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.

Exploring the Association Between Suicide Prevention Public Service Announcements and User Comments on YouTube: A Computational Text Analysis Approach.

In the United States, suicide rates have increased by 30% over the past few decades. Public service announcements (PSAs) are effective health promotion vehicles and social media can help spread PSAs to hard-to-engage individuals who may benefit from intervention efforts, yet the most meaningful characteristics of PSAs for influencing health promotion attitudes and behaviors are inconclusive. This study applied content and quantitative text analyses to suicide prevention PSAs and comments on YouTube to assess the relationships between message frame, message format, and the level of sentiment and help-seeking language within them. Seventy-two PSAs were analyzed for gain/loss-framing and narrative/argument-format, and 4,335 related comments were analyzed for positive/negative sentiment and frequency of help-seeking language use. Results indicate that a higher ratio of positive comments was more likely to be found on gain-framed and narrative-formatted PSAs, and a higher ratio of comments with help-seeking language was more likely to be found on narrative-formatted PSAs. Implications and future research are discussed.

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.

Conformability of the GORE EXCLUDER iliac branch endoprosthesis is associated with freedom from adverse iliac events.

OBJECTIVE: The GORE EXCLUDER iliac branch endoprosthesis (IBE; W.L. Gore & Associates, Flagstaff, Ariz) is designed to preserve internal iliac artery (IIA) patency during endovascular treatment of aneurysms involving the common iliac artery. The device is intended to conform to iliac tortuosity, which may decrease adverse iliac events (AIE). The objective of this study was to evaluate risk factors for AIE after IBE implantation. METHODS: This was a post hoc analysis of the prospective, multicenter GORE 12-04 IBE pivotal trial. Patients with preoperative and postoperative axial imaging were included, with analysis based on each treated iliac system. An independent core laboratory performed all scan measurements, including iliac diameters, lengths, and tortuosity. Conformability was analyzed by the changes in tortuosity after IBE deployment, with less change indicating greater conformation. The end point was AIE, defined as ipsilateral radiographic or clinical complications. Critical nonconformation was defined as a threshold change in tortuosity associated with a significant increase in AIE. RESULTS: We included 98 patients with 101 treated iliac systems. There were eight AIE (8%; six IIA component occlusions, one iliac branch component occlusion, and one EIA dissection requiring reintervention). Patients with AIE had smaller IIA diameters and less IBE conformability. After multivariable logistic regression analysis, an IIA diameter of less than 10 mm and a change in total iliac tortuosity beyond -15% were independently associated with AIE (odds ratio, 12 [interquartile range, 1.4-110] and odds ratio, 8.2 [interquartile range, 1.5-46], respectively), and the latter was used to define critical nonconformation. Critical nonconformation occurred in 11% of treated systems, and was associated with a high rate of AIE (36% vs 4%; P = .004). CONCLUSIONS: Endograft conformation is a novel device property and technical outcome that, along with a larger IIA diameter, is associated with freedom from AIE after IBE deployment. An evaluation of these risk factors may better inform the management of patients with iliac aneurysmal disease. Further research on endograft conformation and patient outcomes is warranted, particularly for those with challenging anatomy undergoing complex procedures.

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.

CT-Derived Pretreatment Thoracic Sarcopenia Is Associated with Late Mortality after Thoracic Endovascular Aortic Repair.

BACKGROUND: Frailty, characterized by physiologic depletion, predicts postoperative morbidity and mortality in vascular surgery patients. CT-derived sarcopenia is a valuable method for objectively staging frailty preoperatively. PURPOSE: With prior analyses primarily measuring psoas cross-sectional area on CT, we compared a method of measuring thoracic sarcopenia to existing techniques of lumbar sarcopenia and assessed the association with long-term survival and outcomes post-Thoracic Endovascular Aortic Repair (TEVAR). METHODS: Prospectively collected data of 217 patients undergoing TEVAR from 2009 to 2012 were reviewed. Thoracic sarcopenia was quantified by measuring total area of the rectus abdominis, latissimus dorsi, intercostal, erector spinae, and external and internal oblique muscles at the T12 vertebral level. Total psoas area at the L3 was used to measure lumbar sarcopenia. RESULTS: 200 patients had preoperative imaging enabling measurements of thoracic sarcopenia, 186 of these patients were also assessed for lumbar sarcopenia. Thoracic sarcopenic patients were older, had lower body mass indices, were more commonly female, and most commonly being treated for aneurysms. Thoracic sarcopenic patients had significantly higher rates of congestive heart failure, hypertension, prior vascular intervention, and TEVAR-related adverse events. Thoracic sarcopenia was associated with significantly higher mortality at 2 and 5 years post-TEVAR (2-year mortality: 19% vs 8%, P = 0.02; 5-year mortality: 31% vs 18%, P = 0.03). Lumbar sarcopenia was not associated with increased mortality at any time point. Patients whose muscle mass degraded over 48-month follow-up did not experience significantly higher rates of adverse events. CONCLUSIONS: CT-derived thoracic sarcopenia, but not lumbar sarcopenia, is significantly associated with 5-year mortality post-TEVAR.

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.

Thromboxane and histamine mediate PVR elevation during xenogeneic pig lung perfusion with human blood.

BACKGROUND: Elevated pulmonary vascular resistance (PVR), platelet adhesion, coagulation activation, and inflammation are prominent features of xenolung rejection. Here, we evaluate the role of thromboxane and histamine on PVR, and their contribution to other lung xenograft injury mechanisms. METHODS: GalTKO.hCD46 single pig lungs were perfused ex vivo with fresh heparinized human blood: lungs were either treated with 1-Benzylimidazole (1-BIA) combined with histamine receptor blocker famotidine (n = 4) or diphenhydramine (n = 6), 1-BIA alone (n = 6) or were left untreated (n = 9). RESULTS: Six of the nine control experiments (GalTKO.hCD46 untreated), "survived" until elective termination at 4 hours. Without treatment, initial PVR elevation within the first 30 minutes resolved partially over the following hour, and increased progressively during the final 2 hours of perfusion. In contrast, 1-BIA, alone or in addition to either antihistamine treatment, was associated with low stable PVR. Combined treatments significantly lowered the airway pressure when compared to untreated reference. Although platelet and neutrophil sequestration and coagulation cascade activation were not consistently altered by any intervention, increased terminal wet/dry weight ratio in untreated lungs was significantly blunted by combined treatments. CONCLUSION: Combined thromboxane and histamine pathway blockade prevents PVR elevation and significantly inhibits loss of vascular barrier function when GalTKO.hCD46 lungs are perfused with human blood. Platelet activation and platelet and neutrophil sequestration persist in all groups despite efficient complement regulation, and appear to occur independent of thromboxane and histamine antagonism. Our work identifies thromboxane and histamine as key mediators of xenolung injury and defines those pathways as therapeutic targets to achieve successful xenolung transplantation.

Interleukin-8 mediates neutrophil-endothelial interactions in pig-to-human xenogeneic models.

BACKGROUND: Human neutrophils are sequestered by pig lung xenografts within minutes during ex vivo perfusion. This phenomenon is not prevented by pig genetic modifications that remove xeno-antigens or added human regulatory molecules intended to down-regulate activation of complement and coagulation pathways. This study investigated whether recipient and donor interleukin-8 (IL-8), a chemokine known to attract and activate neutrophils during inflammation, is elaborated in the context of xenogeneic injury, and whether human or pig IL-8 promote the adhesion of human neutrophils in in vitro xenograft models. METHODS: Plasma levels of pig, human or non-human primate (NHP) IL-8 from ex vivo pig lung perfusion experiments (n = 10) and in vivo pig-to-baboon lung transplantation in baboons (n = 22) were analysed by ELISA or Luminex. Human neutrophils stimulated with human or pig IL-8 were analysed for CD11b expression, CD18 activation, oxidative burst and adhesion to resting or TNF-activated endothelial cells (EC) evaluated under static and flow (Bioflux) conditions. For some experiments, human neutrophils were incubated with Reparixin (IL-8/CXCL8 receptor blocker) and then analysed as in the in vitro experiments mentioned above. RESULTS: Plasma levels of pig IL-8 (~6113 pg/mL) increased more than human (~1235 pg/mL) between one and four hours after initiation of ex vivo lung perfusion. However, pig IL-8 levels remained consistently low (<60 pg/mL) and NHP IL-8 plasma levels increased by ~2000 pg/mL after four hours in a pig-to-baboon lung xenotransplantation. In vitro, human neutrophils' CD11b expression, CD18 activation and oxidative burst all increased in a dose-dependent manner following exposure to either pig or human IL-8, which also were associated with increased adhesion to EC in both static and flow conditions. Reparixin inhibited human neutrophil activation by both pig and human IL-8 in a dose-dependent fashion. At 0.1 mg/mL, Reparixin inhibited the adhesion of IL-8-activated human neutrophils to pAECs by 84 ± 2.5%. CONCLUSIONS: Pig IL-8 increased in an ex vivo model of pig-to-human lung xenotransplantation but is not detected in vivo, whereas human or NHP IL-8 is elevated to a similar degree in both models. Both pig and human IL-8 activate human neutrophils and increase their adhesion to pig aortic ECs, a process significantly inhibited by the addition of Reparixin to human neutrophils. This work implicates IL-8, whether of pig or human origin, as a possible factor mediating in lung xenograft inflammation and injury and supports the evaluation of therapeutic targeting of this pathway in the context of xenotransplantation.

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.