Thoracoabdominal aneurysm repair using the Unitary Manifold Device.

OBJECTIVE: To present a single-center prospective study of 126 consecutively treated patients who underwent endovascular repair of a thoracoabdominal aortic aneurysm with the physician-modified, nonanatomic-based Unitary Manifold (UM) device. METHODS: Data were collected from 126 consecutive all-comer patients treated with the physician-modified, nonanatomic-based UM from 2015 to 2023. Treatment was performed at a single center by a single physician under a Physician Sponsored Investigation Exemption G140207. RESULTS: The UM was indicated for repair of all Crawford extents including juxtarenal, pararenal, and short-neck infrarenal aneurysms (<10 mm) in 126 consecutive patients. Patients were not excluded from the study based on presentation, extent of aneurysm or dissection, or history of a spinal cord event. Patients with a thoracoabdominal aortic aneurysm were categorized by Crawford classification: types I and V (3.3%, n = 4), type II (3.3%, n = 4), type III (1%, n = 1), and type IV (93.3%, n = 117). The type IV classification patients were further categorized with 33 (28.2%) true type IV, 68 (58.1%) pararenal or infrarenal, and 16 (13.7%) with dissection. Technical success was 99.2% (n = 125). The most common major adverse event within both 30 days and 365 days of all patients was respiratory failure (11.9%, n = 15, and 13.5%, n = 17, respectively). One patient (0.8%) experienced persistent paraplegia at 365 days. Reintervention for patients at 365 days was 5.6% (n = 7). Of the 444 branches stented, the primary patency rate was remarkably high as only three patients (2.4%) required reintervention due to loss of limb patency within 365 days. Aneurysm enlargement (≥5 mm) occurred in 1.6% (n = 2) patients, and no patients experienced aneurysm rupture. No patients underwent conversion to open repair. The aneurysm-related mortality at 365 days for all patients was 4.0% (n = 5), whereas all-cause mortality was 16.7% (n = 21). Physician-modified endograft device integrity failure was not observed in any patient. CONCLUSIONS: The UM device demonstrated remarkable technical surgical success, treatment success, and device patency rates with very reasonable major adverse events and reintervention rates. This study is the most representative example of the general population in comparison with other studies of off-the-shelf devices, with 126 consecutive all-comer patients with diverse pathologies.

Developing a Translational Team Training Program using the Wisconsin Interventions in Team Science Framework.

The Clinical and Translational Science Awards (CTSA) Program supports a national network of medical research institutions working to improve the translational process. High-performing translational teams (TTs) are critical for advancing evidence-based approaches that improve human health. When focused on content-appropriate knowledge, skills, and attitudes, targeted training results in the substantial internalization of training content, producing new skills that can be applied to improve team outputs, outcomes, and benefits. More rigorous approaches to develop, test, and evaluate interventions are needed, and we used the Wisconsin Interventions in Team Science framework as a model to systematize our efforts. We designed, built, and tested a five-session TT Training Program for translational researchers. The 90-minute sessions were pilot-tested with 47 postdoctoral fellows and evaluated through a structured evaluation plan. Ninety-five percent of post-session survey respondents indicated that the content and skills provided would make them more effective collaborators, and one hundred percent would recommend the sessions to colleagues. Respondents' scores increased from pretest to posttest for most learning outcomes. Refinements from participant feedback are described. This work provides a foundation for the continued evolution of evidence-based training programs in the CTSA environment.

Freelance information management agents: why information management is so hard on translational teams.

Introduction: To conduct high-quality, rigorous research, and advance scientific knowledge, Translational Teams (TTs) engage in information behaviors, including seeking, using, creating, sharing, storing, and retrieving information, in ways specific to the translational context. Currently, little is known about TTs' approach to information management. This qualitative pilot study explored how TTs at the University of Wisconsin-Madison interact with information, as well as the scientific and organizational impact of their interactions. Methods: We conducted interviews with ten members of UW TTs. Interviews were transcribed and thematic analysis was conducted. Results: Four themes emerged: (1) TT members did not recognize the centrality of information or information behaviors to their scientific work; (2) TT members engaged in similar information behaviors and used similar tools across disciplines and topics; (3) TT members did not receive support or guidance from their institution in managing information; and (4) Individualized choices of TT members conflicted at the team level, causing confusion and increasing the potential for data and information loss. Acting as freelance information management agents, TT members made individualized decisions about what tools to use and how to use them, often in a piecemeal manner and without communicating these decisions to other team members. Conclusion: Research institutions should both encourage teams to discuss their information management approaches at the beginning of a project and provide leaders with training on how to have these conversations and what topics should be included. Additionally, institutions can provide researchers with guidelines for using software platforms to help mitigate information management challenges.

Toward a translational team science hierarchy of needs: Exploring the information management challenges of team science.

Background: Clinical and Translational Research (CTR) requires a team-based approach, with successful teams engaging in skilled management and use of information. Yet we know little about the ways that Translational Teams (TTs) engage with information across the lifecycle of CTR projects. This qualitative study explored the challenges that information management imposes on the conduct of team-based CTR. Methods: We conducted interviews with ten members of TTs at University of Wisconsin. Interviews were transcribed and thematic analysis was conducted. Results: TTs' piecemeal and reactive approaches to information management created conflict within the team and slowed scientific progress. The lack of cohesive information management strategies made it more difficult for teams to develop strong team processes like communication, scientific coordination, and project management. While TTs' research was hindered by the institutional challenges of interdisciplinary team information sharing, TTs who had developed shared approaches to information management that foregrounded transparency, accountability, and trust, described substantial benefits to their teamwork. Conclusion: We propose a new model for the Science of Team Science field - a Translational Team Science Hierarchy of Needs - that suggests interventions should be targeted at the appropriate stage of team development in order to maximize a team's scientific potential.

Single-Site Review of Spinal Cord Protection Protocols Including the Utilization of Spinal Drains versus Medical Management with Branched Endovascular Aortic Repair.

BACKGROUND: Spinal cord ischemia (SCI) continues to be a devastating complication after repair of thoracoabdominal aortic aneurysms. The objective of this review is to present our single-center outcomes after the implementation of a standardized neuroprotective protocol following branched endovascular aortic repair. METHODS: A standardized neuroprotective protocol including preoperative steroids, acetazolamide, intraoperative hemodynamic parameters, and postoperative treatment goals was initiated in November 2019. Physician-modified branched endovascular repairs were completed at a single center from 2012 to 2021 with outcomes reviewed both before (n = 107) and after (n = 67) the implementation of the neuroprotective protocol. The primary end point was the incidence of any SCI event at 30 days. Secondary end points included all-cause mortality, stroke, myocardial infarction, and renal failure at 30 days. Patients with Crawford extents I-III, renal failure, or necessitating emergent repair were deemed high risk for SCI events and underwent a subset analysis. Survivability after SCI was estimated using Kaplan-Meier tables. RESULTS: Of the 174 consecutive patients treated, the 67 patients treated following implementation of the neuroprotective protocol were more likely to have experienced a prior myocardial infarction (26.9% vs. 14%; P = 0.0466) and have a history of chronic obstructive pulmonary disease (64.3% vs. 45.8%; P = 0.02). This group was more likely to be treated for paravisceral aneurysms (53.7% vs. 24.3%; P = 0.0002). Postprotocol implementation, spinal drain use was lower (6% vs. 38.3%; P = <0.0001) with 100% of these drains placed in urgent or unstaged thoracoabdominal aortic aneurysm repairs as a part of the protocol. Rates of any SCI event among all patients before and after implementation of the protocol were 9.3% (n = 10 of 107) and 6% (n = 4 of 67; P = 0.57), respectively. In comparison, the protocol significantly reduced SCI rates to 0 (0% vs. 17.1%; P = 0.0407) in high-risk patients. Frequency of renal failure was reduced (3% vs. 14%; P = 0.018) after initiation of the protocol. Patients in the postprotocol group had significantly improved 1-year mortality rate (9% vs. 27.1%; P = 0.0035) and renal failure rates (2% vs. 15%; P = 0.018). Regression models indicated that patients in the postprotocol group had lower likelihood of mortality and renal failure than patients in preprotocol group (P < 0.05) and that spinal drain reduced mortality (P < 0.1). CONCLUSIONS: Implementation of a standardized neuroprotective protocol that focuses on medical management and fluid dynamics may significantly reduce risk of SCI after branched endovascular repairs, with the most significant improvement of SCI outcomes involving those at greatest risk for developing SCI. Also noteworthy, there was significant improvement to 1-year survivability after the implementation of this neuroprotective protocol.

A leadership model supporting maturation of high-performance translational teams.

Despite understanding its impact on organizational effectiveness, practical guidance on how to train translational team (TT) leaders is lacking. Previously, we developed an evolutionary learning model of TT maturation consisting of three goal-directed phases: (1). team assembly (Formation); (2). conducting research (Knowledge Generation); and (3). dissemination and implementation (Translation). At each phase, the team acquires group-level knowledge, skills, and attitudes (KSAs) that enhance its performance. Noting that the majority of team-emergent KSAs are promoted by leadership behaviors, we examine the SciTS literature to identify the relevant behaviors for each phase. We propose that effective team leadership evolves from a hierarchical, transformational model early in team Formation to a shared, functional leadership model during Translation. We synthesized an integrated model of TT leadership, mapping a generic "functional leadership" taxonomy to relevant leadership behaviors linked to TT performance, creating an evidence-informed Leadership and Skills Enhancement for Research (LASER) training program. Empirical studies indicate that leadership behaviors are stable across time; to enhance leadership skills, ongoing reflection, evaluation, and practice are needed. We provide a comprehensive multi-level evaluation framework for tracking the growth of TT leadership skills. This work provides a framework for assessing and training relevant leadership behaviors for high-performance TTs.

Incidence of Acute and Chronic Renal Failure Following Branched Endovascular Repair of Complex Aortic Aneurysms.

BACKGROUND: The purpose of this study was to examine the incidence of acute kidney injury and chronic renal impairment following branched endovascular aneurysm repair (BEVAR) of complex thoracoabdominal aortic aneurysms (TAAA) using the Medtronic Valiant Thoracoabdominal Aortic Aneurysm stent graft system (MVM), the physician-modified Visceral Manifold, and Unitary Manifold stent graft systems. The objective was to report the acute and chronic renal function changes in patients following complex TAAA aneurysm repair. METHODS: This is an analysis of 139 patients undergoing branched endovascular repair for complex TAAAs between 2012 and 2020. Patient renal function was evaluated using serum creatinine and estimated glomerular filtration rate at baseline, 48 hr, discharge, 1 month, 6 months, and annually to 2 years. Patients on dialysis prior to the procedure were excluded from data analysis. RESULTS: A total of 139 patients (mean age 71.13; 64.7% male) treated for TAAA with BEVAR met inclusion criteria and were evaluated. A total of 530 visceral vessels were stented. A majority of patients (n = 131, 94.2%) underwent a single procedure while 8 required staged procedures. Thirty-day, 1-year and 2-year all-cause mortality rates were 5.8%, 25.2%, and 32.4%, respectively. Primary and secondary patency rates at a median follow-up of 26.9 months (95% CI; 21.1 - 32.7) were 96.2% and 97.5% for all vessels and 95.4% and 96.9% for renal arteries, respectively. Postoperative acute kidney injury (AKI) was identified in 22 (15.8%) patients. At discharge, 16 patients (11.6%) had an increase in CKD stage with 3 requiring permanent dialysis. Five additional patients required permanent dialysis over the 2-year follow-up period for a total of 8 (5.8%). Increasing age (HR = 1.0327, P= 0.0477), hemoglobin < 7 prior to procedure (HR = 2.4812, P= 0.0093), increasing maximum aortic diameter (HR = 1.0189, P= 0.0084), presence of AKI (HR = 2.0757, P= 0.0182), and increase in CKD stage (HR = 1.3520, P= 0.002) at discharge were significantly associated with decreased patient survival. CONCLUSIONS: Postoperative AKI and a chronic decline in renal function continue to be problematic in endovascular repair of complex aortic aneurysms. This study found that BEVAR using the manifold configuration resulted in immediate and mid-term renal function that is comparable to similar analyses of branched and/or fenestrated grafts.

Transcriptomic bases of a polyphenism.

Polyphenism-in which multiple distinct phenotypes are produced from a single genotype owing to differing environmental conditions-is commonplace, but its molecular bases are poorly understood. Here, we examine the transcriptomic bases of a polyphenism in Mexican spadefoot toads (Spea multiplicata). Depending on their environment, their tadpoles develop into either a default "omnivore" morph or a novel "carnivore" morph. We compared patterns of gene expression among sibships that exhibited high versus low production of carnivores when reared in conditions that induce the carnivore morph versus those that do not. We found that production of the novel carnivore morph actually involved changes in fewer genes than did the maintenance of the default omnivore morph in the inducing environment. However, only body samples showed this pattern; head samples showed the opposite pattern. We also found that changes to lipid metabolism (especially cholesterol biosynthesis) and peroxisome contents and function might be crucial for establishing and maintaining differences between the morphs. Thus, our findings suggest that carnivore phenotype might have originally evolved following the breakdown of robustness mechanisms that maintain the default omnivore phenotype, and that the carnivore morph is developmentally regulated by lipid metabolism and peroxisomal form, function, and/or signaling. This study also serves as a springboard for further exploration into the nature and causes of plasticity in an emerging model system.

Adaptive Plasticity as a Fitness Benefit of Mate Choice.

Phenotypic plasticity and sexual selection can each promote adaptation in variable environments, but their combined influence on adaptive evolution is not well understood. We propose that sexual selection can facilitate adaptation in variable environments when individuals prefer mates that produce adaptively plastic offspring. We develop this hypothesis and review existing studies showing that diverse groups display both sexual selection and plasticity in nonsexual traits. Thus, plasticity could be a widespread but unappreciated benefit of mate choice. We describe methods and opportunities to test this hypothesis and describe how sexual selection might foster the evolution of phenotypic plasticity. Understanding this interplay between sexual selection and phenotypic plasticity might help predict which species will adapt to a rapidly changing world.

Combination of mural thrombus and age improves the identification of all-cause mortality following branched endovascular repair.

BACKGROUND: In-hospital and 30-day mortality rates of endovascular repair of thoracoabdominal aortic aneurysms shows a significant improvement over open surgery, although we are not seeing a significant difference at 1 year. We assess the hypothesis that a greater mural thrombus ratio within the aorta could function as an indicator of postoperative mortality. METHODS: The mural thrombus ratio and preoperative comorbidities of 100 consecutive patients from a single center undergoing endo-debranching between 2012 and 2019 were evaluated. Logistic regression, survival analysis, and decision tree methods were used to examine each variable's association with death at 1 year. RESULTS: At the time of analysis, 73 subjects had 1-year outcomes and adequate imaging to assess the parameters. At 1 year, the overall survival for all subjects was 71.2% (21 died, 52 survived). For patients with a favorable mural thrombus ratio (n = 36), the overall 1-year survival was 86.1% (5 died, 31 survived). The subjects with an unfavorable mural thrombus ratio (n = 37), had an overall 1 year survival of 56.8% (16 died, and 21 survived). The only preoperative mortality factor that was statistically significant between the subjects with an unfavorable mural thrombus ratio was age of the patient. The survival for subjects 75 years and older with an unfavorable mural thrombus ratio was 90% (one died, nine survived) vs only 44.4% survival for subjects less than 75 years with an unfavorable mural thrombus ratio (15 died, 12 survived). CONCLUSIONS: This study examined whether a patient's mural thrombus ratio may be an indicator of 1-year survival. These findings suggest that the combination of a patient's aortic mural thrombus ratio and age can function as a preoperative indicator of their underlying cardiac reserve. Identifying patients with low cardiac reserve and fitness to handle the increased cardiac demands owing to the physiologic response to extensive aortic stent grafting before undergoing aortic repair may allow for modification of preoperative patient counseling and postoperative care guidelines to better treat this patient population.

A novel physician-assembled endograft for the repair of pararenal, paravisceral, Crawford type IV thoracoabdominal aortic aneurysms, and aneurysms requiring treatment after prior repair.

OBJECTIVE: In the present study, we reviewed the 30-day and 1-year clinical results of the use of the investigational unitary manifold (UM) stent graft system (Sanford Health, Sioux Falls SDak) for the repair of Crawford type IV, pararenal, paravisceral, juxtarenal, and short-neck infrarenal aneurysms (<10 mm). METHODS: The present study was a single-center, multiarm, prospective review of the first 44 patients who had undergone repair of Crawford type IV, pararenal, juxtarenal, and short-neck infrarenal aneurysms (<10 mm) using the physician-modified UM under a physician-sponsored investigational device exemption. The primary end point was freedom from major adverse events at 30 days, including all-cause mortality, myocardial infarction, stroke, paraplegia, bowel ischemia, respiratory failure, and renal failure. RESULTS: Technical success was achieved in all 44 patients (100%), with a large number of these patients having undergone previous aortic repair (20 of 44; 45.5%). All the intended 170 visceral vessels (100%) had been successfully cannulated and stent grafted. No episodes of paraplegia or in-hospital deaths were recorded. One patient had died of aneurysm-related ischemic stroke (2.3%). The rate of transient nonclinically significant spinal cord ischemia was 4.5%. At the last follow-up, one reintervention had been required owing to branch patency from a thrombotic event. Of the 170 bridging stent grafts, 169 have remained patent through a mean follow-up of 8.8 months (range, 0-36 months). No type I or III endoleaks, migration, or component separation in the investigational device has occurred. CONCLUSIONS: The early and midterm results with the use of the UM suggest it could be a viable option for the repair of Crawford type IV, pararenal, paravisceral, juxtarenal, and short-neck infrarenal aneurysms (<10 mm) without exposing patients to the increased risk of permanent spinal cord ischemia, renal failure, visceral vessel ischemia, or aneurysm-related mortality that results from open thoracoabdominal aortic aneurysm repair. The high technical success rate, in native and previous repairs, supports the utility of this device as a bail-out technique for failed endovascular aneurysm repair or proximal extension of disease after previous aortic repair. However, experience is limited, and this approach requires further study before widespread adoption.

Male sexual signal predicts phenotypic plasticity in offspring: implications for the evolution of plasticity and local adaptation.

In a rapidly changing world, understanding the processes that influence a population's ability to respond to natural selection is critical for identifying how to preserve biodiversity. Two such processes are phenotypic plasticity and sexual selection. Whereas plasticity can facilitate local adaptation, sexual selection potentially impedes local adaptation, especially in rapidly changing or variable environments. Here we hypothesize that, when females preferentially choose males that sire plastic offspring, sexual selection can actually facilitate local adaptation to variable or novel environments by promoting the evolution of adaptive plasticity. We tested this hypothesis by evaluating whether male sexual signals could indicate plasticity in their offspring and, concomitantly, their offspring's ability to produce locally adapted phenotypes. Using spadefoot toads ( Spea multiplicata) as our experimental system, we show that a male sexual signal predicts plasticity in his offspring's resource-use morphology. Specifically, faster-calling males (which are preferred by females) produce more plastic offspring; such plasticity, in turn, enables these males' offspring to respond adaptively to the spadefoots' highly variable environment. The association between a preferred male signal and adaptive plasticity in his offspring suggests that female mate choice can favour the evolution and maintenance of phenotypic plasticity and thereby foster adaptation to a variable environment. This article is part of the theme issue 'The role of plasticity in phenotypic adaptation to rapid environmental change'.

A novel endovascular debranching technique using physician-assembled endografts for repair of thoracoabdominal aneurysms.

OBJECTIVE: The objective of this study was to demonstrate a technique that uses physician-assembled endografts to make use of the benefits of parallel grafts while also providing for circumferential seal and fixation in repair of thoracoabdominal aneurysms in inoperable patients. METHODS: A single-center all-comers retrospective analysis of 14 patients was performed that looked at the early outcomes of patients treated for thoracoabdominal aneurysms. Three Crawford type II, four type III, four type IV, and three type V thoracoabdominal aneurysms were treated. Contrast material, fluoroscopy time, length of stay, clinical success, and technical success were measured. RESULTS: There was no in-hospital, 30-day, or 6-month mortality. We found two type III endoleaks in the early design. One required coil embolization. Average volume of contrast material and average fluoroscopy time were 76.9 mL and 119.1 minutes, respectively. Average length of stay was 10.5 days, and average procedure time was 251.2 minutes. Clinical success was observed in 78.6% of patients to date, and technical success was observed in 85.7% of patients. CONCLUSIONS: Short-term results show that this approach is safe. The device can be safely implanted, is off-the-shelf, and can treat each of the Crawford thoracoabdominal aneurysm types. Finally, the assembly of off-the-shelf components may shorten the regulatory path for this physician-assembled endograft.