Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression.

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Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum and can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides which can have much more branched glycan side chains than relatively less complex O-linked glycans. In this study a re-defined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding 5 glycosylation sites identified. Subsequent experiments tested its utility for human plasma N-glycoproteins. Large-scale studies explored N-glycoproteomics in rat carotid over the course of restenosis progression to investigate potential role of glycosylation. The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. We also anticipate this approach can be readily applied to large-scale O-glycoproteome characterization.

NV1FGF is well tolerated and potentially could be effective for the treatment of patients with end-stage limb ischemia. Biologic parameters indicate improved perfusion after NV1FGF administration. Dose response is not yet evident. The safety of NV1FGF and the magnitude of improvement observed in this study encourage further investigation with a placebo-controlled, double-blind clinical trial.

Objectives Endovascular repair (EVAR) of ruptured abdominal aortic aneurysms (rAAA) has been shown to acutely decrease procedural mortality compared to open aortic repair (OAR). However, little is known about the effect of choice of procedure; EVAR vs OAR, or the impact of physician and institution volume on long-term survival and outcome. Methods Patients hospitalized with rAAA who underwent either OAR or EVAR, were derived from the Medicare inpatient dataset (1995-2004) using ICD9 codes. We evaluated long-term survival after OAR and EVAR in the entire fee-for-service Medicare population, and then in patients matched by propensity score to create two similar cohorts for comparison with Kaplan-Meier analysis. Annual surgeon and hospital volumes of EVAR (elective and ruptured), OAR (elective and ruptured), and rAAA (EVAR and OAR) were divided into quintiles to determine if increasing volumes correlate with decreasing mortality. Predictors of survival were determined by Cox modeling. Results A total of 43,033 Medicare beneficiaries had rAAA repair: 41,969 had OAR and 1,064 had EVAR. The proportions of patients with diabetes, hypertension, cardiovascular, cerebrovascular, renal disease, hyperlipidemia, and cancer were statistically higher in the EVAR than in the OAR group, whereas lower extremity vascular disease was higher in the OAR group. The initial evaluation of EVAR vs OAR, prior to propensity matching, showed no statistical advantage in EVAR-survival after 90 days. The survival analysis of patients matched by propensity score showed a benefit of EVAR over OAR that persisted throughout the 4 years of follow-up P = .0042). (Perioperative and long-term survival after rAAA repair correlated with increasing annual surgeon and hospital volume in OAR and EVAR and also with rAAA experience. EVAR repair had a protective effect (HR = 0.857, P = .0061) on long-term survival controlling for comorbidities, demographics, and hospital and surgeon volume. Conclusion When EVAR and OAR patients are compared using a reliable statistical technique such as propensity analysis, the perioperative survival advantage of rAAA repaired endovascularly is maintained over the long term. Institutional experience with rAAA is critical for survival after either OAR or EVAR.