48 research outputs found

    C2C12 MYOBLASTS RELEASE MICRO-VESICLES CONTAINING mtDNA AND PROTEINS INVOLVED IN SIGNAL TRANSDUCTION

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    none11Micro-vesicles can be released by different cell types and operate as ‘safe containers’ mediatine inter-cellular communication. In this work we investigated whether cultured myoblasts could release exosomes. The reported data demonstrate, for the first time, that C2C12 myoblasts release micro-vesicles as shown by the presence of two exosome markers (Tsg101 and Alix proteins). Using real-time PCR analysis it was shown that these micro-vesicles, like other cell types, carry mtDNA. Proteomic characterization of the released micro-vesicle contents showed the presence of many proteins involved in signal transduction. The bioinformatics assessment of the Disorder Index and Aggregation Index of these proteins suggested that C2C12 micro-vesicles mainly deliver the machinery for signal transduction to target cells rather than key proteins involved in hub functions in molecular networks. The presence of IGFBP-5 in the purified micro-vesicles represents an exception, since this binding protein can play a key role in the modulation of the IGF-1 signalling pathway. In conclusion, the present findings demonstrate that skeletal muscle cells release micro-vesicles, which probably have an important role in the communication processes within skeletal muscles and between skeletal muscles and other organs. In particular, the present findings suggest possibile new diagnostic approaches to skeletal muscle diseases.openM. GUESCINI; D. GUIDOLIN; L. VALLORANI; L. CASADEI; A.M. GIOACCHINI; P. TIBOLLO; M. BATTISTELLI; E. FALCIERI; L. BATTISTIN; L.F. AGNATI; V. STOCCHIGuescini, Michele; D., Guidolin; Vallorani, Luciana; Casadei, Lucia; Gioacchini, ANNA MARIA; P., Tibollo; Battistelli, Michela; Falcieri, Elisabetta; L., Battistin; L. F., Agnati; Stocchi, Vilbert

    A dashboard-based system for supporting diabetes care

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    [EN] Objective To describe the development, as part of the European Union MOSAIC (Models and Simulation Techniques for Discovering Diabetes Influence Factors) project, of a dashboard-based system for the management of type 2 diabetes and assess its impact on clinical practice. Methods The MOSAIC dashboard system is based on predictive modeling, longitudinal data analytics, and the reuse and integration of data from hospitals and public health repositories. Data are merged into an i2b2 data warehouse, which feeds a set of advanced temporal analytic models, including temporal abstractions, care-flow mining, drug exposure pattern detection, and risk-prediction models for type 2 diabetes complications. The dashboard has 2 components, designed for (1) clinical decision support during follow-up consultations and (2) outcome assessment on populations of interest. To assess the impact of the clinical decision support component, a pre-post study was conducted considering visit duration, number of screening examinations, and lifestyle interventions. A pilot sample of 700 Italian patients was investigated. Judgments on the outcome assessment component were obtained via focus groups with clinicians and health care managers. Results The use of the decision support component in clinical activities produced a reduction in visit duration (P¿¿¿.01) and an increase in the number of screening exams for complications (PÂż<Âż.01). We also observed a relevant, although nonstatistically significant, increase in the proportion of patients receiving lifestyle interventions (from 69% to 77%). Regarding the outcome assessment component, focus groups highlighted the systemÂżs capability of identifying and understanding the characteristics of patient subgroups treated at the center. Conclusion Our study demonstrates that decision support tools based on the integration of multiple-source data and visual and predictive analytics do improve the management of a chronic disease such as type 2 diabetes by enacting a successful implementation of the learning health care system cycle.This work was supported by the European Union in the Seventh Framework Programme, grant number 600914.Dagliati, A.; Sacchi, L.; Tibollo, V.; Cogni, G.; Teliti, M.; Martinez-Millana, A.; Traver Salcedo, V.... (2018). A dashboard-based system for supporting diabetes care. Journal of the American Medical Informatics Association. 25(5):538-547. https://doi.org/10.1093/jamia/ocx159S538547255Sim, I., Gorman, P., Greenes, R. A., Haynes, R. B., Kaplan, B., Lehmann, H., & Tang, P. C. (2001). Clinical Decision Support Systems for the Practice of Evidence-based Medicine. Journal of the American Medical Informatics Association, 8(6), 527-534. doi:10.1136/jamia.2001.0080527Palmer, A. J., Roze, S., Valentine, W. J., Minshall, M. E., Foos, V., Lurati, F. M., 
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    International comparisons of laboratory values from the 4CE collaborative to predict COVID-19 mortality

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    Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach

    Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study

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    Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53–3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03–4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55–5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14–1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37–0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17–1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20–1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45–1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80–13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10–1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32–1.67) and 365 days (RR 1.54, 95%CI 1.21–1.96) compared to COVID-19 patients with no AKI. Interpretation: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery. Funding: Authors are supported by various funders, with full details stated in the acknowledgement section

    Health informatics and EHR to support clinical research in the COVID-19 pandemic: An overview

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    The coronavirus disease 2019 (COVID-19) pandemic has clearly shown that major challenges and threats for humankind need to be addressed with global answers and shared decisions. Data and their analytics are crucial components of such decision-making activities. Rather interestingly, one of the most difficult aspects is reusing and sharing of accurate and detailed clinical data collected by Electronic Health Records (EHR), even if these data have a paramount importance. EHR data, in fact, are not only essential for supporting day-by-day activities, but also they can leverage research and support critical decisions about effectiveness of drugs and therapeutic strategies. In this paper, we will concentrate our attention on collaborative data infrastructures to support COVID-19 research and on the open issues of data sharing and data governance that COVID-19 had made emerge. Data interoperability, healthcare processes modelling and representation, shared procedures to deal with different data privacy regulations, and data stewardship and governance are seen as the most important aspects to boost collaborative research. Lessons learned from COVID-19 pandemic can be a strong element to improve international research and our future capability of dealing with fast developing emergencies and needs, which are likely to be more frequent in the future in our connected and intertwined world

    Personalising Symptoms Reporting in Telemonitoring Applications for Cancer Patients

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    Patient reported outcomes have been shown to be predictive of cancer patients' prognosis, and their monitoring through electronic applications have been shown to positively impact survival. On the other hand, patient apps in general show a number of criticalities that often lead patients to abandon their use. One of them is usability. A scarce attention to usability during app development leads to unsatisfactory user experience. In this work, we present an algorithm to facilitate patient symptoms reporting, by personalising the list of symptoms according to their probability of occurrence in the specific patient. This avoids searching long lists of items, thus decreasing the patients' burden in symptom reporting

    Obstructive Sleep Apnea Home-Monitoring Using a Commercial Wearable Device

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    Obstructive sleep apnea (OSA) is a common sleep disorder and polysomnography (PSG) is the gold standard for its diagnosis and treatment monitoring. There are nowadays several activity trackers measuring sleep quality through the detection of sleep stages. To allow an easier monitoring of the treatment efficacy at home, this work explores the possibility of using one of those commercial smart-bands. To this aim, we studied the signals provided by PSG and a Fitbit smart-band on 26 consecutive patients, admitted to the hospital after the diagnosis of OSA, and submitted to ventilation or positional treatment. They underwent monitoring for three nights (basal, titration, and control). We developed both a visualization software allowing doctors to visually compare the two hypnograms, and a set of statistics for assessing the concordance of the two methods. Results indicate that Fitbit can detect normal sleep patterns, while it is less able to detect the abnormal ones

    Artificial intelligence-based prediction of overall survival in metastatic renal cell carcinoma

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    Background and objectives: Investigations of the prognosis are vital for better patient management and decision-making in patients with advanced metastatic renal cell carcinoma (mRCC). The purpose of this study is to evaluate the capacity of emerging Artificial Intelligence (AI) technologies to predict three- and five-year overall survival (OS) for mRCC patients starting their first-line of systemic treatment. Patients and methods: The retrospective study included 322 Italian patients with mRCC who underwent systemic treatment between 2004 and 2019. Statistical analysis included the univariate and multivariate Cox proportional-hazard model and the Kaplan-Meier analysis for the prognostic factors’ investigation. The patients were split into a training cohort to establish the predictive models and a hold-out cohort to validate the results. The models were evaluated by the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. We assessed the clinical benefit of the models using decision curve analysis (DCA). Then, the proposed AI models were compared with well-known pre-existing prognostic systems Results: The median age of patients in the study was 56.7 years at RCC diagnosis and 78% of participants were male. The median survival time from the start of systemic treatment was 29.2 months; 95% of the patients died during the follow-up that finished by the end of 2019. The proposed predictive model, which was constructed as an ensemble of three individual predictive models, outperformed all well-known prognostic models to which it was compared. It also demonstrated better usability in supporting clinical decisions for 3- and 5-year OS. The model achieved (0.786 and 0.771) AUC and (0.675 and 0.558) specificity at sensitivity 0.90 for 3 and 5 years, respectively. We also applied explainability methods to identify the important clinical features that were found to be partially matched with the prognostic factors identified in the Kaplan-Meier and Cox analyses. Conclusions: Our AI models provide best predictive accuracy and clinical net benefits over well-known prognostic models. As a result, they can potentially be used in clinical practice for providing better management for mRCC patients starting their first-line of systemic treatment. Larger studies would be needed to validate the developed model Copyright © 2023 Barkan, Porta, Rabinovici-Cohen, Tibollo, Quaglini and Rizzo
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