RESUMO
OBJECTIVE: Current literature reports conflicting findings regarding the effect of diabetes mellitus (DM) on outcomes of abdominal aortic aneurysm (AAA) repair. In this study we examined the effect of DM and its management on outcomes after open AAA repair (OAR) and endovascular AAA repair (EVAR). METHODS: We identified all patients undergoing OAR or EVAR for infrarenal AAA between 2003 and 2018 in the Vascular Quality Initiative registry data linked with Medicare claims. We excluded patients with missing DM status. Patients were stratified by their preoperative DM status, and then further stratified by DM management: dietary, noninsulin antidiabetic medications (NIMs), or insulin. Outcomes of interest included 1-year aneurysm sac dynamics, 8-year aneurysm rupture, reintervention, and all-cause mortality. These outcomes were analyzed with the χ2 test, Kaplan-Meier methods, and multivariable Cox regression analyses. RESULTS: We identified 34,021 EVAR patients and 4127 OAR patients, of whom 20% and 16% had DM, respectively. Of all DM patients, 22% were managed by dietary management, 59% by NIM, and 19% by insulin. After EVAR, DM patients were more likely to have stable sacs, whereas non-DM patients were more likely to have sac regression at 1 year. Compared with non-DM, DM was associated with a significantly lower risk for 8-year rupture in EVAR (EVAR hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.92). Compared with non-DM, NIM was associated with lower risk of rupture within 8-years for both EVAR and OAR (EVAR HR, 0.64; 95% CI, 0.44-0.94; OAR HR, 0.29; 95% CI, 0.41-0.80), whereas dietary control and insulin had a similar rupture risk compared with non-DM. However, compared with non-DM, DM was associated with a higher risk of 8-year all-cause mortality after EVAR and OAR (DM vs non-DM: EVAR HR, 1.17; 95% CI, 1.11-1.23; OAR HR, 1.16; 95% CI, 1.00-1.36). After further DM management substratification, compared with non-DM, management with NIM and insulin were associated with a higher 8-year mortality in EVAR and OAR (EVAR: NIM HR, 1.12; 95% CI, 1.05-1.20; insulin: HR, 1.40; 95% CI, 1.26-1.55; OAR: NIM HR, 1.27; 95% CI, 1.06-1.54; and insulin: HR, 1.57; 95% CI, 1.15-2.13). Finally, there was a similar risk of reintervention across the DM and non-DM populations for EVAR and OAR. CONCLUSIONS: DM was associated with a lower adjusted risk of rupture after EVAR as well as OAR in patients managed with NIM. Nevertheless, just as in patients without AAA, preoperative DM was associated with a higher adjusted risk of all-cause mortality. Further study is needed to evaluate for differences in aneurysm-related mortality between DM and non-DM patients, and studies are planned to evaluate the independent effect of NIM on aneurysm-related outcomes.
RESUMO
Elongation factor Tu (EF-Tu) is a three-domain protein that is responsible for delivering aminoacyl-tRNA (aa-tRNA) molecules to the ribosome. During the delivery process, EF-Tu undergoes a large-scale (~50Å) conformational transition that results in rearrangement of domain I, relative to the II/III superdomain. Despite the central role of EF-Tu during protein synthesis, little is known about the structural and energetic properties of this reordering process. To study the physical-chemical properties of domain motion, we constructed a multi-basin structure-based (i.e., Go-like) model, with which we have simulated hundreds of spontaneous conformational rearrangements. By analyzing the statistical properties of these events, we show that EF-Tu is likely to adopt a disordered intermediate ensemble during this transition. We further show that this disordered intermediate will favor a specific sequence of conformational substeps when bound to the ribosome, and the disordered ensemble can influence the kinetics of the incoming aa-tRNA molecule. Overall, this study highlights the dynamic nature of EF-Tu by revealing a relationship between conformational disorder and biological function.