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.

Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.

Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.

Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite of the HIV-1 Envelope Glycoprotein and Display a Preference for Quaternary Binding.

One of the goals of HIV-1 vaccine development is the elicitation of neutralizing antibodies against vulnerable regions on the envelope glycoprotein (Env) viral spike. Broadly neutralizing antibodies targeting the Env glycan-V3 region (also called the N332 glycan supersite) have been described previously, with several single lineages each derived from different individual donors. We used a high-throughput B-cell culture method to isolate neutralizing antibodies from an HIV-1-infected donor with high serum neutralization breadth. Clonal relatives from three distinct antibody lineages were isolated. Each of these antibody lineages displayed modest breadth and potency but shared several characteristics with the well-characterized glycan-V3 antibodies, including dependence on glycans N332 and N301, VH4 family gene utilization, a heavy chain complementarity-determining region 2 (CDRH2) insertion, and a longer-than-average CDRH3. In contrast to previously described glycan-V3 antibodies, these antibodies preferentially recognized the native Env trimer compared to monomeric gp120. These data indicate the diversity of antibody specificities that target the glycan-V3 site. The quaternary binding preference of these antibodies suggests that that their elicitation likely requires the presentation of a native-like trimeric Env immunogen. IMPORTANCE: Broadly neutralizing antibodies targeting the HIV-1 glycan-V3 region with single lineages from individual donors have been described previously. Here we describe three lineages from a single donor, each of which targets glycan-V3. Unlike previously described glycan-V3 antibodies, these mature antibodies bind preferentially to the native Env trimer and weakly to the gp120 monomer. These data extend our knowledge of the immune response recognition of the N332 supersite region and suggest that the mode of epitope recognition is more complex than previously anticipated.

Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.

Broadly neutralizing antibodies (bNAbs) against HIV-1 Env V1V2 arise in multiple donors. However, atomic-level interactions had previously been determined only with antibodies from a single donor, thus making commonalities in recognition uncertain. Here we report the cocrystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third donor. These V1V2-directed bNAbs used strand-strand interactions between a protruding antibody loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. Altogether, the multidonor information suggested that V1V2-directed bNAbs form an 'extended class', for which we engineered ontogeny-specific antigens: Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. The ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class.