New frontiers in aortic therapy: focus on current trials and devices in transcatheter aortic valve replacement.

The first decade of clinical experience with transcatheter aortic valve replacement since 2002 saw the development of 2 main valve systems, namely the Edwards Sapien balloon-expandable valve series and the Medtronic self-expanding CoreValve. These 2 valve platforms now have achieved commercial approval and application worldwide in patients with severe aortic stenosis whose perioperative risk for surgical intervention is high or extreme. In the second decade of transcatheter aortic valve replacement, clinical experience and refinements in valve design have resulted in clinical drift towards lower patient risk cohorts. There are currently 2 major trials, PARTNER II and SURTAVI, that are both evaluating the role of transcatheter aortic valve replacement in intermediate-risk patient cohorts. The results from these landmark trials may usher in a new clinical paradigm for transcatheter aortic valve replacement in its second decade.

Perioperative Pain Management for Patients on Chronic Buprenorphine: A Case Report.

Here we present a patient with a Type I Chiari malformation who was receiving buprenorphine for chronic pain who underwent two separate urogynecologic procedures for removal of vaginal mesh with two different pain management regimens. For the first procedure at an outside hospital, the patient's usual dose of buprenorphine (8 mg sublingual every 8 hours) was continued up through her surgery and then a full opioid receptor agonist was used for postoperative pain management. The patient complained that this resulted in very poor pain control for her in the postoperative period. Prior to her second procedure, which was performed at our institution, buprenorphine was switched to a full opioid agonist (oral hydromorphone 4 mg every 4 to 6 hours, maximum 20 mg per day) for 5 days prior to surgery; postoperative pain was managed with full opioid receptor agonists. The patient again reported suboptimal pain control in spite of substantially increased doses of opioids. This case report highlights the difficulty of perioperative pain management for patients on chronic buprenorphine and emphasizes the need for additional investigation.

Structural organization of WrbA in apo- and holoprotein crystals.

Two previously reported holoprotein crystal forms of the flavodoxin-like E. coli protein WrbA, diffracting to 2.6 and 2.0 A resolution, and new crystals of WrbA apoprotein diffracting to 1.85 A, are refined and analysed comparatively through the lens of flavodoxin structures. The results indicate that differences between apo- and holoWrbA crystal structures are manifested on many levels of protein organization as well as in the FMN-binding sites. Evaluation of the influence of crystal contacts by comparison of lattice packing reveals the protein's global response to FMN binding. Structural changes upon cofactor binding are compared with the monomeric flavodoxins. Topologically non-equivalent residues undergo remarkably similar local structural changes upon FMN binding to WrbA or to flavodoxin, despite differences in multimeric organization and residue types at the binding sites. Analysis of the three crystal structures described here, together with flavodoxin structures, rationalizes functional similarities and differences of the WrbAs relative to flavodoxins, leading to a new understanding of the defining features of WrbAs. The results suggest that WrbAs are not a remote and unusual branch of the flavodoxin family as previously thought but rather a central member with unifying structural features.