Identifying barriers and facilitators to follow-up after endovascular aortic repair (EVAR): Qualitative study design and protocol.

Endovascular aortic repair (EVAR) is now first line therapy for most patients with abdominal aortic aneurysms (AAA) as it reduces perioperative morbidity and mortality compared to open surgery. However, up to 40 % of patients do not undergo recommended follow-up, increasing risk of subsequent rupture. Risk factors for loss to follow-up have been studied retrospectively, however, qualitative studies assessing perceived barriers and facilitators to follow-up have not been performed and there are few qualitative protocols within the vascular surgery literature. This article presents a qualitative descriptive study protocol aimed at understanding and improving post-operative follow-up adherence after EVAR developed through an iterative process based on the Theoretical Domains Framework of behavior change. Steps include:•Selection of target behavior and study design•Development of study materials, sampling/recruitment strategy, and data collection•Qualitative data analysis and reporting findingsWe demonstrate the feasibility of this study by pilot testing of the semi-structured interview guides on a small group of patients, healthcare providers, and key personnel. This protocol aims to describe key stakeholder experiences within the healthcare system that will ultimately serve as the basis for future multi-institutional research piloting intervention strategies to improve EVAR follow-up.

Markers of optimal medical therapy are associated with improved limb outcomes after elective revascularization for intermittent claudication.

BACKGROUND: Optimal medical therapy (OMT) is a modifiable factor that decreases mortality and cardiovascular events in patients with severe peripheral arterial disease. We hypothesized that preintervention OMT would be associated with improved 1-year reintervention and major adverse limb event (MALE) rates after elective endovascular revascularization for intermittent claudication (IC). METHODS: Using the Vascular Quality Initiative (2010-2020), we identified patients with IC undergoing elective endovascular, hybrid, and open surgical interventions. Preoperative antiplatelet, statin, and nonsmoking status defined OMT components and created three groups: complete (all components), partial (1-2 components), and no OMT. The primary outcome was 1-year reintervention. Secondary outcomes included MALE and factors associated with OMT usage. Multivariable logistic regression generated adjusted odds ratios (aOR). RESULTS: There were 39,088 patients (14,907 [38.1%] complete, 22,054 [56.4%)] partial, 2127 [5.4%] no OMT) who met our criteria. Patients with any OMT were more frequently older with more cardiovascular diseases and diabetes (P < .0001). Patients without OMT were more likely to be Black or with Medicare or Medicaid (P < .05). Observed 1-year reintervention (5.3% complete OMT, 6.1% partial OMT, 8.3% no OMT; P < .001) and MALE (5.6% complete OMT, 6.3% partial OMT, 8.8% no OMT; P < .001) were decreased by partial or complete OMT compared with no OMT. Complete OMT significantly decreased the adjusted odds of reintervention and MALE by 28% (aOR, 0.72, 95% confidence interval [95% CI], 0.59-0.88) and 30% (aOR, 0.70; 95% CI, 0.58-0.85), respectively, compared with no OMT. Partial OMT decrease the adjusted odds of reintervention and MALE by 24% (aOR, 0.76; 95% CI, 0.63-0.92) and 26% (aOR, 0.74; 95% CI, 0.62-0.89), respectively. CONCLUSIONS: Preintervention OMT is an underused, modifiable risk factor associated with improved 1-year reintervention and MALE. Vascular surgeons are uniquely positioned to initiate and maintain OMT in patients with IC before revascularization to optimize patient outcomes.

Contemporary National Incidence and Outcomes of Acute Limb Ischemia.

BACKGROUND: Acute limb ischemia (ALI) is a morbid and deadly diagnosis. However, existing epidemiologic studies describing ALI predate the introduction of the Affordable Care Act in 2010 and direct oral anticoagulants in 2011. Thus, we synergized the National Inpatient Sample (NIS) and United States Census to define contemporary trends in the incidence, treatment, and outcomes of ALI in the US. METHODS: We included emergent admissions of adults with primary diagnosis of lower extremity ALI in survey-weighted NIS data (2005-2020). Mann-Kendal trend test evaluated ALI incidence (primary outcome), anticoagulation usage, insurance coverage, revascularization type, and in-hospital amputation/death. Multivariable logistic regression quantified covariate associations with in-hospital amputation/death. RESULTS: Of the 582,322,862 estimated hospitalizations in the NIS, 227,440 met the inclusion criteria (mean age 68.80 years, 49.94% women, 76.66% White). ALI incidence peaked in 2006 (7.16/100,000 person-years) but has declined since 2015 to 4.16/100,000 person-years in 2020 (ptrend = 0.008). Endovascular revascularization, anticoagulation, and Medicaid coverage increased, while self-pay insurance decreased (ptrend < 0.05). Amputation rates significantly decreased from 8.04 to 6.54% (ptrend = 0.01) while death rate remained at 5.59% (ptrend = 0.16) over the study period. Prehospitalization anticoagulation was associated with decreased amputation (adjusted odds ratio [aOR] = 0.74 (95% confidence interval [CI] 0.65-0.84)) and death (aOR = 0.50 (95% CI 0.43-0.57)). When controlling for covariates, women had a higher risk of death (aOR = 1.17 (95% CI 1.07-1.27), P < 0.0001), while Black patients had a higher risk of amputation (aOR = 1.24 (95% CI 1.10-1.41), P < 0.0001). CONCLUSIONS: Our US population based epidemiological study demonstrates that ALI incidence and in-hospital amputation rates are decreasing, while mortality remains unchanged. We further highlight the ongoing need for ALI investigation specifically as it relates to access to care, antithrombotic therapy use, treatment strategy, and strategies to combat gender and racial disparities.

The association between frailty and outcomes following ruptured abdominal aortic aneurysm repair.

OBJECTIVE: Endovascular aortic repair (EVAR) is a less invasive method than the more physiologically stressful open surgical repair (OSR) for patients with anatomically appropriate abdominal aortic aneurysms (AAAs). Early postoperative outcomes are associated with both patients; physiologic reserve and the physiologic stresses of the surgical intervention. Among frail patients with reduced physiologic reserve, the stress of an aortic rupture in combination with the stress of an operative repair are less well tolerated, raising the risk of complications and mortality. This study aims to evaluate the difference in association between frailty and outcomes among patients undergoing minimally invasive EVAR and the physiologically more stressful OSR for ruptured AAAs (rAAAs). METHODS: Our retrospective cohort study included adults undergoing rAAA repair in the Vascular Quality Initiative from 2010 to 2022. The validated Risk Analysis Index (RAI) (robust, ≤20; normal, 21-29; frail, 30-39; very frail, ≥40) quantified frailty. The association between the primary outcome of 1-year mortality and frailty status as well as repair type were compared using multivariable Cox models generating adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Interaction terms evaluated the association's moderation. RESULTS: We identified 5806 patients (age, 72 ± 9 years; 77% male; EVAR, 65%; robust, 6%; normal, 48%; frail, 36%; very, frail 10%) with a 53% observed 1-year mortality rate following rAAA repair. OSR (aHR, 1.43; 95% CI, 1.19-1.73) was associated with increased 1-year mortality when compared with EVAR. Increasing frailty status (frail aHR, 1.26; 95% CI, 1.00-1.59; very frail aHR, 1.64; 95% CI, 1.26-2.13) was associated with increased 1-year mortality, which was moderated by repair type (P-interaction < .05). OSR was associated with increased 1-year mortality in normal (aHR, 1.49; 95% CI, 1.20-1.87) and frail (aHR, 1.51; 95% CI, 1.20-1.89), but not among robust (aHR, 0.88; 95% CI, 0.59-1.32) and very frail (aHR, 1.29; 95% CI, 0.97-1.72) patients. CONCLUSIONS: Frailty and OSR were associated with increased adjusted risk of 1-year mortality following rAAA repair. Among normal and frail patients, OSR was associated with an increased adjusted risk of 1-year mortality when compared with EVAR. However, there was no difference between OSR and EVAR among robust patients who can well tolerate the stress of OSR and among very frail patients who are unable to withstand the surgical stress from rAAA regardless of repair type.

Percutaneous thrombectomy for acute limb ischemia is associated with equivalent limb and mortality outcomes compared with open thrombectomy.

BACKGROUND: Acute limb ischemia (ALI) carries a 15% to 20% risk of combined death or amputation at 30 days and 50% to 60% at 1 year. Percutaneous mechanical thrombectomy (PT) is an emerging minimally invasive alternative to open thrombectomy (OT). However, ALI thrombectomy cases are omitted from most quality databases, limiting comparisons of limb and survival outcomes between PT and OT. Therefore, our aim was to compare in-hospital outcomes between PT and OT using the National Inpatient Sample. METHODS: We analyzed survey-weighted National Inpatient Sample data (2015-2020) to include emergent admissions of aged adults (50+ years) with a primary diagnosis of lower extremity ALI undergoing index procedures within 2 days of hospitalization. We excluded hospitalizations with concurrent trauma or dissection diagnoses and index procedures using catheter-directed thrombolysis. Our primary outcome was composite in-hospital major amputation or death. Secondary outcomes included in-hospital major amputation, death, in-hospital reintervention (including angioplasty/stent, thrombolysis, PT, OT, or bypass), and extended length of stay (eLOS; defined as LOS >75th percentile). Adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs) were generated by multivariable logistic regression, adjusting for demographics, frailty (Risk Analysis Index), secondary diagnoses including atrial fibrillation and peripheral artery disease, hospital characteristics, and index procedure data including the anatomic thrombectomy level and fasciotomy. A priori subgroup analyses were performed using interaction terms. RESULTS: We included 23,795 survey-weighted ALI hospitalizations (mean age: 72.2 years, 50.4% female, 79.2% White, and 22.3% frail), with 7335 (30.8%) undergoing PT. Hospitalization characteristics for PT vs OT differed by atrial fibrillation (28.7% vs 36.5%, P < .0001), frequency of intervention at the femoropopliteal level (86.2% vs 88.8%, P = .009), and fasciotomy (4.8% vs 6.9%, P = .006). In total, 2530 (10.6%) underwent major amputation or died. Unadjusted (10.1% vs 10.9%, P = .43) and adjusted (aOR = 0.96 [95% CI, 0.77-1.20], P = .74) risk did not differ between the groups. PT was associated with increased odds of reintervention (aOR = 2.10 [95% CI, 1.72-2.56], P < .0001) when compared with OT, but this was not seen in the tibial subgroup (aOR = 1.31 [95% CI, 0.86-2.01], P = .21, Pinteraction < .0001). Further, 79.1% of PT hospitalizations undergoing reintervention were salvaged with endovascular therapy. Lastly, PT was associated with significantly decreased odds of eLOS (aOR = 0.80 [95% CI, 0.69-0.94], P = .005). CONCLUSIONS: PT was associated with comparable in-hospital limb salvage and mortality rates compared with OT. Despite an increased risk of reintervention, most PT reinterventions avoided open surgery, and PT was associated with a decreased risk of eLOS. Thus, PT may be an appropriate alternative to OT in appropriately selected patients.

Hypertension during transfer is associated with poor outcomes in unstable patients with ruptured abdominal aortic aneurysm.

OBJECTIVE: Limited data exist for optimal blood pressure (BP) management during transfer of patients with ruptured abdominal aortic aneurysm (rAAA). This study evaluates the effects of hypertension and severe hypotension during interhospital transfers in a cohort of patients with rAAA in hemorrhagic shock. METHODS: We performed a retrospective, single-institution review of patients with rAAA transferred via air ambulance to a quaternary referral center for repair (2003-2019). Vitals were recorded every 5 minutes in transit. Hypertension was defined as a systolic BP of ≥140 mm Hg. The primary cohort included patients with rAAA with hemorrhagic shock (≥1 episode of a systolic BP of <90 mm Hg) during transfer. The primary analysis compared those who experienced any hypertensive episode to those who did not. A secondary analysis evaluated those with either hypertension or severe hypotension <70 mm Hg. The primary outcome was 30-day mortality. RESULTS: Detailed BP data were available for 271 patients, of which 125 (46.1%) had evidence of hemorrhagic shock. The mean age was 74.2 ± 9.1 years, 93 (74.4%) were male, and the median total transport time from helicopter dispatch to arrival at the treatment facility was 65 minutes (interquartile range, 46-79 minutes). Among the cohort with shock, 26.4% (n = 33) had at least one episode of hypertension. There were no significant differences in age, sex, comorbidities, AAA repair type, AAA anatomic location, fluid resuscitation volume, blood transfusion volume, or vasopressor administration between the hypertensive and nonhypertensive groups. Patients with hypertension more frequently received prehospital antihypertensives (15% vs 2%; P = .01) and pain medication (64% vs 24%; P < .001), and had longer transit times (36.3 minutes vs 26.0 minutes; P = .006). Episodes of hypertension were associated with significantly increased 30-day mortality on multivariable logistic regression (adjusted odds ratio [aOR], 4.71; 95% confidence interval [CI], 1.54-14.39; P = .007; 59.4% [n = 19] vs 40.2% [n = 37]; P = .01). Severe hypotension (46%; n = 57) was also associated with higher 30-day mortality (aOR, 2.82; 95% CI, 1.27-6.28; P = .01; 60% [n = 34] vs 32% [n = 22]; P = .01). Those with either hypertension or severe hypotension (54%; n = 66) also had an increased odds of mortality (aOR, 2.95; 95% CI, 1.08-8.11; P = .04; 58% [n = 38] vs 31% [n = 18]; P < .01). Level of hypertension, BP fluctuation, and timing of hypertension were not significantly associated with mortality. CONCLUSIONS: Hypertensive and severely hypotensive episodes during interhospital transfer were independently associated with increased 30-day mortality in patients with rAAA with shock. Hypertension should be avoided in these patients, but permissive hypotension approaches should also maintain systolic BPs above 70 mm Hg whenever possible.

Characterization of multiple organ failure after ruptured abdominal aortic aneurysm repair.

BACKGROUND: Multiple organ failure (MOF) is associated with poor outcomes and increased mortality in sepsis and trauma. There are limited data regarding MOF in patients after ruptured abdominal aortic aneurysm (rAAA) repair. We aimed to identify the contemporary prevalence and characteristics of patients with rAAA with MOF. METHODS: We retrospectively reviewed patients with rAAA who underwent repair (2010-2020) at our multihospital institution. Patients who died within the first 2 days after repair were excluded. MOF was quantified by modified (excluding hepatic system) Denver, Sequential Organ Failure Assessment (SOFA) score, and Multiple Organ Dysfunction Score (MODS) for postoperative days 3 to 5 to determine the prevalence of MOF. MOF was defined as a Denver score of >3, dysfunction in two or more organ systems by SOFA score, or a MODS score of >8. Kaplan-Meier curves and log-rank testing were used to evaluate differences in 30-day mortality between multiple organ failure and patients without MOF. Logistic regression was used to assess predictors of MOF. RESULTS: Of 370 patients with rAAA, 288 survived past two days (mean age, 73±10.1 years; 76.7% male; 44.1% open repair), and 143 had data for MOF calculation recorded. From postoperative days 3 to 5, 41 (14.24%) had MOF by Denver, 26 (9.03%) by SOFA, and 39 (13.54%) by MODS criteria. Among these scoring systems, pulmonary and neurological systems were impacted most commonly. Among patients with MOF, pulmonary derangement occurred in 65.9% (Denver), 57.7% (SOFA), and 56.4% (MODS). Similarly, neurological derangement occurred in 92.3% (SOFA) and 89.7% (MODS), but renal derangement occurred in 26.8% (Denver), 23.1% (SOFA), and 10.3% (MODS). MOF by all three scoring systems was associated with increased 30-day mortality (Denver: 11.3% vs 41.5% [P < .01]; DOFA: 12.6% vs 46.2% [P < .01]; MODS: 12.5% vs 35.9% [P < .01]), as was MOF by any criteria (10.8% vs 35.7 %; P < .01). Patients with MOF were more likely to have a higher body mass index (55.9±26.6 vs 49.0±15.0; P = .011) and to have had a preoperative stroke (17.9% vs 6.0%; P = .016). Patients with MOF were less likely to have undergone endovascular repair (30.4% vs 62.1%; P < .001). Endovascular repair was protective against MOF (any criteria) on multivariate analysis (odds ratio, 0.23; 95% confidence interval, 0.08-0.64; P = .019) after adjusting for age, gender, and presenting systolic blood pressure. CONCLUSIONS: MOF occurred in only 9% to 14% of patients after rAAA repair, but was associated with a three-fold increase in mortality. Endovascular repair was associated with a reduced MOF incidence.

Selective Publication within Vascular Surgery: Characteristics of Discontinued and Unpublished Randomized Clinical Trials.

BACKGROUND: Discontinued and unpublished randomized clinical trials (RCTs) are common resulting in biased publication and loss of potential knowledge. The magnitude of selective publication within vascular surgery remains unknown. METHODS: RCT relevant to vascular surgery registered (01/01/2010-10/31/2019) on ClinicalTrials.gov were included. Trials ending normally with conclusion of participant treatment and examination were considered completed whereas discontinued trials stopped early. Publications were identified through automatically indexed PubMed citations on ClinicalTrials.gov or manually identified on PubMed or Google Scholar >30 months after the completion date, the date the final participant was examined, allowing time for publication. RESULTS: Of 108 RCT (n = 37, 837), 22.2% (24/108) were discontinued, including 16.7% (4/24) stopped prior to and 83.3% (20/24) after starting enrollment. Only 28.4% of estimated enrollment was achieved for all discontinued RCT. Nineteen (79.2%) investigators provided a reason for discontinuation, which most commonly included poor enrollment (45.8%), inadequate supplies or funding (12.5%), and trial design concerns (8.3%). Of the 20 trials terminated following enrollment, 20.0% (4/20) were published in peer-reviewed journals and 80.0% (16/20) failed to reach publication. Of the 77.8% trials completed, 75.0% (63/84) were published and 25.0% (21/84) remain unpublished. In a multivariate regression of completed trials, industry funding was significantly associated with decreased likelihood of peer-reviewed publication (OR = 0.18, (95% CI 0.05-0.71), P = 0.01). Of the discontinued and completed trials remaining unpublished, 62.5% and 61.9% failed to report results on ClinicalTrials.gov, respectively, encompassing a total of 4,788 enrollees without publicly available results. CONCLUSIONS: Nearly 25% of registered vascular RCT were discontinued. Of completed RCT, 25% remain unpublished with industry funding associated with decreased likelihood of publication. This study identifies opportunities to report all findings for completed and discontinued vascular surgery RCT, whether industry sponsored, or investigator initiated.

Crimped fiber composites: mechanics of a finite-length crimped fiber embedded in a soft matrix.

Composites comprising crimped fibers of finite length embedded in a soft matrix have the potential to mimic the strain-hardening behavior of tissues containing fibrous collagen. Unlike continuous fiber composites, such chopped fiber composites would be flow-processable. Here, we study the fundamental mechanics of stress transfer between a single crimped fiber and the embedding matrix subjected to tensile strain. Finite element simulations show that fibers with large crimp amplitude and large relative modulus straighten significantly at small strain without bearing significant load. At large strain, they become taut and hence bear increasing load. Analogous to straight fiber composites, there is a region near the ends of each fiber which bears much lower stress than the midsection. We show that the stress-transfer mechanics can be captured by a shear lag model where the crimped fiber can be replaced with an equivalent straight fiber whose effective modulus is lower than that of the crimped fiber, but increases with applied strain. This allows estimating the modulus of a composite at low fiber fraction. The degree of strain hardening and the strain needed for strain hardening can be tuned by changing relative modulus of the fibers and the crimp geometry.

Assessing the Prevalence of Medical Optimization Therapy in Vascular Surgery Clinics.

This cross-sectional study uses checklist data to assess optimal medical therapy prescribed for veterans with atherosclerotic cardiovascular disease.

MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC): randomized clinical trial protocol.

BACKGROUND: Peripheral artery disease (PAD) affects over 230 million people worldwide and is due to systemic atherosclerosis with etiology linked to chronic inflammation, hypertension, and smoking status. PAD is associated with walking impairment and mobility loss as well as a high prevalence of coronary and cerebrovascular disease. Intermittent claudication (IC) is the classic presenting symptom for PAD, although many patients are asymptomatic or have atypical presentations. Few effective medical therapies are available, while surgical and exercise therapies lack durability. Metformin, the most frequently prescribed oral medication for Type 2 diabetes, has salient anti-inflammatory and promitochondrial properties. We hypothesize that metformin will improve function, retard the progression of PAD, and improve systemic inflammation and mitochondrial function in non-diabetic patients with IC. METHODS: 200 non-diabetic Veterans with IC will be randomized 1:1 to 180-day treatment with metformin extended release (1000 mg/day) or placebo to evaluate the effect of metformin on functional status, PAD progression, cardiovascular disease events, and systemic inflammation. The primary outcome is 180-day maximum walking distance on the 6-min walk test (6MWT). Secondary outcomes include additional assessments of functional status (cardiopulmonary exercise testing, grip strength, Walking Impairment Questionnaires), health related quality of life (SF-36, VascuQoL), macro- and micro-vascular assessment of lower extremity blood flow (ankle brachial indices, pulse volume recording, EndoPAT), cardiovascular events (amputations, interventions, major adverse cardiac events, all-cause mortality), and measures of systemic inflammation. All outcomes will be assessed at baseline, 90 and 180 days of study drug exposure, and 180 days following cessation of study drug. We will evaluate the primary outcome with linear mixed-effects model analysis with covariate adjustment for baseline 6MWT, age, baseline ankle brachial indices, and smoking status following an intention to treat protocol. DISCUSSION: MOBILE IC is uniquely suited to evaluate the use of metformin to improve both systematic inflammatory responses, cellular energetics, and functional outcomes in patients with PAD and IC. TRIAL REGISTRATION: The prospective MOBILE IC trial was publicly registered (NCT05132439) November 24, 2021.

Effect of a Decision Aid on Agreement Between Patient Preferences and Repair Type for Abdominal Aortic Aneurysm: A Randomized Clinical Trial.

Importance: Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair. Objective: To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive. Design, Setting, and Participants: In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021. Interventions: Presurgical consultation using a decision aid vs usual care. Main Outcomes and Measures: The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios. Results: Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70). Conclusions and Relevance: Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT03115346.

Updated research priorities of the Society for Vascular Surgery.

In 2011, the Society for Vascular Surgery (SVS) prepared a set of clinical research priorities through a survey of its membership. These priorities were developed with the goal of enhancing clinical research to improve care for vascular patients. In the subsequent decade, several of these priorities served as the focus of clinical trials and significant research efforts. It was understood from the outset that this list of priorities represented a starting point with the intention that they be reevaluated at suitable intervals. In 2021, the SVS Research Council set out to update the research priorities by surveying the SVS membership and engaged a panel of subject matter experts. This process resulted in an updated set of vascular research priorities that more clearly align with current areas of emphasis. Our priorities remain focused on basic areas including aortic disease, carotid disease, lower extremity arterial disease, venous disease, dialysis access, and medical management of vascular disease, along with the topic of health care disparities. The 10 updated priorities reported herein reflect our increasing awareness of the need to understand vascular disease pathogenesis and prevention in the context of a diverse patient population. Importantly, patient-centered outcomes and personalized vascular care are at the core of these updated priorities. Similar to the aims of the original 2011 clinical research priorities, our hope is that this updated list will help to drive large-scale investigations that will improve how we care for our vascular patients.

Association Between Time to Source Control in Sepsis and 90-Day Mortality.

Importance: Rapid source control is recommended to improve patient outcomes in sepsis. Yet there are few data to guide how rapidly source control is required. Objective: To determine the association between time to source control and patient outcomes in community-acquired sepsis. Design, Setting, and Particpants: Multihospital integrated health care system cohort study of hospitalized adults (January 1, 2013, to December 31, 2017) with community-acquired sepsis as defined by Sepsis-3 who underwent source control procedures. Follow-up continued through January 1, 2019, and data analyses were completed March 17, 2022. Exposures: Early (<6 hours) compared with late (6-36 hours) source control as well as each hour of source control delay (1-36 hours) from sepsis onset. Main Outcomes and Measures: Multivariable models were clustered at the level of hospital with adjustment for patient factors, sepsis severity, resource availability, and the physiologic stress of procedures generating adjusted odds ratios (aOR) and 95% CI. Results: Of 4962 patients with sepsis (mean [SD] age, 62 [16] years; 52% male; 85% White; mean [SD] Sequential Organ Failure Assessment score, 3.8 [2.5]), source control occurred at a median (IQR) of 15.4 hours (5.5-21.7) after sepsis onset, with 1315 patients (27%) undergoing source control within 6 hours. The crude 90-day mortality was similar for early and late source control (n = 177 [14%] vs n = 529 [15%]; P = .35). In multivariable models, early source control was associated with decreased risk-adjusted odds of 90-day mortality (aOR, 0.71; 95% CI, 0.63-0.80). This association was greater among gastrointestinal and abdominal (aOR, 0.56; 95% CI, 0.43-0.80) and soft tissue interventions (aOR, 0.72; 95% CI, 0.55-0.95) compared with orthopedic and cranial interventions (aOR, 1.33; 95% CI, 0.96-1.83; P < .001 for interaction). Conclusions and Relevance: Source control within 6 hours of community-acquired sepsis onset was associated with a reduced risk-adjusted odds of 90-day mortality. Prioritizing the rapid identification of septic foci and initiation of source control interventions can reduce the number of avoidable deaths among patients with sepsis.

Characterization of immediate and early mortality after repair of ruptured abdominal aortic aneurysm.

BACKGROUND: We sought to compare immediate and early mortality among patients undergoing ruptured abdominal aortic aneurysm (RAAA) repair. Evaluation of RAAA has focused on 30-day postoperative mortality. Other emergency conditions such as trauma have demonstrated a multimodal mortality distribution within the 30-day window, expanding the pathophysiologic understanding and allowing for intervention investigations with practice changing and lifesaving results. However, the temporal distribution and risk factors of postoperative morbidity and mortality in RAAA have yet to be investigated. METHODS: We evaluated factors associated with RAAA postoperative mortality in immediate (<1 day) and early (1-30 days) postoperative periods in a landmarked retrospective cohort study using data from the Vascular Quality Initiative (2010-2020). RESULTS: We identified 5157 RAAA repairs (mean age, 72 ± 10 years; 77% male; 88% White; 61% endovascular). The mortality rate in the immediate period was 10.2% (528/5157) and the early mortality rate was 22.1% (918/4163). In multivariable regression analyses, signs of hemorrhagic shock (ie, hemoglobin <7 g/dL: adjusted odds ratio [aOR], 1.87 [95% confidence interval [CI], 1.14-3.06]; any preoperative systolic blood pressure <70 mm Hg: aOR, 1.40 [95% CI, 1.04-1.89]; and estimated blood loss >40%: aOR, 3.65 [95% CI, 2.29-5.83]) were associated with an increased risk of immediate mortality. Comorbid conditions (heart failure: aOR, 1.38 [95% CI, 1.00-1.92]; pulmonary disease: aOR, 1.29 [95% CI, 1.05-1.58]; elevated creatinine: aOR 1.26 [95% CI, 1.31-1.41]) were associated with increased risk of early mortality. CONCLUSIONS: Immediate deaths were associated predominantly with shock from massive hemorrhage, whereas early deaths were associated with comorbid conditions predisposing patients to multisystem organ failure despite successful repair. These temporal distinctions should guide future mechanistic and intervention evaluations to improve RAAA mortality.

Factors associated with preference of choice of aortic aneurysm repair in the PReference for Open Versus Endovascular repair of AAA (PROVE-AAA) study.

OBJECTIVE: Patients can choose between open repair and endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). However, the factors associated with patient preference for one repair type over another are not well-characterized. Here we assess the factors associated with preference of choice for open or endovascular AAA repair among veterans exposed to a decision aid to help with choosing surgical treatment. METHODS: Across 12 Veterans Affairs hospitals, veterans received a decision aid covering domains including patient information sources and understanding preference. Veterans were then given a series of surveys at different timepoints examining their preferences for open versus endovascular AAA repair. Questions from the preference survey were used in analyses of patient preference. Results were analyzed using χ2 tests. A logistic regression analysis was performed to assess factors associated with preference for open repair or preference for EVAR. RESULTS: A total of 126 veterans received a decision aid informing them of their treatment choices, after which 121 completed all preference survey questions; five veterans completed only part of the instruments. Overall, veterans who preferred open repair were typically younger (70 years vs 73 years; P = .02), with similar rates of common comorbidities (coronary disease 16% vs 28%; P = .21), and similar aneurysms compared with those who preferred EVAR (6.0 cm vs 5.7 cm; P = .50). Veterans in both preference categories (28% of veterans preferring EVAR, 48% of veterans preferring open repair) reported taking their doctor's advice as the top box response for the single most important factor influencing their decision. When comparing the tradeoff between less invasive surgery and higher risk of long-term complications, more than one-half of veterans preferring EVAR reported invasiveness as more important compared with approximately 1 in 10 of those preferring open repair (53% vs 12%; P < .001). Shorter recovery was an important factor for the EVAR group (74%) and not important in the open repair group (76%) (P = .5). In multivariable analyses, valuing a short hospital stay (odds ratio, 12.4; 95% confidence interval, 1.13-135.70) and valuing a shorter recovery (odds ratio, 15.72; 95% confidence interval, 1.03-240.20) were associated with a greater odds of preference for EVAR, whereas finding these characteristics not important was associated with a greater odds of preference for open repair. CONCLUSIONS: When faced with the decision of open repair versus EVAR, veterans who valued a shorter hospital stay and a shorter recovery were more likely to prefer EVAR, whereas those more concerned about long-term complications preferred an open repair. Veterans typically value the advice of their surgeon over their own beliefs and preferences. These findings need to be considered by surgeons as they guide their patients to a shared decision.

Outcomes after Elective Abdominal Aortic Aneurysm Repair Have Improved Over Time in Patients on Dialysis.

BACKGROUND: Prior studies have demonstrated poor perioperative and long-term survival of patients with end-stage kidney disease (ESKD) on dialysis who undergo abdominal aortic aneurysm repair (AAAR). However, survival in dialysis patients overall has improved over time. We hypothesize that the contemporary rates of perioperative and long-term survival following AAAR in ESKD patients are also improving. METHODS: Data on AAAR procedures in dialysis patients were collected from the United States Renal Data System between 2008 and 2017. Endovascular (EVAR) and open AAA repair (OAR) were identified by Current Procedural Terminology codes. Patients with a functioning renal transplant, a ruptured aneurysm, and insurance other than Medicare were excluded. Demographics, comorbidities, procedural details, and long-term outcomes were collected. Standard statistical methods were used. RESULTS: We identified 3,374 patients who underwent EVAR (86%, 2,914/3,374) and OAR (14%, 460/3,374). The utilization of OAR decreased significantly from 2008 to 2017 (17.34% vs. 7.43%, P < 0.001). Kaplan-Meier survival analysis revealed no significant difference in 5-year survival between OAR and EVAR (24% vs. 17%, P = 0.1, Wilcoxon-Breslow test), but open repair was associated with increased long-term survival (Hazards ratio 0.994, confidence interval 0.990-0.999, P = 0.017) in an adjusted Cox regression model. The cohort was then divided based on the year of AAAR, group 1: 2008-2010 (1,269/3,374), group 2: 2011-2013 (1,071/3,374), and group 3: 2014-2017 (1,034/3,374). Compared to groups 1 and 2, Group 3 was less likely to have coronary artery device, peripheral vascular disease, recent pneumonia, be nonambulatory, live in a nursing facility, or undergo an OAR and more likely to be younger and dialyze through an arteriovenous fistula/arteriovenous graft at the time of AAA repair. Thirty-day postoperative mortality was significantly lower in group 3 compared to groups 1 and 2 (5.4% [56/1,034] vs. 10.3% [131/1,269]/7.3% [78/1,071], P < 0.031). One-year survival by Kaplan-Meier estimate was significantly higher in group 3 (77.7% [803/1,034]) versus groups 1 and 2 (56.7% [719/1,269], 66.9% [716/1,071], P < 0.001, log-rank test). Five-year survival was also significantly higher in group 3 (27.3%) compared to groups 1 and 2 (14.2% and 16.5%, P < 0.001, log-rank test). In a Cox regression model of long-term mortality adjusted for variables significant on a univariate testing, more recent procedure year was associated with increased survival (Hazards ratio 0.81, [0.77, 0.85], P < 0.001). CONCLUSIONS: Postoperative and long-term survival following AAA repair have increased over time in ESKD patients on dialysis. This increased survival persists after accounting for differences in patient demographics and type of procedure over time. Elective AAA repair should be considered in carefully selected good-risk patients on dialysis.

Inflammatory Caspase Activity Mediates HMGB1 Release and Differentiation in Myoblasts Affected by Peripheral Arterial Disease.

Introduction: We previously showed that caspase-1 and -11, which are activated by inflammasomes, mediate recovery from muscle ischemia in mice. We hypothesized that similar to murine models, inflammatory caspases modulate myogenicity and inflammation in ischemic muscle disease. Methods: Caspase activity was measured in ischemic and perfused human myoblasts in response to the NLRP3 and AIM2 inflammasome agonists (nigericin and poly(dA:dT), respectively) with and without specific caspase-1 or pan-caspase inhibition. mRNA levels of myogenic markers and caspase-1 were assessed, and protein levels of caspases-1, -4, -5, and -3 were measured by Western blot. Results: When compared to perfused cells, ischemic myoblasts demonstrated attenuated MyoD and myogenin and elevated caspase-1 mRNA. Ischemic myoblasts also had significantly higher enzymatic caspase activity with poly(dA:dT) (p < 0.001), but not nigericin stimulation. Inhibition of caspase activity including caspase-4/-5, but not caspase-1, blocked activation effects of poly(dA:dT). Ischemic myoblasts had elevated cleaved caspase-5. Inhibition of caspase activity deterred differentiation in ischemic but not perfused myoblasts and reduced the release of HMGB1 from both groups. Conclusion: Inflammatory caspases can be activated in ischemic myoblasts by AIM2 and influence ischemic myoblast differentiation and release of pro-angiogenic HMGB1. AIM2 inflammasome involvement suggests a role as a DNA damage sensor, and our data suggest that caspase-5 rather than caspase-1 may mediate the downstream mediator of this pathway.

Consensus Current Procedural Terminology Code Definition of Source Control for Sepsis.

INTRODUCTION: Unlike antibiotic and perfusion support, guidelines for sepsis source control lack high-quality evidence and are ungraded. Internally valid administrative data methods are needed to identify cases representing source control procedures to evaluate outcomes. METHODS: Over five modified Delphi rounds, two independent reviewers identified Current Procedural Terminology (CPT) codes pertinent to source control. In each round, codes with perfect agreement were retained or excluded, whereas disagreements were reviewed by the panelists. Manual review of 400 patient records meeting Sepsis-3 criteria (2010-2017) clinically adjudicated which encounters included source control procedures (gold standard). The performance of consensus codes was compared with the gold standard to assess sensitivity, specificity, predictive values, and likelihood ratios. RESULTS: Of 5752 CPT codes, 609 consensus codes represented source control procedures. Of 400 hospitalizations for sepsis, 39 (9.8%; 95% confidence interval [CI] 7.0%-13.1%) underwent gold standard source control procedures and 29 (7.3%; 95% CI 4.9-10.3%) consensus code-defined source control procedures. Thirty consensus codes were identified (20.0% gastrointestinal/intraabdominal, 10.0% genitourinary, 13.3% hepatopancreatobiliary, 23.3% orthopedic/cranial, 23.3% soft tissue, and 10.0% intrathoracic), which had 61.5% (95% CI 44.6%-76.6%) sensitivity, 98.6% (95% CI 96.8%-99.6%) specificity, 83.2% (95% CI 66.6%-92.4%) positive, and 95.9% (95% CI 93.9%-97.2%) negative predictive values. With pretest probability at sample prevalence, an identified consensus code had a posttest probability of 83.0% (95% CI 66.0%-92.0%), whereas consensus code absence had a probability of 4.0% (95% CI 3.0-6.0) for undergoing a source control procedure. CONCLUSIONS: Using modified Delphi methodology, we created and validated CPT codes identifying source control procedures, providing a framework for evaluation of the surgical care of patients with sepsis.

Epidemiology of age-, sex-, and race-specific hospitalizations for abdominal aortic aneurysms highlights gaps in current screening recommendations.

BACKGROUND: The detection and elective repair of abdominal aortic aneurysms (AAA) guided by known risk-factor specific screening decrease AAA-related mortality. However, minimal epidemiologic data exist for AAA in female persons and racial minority groups. We established the contemporary risk of US AAA hospitalization across age, sex, and race. METHODS: National Inpatient Sample and US Census (2012-2018) data were used to quantify age-, sex-, and race-specific incidences and adjusted odds ratios (aOR) of AAA hospitalizations (≥18 years), associated risk factors, and in-hospital mortality. Interaction terms evaluated subgroups. RESULTS: Among 1,728,374,183 US residents during the study period (51.3% female; 78.4% White, 12.7% Black, 5.7% Asian), 211,501,703 were hospitalized (aged 57.56 ± 0.04 years; 58.4% female; 64.9% White, 14.3% Black, 2.5% Asian) of which 291,850 were for AAA (aged 73.17 ± 0.04 years; 22.6% female; 81.8% White, 5.6% Black, 1.6% Asian). An estimated 15.2 (95% CI, 15.1-15.3) and 1.7 (95% CI, 1.7-1.7) hospitalizations per 100,000 residents were for intact AAA (iAAA) and ruptured AAA (rAAA) AAA, respectively. In addition, 16.2% of iAAA (83.8% male; 79.1% White) and 18.4% of rAAA (86.4% male; 75.0% White) hospitalizations occurred in patients less than 65 years of age. For iAAA, female sex (aOR, 0.27; 95% CI, 0.27-0.28) compared with male sex and both Black (0.47; 95% CI, 0.45-0.49) and Asian (0.86; 95% CI, 0.83-0.93) persons compared with White persons had a reduced aOR for hospitalization. For rAAA, the reduced aOR persisted for female sex (0.33; 95% CI, 0.32-0.36) and for Black persons (0.52; 95% CI, 0.46-0.58). Although female sex demonstrated an overall decreased odds of AAA hospitalization, female persons who were older, Black, or had peripheral vascular disease (Pinteractions < .001) had a relative increase in AAA hospitalization aOR. Female sex (aOR, 1.54; 95% CI, 1.38-1.70), but not Black or Asian race, was associated with increased mortality which was more pronounced for iAAA (1.93; 95% CI, 1.66-2.25) than rAAA (1.29; 95% CI, 1.13-1.48]; Pinteraction < .001). CONCLUSIONS: We confirmed a substantially decreased adjusted risk of AAA hospitalization for females and racial minority groups; however, aging and comorbid peripheral vascular disease decreased these differences. The disparate risk of AAA hospitalization by sex and race highlights the importance of inclusivity in future AAA studies.