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.

Debates Surrounding the Use of Antithrombotic Therapy in Hemophilic Patients with Cardiovascular Disease: Best Strategies to Minimize Severe Bleeding Risk.

Navigating through antithrombotic therapy in patients with both hemophilia and cardiovascular pathology presents a complex scenario with inherent challenges and opportunities. The presence of hemophilia, characterized by impaired blood clotting, adds a layer of complexity to the management of cardiovascular conditions requiring antiplatelet therapy and anticoagulation. Striking a delicate balance between the necessity for antithrombotic treatment to prevent cardiovascular events and the heightened risk of severe bleeding in individuals with hemophilia demands a nuanced and carefully considered approach. The challenges revolve around identifying an optimal therapeutic strategy that effectively mitigates cardiovascular risks without exacerbating bleeding tendencies. In hemophilic patients with cardiovascular disease, the decision to use antiplatelet therapy requires careful consideration of the individual's bleeding risk profile, considering factors such as the severity of hemophilia, history of bleeding episodes, and concurrent medications. The goal is to provide effective antithrombotic treatment while minimizing the potential for excessive bleeding complications. Conventional anticoagulants like warfarin pose difficulties due to their potential to increase the risk of bleeding. On the other hand, emerging options like novel direct oral anticoagulants (DOACs) present an opportunity, offering predictable pharmacokinetics and user-friendly administration. However, a comprehensive exploration of their safety and efficacy in hemophilic patients is imperative. Achieving the right equilibrium between preventing cardiovascular events and minimizing bleeding risk is pivotal in selecting the most effective therapeutic option for individuals with hemophilia and cardiovascular pathology. A multidisciplinary approach, integrating the expertise of hematologists and cardiologists, becomes essential to customize treatments and address the intricacies of this medical challenge.

Biomarkers Involved in the Pathogenesis of Hemophilic Arthropathy.

Hemophilia, which is a rare disease, results from congenital deficiencies of coagulation factors VIII and IX, respectively, leading to spontaneous bleeding into joints, resulting in hemophilic arthropathy (HA). HA involves complex processes, including synovial proliferation, angiogenesis, and tissue remodeling. Despite ongoing research, factors contributing to HA progression, especially in adults with severe HA experiencing joint pain, remain unclear. Blood markers, particularly collagen-related ones, have been explored to assess joint health in hemophilia. For example, markers like CTX-I and CTX-II reflect bone and cartilage turnover, respectively. Studies indicate elevated levels of certain markers post-bleeding episodes, suggesting joint health changes. However, longitudinal studies on collagen turnover and basement membrane or endothelial cell markers in relation to joint outcomes, particularly during painful episodes, are scarce. Given the role of the CX3CL1/CX3XR1 axis in arthritis, other studies investigate its involvement in HA. The importance of different inflammatory and bone damage biomarkers should be assessed, alongside articular cartilage and synovial membrane morphology, aiming to enhance understanding of hemophilic arthropathy progression.

Osteonecrosis of the Jaws in Patients with Hereditary Thrombophilia/Hypofibrinolysis-From Pathophysiology to Therapeutic Implications.

Osteonecrosis of the jaws (ONJ) usually has a clear etiology. Local infection or trauma, radiotherapy and drugs that disrupt the vascular supply or bone turnover in the jaws are its major contributors. The thrombotic occlusion of the bone's venous outflow that occurs in individuals with hereditary thrombophilia and/or hypofibrinolysis has a less known impact on jaw health and healing capability. Our research provides the most comprehensive, up-to-date and systematized information on the prevalence and significance of hereditary thrombophilia and/or hypofibrinolysis states in ONJ. We found that hereditary prothrombotic abnormalities are common in patients with ONJ refractory to conventional medical and dental treatments. Thrombophilia traits usually coexist with hypofibrinolysis traits. We also found that frequently acquired prothrombotic abnormalities coexist with hereditary ones and enhance their negative effect on the bone. Therefore, we recommend a personalized therapeutic approach that addresses, in particular, the modifiable risk factors of ONJ. Patients will have clear benefits, as they will be relieved of persistent pain and repeated dental procedures.

Difficulties in Performing Daily Activities in Patients with Dry Eye before and after Treatment.

Dry eye disease (DED) represents an important public health problem causing visual discomfort which affects the quality of life. This paper investigates the current comprehension of DED on life quality and vision. METHODS: This research consists of a cross-sectional study of 121 patients, with a mean age of 70 ± 9 years, diagnosed with DED. All patients were treated in the University Clinic for Ophthalmology in "St. Spiridon" Emergency Hospital, Iasi. For all patients, we evaluated visual acuity on the Snellen chart, tear breakup time (TBUT), Schirmer I test scores, and contrast sensitivity. For this study, we used the Visual Functioning Questionnaire-25 (VFQ-25) version 2000, modified and adapted for this research (19 items). RESULTS: Prior to treatment, patients had very high difficulty reading a text in a newspaper or on TV, reading prices on products in shops, or recognizing people they already met. Performing manual work or favorite activities was also very difficult. Post-treatment visual challenges improved in the majority of cases, regardless of the treatment method used. CONCLUSIONS: We found that symptomatic dry eye disease was associated with reduced ability in performing several important vision-related daily tasks and has a significant impact on life quality and visual performance.

Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options.

Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide problem and its association with other metabolic pathologies has been one of the main research topics in the last decade. The aim of this review article is to provide an up-to-date correlation between hypothyroidism and NAFLD. We followed evidence regarding epidemiological impact, immunopathogenesis, thyroid hormone-liver axis, lipid and cholesterol metabolism, insulin resistance, oxidative stress, and inflammation. After evaluating the influence of thyroid hormone imbalance on liver structure and function, the latest studies have focused on developing new therapeutic strategies. Thyroid hormones (THs) along with their metabolites and thyroid hormone receptor ß (THR-ß) agonist are the main therapeutic targets. Other liver specific analogs and alternative treatments have been tested in the last few years as potential NAFLD therapy. Finally, we concluded that further research is necessary as well as the need for an extensive evaluation of thyroid function in NAFLD/NASH patients, aiming for better management and outcome.

The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity.

Acute kidney injury (AKI) following platinum-based chemotherapeutics is a frequently reported serious side-effect. However, there are no approved biomarkers that can properly identify proximal tubular injury while routine assessments such as serum creatinine lack sensitivity. Kidney-injury-molecule 1 (KIM-1) is showing promise in identifying cisplatin-induced renal injury both in vitro and in vivo studies. In this review, we focus on describing the mechanisms of renal tubular cells cisplatin-induced apoptosis, the associated inflammatory response and oxidative stress and the role of KIM-1 as a possible biomarker used to predict cisplatin associated AKI.

The Anatomy of Papal Tiara: A Story About Popes' Contribution and Protection of Anatomists.

Beginning with the thirteenth century, the papacy has exerted an important role in the development of anatomy and medical sciences through the protection and support provided to anatomists, who were in most cases the personal physicians of the popes as well. The work is intended to be a lesson of anatomy of Papal tiara, presenting the most important contributing popes, the anatomists-physicians whom they supported and protected and the relations between papacy and medical sciences.

The beneficial effects on blood pressure, dyslipidemia and oxidative stress of Sambucus nigra extract associated with renin inhibitors.

CONTEXT: The health effects of Sambucus nigra L. (Caprifoliaceae) could be due to polyphenols whose modes of action differ from the traditional one proposed for exogenous antioxidants. OBJECTIVE: The study emphasizes the effects of the association between the renin inhibitor and the polyphenolic extract on biochemical parameters and systolic (TAS) and diastolic (TAD) blood pressure within an L NAME-induced experimental model of arterial hypertension (AHT). MATERIALS AND METHODS: The polyphenols are extracted with ethanol from isolated and purified vegetable material represented by the mature fruit of the S. nigra with a dosage of 0.046 g/kg body weight (PS), every 2 days, for 8 weeks. The dose represents 1/20 of LD50. The Wistar white rat blood pressure values were recorded using a CODA™ system, which uses a non-invasive blood pressure measuring method. RESULTS AND DISCUSSION: The total antioxidant capacity levels were significantly decreased (p < 0.001) in AHT group as compared to the rats in the AHT + PS group. A combination of a renin inhibitor (Aliskiren) and polyphenolic extract generated a superior antioxidant effect compared to administering the two separately. Both TAS and TAD in rats with drug-induced hypertension were reduced by polyphenolic extract. The homogeneous values of TAS record a significant decrease (p < 0.001) of the average values in AHT + PS group or AHT + Aliskiren group. CONCLUSION: The combination of two different classes of substances, namely, renin inhibitors and natural polyphenol extracts, reduces arterial pressure and also might reduce the side effects of the major classes of antihypertensive agents and improve the quality of live.

Effects of Sambucus nigra and Aronia melanocarpa extracts on immune system disorders within diabetes mellitus.

CONTEXT: The fruits of Aronia melanocarpa Elliot (Rosaceae), (black chokeberry), and Sambucus nigra L. (Caprifoliaceae), elderberries are rich in anthocyanins. Many studies have reported that anthocyanins are beneficial in diabetes due to their capacity to stimulate insulin secretion and reduce oxidative stress. OBJECTIVE: The purpose of this study is to prove the biologically active properties of polyphenols extracted from S. nigra and A. melanocarpa fruit. The study also details the influence of plant polyphenols on immune system imbalances within diabetes mellitus. MATERIALS AND METHODS: Polyphenolic extract was administered to Wistar rats 0.040 g/kg body every 2 d for 16 weeks. The absorbencies of all the solutions were determined using a V-550 Able Jasco UV-VIS spectrophotometer. The immunomodulatory capacity of vegetal extracts was assessed by studying cytokines TNF-α and IFN-γ through the ELISA method and fibrinogen values. RESULTS AND DISCUSSION: At 48 h, the anti-inflammatory effects of S. nigra and A. melanocarpa substances have been revealed by an increase of the TNF-α and IFN-γ levels in the diabetic group protected by these extracts. Seventy-two hours post-administration of both substances in the diabetic groups, the TNF-α level returns to the values read 24 h after substance administration. The vegetal extracts limit the production of fibrinogen in the diabetic rats under polyphenolic protection, the values being highly significant compared with the diabetic group. CONCLUSIONS: Natural polyphenols extracted from S. nigra and A. melanocarpa modulate specific and non-specific immune defenses in insulin-deficiency diabetes and reduce the inflammatory status and self-sustained pancreatic insulitis.

Thrombotic Disease in Hemophilic Patients: Is This a Paradox in a State of Hypocoagulability?

Hemophilia patients have a deficiency in or dysfunction of clotting factors, which can lead to a bleeding tendency. However, paradoxically, some hemophilia patients may also be at an increased risk of developing thrombotic events such as deep vein thrombosis or pulmonary embolism. The pathophysiology of thrombosis in hemophilia patients is not fully understood, but it is thought to involve a complex interplay of various factors, including the severity of the hemophilia, the presence of other risk factors such as obesity, smoking, or the use of hormonal therapies, and the presence of certain genetic mutations that increase the risk of thrombosis. In addition, it has been suggested that the use of clotting factor replacement therapy, which is a standard treatment for hemophilia, may also contribute to the development of thrombosis in some cases.

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.

New Insights into the Pathophysiology of Coronary Artery Aneurysms.

Coronary aneurysms are typically defined as sections of a coronary artery where the diameter is more than 1.5 times that of an adjacent normal segment. In rare circumstances, these aneurysms can become exceedingly large, leading to the classification of giant coronary artery aneurysms. Despite their occurrence, there is no clear consensus on the precise definition of giant coronary artery aneurysms, and their etiology remains somewhat ambiguous. Numerous potential causes have been suggested, with atherosclerosis being the most prevalent in adults, accounting for up to 50% of cases. In pediatric populations, Kawasaki disease and Takayasu arteritis are the primary causes. Although often discovered incidentally, coronary artery aneurysms can lead to severe complications. These complications include local thrombosis, distal embolization, rupture, and vasospasm, which can result in ischemia, heart failure, and arrhythmias. The optimal approach to medical, interventional, or surgical management of these aneurysms is still under debate and requires further clarification. This literature review aims to consolidate current knowledge regarding coronary artery aneurysms' pathophysiology, emphasizing their definition, causes, complications, and treatment strategies. Recent research has begun to explore the molecular mechanisms involved in the formation and progression of coronary artery aneurysms. Various molecules, such as matrix metalloproteinases (MMPs), inflammatory cytokines, and growth factors, play crucial roles in the degradation of the extracellular matrix and the remodeling of vascular walls. Elevated levels of MMPs, particularly MMP-9, have been associated with the weakening of the arterial wall, contributing to aneurysm development. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1ß and IL-6) have been implicated in promoting inflammatory responses that further degrade vascular integrity. Additionally, growth factors such as vascular endothelial growth factor (VEGF) may influence angiogenesis and vascular remodeling processes. Understanding these molecular pathways is essential for developing targeted therapies aimed at preventing the progression of coronary artery aneurysms and improving patient outcomes.

Duality of Branched-Chain Amino Acids in Chronic Cardiovascular Disease: Potential Biomarkers versus Active Pathophysiological Promoters.

Branched-chain amino acids (BCAAs), comprising leucine (Leu), isoleucine (Ile), and valine (Val), are essential nutrients vital for protein synthesis and metabolic regulation via specialized signaling networks. Their association with cardiovascular diseases (CVDs) has become a focal point of scientific debate, with emerging evidence suggesting both beneficial and detrimental roles. This review aims to dissect the multifaceted relationship between BCAAs and cardiovascular health, exploring the molecular mechanisms and clinical implications. Elevated BCAA levels have also been linked to insulin resistance (IR), type 2 diabetes mellitus (T2DM), inflammation, and dyslipidemia, which are well-established risk factors for CVD. Central to these processes are key pathways such as mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-light-chain-enhancer of activate B cells (NF-κB)-mediated inflammation, and oxidative stress. Additionally, the interplay between BCAA metabolism and gut microbiota, particularly the production of metabolites like trimethylamine-N-oxide (TMAO), adds another layer of complexity. Contrarily, some studies propose that BCAAs may have cardioprotective effects under certain conditions, contributing to muscle maintenance and metabolic health. This review critically evaluates the evidence, addressing the biological basis and signal transduction mechanism, and also discusses the potential for BCAAs to act as biomarkers versus active mediators of cardiovascular pathology. By presenting a balanced analysis, this review seeks to clarify the contentious roles of BCAAs in CVD, providing a foundation for future research and therapeutic strategies required because of the rising prevalence, incidence, and total burden of CVDs.

Modern Treatment of Valvulopathies in Patients with Congenital Hemophilia.

Hemophiliacs can develop cardiovascular diseases, including valvulopathies of various etiologies and severities. Some require surgical treatment. Performing cardiac surgery in hemophiliacs is a challenge because they maintain an increased risk of bleeding throughout their lives. Our review shows that with a multidisciplinary team and careful planning, cardiac surgery can be safely performed in these patients. Valve repair and bioprosthetic valves should be preferred over mechanical valves to avoid life-long anticoagulation. In patients who cannot receive a bioprosthetic valve, the use of the On-X mechanical valve might be considered because it requires less intensive anticoagulation after 3 months of treatment. Antithrombotic treatment is feasible in hemophiliacs only if the coagulation factor level is kept constantly above a specific trough limit. Our review is valuable because, for the first time, the available data on the modern surgical treatment of valvular disease in hemophiliacs have been synthesized and systematized.

Interleukin-1-beta and dyslipidemic syndrome as major risk factors for thrombotic complications in type 2 diabetes mellitus.

Diabetes mellitus (DM) is a complex disease characterized by chronic hyperglycemia, a known risk factor for accelerated atherosclerosis and vascular disease. The aim of this study was to show that the connection between DM and other risk factors, such as dyslipidemia, inflammatory phenomena, or the development of certain vascular injuries, leads to a high frequency of thrombotic events in diabetic patients compared to the nondiabetic population. The study included one hundred eighty patients divided in the following groups: diabetic without ischemic cardiopathy-related disorders (DM), diabetic with clinical or off-clinical (electrocardiogram, cardiac ultrasound) ischemic cardiopathy-related disorders (DM + IC), and nondiabetic with ischemic cardiopathy-related disorders (IC). We investigated the following parameters: von Willebrand Factor, HDL-cholesterol, LDL-cholesterol, interleukin-1-beta, protein C, and plasminogen activator inhibitor type 1. The results achieved in our study have revealed the highest thrombotic risk among the groups of diabetic patients, which is in direct correlation with the high values of interleukin-1-beta and the modifications of lipid parameters, acknowledging the data in the literature, according to which hyperglycemia alters endothelial functions directly and indirectly by synthesis of growth factors and cytokines and generates metabolic disorders which would explain the high risk for thrombotic events.

Artificial Neural Network Models for Accurate Predictions of Fat-Free and Fat Masses, Using Easy-to-Measure Anthropometric Parameters.

Abdominal fat and fat-free masses report a close association with cardiometabolic risks, therefore this specific body compartment presents more interest than whole-body masses. This research aimed to develop accurate algorithms that predict body masses and specifically trunk fat and fat-free masses from easy to measure parameters in any setting. The study included 104 apparently healthy subjects, but with a higher-than-normal percent of adiposity or waist circumference. Multiple linear regression (MLR) and artificial neural network (ANN) models were built for predicting abdominal fat and fat-free masses in patients with relatively low cardiometabolic risks. The data were divided into training, validation and test sets, and this process was repeated 20 times per each model to reduce the bias of data division on model accuracy. The best performance models used a maximum number of five anthropometric inputs, with higher R2 values for ANN models than for MLR models (R2 = 0.96-0.98 vs. R2 = 0.80-0.94, p = 0.006). The root mean square error (RMSE) for all predicted parameters was significantly lower for ANN models than for MLR models, suggesting a higher accuracy for ANN models. From all body masses predicted, trunk fat mass and fat-free mass registered the best performance with ANN, allowing a possible error of 1.84 kg for predicting the correct trunk fat mass and 1.48 kg for predicting the correct trunk fat-free mass. The developed algorithms represent cost-effective prediction tools for the most relevant adipose and lean tissues involved in the physiopathology of cardiometabolic risks.

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.

Long-Term Adherence in Overweight Patients with Obstructive Sleep Apnea and Hypertension-A Pilot Prospective Cohort Study.

Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk, sedentarism, depression, anxiety and impaired quality of life. The long-term effectiveness of positive airway pressure (PAP) is insufficiently studied and limited by poor patient compliance. The aim of this pilot prospective cohort study was to evaluate long-term adherence in overweight patients with moderate-severe OSA and hypertension and to analyze changes in weight, sleepiness and quality of life. We performed a prospective study that included overweight patients with moderate-severe OSA and hypertension who had not undergone previous PAP therapy. All subjects received a standard physical examination, education regarding lifestyle changes and free PAP therapy for 2 months. After five years, the patients were invited to participate in a telephone-based interview regarding PAP compliance and completed standard questionnaires assessing adherence to medication, physical activity, diet, anxiety and quality of life (QoL). Only 39.58% of the patients were adherent to PAP 5 years (58.42 ± 3.70 months) after being diagnosed with moderate-severe OSA. Long-term PAP use results in sustained weight loss; improved blood pressure control, sleepiness and QOL; and lower anxiety and depression scores. PAP compliance was not associated with a higher level of daily physical activity or a healthier diet.

Could Endothelin-1 Be a Promising Neurohormonal Biomarker in Acute Heart Failure?

Acute heart failure (AHF) is a life-threatening condition with high morbidity and mortality. Even though this pathology has been extensively researched, there are still challenges in establishing an accurate and early diagnosis, determining the long- and short-term prognosis and choosing a targeted therapeutic strategy. The use of reliable biomarkers to support clinical judgment has been shown to improve the management of AHF patients. Despite a large pool of interesting candidate biomarkers, endothelin-1 (ET-1) appears to be involved in multiple aspects of AHF pathogenesis that include neurohormonal activation, cardiac remodeling, endothelial dysfunction, inflammation, atherosclerosis and alteration of the renal function. Since its discovery, numerous studies have shown that the level of ET-1 is associated with the severity of symptoms and cardiac dysfunction in this pathology. The purpose of this paper is to review the existing information on ET-1 and answer the question of whether this neurohormone could be a promising biomarker in AHF.