performed involving patients presenting with BTAI treated with TEVAR. Only patients with at least 12 months follow-up were included. Aortic diameter, defined as the outer-to-outer diameter on 3D center-line imaging, was measured at six locations along the proximal and mid thoracic aorta. The first postoperative CT (≤1 month) served as a baseline from which interval measurements were compared. RESULTS: Twenty patients with BTAI treated from 2011 to 2017 had adequate imaging available for review and were included in this study cohort. Median follow-up time was 46.8 (12-80, range) months. At the latest follow-up, AD occurred at all measured locations within the endograft, starting from the proximal graft edge (0.62 ± 0.69 mm, P = 0.027) to the distal graft edge (1.21 ± 1.28 mm, P = 0.003). AD was most pronounced in the distal graft segment 2 cm proximal to the distal graft edge, with a mean AD of 1.32 ± 1.59 mm (+5.3%, P < 0.001). At this location, AD was found to increase in a linear manner with an estimated rate of 0.67 ± 0.20 mm/year (P = 0.006). The native aorta proximal and distal to the endograft was not found to significantly dilate during follow-up (P = 0.280-0.897). Seventy percent of the patients were found to have AD >5%. The amount of AD was not found to be associated with either graft oversizing (P = 0.151) or age (P = 0.340). There were no cases of graft migration, erosion, or endoleak. CONCLUSIONS: AD is a common benign finding after TEVAR for BTAI. AD is most pronounced at the near the distal end of the stent graft. In late-term follow-up, there are no known associated complications related to AD.

Outcomes of Arterial Grafts for the Reconstruction of Military Lower Extremity Arterial Injuries.

INTRODUCTION: Lower extremity (LE) arterial injuries are common in military casualties and limb salvage is a primary goal. Bypass grafts are the most common reconstructions; however, their specific outcomes are largely unreported. We sought to describe the outcomes of LE arterial grafts among combat casualties and their association with limb loss. METHODS: Retrospective cohort study of 2004-2012 Iraq/Afghanistan casualties with LE arterial injury undergoing bypass graft from a database containing follow-up until amputation, death, or military discharge. Primary outcome was composite graft complications (GC-thrombosis, stenosis, pseudoaneurysm, blowout, and/or arteriovenous fistula). RESULTS: Two hundred and twenty-two grafts were included (99 femoral, 73 popliteal, 48 tibial). 56 (26%) had at least one GC; thrombosis was most common in femoral, stenosis most common in popliteal and tibial. GC was not associated with graft level but was associated with synthetic conduit (P = 0.01) and trended towards an association with multiple-level arterial injuries (P = 0.07). Four of eight (50%) synthetic grafts had amputations, all within 72h. Two of the eight synthetic grafts thrombosed, and both limbs were amputated. There were 52 total amputations. Amputation was performed in 13 (23%) of limbs with a GC and 24% of those without (P = 0.93) Overall, 24 (11%) of grafts thrombosed, 16 within 48h and 13 (25%) in limbs undergoing amputation (P = 0.001 for association of thrombosis with amputation). CONCLUSION: GC are common among LE bypass grafts in combat casualties but are not associated with limb loss. Thrombosis is predominantly early and is associated with amputation. Closer attention to ensuring early patency may improve limb salvage.