Left ventricular remodeling in hypertrophic cardiomyopathy: an overview of current knowledge

While most patients with hypertrophic cardiomyopathy (HCM) show a relatively stable morphologic and clinical phenotype, in some others, progressive changes in the left ventricular (LV) wall thickness, cavity size, and function, defined, overall, as "LV remodeling", may occur. The interplay of multiple pathophysiologic mechanisms, from genetic background to myocardial ischemia and fibrosis, is implicated in this process. Different patterns of LV remodeling have been recognized and are associated with a specific impact on the clinical course and management of the disease. These findings underline the need for and the importance of serial multimodal clinical and instrumental evaluations to identify and further characterize the LV remodeling phenomenon. A more complete definition of the stages of the disease may present a chance to improve the management of HCM patients

Risk stratification in transthyretin-related cardiac amyloidosis

Transthyretin related cardiac amyloidosis (TTR-CA) is an infiltrative cardiomyopathy that cause heart failure with preserved ejection fraction, mainly in aging people. Due to the introduction of a non invasive diagnostic algorithm, this disease, previously considered to be rare, is increasingly recognized. The natural history of TTR-CA includes two different stages: a presymptomatic and a symptomatic stage. Due to the availability of new disease-modifying therapies, the need to reach a diagnosis in the first stage has become impelling. While in variant TTR-CA an early identification of the disease may be obtained with a genetic screening in proband's relatives, in the wild-type form it represents a challenging issue. Once the diagnosis has been made, in order to identifying patients with a higher risk of cardiovascular events and death it is necessary to focus on risk stratification. Two prognostic scores have been proposed both based on biomarkers and laboratory findings. However, a multiparametric approach combining information from electrocardiogram, echocardiogram, cardiopulmonary exercise test and cardiac magnetic resonance may be warranted for a more comprehensive risk prediction. In this review, we aim at evaluating a step by step risk stratification, providing a clinical diagnostic and prognostic approach for the management of patients with TTR-CA

Exploring the influence of takotsubo syndrome on oncologic patients' mortality

It has been reported that patients affected by takotsubo syndrome (TTS) with a concurrent diagnosis of cancer suffer from greater mortality as compared to their non-cancer counterpart. It remains unclear whether TTS worsens the prognosis of cancer patients as well. Aim of this study was to compare outcomes of cancer patients with and without TTS. We combined data from two independent cohorts: one consisted of a prospective multicentre TTS registry; the second cohort consisted of all oncologic patients from two Cardio-Oncology Outpatient Clinics, who did not have cardiovascular conditions at the time of the cardio-oncologic visit. From the TTS registry, we selected patients with cancer (cancer-TTS patients). Next, we matched these patients with those from the cardio-oncologic cohort (cancer non-TTS patients) in a 1:2 fashion by age, sex, and type and cancer staging. Study endpoint was all-cause mortality. Among 318 TTS patients, 42 (13%) had a concurrent diagnosis of cancer. Characteristics of cancer-TTS patients and of the 84 matched cancer non-TTS subjects were comparable with the exception of diabetes mellitus, which was more common in cancer non-TTS patients. All-cause mortality was similar between cancer-TTS and cancer non-TTS patients. At Cox regression analysis TTS was not associated with mortality (OR 1.4, 95% CI 0.6-3.3, p = 0.43). Our findings show that even in the presence of acute heart failure due to TTS, the prognosis of oncologic patients is driven by the malignancy itself. Our results may prove useful for integrated management of cardio-oncologic patients

WHAAM: A new online service supporting parents and teachers of children with ADHD

info:eu-repo/semantics/publishedVersio

Web Health Application for ADHD Monitoring (WHAAM): Context-Driven Framework

The Framework (FW) summarizes the experiences and vision of the WHAAM project partners, providing the basis for the development of the WHAAM app and online services. There are many approaches to the treatment of ADHD, with excellent resources available. This FW is a working tool based on partners' experiences, inspiring subsequent project activities. It is divided into three parts: part A explores general issues related to ADHD, focusing on key life contexts such as school, family, and social relationships. Each context is explored in terms of assessment, intervention and support. Part B delves into the relationship between ICT use and ADHD treatment. Finally, Part C briefly explains the main features of the WHAAM app, including functionality and interfaces. The WHAAM project considers the app and online service accessible via PC and mobile devices as a significant advancement in monitoring process management

Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage

FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome

Update on the Combined Analysis of Muon Measurements from Nine Air Shower Experiments

Over the last two decades, various experiments have measured muon densities in extensive air showers over several orders of magnitude in primary energy. While some experiments observed differences in the muon densities between simulated and experimentally measured air showers, others reported no discrepancies. We will present an update of the meta-analysis of muon measurements from nine air shower experiments, covering shower energies between a few PeV and tens of EeV and muon threshold energies from a few 100 MeV to about 10GeV. In order to compare measurements from different experiments, their energy scale was cross-calibrated and the experimental data has been compared using a universal reference scale based on air shower simulations. Above 10 PeV, we find a muon excess with respect to simulations for all hadronic interaction models, which is increasing with shower energy. For EPOS-LHC and QGSJet-II.04 the significance of the slope of the increase is analyzed in detail under different assumptions of the individual experimental uncertainties

Search for Spatial Correlations of Neutrinos with Ultra-high-energy Cosmic Rays

For several decades, the origin of ultra-high-energy cosmic rays (UHECRs) has been an unsolved question of high-energy astrophysics. One approach for solving this puzzle is to correlate UHECRs with high-energy neutrinos, since neutrinos are a direct probe of hadronic interactions of cosmic rays and are not deflected by magnetic fields. In this paper, we present three different approaches for correlating the arrival directions of neutrinos with the arrival directions of UHECRs. The neutrino data are provided by the IceCube Neutrino Observatory and ANTARES, while the UHECR data with energies above ∼50 EeV are provided by the Pierre Auger Observatory and the Telescope Array. All experiments provide increased statistics and improved reconstructions with respect to our previous results reported in 2015. The first analysis uses a high-statistics neutrino sample optimized for point-source searches to search for excesses of neutrino clustering in the vicinity of UHECR directions. The second analysis searches for an excess of UHECRs in the direction of the highest-energy neutrinos. The third analysis searches for an excess of pairs of UHECRs and highest-energy neutrinos on different angular scales. None of the analyses have found a significant excess, and previously reported overfluctuations are reduced in significance. Based on these results, we further constrain the neutrino flux spatially correlated with UHECRs

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Clinical translation of genetic testing in TTR Amyloidosis: genotype-phenotype correlations, management of asymptomatic carriers and familial screening

Transthyretin (TTR)-related amyloidosis (ATTR) is a heterogeneous disease with different organ involvement depending on the type of TTR infiltration [mutated (vTTR) or wild-type (wtTTR)]. Genetic testing in ATTR is required to define diagnosis and identify asymptomatic at-risk family members. Since new therapies are maximally effective in the early stages of the disease, there is a growing agreement about the need for close monitoring of genotype-positive, phenotype-negative individuals to assure a prompt treatment when minor disease signs are detected. This review summarizes the complexity of genotype-phenotype correlation and revises the current indications with respect to familiar screening and management of asymptomatic carriers