Myocardial infarction in two cousins heterozygous for ASN41HIS autosomal dominant variant of Bernard–Soulier syndrome

Bernard?CSoulier Syndrome is characterized by thrombocytopenia with large platelets and defective aggregation to ristocetin. The bleeding tendency is variable but may be severe. The syndrome is due to genetic defects of the GPIb-V-IX complex and it has been maintained to be protective from thrombotic events. Here we present the first two cases of documented M.I. in two cousins, heterozygous for the Arg41His mutation which is responsible for a dominant form of Bernard?CSoulier Syndrome. In one of the two patients an aneurysm of the aorta was also present. The patients had a mild bleeding tendency which was severely aggravated by treatment with antiplatelet drugs. These clinical observations are in contrast with experimental studies which demonstrate that Bernard?CSoulier-like strains of mice show a decreased thrombus generation in several experimental settings.     

Fragment length analysis screening for detection of CEBPA mutations in intermediate-risk karyotype acute myeloid leukemia

During last years, molecular markers have been increased as prognostic factors routinely screened in acute myeloid leukemia (AML). Recently, an increasing interest has been reported in introducing to clinical practice screening for mutations in the CCAAT/enhancer-binding protein ?? (CEBPA) gene in AML, as it seems to be a good prognostic factor. However, there is no reliable established method for assessing CEBPA mutations during the diagnostic work-up of AMLs. We describe here a straightforward and reliable fragment analysis method based in PCR capillary electrophoresis (PCR-CE) for screening of CEBPA mutations; moreover, we present the results obtained in 151 intermediate-risk karyotype AML patients (aged 16?C80?years). The method gave a specificity of 100% and sensitivity of 93% with a lower detection limit of 1?C5% for CEBPA mutations. The series found 19 mutations and four polymorphisms in 12 patients, seven of whom (58%) presented two mutations. The overall frequency of CEBPA mutations in AML was 8% (n?=?12). CEBPA mutations showed no coincidence with FLT3-ITD or NPM1 mutations. CEBPA mutation predicted better disease-free survival in the group of patients without FLT3-ITD, NPM, or both genes mutated (HR 3.6, IC 95%; 1.0?C13.2, p?=?0.05) and better overall survival in patients younger than 65 of this group without molecular markers (HR 4.0, IC 95%; 1.0?C17.4, p?=?0.05). In conclusion, the fragment analysis method based in PCR-CE is a rapid, specific, and sensitive method for CEBPA mutation screening and our results confirm that CEBPA mutations can identify a subgroup of patients with favorable prognosis in AML with intermediate-risk karyotype.     

Patient-reported outcomes and low-level residual HIV-RNA in adolescents perinatally infected with HIV-1 after switching to one-pill fixed-dose regimen

The choice of an antiretroviral regimen can often impact on adherence, treatment satisfaction and therefore influence on clinical outcome. These concerns are particularly true in adolescents. In this setting, adherence is usually affected by multifactor events and biopsychosocial factors, which connect and changeover time. We evaluated the effect of a switch to a single-pill fixed-dose regimen on patient-reported outcomes, virologic and immunologic outcomes, and safety in a cohort of adolescents with perinatal HIV-1 infection. In addition, we evaluated the effect on low-level residual HIV-RNA. An open-label, non-randomised study was performed: 12 adolescents with a confirmed viremia <50 copies/mL treated with lamivudine or emtricitabine, tenofovir and efavirenz were switched to one-pill fixed-dose regimen of emtricitabine/tenofovir/efavirenz. At the end of follow-up, the new regimen was associated with improvements in treatment satisfaction, HIV-symptoms, whereas adherence remained high. No immunological or virological significative changes were observed. No side-effects were registered. Moreover, the low-level residual HIV-RNA was <3 copie/mL in all patients. One-pill fixed-dose regimen is an added value that favours adherence, reduces HIV-symptoms, improves patients' satisfaction and could better control of HIV-RNA in adolescents, too.     

Affective Decision-Making Is Predictive of Three-Month Relapse in Polysubstance-Dependent Alcoholics

Background/Aims: Common and long-lasting deficits in decision-making in polysubstance-dependent alcoholics (PSA) reflect neurobiological alterations that define the chronic nature of addiction. These deficits affect goal-directed behavior and might be critical risk factors predicting relapse in PSA. Methods: The Delay Discounting Task (DDT) and the Iowa Gambling Task (IGT) assessed the delay-discounting and decision-making skills among 37 abstinent PSA. Results: The findings indicated that IGT but not DDT performances were associated with 3-month abstinence, irrespective of the influence of personality traits and coexistent medications. Conclusion: The results show that the IGT, which assesses processes that are important in the latter stages of addiction, is ecologically more valid compared to the DDT, which assesses processes important in the early stages. They underline the importance of using neurocognitive measures to identify high relapse risk patients and emphasize the relevance of promoting new treatments.     

Planetary change and biochemical adaptation: molecular evolution of corrinoid and heme biosyntheses

This review examines the evidence suggesting that the anaerobic biosynthesis of cobalamin (vitamin B12) evolved during early stages of cell evolution and was quickly recruited in the pathway leading to deoxyribonucleotides, the building blocks of DNA genomes. Biochemical evolution preceding the synthesis of the heme group and related molecules is discussed within the framework of geological evolution in which the appearance and accumulation of an oxygen-rich atmosphere stands as one of the major events in the evolution of the planet and the biosphere.     

Long-term successful percutaneous coronary intervention in factor VII deficiency

Factor VII deficiency (FVIId) is a congenital coagulation disorder with a wide spectrum of bleeding phenotypes. Percutaneous coronary intervention requires full anticoagulation during stent implantation to avoid acute coronary thrombosis and long-term dual antiplatelet therapy. Feasibility of percutaneous coronary intervention in FVIId is not described in literature. We present a successful case of percutaneous coronary intervention in a 55-year-old male with FVIId, discussing briefly the periprocedural handicaps (anticoagulation regimen and hemostasis at arterial puncture site) as the safety of long-term antiplatelet therapy, and future implications for recombinant FVIId administration in a patient with a previous coronary stent.     

Ablation of perimitral flutter following catheter ablation of atrial fibrillation: impact on outcomes from a randomized study (PROPOSE)

MVI Block vs Trigger Ablation in PMFL . Introduction: Patients with previous ablation for atrial fibrillation (AF) may experience recurrence of perimitral flutter (PMFL). These arrhythmias are usually triggered from sources that may also induce AF. This study aims at determining whether ablation of triggers or completing mitral valve isthmus (MVI) block prevents more arrhythmia recurrences. Methods and Results: Sixty‐five patients with recurrent PMFL after initial ablation of long standing persistent AF were included in this study. Thirty‐two patients were randomized to MVI ablation only (Group 1) and 33 were randomized to cardioversion and repeat pulmonary vein (PV) isolation plus ablation of non‐PV triggers (Group 2). MVI bidirectional block was achieved in all but 1 patient from Group 1. In Group 2, reconnection of 17 PVs was detected in 14 patients (42%). With isoproterenol challenge, 44 non‐PV trigger sites were identified in 28 patients (85%, 1.57 sites per patient). At 18‐month follow‐up, 27 patients (84%) from Group 1 had recurrent atrial tachyarrhythmias, of whom 15 remained on antiarrhythmic drug (AAD); however, 28 patients from Group 2 (85%, P < 0.0001 vs Group 1) were free from arrhythmia off AAD. The ablation strategy used in Group 2 was associated with a lower risk of recurrence (hazard ratio = 0.10, 95% CI 0.04–0.28, P < 0.001) and an improved arrhythmia‐free survival (log rank P < 0.0001). Conclusion: In patients presenting with PMFL after ablation for longstanding persistent AF, MVI block had limited impact on arrhythmia recurrence. On the other hand, elimination of all PV and non‐PV triggers achieved higher freedom from atrial arrhythmias at follow‐up. (J Cardiovasc Electrophysiol, Vol. 23, pp. 137‐144, February 2012)