Apolipoprotein(a) kringle-IV type 2 copy number variation is associated with venous thromboembolism

In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6-17) vs 15(9-25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women

Carotid plaque detection improves the predictive value of CHA2DS2-VASc score in patients with non-valvular atrial fibrillation::The ARAPACIS Study

BACKGROUND AND AIMS: Vascular disease (VD), as assessed by history of myocardial infarction or peripheral artery disease or aortic plaque, increases stroke risk in atrial fibrillation (AF), and is a component of risk assessment using the CHA2DS2-VASc score. We investigated if systemic atherosclerosis as detected by ultrasound carotid plaque (CP) could improve the predictive value of the CHA2DS2-VASc score. METHODS: We analysed data from the ARAPACIS study, an observational study including 2027 Italian patients with non-valvular AF, in whom CP was detected using Doppler Ultrasonography. RESULTS: VD was reported in 351 (17.3%) patients while CP was detected in 16.6% patients. Adding CP to the VD definition leaded to higher VD prevalence (30.9%). During a median [IQR] follow-up time of 36months, 56 (2.8%) stroke/TIA events were recorded. Survival analysis showed that conventional VD alone did not increase the risk of stroke (Log-Rank: 0.009, p=0.924), while addition of CP to conventional VD was significantly associated to an increased risk of stroke (LR: 5.730, p=0.017). Cox regression analysis showed that VD+CP was independently associated with stroke (HR: 1.78, 95% CI: 1.05-3.01, p=0.0318). Reclassification analysis showed that VD+CP allowed a significant risk reclassification when compared to VD alone in predicting stroke at 36months (NRI: 0.192, 95% CI: 0.028-0.323, p=0.032). CONCLUSIONS: In non-valvular AF patients the addition of ultrasound detection of carotid plaque to conventional VD significantly increases the predictive value of CHA2DS2-VASc score for stroke

An Approach to Differential Diagnosis of Antiphospholipid Antibody Syndrome and Related Conditions

The antiphospholipid antibody syndrome is a systemic, acquired, immune-mediated disorder characterized by episodes of venous, arterial, or microcirculation thrombosis and/or pregnancy abnormalities, associated with the persistent presence of autoantibodies, confirmed at least in two occasions 12 weeks apart, directed to molecular complexes consisting of phospholipids and proteins. Antiphospholipid antibody syndrome should always be considered as a potential diagnosis especially for young patients presenting with a history of thrombotic events, in particular when they occur without any obvious external trigger or any inherited thrombophilic mutation (even if 2006 criteria do not exclude antiphospholipid antibody syndrome in patients with other inherited or acquired prothrombotic conditions), or for women with recurrent pregnancy losses or later fetal deaths. Many other disorders are able to mimic antiphospholipid antibody syndrome, so a broad range of alternative diagnoses should be investigated and ruled out during clinical workup

Azienda Ospedaliera Universitaria Meyer. Attività sanitaria e scientifica 2011

The Meyer University Hospital Report on health and scientific activity is a valuable tool for sharing and disseminating information that summarises the working methods, the results and the lines of improvement that must be particularly committed. It is an instrument of knowledge and evaluation which is therefore intended for a use both inside and outside the hospital. A dynamic tool, which must be perfected, together with the improvements pursued by the hospital

Il principio di offensività. Dalla penalistica italiana ai programmi europei

Sommario: 1. Principio di offensività e idea del bene giuridico. Differenze. 2. Ancora su tutela di beni vs. tutela di regole. Il contenuto essenziale, minimo, del principio di offensività e le sue fonti normative. 3. (Segue). Tecniche di tutela penale e parametri oggettivi che identificano l’offesa. 4. La parte oggi dimostrativa del principio riguardante le sue premesse quale espressione del diritto penale del fatto e il suo nucleo più specifico. 5. Offensività e proporzione. Natura giuspositivistica dell’offensività a base costituzionale ed esportabilità del modello. 6. Dalla Germania all’Italia, dalle categorie ai principi. Caratteristiche dell’approccio costituzionalistico italiano all’offensività. 7. Esperienze (più o meno) recenti. Bicamerale (1997), Progetti di riforma del codice penale (Pagliaro, Grosso, Nordio, Pisapia), codice penale spagnolo (1995), attuazione (con d. l.gs. n. 121/2011) della direttiva europea sui reati ambientali, legge-quadro 24 dicembre 2012, n. 234. 8. Concretizzazioni post-costituzionali sul nesso illecito/sanzione. Pene (sostanzialmente) non criminali, e sanzioni (solo) sostanzialmente criminali. 9. Un contributo dall’Europa all’offensività: a) onere di motivazione su proporzione e sussidiarietà; b) catalogo dei reati dell’art. 83 TFUE. Il carattere nazionale, più che europeo, dei modelli d’illecito penale minore. 10. Dalle contravvenzioni ai modelli “sostanziali” d’illecito penale minore nella legislazione penale complementare. Il ruolo della responsabilità degli enti. 11. La scarsità delle pronunce “di accoglimento” della Corte costituzionale, e l’uso del bene giuridico in chiave “estensiva”, non sono un argomento contro l’offensività. 12. Riserva di legge, potenzialità ermeneutiche e limiti all’interpretazione conforme (all’offensività). 13. Il paradigma epistemologico-causale dell’offensività, tra democrazia e scienza penale. 14. Conclusione