Aims: The aim of this study was to conduct a meta-analysis of prospective studies assessing the relationship between bundle branch block (BBB) or wide QRS and risk of all-cause mortality in patients with acute heart failure (AHF).
Methods And Results: We searched the PubMed, Scopus and Web of Science database from inception to February 2022 to identify single centre or multicentre studies including a minimum of 400 patients and assessing the association between BBB or wide QRS and mortality in patients with AHF. Study-specific hazard ratio (HR) estimates were combined using a random-effects meta-analysis. Two meta-analyses were performed: (1) grouping by conduction disturbance and follow-up length and, (2) using the results from the longest follow-up for each study and grouping by the type of BBB. The meta-analysis included 21 publications with a total of 116,928 patients. Wide QRS (considering right (RBBB) and left (LBBB) altogether) was associated with a significant increment in the risk of all-cause mortality (pooled adjusted HR 1.112, 95% CI 1.065-1.160). The increased risk of death was also present when LBBB (HR 1.121, 95% CI 1.042-1.207) and RBBB (HR 1.187, 95% CI 1.045-1.348) were considered individually. There was no difference in risk between LBBB and RBBB (P for interaction = 0.533). Other outcomes including sudden death, rehospitalization and a combination of cardiovascular death or rehospitalization were also increased in patients with BBB or wide QRS.
Conclusions: This meta-analysis suggests a modest increase in the risk of all-cause mortality among patients with AHF and BBB or wide QRS, irrespective of the type of BBB.
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http://dx.doi.org/10.1007/s00392-022-02105-z | DOI Listing |
J Pharm Anal
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Laboratory of Neuropharmacology, EBRI Rita Levi-Montalcini Foundation, Rome, 00161, Italy.
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State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
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Department of Pharmacy, Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do, 15588, Republic of Korea. Electronic address:
JNK3, a brain-specific stress-activated protein kinase, plays a critical role in Alzheimer's disease pathogenesis through phosphorylation of Tau and APP. This study aimed to develop selective JNK3 inhibitors based on a pyrazole scaffold, focusing on (E)-1-(2-aminopyrimidin-4-yl)-4-styryl-1H-pyrazole-3-carboxamide derivatives. Through systematic structural modifications and extensive SAR analysis, we identified compounds 24a and 26a as highly potent JNK3 inhibitors, with IC values of 12 and 19 nM, respectively.
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Traumatic brain injury (TBI) is a global public health concern. It remains one of the leading causes of morbidity and mortality. TBI pathology involves complex secondary injury cascades that are associated with cellular and molecular dysfunction, including oxidative stress, coagulopathy, neuroinflammation, neurodegeneration, neurotoxicity, and blood-brain barrier (BBB) dysfunction, among others.
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