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This letter presents a novel reference governor scheme for overshoot mitigation in a tracking control system. Our proposed scheme, referred to as the Reference Governor with Dynamic Constraint (RG-DC), recasts the overshoot mitigation problem as a constraint management problem. The outcome of this reformulation is a dynamic Maximal Admissible Set (MAS), which varies in real-time as a function of the reference signal. The RG-DC employs the dynamic MAS, as well as a novel switching logic, to modify the reference signal to prevent or mitigate overshoot. We present several properties of the dynamic MAS and the algorithms required to compute it. We also investigate the stability and recursive feasibility of the RG-DC. Simulation results demonstrate the efficacy of the approach, and also highlight its limitations.Von Willebrand disease (VWD) is a bleeding disorder caused by qualitative or quantitative defects of von Willebrand factor (VWF). This case report of a patient with systemic sclerosis and gastrointestinal bleeding from angiodysplasias seeks to address the key clinical question of a useful diagnostic and therapeutic approach in this setting. The extent of vascular malformations and the frequency of bleeding episodes were unusually severe, and we reached a diagnosis of inherited type 2A VWD. After an insufficient effect of treatment with factor VIII (FVIII)/VWF, prophylactic administration of vonicog alfa, a recombinant VWF preparation without FVIII, was initiated. This therapy led to a substantial reduction of transfusion requirements and the improvement of angiodysplasias. In refractory gastrointestinal bleeding, hemostaseological evaluation is crucial, as inherited disorders of hemostasis may go unnoticed, especially in patients with underlying autoimmune diseases, where complications may be ascribed to the underlying disease.Thrombosis in COVID-19 is increasingly recognized and is generally associated with a high mortality rate. The key clinical question of this report was whether COVID-19 could be complicated with cardiac thrombus and pulmonary embolism in Asian population. We demonstrated the case series of thrombosis in Thai patients with confirmed severe acute respiratory syndrome coronavirus 2 infection. One patient had the first case of a large left ventricular thrombus, and three other patients had pulmonary embolism. All patients were male and had low absolute lymphocyte count, while lactate dehydrogenase level and d-dimer were markedly elevated, especially at the time when the thrombosis was diagnosed. All patients had severe COVID-19 with pneumonia. Two patients who needed mechanical ventilation were successfully extubated. After hospitalization for 13-49 days, pneumonia and thrombosis improved and all of them could be discharged from the hospital. Thrombosis is common in COVID-19 and could present in both arterial and venous sites even in Asian populations. d-dimer is a strong marker to predict thrombosis and could be a prognostic predictor for severity of COVID-19.

Distal deep vein thrombosis (infrapopliteal DVT without proximal DVT or pulmonary embolism [PE]) generally shares the same triggering risks factors as proximal DVT. In women of childbearing age, a frequent triggering risk factor is the use of combined oral contraceptive (COC) pills. However, data on the epidemiology and long-term outcomes of COC-associated distal DVT are lacking.

To assess the epidemiology and long-term outcomes of COC-associated distal DVT.

Using data from the OPTIMEV (Optimisation de l'Interrogatoire dans l'évaluation du risque thrombo-Embolique Veineux [Optimization of Interrogation in the Assessment of Thromboembolic Venous Risk]) multicenter cohort study of patients with objectively confirmed venous thromboembolism (VTE) enrolled between 2004 and 2006, we assessed in nonpregnant or postpartum women aged≤50years without cancer or history of VTE (i) proportion of COC-associated distal DVTs among women with distal DVTs and among women with COC-associated VTEs (distal DVT, proximal DVT, or PE) and (ii) 3-year incidence of death, bleeding, and VTE recurrence.

COC-associated distal DVTs (n=54) represented 43.9% of all distal DVTs and 51.9% of COC-associated VTEs. All but one woman with a COC-associated distal DVT received therapeutic anticoagulation for a median of 3months. At 3-year follow-up, all women with COC-associated distal DVTs were alive, and none had bled during anticoagulant treatment or had experienced a DVT or PE recurrence after stopping anticoagulants. Similar results were found in patients with COC-associated proximal DVT and PE The VTE recurrence rate was 1.7% per patient-year (PY) and 0% PY, respectively, and there were no deaths or major bleeds in either group.

Distal DVT was the most frequent clinical presentation of COC-associated VTE and had similarly favorable long-term outcomes as other COC-associated VTE.

Distal DVT was the most frequent clinical presentation of COC-associated VTE and had similarly favorable long-term outcomes as other COC-associated VTE.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. Expert consensus recommends a risk-based approach to guide prophylactic anticoagulation to prevent VTE in ambulatory patients with cancer receiving chemotherapy. However, oncology practice patterns for VTE prevention remain unclear.

We conducted (i) a retrospective, single-center cohort study of patients with pancreatic and gastric cancers to examine rates of prophylactic anticoagulation prescription for eligible patients at high risk of VTE based on the validated Khorana score, and (ii) a 15-question survey of oncology clinicians at the same institution to assess current practice patterns and knowledge regarding VTE risk assessment and primary thromboprophylaxis in February 2020.

Of 437 patients who met study criteria, 181 (41%) had a score of≥3 (high-risk), and none had an anticoagulation prescription for prophylaxis without an alternate treatment indication. In a survey sent to 98 oncology clinicians, of which 34 participated, 67% were unfamiliar with the Khorana score or guideline recommendations regarding risk-based VTE prophylaxis, and 90% "never" or "rarely" used VTE risk assessment.

Despite available evidence and existing guideline recommendations for VTE risk assessment for ambulatory patients with cancer, and primary prophylaxis for high-risk patients, this study demonstrates that there is limited uptake in clinical practice.

Despite available evidence and existing guideline recommendations for VTE risk assessment for ambulatory patients with cancer, and primary prophylaxis for high-risk patients, this study demonstrates that there is limited uptake in clinical practice.

In multiple myeloma, venous thromboembolism (VTE) is common, and treatments for myeloma, such as lenalidomide, increase the risk of thrombosis while improving survival. The association between VTE and survival is not well known.

To determine the association between VTE and survival in multiple myeloma (MM) while adjusting for known confounders that affect risk of thrombosis and survival, including patient characteristics and treatment in a retrospective cohort of US veterans.

A cohort of patients with newly diagnosed MM treated within Veterans Health Administration between September 1, 1999, and June 30, 2014, was created to assess the association between VTE and mortality using Cox proportional hazards regression modeling while accounting for known prognostic factors and treatments.

The cohort comprised 4446 patients with myeloma, including 2837 patients diagnosed after lenalidomide approval in July 2006. selleck chemicals llc VTE occurred in 327 (7.4%) patients within 1year and occurred at a median of 77days (interquartile range, 37-153) after starting therapy for MM. In all patients, VTE was associated with increased mortality at 6months (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.18-2.37). Patients in the post-lenalidomide cohort with VTE had an increased mortality at both 6months (aHR, 2.31; 95% CI, 1.52-3.51) and 12months (aHR, 1.66; 95% CI, 1.19-2.33) after treatment initiation.

This study shows that VTE during the first 6-12months of therapy is associated with increased mortality in patients with MM. Studies evaluating thromboprophylaxis in patients at high risk of thrombosis are needed.

This study shows that VTE during the first 6-12 months of therapy is associated with increased mortality in patients with MM. Studies evaluating thromboprophylaxis in patients at high risk of thrombosis are needed.

Anticoagulant treatment of splanchnic (SVT) and cerebral vein thrombosis (CVT) can be challenging due to the rarity of these conditions, the concomitantly high thrombotic and bleeding risks, and the available low-quality evidence.

To explore the current therapeutic approaches to SVT and CVT, and the rationale behind the anticoagulant treatment choice.

A cross-sectional survey was conducted (October 2018-April 2019) among members of three thrombosis and hemostasis societies. The survey consisted of four vignette cases (i) SVT secondary to transient risk factor; (ii) cirrhotic SVT with esophageal varices; (iii) CVT secondary to transient risk factor; and (iv) unprovoked CVT with intracranial hemorrhage.

A total of 397 physicians responded to the survey. There was wide variability in anticoagulant treatment options, starting time, and duration. Vitamin K antagonists were the commonest choice across the four vignette cases (44.2%-63.0%). The direct oral anticoagulants (DOACs) were the second commonest choice in low-bleeding-risk scenarios (27.7% in case 1, 22.9% in case 3), while parenteral anticoagulation alone was the second commonest choice in high-bleeding-risk scenarios (39.9% in case 2, 39.8% in case 4). The most frequent reasons for selecting DOACs were oral route of administration (50.6%), lack of need for laboratory monitoring (48.1%), and favorable safety profile of these drugs (43.4%).

The results of our study showed that, despite being off-label, the DOACs were considered for the treatment of unusual-site venous thromboembolism. The wide variability among different physicians reflected the clinical difficulties and raised the need for more collaborative trials on these disorders.

The results of our study showed that, despite being off-label, the DOACs were considered for the treatment of unusual-site venous thromboembolism. The wide variability among different physicians reflected the clinical difficulties and raised the need for more collaborative trials on these disorders.

Tyrosyl-tRNA synthetase (YRS) belongs to the family of enzymes that catalyzes the tRNA aminoacylation reaction for protein synthesis, and it has been recently shown to exert noncanonical functions. Although database results indicate extremely low levels of YRS mRNA in platelets, YRS protein is abundantly present. The source of YRS in platelets, as well as the physiological role of platelet-stored YRS, remains largely unknown.

To clarify how YRS accumulates in platelets and determine the potential role of platelet-stored YRS.

Recombinant YRS proteins with epitope tags were prepared and tested in vitro for proteolytic cleavage in human plasma. Fluorescent-labeled YRS was examined for uptake by platelets, as demonstrated by western blotting and confocal microscopy analysis. Using RAW-Dual reporter cells, Toll-like receptor and type I interferon activation pathways were analyzed after treatment with YRS.

Full-length YRS was cleaved by both elastase and matrix metalloproteinases in the plasma. The cleaved, N-terminal YRS fragment corresponds to the endogenous YRS detected in platelet lysate by western blotting.

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