Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry

Aims: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting. Methods and results: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016). Conclusion: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

BACKGROUND AND AIMS: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). METHODS: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. RESULTS AND CONCLUSIONS: From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score 656. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Tecniche di risoluzione delle ambiguità in distanza e in frequenza nelle applicazioni radar

Simulazione di un ricevitore Radar che opera con PRF multiple con l'obiettivo di risolvere le ambiguità in distanza e in frequenza mediante il Clustering Algorithm e il Teorema del Resto Cinese

Development of a Multi-Radio Device for Dry Container Monitoring and Tracking

Maritime shipping companies have identified continuous tracking of intermodal containers as a key tool for increasing shipment reliability and generating important economies of scale. Equipping all dry containers with an Internet-connected tracking device is a need in the global shipping market that is still waiting to be met. This paper presents the methods and tools to build and test a prototype of a Container Tracking Device (CTD) that integrates NB-IoT, BLE Mesh telecommunication and low-power consumption technologies for the massive deployment of the IoT. The work was carried out as part of a project to build the so-called “5G Global Tracking System”, enabling several different logistic applications relying on massive IoT, M2M standard platforms, as well as satellite networks to collect data from dry containers when the vessel is in open sea. Starting from a preliminary phase, in which state-of-the-art technologies, research approaches, industrial initiatives and developing standards were investigated, a prototype version of the CTD has been designed, verified and developed as the first fundamental step for subsequent industrial engineering. The results of specific tests are shown: after verifying that the firmware is capable of handling the various functions of the device, a special focus is devoted to the power consumption measurements of the CTD to size the battery pack

Experimental Evaluation of an IoT-Based Platform for Maritime Transport Services

In recent years, the adoption of innovative technologies in maritime transport and logistics systems has become a key aspect towards their development and growth, especially due to the complex and heterogeneous nature of the maritime environment. On the other hand, Internet of Things (IoT) solutions are gaining importance in the shipping industry thanks to the huge number of distributed cameras and sensors in modern ships, cargoes and sea ports, which can be exploited to improve safety, costs and productivity. This paper presents an experimental evaluation of a maritime platform, which enables a wide range of 5G-based services in the context of logistics and maritime transportation. Its core is a Narrow Band (NB)-IoT framework used to run massive IoT services on top of a hybrid terrestrial–satellite network and feed a OneM2M platform with significant data on maritime transport to develop high-level and value-added logistic applications on top. Among the many different services that could be provided by the maritime platform, we focus on the cargo-ship container tracking use case through the Global Tracking System, which allows for continuous container monitoring all over the seas in a port-to-port service scenario. The results of the experimental tests illustrate the capacity of the platform in managing the high number of messages transmitted by the container tracking devices (i.e., more than 3000) and its efficiency in limiting the average maximum latency and packet loss below 5.5 s and 0.9%, respectively

Autonomous Driving Progressed by oneM2M : The Experience of the AUTOPILOT Project

The European Commission Horizon 2020 AUTOPILOT (AUTOmated driving Progressed by Internet Of Things) is aiming to exploit the IoT ecosystem to integrate connected cars and transform them in automated moving "objects". One of the key challenges encountered in the project is to ensure the interoperability of the different components and IoT platforms serving e.g. in-vehicle and road-side devices and sensors. The adopted solution is the use of Federated IoT platforms, with the oneM2M Interoperability Platform used to ensure that all components are able to communicate with each other. This paper provides a high-level description of the project and its goals and then concentrates on the importance to ensure interoperability support for IoT platforms using the standard IoT platform provided by oneM2M. © 2019 IEEE

Contribution of Metabolomics to the Understanding of NAFLD and NASH Syndromes: A Systematic Review

Several differential panels of metabolites have been associated with the presence of metabolic syndrome and its related conditions, namely non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). This study aimed to perform a systematic review to summarize the most recent finding in terms of circulating biomarkers following NAFLD/NASH syndromes. Hence, the research was focused on NAFLD/NASH studies analysed by metabolomics approaches. Following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, a systematic search was conducted on the PubMed database. The inclusion criteria were (i) publication date between 2010 and 2021, (ii) presence of the combination of terms: metabolomics and NAFLD/NASH, and (iii) published in a scholarly peer-reviewed journal. Studies were excluded from the review if they were (i) single-case studies, (ii) unpublished thesis and dissertation studies, and (iii) not published in a peer-reviewed journal. Following these procedures, 10 eligible studies among 93 were taken into consideration. The metabolisms of amino acids, fatty acid, and vitamins were significantly different in patients affected by NAFLD and NASH compared to healthy controls. These findings suggest that low weight metabolites are an important indicator for NAFLD/NASH syndrome and there is a strong overlap between NAFLD/NASH and the metabolic syndrome. These findings may lead to new perspectives in early diagnosis, identification of novel biomarkers, and providing novel targets for pharmacological interventions