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.

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.

Myocardial Ischemia Related to Common Cancer Therapy-Prevention Insights.

Modern antineoplastic therapy improves survival and quality of life in cancer patients, but its indisputable benefits are accompanied by multiple and major side effects, such as cardiovascular ones. Endothelial dysfunction, arterial spasm, intravascular thrombosis, and accelerated atherosclerosis affect the coronary arteries, leading to acute and chronic coronary syndromes that negatively interfere with the oncologic treatment. The cardiac toxicity of antineoplastic agents may be mitigated by using adequate prophylactic measures. In the absence of dedicated guidelines, our work provides the most comprehensive, systematized, structured, and up-to-date analyses of the available literature focusing on measures aiming to protect the coronary arteries from the toxicity of cancer therapy. Our work facilitates the implementation of these measures in daily practice. The ultimate goal is to offer clinicians the necessary data for a personalized therapeutic approach for cancer patients receiving evidence-based oncology treatments with potential cardiovascular toxicity.

Hereditary Thrombophilia in the Era of COVID-19.

Thrombophilia, also called hypercoagulability or prothrombotic condition, usually reflects a certain imbalance that occurs either in the coagulation cascade or in the anticoagulation/fibrinolytic system. A similar imbalance may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thrombotic complications are associated with multiorgan failure and increased mortality. In this context, activation of coagulation and thrombocytopenia appeared as prognostic markers in COVID-19. Our work provides a structured and updated analysis of inherited thrombophilia and its involvement in COVID-19, emphasizing the importance of diagnosing and initiating thromboprophylaxis. Since the state of hypercoagulation is directly correlated with COVID-19, we consider that studies on the genetic profiles of proteins involved in thrombophilia in patients who have had COVID-19 and thrombotic events are of great importance, both in treating and in preventing deaths due to COVID-19.

Concept, Design, and Early Prototyping of a Low-Cost, Minimally Invasive, Fully Implantable Left Ventricular Assist Device.

Despite evidence associating the use of mechanical circulatory support (MCS) devices with increased survival and quality of life in patients with advanced heart failure (HF), significant complications and high costs limit their clinical use. We aimed to design an innovative MCS device to address three important needs: low cost, minimally invasive implantation techniques, and low risk of infection. We used mathematical modeling to calculate the pump characteristics to deliver variable flows at different pump diameters, turbomachinery design software CFturbo (2020 R2.4 CFturbo GmbH, Dresden, Germany) to create the conceptual design of the pump, computational fluid dynamics analysis with Solidworks Flow Simulation to in silico test pump performance, Solidworks (Dassault Systèmes SolidWorks Corporation, Waltham, MA, USA) to further refine the design, 3D printing with polycarbonate filament for the initial prototype, and a stereolithography printer (Form 2, Formlabs, Somerville, MA, USA) for the second variant materialization. We present the concept, design, and early prototyping of a low-cost, minimally invasive, fully implantable in a subcutaneous pocket MCS device for long-term use and partial support in patients with advanced HF which unloads the left heart into the arterial system containing a rim-driven, hubless axial-flow pump and the wireless transmission of energy. We describe a low-cost, fully implantable, low-invasive, wireless power transmission left ventricular assist device that has the potential to address patients with advanced HF with higher impact, especially in developing countries. In vitro testing will provide input for further optimization of the device before proceeding to a completely functional prototype that can be implanted in animals.

Thromboembolic Disease in Haemophilic Patients Undergoing Major Orthopaedic Surgery: Is Thromboprophylaxis Mandatory?

Haemophilia is a rare genetic disorder, that results from various degrees of deficiency of coagulation factor VIII (haemophilia A), or factor IX (haemophilia B), with an X-linked transmission. The patients affected are in the majority of cases males (who inherit the affected X-chromosome from the maternal side), with rare cases of females with haemophilia (FVIII or FIX < 40 IU/dL), situations in which both X-chromosomes are affected, or one is affected, and the other one is inactive (known as carrier). The hypocoagulable state due to the deficiency of clotting factors, manifests as an excessive, recurrent tendency to bleeding, which positively correlates with plasmatic levels. Severe haemophilia results in hemarthrosis, although recent data have shown that moderate or even mild disease can lead to joint bleeding. Recurrent episodes of haemorrhages, usually affecting large joints such as knees, elbows, or ankles, lead to joint remodelling and subsequent haemophilic arthropathy, which may require arthroplasty as a last therapeutic option. Orthopaedic patients have the highest risk among all for deep vein thrombosis (DVT) and venous thromboembolism (VTE) with morbid and potentially fatal consequences. While for the rest of the population thromboprophylaxis in orthopaedic surgery is efficient, relatively safe, and widely used, for patients with haemophilia who are considered to have a low thromboembolic risk, there is great controversy. The great heterogeneity of this particular population, and the lack of clinical trials, with only case reports or observational studies, makes thromboprophylaxis in major orthopaedic surgery a tool to be used by every clinician based on experience and case particularities. This review aims to briefly summarise the latest clinical data and to offer an insight into the current recommendations that readers would find useful in daily practice.

Orthopedic surgery in hemophilic patients with musculoskeletal disorders: A systematic review.

Hemophilia is a hereditary coagulopathy caused by factor VIII (hemophilia type A) or by coagulation factor IX (hemophilia type B) dysfunction, characterized by an increased bleeding predisposition, which is either spontaneous or secondary to minimal trauma. Currently, hemophilia may also be considered an 'orthopedic' condition, due to the fact that it affects the musculoskeletal system of most hemophilic patients. In recent years, constant prophylaxis using coagulation factors has led to a significant improvement in the hemophilic patient's quality of life, by reducing both life-threatening hemorrhagic phenomena, as well as the occurrence of chronic complications. Nevertheless, progressive joint bleeding remains unavoidable in this category of patients, and the onset of chronic arthropathy with secondary motor deficiency remains the main complication with an invalidating character. In such cases, orthopedic management is imperative; osteoarticular complications being managed most often with the help of conservative or surgical techniques. The purpose of this review is to provide an overview of modern orthopedic practices which are useful in the management of hemophilic patients suffering from osteoarticular disorders.

Current practices in haemophilic patients undergoing orthopedic surgery - a systematic review.

Haemophilia is an inherited disease that requires a different approach in order to evaluate, monitor and treat patients. Despite the great advances in therapeutic agents that have emerged, reports on the impact of monitoring outcomes on treatment decisions are rarely presented. Haemophilia A and haemophilia B are inherited bleeding disorders caused by deficiencies in blood clotting factor proteins. A systematic review was performed to identify literature reports on the current practices in haemophilic patients undergoing orthopedic surgery. The best therapy for haemophilic patients consists in performing primary prophylaxis to prevent joint bleeding and other complications. Besides the primary prophylaxis, thromboprophylaxis is used to prevent venous thrombosis in patients with hemophilia who undergo surgical orthopedic procedures. Further research is needed to better manage the pharmacologic approaches in haemophilic patients undergoing orthopedic surgery. Although patients with haemophilia present low risk for thromboembolic complications, such events have been reported in surgical procedures. The recommendations in patients with haemophilia are considerably variable in the current guidelines and clinical practice. The best therapy for haemophilic patients consists in performing primary prophylaxis to prevent joint bleeding and other complications.