High-grade serous ovarian cancer (HGSOC) with fallopian tube involvement.

INTRODUCTION: Literature data present new studies about precancerous lesions of pelvic serous carcinoma that originate from the tubal secretory cells. It has long been thought that ovarian cancer cannot be prevented by prophylactic screening or surgery. In recent years, gynecologists have adapted to new principles and so, during routine hysterectomies in perimenopausal women for benign uterine pathologies, salpingo-oophorectomy is performed as a prophylactic approach. AIM: The purpose of our article was to draw attention to the association between abnormal fallopian tube pathology and the presence of serous ovarian neoplasia in perimenopausal women at risk. CASE PRESENTATION: We report the case of a 45-year-old woman who had unspecific symptoms of abdominal pain and loss of appetite and weight. A pelvic magnetic resonance imaging was performed, and an ovarian mass was detected. Our case shows that the fallopian tube can be the primary point of origin for a pelvic disease, therefore prevention is possible with early computed tomography scan and annual ultrasound. The patient presented with a T1c staging post-surgery and her chances of survival could have decreased if she had postponed medical examination longer. We found a significant increase in the absolute number of tubal secretory cells in patients with ovarian neoplasia, which supports the assumption that serous tubal intraepithelial carcinoma lesions are found especially in the serous ovarian type. CONCLUSIONS: Our article is a strong suggestion that serous ovarian cancer originates from the fallopian tube and can potentially serve as a sensitive biomarker for early serous carcinogenesis within the fallopian tube.

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.

An Overview of the Pharmacokinetics and Pharmacodynamics of Landiolol (an Ultra-Short Acting ß1 Selective Antagonist) in Atrial Fibrillation.

Landiolol is an ultra-short-acting, selective ß1-adrenergic receptor blocker that was originally approved in Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high ß1-selectivity, potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half-life (around 4 min); moreover, it may have a potential therapeutic effects for sepsis and pediatric patients. Landiolol seems to be superior to other short-acting and selective beta-blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

Accidental Hypothermia in the Largest Emergency Hospital in North-Eastern Romania.

INTRODUCTION: Accidental hypothermia (AH) presents a significant mortality risk, even in individuals with good health. Early recognition of the parameters associated with negative prognosis could save more lives. METHODS: This was a pilot, retrospective observational study, conducted in the largest Emergency Hospital in North Eastern Romania, which included all patients with AH (defined as body temperature below 35°C), hospitalized and treated in our hospital between 2019 and 2022. RESULTS: A total of 104 patients with AH were included in our study, 90 of whom had data collected and statistically analyzed. The clinical, biological, and therapeutic parameters associated with negative outcomes were represented by a reduced GCS score (p=0.024), diminished systolic and diastolic blood pressure (p=0.007 respectively, 0.013), decreased bicarbonate (p=0.043) and hemoglobin levels (p=0.002), the presence of coagulation disorders (p=0.007), as well as the need for administration of inotropic or vasopressor medications (p=0.04). CONCLUSION: In this pilot, retrospective, observational study, the negative outcomes observed in patients with AH hospitalized in the largest Emergency Hospital in North-Eastern Romania were associated with several clinical, biochemical, and therapeutic factors, which are easy to identify in clinical practice. Recognizing the significance of these associated factors empowers healthcare practitioners to intervene at an early stage to save more lives.

Epidemiological and histopathological aspects of ocular melanomas in Northeastern Romania.

Ocular melanoma is a rare but complex disease in current medical practice. Our retrospective study spans over a period of 28 years and analyzed uveal and conjunctival melanomas that were consecutively admitted, diagnosed, and treated in the 2nd Ophthalmology Clinic of Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania. The patients were selected from the records of the Department of Pathology of our Hospital, being diagnosed by standard histopathological techniques. The aim of this study was to summarize the epidemiological and pathological aspects of uveal and conjunctival melanomas in Northeastern region of Romania. In our study, we did not notice a predilection of uveal and conjunctival melanoma to one particular gender. The most common histological subtypes of ocular melanomas were the heavily pigmented spindle cell subtype, followed by the epithelioid subtype. Our patients sought medical help in a timely manner, before the systemic invasion of the disease could develop.

Multimodality Imaging in Right Heart Tumors: Proposed Algorithm towards an Appropriate Diagnosis.

A right heart tumor can be identified by transthoracic echocardiography during a routine examination or due to cardiac symptoms. The first step is the assessment by echocardiography, with its multiple techniques, and the obtained information must be judged in a clinical and biological context. The second step comprises one, sometimes even two, of the more complex modality imaging methods. The choice is driven not only by the advantages of each imaging technique but also by local expertise or the preferred imaging modality in the center. This step is followed by staging, follow-up, and/or imaging-guided excision or biopsy, which is performed in selected cases in order to obtain anatomopathological confirmation. In the presence of features suggestive of malignancy or causing hemodynamic impairment, a transvenous biopsy is essential before the more complex imaging modalities (which are still relevant in the staging process). Using a structured imaging approach, it is possible to reach an appropriate diagnosis without a biopsy. Frequently, these imaging techniques have a complementary role, so an integrated imaging approach is recommended. This proposed algorithm for appropriate diagnosis of right heart tumors could serve as a practical guide for clinicians (not only imaging specialists).

Depiction of Branched-Chain Amino Acids (BCAAs) in Diabetes with a Focus on Diabetic Microvascular Complications.

Type 2 diabetes mellitus (T2DM) still holds the title as one of the most debilitating chronic diseases with rising prevalence and incidence, including its complications such as retinal, renal, and peripheral nerve disease. In order to develop novel molecules for diagnosis and treatment, a deep understanding of the complex molecular pathways is imperative. Currently, the existing agents for T2DM treatment target only blood glucose levels. Over the past decades, specific building blocks of proteins-branched-chain amino acids (BCAAs) including leucine, isoleucine, and valine-have gained attention because they are linked with insulin resistance, pre-diabetes, and diabetes development. In this review, we discuss the hypothetical link between BCAA metabolism, insulin resistance, T2DM, and its microvascular complications including diabetic retinopathy and diabetic nephropathy. Further research on these amino acids and their derivates may eventually pave the way to novel biomarkers or therapeutic concepts for the treatment of diabetes and its accompanied complications.

Mitral Annular Calcification and Thromboembolic Risk.

Thromboembolic (TE) risk scores used for atrial fibrillation (AF) patients do not include mitral annular calcification (MAC) as a potential indicator of vascular disease. This research evaluated the correlation between MAC and TE risk scores (CHADS2 and CHA2DS2-VASc). We compared TE risk score values and clinical and echocardiographic data in patients with and without MAC. We included, prospectively, 103 patients: 40.8% with AF, 83.5% with hypertension, 30.1% with type II diabetes mellitus, 79.6% with chronic heart failure, and 7.8% with a history of stroke. We identified MAC in 50.5% of patients. The mean CHADS2 and CHA2DS2-VASc scores were 2.56 ± 1.135 and 4.57 ± 1.61, respectively. In MAC patients, both scores tended to increase significantly compared with the control (2.88 ± 1.114 versus 2.24 ± 1.06, p = 0.005, and 5.21 ± 1.51 versus 3.92 ± 1.46, p < 0.001, respectively). The left ventricular ejection fraction negatively correlated with the presence of MAC (r = -0.254, p = 0.01). The presence of MAC was a risk factor for vascular disease (OR = 2.47, χ2 = 34.32, p < 0001). Conclusions: The presence of MAC is associated with greater TE risk scores and a higher risk of vascular disease. It appears that adding MAC as a vascular disease parameter to TE risk scores may have benefits for patients by improving their predictive value.

Managing Anemia: Point of Convergence for Heart Failure and Chronic Kidney Disease?

The pathologic triangle formed by chronic heart failure (HF), chronic kidney disease (CKD), and anemia carries high morbidity and mortality rates and decreases quality of life. Anemia represents a common condition in patients with advanced HF and CKD, with a total prevalence in cardiorenal syndrome (CRS) ranging from 5% to 55%. Searching for a pragmatic approach for these patients with guided and disease-specific recommendations beyond just targeted hemoglobin therapeutic behavior represents the core of research for ongoing clinical trials. It is well known that the prevalence of anemia increases with the advancement of CKD and HF. The physiopathological mechanisms of anemia, such as the reduction of endogenous erythropoietin and the decrease in oxygen transport, are leading to tissue hypoxia, peripheral vasodilation, stimulating neurohormonal activity, and maintenance of the progressive renal and cardiac dysfunction. Given the challenges with the treatment options for patients with cardiorenal anemia syndrome (CRSA), new therapeutic agents such as hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PH) or hepcidin antagonists are emerging in the light of recent research. This review summarizes the potential therapeutic tools for anemia therapy in the cardiorenal population.

Atrial Fibrillation and Chronic Coronary Ischemia: A Challenging Vicious Circle.

Atrial fibrillation, the most frequent arrhythmia in clinical practice and chronic coronary syndrome, is one of the forms of coronary ischemia to have a strong dual relationship. Atrial fibrillation may accelerate atherosclerosis and may increase oxygen consumption in the myocardium, creating a mismatch between supply and demand, thus promoting the development or worsening of coronary ischemia. Chronic coronary syndrome alters the structure and function of gap junction proteins, affecting the conduction of action potential and leading to ischemic necrosis of cardiomyocytes and their replacement with fibrous tissue, in this way sustaining the focal ectopic activity in atrial myocardium. They have many risk factors in common, such as hypertension, obesity, type 2 diabetes mellitus, and dyslipidemia. It is vital for the prognosis of patients to break this vicious circle by controlling risk factors, drug therapies, of which antithrombotic therapy may sometimes be challenging in terms of prothrombotic and bleeding risk, and interventional therapies (revascularization and catheter ablation).

Gastro-Esophageal Reflux Disease and Paroxysmal Atrial Fibrillation Ablation.

Patients undergoing ablation for atrial fibrillation may be at increased risk of developing gastroesophageal reflux disease. We prospectively studied the presence of symptomatic gastroesophageal reflux disease in naïve patients who underwent atrial fibrillation ablation. METHODS: The presence of typical symptoms suggestive of gastroesophageal reflux disease was clinically assessed by the gastroenterologist at baseline and at 3 months after ablation. In addition to that, all patients underwent upper gastrointestinal endoscopy. RESULTS: Seventy-five patients were included in two groups: 46 patients who underwent atrial fibrillation ablation (study group) and 29 patients without ablation (control group). Patients with atrial fibrillation ablation were younger (57.76 ± 7.66 years versus 67.81 ± 8.52 years; p = 0.001), predominantly male (62.2% versus 33.3%; p = 0.030) and with higher body mass index (28.96 ± 3.12 kg/m2 versus 26.81 ± 5.19 kg/m2; p = 0.046). At three months after the ablation, in the study and control groups, there were 88.9% and 57.1% patients in sinus rhythm, respectively, (p = 0.009). Symptomatic gastroesophageal reflux disease was not more frequent in the study group (42.2% versus 61.9%; p = 0.220). There was no difference in terms of sinus rhythm prevalence in patients with versus without symptomatic gastroesophageal reflux disease (89.5% versus 88.5%; p = 0.709). CONCLUSION: In this small prospective study, typical symptoms suggestive of gastroesophageal reflux disease were not more frequent three months following atrial fibrillation ablation.

Portrayal of NLRP3 Inflammasome in Atherosclerosis: Current Knowledge and Therapeutic Targets.

We are witnessing the globalization of a specific type of arteriosclerosis with rising prevalence, incidence and an overall cardiovascular disease burden. Currently, atherosclerosis increasingly affects the younger generation as compared to previous decades. While early preventive medicine has seen improvements, research advances in laboratory and clinical investigation promise to provide us with novel diagnosis tools. Given the physio-pathological complexity and epigenetic patterns of atherosclerosis and the discovery of new molecules involved, the therapeutic field of atherosclerosis has room for substantial growth. Thus, the scientific community is currently investigating the role of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a crucial component of the innate immune system in different inflammatory disorders. NLRP3 is activated by distinct factors and numerous cellular and molecular events which trigger NLRP3 inflammasome assembly with subsequent cleavage of pro-interleukin (IL)-1ß and pro-IL-18 pathways via caspase-1 activation, eliciting endothelial dysfunction, promotion of oxidative stress and the inflammation process of atherosclerosis. In this review, we introduce the basic cellular and molecular mechanisms of NLRP3 inflammasome activation and its role in atherosclerosis. We also emphasize its promising therapeutic pharmaceutical potential.

Role of arterial hypertension and angiotensin II in chronic kidney disease (Review).

Chronic kidney disease (CKD) is a major public health issue, due to its effect on the quality of life of patients and by the huge costs incurred in treating this disease. It is an irreversible process, characterized by the progressive loss of functional nephrons. CKD ultimately requires the support of renal function by dialysis or even renal transplantation. It has a multiple etiology, but the most common causes remain arterial hypertension and diabetes. High arterial blood pressure affects the target organs (kidneys) and this leads to a vicious circle involved in maintaining high blood pressure. Arterial hypertension is closely related to the renal pathology of CKD. The result of excessive activation of the renin angiotensin system (RAS) is increased angiotensin II (Ang II), which acts upon the systemic circulation and especially upon the kidneys. The outcome is high blood pressure and also the stimulation of proinflammatory and profibrotic effects in the kidneys. Collectively these ultimately lead to CKD. The aim of this review was to provide a brief overview of the pathophysiological associations between CKD, arterial hypertension, and Ang II.