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Aim: Evaluate the diagnostic and prognostic performance of the ESC 0/1H Algorithm and its utility in safely discharging patients with suspected Acute Coronary Syndrome (ACS) in the Emergency Department. Methods: This analysis is a retrospective cohort study of 3,156 patients presenting to an academic medical center emergency department (ED) between May 20, 2019 and May 31, 2020. After completing the Beckman Coulter Access High Sensitivity Troponin I (hs-TnI) assay per current institution protocol (T0, T1H, T3H), patients identified to have symptoms concerning ACS were retrospectively analyzed using the ESC 0/1H Algorithm to assess the safety and efficacy of a rule-out algorithm for early discharge. Results: The negative predictive value (NPV) of the protocol (T₀ < 6 pg/mL; or females with T₀ ≤ 15 pg/mL and T₁ ≤ 15 pg/mL; or males with T₀ ≤ 20 pg/mL and T₁ ≤ 20 pg/mL) was 99.4% (95%CI: 99.0-99.7%) for acute myocardial injury at the initial ED visit (index ED visit) and/or 30-day cardiac-related death. The negative likelihood ratio was 0.08 (95%CI: 0.05%-0.13%), and the specificity was 86.3% (95%CI: 85.0-87.5%).Conclusion: The protocol was found to have a NPV greater than 99% and a negative likelihood ratio of 0.08, suggesting it is safe to use for patients presenting to the ED with ACS symptoms no matter the time of symptom onset. LESS      Full article

Total arch replacement via frozen elephant trunk (FET) is a strategy for managing complex thoracic aortic pathologies involving the arch and descending thoracic aorta (DTA). The FET procedure involves the distal anastomosis of the FET hybrid prosthesis at a chosen aortic arch zone. Though distal anastomosis has been traditionally performed at Zone 3 (Z-3-FET) of the aortic arch, recent practice has seen a significant increase in Zone 2 FET (Z-2-FET). The literature concerning independent Zone 2 and 3 studies and head-to-head comparative studies suggest that Z-2-FET is the superior approach, yielding more favourable results overall, except for aortic remodelling. The improved clinical outcomes achieved with Z-2-FET can be attributed to the shorter operative times, including cardiopulmonary bypass duration, due to the ease and increased surgical site exposure at the aortic arch using this technique. The slightly inferior aortic remodelling observed in Z-2-FET can be explained by the decreased coverage of the DTA distally by the FET stent graft. However, this difference in results can also be attributed to the complexity and severity of the underlying pathology and the surgical approach adopted. The prospect of utilising Zone 0 FET (Z-0-FET) is highly promising, with some studies hinting at its superiority over Z-2-FET. Nevertheless, studies are needed to determine the efficacy of Z-0-FET and directly compare it to Z-2-FET to reach a definitive consensus on the most optimal FET technique. The present literature review aims to provide an overview of major intraoperative and postoperative outcomes achieved with Z-2-FET and Z-3-FET and summarise evidence from studies directly comparing them. Another aim of this narrative review is to explore current literature trends on Z-0-FET uptake. LESS      Full article

Open total arch replacement (TAR) remains the mainstay management strategy for thoracic aortic diseases involving the aortic arch. TAR evolved from the 2-stage conventional elephant trunk (CET) technique to the hybrid frozen elephant trunk (FET) which combined open surgical repair (OSR) with thoracic endovascular aortic repair (TEVAR) into a 1-stage procedure. Although FET has been able to achieve superior results to CET, including excellent survival, it still carries a risk of certain complications that may even require secondary reintervention. The era of elephant trunk is being overtaken by the new generation of TEVAR devices being used for total endovascular aortic arch (or endoarch) repair. Total endoarch repair (TER) is currently indicated in patients deemed high-risk for open surgery; however, it has shown strong potential for becoming the gold stand treatment for aortic arch pathologies. Despite the minimally-invasive nature of TER providing an obvious advantage over OSR in certain cases, TER remains associated with comparable mortality rates and key complications such as technical failure, neurological injury, need for reintervention, and loss of or failure to achieve target vessel patency. Upon comprehensively searching the literature, the technical success of TER ranged from 91%-100%, mortality 0%-19%, stroke 0%-16.7% and reintervention 0%-30.3%, using different commercially available endografts. Given its novelty, further studies with larger cohorts and longer follow-up periods are necessary to solidify the evidence on TER, taking into account the significant learning curve associated with TEVAR. In addition, studies directly comparing arch OSR to TER are warranted to determine superiority. This review aimed to highlight the evolution of aortic arch repair, focusing on TER device development, intervention criteria and clinical outcomes. LESS      Full article

Immune-inflammatory rheumatological diseases are a large group of pathological conditions that lead to chronic inflammation and organ damage. Many autoimmune diseases are associated with a high risk of cardiovascular complications, including atherosclerosis. Inflammation plays a significant role in the development and accelerated course of atherosclerotic lesions. Disorders of lipid metabolism are closely associated with the functions of cells of the immune system and can contribute to the development of these diseases. Cholesterol and lipids are involved in various cellular processes, including intercellular recognition, signal transmission and energy supply. The effect of cholesterol metabolism on the immune response is of great importance and is being actively investigated. Further study of the mechanism of cholesterol efflux from cells may be the key to understanding the relationship between immune-inflammatory and cardiovascular diseases. In this review, we have summarized data on cholesterol metabolism and its effect on the development of pathological conditions. LESS      Full article

Atherosclerosis plays a significant role in the development of cardiovascular diseases, the leading cause of death worldwide. Modification of low-density lipoproteins (LDLs) is a critical event in atherogenesis. Native LDL undergoes several modifications that can lead to the formation of atherogenic modified LDLs. LDL modifications change their physicochemical and biological properties. Possible modifications include changes in the lipoprotein particle’s structure, size, charge, and composition. Uptake and utilization of modified LDLs are impaired in cells. Macrophages take up modified LDLs that promote forming of foam cells, one of the critical cellular components of atherosclerotic lesions. Nevertheless, the direct role of each atherogenic LDL modification in atherogenesis remains uncertain. This review highlights LDL's most critical atherogenic modifications, including oxidized, enzyme-modified, non-oxidative, desialylated, glycated and carbamylated LDLs. Studying the role of each type of LDL modification will clarify the unknown elements of atherosclerosis progression and facilitate the development of effective methods for its diagnosis, treatment, and prevention. LESS      Full article

Cerebral complications, especially intracranial hemorrhage (ICH), are critical determinants of the early outcomes of cardiac surgery for active infective endocarditis (AIE). Relevant society guidelines still recommend delaying cardiac surgery for AIE complicated by ICH for 4 weeks. Some early studies indicated that the mortality decreases when cardiac surgery for ICH is delayed. In contrast, some reported that surgical intervention should not be delayed if an early operation is indicated, even in patients with ICH. The current literature on early versus late surgery for AIE with ICH is conflicting. ICH is classified by its mechanism which includes primary intraparenchymal hemorrhage, hemorrhagic transformation of ischemic infarcts, and rupture of intracranial infectious aneurysms. Some reported that for AIE with a mycotic cerebral aneurysm, early cardiac surgery should be done after repair of the aneurysm, either surgically or endovascularly. Except for the rupture of mycotic aneurysm, primary intraparenchymal hemorrhage and hemorrhagic transformation of ischemic infarcts remain a critical and challenging dilemma. Modifying the cardiopulmonary bypass (CPB) strategy might be necessary to improve the surgical outcomes of AIE with ICH. Some studies reported that cardiac surgery using nafamostat mesylate as an alternative anticoagulant during CPB (NM-CPB) was performed successfully. The NM-CPB can be a useful option as an anticoagulant in critical situations of cardiac surgery with ICH. The timing of surgery should be decided on a case-by-case basis with multidisciplinary specialties including cardiac and neurological teams. LESS      Full article

Chronic venous disease (CVD) is a common venous disorder of the lower extremities. CVD can be manifested as varicose veins (VVs), with dilated and tortuous veins, dysfunctional valves and venous reflux. If not adequately treated, VVs could progress to chronic venous insufficiency (CVI) and lead to venous leg ulcer (VLU). Predisposing familial and genetic factors have been implicated in CVD. Additional environmental, behavioral and dietary factors including sedentary lifestyle and obesity may also contribute to CVD. Alterations in the mRNA expression, protein levels and proteolytic activity of matrix metalloproteinases (MMPs) have been detected in VVs and VLU. MMP expression/activity can be modulated by venous hydrostatic pressure, hypoxia, tissue metabolites, and inflammation. MMPs in turn increase proteolysis of different protein substrates in the extracellular matrix particularly collagen and elastin, leading to weakening of the vein wall. MMPs could also promote venous dilation by increasing the release of endothelium-derived vasodilators and activating potassium channels, leading to smooth muscle hyperpolarization and relaxation. Depending on VVs severity, management usually includes compression stockings, sclerotherapy and surgical removal. Venotonics have also been promoted to decrease the progression of VVs. Sulodexide has also shown benefits in VLU and CVI, and recent data suggest that it could improve venous smooth muscle contraction. Other lines of treatment including induction of endogenous tissue inhibitors of metalloproteinases and administration of exogenous synthetic inhibitors of MMPs are being explored, and could provide alternative strategies in the treatment of CVD. LESS      Full article

Cerebral cavernous malformations (CCMs), one of the most common vascular malformations, are characterized by abnormally dilated intracranial microvascular capillaries resulting in increased susceptibility to hemorrhagic stroke. As an autosomal dominant disorder with incomplete penetrance, the majority of CCMs gene mutation carriers are largely asymptomatic, but, when symptoms occur, the disease has typically reached the stage of focal hemorrhage with irreversible brain damage, while the molecular “trigger” initiating the occurrence of CCM pathology remain elusive. Currently, the invasive neurosurgery removal of CCM lesions is the only option for the treatment, despite the recurrence of worse symptoms frequently occurring after surgery. Therefore, there is a grave need for the identification of molecular targets for therapeutic treatment and biomarkers as risk predictors for hemorrhagic stroke prevention. Based on the various perturbed angiogenic signaling cascades mediated by the CCM signaling complex (CSC) reported, there have been many proposed candidate drugs, targeting potentially angiogenic-relevant signaling pathways dysregulated by loss of function of one of the CCM proteins, which might not be enough to correct the pathological phenotype, hemorrhagic CCMs. In this review, we describe a new paradigm for the mechanism of hemorrhagic CCM lesions and propose a new concept for the assurance of CSC stability to prevent the devastating outcome of hemorrhagic CCMs. LESS      Full article

Atherosclerosis is the main pathological basis of most cardiovascular diseases and the leading health threat in the world. Of note, lipid-lowering therapy cannot completely retard atherosclerosis progression, even in patients treated with combined statins and PCSK9 inhibitors. This failure further impels researchers to explore other underlying therapeutic strategies except for lipid-lowering. Monocytes and macrophages are the major immune cell groups in atherosclerotic plaques. They play important roles in all stages of atherosclerosis, including the occurrence, advance, and regression. It is interesting that macrophages are demonstrated to have plastic and heterogenous characteristics within the dynamic atherosclerotic plaque microenvironment. Furthermore, the phenotype of macrophages can switch upon different microenvironmental stimulus. Therefore, macrophages have become a potential therapeutic target for anti-atherosclerosis treatment. This article reviews the phenotypic diversity of macrophages and their roles in dynamic atherosclerotic plaque microenvironment, especially the related signaling pathways involved in macrophage polarization and compounds exhibiting therapeutic effects. LESS      Full article

Age-related macular degeneration (AMD) is the leading cause of vision loss in adults over 60 years old globally. There are two forms of advanced AMD: “dry” and “wet”. Dry AMD is characterized by geographic atrophy of the retinal pigment epithelium and overlying photoreceptors in the macular region; whereas wet AMD is characterized by vascular penetrance from the choroid into the retina, known as choroidal neovascularization (CNV). Both phenotypes eventually lead to loss of central vision. The pathogenesis of AMD involves the interplay of genetic polymorphisms and environmental risk factors, many of which elevate retinal oxidative stress. Excess reactive oxygen species react with cellular macromolecules, forming oxidation-modified byproducts that elicit chronic inflammation and promote CNV. Additionally, genome-wide association studies have identified several genetic variants in the age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2-HTRA1) locus associated with the progression of late-stage AMD, especially the wet subtype. In this review, we will focus on the interplay of oxidative stress and HTRA1 in drusen deposition, chronic inflammation, and chronic angiogenesis. We aim to present a multifactorial model of wet AMD progression, supporting HTRA1 as a novel therapeutic target upstream of vascular endothelial growth factor (VEGF), the conventional target in AMD therapeutics. By inhibiting HTRA1’s proteolytic activity, we can reduce pro-angiogenic signaling and prevent proteolytic breakdown of the blood-retina barrier. The anti-HTRA1 approach offers a promising alternative treatment option to wet AMD, complementary to anti-VEGF therapy. LESS      Full article