ANMCO Position Paper: diagnostic-therapeutic pathway in patients with hypercholesterolaemia and statin intolerance

Statins are a class of drugs used to lower total and low-density lipoprotein (LDL)-cholesterol. Clinical trials performed over the last 25 years have shown that these agents are effective in improving cardiovascular outcomes in several different clinical settings. However, in some cases statin treatment may be associated with significant side effects and adverse reactions. The occurrence of these adverse events during statin therapy may cause discontinuation of treatment, and hence the impossibility of achieving recommended lipid goals. The clinical condition in which patients experience major unacceptable symptoms and/or develop laboratory abnormalities during statin therapy is defined as statin intolerance. This document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolaemia and statin intoleranc

ANMCO Scientific Statement: clinical management of hypercholesterolaemia in patients with acute coronary syndromes

LDL cholesterol (LDL-C) reduction after Acute Coronary Syndromes (ACS) is associated with a significant decrease in subsequent atherosclerotic cardiovascular events. Accordingly, international guidelines recommend a reduction of LDL-C below 70 mg/dL in ACS patients. Such a result can be effectively accomplished in most cases by using high intensity statins. In selected cases, the association with ezetimibe may be necessary in order to achieve recommended LDL-C targets. This document outlines management strategies that can be consistently implemented in clinical practice in order to achieve and maintain guidelines recommended therapeutic goals

Eccrine porocarcinoma of the head: An important differential diagnosis in the elderly patient

Background: Eccrine porocarcinoma is a rare malignant tumor of the sweat gland, characterized by a broad spectrum of clinicopathologic presentations. Surprisingly, unlike its benign counterpart eccrine poroma, eccrine porocarcinoma is seldom found in areas with a high density of eccrine sweat glands, like the palms or soles. Instead, eccrine porocarcinoma frequently occurs on the lower extremities, trunk and abdomen, but also on the head, resembling various other skin tumors, as illustrated in the patients described herein. Observations: We report 5 cases of eccrine porocarcinoma of the head. All patients were initially diagnosed as having epidermal or melanocytic skin tumors. Only after histopathologic examination were they classified as eccrine porocarcinoma, showing features of epithelial tumors with abortive ductal differentiation. Characteristic clinical, histopathologic and immunohistochemical findings of eccrine porocarcinomas are illustrated. Conclusion: Eccrine porocarcinomas are potentially fatal adnexal malignancies, in which extensive metastatic dissemination may occur. Porocarcinomas are commonly overlooked, or misinterpreted as squamous or basal cell carcinomas as well as other common malignant and even benign skin tumors. Knowledge of the clinical pattern and histologic findings, therefore, is crucial for an early therapeutic intervention, which can reduce the risk of tumor recurrence and serious complications. Copyright (c) 2008 S. Karger AG, Basel

Direct Injection of Functional Single-Domain Antibodies from E. coli into Human Cells

Intracellular proteins have a great potential as targets for therapeutic antibodies (Abs) but the plasma membrane prevents access to these antigens. Ab fragments and IgGs are selected and engineered in E. coli and this microorganism may be also an ideal vector for their intracellular delivery. In this work we demonstrate that single-domain Ab (sdAbs) can be engineered to be injected into human cells by E. coli bacteria carrying molecular syringes assembled by a type III protein secretion system (T3SS). The injected sdAbs accumulate in the cytoplasm of HeLa cells at levels ca. 105–106 molecules per cell and their functionality is shown by the isolation of sdAb-antigen complexes. Injection of sdAbs does not require bacterial invasion or the transfer of genetic material. These results are proof-of-principle for the capacity of E. coli bacteria to directly deliver intracellular sdAbs (intrabodies) into human cells for analytical and therapeutic purposes

Exercise-induced myocardial ischemia detected by cardiopulmonary exercise testing

BACKGROUND: The objective of the study was to identify the parameter(s) of cardiopulmonary exercise testing (CPET) that can detect exercise-induced myocardial ischaemia (EIMI), and to determine its diagnostic accuracy for identifying patients with coronary artery disease (CAD). METHODS AND RESULTS: We prospectively studied 202 consecutive patients (173 men, 29 women, mean age 55.7+/-10.8 years) with documented CAD. All patients underwent an incremental exercise stress testing (ECG-St) with breath-by-breath gas exchange analysis, followed by a 2-day stress/rest gated SPECT myocardial scintigraphy (GSMS) as the gold standard for ischaemia detection. ROC analysis selected a two-variable model-O(2)pulse flattening duration, calculated from the onset of myocardial ischaemia to peak exercise, and deltaVO(2)/deltawork rate slope-to predict EIMI by CPET. GSMS identified 140 patients with reversible myocardial defects, with a Summed Difference Score (SDS) of 9.7+/-2.8, and excluded EIMI in 62 (SDS 1.3+/-1.6). ECG-St had low sensitivity (46%) and specificity (66%) to diagnose EIMI as compared with CPET (87% and 74%, respectively). CONCLUSIONS: The addition of gas exchange analysis improves the diagnostic accuracy of standard ECG stress testing in identifying EIMI. A two-variable model based on O(2)pulse flattening duration and deltaVO(2)/deltawork rate slope had the highest predictive ability to identify EIMI

ANMCO Position paper: Diagnostic and therapeutic pathways in patients with hypercholesterolemia and statin intolerance

Secondary prevention after acute coronary syndromes should be aimed at reducing the risk of further adverse cardiovascular events, thereby improving quality of life, and lengthening survival. Despite compelling evidence from large randomized controlled trials, secondary prevention is not fully implemented in most cases after hospitalization for acute coronary syndrome. The Lazio Region (Italy) has about 5.3 million inhabitants (9% of the entire Italian population). Every year about 11 000 patients are admitted for acute coronary syndrome in hospitals of the Lazio Region. Most of these patients receive state-of-the art acute medical and interventional care during hospitalization. However, observational data suggest that after discharge acute coronary syndrome patients are neither properly followed nor receive all evidence-based treatments. This consensus document has been developed by 11 Scientific Societies of Cardiovascular and Internal Medicine in order develop a sustainable and effective clinical approach for secondary cardiovascular prevention after acute coronary syndrome in the local scenario of the Lazio Region. An evidence-based simplified decalogue for secondary cardiovascular prevention is proposed as the cornerstone of clinical intervention, taking into account regional laws and relative shortage of resources. The following appropriate interventions should be consistently applied: smoking cessation, blood pressure control (blood pressure < 130/80 mmHg), optimal lipid management (LDL cholesterol < 80 mmHg), weight and diabetes management, promotion of physical activity and rehabilitation, correct use of antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers