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Objectives. This study aimed to evaluate the efficacy and safety of once-per-cycle balugrastim versus pegfilgrastim for neutro-phil support in breast cancer patients receiving myelosuppressive chemotherapy. Methods. Breast cancer patients (n =256) were randomized to 40 or 50 mg of subcutaneous balugrastim or 6 mg of pegfilgrastim ≈24 hours after chemotherapy (60 mg/m² doxorubicin and 75 mg/m² docetaxel, every 21 days for up to 4 cycles).The primary efficacy parameter was the duration of severe neutropenia (DSN) in cycle 1. Secondary parameters included DSN (cycles 2-4), absolute neutrophil count (ANC) nadir, febrile neutropenia rates, and time to ANC recovery (cycles 1-4). Safety, pharmacokinetics, and immunogenicity were assessed. Results. Mean cycle 1 DSN was 1.0 day with 40 mg of balugrastim, 1.3 with 50 mg of balugrastim, and 1.2 with pegfilgrastim (upper limit of 95% confidence intervals for between-group DSN differences was <1.0 day for both balugrastim doses versus pegfilgrastim). Between-group efficacy parameters were comparable except for time to ANC recovery in cycle 1 (40 mg of balugrastim, 2.0 days; 50 mg of balugrastim, 2.1; pegfilgrastim, 2.6). Median terminal elimination half-life was ≈37 hours for 40 mg of balugrastim, ≈36 for 50 mg of balugrastim, and ≈45 for pegfilgrastim. Antibody response to balugrastim was low and transient, with no neutralizing effect. Conclusion. Once-per-cycle balugrastim is not inferior to pegfilgrastim in reducing cycle 1 DSN in breast cancer patients receiving chemotherapy; both drugs have comparable safety profiles. [ABSTRACT FROM AUTHOR]

G-protein coupled receptors (GPCRs) are a major group of drug targets for which only one x-ray structure is known (the nondrugable rhodopsin), limiting the application of structure-based drug discovery to GPCRs. In this paper we present the details of PREDICT, a new algorithmic approach for modeling the 3D structure of GPCRs without relying on homology to rhodopsin. PREDICT, which focuses on the transmembrane domain of GPCRs, starts from the primary sequence of the receptor, simultaneously optimizing multiple 'decoy' conformations of the protein in order to find its most stable structure, culminating in a virtual receptor-ligand complex. In this paper we present a comprehensive analysis of three PREDICT models for the dopamine D2, neurokinin NK1, and neuropeptide Y Y1 receptors. A shorter discussion of the CCR3 receptor model is also included. All models were found to be in good agreement with a large body of experimental data. The quality of the PREDICT models, at least for drug discovery purposes, was evaluated by their successful utilization in in-silico screening. Virtual screening using all three PREDICT models yielded enrichment factors 9-fold to 44-fold better than random screening. Namely, the PREDICT models can be used to identify active small-molecule ligands embedded in large compound libraries with an efficiency comparable to that obtained using crystal structures for non-GPCR targets. Proteins 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Transcatheter therapies to treat tricuspid regurgitation are being developed, but few have attempted the gold standard of surgical repair: ring annuloplasty. We describe the first-ever fully percutaneous implantation of a circumferential, semirigid annuloplasty ring to treat massive secondary tricuspid regurgitation. ( Level of Difficulty: Advanced. )., Competing Interests: This report discusses a case from a study funded by Cardiac Implants LLC. Dr. Reddy has consulted for Cardiac Implants LLC; and has an equity interest in Cardiac Implants LLC. Dr. Abbo has an equity interest in Cardiac Implants LLC; and has been employed by Cardiac Implants LLC. Drs. Ruiz and Kerner has consulted for Cardiac Implants LLC; and has an equity interest in Cardiac Implants LLC. Mr. Kipshidze is employed by Cardiac Implants LLC. Dr. Avisar is employed by Cardiac Implants LLC. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2020 The Authors.)