Faculty Bibliography

BACKGROUND:This study aims to investigate the relationship of increased age on post-endovascular aneurysm repair (EVAR) outcomes. METHODS:A total of 1,380 of 1,853 consecutive patients who underwent EVAR between 1992 and 2012 met our inclusion criteria and were reviewed. Five hundred of the 1,380 patients had computed tomography angiography data to characterize anatomic differences. Age <70 years and ≥70 years were compared. RESULTS:Older patients had higher Glasgow Aneurysm Scores (85.8 ± 8.2 vs. 70.9 ± 8.5, P < 0.0001), indicating higher preoperative risk in patients ≥70 years of age. Patients ≥70 years had increased tortuosity indices, angulation, and iliac calcification. Older patients required higher transfusion volumes (101.1 ± 266.8 vs. 57.6 ± 202.6 mL, P = 0.018). Overall comorbidities, blood loss, and procedure times were similar between groups. The older cohort had higher major and minor perioperative complication rates (10.7% vs. 7.0%, P = 0.007), with a trend toward more major perioperative complications (7.5% vs. 4.8%, P = 0.077). AAA-related perioperative mortality, all-cause perioperative mortality, and intraoperative complication rates were similar between the 2 cohorts. Patients <70 years were more likely to be discharged on postoperative day 1 (76.1% vs. 67.6%, P < 0.0001). Older patients were more likely to develop endoleaks (21.9% vs. 12.8%, P < 0.0001) and required more reinterventions (7.2% vs. 4.7%, P = 0.003). Freedom from AAA-related mortality was similar between the 2 groups (P = nonsignificant); however, patients <70 years had improved overall survival (P < 0.001). CONCLUSIONS:Older age is associated with more complex aneurysm morphology. These features likely resulted in more endoleaks, reinterventions, and complications observed in patients ≥70 years following EVAR.

Type V collagen (COLV) is a regulatory fibril-forming collagen. It has at least three different molecular isoforms-α1(V)2 α2(V), α1(V)3, and α1(V)α2(V)α3(V)-formed by combinations of three different polypeptide α chains-α1(V), α2(V), and α3(V). COL V is a relatively minor collagen of the extracellular matrix (ECM). Morphologically, COLV occurs as heterotypic fibrils with type I collagen (COLI), microfilaments, or 12-nm-thick fibrils. COLV is synthesized in various mesenchymal cells and its gene expression is modulated by TGF-β and growth factors. While resistant to digestion by interstitial collagenases, native and denatured COLV are degraded by metalloproteinases and gelatinases, thereby promoting ECM remodeling. COLV interacts with matrix collagens and structural proteins, conferring structural integrity to tissue scaffolds. It binds matrix macromolecules, modulating cellular behavior, and functions. COLV co-assembles with COLI into heterotypic fibrils in the cornea and skin dermis, acting as a dominant regulator of collagen fibrillogenesis. COLV deficiency is associated with loss of corneal transparency and classic Ehlers-Danlos syndrome, while COLV overexpression is found in cancer, granulation tissue, inflammation, atherosclerosis, and fibrosis of lungs, skin, kidneys, adipose tissue, and liver. COLV isoform containing the α3(V) chain is involved in mediating pancreatic islet cell functions. In the liver, COLV is a minor but regular component of the ECM. Increases in COLV are associated with both early and advanced hepatic fibrosis. The neoepitopes of COLV have been shown to be a useful noninvasive serum biomarker for assessing fibrotic progression and resolution in experimental hepatic fibrosis. COLV is multifunctional in health, disease, and fibrosis.

The insulin hexamer is resistant to degradation and fibrillation, which makes it an important quaternary structure for its in vivo storage in Zn(2+)- and Ca(2+)-rich vesicles in the pancreas and for pharmaceutical formulations. In addition to the two Zn(2+) ions that are required for its formation, three other species, Zn-coordinating anions (e.g., Cl(-)), Ca(2+), and phenols (e.g., resorcinol), bind to the hexamer and affect the subunit conformation and stability. The contributions of these four species to the thermodynamics of insulin unfolding have been quantified by differential scanning calorimetry and thermal unfolding measurements to determine the extent and nature of their stabilization of the insulin hexamer. Both Zn(2+) and resorcinol make a significant enthalpic contribution, while Ca(2+) primarily affects the protein heat capacity (solvation) by its interactions in the central cation-binding cavity, which is modulated by the surrounding subunit conformations. Coordinating anions have a negligible effect on the stability of the hexamer, even though subunits shift to an alternate conformation when these anions bind to the Zn(2+) ions. Finally, Zn(2+) in excess of the two that are required to form the hexamer further stabilizes the protein by additional enthalpic contributions.