RICOVERI PER EFFETTI INDESIDERATI DA SOVRADOSAGGIO DI FARMACI PRESSO UN\u2019UNIT\uc0 OPERATIVA CARDIOLOGICA NEL PERIODO 2011-2013

Introduzione: Le statistiche dei casi di ricovero ospedaliero per effetti indesiderati da sovradosaggio farmacologico sono utili per valutare l\u2019incidenza di tale fenomeno nel mondo reale. Un sovradosaggio farmacologico pu\uf2 avvenire come conseguenza di un\u2019insufficiente o inadeguata comunicazione tra medico e paziente, per autoprescrizione o erronea assunzione di dosaggi superiori a quelli necessari, per erronea assunzione di due farmaci identici come molecola ma con nome commerciale diverso o per effetti collaterali imprevisti. Materiali e metodi: Sono state esaminate, retrospettivamente, le cartelle cliniche relative a tutti i ricoveri avvenuti presso l\u2019Unit\ue0 Operativa di Cardiologia del P.O. S. Antonio Abate di Trapani (ASP 9 - Sicilia) nel triennio compreso tra gennaio 2011 e dicembre 2013. Sono state ricercate le ospedalizzazioni avvenute per effetti indesiderati da sovradosaggio di farmaci appartenenti a varie classi quali digitalici, ACE-inibitori, betabloccanti e antiaritmici, in particolare l\u2019amiodarone. Risultati: Nel triennio in oggetto, su un totale di 7269 ospedalizzazioni, quelli per effetti indesiderati da sovradosaggio farmacologico sono stati 76 (1.05% del totale dei ricoveri). I pazienti ricoverati per tale motivo, 33 di sesso maschile e 43 di sesso femminile, avevano un\u2019et\ue0 compresa tra 62 e 90 anni. La Figura1 mostra le percentuali relative ai singoli farmaci interessati, secondo cui la principale causa di ricovero ospedaliero per effetti indesiderati da sovradosaggio farmacologico \ue8 attribuibile all\u2019amiodarone, antiaritmico di classe III, per i noti effetti collaterali a carico della tiroide e degli occhi. Segue la digitale, che ha causato nei pazienti bradiaritmie e in alcuni casi vere e proprie intossicazioni e, in percentuali minori, gli ACE-inibitori, cause di ipotensione e i betabloccanti, causa di bradicardia e ipotensione. Per tutti i casi l\u2019intervento mirava alla reversione della sintomatologia e alla momentanea sospensione dell\u2019assunzione. Per nessuno dei casi monitorati si \ue8 proposto il ricovero in terapia intensiva. Discussione: I ricoveri ospedalieri per effetti indesiderati da sovradosaggio farmacologico sono ancora un problema abbastanza diffuso nel mondo reale. Gli operatori sanitari, tra cui Medici e Farmacisti, dovrebbero ulteriormente mirare a una corretta informazione dei pazienti e dei loro familiari, in particolare al momento della dimissione, come prezioso e fondamentale strumento di prevenzione di questi danni iatrogenici che, a prescindere dei costi evitabili per il Sistema Sanitario Nazionale, possono comportare, se non adeguatamente trattati, rischi e gravi conseguenze per la salute

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

IL-10 producing regulatory and helper T-cells in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterised by the production of pathogenic autoantibodies against nuclear self-antigens. The anti-inflammatory and tolerogenic cytokine Interleukin-10 appears to play a paradoxical pathogenic role in SLE and is therefore currently therapeutically targeted in clinical trials. It is generally assumed that the pathogenic effect of IL-10 in SLE is due to its growth and differentiation factor activity on autoreactive B-cells, but effects on other cells might also play a role. To date, a unique cellular source of pathogenic IL-10 in SLE has not been identified. In this review, we focus on the contribution of different CD4+T-cell subsets to IL-10 and autoantibody production in SLE. In particular, we discuss that IL-10 produced by different subsets of adaptive regulatory T-cells, follicular helper T-cells and extra-follicular B-helper T-cells is likely to have different effects on autoreactive B-cell responses. A better understanding of the role of IL-10 in B-cell responses and lupus would allow to identify the most promising therapies for individual SLE patients in the future

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

CombiROC : an interactive web tool for selecting accurate marker combinations of omics data

Diagnostic accuracy can be improved considerably by combining multiple markers, whose performance in identifying diseased subjects is usually assessed via receiver operating characteristic (ROC) curves. The selection of multimarker signatures is a complicated process that requires integration of data signatures with sophisticated statistical methods. We developed a user-friendly tool, called CombiROC, to help researchers accurately determine optimal markers combinations from diverse omics methods. With CombiROC data from different domains, such as proteomics and transcriptomics, can be analyzed using sensitivity/specificity filters: the number of candidate marker panels rising from combinatorial analysis is easily optimized bypassing limitations imposed by the nature of different experimental approaches. Leaving to the user full control on initial selection stringency, CombiROC computes sensitivity and specificity for all markers combinations, performances of best combinations and ROC curves for automatic comparisons, all visualized in a graphic interface. CombiROC was designed without hard-coded thresholds, allowing a custom fit to each specific data: this dramatically reduces the computational burden and lowers the false negative rates given by fixed thresholds. The application was validated with published data, confirming the marker combination already originally described or even finding new ones. CombiROC is a novel tool for the scientific community freely available at http://CombiROC.eu

miRiadne : a web tool for consistent integration of miRNA nomenclature

The miRBase is the official miRNA repository which keeps the annotation updated on newly discovered miRNAs: it is also used as a reference for the design of miRNA profiling platforms. Nomenclature ambiguities generated by loosely updated platforms and design errors lead to incompatibilities among platforms, even from the same vendor. Published miRNA lists are thus generated with different profiling platforms that refer to diverse and not updated annotations. This greatly compromises searches, comparisons and analyses that rely on miRNA names only without taking into account the mature sequences, which is particularly critic when such analyses are carried over automatically. In this paper we introduce miRiadne, a web tool to harmonize miRNA nomenclature, which takes into account the original miRBase versions from 10 up to 21, and annotations of 40 common profiling platforms from nine brands that we manually curated. miRiadne uses the miRNA mature sequence to link miRBase versions and/or platforms to prevent nomenclature ambiguities. miRiadne was designed to simplify and support biologists and bioinformaticians in re-annotating their own miRNA lists and/or data sets. As Ariadne helped Theseus in escaping the mythological maze, miRiadne will help the miRNA researcher in escaping the nomenclature maze. miRiadne is freely accessible from the URL http://www.miriadne.org

Inhibition of Natural Killer Cells through Engagement of CD81 by the Major Hepatitis C Virus Envelope Protein

The immune response against hepatitis C virus (HCV) is rarely effective at clearing the virus, resulting in ∼170 million chronic HCV infections worldwide. Here we report that ligation of an HCV receptor (CD81) inhibits natural killer (NK) cells. Cross-linking of CD81 by the major envelope protein of HCV (HCV-E2) or anti-CD81 antibodies blocks NK cell activation, cytokine production, cytotoxic granule release, and proliferation. This inhibitory effect was observed using both activated and resting NK cells. Conversely, on NK-like T cell clones, including those expressing NK cell inhibitory receptors, CD81 ligation delivered a costimulatory signal. Engagement of CD81 on NK cells blocks tyrosine phosphorylation through a mechanism which is distinct from the negative signaling pathways associated with NK cell inhibitory receptors for major histocompatibility complex class I. These results implicate HCV-E2–mediated inhibition of NK cells as an efficient HCV evasion strategy targeting the early antiviral activities of NK cells and allowing the virus to establish itself as a chronic infection

HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial.

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 μg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV-RNA levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg-IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies

Role of Mediterranean diet in the development and recurrence of meningiomas: a narrative review

: Several studies through the years have proven how an unhealthy nutrition, physical inactivity, sedentary lifestyle, obesity, and smoking represent relevant risk factors in cancer genesis. This study aims to provide an overview about the relationship between meningiomas and food assumption in the Mediterranean diet and whether it can be useful in meningioma prevention or it, somehow, can prevent their recurrence. The authors performed a wide literature search in PubMed and Scopus databases investigating the presence of a correlation between Mediterranean diet and meningiomas. The following MeSH and free text terms were used: "Meningiomas" AND "Diet" and "Brain tumors" AND "diet." Databases' search yielded a total of 749 articles. After duplicate removal, an abstract screening according to the eligibility criteria has been performed and 40 articles were selected. Thirty-one articles were excluded because they do not meet the inclusion criteria. Finally, a total of 9 articles were included in this review. It is widely established the key and protective role that a healthy lifestyle and a balanced diet can have against tumorigenesis. Nevertheless, studies focusing exclusively on the Mediterranean diet are still lacking. Thus, multicentric and/or prospective, randomized studies are mandatory to better assess and determine the impact of food assumptions in meningioma involvement

Eomesodermin controls a unique differentiation program in human IL-10 and IFN-γ coproducing regulatory T cells

Whether human IL-10-producing regulatory T&nbsp;cells (“Tr1”) represent a distinct differentiation lineage or an unstable activation stage remains a key unsolved issue. Here, we report that Eomesodermin (Eomes) acted as a lineage-defining transcription factor in human IFN-γ/IL-10 coproducing Tr1-like cells. In vivo occurring Tr1-like cells expressed Eomes, and were clearly distinct from all other CD4 + T-cell subsets, including conventional cytotoxic CD4 + T&nbsp;cells. They expressed Granzyme (Gzm) K, but had lost CD40L and IL-7R expression. Eomes antagonized the Th17 fate, and directly controlled IFN-γ and GzmK expression. However, Eomes binding to the IL-10 promoter was not detectable in human CD4 + T&nbsp;cells, presumably because critical Tbox binding sites of the mouse were not conserved. A precommitment to a Tr1-like fate, i.e. concominant induction of Eomes, GzmK, and IFN-γ, was promoted by IL-4 and IL-12-secreting myeloid dendritic cells. Consistently, Th1 effector memory cells contained precommitted Eomes + GzmK + T&nbsp;cells. Stimulation with T-cell receptor (TCR) agonists and IL-27 promoted the generation of Tr1-like effector cells by inducing switching from CD40L to IL-10. Importantly, CD4 + Eomes + T-cell subsets were present in lymphoid and nonlymphoid tissues, and their frequencies varied systemically in patients with inflammatory bowel disease and graft-versus-host disease. We propose that Eomes + Tr1-like cells are effector cells of a unique GzmK-expressing CD4 + T-cell subset