Relation between bioresorbable scaffold sizing using QCA-Dmax and clinical outcomes at 1 year in 1,232 patients from 3 study cohorts (ABSORB Cohort B, ABSORB EXTEND, and ABSORB II)

Objectives This study sought to investigate the clinical outcomes based on the assessment of quantitative coronary angiography-maximal lumen diameter (Dmax). Background Assessment of pre-procedural Dmax of proximal and distal sites has been used for Absorb scaffold size selection in the ABSORB studies. Methods A total of 1,248 patients received Absorb scaffolds in the ABSORB Cohort B (ABSORB Clinical Investigation, Cohort B) study (N = 101), ABSORB EXTEND (ABSORB EXTEND Clinical Investigation) study (N = 812), and ABSORB II (ABSORB II Randomized Controlled Trial) trial (N = 335). The incidence of major adverse cardiac events (MACE) (a composite of cardiac death, any myocardial infarction [MI], and ischemia-driven target lesion revascularization) was analyzed according to the Dmax subclassification of scaffold oversize group versus scaffold nonoversize group. Results Of 1,248 patients, pre-procedural Dmax was assessed in 1,232 patients (98.7%). In 649 (52.7%) patients, both proximal and distal Dmax values were smaller than the nominal size of the implanted scaffold (scaffold oversize group), whereas in 583 (47.3%) of patients, the proximal and/or distal Dmax were larger than the implanted scaffold (scaffold nonoversize group). The rates of MACE and MI at 1 year were significantly higher in the scaffold oversize group than in the scaffold nonoversize group (MACE 6.6% vs. 3.3%; log-rank p < 0.01, all MI: 4.6% vs. 2.4%; log-rank p = 0.04), mainly driven by a higher MI rate within 1 month post-procedure (3.5% vs. 1.9%; p = 0.08). The independent MACE determinants were both Dmax smaller than the scaffold nominal size (odds ratio [OR]: 2.13, 95% confidence interval [CI]: 1.22 to 3.70; p < 0.01) and the implantation of overlapping scaffolds (OR: 2.10, 95% CI: 1.17 to 3.80; p = 0.01). Conclusions Implantation of an oversized Absorb scaffold in a relatively small vessel appears to be associated with a higher 1-year MACE rate driven by more frequent early MI. (ABSORB Clinical Investigation, Cohort B [ABSORB Cohort B], NCT00856856; ABSORB EXTEND Clinical Investigation [ABSORB EXTEND], NCT01023789; ABSORB II Randomized Controlled Trial [ABSORB II], NCT01425281)

The filamentous bacteriophage assembly proteins require the bacterial SecA protein for correct localization to the membrane.

The noncapsid assembly proteins pI and pI of the filamentous bacteriophage f1 are inserted into the inner membrane of Escherichia coli via an internal signal sequence. Inhibition of the activity of SecA with low concentrations of sodium azide results in rapid accumulation of pI and pI proteins in the cytoplasm. However, both proteins are inserted into the membrane under the same conditions when synthesized in bacteria containing a secA azide resistance mutation. The other noncapsid assembly protein, pIV, is an outer membrane protein synthesized with a cleavable signal sequence. Wild-type bacteria accumulate the precursor to pIV when protein synthesis is in the presence of low concentrations of sodium azide. These results suggest that the f1 bacteriophage assembly proteins require SecA and consequently the bacterial Sec system to reach their proper membrane location

Membrane localization and topology of a viral assembly protein.

The gene I protein (pI) of the filamentous bacteriophage f1 is required for the assembly of this virus. Antibodies specific to either the amino or carboxyl terminus of this protein were used to determine the location and topology of the gene I protein in f1-infected bacteria. pI is anchored in the inner membrane of Escherichia coli cells via a 20-amino-acid hydrophobic stretch, with its carboxyl-terminal 75 residues located in the periplasm and its amino-terminal 253 amino acids residing in the cytoplasm. By using the carboxyl-terminal pI antibody, a smaller protein, pI*, is also detected in f1-infected cells at a ratio of one to two molecules per molecule of pI. Analysis of proteins produced from a gene I amber mutant plasmid or bacteriophage suggests that pI* is most likely the result of an in-frame internal translational initiation event at methionine 241 of the 348-amino-acid pI. pI* is shown to be an integral inner membrane protein inserted in the same orientation as pI. The relation of the cellular locations of pI and pI* to some of the proposed functions of pI is discussed