Dose-responsive characteristics of meperidine sedation in preschool children

Using double-blind conditions, 60 uncooperative and fearful preschool children (24-66 months) received intramuscular injections of meperidine 0.25, 0.50, 1.00 mg/lb or placebo prior to restorative dental treatment. Behavior was assessed by the dentist and an independent observer during five specific treatment procedures. Behavioral ratings found meperidine to be an effective sedative, with 0.50 mg/lb and 1.00 mg/lb being significantly more effective than placebo (P less than 0.05, Kruskal-Wallis). Children receiving 1.0 mg/lb of meperidine had significantly more nausea and vomiting than patients receiving lower doses of the drug (P less than 0.05, Chisquare). Physiologic monitoring demonstrated that the highest dose of meperidine was associated with transient drops in arterial oxygen saturation. Meperidine sedation was found to be more effective for older children (37-66 months) and for children initially rated as being only moderately uncooperative and fearful.     

David's procedure for pulmonary artery aneurysm

Pulmonary artery aneurysm (PAA) is a rare entity with fatal complications. Its silent course contributes to large aneurysms with compression symptoms. We present a 39-year-old female idiopathic pulmonary arterial hypertension patient with a giant PAA causing severe pulmonary regurgitation (PR) and symptomatic left main coronary artery compression (LMCA). Since she had a failed LMCA stenting attempt, she underwent surgery. A valve-sparing David-like pulmonary trunk reconstruction and coronary artery bypass were performed. This case illustrates that David-like reconstruction procedure can be applied to the PAA with severe PR.     

Global analysis of proteasomal substrate specificity using positional-scanning libraries of covalent inhibitors

The proteasome is a large protease complex consisting of multiple catalytic subunits that function simultaneously to digest protein substrates. This complexity has made deciphering the role each subunit plays in the generation of specific protein fragments difficult. Positional scanning libraries of peptide vinyl sulfones were generated in which the amino acid located directly at the site of hydrolysis (P1 residue) was held constant and sequences distal to that residue (P2, P3, and P4 positions) were varied across all natural amino acids (except cysteine and methionine). Binding information for each of the individual catalytic subunits was obtained for each library under a variety of different conditions. The resulting specificity profiles indicated that substrate positions distal to P1 are critical for directing substrates to active subunits in the complex. Furthermore, specificity profiles of IFN-gamma-regulated subunits closely matched those of their noninducible counterparts, suggesting that subunit swapping may modulate substrate processing by a mechanism that does require a change in the primary sequence specificity of individual catalytic subunits in the complex. Finally, specificity profiles were used to design specific inhibitors of a single active site in the complex. These reagents can be used to further establish the role of each subunit in substrate processing by the proteasome.     

Transcatheter aortic valve replacement: The year in review 2017

This article is a continuation of our previously published annual reviews of transcatheter aortic valve replacement (TAVR). In 2017, TAVR further established a foothold in the management of intermediate risk patients with the publication of SURTAVI trial. Randomized trials also addressed the use of cerebral protection during TAVR and single versus dual antiplatelet therapy after TAVR. Newer generation valve systems continued to be studied for their efficacy and safety. This paper summarizes the major studies published in 2017.

     

Postoperative Atrial Fibrillation or Flutter Following Transcatheter or Surgical Aortic Valve Replacement: PARTNER 3 Trial

ObjectivesThe aim of this study was to assess the incidence and prognostic impact of early and late postoperative atrial fibrillation or flutter (POAF) in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).BackgroundThere is an ongoing controversy regarding the incidence, recurrence rate, and prognostic impact of early (in-hospital) POAF and late (postdischarge) POAF in patients with AS undergoing TAVR or SAVR.MethodsIn the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial, patients with severe AS at low surgical risk were randomized to TAVR or SAVR. Analyses were performed in the as-treated population excluding patients with preexistent atrial fibrillation or flutter.ResultsAmong 781 patients included in the analysis, early POAF occurred in 152 (19.5%) (18 of 415 [4.3%] and 134 of 366 [36.6%] following TAVR and SAVR, respectively). Following discharge, 58 new or recurrent late POAF events occurred within 1 year following the index procedure in 55 of 781 patients (7.0%). Early POAF was not an independent predictor of late POAF following discharge (odds ratio: 1.04; 95% CI: 0.52-2.08; P = 0.90). Following adjustment, early POAF was not an independent predictor of the composite outcome of death, stroke, or rehospitalization (hazard ratio: 1.10; 95% CI: 0.64-1.92; P = 0.72), whereas late POAF was associated with an increased adjusted risk for the composite outcome (hazard ratio: 8.90; 95% CI: 5.02-15.74; P < 0.0001), irrespective of treatment modality.ConclusionsIn the PARTNER 3 trial, early POAF was more frequent following SAVR compared with TAVR. Late POAF, but not early POAF, was significantly associated with worse outcomes at 2 years, irrespective of treatment modality.