Balloon-expandable versus self-expanding transcatheter aortic valve replacement for bioprosthetic dysfunction: A systematic review and meta-analysis.

BACKGROUND:Transcatheter aortic valve-in-valve (VIV) procedure is a safe alternative to conventional reoperation for bioprosthetic dysfunction. Balloon-expandable valve (BEV) and self-expanding valve (SEV) are the 2 major types of devices used. Evidence regarding the comparison of the 2 valves remains scarce. METHODS:A systematic review and meta-analysis was conducted to compare the outcomes of BEV and SEV in transcatheter VIV for aortic bioprostheses dysfunction. A computerized search of Medline, PubMed, Embase, and Cochrane databases was performed. English-language journal articles reporting SEV or BEV outcomes of at least 10 patients were included. RESULTS:In total, 27 studies were included, with 2,269 and 1,671 patients in the BEV and SEV groups, respectively. Rates of 30-day mortality and stroke did not differ significantly between the 2 groups. However, BEV was associated with significantly lower rates of postprocedural permanent pacemaker implantation (3.8% vs. 12%; P < 0.001). Regarding echocardiographic parameters, SEV was associated with larger postprocedural effective orifice area at 30 days (1.53 cm2 vs. 1.23 cm2; P < 0.001) and 1 year (1.55 cm2 vs. 1.22 cm2; P < 0.001). CONCLUSIONS:For patients who underwent transcatheter aortic VIV, SEV was associated with larger postprocedural effective orifice area but higher rates of permanent pacemaker implantation. These findings provide valuable information for optimizing device selection for transcatheter aortic VIV

Development of Stem-Cell-Mobilizing Agents Targeting CXCR4 Receptor for Peripheral Blood Stem Cell Transplantation and Beyond

The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4⁺ cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., <b>16</b>) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug <b>1</b> (AMD3100), and thus considered a potential drug candidate for PBSCT indication. Docking compound <b>16</b> into the X-ray crystal structure of CXCR4 receptor revealed that it adopted a spider-like conformation striding over both major and minor subpockets. This putative binding mode provides a new insight into CXCR4 receptor–ligand interactions for further structural modifications

Discovery of 1‑(2,4-Dichlorophenyl)‑<i>N</i>‑(piperidin-1-yl)-4-((pyrrolidine-1-sulfonamido)methyl)-5-(5-((4-(trifluoromethyl)phenyl)ethynyl)thiophene-2-yl)‑1<i>H</i>‑pyrazole-3-carboxamide as a Novel Peripherally Restricted Cannabinoid‑1 Receptor Antagonist with Significant Weight-Loss Efficacy in Diet-Induced Obese Mice

After extensive synthetic efforts, we found that many structurally diverse bioisosteres could be generated via derivatizing the C-4 alkyl chain on the pyrazole ring of compound <b>3</b> (B/P = 1/33) with different electronegative groups. Especially when a sulfonamide or sulfamide moiety was added, resulting compounds exhibited not only potent CB1R activity but also a desired tPSA value over 90 Ų, a threshold considered to possess a low probability to cross BBB, leading to the identification of compound <b>4</b> (B/P = 1/64) as a peripherally restricted CB1R antagonist. Apart from its significant weight-loss efficacy in DIO mice, compound <b>4</b> also displays 163 clean off-target profiles and is currently under development for treating obesity and the related metabolic syndrome

Development of Stem-Cell-Mobilizing Agents Targeting CXCR4 Receptor for Peripheral Blood Stem Cell Transplantation and Beyond

The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4⁺ cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., <b>16</b>) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug <b>1</b> (AMD3100), and thus considered a potential drug candidate for PBSCT indication. Docking compound <b>16</b> into the X-ray crystal structure of CXCR4 receptor revealed that it adopted a spider-like conformation striding over both major and minor subpockets. This putative binding mode provides a new insight into CXCR4 receptor–ligand interactions for further structural modifications