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.

The Molecular Mechanisms Underlying the Systemic Effects Mediated by Parathormone in the Context of Chronic Kidney Disease.

Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone-Vitamin D-Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated "trade-off hypothesis" reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient's prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin-Angiotensin-Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.

A Histological Evaluation of the Efficiency of Using Periprosthetic Autologous Fat to Prevent Capsular Contracture Compared to Other Known Methods-An Experimental Study.

BACKGROUND: Capsular contracture remains a common complication in silicone breast implantation. The etiology, formation mechanisms, predisposing and favoring factors are still subjects of research. This study aims to demonstrate the effectiveness of using autologous fat introduced periprosthetically in preventing capsular contracture compared to other known methods: antibiotics and corticosteroids. METHODS: A cohort of 80 Wistar rats was included in the study, divided into four subgroups. All subjects received a silicone implant, implanted in a pocket created along the abdominal midline. The first subgroup served as the control group, with subjects having the implant placed without any treatment. For the second and third subgroups, the implants were treated with an antibiotic solution and intramuscular injections of dexamethasone, respectively. The subjects in the last subgroup received centrifuged autologous fat introduced periprosthetically. RESULTS: The subgroup with autologous fat exhibited a significantly smaller capsule thickness, which was poorly represented, with a smooth surface. The use of autologous fat for treating silicone prosthesis was linked with the lack of acute inflammation around the prosthetic site. CONCLUSIONS: Autologous fat helps to minimize the "non-self" reaction, which results in the development of a periprosthetic capsule consisting of mature collagen fibers interspersed with adipocytes.

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.

The Renin-Angiotensin System: The Challenge behind Autoimmune Dermatological Diseases.

Autoimmune dermatological diseases (AIDD) encompass a diverse group of disorders characterized by aberrant immune responses targeting the skin and its associated structures. In recent years, emerging evidence suggests a potential involvement of the renin-angiotensin system (RAS) in the pathogenesis and progression of these conditions. RAS is a multicomponent cascade, primarily known for its role in regulating blood pressure and fluid balance. All of the RAS components play an important role in controlling inflammation and other immune responses. Angiotensin II, the main effector, acts on two essential receptors: Angiotensin Receptor 1 and 2 (AT1R and AT2R). A disturbance in the axis can lead to many pathological processes, including autoimmune (AI) diseases. AT1R activation triggers diverse signaling cascades involved in inflammation, fibrosis and tissue remodeling. Experimental studies have demonstrated the presence of AT1R in various cutaneous cells and immune cells, further emphasizing its potential contribution to the AI processes in the skin. Furthermore, recent investigations have highlighted the role of other RAS components, beyond angiotensin-converting enzyme (ACE) and Ang II, that may contribute to the pathophysiology of AIDD. Alternative pathways involving ACE2, Ang receptors and Ang-(1-7) have been implicated in regulating immune responses and tissue homeostasis within the skin microenvironment. Understanding the intricate involvement of the RAS in AIDD may provide novel therapeutic opportunities. Targeting specific components of the RAS, such as angiotensin receptor blockers (ARBs), ACE inhibitors (ACEIs) or alternative RAS pathway modulators, could potentially ameliorate inflammatory responses, reduce tissue damage and lessen disease manifestations. Further research is warranted to outline the exact mechanisms underlying RAS-mediated immune dysregulation in AIDD. This abstract aims to provide a concise overview of the intricate interplay between the RAS and AIDD. Therefore, we elaborate a systematic review of the potential challenge of RAS in the AIDD, including psoriasis, systemic sclerosis, vitiligo, lupus erythematosus and many more.

The Usefulness of Nanotechnology in Improving the Prognosis of Lung Cancer.

Lung cancer remains a major public health problem both in terms of incidence and specific mortality despite recent developments in terms of prevention, such as smoking reduction policies and clinical management advances. Better lung cancer prognosis could be achieved by early and accurate diagnosis and improved therapeutic interventions. Nanotechnology is a dynamic and fast-developing field; various medical applications have been developed and deployed, and more exist as proofs of concepts or experimental models. We aim to summarize current knowledge relevant to the use of nanotechnology in lung cancer management. Starting from the chemical structure-based classification of nanoparticles, we identify and review various practical implementations roughly organized as diagnostic or therapeutic in scope, ranging from innovative contrast agents to targeted drug carriers. Available data are presented starting with standards of practice and moving to highly experimental methods and proofs of concept; particularities, advantages, limits and future directions are explored, focusing on the potential impact on lung cancer clinical prognosis.

The RAAS Axis and SARS-CoV-2: From Oral to Systemic Manifestations.

One of the essential regulators of arterial blood pressure, the renin-angiotensin-aldosterone system (RAAS) seems to be one of the most complex mechanisms in the human body. Since the discovery of its key components and their actions, new substances and functions are still being unraveled. The main pathway begins with the secretion of renin in the kidney and culminates with the synthesis of angiotensin II (Ang II)-a strong vasoconstrictor-thanks to the angiotensin-converting enzyme (ACE). Research conducted in 2000 identified another enzyme, named ACE2, that converts Ang II into Ang-(1-7), a heptapeptide with opposing effects to those of Ang II: vasodilation and anti-inflammatory properties. This particular enzyme became of paramount importance during the last two decades, as a result of the confrontation of the human race with life-threatening epidemics. Multiple studies have been performed in order to uncover the link between ACE2 and human coronaviruses, the results of which we systemized in order to create an overview of the pathogenic mechanism. Human coronaviruses, such as SARS-CoV and SARS-CoV-2, attach to ACE2 via their spike proteins (S), causing the destruction of the enzyme. Because ACE2 limits the production of Ang II (by converting it into Ang-(1-7)), its destruction leads to a dysregulated inflammatory response. The purpose of this review is to decipher the complex pathophysiological mechanisms underlying the multiorgan complications (oral, cardiac, pulmonary, systemic) that appear as a result of the interaction of the SARS CoV-2 virus with the angiotensin-converting enzyme type 2.

Hemoperitoneum as a Life-Threatening Complication of an Acute Cholecystitis in a Patient with Hemophilia A with Inhibitors: A Case Report.

We present the case of a 52-year-old male with severe hemophilia A with inhibitors, who was diagnosticated with acute lithiasic cholecystitis that required surgical intervention due to lack of favorable response to conservatory treatment. During surgery, hemostatic support was performed with activated recombinant factor VII (rFVIIa, NovoSeven®). The surgery was performed first laparoscopically with adhesiolysis, followed by subcostal laparotomy and cholecystectomy because of the findings of a pericholecystic plastron with abscess and massive inflammatory anatomical modifications. The patient presented postoperative complications, requiring a second surgical intervention, due to the installation of a hemoperitoneum. Hemostatic treatment with rFVIIa was given for a further 3 weeks postoperatively, and the patient was discharged in safe condition. A surgical intervention increases the risk of bleeding in hemophilic patients, which may have vital complications in the absence of adequate hemostatic support and the support of a multidisciplinary team with experience in hemophilic surgery.

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.

Pain Intensity and Degree of Disability after Fragility Fractures of the Pelvis.

Background and objectives: Fragility fractures of the pelvis (FFP) are of increasing interest lately, being associated with a loss of mobility and affecting the quality of life. The aim of our study was to investigate the effect of FFP on disability and pain in patients, after one year since injury. Materials and Methods: In the study, we included 76 patients diagnosed with FFP, who were admitted to our trauma department between January 2016 and January 2019, and were above 65 years of age. The Von Korff pain intensity and disability scores were calculated in the hospital at 6 months and after 1 year. Results: Fifty-four patients were female (71%), with an average age of 75.9 ± 7.19 years. Twenty-two patients were male (29%) and had a mean age of 77.22 ± 7.33 years. We did not record significant differences regarding age between the men and women (p > 0.05). Significant improvements appeared between the baseline and the 6 month follow-up; the average pain intensity score at 6 months was 44.94 (SD 21.20) (p < 0.001), and the disability score was 54.30 (SD 21.62). The following average pain intensity and disability scores after 12 months were similar to the values at6 months: 44.48 (SD 21.74) for pain intensity and 52.36 (SD 24.53) for disability. The Von Korff pain score at 6 months and after 1 year depends on gender and on the initial Von Korff pain score (p = 0.02). The Von Korff disability score at 6 months depends on gender, the baseline pain score and the baseline disability score (p = 0.001). Conclusions: our patients reported long-lasting pain that had a severe effect on their daily routines, and they could not return to their normal status prior to injury.

Vitamin D Deficiency in Both Oral and Systemic Manifestations in SARS-CoV-2 Infection: Updated Review.

The specialized literature emphasizes the fact that vitamin D has a potentially beneficial effect in the context of the current COVID-19 pandemic. The purpose of this article is to highlight the role of vitamin D, both prophylactic and curative, in the treatment of patients diagnosed with COVID-19. Even though its relevance is still unknown and causes various controversies, there is currently no specific treatment for patients diagnosed with COVID-19. There are various prevention strategies with new vaccination schedules, but additional randomized and clinical trials are still needed to combat this pandemic. In addition to the systemic manifestations of SARS-CoV-2 infection, oral manifestations of this disease have also been described in the literature. The etiology of oral manifestations associated with COVID-19 infection and vitamin D deficiency remains controversial. In the present studies, oral manifestations such as salivary gland infections, aphthae, erythema, gingivitis, ulcers, etc. have been reported. This is a new topic, and the prevalence of manifestations is described in only a few studies, which is inconsistent with the number of COVID-19 cases reported since the beginning of the pandemic. The clinical symptomatology in patients with current COVID-19 infection is polymorphic. Whether the oral manifestation is directly caused by SARS-CoV-2 or a secondary manifestation remains an important topic to analyze and discuss.

SARS-CoV-2 Infection: What Is Currently Known about Homocysteine Involvement?

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world causing health, social and economic instability. The severity and prognosis of patients with SARS-CoV-2 infection are associated with the presence of comorbidities such as cardiovascular disease, hypertension, chronic lung disease, cerebrovascular disease, diabetes, chronic kidney disease, and malignancy. Thrombosis is one of the most serious complications that can occur in patients with COVID-19. Homocysteine is a non-proteinogenic α-amino acid considered a potential marker of thrombotic diseases. Our review aims to provide an updated analysis of the data on the involvement of homocysteine in COVID-19 to highlight the correlation of this amino acid with disease severity and the possible mechanisms by which it intervenes.

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.

Hypolipemiant Actions and Possible Cardioprotective Effects of Valine and Leucine: An Experimental Study.

Background and Objectives: Considering atherosclerosis as one of the more challenging threats to healthcare worldwide, any novel therapy that counteracts the risks for developing it, provides new opportunities for the management of this process. Material and methods: We performed an experimental research in which we induced a hypercholesterolemia via a cholesterol-rich diet. Our aim was to demonstrate the antiatherogenic potential of two essential amino acids (valine and leucine). The experimental study was carried out over a period of 60 days. Male Wistar rats weighing between 250-280 g were used and divided into 4 groups, each group including 8 animals. Group I-control was fed with a standard diet. Group II received cholesterol, group III cholesterol and valine and group IV cholesterol and leucine. Blood samples were collected from the retro-orbital plexus, under anesthesia with 75 mg/kg of intraperitoneal ketamine, in three different moments (R0-1st day, R1-the 30th day, R2-the 60th day) in order to measure the levels of triglycerides. Results: In R0, there were no significant differences between the average levels of triglycerides across all the groups (p < 0.05). Compared to the group I, in R1 and R2, the average levels of triglycerides were significantly higher in all groups (p < 0.001). Also, in R1 and R2, the average triglycerides in group II receiving cholesterol (C) were significantly higher than those in group III receiving valine (C + V) as well as in group IV receiving leucine (C + L) (p < 0.001; p < 0.05). In R2, the average triglycerides in group III were significantly lower than in group IV (p < 0.001). Conclusions: Our data provides evidence that valine and leucine have a direct impact on the lipid metabolism parameters by lowering the level of triglycerides. The comparison of the two essential amino acids indicates that valine acts more promptly and rapidly than leucine.

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.