The Effects of Different Hormones on Supraventricular and Ventricular Premature Contractions in Healthy Premenopausal Women.

Background and Objectives: The effects of gender differences on cardiac parameters have been well-established. In this study, we aimed to evaluate the possible associations of plasma levels of different sex hormones with premature atrial or ventricular contractions in premenopausal women. Materials and Methods: We conducted a prospective study which included women in late reproductive age who presented with palpitations during an eight-month period. A 12-lead electrocardiography, a transthoracic echocardiogram, blood samples, and 24-hour rhythm Holter were conducted on the third day of the menstrual cycle. Results Overall, 93 healthy premenopausal women with a median age of 42 years were enrolled. QTc interval was within normal limits in all patients. The 24 h range of premature atrial contractions (PACs) and premature ventricular contractions (PVCs) was 0-6450 and was 0-21,230, respectively. The median number of PVCs was 540 and the median number of PACs was 212, respectively. In total, 51 patients (54.8%) had a frequency of PVCs > 500/24 h and 37 patients (39.8%) had a frequency of PACs > 500/24 h, respectively. No statistically significant association was shown between any hormone and the frequency of PACs. Regarding PVCs, patients with a PVCs frequency > 500/24 h had higher estradiol levels compared to patients with PVCs less than 500/24 h (median 60 pg/mL versus 42 pg/mL, p = 0.02, OR: 1.01). No association was found between PVCs and other hormones. Conclusions: In premenopausal healthy women, higher estradiol levels are independently associated with increased PVCs. This suggests that estradiol in late reproductive stages may exert proarrhythmic effects.

Type 1 Diabetes Mellitus in the SARS-CoV-2 Pandemic: Oxidative Stress as a Major Pathophysiological Mechanism Linked to Adverse Clinical Outcomes.

Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a major role. Severe, life-threatening COVID-19 disease is characterized by the excessive release of pro-inflammatory cytokines, known as a "cytokine storm". Patients with T1DM present elevated levels of cytokines including interleukin-1a (IL), IL-1ß, IL-2, IL-6 and tumor necrosis factor alpha (TNF-α), suggesting the pre-existence of chronic inflammation, which, in turn, has been considered the major risk factor of adverse COVID-19 outcomes in many cohorts. Even more importantly, oxidative stress is a key player in COVID-19 pathogenesis and determines disease severity. It is well-known that extreme glucose excursions, the prominent feature of T1DM, are a potent mediator of oxidative stress through several pathways including the activation of protein kinase C (PKC) and the increased production of advanced glycation end products (AGEs). Additionally, chronic endothelial dysfunction and the hypercoagulant state observed in T1DM, in combination with the direct damage of endothelial cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may result in endothelial and microcirculation impairment, which contribute to the pathogenesis of acute respiratory syndrome and multi-organ failure. The binding of SARS-CoV-2 to angiotensin converting enzyme 2 (ACE2) receptors in pancreatic b-cells permits the direct destruction of b-cells, which contributes to the development of new-onset diabetes and the induction of diabetic ketoacidosis (DKA) in patients with T1DM. Large clinical studies are required to clarify the exact pathways through which T1DM results in worse COVID-19 outcomes.

Stress Hyperglycemia in Children and Adolescents as a Prognostic Indicator for the Development of Type 1 Diabetes Mellitus.

Hyperglycemia is a common manifestation in the course of severe disease and is the result of acute metabolic and hormonal changes associated with various factors such as trauma, stress, surgery, or infection. Numerous studies demonstrate the association of adverse clinical events with stress hyperglycemia. This article briefly describes the pathophysiological mechanisms which lead to hyperglycemia under stressful circumstances particularly in the pediatric and adolescent population. The importance of prevention of hyperglycemia, especially for children, is emphasized and the existing models for the prediction of diabetes are presented. The available studies on the association between stress hyperglycemia and progress to type 1 diabetes mellitus are presented, implying a possible role for stress hyperglycemia as part of a broader prognostic model for the prediction and prevention of overt disease in susceptible patients.

The Effect of Antioxidant and Anti-Inflammatory Capacity of Diet on Psoriasis and Psoriatic Arthritis Phenotype: Nutrition as Therapeutic Tool?

Chronic inflammation and increased oxidative stress are contributing factors to many non-communicable diseases. A growing body of evidence indicates that dietary nutrients can activate the immune system and may lead to the overproduction of pro-inflammatory cytokines. Fatty acids as macronutrients are key players for immunomodulation, with n-3 polyunsaturated fatty acids having the most beneficial effect, while polyphenols and carotenoids seem to be the most promising antioxidants. Psoriasis is a chronic, immune-mediated inflammatory disease with multifactorial etiology. Obesity is a major risk factor for psoriasis, which leads to worse clinical outcomes. Weight loss interventions and, generally, dietary regimens such as gluten-free and Mediterranean diet or supplement use may potentially improve psoriasis' natural course and response to therapy. However, data about more sophisticated nutritional patterns, such as ketogenic, very low-carb or specific macro- and micro-nutrient substitution, are scarce. This review aims to present the effect of strictly structured dietary nutrients, that are known to affect glucose/lipid metabolism and insulin responses, on chronic inflammation and immunity, and to discuss the utility of nutritional regimens as possible therapeutic tools for psoriasis and psoriatic arthritis.

Bariatric Surgery and Type 1 Diabetes: Unanswered Questions.

In recent decades there has been an alarming increase in the prevalence of obesity in patients with type 1 diabetes leading to the development of insulin resistance and cardiometabolic complications, with mechanisms poorly clarified. While bariatric surgery has long been considered an effective treatment option for patients with type 2 diabetes, the evidence regarding its benefits on weight loss and the prevention of complications in T1DM patients is scarce, with controversial outcomes. Bariatric surgery has been associated with a significant reduction in daily insulin requirement, along with a considerable reduction in body mass index, results which were sustained in the long term. Furthermore, studies suggest that bariatric surgery in type 1 diabetes results in the improvement of comorbidities related to obesity including hypertension and dyslipidemia. However, regarding glycemic control, the reduction of mean glycosylated hemoglobin was modest or statistically insignificant in most studies. The reasons for these results are yet to be elucidated; possible explanations include preservation of beta cell mass and increased residual function post-surgery, improvement in insulin action, altered GLP-1 function, timing of surgery, and association with residual islet cell mass. A number of concerns regarding safety issues have arisen due to the reporting of peri-operative and post-operative adverse events. The most significant complications are metabolic and include diabetic ketoacidosis, severe hypoglycemia and glucose fluctuations. Further prospective clinical studies are required to provide evidence for the effect of bariatric surgery on T1DM patients. The results may offer a better knowledge for the selection of people living with diabetes who will benefit more from a metabolic surgery.

Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy.

BACKGROUND: Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. PATIENTS AND METHODS: Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. RESULTS: A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. CONCLUSION: Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group.

Dietary Composition and Cardiovascular Risk: A Mediator or a Bystander?

The role of nutrition in the pathogenesis of cardiovascular disease has long been debated. The established notion of the deleterious effects of fat is recently under question, with numerous studies demonstrating the benefits of low-carbohydrate, high-fat diets in terms of obesity, diabetes, dyslipidemia, and metabolic derangement. Monounsaturated and polyunsaturated fatty acids, especially n-3 PUFAs (polyunsaturated fatty acids), are the types of fat that favor metabolic markers and are key components of the Mediterranean Diet, which is considered an ideal dietary pattern with great cardioprotective effects. Except for macronutrients, however, micronutrients like polyphenols, carotenoids, and vitamins act on molecular pathways that affect oxidative stress, endothelial function, and lipid and glucose homeostasis. In relation to these metabolic markers, the human gut microbiome is constantly revealed, with its composition being altered by even small dietary changes and different microbial populations being associated with adverse cardiovascular outcomes, thus becoming the target for potential new treatment interventions. This review aims to present the most recent data concerning different dietary patterns at both the macro- and micronutrient level and their association with atherosclerosis, obesity, and other risk factors for cardiovascular disease.

Cytokines, diabetes mellitus and psychopathology: a challenging combination.

OBJECTIVES: The aim of this study was to investigate the association of IL-6, IL-12, and TNF-α with trait and state psychological factors in type 2 diabetic patients. DESIGN: Patients were divided in two groups. Group A consisted of 86 controlled diabetic patients (HbA1c<7) and the Group B consisted of 45 uncontrolled diabetic patients (HbA1c ≥ 7). SETTINGS: During the initial phase of the study (T0), blood samples were taken for measuring IL-6, IL-12 and TNF-α serum levels as well as a battery of psychometric instruments. One year later (T1), the uncontrolled diabetic patients were re-evaluated with the use of the same psychometric instruments and with the identical blood analysis. RESULTS: The average values of tnf-α were significantly different among controlled (7.73 ± 5.51) and uncontrolled patients (9.29 ± 4.52) at a significance level of 5% (p=0.009). Controlled diabetic patients show a statistically significant relationship between IL-6 and neuroticism (rp=0.303, p=0.010), and between IL-12 and psychotism, (rsp=0.382, p=0.001). Controlled diabetic patients show a statistically significant relationship between IL-12 and the act out hostility (rsp=-0.307, p=0.009). The scores of the psychometric tests differ significantly between the first and second evaluation. Acting out hostility and the direction of hostility increased when HbA1c values fell below the threshold of 7, while the total hostility index, as well as all other scales, dropped when patients controlled their metabolic profile. CONCLUSIONS: The present results provide evidence that IL-6, IL-12 and TNF-α are closely related to the course and treatment of type 2 diabetes.

Insulin resistance in hyperthyroidism: the role of IL6 and TNF alpha.

OBJECTIVE: Although insulin resistance is a common finding in hyperthyroidism, the implicated mechanisms are obscure. The aim of this study was to investigate whether interleukin 6 (IL6) and tumour necrosis factor alpha (TNFalpha) are related to the development of insulin resistance in hyperthyroidism of nonautoimmune origin. DESIGN AND METHODS: A meal was given to ten hyperthyroid (HR) and ten euthyroid (EU) women. Plasma samples were taken for 360 min from the radial artery for measurements of glucose, insulin, and nonesterified fatty acids (NEFA). IL6 and TNFalpha were measured preprandially from the superficial epigastric vein and from the radial artery. RESULTS: i) In HR versus EU: (a) arterial glucose was similar (AUC(0-360) 2087+/-57 vs 2010+/-43 mM x min), but insulin was increased (AUC(0-360) 17 267+/-2447 vs 10 331+/-666 microU/ml x min, P=0.01), (b) homeostasis model assessment (HOMA) was increased (2.3+/-0.4 vs 1+/-0.1 kg/m(2), P=0.007), (c) arterial NEFA were increased (AUC(0-360) 136+/-18 vs 89+/-7 mmol/lxmin, P=0.03), (d) arterial IL6 (2+/-0.3 vs 0.9+/-0.1 pg/ml, P=0.0009) and TNFalpha (4.2+/-0.8 vs 1.5+/-0.2 pg/ml, P=0.003) were increased, and (e) IL6 production from the subcutaneous adipose tissue (AT) was increased (18+/-6 vs 5+/-1 pg/min per 100 ml tissue, P=0.04). ii) (a) Subcutaneous venous IL6 was positively associated with HOMA (beta-coefficient=1.7+/-0.7, P=0.049) and (b) although TNFalpha was not produced by the subcutaneous AT, arterial TNFalpha was positively associated with NEFA (AUC(0-360); beta-coefficient=0.045+/-0.01, P=0.005). CONCLUSIONS: In hyperthyroidism: i) glucose and lipid metabolism are resistant to insulin, ii) subcutaneous AT releases IL6, which could then act as an endocrine mediator of insulin resistance, iii) although there is no net secretion of TNFalpha by the subcutaneous AT, increased systemic TNFalpha levels may be related to the development of insulin resistance in lipolysis.