Residual vein thrombosis and onset of post-thrombotic syndrome: Influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. PATIENTS/METHODS: In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity. Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n=85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n=83). All patients were treated according to current protocols and re-examined after 3, 12 and 36months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. RESULTS: We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment. CONCLUSIONS: These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis

Iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis and the quality of life: a new therapeutic protocol

Objectives: to evaluate the clinical efficacy and the effects on the quality of life of Iloprost, a prostacyclin analogue, used, according to a new protocol, in patients with Raynaud’s phenomenon secondary to Systemic Sclerosis. Methods: in this randomized study we treated 30 patients with Iloprost given by intravenous infusion, at progressively increasing doses (starting from 0.5 ng/Kg/min up 2 ng/Kg/min) over a period of 6 hours a day for ten days in two consecutive weeks, with repeated cycles at regular intervals of three months for 18 months. The results were compared with those obtained in 30 other patients, who had received the same drug but with different posologic schemes. Results: the total average daily duration of the attacks, the average duration of a single attack and the average daily frequency of the attacks were reduced significantly in all groups of treatment, but the comparison between the groups demonstrated significant differences between patients treated with the new protocol and the others at later times (T12 and T18). The effects on the quality of life, evaluated by SF-36, demonstrate, in the group treated with the new protocol, a marked improvement both regarding the scale relative to the physical aspect of the illness, and especially regarding the scale relative to the mental aspect. Conclusions: in SSc patients, cyclic intravenous Iloprost infusion is efficacious in the treatment of Raynaud’s phenomenon. The protocol that we used, compared with others, is able to determine not only favourable clinical effects but also a marked improvement in the quality of life

Soluble CD40L and cardiovascular risk in asymptomatic low-grade carotid stenosis

Background and Purpose-We investigated whether soluble CD40L (sCD40L) may predict the risk of cardiovascular (CV) events in patients with asymptomatic carotid plaques. Methods-Forty-two patients with asymptomatic low-grade carotid stenosis (ALCS) and 21 controls without any carotid stenosis were enrolled. All subjects had at least a major cardiovascular risk factor (CRF). Plasma levels of C-reactive protein (CRP), IL-6, and sCD40L were measured. Subjects were reviewed every 12 months (median follow-up, 8 years). Results-ALCS patients had higher (P<0.0001) CRP, IL-6, and sCD40L than controls. Fourteen patients experienced a CV event. Cox regression analysis showed that only high sCD40L levels (P=0.003) independently predicted cardiovascular risk. Conclusions-High levels of sCD40L may predict the risk of CV events in ALCS

Threshold J/ψ−J/\psi- production in nucleon-nucleon collisions

We analyze $J/\psi-$ production in nucleon-nucleon collisions near threshold in the framework of a general model independent formalism, which can be applied to any reaction $N+N\to N+N+V^0$, where $V^0=\omega$, $\phi$, or $J/\psi$. Such reactions show large isotopic effects: a large difference for $pp$- and $pn$-collisions, which is due to the different spin structure of the corresponding matrix elements. The analysis of the spin structure and of the polarization observables is based on symmetry properties of the strong interaction. Using existing experimental data on the different decays of $J/\psi-$meson, we suggest a model for $N+N\to N+N+J/\psi$, based on $t-$channel $\eta+\pi$-exchanges. We predict polarization phenomena for the $n+p\to n+p+J/\psi$-reaction and the ratio of cross sections for $np$ and $pp$-collisions. For the processes $\eta(\pi)+N\to N+J/\psi$ we apply two different approaches: vector meson exchange and local four-particle interaction. In both cases we find larger $J/\psi$-production in $np$-collisions, with respect to $pp$-collisions.Comment: 17 pages, 6 figure

Brazilian Buffalo Genetic Variability by Cross-Specific Microsatellite Set

Buffaloes (Bubalus bubalis) are widely distributed and were introduced to Brazil in 1895. Most of the molecular genetic characterization of buffaloes has been done with cross-specific (cattle) markers, but few of them include Brazilian populations. Nineteen commonly used cattle microsatellites were tested to develop a multiplexed set of microsatellites and characterize Brazilian buffalo. Three PCR mixes were finally developed with the 11 markers that succeed in amplify and were polymorphic (58%). The average number of alleles was 5.42, with an average observed and expected heterocigozity of 0.441 and 0.695, respectively. As it was expected, Brazilian buffalo variability was lower than the previously reported from the domestication centres (China and India), but higher than the seriously selected European populations. The exclusion power calculated for the eleven markers in Brazilian buffalo was 0.9999999996, this allows its use in DNA based traceability.Instituto de Genética Veterinari

Swiss Recommendations for Cutaneous Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer in Switzerland and worldwide. Most BCCs can be treated in a curative setting. However, patients can develop locally destructive and, rarely, metastatic tumors that require a different treatment approach. The clinical subtype of individual lesions provides prognostic information and influences management decisions. Surgical excision, topical therapies, and radiotherapy are highly effective in the majority of subtypes as well as in low- and high-risk diseases. For patients with low-risk diseases and superficial tumors not amenable to surgery, several nonsurgical alternatives are available. Systemic therapy is indicated for high-risk BCCs, which are not amenable to either surgery or radiotherapy. Hedgehog pathway inhibitors (HHI) are currently approved. Other therapeutic options such as immune checkpoint inhibitors show promising results in clinical trials. This first version of Swiss recommendations for diagnosis and management of BCC was prepared through extensive literature review and an advisory board consensus of expert dermatologists and oncologists in Switzerland. The present guidelines recommend therapies based on a multidisciplinary team approach and rate of recurrence for individual lesions. Based on the risk of recurrence, two distinct groups have been identified: low-risk (easy-to-treat) and high-risk (difficult-to-treat) tumors. Based on these classifications, evidence-based recommendations of available therapies are presented herein

TIGIT expressing CD4+T cells represent a tumor-supportive T cell subset in chronic lymphocytic leukemia

While research on T cell exhaustion in context of cancer particularly focuses on CD8C cytotoxic T cells, the role of inhibitory receptors on CD4C T-helper cells have remained largely unexplored. TIGIT is a recently identified inhibitory receptor on T cells and natural killer (NK) cells. In this study, we examined TIGIT expression on T cell subsets from CLL patients. While we did not observe any differences in TIGIT expression in CD8C T cells of healthy controls and CLL cells, we found an enrichment of TIGITC T cells in the CD4C T cell compartment in CLL. Intriguingly, CLL patients with an advanced disease stage displayed elevated numbers of CD4C TIGITC T cells compared to low risk patients. Autologous CLL-T cell co-culture assays revealed that depleting CD4C TIGITC expressing T cells from co-cultures significantly decreased CLL viability. Accordingly, a supportive effect of TIGITCCD4C T cells on CLL cells in vitro could be recapitulated by blocking the interaction of TIGIT with its ligands using TIGIT-Fc molecules, which also impeded the T cell specific production of CLL-prosurvival cytokines. Our data reveal that TIGITCCD4CT cells provide a supportive microenvironment for CLL cells, representing a potential therapeutic target for CLL treatment

The reaction Δ+N→N+N+ϕ\Delta+N\to N+N+\phi in ion-ion collisions

We study the threshold $\phi$-meson production in the process $\Delta+N\to N+N+\phi$, which appears as a possible important mechanism in high energy nuclei-nuclei collisions. The isotopic invariance of the strong interaction and the selection rules due to P-parity and total angular momentum result in a general and model independent parametrization of the spin structure of the matrix element in terms of three partial amplitudes. In the framework of one-pion exchange model these amplitudes can be derived in terms of the two threshold partial amplitudes for the process $\pi+N\to N+\phi$. We predict the ratio of cross sections for $\phi-$meson production in $pp$- and $\Delta N$-collisions and the polarization properties of the $\phi$-meson, in $\Delta+N\to N+N+\phi$, as a function of a single parameter, which characterizes the relative role of transversal and longitudinal $\phi$-meson polarizations in the process $\pi+N\to N+\phi$.Comment: 10 pages 3 figure