1.Trends in cardiovascular death related to mechanical complications of cardiac electronic devices in the United States from 1999 to 2020
Min Choon TAN ; Yong Hao YEO ; Boon Jian SAN ; Jian Liang TAN
International Journal of Arrhythmia 2023;24(3):19-
Background:
While cardiac implantable electronic devices (CIED) are increasingly used, real-world data on the mortality rate due to mechanical complications of CIED is scarce.
Objective:
This study aimed to determine longitudinal trends in mortality attributed to mechanical complications of CIED.
Methods:
We queried the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research and performed serial cross-sectional analyses of national death certificate data for mechanical complications of CIED-related mortality among the United States population aged ≥ 35 years from 1999 to 2020. Cardiovascular disease (ICD-10: I00–I99) was listed as the underlying cause of death, and mechanical complication of the cardiac electronic device (ICD-10: T82.1) was stated as the contributing cause of death. We calculated age-adjusted mortality rates (AAMRs) per 1,000,000 individuals. Linear regression was used to calculate for the significance of the annual percent of changes in AAMRs.
Results:
1237 cardiovascular deaths related to mechanical complications of CIED were identified between 1999 and 2020. The AAMR dropped significantly from 0.45 per 1,000,000 individuals in 1999 to 0.21 per 1,000,000 individuals in 2020 (p < 0.01). Cumulative AAMRs were higher in males than females (0.39 per 1,000,000 individuals vs. 0.26 per 1,000,000 individuals, p < 0.01), higher in White populations than African American populations (0.32 per 1,000,000 individuals vs. 0.30 per 1,000,000 individuals, p < 0.01), and higher in the rural areas than in the urban areas (0.50 per 1,000,000 individuals vs. 0.27 per 1,000,000 individuals, p < 0.01).
Conclusion
While the cardiovascular deaths related to mechanical complications of CIED were decreasing over the past decades, disparities in the AAMRs across sex, races and geographical region still present.
2.The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses.
Kan Xing WU ; Thinesshwary YOGARAJAH ; Marcus Wing Choy LOE ; Parveen KAUR ; Regina Ching Hua LEE ; Chee Keng MOK ; Yi Hao WONG ; Patchara PHUEKTES ; Li Sze YEO ; Vincent T K CHOW ; Yong Wah TAN ; Justin Jang Hann CHU
Acta Pharmaceutica Sinica B 2023;13(5):2039-2055
Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.