Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients.

Introduction: In a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization. Materials and Methods: Intensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed. Results: Patients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding. Conclusion: This study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.

ARTe: Providing real-time multitasking to Arduino

In the last decade, thanks to its modular hardware and straightforward programming model, the Arduino ecosystem became a reference for learning the development of embedded systems by various users, ranging from amateurs and students to makers. However, while the latest released platforms are equipped with modern microcontrollers, the programming model is still tied to a single-threaded, legacy approach. This limits the exploitation of the underlying hardware platform and poses limitations in new application scenarios, such as IoT and UAVs. This paper presents the Arduino real-time extension (ARTe), which seamlessly extends the Arduino programming model to enable the concurrent execution of multiple loops at different rates configurable by the programmer. This is obtained by embedding a low-footprint, real-time operating system in the Arduino framework. The adherence to the original programming model, together with the hidden support for managing the inherent complexity of concurrent software, allows expanding the applicability of the Arduino framework while ensuring a more efficient usage of the computational resources. Furthermore, the proposed approach allows a finer control of the latencies and the energy consumption. Experimental results show that such advantages are obtained at the cost of a small additional overhead and memory footprint. To highlight the benefits introduced by ARTe, the paper finally presents two case studies, one of such in which ARTe has been leveraged to rapidly prototype a mechanical ventilator for acute COVID-19 cases. We found that ARTe allowed our ventilator design to rapidly adapt to changes in the available components and to the evolving needs of Intensive Care Units (ICU) in the Americas.

Endothelium Activation Markers in Severe Hospitalized COVID-19 Patients: Role in Mortality Risk Prediction.

Introduction Endothelial damage and hypercoagulability are major players behind the hemostatic derangement of SARS-CoV-2 infection. Aim In this prospective study we assessed endothelial and inflammatory biomarkers in a cohort of COVID-19 patients, aiming to identify predictive factors of in-hospital mortality. Methods COVID-19 patients hospitalized in intensive care (ICU) and non-ICU units at 2 Bergamo (Italy) hospitals from March 23 to May 30, 2020, were enrolled. Markers of endothelium activation including von-Willebrand factor (vWF), soluble thrombomodulin (sTM), and fibrinolytic proteins (t-PA and PAI-1) were measured. Additionally, D-dimer, Fibrinogen, FVIII, nucleosomes, C reactive protein (CRP) and procalcitonin were assessed. Results Sixty-three (45 ICU, and 18 non-ICU) patients, with a median age of 62 years were analyzed. Increased plasma levels of D-dimer, FVIII, fibrinogen, nucleosomes, CRP, and procalcitonin were observed in the whole cohort. Extremely elevated vWF levels characterized all patients (highest values in ICU-subjects). After a median time of 30 days, death occurred in 13 (21%) patients. By multivariable analysis, vWF-activity, neutrophil-count and PaO2/FiO2 were significantly associated with death. Using these variables, a linear score with 3-risk groups was generated that provided a cumulative incidence of death of 0% in the low-, 32% in the intermediate-, and 78% in the high-risk group. Conclusions COVID-19-induced hemostatic abnormalities are exacerbated by the severity of the disease and strongly correlate with the inflammatory status, underlying the link between coagulation, endothelial activation, and inflammation. Our study provides evidence for a role of vWF, together with neutrophils and PaO2/FiO2, as a significant predictor of in-hospital mortality by SARSCoV-2 infection.

A Remote Control System for Emergency Ventilators During SARS-CoV-2.

As COVID-19 began to grip healthcare systems worldwide, worst-case models predicted huge demands for ventilators. The global community sprang to action, producing a large number of emergency "makeshift" ventilator designs. This brought about another problem: a gap between the quantity of new mechanical ventilators and the number of skilled physicians to operate them. New physicians could not complete training at the pace of ventilator production, which threatened to leave patients sitting untreated, next to unusable ventilators. To address this challenge, we developed a universal remote control system for makeshift ventilators that uses low-cost hardware add-on modules to connect to different ventilators, and a three-tier control architecture to interface the ventilators with telemedicine software. We demonstrate system integration with two representative ventilator designs, adding a remote control option that allows caregivers to quickly and easily monitor and control these ventilators remotely.