Increased human complement pathway regulatory protein gene dose is associated with increased endothelial expression and prolonged survival during ex-vivo perfusion of GTKO pig lungs with human blood.

INTRODUCTION: Expression of human complement pathway regulatory proteins (hCPRP's) such as CD46 or CD55 has been associated with improved survival of pig organ xenografts in multiple different models. Here we evaluate the hypothesis that an increased human CD46 gene dose, through homozygosity or additional expression of a second hCPRP, is associated with increased protein expression and with improved protection from injury when GTKO lung xenografts are perfused with human blood. METHODS: Twenty three GTKO lungs heterozygous for human CD46 (GTKO.heteroCD46), 10 lungs homozygous for hCD46 (GTKO.homoCD46), and six GTKO.homoCD46 lungs also heterozygous for hCD55 (GTKO.homoCD46.hCD55) were perfused with human blood for up to 4 h in an ex vivo circuit. RESULTS: Relative to GTKO.heteroCD46 (152 min, range 5-240; 6/23 surviving at 4 h), survival was significantly improved for GTKO.homoCD46 (>240 min, range 45-240, p = .034; 7/10 surviving at 4 h) or GTKO.homoCD46.hCD55 lungs (>240 min, p = .001; 6/6 surviving at 4 h). Homozygosity was associated with increased capillary expression of hCD46 (p < .0001). Increased hCD46 expression was associated with significantly prolonged lung survival (p = .048),) but surprisingly not with reduction in measured complement factor C3a. Hematocrit, monocyte count, and pulmonary vascular resistance were not significantly altered in association with increased hCD46 gene dose or protein expression. CONCLUSION: Genetic engineering approaches designed to augment hCPRP activity - increasing the expression of hCD46 through homozygosity or co-expressing hCD55 with hCD46 - were associated with prolonged GTKO lung xenograft survival. Increased expression of hCD46 was associated with reduced coagulation cascade activation, but did not further reduce complement activation relative to lungs with relatively low CD46 expression. We conclude that coagulation pathway dysregulation contributes to injury in GTKO pig lung xenografts perfused with human blood, and that the survival advantage for lungs with increased hCPRP expression is likely attributable to improved endothelial thromboregulation.

Expression of human thrombomodulin by GalTKO.hCD46 pigs modulates coagulation cascade activation by endothelial cells and during ex vivo lung perfusion with human blood.

Thrombomodulin is important for the production of activated protein C (APC), a molecule with significant regulatory roles in coagulation and inflammation. To address known molecular incompatibilities between pig thrombomodulin and human thrombin that affect the conversion of protein C into APC, GalTKO.hCD46 pigs have been genetically modified to express human thrombomodulin (hTBM). The aim of this study was to evaluate the impact of transgenic hTBM expression on the coagulation dysregulation that is observed in association with lung xenograft injury in an established lung perfusion model, with and without additional blockade of nonphysiologic interactions between pig vWF and human GPIb axis. Expression of hTBM was variable between pigs at the transcriptional and protein level. hTBM increased the activation of human protein C and inhibited thrombosis in an in vitro flow perfusion assay, confirming that the expressed protein was functional. Decreased platelet activation was observed during ex vivo perfusion of GalTKO.hCD46 lungs expressing hTBM and, in conjunction with transgenic hTBM, blockade of the platelet GPIb receptor further inhibited platelets and increased survival time. Altogether, our data indicate that expression of transgenic hTBM partially addresses coagulation pathway dysregulation associated with pig lung xenograft injury and, in combination with vWF-GP1b-directed strategies, is a promising approach to improve the outcomes of lung xenotransplantation.

Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments.

Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the ß4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.hCD46 lung function was consistently observed in association with either hEPCR (n = 15), hTBM (n = 4), or hEPCR.hTFPI (n = 11), but the loss of vascular barrier function in the xenograft and systemic inflammation in the recipient typically occurred within 24 h. Co-expression of hEPCR and hTBM (n = 11) and additionally blocking multiple pro-inflammatory innate and adaptive immune mechanisms was more consistently associated with survival >1 day, with one recipient surviving for 31 days. Combining targeted genetic modifications to the lung xenograft with selective innate and adaptive immune suppression enables prolonged initial life-supporting lung function and extends lung xenograft recipient survival, and illustrates residual barriers and candidate treatment strategies that may enable the clinical application of other organ xenografts.

Evaluation of a standardized protocol for medical management of uncomplicated acute type B aortic dissection.

OBJECTIVES: The goals of medical management for uncomplicated acute type B aortic dissection (TBAD) are to prevent expansion of the false lumen and malperfusion syndrome. This is accomplished with antihypertensive agents, but medication selection and titration are typically provider-dependent. Given the paucity of data on evidence-based management of this population, we hypothesized that a standardized TBAD medical management protocol would reduce resource utilization and costs, without compromising patient outcomes. METHODS: A multidisciplinary team developed a goal-directed protocol to standardize the medical management of uncomplicated acute TBAD, with an emphasis on early initiation of oral medications, weaning of anti-hypertensive infusions, and frequent assessment for de-escalation of care. Implementation was in April 2018. A retrospective review of patients with acute TBAD presenting to our institution from April 2016 to April 2020 was performed. Patients requiring aortic or peripheral intervention were excluded. Included patients were analyzed based on treatment before or after protocol implementation. Patient demographics, systolic blood pressure, presence of acute kidney injury at presentation, length of stay, cost metrics, and 30-day mortality were compared. RESULTS: Thirty-nine patients were included, 21 pre- and 18 post-protocol implementation. Baseline demographics, systolic blood pressure, and presence of acute kidney injury at presentation were similar between the groups. Post-protocol patients had shorter total (8.6 vs 5.5 days; P = .02) and intensive care unit (3.2 vs 1.8 days; P = .002) length of stay. The protocol was associated with significantly decreased total hospital ($38,928 vs $28,066; P = .04), total variable ($23,115 vs $15,627; P = .02), and pharmacy ($5094 vs $1181; P < .001) costs, whereas inpatient care costs ($15,152 vs $11,467; P = .09) trended down. Post-protocol patients required fewer oral antihypertensive agents at discharge (3.8 vs 2.7; P = .005). No significant difference in 30-day mortality was observed. CONCLUSIONS: A goal-directed protocol reduces resource utilization and costs without compromising early mortality rates for patients with uncomplicated acute TBAD. Such a strategy may have broader application in medical management of acute aortic syndromes.

A Frailty-Based Risk Score Predicts Morbidity and Mortality After Elective Endovascular Repair of Descending Thoracic Aortic Aneurysms.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has expanded access to descending thoracic aortic aneurysm (DTAA) repair particularly for elderly and frail patients. This high-risk population has limited long-term overall survival, such that appropriate patient selection is required to optimize patient benefit and resource utilization. Our objective is to develop and validate a frailty-based, procedure-specific risk score for patients undergoing elective TEVAR for DTAA. METHODS: Patients undergoing nonemergent TEVAR for DTAA during 2005-2016 were identified in the National Surgical Quality Improvement Program database. Those with concurrent cardiac or open aortic surgery, abdominal visceral intervention, or Zone 0 deployment were excluded. Patients were randomly divided between derivation and validation samples. The primary outcome was 30-day major adverse events (MAE), including mortality and major systemic complications. Using the derivation cohort, variables associated with MAE were identified by univariable analyses. Those with P < 0.05 were included in multivariable logistic regression analysis. Independent procedure-specific and frailty-related risk factors for MAE were used to develop a pragmatic score to assess risk for TEVAR. RESULTS: Overall, 1,784 patients were included. 14% of the derivation patients had MAE (14% major complications, 4% mortality). Independent risk factors for MAE were primarily associated with markers of frailty and TEVAR extent and complexity and included functional dependence (OR 2.9, 95% CI 1.6-5.4), pulmonary disease (1.6, 1.1-2.4), thoracoabdominal extent (2.2 (1.4-3.4), need for iliac access (2.1, 1.1-3.8), and Zone I or II deployment (OR 1.7, 1.1-2.5). According to their respective beta coefficients, each variable was assigned a single point. Based on total points, patients were stratified as low- (0 points), intermediate- (1 point), or high-risk (≥2 points), with stepwise increases in mortality (0%, 4%, and 9%) and major complications (7%, 11%, and 23%) between strata. Validation patients had similar characteristics, risk strata distribution, and outcomes as the derivation patients, and the risk model had similar performance in both groups. CONCLUSIONS: Markers of frailty and procedure complexity strongly predict MAE after TEVAR for DTAA and can improve patient selection by enabling patient and procedure-specific risk stratification. While TEVAR is safe in low-risk patients, intermediate-risk patients warrant careful discussion of the risks and benefits of aortic intervention; under certain circumstances, high-risk patients may not benefit. Further study is required to define the association between frailty and long-term outcomes.

Derivation and validation of thoracic sarcopenia assessment in patients undergoing thoracic endovascular aortic repair.

OBJECTIVE: Sarcopenia, as assessed by computed tomography (CT)-based measurements of muscle mass, is an objective and patient-specific indicator of frailty, which is an important predictor of operative morbidity and mortality. Studies to date have primarily focused on psoas-defined sarcopenia, which may not be valid among patients with thoracic aortic disease. Using psoas sarcopenia as the reference for sarcopenia, the purpose of this study was to create and to validate a new thoracic-level method of measuring sarcopenia as a novel method to assess frailty among patients undergoing thoracic endovascular aortic repair. METHODS: Prospectively collected data of patients undergoing thoracic endovascular aortic repair for thoracic aortic dissection, aneurysm, or injury using a conformable thoracic graft were reviewed. Patients with preoperative abdominal and thoracic CT imaging were included. Thoracic muscle mass was measured on axial images at the T12 level using our newly established standardized computer-assisted protocol. Psoas sarcopenia was measured at the L3 level using standard methods. Optimal sex-specific diagnostic T12 measurements were determined by receiver operating characteristic (ROC) curve analysis. A subset of scans were reviewed in duplicate by two trained observers and intraobserver and interobserver reliability tested by intraclass correlation coefficient. Agreement between T12 and L3 sarcopenia was tested by Cohen κ (scale, 0-1). RESULTS: There were 147 patients included for analysis, including 34 dissection, 80 trauma, and 33 aneurysm patients. ROC curve analysis yielded sarcopenic cutoff values of 106.00 cm2/m2 for women and 110.00 cm2/m2 for men at the T12 level. Based on ROC curve analysis, overall accuracy of T12 measurements was high (area under ROC curve, 0.91 for men and 0.90 for women). Quantitative interobserver and intraobserver reliability yielded excellent intraclass correlation coefficient values (>0.95). Qualitative interobserver reliability yielded nearly perfect Cohen κ values (>0.85). Qualitative intraobserver reliability of calculating sarcopenia at both the T12 and L3 levels was fair for both readers (0.361 and 0.288). There was additionally a general correlation between changes in muscle area at L3 with changes at T12 during 48 months. CONCLUSIONS: Thoracic sarcopenia can be readily and reliably reproduced from CT-derived measurement of T12-level muscle area. This approach may be used as an alternative method to objectively define sarcopenia in patients without abdominal CT imaging. Future studies to assess the predictability of thoracic vs abdominal sarcopenia on postoperative outcomes will enhance the utility of these tools.

Early Treatment at a Referral Center Improves Outcomes for Patients with Acute Vascular Disease.

BACKGROUND: Patients with acute vascular disease frequently need specialized management that may require transfer to a vascular referral center. Although transfer may be medically necessary, it can delay definitive care and is an indicator of incorrect triage to the initial hospital. Regionalization of acute vascular care could improve patient triage and subsequent outcomes. To evaluate the potential benefit from regionalization, we analyzed outcomes of patients treated for acute vascular disease at vascular referral centers. METHODS: Using a statewide database capturing all inpatient admissions in Maryland during 2013-2015, patients undergoing noncardiac vascular procedures on an acute basis were identified. Patients admitted to a vascular referral center were stratified by admission status as direct or transfer. The primary outcome was inpatient mortality, and the secondary outcome was resource use. Patient groups were compared by univariable analyses, and the effect of admission status on mortality was assessed by multivariable logistic regression. RESULTS: Of 4,873 patients with acute vascular disease managed at vascular referral centers, 2,713 (56%) were admitted directly, whereas 2,160 (44%) were transferred. Transfers to referral centers accounted for 71% of all interhospital transfers. The transfer-group patients were older, had more comorbidities, and higher illness severities. Patients who were transferred had higher mortality (14% vs. 9%, P < 0.0001), longer hospital lengths of stay, greater critical care-resource utilization, and higher costs. After adjusting for demographics, comorbidities, and illness severity, transfer status was independently associated with higher inpatient mortality. CONCLUSIONS: Primary treatment at a referral center is independently associated with improved outcomes for patients with acute vascular disease. Direct admission or earlier triage to a specialty center may improve patient and system outcomes and could be facilitated by standardization and regionalization of complex acute vascular care.

Contemporary Single-Center Experience With Prophylactic Cerebrospinal Fluid Drainage for Thoracic Endovascular Aortic Repair in Patients at High Risk for Ischemic Spinal Cord Injury.

OBJECTIVE: To review rates of permanent paraplegia and lumbar drain-related complications in patients undergoing thoracic endovascular aortic repair (TEVAR) surgery with prophylactic cerebrospinal fluid (CSF) drainage at the authors' institution. DESIGN: Retrospective cohort study. SETTING: Tertiary care, academic medical center. PARTICIPANTS: Patients who underwent TEVAR with a high risk for ischemic spinal cord injury and prophylactic lumbar CSF drainage over a 5-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred and two patients underwent TEVAR with lumbar CSF drainage. Thirty-day mortality was 5.9%, and the rate of permanent paraplegia was 2%. Drain complications occurred in 4 (3.9%) patients, but no patient experienced permanent injury related to CSF drainage. Two patients in the cohort had complete resolution of paraplegia with increased CSF drainage and mean arterial blood pressure increases aimed to increase spinal cord perfusion pressure by 25%. A third patient experienced improvement in lower extremity strength but remained paraplegic, and a fourth patient demonstrated no improvement in symptoms. The 6 patients taking clopidogrel experienced no bleeding complications, and there were no apparent risk factors for bleeding in the 5 patients who had bloody drain output or in 1 patient who developed an epidural hematoma. CONCLUSION: Prophylactic CSF drainage was associated with low paraplegia and drain-related complication rates. These data further support the safety of prophylactic CSF drainage in patients undergoing TEVAR with a high risk for ischemic spinal cord injury.

Management and outcomes of carotid artery extension of aortic dissections.

BACKGROUND: Aortic dissection (AD) is the most common aortic catastrophe. Carotid artery dissection due to extension of AD (CAEAD) is one severe complication of this condition. Despite years of refinement in the techniques for repair of AD, the optimal management strategy for CAEAD remains yet to be described. We hypothesized that CAEAD eventually resolves on antiplatelet therapy with a low but not insignificant risk of cerebrovascular accident (CVA). METHODS: This was a single-institution retrospective review of patients admitted with nontraumatic coincident aortic and carotid dissection between 2001 and 2013. RESULTS: CAEAD was present in 38 patients (24 men [53%]). The median age was 59.5 years (range, 25-85 years). A Stanford type A AD was diagnosed in 36 patients (95%). CVA or transient ischemic attack was identified in 11 patients (29%). Eight were potentially attributable to the carotid lesion. Two of these eight strokes resulted in death. Of the 11 CVAs and transient ischemic attacks, 8 were evident at presentation, 2 were diagnosed postoperatively during hospitalization, and 1 was diagnosed during early follow-up. Only one of these three postadmission strokes was attributable to the carotid lesion. Nonoperative management of aortic and carotid dissections was pursued in 9 patients (24%), 26 (68%) underwent open repair, and 4 (11%) had endovascular management of AD (2 thoracic endovascular aortic repair, 2 endovascular fenestrations), including 1 patient with a staged hybrid procedure (frozen elephant trunk). There were eight inpatient deaths (21%) and nine deaths in the follow-up period. Of the 30 patients who survived to discharge, 24 (80%) were managed with antiplatelet therapy. At a median follow-up of 14.5 months in 22 patients with follow-up computed tomography scans available, a minority of lesions had resolved, and only one CVA was reported. CONCLUSIONS: This study found that CAEAD was associated almost exclusively with type A AD, was typically unilateral, most often on the left, and usually persisted at follow-up. Many CAEAD patients presented with CVA and experienced significant early mortality. Notably, not all CVA events were attributable to the CAEAD. CVAs were not common after admission, and there appeared to be a low risk of new or subsequent stroke during follow-up with routine antiplatelet and antihypertensive therapy.

Functional status predicts major complications and death after endovascular repair of abdominal aortic aneurysms.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is considered a lower risk option for treating abdominal aortic aneurysms and is of particular utility in patients with poor functional status who may be poor candidates for open repair. However, the specific contribution of preoperative functional status to EVAR outcomes remains poorly defined. We hypothesized that impaired functional status, based simply on the ability of patients to perform activities of daily living, is associated with worse outcomes after EVAR. METHODS: Patients undergoing nonemergent EVAR for abdominal aortic aneurysm between 2010 and 2014 were identified in the National Surgical Quality Improvement Program (NSQIP) database. The primary outcomes were 30-day mortality and major operative and systemic complications. Secondary outcomes were inpatient length of stay, need for reoperation, and discharge disposition. Using the NSQIP-defined preoperative functional status, patients were stratified as independent or dependent (either partial or totally dependent) and compared by univariate and multivariable analyses. RESULTS: Of 13,432 patients undergoing EVAR between 2010 and 2014, 13,043 were independent (97%) and 389 were dependent (3%) before surgery. Dependent patients were older and more frequently minorities; had higher rates of chronic pulmonary, heart, and kidney disease; and were more likely to have an American Society of Anesthesiologists score of 4 or 5. On multivariable analysis, preoperative dependent status was an independent risk factor for operative complications (odds ratio [OR], 3.1; 95% confidence interval [CI], 2.5-3.9), systemic complications (OR, 2.8; 95% CI, 2.0-3.9), and 30-day mortality (OR, 3.4; 95% CI, 2.1-5.6). Secondary outcomes were worse among dependent patients. CONCLUSIONS: Although EVAR is a minimally invasive procedure with substantially less physiologic stress than in open aortic repair, preoperative functional status is a critical determinant of adverse outcomes after EVAR in spite of the minimally invasive nature of the procedure. Functional status, as measured by performance of activities of daily living, can be used as a valuable marker of increased perioperative risk and may identify patients who may benefit from preoperative conditioning and specialized perioperative care.

Defining the burden, scope, and future of vascular acute care surgery.

OBJECTIVE: The paradigm of acute care surgery has revolutionized nonelective general surgery. Similarly, nonelective vascular surgery may benefit from specific management and resource capabilities. To establish the burden and scope of vascular acute care surgery, we analyzed the characteristics and outcomes of patients hospitalized for vascular surgical procedures in Maryland. METHODS: A retrospective analysis of a statewide inpatient database was performed to identify patients undergoing noncardiac vascular procedures in Maryland from 2009 to 2013. Patients were stratified by admission acuity as elective, urgent, or emergent, with the last two groups defined as acute. The primary outcome was inpatient mortality, and secondary outcomes were critical care and hospital resource requirements. Groups were compared by univariate analyses, with multivariable analysis of mortality based on acuity level and other potential risk factors for death. RESULTS: Of 3,157,499 adult hospital admissions, 154,004 (5%) patients underwent a vascular procedure; most were acute (54% emergent, 13% urgent), whereas 33% were elective. Acute patients had higher rates of critical care morbidity and required more hospital resource utilization. Admission for acute vascular surgery was independently associated with mortality (urgent odds ratio, 2.1; emergent odds ratio, 3.0). CONCLUSIONS: The majority of inpatient vascular care in Maryland is for acute vascular surgery, which is an independent risk factor for mortality. Acute vascular surgical care entails greater critical care and hospital resource utilization and-similar to emergency general surgery-may benefit from dedicated training and practice models.

Percutaneous Treatment of Multiple Recurrent Thromboembolization from a Descending Thoracic Aortic Intimal Sarcoma.

Aortic intimal sarcomas are rare tumors that may result in distal embolic ischemia. Here, we present a patient who presented with crescendo lower extremity and mesenteric ischemic events from malignant macroembolism. Management with percutaneous pharmacomechanical thromboembolectomy enabled restoration of distal perfusion and minimally invasive collection of tumor sample to confirm the suspected diagnosis of aortic sarcoma. The patient underwent definitive aortectomy and reconstruction and is recovering well.

Thoracic Endovascular Repair of Blunt Thoracic Aortic Injury in the Setting of an Aberrant Right Subclavian Artery.

Blunt thoracic aortic injury (BTAI) in a patient with an aberrant right subclavian artery (ARSA) presents unique challenges for patient management and aortic repair. Specific considerations include the need to treat coincidental ARSA, subclavian revascularization, and ARSA exclusion. Despite the rise of endovascular repair as the primary modality for aortic repair for BTAI, reports of this technique in the setting of ARSA are limited. Here we describe 3 patients with ARSA who underwent TEVAR for BTAI, and discuss critical management and technical issues in these patients.

Evolution of lesion-specific management of blunt thoracic aortic injury.

Developments in diagnosis and treatment have transformed the management of blunt thoracic aortic injuries (BTAIs). For patients in stable condition, treatment practice has shifted from early open repair to nonoperative management for low-grade lesions and routine delayed endovascular repair for more significant injuries. However, effective therapy depends on accurate staging of injury grade and stability to select patients for appropriate management. Recent developments in BTAI risk stratification enable lesion-specific management tailored to the patient and aortic lesion. This review summarizes advances in lesion assessment and treatment and proposes an integrated scheme for the modern management of BTAI.

Repair of ruptured abdominal aortic aneurysm after cardiac arrest.

OBJECTIVE: Cardiac arrest in patients with ruptured abdominal aortic aneurysm (rAAA) is not uncommon and associated with significantly increased mortality. Although it has been suggested as a contraindication to aortic repair, the prognostic implications of preoperative cardiac arrest in the face of rAAA are controversial. The purpose of this structured review is to analyze the reported outcomes of patients with rAAA and preoperative cardiac arrest. METHODS: English language single- and multi-institutional series reporting outcomes of patients with rAAA and cardiac arrest were identified by systematic literature search and review. An aggregate analysis and structured review of outcomes after subsequent aortic repair was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The primary outcome was short-term overall mortality. RESULTS: Sixteen studies involving 2669 patients with rAAA were analyzed, including 334 (13%) with preoperative cardiac arrest. Cardiac arrest was associated with significantly increased mortality compared with patients with rAAA without arrest (86% vs 44%; P < .0001), although cardiac arrest in isolation was poorly predictive of mortality. Four patients were treated by endovascular aortic repair, and all survived. Shorter resuscitation times and return of signs of life prior to aortic repair are associated with improved survival, and long-term functional outcomes among survivors have been reported. CONCLUSIONS: Mortality among patients with rAAA and preoperative cardiac arrest is high but not prohibitive. Aortic repair should not be withheld from such patients who are otherwise reasonable candidates for intervention, provided resources for emergent aortic repair are available.

Nonoperative Management of Traumatic Aortic Pseudoaneurysms.

BACKGROUND: Current blunt thoracic aortic injury (BTAI) guidelines recommend early repair of traumatic pseudoaneurysms (PSAs) due to risk for subsequent aortic rupture. Recent analyses indicate that early repair is required only in the setting of high-risk features, while delayed repair is safe and associated with lower morbidity and mortality in appropriately selected patients. To evaluate the appropriate indications for nonoperative management (NOM) of traumatic PSAs, we performed a systematic review of studies reporting outcomes for this management strategy. We hypothesized that NOM is safe in appropriately selected patients with traumatic aortic PSAs. METHODS: English language single- and multi-institutional series reporting NOM of traumatic thoracic aortic PSAs were identified by systematic literature search and review. A descriptive analysis was performed of NOM, with stratification by lesion size and patient follow-up. The primary outcomes were late aortic intervention, aortic-related death, and all-cause mortality. RESULTS: Eighteen studies, which included 937 patients with traumatic PSAs, were analyzed. One hundred ninety-one patients were managed nonoperatively. The primary indication for NOM was prohibitive risk for aortic repair due to severe comorbidities or concurrent injuries. Where reported, PSAs with <50% circumferential involvement accounted for 88% of lesions selected for NOM. Late interventions were required in 4% of patients. Inpatient aortic-related mortality was 2%, and all-cause inpatient mortality was 32%. Although survival at up to 4-7 years was reported, postdischarge follow-up after PSA NOM was limited to <1 year in most studies. CONCLUSIONS: NOM of traumatic aortic PSAs is a common practice in BTAI series reporting lesion-specific management, and is associated with low rates of treatment failure. These findings suggest that routine early repair may not be required for traumatic PSAs, particularly for lesions limited to <50% of the aortic circumference. Definitive repair can be delayed until patient stability and repair timing can be guided by assessment of lesion stability on follow-up imaging.

A new aortic injury score predicts early rupture more accurately than clinical assessment.

OBJECTIVE: The optimal timing for repair of a high-grade blunt thoracic aortic injury (BTAI) is uncertain. Delayed repair is common and associated with improved outcomes, but some lesions may rupture during observation. To determine optimal patient selection for appropriate management, we developed a pilot clinical risk score to evaluate aortic stability and predict rupture. METHODS: Patients presenting in stable condition with Society for Vascular Surgery grade III or IV BTAI diagnosed on computed tomography (CT) were retrospectively reviewed. To determine clinical and radiographic factors associated with aortic rupture, patients progressing to aortic rupture (defined by contrast extravasation on CT or on operative or autopsy findings) were compared with those who had no intervention ≤48 hours of admission. A model targeting 100% sensitivity for rupture was generated and internally validated by bootstrap analysis. Clinical utility was tested by comparison with clinical assessment by surgeons experienced in BTAI management who were provided with CT images and clinical data but were blinded to outcome. RESULTS: The derivation cohort included 18 patients whose aorta ruptured and 31 with stable BTAI. There was no difference in age, gender, injury mechanism, nonchest injury severity, blood pressure, or Glasgow Coma Scale on admission between patient groups. As dichotomous factors, admission lactate >4 mM, posterior mediastinal hematoma >10 mm, and lesion/normal aortic diameter ratio >1.4 on the admission CT were independently associated with aortic rupture. The model had an area under the receiver operator curve of .97, and in the presence of any two factors, was 100% sensitive and 84% specific for predicting aortic rupture. No aortic lesions ruptured in patients with fewer than two factors. In contrast, clinical assessment had lower accuracy (65% vs 90% total accuracy, P < .01). CONCLUSIONS: This novel risk score can be applied on admission using clinically relevant factors that incorporate patient physiology, size of the aortic lesion, and extent of the mediastinal hematoma. The model reliably identifies and distinguishes patients with high-grade BTAI who are at risk for early rupture from those with stable lesions. Although preliminary, because it is more accurate than clinical assessment alone, the score may improve patient selection for emergency or delayed intervention.

Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood.

BACKGROUND: Genetically modified pigs are a promising potential source of lung xenografts. Ex vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series. METHODS: Data from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had one genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 h of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype. RESULTS: Each increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 h generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO-1, hCD55, or hEPCR were associated with improved survival. hTBM, HLA-E, and hCD39 were associated with no significant effect on the primary outcome. CONCLUSION: This meta-analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression and pathway-specific injury and explore why some genes apparently exhibit neutral (hTBM, HLA-E) or inconclusive (CD39) effects, GalTKO, hCD46, HO-1, hCD55, and hEPCR modifications were associated with significant lung xenograft protection. This analysis supports the hypothesis that multiple genetic modifications targeting different known mechanisms of xenograft injury will be required to optimize lung xenograft survival.

Management and outcomes of blunt common and external iliac arterial injuries.

OBJECTIVE: Blunt iliac arterial injuries (BIAI) require complex management but are rare and poorly studied. We investigated the presentation, management, and outcomes of patients with blunt common or external iliac arterial injuries. METHODS: We identified and reviewed 112 patients with BIAI admitted between 2000 and 2011 at a Level I trauma center. Patients with common/external iliac artery injuries (CE group) were primarily analyzed, with patients with injuries of the internal iliac artery or its major branches (IB group) included for comparison of pelvic arterial trauma. RESULTS: Twenty-four patients had CE and 88 had IB injuries. Mean ages (45 ± 19 years) and gender (86% male) were similar between groups. The mean injury severity score was 40 ± 14 (CE, 36 ± 15; IB, 40 ± 14; P = .19), indicating severe trauma. Twenty (83%) of the CE patients presented with signs of leg malperfusion. Admission factors associated with CE injury were crush mechanism of injury (37% vs 17%; P = .03) and pelvic soft tissue trauma (50% vs 15%; P < .01). The CE group had higher early mortality rates, both within 3 hours of admission (50% vs 19%; P = .04) and prior to iliac intervention (42% vs 3%; P < .01). Among those surviving to management, CE patients were more likely to undergo open repair or revascularization (68% vs 3%; P < .01) and had a higher rate of leg amputation (50% vs 6%; P < .01), with 8/12 (67%) culminating in hemipelvectomy. Risk factors for amputation included leg malperfusion, high-grade pelvic fractures, pelvic soft tissue trauma, and increasing leg injury severity. Overall mortality was 40%, and was similar between the injury groups. Among CE patients, need for amputation, pelvic fractures, and wounds were associated with inpatient mortality. CONCLUSIONS: This is the largest series to date of blunt CE injuries and demonstrates distinct clinical features and outcomes for these patients. They have high risk for early death and proximal leg amputation. CE injury is specifically associated with serious open pelvic soft tissue injury, which, along with high-grade pelvic fractures, is a risk factor for amputation and death. On-demand emergent endovascular intervention may play an important role in improving management of these complex injuries.

Lung xenotransplantation: recent progress and current status.

Xenotransplantation has undergone important progress in controlling initial hyperacute rejection in many preclinical models, with some cell, tissue, and organ xenografts advancing toward clinical trials. However, acute injury, driven primarily by innate immune and inflammatory responses, continues to limit results in lung xenograft models. The purpose of this article is to review the current status of lung xenotransplantation--including the seemingly unique challenges posed by this organ-and summarize proven and emerging means of overcoming acute lung xenograft injury.