Using machine learning to predict outcomes of patients with blunt traumatic aortic injuries.

BACKGROUND: The optimal management of blunt thoracic aortic injury (BTAI) remains controversial, with experienced centers offering therapy ranging from medical management to TEVAR. We investigated the utility of a machine learning (ML) algorithm to develop a prognostic model of risk factors on mortality in patients with BTAI. METHODS: The Aortic Trauma Foundation registry was utilized to examine demographics, injury characteristics, management and outcomes of patients with BTAI. A STREAMLINE (A Simple, Transparent, End-To-End Automated Machine Learning Pipeline Facilitating Data Analysis and Algorithm Comparison) model as well as logistic regression (LR) analysis with imputation using chained equations was developed and compared. RESULTS: From a total of 1018 patients in the registry, 702 patients were included in the final analysis. Of the 258 (37%) patients who were medically managed, 44 (17%) died during admission, 14 (5.4%) of which were aortic related deaths. Four hundred forty-four (63%) patients underwent TEVAR and 343 of which underwent TEVAR within 24 hours of admission. Among TEVAR patients, 39 (8.8%) patients died and 7 (1.6%) had aortic related deaths ( Table 1 ). Comparison of the STREAMLINE and LR model showed no significant difference in ROC curves and high AUCs of 0.869 (95% confidence interval, 0.813-0.925) and 0.840 (95% confidence interval, 0.779-0.900) respectively in predicting in-hospital mortality. Unexpectedly, however, the variables prioritized in each model differed between models. The top 3 variables identified from the LR model were similar to that from existing literature. The STREAMLINE model, however, prioritized location of the injury along the lesser curve, age and aortic injury grade. CONCLUSION: Machine learning provides insight on prioritization of variables not typically identified in standard multivariable logistic regression. Further investigation and validation in other aortic injury cohorts are needed to delineate the utility of ML models. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Simultaneous submission of seven CTSA proposals: UM1, K12, R25, T32-predoctoral, T32-postdoctoral, and RC2: strategies, evaluation, and lessons learned.

Translation is the process of turning observations in the research laboratory, clinic, and community into interventions that improve people's health. The Clinical and Translational Science Awards (CTSA) program is a National Center for Advancing Translational Sciences (NCATS) initiative to advance translational science and research. Currently, 64 "CTSA hubs" exist across the nation. Since 2006, the Houston-based Center for Clinical Translational Sciences (CCTS) has assembled a well-integrated, high-impact hub in Texas that includes six partner institutions within the state, encompassing ∼23,000 sq. miles and over 16 million residents. To achieve the NCATS goal of "more treatments for all people more quickly," the CCTS promotes diversity and inclusion by integrating underrepresented populations into clinical studies, workforce training, and career development. In May 2023, we submitted the UM1 application and six "companion" proposals: K12, R25, T32-Predoctoral, T32-Postdoctoral, and RC2 (two applications). In October 2023, we received priority scores for the UM1 (22), K12 (25), T32-Predoctoral (20), and T32-Postdoctoral (23), which historically fall within the NCATS funding range. This report describes the grant preparation and submission approach, coupled with data from an internal survey designed to assimilate feedback from principal investigators, writers, reviewers, and administrative specialists. Herein, we share the challenges faced, the approaches developed, and the lessons learned.

Insights From the Histopathologic Analysis of Acquired and Genetic Thoracic Aortic Aneurysms and Dissections.

OBJECTIVE: The purpose of this study was to apply contemporary consensus criteria developed by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology to the evaluation of aortic pathology, with the expectation that the additional pathologic information may enhance the understanding and management of aortic diseases. METHODS: A scoring system was applied to ascending aortic specimens from 42 patients with heritable thoracic aortic disease and known genetic variations and from 86 patients from a single year, including patients with known genetic variations (n = 12) and patients with sporadic disease (n = 74). RESULTS: The various types of lesions of medial degeneration and the overall severity of medial degeneration overlapped considerably between those patients with heritable disease and those with sporadic disease; however, patients with heritable thoracic aortic disease had significantly more overall medial degeneration (P = .004) and higher levels of elastic fiber fragmentation (P = .03) and mucoid extracellular matrix accumulation (P = .04) than patients with sporadic thoracic aortic disease. Heritable thoracic aortic disease with known genetic variation was more prevalent in women than in men (27.2% vs 9.8%; P = .04), and women had more severe medial degeneration than men (P = .04). Medial degeneration scores were significantly lower for patients with bicuspid aortic valves than for patients with tricuspid aortic valves (P = .03). CONCLUSION: The study's findings indicate considerable overlap in the pattern, extent, and severity of medial degeneration between sporadic and hereditary types of thoracic aortic disease. This finding suggests that histopathologic medial degeneration represents the final common outcome of diverse pathogenetic factors and mechanisms.

Development and Validation of a Risk Prediction Tool for In-hospital Mortality After Thoracic Endovascular Repair in Patients with Blunt Thoracic Aortic Injury Using the Aortic Trauma Foundation Registry.

BACKGROUND: The objective of our present effort was to use an international blunt thoracic aortic injury (BTAI) registry to create a prediction model identifying important preoperative and intraoperative factors associated with postoperative mortality, and to develop and validate a simple risk prediction tool that could assist with patient selection and risk stratification in this patient population. METHODS: For the purpose of the present study, all patients undergoing thoracic endovascular aortic repair (TEVAR) for BTAI and registered in the Aortic Trauma Foundation (ATF) database from January 2016 as of June 2022 were identified. Patients undergoing medical management or open repair were excluded. The primary outcome was binary in-hospital all-cause mortality. Two predictive models were generated: a preoperative model (i.e. only including variables before TEVAR or intention-to-treat) and a full model (i.e. also including variables after TEVAR or per-protocol). RESULTS: Out of a total of 944 cases included in the ATF registry until June 2022, 448 underwent TEVAR and were included in the study population. TEVAR for BTAI was associated with an 8.5% in-hospital all-cause mortality in the ATF dataset. These study subjects were subsequently divided using 3:1 random sampling in a derivation cohort (336; 75.0%) and a validation cohort (112; 25.0%). The median age was 38 years, and the majority of patients were male (350; 78%). A total of 38 variables were included in the final analysis. Of these, 17 variables were considered in the preoperative model, 9 variables were integrated in the full model, and 12 variables were excluded owing to either extremely low variance or strong correlation with other variables. The calibration graphs showed how both models from the ATF dataset tended to underestimate risk, mainly in intermediate-risk cases. The discriminative capacity was moderate in all models; the best performing model was the full model from the ATF dataset, as evident from both the Receiver Operating Characteristic curve (Area Under the Curve 0.84; 95% CI 0.74-0.91) and from the density graph. CONCLUSIONS: In this study, we developed and validated a contemporary risk prediction model, which incorporates several preoperative and postoperative variables and is strongly predictive of early mortality. While this model can reasonably predict in-hospital all-cause mortality, thereby assisting physicians with risk-stratification as well as inform patients and their caregivers, its intrinsic limitations must be taken into account and it should only be considered an adjunctive tool that may complement clinical judgment and shared decision-making.

Emergency vascular repairs in trauma: Predictors of poor prognosis and a novel scoring system.

BACKGROUND: Vascular injuries comprise 1% to 4% of all trauma patients, and there are no widely used risk-stratification tools. We sought to establish predictors of revascularization failures and compare outcomes of trauma and vascular surgeons. METHODS: We performed a single-institution, case-control study of consecutive patients with traumatic arterial injuries who underwent open repair between 2016 and 2021. Multivariable logistic regression was used to investigate covariates impacting the primary composite outcome of repair failure/revision, amputation, or in-hospital mortality. RESULTS: Among 165 patients, the median age was 34 years, 149 (90%) were male, and 99 (60%) suffered penetrating injury. Popliteal (46%) and superficial femoral (44%) arterial injuries were most common. Interposition graft/bypass was the most frequent repair (n = 107 [65%]). Revascularization failure was observed in 24 patients (15%). Compared with trauma surgeons, vascular surgeons more frequently repaired blunt injuries (66% vs. 20%, p < 0.001), anterior tibial (18% vs. 5%, p = 0.012), or tibioperoneal injuries (28% vs. 4%, p < 0.001), with a below-knee bypass (38% vs. 20%, p = 0.019). Revascularization failure occurred in 10% (9 of 93) of repairs by trauma surgeons and 21% (13 of 61) of repairs by vascular surgeons. Mangled Extremity Severity Score >8 (odds ratio, 15.6; 95% confidence interval, 4.4-55.9; p < 0.001) and concomitant laparotomy or orthopedic procedure (odds ratio, 6.7; 95% confidence interval, 1.6-28.6; p = 0.010) were independently associated with revascularization failure. A novel composite scoring system (UT Houston Score) was developed by combining Mangled Extremity Severity Score, concomitant procedure, mechanism of injury, and injury location. This score demonstrated a sensitivity of 100% with a score of 0 and a specificity of 95% with a score of >3. CONCLUSION: After traumatic arterial injury, trauma surgeons repaired less-complex injuries but with fewer revascularization failures than vascular surgeons. The UT Houston Score may be used to risk stratify patients to determine who may benefit from vascular surgery consultation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Addition of aspirin to venous thromboembolism chemoprophylaxis safely decreases venous thromboembolism rates in trauma patients.

Background: Trauma patients exhibit a multifactorial hypercoagulable state and have increased risk of venous thromboembolism (VTE). Despite early and aggressive chemoprophylaxis (CP) with various heparin compounds ("standard" CP; sCP), VTE rates remain high. In high-quality studies, aspirin has been shown to decrease VTE in postoperative elective surgical and orthopedic trauma patients. We hypothesized that inhibiting platelet function with aspirin as an adjunct to sCP would reduce the risk of VTE in trauma patients. Methods: We performed a retrospective observational study of prospectively collected data from all adult patients admitted to an American College of Surgeons Level I Trauma center from January 2012 to June 2015 to evaluate the addition of aspirin (sCP+A) to sCP regimens for VTE mitigation. Cox proportional hazard models were used to assess the potential benefit of adjunctive aspirin for symptomatic VTE incidence. Results: 10,532 patients, median age 44 (IQR 28 to 62), 68% male, 89% blunt mechanism of injury, with a median Injury Severity Score (ISS) of 12 (IQR 9 to 19), were included in the study. 8646 (82%) of patients received only sCP, whereas 1886 (18%) patients received sCP+A. The sCP+A cohort displayed a higher median ISS compared with sCP (13 vs 11; p<0.01). The overall median time of sCP initiation was hospital day 1 (IQR 0.8 to 2) and the median day for aspirin initiation was hospital day 3 (IQR 1 to 6) for the sCP+A cohort. 353 patients (3.4%) developed symptomatic VTE. Aspirin administration was independently associated with a decreased relative hazard of VTE (HR 0.57; 95% CI 0.36 to 0.88; p=0.01). There were no increased bleeding or wound complications associated with sCP+A (point estimate 1.23, 95% CI 0.68 to 2.2, p=0.50). Conclusion: In this large trauma cohort, adjunctive aspirin was independently associated with a significant reduction in VTE and may represent a potential strategy to safely mitigate VTE risk in trauma patients. Further prospective studies evaluating the addition of aspirin to heparinoid-based VTE chemoprophylaxis regimens should be sought. Level of evidence: Level III/therapeutic.

Automated Large Vessel Occlusion Detection Software and Thrombectomy Treatment Times: A Cluster Randomized Clinical Trial.

Importance: The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical. Objective: To determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows. Design, Setting, and Participants: This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion criteria included patients presenting as transfers from an outside hospital (n = 158), in-hospital stroke (n = 39), and patients treated with EVT through randomization in a large core clinical trial (n = 3). Intervention: Artificial intelligence (AI)-enabled automated LVO detection from CT angiogram coupled with secure messaging was activated at the 4 CSCs in a random-stepped fashion. Once activated, clinicians and radiologists received real-time alerts to their mobile phones notifying them of possible LVO within minutes of CT imaging completion. Main Outcomes and Measures: Primary outcome was the effect of AI-enabled LVO detection on door-to-groin (DTG) time and was measured using a mixed-effects linear regression model, which included a random effect for cluster (CSC) and a fixed effect for exposure status (pre-AI vs post-AI). Secondary outcomes included time from hospital arrival to intravenous tissue plasminogen activator (IV tPA) bolus in eligible patients, time from initiation of CT scan to start of EVT, and hospital length of stay. In exploratory analysis, the study team evaluated the impact of AI implementation on 90-day modified Rankin Scale disability outcomes. Results: Among 243 patients who met inclusion criteria, 140 were treated during the unexposed period and 103 during the exposed period. Median age for the complete cohort was 70 (IQR, 58-79) years and 122 were female (50%). Median National Institutes of Health Stroke Scale score at presentation was 17 (IQR, 11-22) and the median DTG preexposure was 100 (IQR, 81-116) minutes. In mixed-effects linear regression, implementation of the AI algorithm was associated with a reduction in DTG time by 11.2 minutes (95% CI, -18.22 to -4.2). Time from CT scan initiation to EVT start fell by 9.8 minutes (95% CI, -16.9 to -2.6). There were no differences in IV tPA treatment times nor hospital length of stay. In multivariable logistic regression adjusted for age, National Institutes of Health Stroke scale score, and the Alberta Stroke Program Early CT Score, there was no difference in likelihood of functional independence (modified Rankin Scale score, 0-2; odds ratio, 1.3; 95% CI, 0.42-4.0). Conclusions and Relevance: Automated LVO detection coupled with secure mobile phone application-based communication improved in-hospital acute ischemic stroke workflows. Software implementation was associated with clinically meaningful reductions in EVT treatment times. Trial Registration: ClinicalTrials.gov Identifier: NCT05838456.

Deep Hypothermic Circulatory Arrest With Retrograde Cerebral Perfusion: How Long Is Safe?

BACKGROUND: Cerebral protection strategies during proximal aortic repair remains controversial due to lack of evidence and large patient cohort studies. We herein evaluated our 3-decade experience using hypothermic circulatory arrest with retrograde cerebral perfusion (DHCA/RCP) to evaluate for its safety and safe duration during proximal aortic repair. METHODS: All proximal aortic repairs using DHCA/RCP from January 1991 to December 2020 performed at our institution were included in the analyses. Perioperative variables were evaluated for mortality and cerebrovascular accident (CVA; combined stroke and transient ischemic attack). RESULTS: In all, 1429 repairs were performed using DHCA/RCP. Of these, 464 (32%) were acute aortic dissection and 297 (21%) were resternotomy. The median age was 61 years (interquartile range 50-70 years). Operative mortality was 8.9% and CVA occurred in 8.4% (stroke 7.8%, transient ischemic attack 0.6%). There was a linear relationship between the RCP time and the incidence of immediate postoperative CVA. Incidence of CVA was less than 5% when RCP time was less than 20 minutes, 6.3% at 30 minutes, and 11.5% at 60 minutes. Multivariable analysis demonstrated acute type A aortic dissection (odds ratio 2.58, 95% CI1.49-4.48, P = .001) was the only predictor for postoperative CVA but RCP time was not (odds ratio 0.991, 95% CI 0.962-1.02, P = .527). CONCLUSIONS: DHCA/RCA provided satisfactory outcomes after proximal aortic operations. The safe duration of RCP with DHCA was up to 30 minutes in our experience. When the circulatory arrest time is expected to exceed 60 minutes, other adjuncts for cerebral protection should be recommended.

Mortality in Congenital Diaphragmatic Hernia: A Multicenter Registry Study of Over 5000 Patients Over 25 Years.

OBJECTIVE: To determine if risk-adjusted survival of patients with CDH has improved over the last 25 years within centers that are long-term, consistent participants in the CDH Study Group (CDHSG). SUMMARY BACKGROUND DATA: The CDHSG is a multicenter collaboration focused on evaluation of infants with CDH. Despite advances in pediatric surgical and intensive care, CDH mortality has appeared to plateau. Herein, we studied CDH mortality rates amongst long-term contributors to the CDHSG. METHODS: We divided registry data into 5-year intervals, with Era 1 (E1) beginning in 1995, and analyzed multiple variables (operative strategy, defect size, and mortality) to assess evolution of disease characteristics and severity over time. For mortality analyses, patients were risk stratified using a validated prediction score based on 5-minute Apgar (Apgar5) and birth weight. A risk-adjusted, observed to expected (O:E) mortality model was created using E1 as a reference. RESULTS: 5203 patients from 23 centers with >22years of participation were included. Birth weight, Apgar5, diaphragmatic agenesis, and repair rate were unchanged over time (all P > 0.05). In E5 compared to E1, minimally invasive and patch repair were more prevalent, and timing of diaphragmatic repair was later (all P < 0.01). Overall mortality decreased over time: E1 (30.7%), E2 (30.3%), E3 (28.7%), E4 (26.0%), E5 (25.8%) ( P = 0.03). Risk-adjusted mortality showed a significant improvement in E5 compared to E1 (OR 0.78, 95% CI 0.62-0.98; P = 0.03). O:E mortality improved over time, with the greatest improvement in E5. CONCLUSIONS: Risk-adjusted and observed-to-expected CDH mortality have improved over time.

Reappraisal of the role of motor and somatosensory evoked potentials during open distal aortic repair.

OBJECTIVE: Intraoperative motor and somatosensory evoked potentials have been applied to monitor spinal cord ischemia during repair. However, their predictive values remain controversial. The purpose of this study was to evaluate the impact of motor evoked potentials and somatosensory evoked potentials on spinal cord ischemia during open distal aortic repair. METHODS: Our group began routine use of both somatosensory evoked potentials and motor evoked potentials at the end of 2004. This study used a historical cohort design, using risk factor and outcome data from our department's prospective registry. Univariate and multivariable statistics for risk-adjusted effects of motor evoked potentials and somatosensory evoked potentials on neurologic outcome and model discrimination were assessed with receiver operating characteristic curves. RESULTS: Both somatosensory evoked potentials and motor evoked potentials were measured in 822 patients undergoing open distal aortic repair between December 2004 and December 2019. Both motor evoked potentials and somatosensory evoked potentials were intact for the duration of surgery in 348 patients (42%). Isolated motor evoked potential loss was observed in 283 patients (34%), isolated somatosensory evoked potential loss was observed in 18 patients (3%), and both motor evoked potential and somatosensory evoked potential loss were observed in 173 patients (21%). No spinal cord ischemia occurred in the 18 cases with isolated somatosensory evoked potential loss. When both signals were lost, signal loss happened in the order of motor evoked potentials and then somatosensory evoked potentials. Immediate spinal cord ischemia occurred in none of those without signal loss, 4 of 283 (1%) with isolated motor evoked potential loss, and 15 of 173 (9%) with motor evoked potential plus somatosensory evoked potential loss. Delayed spinal cord ischemia occurred in 12 of 348 patients (3%) with intact evoked potentials, 24 of 283 patients (8%) with isolated motor evoked potentials loss, and 27 of 173 patients (15%) with motor evoked potentials + somatosensory evoked potentials loss (P < .001). Motor evoked potentials and somatosensory evoked potentials loss were each independently associated with spinal cord ischemia. For immediate spinal cord ischemia, no return of motor evoked potential signals at the conclusion of the surgery had the highest odds ratio of 15.87, with a receiver operating characteristic area under the curve of 0.936, whereas motor evoked potential loss had the highest odds ratio of 3.72 with an area under the curve of 0.638 for delayed spinal cord ischemia. CONCLUSIONS: Somatosensory evoked potentials and motor evoked potentials are both important monitoring measures to predict and prevent spinal cord ischemia during and after open distal aortic repairs. Intraoperative motor evoked potential loss is a risk for immediate and delayed spinal cord ischemia after open distal aortic repair, and somatosensory evoked potential loss further adds predictive value to the motor evoked potential.

Endovascular treatment of complicated versus uncomplicated acute type B aortic dissection.

OBJECTIVE: The study objective was to analyze the outcomes of thoracic endovascular aortic repair performed for complicated and uncomplicated acute type B aortic dissections. METHODS: Patients from WL Gore's Global Registry for Endovascular Aortic Treatment who underwent thoracic endovascular aortic repair for acute type B aortic dissections were included, and data were retrospectively analyzed. RESULTS: Of 5014 patients enrolled in the Global Registry for Endovascular Aortic Treatment, 172 underwent thoracic endovascular aortic repair for acute type B aortic dissections. Of these repairs, 102 were for complicated acute type B aortic dissections and 70 were for uncomplicated acute type B aortic dissections. There were 46 (45.1%) procedures related to aortic branch vessels versus 15 (21.4%) in complicated type B aortic dissections and uncomplicated type B aortic dissections (P = .002). The mean length of stay was 14.3 ± 10.6 days (median, 11; range, 2-75) versus 9.8 ± 7.9 days (median, 8; range, 0-42) in those with complicated type B aortic dissections versus those with uncomplicated acute type B aortic dissections (P < .001). Thirty-day mortality was not different between groups (complicated type B aortic dissections 2.9% vs uncomplicated acute type B aortic dissections 1.4%, P = .647), as well as aortic complications (8.8% vs 5.7%, P = .449). Aortic event-free survival was 62.9% ± 37.1% versus 70.6% ± 29.3% at 3 years (P = .696). CONCLUSIONS: In the Global Registry for Endovascular Aortic Treatment, thoracic endovascular aortic repair results for complicated type B aortic dissections versus uncomplicated acute type B aortic dissections showed that 30-day mortality and perioperative complications were equally low for both. The midterm outcome was positive. These data confirm that thoracic endovascular aortic repair as the first-line strategy for treating complicated type B dissections is associated with a low risk of complications. Further studies with longer follow-up are necessary to define the role of thoracic endovascular aortic repair in uncomplicated acute type B dissections compared with medical therapy. However, in the absence of level A evidence from randomized trials, results of the uncomplicated acute type B aortic dissection patient cohort treated with thoracic endovascular aortic repair from registries are important to understand the related risk and benefit.

Rapid cooling is a safe technique in patients undergoing circulatory arrest for aortic repair.

Objective: To evaluate our institutional experience with rapid cooling for hypothermic circulatory arrest in proximal aortic repair. Methods: We retrospectively reviewed data from 2171 patients who underwent proximal aortic surgery requiring hypothermic circulatory arrest between 1991 and 2020. Cooling times were divided into quartiles and clinical outcome event rates were compared across quartiles using contingency table methods. Incremental effect of cooling time was assessed in the context of other perfusion time variables using multiple logistic regression analysis. Results: Median age was 61 years (interquartile range, 49-70 years) and 34.1% of patients were women. The procedure was emergent in 33.5% of patients, 22.9% had a previous sternotomy. The median circulatory arrest time was 22 minutes, with retrograde cerebral perfusion used in 94% of cases. Median cardiopulmonary bypass time was 149 minutes, with an aortic crossclamp time of 90 minutes. Patients were cooled to deep hypothermia. The first quartile had cooling times ranging from 5 to 13 minutes, second 14 to 18 minutes, third 19-23 minutes, and fourth 24-81 minutes. Overall, 30-day mortality was 9.4%, and was not significantly different across quartiles. There was a statistically significant trend toward lower rates of postoperative encephalopathy, gastrointestinal complications, and respiratory failure with shorter cooling times (P < .001, .006, and < .001, respectively). There was no significant difference in rates of postoperative stroke or dialysis. Conclusions: Rapid cooling can be performed safely in patients undergoing aortic surgery requiring circulatory arrest without increasing mortality or stroke. There were significantly lower rates of coagulopathy, respiratory failure, and postoperative encephalopathy with shorter cooling times.

In vivo evaluation of a new hybrid graft using retrograde visceral perfusion for thoracoabdominal aortic repair in an animal model.

Objectives: The SPIDER technique for hybrid thoracoabdominal aortic aneurysm repair can avoid thoracotomy and extracorporeal circulation. To improve technical feasibility and safety, the new Thoracoflo graft, consisting of a proximal stent graft connected to a 7-branched abdominal prosthesis, was evaluated in a pig model for technical feasibility testing, before implantation in humans. Methods: Retroperitoneal exposure of the infradiaphragmatic aorta, including visceral and renal arteries, was performed in 7 pigs (75-85 kg). One iliac branch was temporarily attached to the distal aorta to maintain retrograde visceral and antegrade iliac perfusion after deployment of the thoracic stent graft segment (SPIDER technique). The proximal stent-grafted segment was deployed in the thoracic aorta via direct aortic puncture over the wire without fluoroscopy. The graft was deaired before flow via the iliac side branch to the visceral and iliac arteries was established. Visceral, renal, and lumbar arteries were subsequently sutured to the corresponding side branches of the graft. Technical feasibility, operating and clamping time, blood flow, and tissue perfusion in the related organs were evaluated before implantation and after 3 and 6 hours using transit-time flow measurement and fluorescent microspheres. Final angiography or postprocedural computed tomography angiography were performed. Results: Over-the-wire graft deployment was successful in 6 animals without hemodynamic alteration (P = n.s.). In 1 pig, the proximal stent graft section migrated as the guidewire was not removed, as recommended, before release of the proximal fixation wire. Angiography and computed tomography scan confirmed successful graft implantation and transit-time flow measurement confirmed good visceral and iliac blood flow. Fluorescent microspheres confirmed good spinal cord perfusion. Conclusions: Over-the-wire implantation of the Thoracoflo graft using the SPIDER technique is feasible in a pig model. No fluoroscopy was required. For safe implantation, it is mandatory to follow the single steps of implantation.

Informed Consent for Placebo-Controlled Trials: Do Ethics and Science Conflict?

The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled trials, and we explore the fundamental ethical and scientific complexities involved with each.

Differences in Mid-Term Outcomes Between Patients Undergoing Thoracic Endovascular Aortic Repair for Aneurysm or Acute Aortic Syndromes: Report From the Global Registry for Endovascular Aortic Treatment.

PURPOSE: To analyze differences in baseline characteristics, overall mortality, device-related mortality, and re-intervention rates in patients who underwent thoracic endovascular aortic repair (TEVAR) for descending thoracic aortic aneurysm (DTAA) with atherosclerotic/degenerative cause or acute aortic syndrome (AAS), using the Global Registry For Endovascular Aortic Treatment (GREAT). MATERIALS AND METHODS: Patients submitted to TEVAR for AAS or DTAA, included in GREAT, were eligible for this analysis. Primary outcome was 30-day all-cause mortality rate. Secondary outcomes were 30-day aorta-related mortality and re-intervention rate, 1-year and 3-year all-cause mortality, aorta-related mortality and re-intervention rate. RESULTS: Five-hundred and seventy-five patients were analyzed (305 DTAA and 270 AAS). Thirty-day mortality rate was 1.3% and 1.8% for DTAA and AAS, respectively (p=0.741). One-year and 3-year mortality rates were 6.2% versus 9.3 and 17.3% versus 15.9% for DTAA and AAS, respectively (p=0.209 and p=0.655, respectively). Aorta-related mortality rates at 30 days, 1 year and 3 years were 1.3%, 1.3%, and 2.6% for DTAA, 1.8%, 4.2%, and 4.2% for AAS (p=ns). Re-intervention rates at 30 days, 1 year, and 3 years were 1.3%, 4.3%, and 7.5% for DTAA, 3.3%, 8.1%, and 10.7% for AAS (p=ns). Furthermore, a specific analysis with similar outcomes was performed dividing follow-up in 3 periods (1-30 days, 31-365 days, 366-1096 days) and describing mutual differences between 2 groups and temporal trends in each group. CONCLUSION: Patients who underwent TEVAR for DTAA or AAS experienced different mortality and re-intervention rates among years during mid-term follow-up. Although all-cause related deaths within 30 days were TEVAR-related, aorta-related deaths were more common for AAS patients within 1 year. A greater re-intervention rate was described for AAS patients, although only 1 year after TEVAR.

Extensive cell salvage and postoperative outcomes following thoracoabdominal and descending aortic repair.

OBJECTIVE: Cell salvage (CS) reduces intraoperative blood transfusion. However, it may cause deformity of the red blood cells and loss of coagulation factors, which may lead to unwanted sequelae. Thus, we hypothesized that extensive CS would lead to adverse outcomes after descending/thoracoabdominal aortic aneurysm (D/TAAA) repair. METHODS: Between 1991 and 2017, 2012 patients undergoing D/TAAA repair were retrospectively reviewed. After we excluded patients without reported intraoperative CS amount, patients were enrolled in the study (N = 1474) and divided into 2 groups: low CS (salvaged units <40, N = 983) and high CS (salvaged units ≥40, N = 491). Analyses were performed to verify the extensive CS as the risk factor for adverse outcomes. RESULTS: Preoperative demographics showed that the high-CS group had a significantly greater incidence of male patients (72% vs 58%), heritable aortic disease (24% vs 17%), redo (27% vs 20%), greater glomerular filtration rate (mL/min/1.73 m2, 75 vs 66) and more extensive aneurysms (TAAA extent II-IV). The high-CS group had significantly more postoperative complications compared with the low-CS group, including respiratory failure, renal failure, cardiac complications, neurologic deficits, bleeding, and 30-day mortality. Multivariable analysis confirmed high CS was an independent risk factor for renal failure along with long bypass time, older age, and extent of repairs. There was an incremental risk of renal failure and 30-day mortality proportional to salvaged cell unit (P < .001 in both). CONCLUSIONS: Increased salvaged cell units were associated with adverse postoperative outcomes after D/TAAA repairs. Risk of renal failure and mortality increased proportionally to the salvaged cell units.

In-hospital outcomes and long-term survival of women of childbearing age with aortic dissection.

OBJECTIVE: In the present study, we defined the outcomes and effects of pregnancy in a cohort of women of childbearing age with acute aortic dissection (AAD). METHODS: We reviewed our database of AAD to identify all eligible female patients. Women aged <45 years were included. Data on pregnancy timing with respect to the occurrence of dissection, the demographic data, dissection extent, dissection treatment, dissection-related outcomes, overall maternal and fetal mortality, and genetic testing results were analyzed. RESULTS: A total of 62 women aged <45 years had presented to us with AAD from 1999 to 2017. Of the 62 women, 37 (60%) had had a history of pregnancy at AAD. Of these 37 patients, 10 (27%) had had a peripartum aortic dissection, defined as dissection during pregnancy or within 12 months postpartum. Of the 10 AADs, 5 were type A and 5 were type B. Three patients had presented with AAD during pregnancy (one in the second and two in the third trimester). Five patients (50%) had developed AAD in the immediate postpartum period (within 3 months) and two (20%) in the late postpartum period. For the immediate postpartum AADs (<3 months), four of the five patients delivered via cesarean section. Of these 10 peripartum AADs, 3 (30%) had occurred in patients with known Marfan syndrome. In-hospital mortality for those with peripartum AAD was 10% (1 of 10). Fetal mortality was 20% (2 of 10). CONCLUSIONS: The frequency of aortic dissection in women of childbearing age at our institution was low. However, pregnancy might increase the risk of those young women genetically predisposed to dissection events. From these data, this risk appears to be greatest in the immediate postpartum period, even for those who undergo cesarean section. Close clinical and radiographic surveillance is required for all women with suspected aortopathy, especially in the third trimester and early postpartum period.

Effectiveness of Standard Local Anesthetic Bupivacaine and Liposomal Bupivacaine for Postoperative Pain Control in Patients Undergoing Truncal Incisions: A Randomized Clinical Trial.

Importance: Liposomal bupivacaine for pain relief is purported to last 3 days compared with 8 hours with standard bupivacaine. However, its effectiveness is unknown in truncal incisions for cardiothoracic or vascular operations. Objective: To compare the effectiveness of single-administration standard bupivacaine vs liposomal bupivacaine in patients undergoing truncal incisions. Design, Setting, and Participants: This randomized clinical trial enrolled patients undergoing sternotomy, thoracotomy, minithoracotomy, and laparotomy from a single cardiovascular surgery department in an academic medical center between November 2012 and June 2018. The study was powered to detect a Cohen effect size of 0.35 with a power of greater than 80%. Data analysis was performed from July to December 2018. Intervention: Patients were randomized to standard bupivacaine or liposomal bupivacaine. Main Outcomes and Measures: Pain was assessed over 3 postoperative days by the Numeric Rating Scale (NRS). Adjunctive opioids were converted to morphine equivalents units (MEU). NRS scores were compared using Wilcoxon rank-sum (3-day area under the curve) and 2-way nonparametric mixed models (daily scale score) to assess time-by-group interaction. Secondary outcomes included cumulative opioid consumption. Results: A total of 280 patients were analyzed, with 140 in each group (single-administration standard bupivacaine vs liposomal bupivacaine). Mean (SD) age was 60.2 (14.4) years, and 101 of 280 patients (36%) were women. Irrespective of treatment assignment, pain decreased by a mean of approximately 1 point per day over 3 days (ß = -0.87; SE = 0.11; mixed model regression P < .001). Incision type was associated with pain with patients undergoing thoracotomy (including minithoracotomy) reporting highest median (interquartile range [IQR]) pain scores on postoperative days 1 (liposomal vs standard bupivacaine, 6 [4-8] vs 5 [3-7]; P = .049, Wilcoxon rank-sum) and 2 (liposomal vs standard bupivacaine, 5 [4-7] vs 4 [2-6]; P = .003, Wilcoxon rank-sum) but not day 3 (liposomal vs standard bupivacaine, 3 [2-6] vs 3 [1-5]; P = .10, Wilcoxon rank-sum), irrespective of treatment group. Median (IQR) 3-day cumulative NRS was 12.0 (8.0-16.5) for bupivacaine and 13.5 (9.0-17.0) for liposomal bupivacaine (P = .15, Wilcoxon rank-sum) Furthermore, use of opioids was greater following liposomal bupivacaine compared with standard bupivacaine (median [IQR], 41.5 [21.3-73.8] MEU vs 33.0 [17.8-62.5] MEU; P = .03, Wilcoxon rank-sum). On multivariable analysis, no interaction by incision type was observed for mean pain scores or opioid use. Conclusions and Relevance: In this randomized clinical trial involving truncal incisions for cardiovascular procedures, liposomal bupivacaine did not provide improved pain control and did not reduce adjunctive opioid use compared with conventional bupivacaine formulation over 3 postoperative days. Trial Registration: ClinicalTrials.gov Identifier: NCT02111746.

Outcomes of open repairs of chronic distal aortic dissection anatomically amenable to endovascular repairs.

OBJECTIVE: To review short-term outcomes and long-term survival and durability after open surgical repairs for chronic distal aortic dissections in patients whose anatomy was amenable to thoracic endovascular aortic repair (TEVAR). METHODS: Between February 1991 and August 2017, we repaired chronic distal dissections in 697 patients. Of those patients, we enrolled 427 with anatomy amenable to TEVAR, which included 314 descending thoracic aortic aneurysms (DTAAs) and 105 extent I thoracoabdominal aortic aneurysms (TAAAs). One hundred eighty-five patients (44%) had a history of type A dissection, and 33 (7.9%) had a previous DTAA/TAAA repair. Variables were assessed with logistic regression for 30-day mortality and Cox regression for long-term mortality. Time-to-event analysis was performed using Kaplan-Meier methods. RESULTS: Thirty-day mortality was 8.4% (n = 36). In all, 22 patients (5.2%) developed motor deficit (paraplegia/paraparesis), and 17 (4.0%) experienced stroke. Multivariable analysis identified low estimated glomerular filtration rate (eGFR; <60 mL/min/1.73 m2), previous DTAA/TAAA repair, and chronic obstructive pulmonary disease (COPD) as associated with 30-day mortality. Patients without all 3 risk factors had a 30-day mortality rate of 2.6%. During a median follow-up of 6.5 years, 160 patients died. The survival rate was 81% at 1 year and 61% at 10 years. Cox regression analysis identified preoperative aortic rupture, eGFR <60 mL/min/1.73 m2, previous DTAA/TAAA repair, COPD, and age >60 years as predictive of long-term mortality. Forty-five patients required subsequent aortic procedures, including 8 reinterventions to the treated segment. Freedom from any aortic procedures was 85% at 10 years, and aortic procedure-free survival was 45% at 10 years. Hereditary aortic disease was the sole predictor for any aortic interventions (hazard ratio, 3.2; P = .004). CONCLUSIONS: Open surgical repair provided satisfactory low neurologic complication rates and durable repairs in chronic distal aortic dissection. Patients without low eGFR, redo, and COPD are the low-risk surgical candidates and may benefit from open surgical repair at centers with similar experience to ours. Patients with hereditary aortic disease warrant close surveillance.

Resection and replacement of thoracic aortic graft infections.

OBJECTIVES: Thoracic aortic graft infection (TAGI) presents a formidable challenge with high mortality. We evaluated our 22-year experience managing TAGI with extensive debridement, graft replacement, vascularized tissue coverage, and aggressive antibiotics. METHODS: We reviewed all consecutive patients with TAGI from 1991 to 2013. We also compared infected cases versus noninfected reoperative controls using a case-control design. Standard statistical methods were used for descriptive analysis, and Kaplan-Meier for survival analysis. RESULTS: We treated 32 TAGI patients, involving 19 ascending/arch (A/A) and 13 descending/thoracoabdominal (D/TAA) grafts, including 4 endografts. In total, 19 (59.4%) presented with pseudoaneurysm and 11 (34.4%) with aortic fistula. Vascularized tissue (omentum or muscle) coverage was possible in 22 (71.0%) patients. Thirty-day mortality occurred in 3 (9.4%) patients, with no 30-day mortality among those receiving vascularized graft coverage (P = .018). During follow-up, reinfection occurred in 8 patients (25% [4 A/A and 4 D/TAA]). Five-year overall (A/A 45.4% vs D/TAA 28.9%, P = .434) and reinfection-free (A/A 19.2%, D/TAA 27%, P = .409) survival was similar between groups. Long-term mortality was greater after endograft infection (100% vs 25% at 2.5 months, P = .0007) or aortobronchial fistulization (100% vs 37.9% at 6 months, P = .026). Time to reintervention was shorter in infected versus non-infected reoperative cases (31 vs 83 months, P < .0001), but there were no significant differences in long-term mortality after reoperation. CONCLUSIONS: TAGI continues to represent a highly morbid surgical challenge. Prompt antimicrobial coverage, debridement, graft replacement, and vascularized graft coverage, yielded best long-term results. Endograft infection and aortobronchial fistula had very poor prognoses.