Severe left ventricular hypertrophy with left atrial dilatation can develop from severe aortic stenosis, even without symptoms. These changes can persist, are associated with decreased long-term survival even after successful aortic valve replacement, and could be indications for early aortic valve replacement if supported by findings from an appropriate prospective study.
Objectives
Endovascular abdominal aortic aneurysm repair (EVAR) is increasingly used for emergent treatment of ruptured abdominal aortic aneurysm (rAAA). We sought to compare the perioperative and long-term mortality, procedure-related complications and rates of re-intervention of EVAR versus open aortic repair of rAAA in Medicare beneficiaries.
Methods
We examined perioperative and long-term mortality and complications after EVAR or open aortic repair performed for rAAA in all traditional Medicare beneficiaries discharged from a US hospital from 2001–2008. Patients were propensity score matched on baseline demographics, coexisting conditions, admission source, and hospital volume of rAAA repair and sensitivity analyses were performed to evaluate the impact of bias that might have resulted from unmeasured confounders
Results
Of 10,998 patients with repaired rAAA, 1126 underwent EVAR and 9872 underwent open repair. Propensity score matching yielded 1099 patient pairs. The average age was 78 years, and 72.4% were male. Perioperative mortality for EVAR and open repair were 33.8% and 47.7% respectively (p<0.001) and this difference persisted for more than four years. EVAR patients had higher rates of AAA-related reinterventions when compared with open repair patients (endovascular reintervention at 36 months 10.9% vs 1.5%, p<0.001), whereas open patients had more laparotomy related complications (incisional hernia repair at 36 months 1.8% vs. 6.2% p<0.001, all surgical complications at 36 months 4.4% vs. 9.1%, p<0.001). Use of EVAR for rAAA has increased from 6% of cases in 2001 to 31% of cases in 2008, while over the same time period overall 30-day mortality for admission for rAAA regardless of treatment has decreased from 55.8% to 50.9%.
Conclusions
EVAR for rAAA is associated with lower perioperative and long term mortality in Medicare beneficiaries. Increasing adoption of EVAR for rAAA is associated with an overall decrease in mortality of patients hospitalized for rAAA over the last decade.
Summary
Background
Incorporation of secretory proteins into ER-derived vesicles involves recognition of cytosolic signals by the COPII coat protein, Sec24. Additional cargo diversity is achieved through cargo receptors, which include the Erv14/Cornichon family that mediate export of transmembrane proteins despite the potential for such clients to directly interact with Sec24. The molecular function of Erv14 thus remains unclear, with possible roles in COPII-binding, membrane domain chaperoning and lipid organization.
Results
Using a targeted mutagenesis approach to define the mechanism of Erv14 function, we identify conserved residues in the second transmembrane domain of Erv14 that mediate interaction with a subset of Erv14 clients. We further show that interaction of Erv14 with a novel cargo-binding surface on Sec24 is necessary for efficient trafficking of all of its clients. However, we also determine that some Erv14 clients also engage directly an adjacent cargo-binding domain of Sec24, suggesting a novel mode of dual interaction between cargo and coat.
Conclusions
We conclude that Erv14 functions as a canonical cargo receptor that couples membrane proteins to the COPII coat, but that maximal export requires a bivalent signal that derives from motifs on both the cargo protein and Erv14. Sec24 can thus be considered a coincidence detector that binds simultaneously to multiple signals to drive packaging of polytopic membrane proteins. This mode of dual signal binding to a single coat protein might serve as a general mechanism to trigger efficient capture, or may be specifically employed in ER export to control deployment of nascent proteins.
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