Gender-Specific Aspects in the Clinical Presentation of Cardiovascular Disease

More than a quarter of a million women die each year in the industrialized countries from cardiovascular diseases (CVD), and current projections indicate that this number will continue to rise with our ageing population. Important sex-related differences

Pharmacokinetic drug-drug interaction and their implication in clinical management

Drug-drug interactions (DDIs) are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications

Living with phenylketonuria in adulthood: the PKU ATTITUDE study

Dietary treatment is the cornerstone of therapy for phenylketonuria (PKU), but adherence to low- phenylalanine diet progressively decreases after adolescence. We designed a survey to characterize the dietary habits of Italian adult PKU patients and to identify psychological factors influencing disease perception and adherence to diet. Participants to the survey (n = 111; response rate 94%) were asked to complete a structured questionnaire. Patients appeared to have an altered perception and awareness of the disease. About 40% of them did not consider PKU a disease and, despite declaring regular monitoring of phenylalanine levels (85%), nearly half of them reported a high plasma value over the last 6 months (>600 μmol/L, 48%) or were unable to specify it (31%). Adherence to PKU diet was unsatisfactory, with increased consumption of natural protein sources and reduced daily use of amino-acid supplements (<4–5 times/day in 82% patients). In addition to the intrinsic characteristics of AA formula (palatability, ease of use), the most important factor influencing their consumption was the increased social pressure associated with their use (55%). Plasma phenylalanine periodical measurements (61%) and examinations at metabolic centers (49%) were considered relevant for compliance to diet. In Italian adult PKU patients dietary management was found to be inadequate, likely due to inappropriate perception and knowledge of the disease, and lack of awareness of the negative impact of poor metabolic control in adult life. Clinicians should consider implementing more intense and tailored educational measures, as well as structured transitional care processes

Balloon aortic valvuloplasty as a palliative treatment in patients with severe aortic stenosis and limited life expectancy : a single center experience

Whether balloon aortic valvuloplasty (BAV) may provide an effective palliation in symptomatic high-risk patients is uncertain. Therefore, we aimed to evaluate outcomes in symptomatic high-risk patients with severe aortic stenosis (AS), who underwent BAV. All-cause mortality and length of hospitalization for heart failure (HF) up to death or to 1-year follow up were collected after BAV. One hundred thirty-two (132) patients (62% women), mean age 85±7 years, underwent BAV with a substantial reduction of the peak-to-peak aortic gradient from 53±21 to 29±15 mmHg (p<0.001). The median of days of HF hospitalization prior to BAV was 9 (0-19), and decreased after BAV to 0 (0-9), p<0.001. During 1-year follow-up patients with untreated CAD (85, 64%) had a higher mortality compared to patients with insignificant/treated CAD (47, 36%): 1-year survival: 45±7% vs. 66± 7%; p=0.02. After adjustment for STS risk score and severity of residual AS, patients with untreated CAD remained at higher risk of mortality (adjusted HR 1.74 [1.01-2.91]; p=0.04). Thus, in this series of symptomatic high-risk patients, BAV was associated with a significant reduction in aortic valve gradient and hospitalization time for HF post-BAV. In patients with significant CAD, percutaneous intervention might be considered in order to improve survival

GMLD: A TOOL TO INVESTIGATE AND DEMONSTRATE THE USE OF ML IN VARIOUS AREAS OF GNSS DOMAIN

This paper presents relevant results achieved during the NAVISP- EL1-035.02 project funded by the European Space Agency, which aimed to investigate the possible uses of Machine Learning (ML) based techniques for the processing of data in the field of Global Navigation Satellite Systems (GNSSs). For this purpose, we explored different kind of data present in the entire chain of the positioning process and different kind of ML approaches. In particular, this paper presents the system architecture and technologies adopted for developing the GNSS ML Demonstrator (GMLD), as well as the approaches and the results obtained for one of the most promising GNSS implemented applications, which is the prediction of daily maps of the ionosphere. Results show how, based on the historical data and the time correlation of the values, ML methods outperformed benchmark methods for the majority of the applications approached, improving the positioning performance at GNSS user level. Since the GMLD has been designed and implemented providing the general data management and ML capabilities as part of the framework, it can be easily reused to execute further investigation and implement new applications

Prognostic implications of functional mitral regurgitation according to the severity of the underlying chronic heart failure: A long-term outcome study

AimsTo examine the independent prognostic role of functional mitral regurgitation (FMR) and its impact across the severity of chronic heart failure (CHF) in a large population of outpatients with systolic CHF followed at two multidisciplinary clinics.Methods and resultsEchocardiography was performed upon enrolment in 469 CHF patients. Follow-up for death and heart transplant was updated on January 2007. Five-year transplant-free survival was 82.7 in patients with no or Grade I FMR, 64.4 in Grade II, 58.5 in Grade III, and 46.5 in Grade IV (P < 0.0001). There was a strong graded association between FMR and the long-term risk of death and heart transplant, which remained significant after multivariable adjustment (P = 0.0003). The association between FMR and events was strong and independent in patients with less severe symptoms and in those at lower overall risk based on a propensity score analysis, while it was not significant in patients with more advanced CHF or in the high-risk subgroup (P < 0.0001 for interactions).ConclusionThis study clarifies previous apparently discrepant results by demonstrating that FMR is an independent determinant of death and heart transplantation only in less severe CHF and in patients with a lower risk profile. This finding indicates that FMR plays a major role in the early phase of CHF, suggesting that this should be the focus of strategies attempting to reduce it. \uc2\ua9 The Author 2010

Childhood-onset dystonia-causing KMT2B variants result in a distinctive genomic hypermethylation profile

Background: Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements and/or postures. Heterozygous variants in lysine methyltransferase 2B (KMT2B), encoding a histone H3 methyltransferase, have been associated with a childhood-onset, progressive and complex form of dystonia (dystonia 28, DYT28). Since 2016, more than one hundred rare KMT2B variants have been reported, including frameshift, nonsense, splice site, missense and other in-frame changes, many having an uncertain clinical impact. Results: We characterize the genome-wide peripheral blood DNA methylation profiles of a cohort of 18 patients with pathogenic and unclassified KMT2B variants. We resolve the “episignature” associated with KMT2B haploinsufficiency, proving that this approach is robust in diagnosing clinically unsolved cases, properly classifying them with respect to other partially overlapping dystonic phenotypes, other rare neurodevelopmental disorders and healthy controls. Notably, defective KMT2B function in DYT28 causes a non-random DNA hypermethylation across the genome, selectively involving promoters and other regulatory regions positively controlling gene expression. Conclusions: We demonstrate a distinctive DNA hypermethylation pattern associated with DYT28, provide an epigenetic signature for this disorder enabling accurate diagnosis and reclassification of ambiguous genetic findings and suggest potential therapeutic approaches

Brain MR patterns in inherited disorders of monoamine neurotransmitters: An analysis of 70 patients

Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analysed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs