Percutaneous Coronary Intervention Versus Medical Therapy for Chronic Total Occlusion of Coronary Arteries:A Systematic Review and Meta-Analysis

PURPOSE OF REVIEW: Chronic total occlusion (CTO) of the coronary arteries is a significant clinical problem and has traditionally been treated by medical therapy or coronary artery bypass grafting. Recent studies have examined percutaneous coronary intervention (PCI) as an alternative option. RECENT FINDINGS: This systematic review and meta-analysis compared medical therapy to PCI for treating CTOs. PubMed and Embase were searched from their inception to March 2019 for studies that compared medical therapy and PCI for clinical outcomes in patients with CTOs. Quality of the included studies was assessed by Newcastle-Ottawa scale. The results were pooled by DerSimonian and Laird random- or fixed-effect models as appropriate. Heterogeneity between studies and publication bias was evaluated by I2 index and Egger's regression, respectively. Of the 703 entries screened, 17 studies were included in the final analysis. This comprised 11,493 participants. Compared to PCI, medical therapy including randomized and observational studies was significantly associated with higher risk of all-cause mortality (risk ratio (RR) 1.99, 95% CI 1.38-2.86), cardiac mortality (RR 2.36 (1.97-2.84)), and major adverse cardiac event (RR 1.25 (1.03-1.51)). However, no difference in the rate of myocardial infarction and repeat revascularization procedures was observed between the two groups. Univariate meta-regression demonstrated multiple covariates as independent moderating factors for myocardial infarction and repeat revascularization but not cardiac death and all-cause mortality. However, when only randomized studies were included, there was no difference in overall mortality or cardiac death. In CTO, when considering randomized and observational studies, medical therapy might be associated with a higher risk of mortality and myocardial infarction compared to PCI treatment

Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma

Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca 2+ channel inhibitor Lomerizine (Lom), the Ca 2+ permeable AMPA receptor inhibitor YM872 and the P2X 7 receptor inhibitor oxATP. Results: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs

Retinal genes are differentially expressed in areas of primary versus secondary degeneration following partial optic nerve injury

Background: Partial transection (PT) of the optic nerve is an established experimental model of secondary degeneration in the central nervous system. After a dorsal transection, retinal ganglion cells (RGCs) with axons in ventral optic nerve are intact but vulnerable to secondary degeneration, whereas RGCs in dorsal retina with dorsal axons are affected by primary and secondary injuries. Using microarray, we quantified gene expression changes in dorsal and ventral retina at 1 and 7 days post PT, to characterize pathogenic pathways linked to primary and secondary degeneration. Results: In comparison to uninjured retina Cryba1, Cryba2 and Crygs, were significantly downregulated in injured dorsal retina at days 1 and 7. While Ecel1, Timp1, Mt2A and CD74, which are associated with reducing excitotoxicity, oxidative stress and inflammation, were significantly upregulated. Genes associated with oxygen binding pathways, immune responses, cytokine receptor activity and apoptosis were enriched in dorsal retina at day 1 after PT. Oxygen binding and apoptosis remained enriched at day 7, as were pathways involved in extracellular matrix modification. Fewer changes were observed in ventral retina at day 1 after PT, most associated with the regulation of protein homodimerization activity. By day 7, apoptosis, matrix organization and signal transduction pathways were enriched. Discriminant analysis was also performed for specific functional gene groups to compare expression intensities at each time point. Altered expression of selected genes (ATF3, GFAP, Ecel1, TIMP1, Tp53) and proteins (GFAP, ECEL1 and ATF3) were semi-quantitatively assessed by qRT-PCR and immunohistochemistry respectively. Conclusion: There was an acute and complex primary injury response in dorsal retina indicative of a dynamic interaction between neuroprotective and neurodegenerative events; ventral retina vulnerable to secondary degeneration showed a delayed injury response. Both primary and secondary injury resulted in the upregulation of numerous genes linked to RGC death, but differences in the nature of these changes strongly suggest that death occurred via different molecular mechanisms