The Etiology of the Thrombotic Phenomena Involved in the Process of Coronary Artery Disease-What Is the Role of Thrombophilic Genes in the Development of This Pathology?

Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of "traditional" risk factors, but also more recent studies identified over 100 "novel" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor-1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets.

Environmental and Metabolic Risk Factors Linked to Gallbladder Dysplasia.

Gallbladder disorders encompass a spectrum from congenital anomalies to inflammatory and neoplastic conditions, frequently requiring surgical intervention. Epithelial abnormalities like adenoma and metaplasia have the potential to progress to carcinoma, emphasizing the importance of histopathological assessment for early detection of malignancy. Gallbladder cancer (GBC) may be incidentally discovered during cholecystectomy for presumed benign conditions, underscoring the need for a thorough examination. However, the lack of clarity regarding the molecular mechanisms of GBC has impeded diagnostic and therapeutic advancements. Timely detection is crucial due to GBC's aggressive nature and poor prognosis. Chronic inflammation plays a central role in carcinogenesis, causing DNA damage and oncogenic alterations due to persistent insults. Inflammatory cytokines and microRNAs are among the various mediators contributing to this process. Gallbladder calcifications, particularly stippled ones, may signal malignancy and warrant preemptive removal. Molecular pathways involving mutations in oncogenes and tumor suppressor genes drive GBC pathogenesis, with proposed sequences such as gallstone-induced inflammation leading to carcinoma formation. Understanding these mechanisms, alongside evaluating mucin characteristics and gene mutations, can deepen comprehension of GBC's pathophysiology. This, in turn, facilitates the identification of high-risk individuals and the development of improved treatment strategies, ultimately enhancing patient outcomes. Thus, in this review, our aim has been to underscore the primary mechanisms underlying the development of gallbladder dysplasia and neoplasia.

Molecular and Cellular Mechanisms Involved in Aortic Wall Aneurysm Development.

Aortic aneurysms represent a very common pathology that can affect any segment of the aorta. These types of aneurysms can be localized on the thoracic segment or on the abdominal portion, with the latter being more frequent. Though there are similarities between thoracic and abdominal aortic aneurysms, these pathologies are distinct entities. In this article, we undertook a review regarding the different mechanisms that can lead to the development of aortic aneurysm, and we tried to identify the different manners of treatment. For a long time, aortic wall aneurysms may evolve in an asymptomatic manner, but this progressive dilatation of the aneurysm can lead to a potentially fatal complication consisting in aortic rupture. Because there are limited therapies that may delay or prevent the development of acute aortic syndromes, surgical management remains the most common manner of treatment. Even though, surgical management has improved much in the last years, thus becoming less invasive and sophisticated, the morbi-mortality linked to these therapies remains increased. The identification of the cellular and molecular networks triggering the formation of aneurysm would permit the discovery of modern therapeutic targets. Molecular and cellular mechanisms are gaining a bigger importance in the complex pathogenesis of aortic aneurysms. Future studies must be developed to compare the findings seen in human tissue and animal models of aortic aneurysm, so that clinically relevant conclusions about the aortic aneurysm formation and the pharmacological possibility of pathogenic pathways blockage can be drawn.

Cardiovascular Risk Factors in Patients with Congenital Hemophilia: A Focus on Hypertension.

Aging hemophiliacs face cardiovascular disease. Lots of evidence has been gathered that hemophiliacs have a more unfavorable cardiovascular profile than the general population does, especially due to the increased prevalence of hypertension (HTN). Among the existing scattered evidence, our study provides the most comprehensive and systematized analysis of the determinants of HTN in hemophiliacs. We discussed the contribution to the HTN substrate of hemophilia-specific factors, such as type, severity and the presence of inhibitors. The complex mechanism of kidney dysfunction in relation to hematuria and viral infections was meticulously addressed. Furthermore, we highlighted the new pathogenic concepts of endothelial dysfunction and the association between HTN and hemophilic arthropathy. The clustering of cardiovascular risk factors is common in hemophiliacs, and it enhances the negative vascular effect of HTN and aggravates HTN. It usually leads to an increased risk for coronary and cerebrovascular events. Our work provides reliable evidence to guide and improve the management of HTN in hemophiliacs.

Understanding the mechanisms of gallbladder lesions: A systematic review.

The gallbladder undergoes different types of pathologies, ranging from inflammatory to preneoplasia and finally to malignant lesions. Gallbladder carcinoma can be highly invasive, and it is known that chronic inflammation of the gallbladder can lead to preneoplastic abnormalities and subsequently malignant phenotypes. Gallbladder neoplasia has a low incidence but is associated with a very poor prognosis. An early diagnosis is therefore extremely important in order to improve the prognosis of patients. Immunohistochemical markers of the mucin family can distinguish between different types of gallbladder lesions. Mucins are glycoproteins that can be attached to threonine residues that are O-glycosylated (due to the hydroxyl group of this amino acid). Mucins are divided into two types: those that bind to the membrane, such as MUC1, and those that form gels or are secreted, such as MUC5AC. Various alterations in mucin expression have been revealed to be associated with the development of neoplasia, as they modulate cell growth, karyokinetic transformation, dedifferentiation, adhesion, invasion and immune surveillance. p53 is a tumor suppressor gene and is linked to the development of different types of neoplasia. The incidence of the p53 gene is variable in the pathophysiology of gallbladder cancer. Several studies have revealed an incidence of ~50% of the p53 gene in gallbladder tumors. Studying the immunohistochemical profile of mucins and the presence of different gene mutations in neoplastic lesions of the gallbladder and surrounding mucosa may contribute to the understanding of the pathophysiology of the disease and the mechanisms involved in tumor development, allowing the identification of patients at increased risk of developing neoplasia, thus leading to improved management.

Prediction of bleeding events using the VTE-BLEED risk score in patients with venous thromboembolism receiving anticoagulant therapy (Review).

Venous thromboembolism (VTE) is a major healthcare problem due to its high incidence, significant mortality rate from pulmonary embolism, high recurrence rate and morbidity from long-term complications. After a first episode of VTE all patients must receive anticoagulant treatment for 3 months. Further anticoagulation is recommended in patients without transient risk factors for VTE or patients with active cancer, if they are not at a high risk for bleeding. The VTE-BLEED risk score was created with the purpose of enabling a better stratification of the bleeding risk during stable anticoagulation after a first VTE. Currently, it is the most validated risk score in VTE settings (selected and non-selected cohorts). It has a good prediction power for major bleeding events in patients receiving any of the currently available classes of oral anticoagulants, and it can identify patients at risk of intracranial and fatal bleeding events. The aim of our review was to highlight the strengths of the VTE-BLEED risk score, to acknowledge its weak points and to properly position its use in current medical practice.

Angiotensin-converting enzyme gene D-allele and the severity of coronary artery disease.

Coronary artery disease (CAD) is the first cause of morbidity and mortality worldwide. An important goal is to diagnose patients in early stages, in order to reduce acute cardiovascular events. The angiotensin-converting enzyme (ACE) is an important element for the cardiovascular system, through its actions on hydro-salin balance and vascular tone. ACE polymorphism consists of insertions (I)/deletions (D) and there are 3 genotypes: II, ID, DD. It is speculated that the DD genotype may be a genetic basis for severe CAD, while the II genotype may have a protective effect on the coronary arteries. The present study included 154 patients with acute coronary syndroms admitted to the Institute for Cardiovascular Disease 'George I.M. Georgescu', Iasi. The patients underwent coronary angiography in order to assess the severity of the lesions and the ACE genotypes were determined for each patient. The genotypes were correlated with the severity of the vessel-disease and the exposure to classic risk factors. It was concluded that the D-allele is associated with a greater risk for acute coronary events and severe coronary stenosis, especially when risk genotype and risk phenotype interact.