IPO-V2: A prospective, multicenter, randomized, comparative clinical investigation of the effects of sulodexide in preventing cardiovascular accidents in the first year after acute myocardial infarction

AbstractObjectives. This study was conducted to assess the efficacy of sulodexide, a glycosaminoglycan compound with antithrombotic properties, in preventing death and thromboembotic events after acute myocardial infarction.Background. Antithrombotic therapy has been found to play an important role in the prevention of cardiovascular events and death after acute myocardial infarction. Glycosaminoglycan-containing compounds, including sulodexide, show profibrinolytic and antithrombotic properties that render them suitable for use in patients after infarction.Methods. A total of 3,986 patients who had recovered from acute myocardial infarction were randomized to receive either the standard therapy routinely administered at each study center, excluding antiplatelet and anticoagulant drugs (control group, 1,970 patients), or the standard therapy plus sulodexide (treated group, 2,016 patients). Between 7 and 10 days after the episode of acute myocardial infarction, sulodexide was administered as a single daily 600-lipoprotein-lipase-releasing unit (LRU) intramuscular injection for the 1st month, followed by oral capsules of 500 LRU twice daily. Patients were evaluated for ≥12 months.Results. At the end of the study, 140 (7.1%) were recorded in the control group and 97 (4.8%) in the sulodexide group (32% risk reduction, p = 0.0022, chi-square test). A total of 90 patients (4.6%) in the control group had a further infarction, compared with 66 (33%) in the sulodexide group (28% risk reduction, p = 0.035). Furthermore, a reduction in left ventricular thrombus formation (evaluated by echocardiography) was observed in the sulodeside group (n = 12; 0.6%), compared with values in the control group (n = 25; 1.3%) (53% risk reduction, p = 0.027). Sulodexide was well tolerated and devoid of significant adverse events. All significant results were confirmed by “actual treatment” analyses.Conclusions. The study provides evidence that long-term therapy with sulodexide started early after an episode of acute myocardial infarction is associated with reductions in total mortality, rate of reinfarction and mural thrombus formation

Responses of peripheral blood mononucleated cells from non-celiac gluten sensitive patients to various cereal sources

Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome whose triggering mechanisms remain unsettled. This study aimed to clarify how cultured peripheral blood mononucleated cells (PBMC) obtained from NCGS patients responded to contact with wheat proteins. Results demonstrated that wheat protein induced an overactivation of the proinflammatory chemokine CXCL10 in PBMC from NCGS patients, and that the overactivation level depends on the cereal source from which proteins are obtained. CXCL10 is able to decrease the transepithelial resistance of monolayers of normal colonocytes (NCM 460) by diminishing the mRNA expression of cadherin-1 (CDH1) and tight junction protein 2 (TJP2), two primary components of the tight junction strands. Thus, CXCL10 overactivation is one of the mechanisms triggered by wheat proteins in PBMC obtained from NCGS patients. This mechanism is activated to a greater extent by proteins from modern with respect to those extracted from ancient wheat genotypes

Aree di studio, siti e strategie di campionamento, difficolt? complessive e sintesi dei principali risultati. Parte B: Laghi

After the preliminary actions for the selection of sites, a successive step was reached: the definition of the lakes under investigation within the project INHABIT. In this deliverable we report a brief description of each morphological and morphometric, geological and geomorphological features, with the description of the origin of the lakes, of land use, particularly important to understand and define the insistent pressure of the lake and imposed from the basin, of hydrology, an integral part of the characteristics and the ecological quality of a lake, and of the pressures due to sewage, industry, agriculture and livestock. In some lakes, we also reported the current trophic status and its evolution over time and the actions planned to improve water quality on the basis of the European Directive 2000/60/EC, the Water Framework Directive (WFD). Furthermore, for all studied lakes we also reported the regional maps for showing the watershed and its hydrography, and an aerial photo to help to identify the morphological characteristics of the lake cuvette. On each lake under study, the project involves the collection of biological samples for the four parameters of quality, as indicated by the WFD, and hydro-morphological characteristics, according to the sampling protocols defined at the national level and presently subject of international harmonization. Chapter 1 provides a description of sampling methods and procedures for the four biological parameters investigated: macroinvertebrates, phytoplankton, macrophytes and fish. Each sampling protocol identifies the sampling period, different for each parameter. For example, for the macrobenthos were identified two annual periods (one spring and one fall), for macrophytes the sampling period is during the maximum vegetative growth of plants. Phytoplankton, on the contrary, is sampled periodically several times during the year and, finally, fishes are sampled from spring to autumn. In the description of the protocols and procedures, sampling sites are also identified. The point of investigation vary from element to element. For example, macrophytes and macrobenthos are sampled along transects, i.e. "lines" distributed in a different way to cover the entire lake. On the contrary, phytoplankton is sampled at the deepest point of the lake, and fishes are collected in different areas arranged in different areas of the lake. In this chapter are also included photos of the equipment used for sampling, and of the sampling procedure when relevant. During the collection of macroinvertebrates and phytoplankton samples, water samples for chemical analysis are also collected. Chemical data are used to support and complete the description and the ecological characterization of the lakes. Furthermore, during macroinvertebrates samples, we also collected sediment samples for particle size and chemical analysis, to define the correct placement of transects on the basis of sediment characteristics and to collect basic information needed for the interpretation of data. In addition to the biological parameters, hydro-morphological characteristics of the studied lakes were also investigated, using the Lake Habitat Survey (LHS), a method developed for the English lakes and the being presently standardized at the European level. In this project, LHS will be validated for the Italian lakes. The lakes selected for investigation are 12, including natural and heavily modified waterbodies, and located in two regions: Piedmont and Sardinia. Seven sites are in Piedmont and 5 in Sardinia. The project originally planned 6 sites for each region, including the only natural lake in Sardinia: Lake Baratz. During the first sampling campaign in Sardinia, when macrobenthos was collected, he became aware of the presence of unexploded ordnance on the lake bottom. Working on, and in proximity of the bottom of the lake was excessively dangerous, and it was decided to transfer the activities on the four biological parameters in another lake, Lake Piccolo di Avigliana, a natural lake in Piedmont, lying in a natural park and of particular ecological interest . However, it was decided to keep the sampling of Lake Baratz for the biological parameters which can be sampled without danger, i.e. phytoplankton and macrophytes. In effect, being this lake the only natural lake in Sardinia, it can provide information on natural lakewater communities in the Region, otherwise missing. Selected lakes in Piedmont are the following: Lake Piccolo di Avigliana, in a Regional Park, Lake Candia, in a Provincial Park, Lake Viverone, subject to strong touristic pressure, Lake Sirio, less impacted by tourism, and two heavily modified waterbodies: Morasco, in the basin of River Toce and Serr? in the Gran Paradiso National Park, both built for hydroelectric purposes. In Sardinia, all the 5 fully investigated lakes are heavily modified waterbodies, namely Bidighinzu, Sos Canales, Liscia, Posada and Torrei. The main use for most of these basins is providing drinking water, only for Posada is providing water for agriculture. However, waters from Liscia and Posada are also used for other purposes, irrigation for the former and industry, drinking water and hydroelectric power for the latter. During the sampling campaigns, and particularly during the application of the LHS method which requires to examine the transition between an observation point and the following along the entire lake shore, we made a number of pictures of each lake in order to document the pressures on the coast, such as beaches, docks, artworks, human activities, and to show peculiar coastal and subcoastal habitats, such as sandy areas, reed beds, rocky areas, oxbow lakes, wetlands, riparian vegetation and macrophytes. A small selection of this vast collection of pictures is used in chapters 3 and 4, to show the features of each sampled lake. Sampling activities are not yet finished for all quality parameters, both because of the late selection Lake Piccolo di Avigliana, and because of difficulties due to weather conditions. It is expected to complete all sampling and analyses by Summer 2012. Preliminary data can be found in Chapter 5 for both regions, but only for some parameters and some lakes. In effect, biological analyses require different time and commitment for the different biological elements quality, so that the results the could be obtained faster are reported in this deliverable. A further activity in preparation for the near future is the preparation of a database for the hydromorphological parameters to be used for the calibration and the development of synthetic indices of morphological alteration and habitat quality. This adjustment is necessary because, in an earlier phase of verification of the applicability of the LHS method to the hydromorphological characteristics of the Italian lakes, it emerged the necessity to change some entries in the field card. These changes must also be included in the database associated with the method and in the formulation of the index.Dopo le azioni preliminari per la scelta dei siti si ? giunti, a passi successivi, alla definizione dei laghi oggetto di indagine all\u27interno del progetto INHABIT. In questo deliverable si riporta una sintetica descrizione delle caratteristiche morfologiche e morfometriche di ciascuno, le caratteristiche geologiche e geomorfologiche, con la descrizione della formazione di alcuni laghi, l\u27uso del suolo, particolarmente importante per capire e definire le pressioni insistenti sul lago e gravanti dal bacino, l\u27idrologia, parte integrante delle caratteristiche e della qualit? ecologica di un lago, le pressioni puntuali dovute a scarichi fognari e/o industriali, agricoli e zootecnici. Di alcuni laghi, si ? anche riportato lo stato trofico attuale e la sua evoluzione nel tempo e le azioni regionali intraprese o che si intendono intraprendere per migliorarne la qualit? alla luce delle indicazione della WFD 2000/60. Inoltre, per tutti i laghi studiati si sono riportate anche la cartografia tecnica regionale per l\u27individuazione di ciascun bacino imbrifero e della rete idrografica principale che lo caratterizza, e una foto aerea per meglio identificare le caratteristiche morfologiche della cuvetta lacustre. Su ciascun lago oggetto di studio, il progetto prevede la raccolta di campioni per i quattro parametri biologici di qualit?, cos? come indicati dalla Direttiva Quadro sulle Acque, e delle caratteristiche idromorfologiche, secondo i protocolli di campionamento definiti a livello nazionale e oggetto di intercalibrazione a livello internazionale. Nel capitolo 1 sono riportate una descrizione delle metodiche e delle modalit? di campionamento per i quattro parametri biologici indagati, macroinvertebrati, fitoplancton, macrofite e pesci. Ogni protocollo di campionamento individua il periodo di campionamento, diverso per ciascun parametro, ad esempio per il macrobenthos si sono individuati due periodi annuali (uno primaverile e l\u27altro autunnale), per le macrofite il periodo di campionamento ? quello del massimo sviluppo vegetativo delle piante, mentre il fitoplancton viene raccolto periodicamente diverse volte, durante l\u27anno di campionamento. Infine i pesci sono campionati da primavera ad autunno. Nella descrizione del protocollo e delle modalit? di campionamento, vengono anche individuati i siti di lavoro, ovvero i punti di indagine, che variano molto da elemento a elemento. Ad esempio, le macrofite e il macrobenthos vengono campionati lungo un transetto, quindi su diverse "linee" distribuite in modo diverso fino a coprire tutto il lago. Il fitoplancton viene campionato nel punto pi? profondo del lago, quindi risulta un campionamento "puntuale" e i pesci vengono raccolti in diverse aree disposte in diverse zone del lago, si possono quindi pensare come campioni "areali". Nel suddetto capitolo si sono riportate anche foto della strumentazione necessaria e utilizzata per il campionamento e altre relative ad alcune fasi di raccolta dei campioni. Unitamente alla raccolta della fauna a macroinvertebrati e del fitoplancton vengono anche raccolti campioni di acqua per le analisi chimiche da utilizzare a sostegno e a completamento delle indagini e della caratterizzazione ecologica del lago. Inoltre, sempre unitamente al campionamento dei macroinvertebrati vengono prelevati campioni di sedimento per l\u27analisi granulometrica e chimica, per definire il corretto posizionamento dei transetti e raccogliere informazioni complementari ma basilari, per l\u27interpretazione dei dati. Oltre ai parametri biologici si sono indagate anche le caratteristiche idromorfologiche di ciascun lago scelto, utilizzando il metodo Lake Habitat Survey (LHS), nato per i laghi inglesi e oggetto di standardizzazione a livello europeo, e in questo progetto, oggetto di validazione per i laghi italiani. I laghi su cui effettuare campionamento e indagine sono 12, tra naturali e fortemente modificati, e situati nelle due regioni Piemonte e Sardegna, suddivisi in 7 laghi in Piemonte e 5 in Sardegna. Inizialmente erano previsti 6 laghi ciascuna regione con l\u27inclusione dell\u27unico lago naturale sardo: il Lago Baratz. Dopo la prima campagna di campionamento in Sardegna, quella relativa al macrobenthos, si ? venuti a conoscenza della presenza di ordigni inesplosi sul fondo del lago. Giudicando pericoloso lavorare sui suoi sedimenti ma anche nelle vicinanze del fondo stesso, si ? deciso di continuare l\u27attivit? sui quattro parametri biologici in un altro lago, il Lago Piccolo di Avigliana, lago naturale piemontese, zona di Parco Naturale e di particolare interesse ecologico. Si ? comunque deciso di mantenere il campionamento del Lago Baratz per quei parametri giudicati non pericolosi, fitoplancton e macrofite in quanto, essendo l\u27unico lago naturale sardo riveste una particolare importanza sia per la Regione Sardegna sia per la raccolta di informazioni biologiche nella Regione, altrimenti mancanti. I laghi scelti quindi sono, in Piemonte: il Piccolo di Avigliana, il Candia e il Viverone nell\u27anfiteatro morenico di Ivrea, il primo Parco Provinciale, il secondo meta turistica e oggetto quindi di forti pressioni sia sulle rive che sull\u27intero lago; il Sirio di particolare interesse sia turistico che naturalistico e due corpi idrici fortemente modificati: il Morasco, nel bacino dell\u27Alto Toce e il Serr? all\u27interno del Parco del Gran Paradiso, entrambi creati a scopo idroelettrico. Per quanto riguarda la Sardegna i 5 laghi indagati in modo completo sono tutti corpi idrici fortemente modificati e sono: il Bidighinzu, il Sos Canales, il Liscia, il Posada e il Torrei; l\u27utilizzo prevalente per questi bacini ? quello potabile tranne che per il Posada che ? irriguo. Le acque del Liscia e del Posada sono utilizzate anche per altri scopi, irriguo e industriale il primo, potabile e idroelettrico il secondo. Durante le campagne di campionamento e soprattutto, durante l\u27applicazione del metodo idromorfologico che prevede il passaggio tra un punto di osservazione e l\u27altro, lungo tutto il perimetro sotto costa, si sono effettuate numerose fotografie di ciascun lago, per documentare sia le pressioni sulla costa, come spiagge attrezzate, banchine, artificializzazioni di varia natura, attivit? presenti, che particolari habitat litorali e sub litorali, come zone sabbiose, canneti, zone rocciose, lanche, aree umide, nonch? vegetazione spondale e riparia e macrofite. Del vasto repertorio fotografico raccolto si sono riportate solo alcune delle principali caratteristiche rilevate e sopra descritte, inserite nei capitoli 3 e 4, relativi ai singoli laghi campionati, rispettivamente in Piemonte e in Sardegna. Il lavoro di campionamento non ? ancora finito per tutti i parametri di qualit?, sia a causa della scelta tardiva del Lago Piccolo di Avigliana, sia per difficolt? di varia natura dovute alle condizioni meteorologiche. Si prevede di concludere tali attivit? entro l\u27estate del 2012. Le prime elaborazioni disponibili sono riportate nel capitolo 5 per entrambe le regioni, ma solo per alcuni parametri e per alcuni laghi. La determinazione delle specie presenti non richiede lo stesso tempo e lo stesso impegno per tutti i parametri di qualit? di conseguenza la chiusura dell\u27identificazione dei campioni raccolti sar? effettuata nelle attivit? prossime future. Un\u27altra attivit? in previsione per il prossimo futuro ? quella della taratura del database per i parametri idromorfologici per l\u27elaborazione degli indici sintetici di alterazione morfologica e di qualit? degli habitat. Tale taratura risulta necessaria in quanto, in una precedente fase di verifica dell\u27applicabilit? del metodo LHS alle caratteristiche idromorfologiche dei laghi italiani, ? stato necessario variare qualche voce nella scheda di campo. Tali variazioni dovranno essere inserite anche nel database associato al metodo

Ancient pathogen-driven adaptation triggers increased susceptibility to non-celiac wheat sensitivity in present-day European populations

Details of sequence profiles for each NCWS subject. (XLSX 47 kb

Delayed diagnosis of coeliac disease increases cancer risk

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Prediction of second neurological attack in patients with clinically isolated syndrome using support vector machines

The aim of this study is to predict the conversion from clinically isolated syndrome to clinically definite multiple sclerosis using support vector machines. The two groups of converters and non-converters are classified using features that were calculated from baseline data of 73 patients. The data consists of standard magnetic resonance images, binary lesion masks, and clinical and demographic information. 15 features were calculated and all combinations of them were iteratively tested for their predictive capacity using polynomial kernels and radial basis functions with leave-one-out cross-validation. The accuracy of this prediction is up to 86.4% with a sensitivity and specificity in the same range indicating that this is a feasible approach for the prediction of a second clinical attack in patients with clinically isolated syndromes, and that the chosen features are appropriate. The two features gender and location of onset lesions have been used in all feature combinations leading to a high accuracy suggesting that they are highly predictive. However, it is necessary to add supporting features to maximise the accuracy. © 2013 IEEE

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)