Causes of Adult Splanchnic Vein Thrombosis in the Mediterranean Area

The term splanchnic vein thrombosis encompasses Budd-Chiari syndrome (BCS), extrahepatic portal vein obstruction (EHPVO), and mesenteric vein thrombosis

Deriving session and union types for objects

Guaranteeing that the parties of a network application respect a given protocol is a crucial issue. Session types offer a method for abstracting and validating structured communication sequences (sessions). Object-oriented programming is an established paradigm for large scale applications. Union types, which behave as the least common supertypes of a set of classes, allow the implementation of unrelated classes with similar interfaces without additional programming. We have previously developed an integration of the features above into a class-based core language for building network applications, and this successfully amalgamated sessions and methods so that data can be exchanged flexibly according to communication protocols (session types). The first aim of the work reported in this paper is to provide a full proof of the type safety property for that core language by renewing syntax, typing and semantics. In this way, static typechecking guarantees that after a session has started, computation cannot get stuck on a communication deadlock. The second aim is to define a constraint-based type system that reconstructs the appropriate session types of session declarations instead of assuming that session types are explicitly given by the programmer. Such an algorithm can save programming work, and automatically presents an abstract view of the communications of the session

Improvement in ACE I/D polymorphism detection

The ACE I/D polymorphism has been reported to influence predisposition to cardiovascular disease. Conflicting results in its detection may be due to mistyping of I/D genotypes as D/D genotypes occurring in the traditional genotyping method. In order to resolve mistyping troubles and to permit a rapid and accurate analysis, we performed a stepdown PCR reaction followed by detection using Nanogen technology, and we compared these results with those obtained from traditional genotyping methods, such as conventional and confirmatory PCR. The Nanogen stepdown method showed a 100% sensitivity and 99.6% specificity, when compared with the confirmatory PCR. Our experiments provide evidence that, by using the Nanogen stepdown method, the DD mistyping was markedly decreased, thus representing a useful tool suitable for performing large-scale screening or research

Marfan syndrome: Current perspectives

Marfan syndrome (MFS) is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, due to mutations in the FBN1 gene encoding fibrillin 1. It is an important protein of the extracellular matrix that contributes to the final structure of a microfibril. Few cases displaying an autosomal recessive transmission are reported in the world. The FBN1 gene, which is made of 66 exons, is located on chromosome 15q21.1. This review, after an introduction on the clinical manifestations that leads to the diagnosis of MFS, focuses on cardiovascular manifestations, pharmacological and surgical therapies of thoracic aortic aneurysm and/or dissection (TAAD), mechanisms underlying the progression of aneurysm or of acute dissection, and biomarkers associated with progression of TAADs. A Dutch group compared treatment with losartan, an angiotensin II receptor-1 blocker, vs no other additional treatment (COMPARE clinical trial). They observed that losartan reduces the aortic dilatation rate in patients with Marfan syndrome. Later on, they also reported that losartan exerts a beneficial effect on patients with Marfan syndrome carrying an FBN1 mutation that causes haploinsufficiency (quantitative mutation), while it has no significant effect on patients displaying dominant negative (qualitative) mutations. Moreover, a French group in a 3-year trial compared the administration of losartan vs placebo in patients with Marfan syndrome under treatment with beta-receptor blockers. They observed that losartan decreases blood pressure but has no effect on aortic diameter progression. Thus, beta-receptor blockers remain the gold standard therapy in patients with Marfan syndrome. Three potential biochemical markers are mentioned in this review: total homocysteine, serum transforming growth factor beta, and lysyl oxidase. Moreover, markers of oxidative stress measured in plasma, previously correlated with clinical features of Marfan syndrome, may be explored as potential biomarkers of clinical severity

CD4(+) and CD4(-) CD1D-restricted natural killer T cells in perinatally HIV-1 infected children receiving highly active antiretroviral therapy.

We conducted a cross-sectional study on 43 Italian perinatally human immunodeficiency virus-type 1 (HIV-1) infected children receiving highly active antiretroviral therapy (HAART) and 26 age-matched healthy controls to explore CD1d-restricted NKT subsets. CD4+CD1d-rectricted natural killer (NKT) cell depletion was evidenced in 26 HIV-1 infected children with active viral replication despite HAART. Conversely, no alteration was evidenced in 17 children with undetectable viral load, suggesting full recovery in both CD4+ and CD4− CDld-rectricted NKT cell subsets. The loss of CD4+ NKT cells in unresponsive children may have clinical consequences, including autoimmune disorders or cancer development. Future therapeutic perspectives are suggested

Non-traumatic splenic rupture on dual antiplatelet therapy with aspirin and ticagrelor after stenting for acute coronary syndrome

AbstractWe report a case of non-traumatic splenic rupture in a 57-year-old man on dual antiplatelet therapy (DAPT) with aspirin and ticagrelor, seven months after percutaneous coronary intervention and drug-eluting stent implantation for non-ST elevation myocardial infarction. No splenic abnormalities were found at histopathological analysis after splenectomy, and no history of recent trauma was reported. Once restarted, DAPT after splenectomy, assessment of platelet function was performed by light transmittance aggregometry, showing a profound inhibition of platelet function by adenosine diphosphate, arachidonic acid, and collagen. Taking into account the bleeding risk associated with low on-treatment platelet reactivity, and to switch the patient from ticagrelor to a less potent P2Y12 inhibitor such as clopidogrel, cytochrome P450, genetic polymorphisms accounting for clopidogrel response variability were analyzed. The polymorphisms associated with lower response (CYP2C19*2, CYP2C19*3) were absent. Therefore, ticagrelor was withdrawn, and DAPT was continued with aspirin and clopidogrel. Rupture of the spleen may occur in the absence of major trauma or previous splenic diseases, and could be a complication of antithrombotic treatments. Moreover, low on-treatment platelet reactivity during DAPT is emerging as a possible risk factor for bleeding complications, so underlining the usefulness of assessing platelet function in special conditions to ensure that the patient receives the best tailored antiplatelet therapy.<Learning objective: Non-traumatic splenic rupture is a rare event, and is more often associated with pre-existing splenic abnormalities. However, it may be also a complication of medical treatments, especially with antithrombotic drugs. Low on-treatment platelet reactivity is emerging as a possible risk factor for bleeding complications; therefore, assessing platelet function in special conditions could be useful to ensure the patient receives the best-tailored antiplatelet therapy.

A Case Based Approach to Clinical Genetics of Thoracic Aortic Aneurysm/Dissection

Thoracic aortic aneurysm/dissection (TAAD) is a potential lethal condition with a rising incidence. This condition may occur sporadically; nevertheless, it displays familial clustering in >20% of the cases. Family history confers a six- to twentyfold increased risk of TAAD and has to be considered in the identification and evaluation of patients needing an adequate clinical follow-up. Familial TAAD recognizes a number of potential etiologies with a significant genetic heterogeneity, in either syndromic or nonsyndromic forms of the manifestation. The clinical impact and the management of patients with TAAD differ according to the syndromic and nonsyndromic forms of the manifestation. The clinical management of TAAD patients varies, depending on the different forms. Starting from the description of patient history, in this paper, we summarized the state of the art concerning assessment of clinical/genetic profile and therapeutic management of TAAD patients

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