A self-driven approach for multi-class discrimination in Alzheimer’s disease based on wearable EEG

Early detection is critical to control Alzheimer’s disease (AD) progression and postpone cognitive decline. Traditional medical procedures such as magnetic resonance imaging are costly, involve long waiting lists, and require complex analysis. Alternatively, for the past years, researchers have successfully evaluated AD detection approaches based on machine learning and electroencephalography (EEG). Nonetheless, these approaches frequently rely upon manual processing or involve non-portable EEG hardware. These aspects are suboptimal regarding automated diagnosis, since they require additional personnel and hinder porta- bility. In this work, we report the preliminary evaluation of a self-driven AD multi-class discrimination approach based on a commercial EEG acquisition system using sixteen channels. For this purpose, we recorded the EEG of three groups of participants: mild AD, mild cognitive impairment (MCI) non-AD, and controls, and we implemented a self-driven analysis pipeline to discriminate the three groups. First, we applied automated artifact rejection algorithms to the EEG recordings. Then, we extracted power, entropy, and complexity features from the preprocessed epochs. Finally, we evaluated a multi-class classification problem using a multi-layer perceptron through leave-one-subject-out cross-validation. The preliminary results that we obtained are comparable to the best in literature (0.88 F1-score), what suggests that AD can potentially be detected through a self-driven approach based on commercial EEG and machine learn- ing. We believe this work and further research could contribute to opening the door for the detection of AD in a single consultation session, therefore reducing the costs associated to AD screening and poten- tially advancing medical treatment.Spanish Government PGC2018-098813-B-C31European Commission Operative Program FEDER 2014-2020 BTIC-352-UGR20Economy, Universities and Science Office of the Andalusian Regional GovernmentUniversidad de Granada/CBU

An Automated Approach for the Detection of Alzheimer’s Disease From Resting State Electroencephalography

Early detection is crucial to control the progression of Alzheimer’s disease and to postpone intellectual decline. Most current detection techniques are costly, inaccessible, or invasive. Furthermore, they require laborious analysis, what delays the start of medical treatment. To overcome this, researchers have recently investigated AD detection based on electroencephalography, a non-invasive neurophysiology technique, and machine learning algorithms. However, these approaches typically rely on manual procedures such as visual inspection, that requires additional personnel for the analysis, or on cumbersome EEG acquisition systems. In this paper, we performed a preliminary evaluation of a fully-automated approach for AD detection based on a commercial EEG acquisition system and an automated classification pipeline. For this purpose, we recorded the resting state brain activity of 26 participants from three groups: mild AD, mild cognitive impairment (MCI-non-AD), and healthy controls. First, we applied automated data-driven algorithms to reject EEG artifacts. Then, we obtained spectral, complexity, and entropy features from the preprocessed EEG segments. Finally, we assessed two binary classification problems: mild AD vs. controls, and MCI-non-AD vs. controls, through leave-one-subject-out cross-validation. The preliminary results that we obtained are comparable to the best reported in literature, what suggests that AD detection could be automatically detected through automated processing and commercial EEG systems. This is promising, since it may potentially contribute to reducing costs related to AD screening, and to shortening detection times, what may help to advance medical treatment.PID2021-128529OA-I00 Spanish Ministry of Science, Innovation and UniversitiesEuropean Regional Development FundsBTIC- 352-UGR20Operative Program FEDER 2014–2020Economy, Universities and Science Office of the Andalusian Regional Governmen

High frequency of acute decompensation and cancer in patients with compensated cirrhosis due to nonalcoholic fatty liver disease : A retrospective cohort study

The natural history of compensated cirrhosis due to nonalcoholic fatty liver disease (NAFLD) has not been completely characterized. The aim of the present study was to assess the incidence and risk factors of acute decompensation of cirrhosis, hepatocellular carcinoma, and extrahepatic cancers. This was a multicenter, retrospective, cohort study including 449 patients with compensated cirrhosis due to NAFLD. We calculated cumulative incidences and used competitive risk analysis to determine the risk factors associated with decompensation and cancer development. Over a median of 39 months of follow-up, 124 patients (28%) presented acute decompensation. The most frequent decompensation was ascites (21%) followed by hepatic encephalopathy (15%), variceal bleeding (9%), and spontaneous bacterial peritonitis (3%). Acute-on-chronic liver failure was diagnosed in 6% of patients during follow-up. Liver function parameters and specifically an albumin level below 40 g/L were independently associated with an increased risk of decompensation. The presence of ischemic heart disease was independently associated with acute decompensation. Seventy-eight patients (18%) developed hepatocellular carcinoma or extrahepatic cancers during follow-up (51 and 27, respectively). Conclusion : Patients with compensated cirrhosis due to NAFLD are at high risk of severe liver complications, such as the development of acute decompensation, in a relative short follow-up time. This population is at high risk of hepatic and extrahepatic cancers. The analysis of a large contemporary cohort of 449 patients with compensated cirrhosis due to non-alcoholic fatty liver disease shows a high frequency of acute decompensations (AD) and development of cancer during 39 months of follow-up. Almost 28% of the cohort developed acute decompensation and 18% developed hepatocellular carcinoma (HCC) or extrahepatic cancer. Predictors of decompensation are mainly related to liver function and portal hypertension

The RADMED monitoring program as a tool for MSFD implementation: toward an ecosystem based approach

In the western Mediterranean Sea, the RADMED monitoring programme is already conducting several of the evaluations required under the Marine Strategy Framework Directive (MFSD) along the Spanish Mediterranean coast. The different aspects of the ecosystem that are regularly sampled under this monitoring programme are the physical environment and the chemical and biological variables of the water column, together with the planktonic communities, biomass and structure. Moreover, determinations of some anthropogenic stressors on the marine environment, such as contaminants and microplastics, are under development. Data are managed and stored at the Instituto Español de Oceanografía (IEO) Data Centre that works under the Sea- DataNet infrastructure, and are also stored in the IBAMar database. In combination with remote sensing data, they are used to address open questions on the ecosystems in the western Mediterranean Sea.Postprint2,293

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects

[Background and Aim] Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD).[Methods] Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years).[Results] Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these.[Conclusions] The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.This project has been partially funded by the ‘Consejería de Salud de la Junta de Andalucía’ (PI-0075-2014) and the ‘Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI17/00535 and GLD19/00100).Peer reviewe

Guia per a la prevenció i el control de l'hepatitis C

Hepatitis C; Prevenció; TractamentHepatitis C; Prevención; TratamientoHepatitis C; Prevention; TreatmentL'objectiu d'aquesta guia és posar a l'abast dels professionals mèdics de Catalunya un resum dels coneixements disponibles sobre l'agent causal, l'epidemiologia, la part clínica i especialment sobre el diagnòstic, el tractament i la prevenció de l'hepatitis C.El objetivo de esta guía es poner al alcance de los profesionales médicos de Cataluña un resumen de los conocimientos disponibles sobre el agente causal, la epidemiología, la parte clínica y especialmente sobre el diagnóstico, el tratamiento y la prevención de la hepatitis C.The purpose of this guide is to make available to medical professionals in Catalonia a summary of the knowledge available on the causative agent, the epidemiology, the clinical part and especially on the diagnosis, treatment and prevention of the disease hepatitis C

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4

[Abstract] Background and Aims. Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real‐world clinical practice, showed high rates of sustained virological response (SVR) in non‐cirrhotic genotype (GT)‐1 and GT‐4 patients. These results were slightly lower in cirrhotic patients. We investigated real‐life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. Methods. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV‐GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January‐2014 and December‐2015. Demographic, clinical, virological and safety data were analysed. Results. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109/L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%‐91.9%) than patients with less advanced liver disease (93.8%‐95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE‐associated discontinuation events occurred in 5.9% and 2.6%. Conclusions. In this large cohort of cirrhotic patients managed in the real‐world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.Instituto de Salud Carlos III; PI15/0015

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

Background: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Methods: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country

Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium.</p> <p>Methods</p> <p>CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in <it>ADH1C</it>, <it>APC</it>, <it>CCDN1</it>, <it>IL6</it>, <it>IL8</it>, <it>IRS1</it>, <it>MTHFR</it>, <it>PPARG</it>, <it>VDR </it>and <it>ARL11</it>, and 18 selected variants in the mucin gene family.</p> <p>Results</p> <p>None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a <it>P</it>-value < 0.05 in EPICOLON stage 1 [rs698 in <it>ADH1C </it>(OR = 1.63, 95% CI = 1.06-2.50, <it>P</it>-value = 0.02, recessive), rs1800795 in <it>IL6 </it>(OR = 1.62, 95% CI = 1.10-2.37, <it>P</it>-value = 0.01, recessive), rs3803185 in <it>ARL11 </it>(OR = 1.58, 95% CI = 1.17-2.15, <it>P</it>-value = 0.007, codominant), and rs2102302 in <it>GALNTL2 </it>(OR = 1.20, 95% CI = 1.00-1.44, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, <it>P</it>-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, <it>P</it>-value = 0.09, log-additive 0, 1, 2 alleles).</p> <p>Conclusions</p> <p><it>ARL11</it>, <it>ADH1C</it>, <it>GALNTL2 </it>and <it>IL6 </it>genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.</p