Autoimmune polyendocrine syndrome type 2 in patient with severe allergic asthma treated with omalizumab.

Asthma therapy with monoclonal antibodies is a promising and effective approach for those with a severe and refractory type of disease. Although such a targeted therapy is considered to be safe, unusual complications may occur. We present a case of a 45 year-old female patient with severe allergic asthma and chronic spontaneous urticaria, who developed autoimmune polyendocrine syndrome type 2 (APS-2) after 26 months of omalizumab administration. The patient was diagnosed with primary adrenal insufficiency (Addison's disease) and Hashimoto's thyroiditis accompanied by autoimmune atrophic gastritis. According to our knowledge this is the first description of APS-2 that developed in conjunction with omalizumab treatment, although we have no evidence that the observed phenomenon indicated a cause-effect relationship to omalizumab.

Association of adipokines and inflammatory markers with lipid control in type 2 diabetes.

INTRODUCTION: Data regarding the effect of certain adipokines on lipid metabolism are equivocal. OBJECTIVES: The aim of this study was to evaluate the association of lipid control with adipokines and inflammatory markers in patients with type 2 diabetes. PATIENTS AND METHODS: The analysis included 195 patients with type 2 diabetes. The achievement of treatment targets in terms of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides was assessed in accordance with the current guidelines. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index as well as concentrations of highmolecular-weight (HMW) adiponectin, leptin, resistin, high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor α (TNF-α) were measured in all patients. Logistic regression analyses were performed to determine the risk factors for inadequate lipid control. RESULTS: Optimal control in terms of total cholesterol, LDL, HDL, and triglycerides was achieved in 61%, 43%, 53%, and 68% of the patients, respectively. In multivariate analyses, female sex, lower resistin concentrations, and the absence of statin treatment were predictors of total cholesterol levels above the treatment target; older age and lower statin dose--of LDL cholesterol levels above the treatment targets; female sex, higher HOMA-IR index, lower HMW adiponectin concentrations, and higher TNF-α concentration-o-f HDL levels below the treatment targets; and higher HOMA-IR, lower HMW adiponectin concentration, and the absence of statin treatment--of triglycerides above the treatment target. CONCLUSIONS: In type 2 diabetes, lower HMW adiponectin concentrations are associated with inadequate triglyceride and HDL control; higher TNF-α, with inadequate HDL control, and lower resistin concentrations, with inadequate total cholesterol control.

Phosphatidylcholine-fatty Alcohols Equilibria in Monolayers at the Air/Water Interface.

Monolayers of phosphatidylcholine (PC), tetradecanol (TD), hexadecanol (HD), octadecanol (OD) and eicosanol (E) and their binary mixtures were investigated at the air/water interface. The surface tension values of pure and mixed monolayers were used to calculate π-A isotherms. The surface tension measurements were carried out at 22 °C using a Teflon trough and a Nima 9000 tensiometer. The interactions between phosphatidylcholine and fatty alcohols (tetradecanol, hexadecanol, octadecanol, eicosanol) result in significant deviations from the additivity rule. An equilibrium theory to describe the behavior of monolayer components at the air/water interface was developed in order to obtain the stability constants, Gibbs free energy values and areas occupied by one molecules of PC-TD, PC-HD, PC-OD and PC-E complexes. We considered the equilibrium between the individual components and the complex and established that phosphatidylcholine and fatty alcohols formed highly stable 1:1 complexes.

A core curriculum for the continuing professional development of nurses: Developed by the Education Committee on behalf of the Council on Cardiovascular Nursing and Allied Professions of the ESC.

BACKGROUND: The European Society of Cardiology and the Council on Cardiovascular Nursing and Allied Professions share a vision; to decrease the burden of cardiovascular disease in Europe. Nurses represent the largest sector of the health professional workforce and have a significant contribution to make, which has not yet been fully realised. Recent evidence highlights an association between the level of nurse education and inpatient mortality making this an important topic, particularly as the provision of nurse education in Europe is variable. AIM: To develop a core curriculum to inform the education of nurses following initial qualification for work in cardiovascular settings. METHOD: A syllabus was developed using published literature, policy documents and existing curricula with expert input from service users, specialist nurses, cardiologists, educationalists and academics. The syllabus formed the framework for the development of the core curriculum. RESULTS: Eight key themes characterise the core curriculum which are presented together with an account of the development process. While the curriculum is not intended to cover all aspects of the highly complex role of the cardiovascular nurse, the themes do exemplify the science and art of nursing and are transferable across different levels of clinical practice and settings. The curriculum functions both as a 'map', which identifies key themes to include in nurse education, and as a 'tool' to inform educational provision that bridges' the gap between initial nurse education and advanced specialist practice. Content can be adapted for use to fit the national context and reflects the specific needs, health priorities, legislative and regulatory standards that govern safe nursing practice across different countries. CONCLUSION: The core curriculum can be used as a learning framework to guide nurse education, in particular the continuing professional education of post-qualifying nurses working in cardiovascular settings. This represents a significant step towards streamlining cardiovascular nurse education in Europe.

Younger age, higher body mass index and lower adiponectin concentration predict higher serum thromboxane B2 level in aspirin-treated patients with type 2 diabetes: an observational study.

BACKGROUND: Evidence from the literature suggests diminished acetylsalicylic acid (ASA) treatment efficacy in type 2 diabetes (DM2). High on-aspirin platelet reactivity (HAPR) in DM2 has been linked to poor glycemic and lipid control. However, there are no consistent data on the association between HAPR and insulin resistance or adipose tissue metabolic activity. The aim of this study was to assess the relationship between laboratory response to ASA and metabolic control, insulin resistance and adipokines in DM2. METHODS: A total of 186 DM2 patients treated with oral antidiabetic drugs and receiving 75 mg ASA daily were included in the analysis. Response to ASA was assessed by measuring serum thromboxane B2 (TXB2) concentration and expressed as quartiles of TXB2 level. The achievement of treatment targets in terms of glycemic and lipid control, insulin resistance parameters (including Homeostatic Model Assessment-Insulin Resistance, HOMA-IR, index), and serum concentrations of high-molecular weight (HMW) adiponectin, leptin and resistin, were evaluated in all patients. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors of serum TXB2 concentration above the upper quartile and above the median. RESULTS: Significant trends in age, body mass index (BMI), HOMA-IR, HMW adiponectin concentration, C-reactive protein concentration and the frequency of achieving target triglyceride levels were observed across increasing quartiles of TXB2. In a multivariate analysis, only younger age and higher BMI were independent predictors of TXB2 concentration above the upper quartile, while younger age and lower HMW adiponectin concentration were predictors of TXB2 concentration above the median. CONCLUSIONS: These results suggest that in DM2, the most important predictor of HAPR is younger age. Younger DM2 patients may therefore require total daily ASA doses higher than 75 mg, preferably as a twice-daily regimen, to achieve full therapeutic effect. Higher BMI and lower HMW adiponectin concentration were also associated with less potent ASA effect. This is the first study to demonstrate an association of lower adiponectin concentration with higher serum TXB2 level in patients treated with ASA.

Predictors of high platelet reactivity during aspirin treatment in patients with type 2 diabetes.

BACKGROUND: Diabetes mellitus type 2 (DM2) is associated with high platelet reactivity both in patients who do not receive antiplatelet drugs and in those treated with acetylsalicylic acid (ASA). The pathomechanism of this phenomenon has not been fully understood. AIM: 1. To evaluate variability of platelet reactivity in patients with DM2 treated with oral antidiabetic drugs and receiving chronic ASA therapy. 2. To identify independent predictors of high platelet reactivity during ASA therapy in patients with DM2. METHODS: We studied 171 patients with DM2 treated with oral antidiabetic drugs and receiving long-term treatment with 75 mg of ASA daily, selected among the participants of the prospective AVOCADO study. Platelet function was simultaneously evaluated using 4 methods: 1. measurement of serum thromboxane B2 (TXB2) concentration; 2. measurement of urinary 11-dehydrothromboxane B2 (11-dhTXB2) concentration; 3. VerifyNow® automated analyser; 4. PFA-100® automated analyser.High platelet reactivity was defined as at least 3 of the following criteria: 1. serum TXB2 concentration in the upper quartile;2. urinary 11-dhTXB2 concentration in the upper quartile; 3. value ≥ 550 aspirin reaction units (ARU) by VerifyNow®;4. collagen-epinephrine closure time (CEPI-CT) below median of readings other than 300 s by PFA-100®. In all patients, DM2 control was evaluated, insulin resistance was measured using HOMA-IR, and routine laboratory tests were performed, including full blood count, renal function parameters, and inflammation markers. RESULTS: Mean patient age was 67.8 years, and median duration of DM2 was 5 years. We found poor agreement between different tests of platelet function. ARU ≥ 550 (VerifyNow®) was found in 14.0% of patients, and CEPI-CT below median of readings other than 300 s (PFA-100®) was found in 32.8% of patients. Our criteria of high platelet reactivity were met by 9.9% of patients. In multivariate logistic regression analysis, independent predictors of high platelet reactivity despite ASA therapy included chronic heart failure, current smoking, and higher leukocyte count. CONCLUSIONS: 1. Patients with DM2 are characterised by large variability of platelet reactivity, with little agreement between various methods. 2. Smoking, chronic heart failure, and subclinical inflammation may be associated with high platelet reactivity in patients with DM2 treated with ASA.

Factors responsible for "aspirin resistance" - can we identify them?

BACKGROUND: Aspirin (ASA) is an effective antiplatelet drug that reduces the risk of myocardial infarction, stroke, or death by approximately 25% in patients who are at increased risk of cardiovascular events. However, many patients with cardiovascular disease do not respond to ASA treatment and are deemed ASA resistant. The term "ASA resistance" has been used to describe not only the lack of expected pharmacologic effects of ASA on platelets but also poor clinical outcomes, such as recurrent vascular events, in patients treated with ASA. AIM: In this prospective observation of patients with stable coronary artery disease (CAD) who received ASA for secondary prevention, we investigated factors responsible for ASA resistance by determining ASA response using the PFA-100 analyser and evaluating relation of ASA resistance to various studied parameters. METHODS: Platelet function tests with the PFA-100 point-of-care system were performed in 92 patients with CAD (mean age 68 +/- 8 years, 36 females) who had been taking 75-150 mg of ASA daily for secondary prevention for at least 3 months. Each patient had an angiographically documented CAD with stable angina. ASA resistance was defined as a normal collagen/epinephrine closure time (CEPI-CT) on the PFA-100 (< or = 150 s). Patients with CT > or = 250 s were defined as ASA responders and patients with CT between 150 and 250 s as semi-responders. RESULTS: Using a collagen/epinephrine-coated cartridge on the PFA-100, the prevalence of platelet inhibition failure was 29%, while 30% of patients were semi-responders. In our study population, adequate response to ASA was found in 40% of patients. In multivariate logistic regression analysis, parameters independently related to platelet inhibition failure included compliance to ASA therapy [odds ratio (OR) 0.8, 95% confidence interval (CI) 0.20-0.35, p = 0.001], total cholesterol/HDL cholesterol level ratio > 2.99 (OR 0.19, 95% CI 0.05-0.81, p = 0.02), and heart rate > 69 bpm (OR 4.44, 95% CI 1.37-14.38, p = 0.01). CONCLUSIONS: In patients with stable CAD, about one third of the subjects were ASA resistant by PFA-100. Our study shows that non-compliance could be one of the most important risk factors responsible for high residual platelet activity in patients with stable CAD taking ASA. Thus, non-compliant patients should be carefully educated about the mechanism of action of this drug to understand the necessity and long-term benefits of treatment with ASA.

Influence of C3435T multidrug resistance gene-1 (MDR-1) polymorphism on platelet reactivity and prognosis in patients with acute coronary syndromes.

BACKGROUND: Genetic C3435T polymorphism of the multidrug resistance gene-1 (MDR-1) limits oral bioavailability of clopidogrel and influences prognosis in patients with myocardial infarction. AIM: To assess the effects of C3435T polymorphism on platelet reactivity and prognosis in patients with acute coronary syndromes treated with percutaneous coronary intervention with stenting. METHODS: Ninety-eight patients were divided into subgroups according to closure time (CT) measured with the Platelet Function Analyzer-100 by means of collagen/adenosine diphosphate (CADP) and collagen/epinephrine (CEPI) cartridges. Patients with CADP-CT<130 s and patients with CEPI-CT