Reliability and longevity of implantable defibrillators.

PURPOSE: We hypothesized that data in manufacturers' product performance reports (PPRs) can provide clinically valuable ICD and cardiac resynchronization defibrillator (CRT-D) reliability and longevity information. METHODS: Data were obtained from 2019 PPRs. Kaplan-Meier (K-M) probabilities of freedom from malfunction, normal battery depletion (NBD), and NBD + malfunction were calculated for ICD and CRT-D pulse generators (PGs) with LiMnO2 or LiSVO/CFx batteries marketed in the USA from 2010 to 2019 and compared using the log-rank test. Malfunctions (MAL) included PGs that were found outside specifications. RESULTS: Study population included 1,149,803 ICD and CRT-D PGs: Abbott (ABT; 35.1%), Biotronik (BIO; 4.6%), Boston Scientific (BSC; 23.5%), and Medtronic (MDT; 36.9%). Significant differences in reliability (p < 0.001), defined by freedom from MAL, were found between manufacturers; the majority of 6808 MAL occurred in ABT devices (n = 4045; 59.4%), followed by BSC (n = 2384; 35.0%), MDT (n = 338;5.0%), and BIO (n = 41; 0.6%). Battery failure (n = 890; 57.9%) was the most common cause of MAL compromising therapy; analysis of unique ABT battery MAL-indicated problem appeared a year prior to advisory. Significant differences (p < 0.001) in battery longevity, as defined by freedom from NBD, were found between manufacturers. Overall performance (freedom from NBD + MAL) favored BSC for CRT-D PGs and MDT and BIO for ICDs. BSC subcutaneous ICD reliability was inferior to its transvenous ICD (p < 0.001). CONCLUSION: PPRs contain valuable data that can be aggregated and analyzed to inform physicians. Differences in product reliability exist between manufacturers. Battery longevity has improved, but MAL have significantly impacted performance. PPR data may be useful for assessing product problems and new technology.

Haspin inhibition delays cell cycle progression through interphase in cancer cells.

Haspin (Haploid Germ Cell-Specific Nuclear Protein Kinase) is a serine/threonine kinase pertinent to normal mitosis progression and mitotic phosphorylation of histone H3 at threonine 3 in mammalian cells. Different classes of small molecule inhibitors of haspin have been developed and utilized to investigate its mitotic functions. We report herein that applying haspin inhibitor CHR-6494 or 5-ITu at the G1/S boundary could delay mitotic entry in synchronized HeLa and U2OS cells, respectively, following an extended G2 or the S phase. Moreover, late application of haspin inhibitors at S/G2 boundary is sufficient to delay mitotic onset in both cell lines, thereby, indicating a direct effect of haspin on G2/M transition. A prolonged interphase duration is also observed with knockdown of haspin expression in synchronized and asynchronous cells. These results suggest that haspin can regulate cell cycle progression at multiple stages at both interphase and mitosis.