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MicroRNAs (miRNAs) are small noncoding RNAs modulating protein production. They are key players in regulation of cell function and are considered as biomarkers in several diseases. The identification of the proteins they regulate, and their impact on cell physiology, may delineate their role as diagnostic or prognostic markers and identify new therapeutic strategies. During the last 3 decades, development of a large panel of techniques has given rise to multiple models dedicated to the study of miRNAs. Since plasma samples are easily accessible, circulating miRNAs can be studied in clinical trials. To quantify miRNAs in numerous plasma samples, the choice of extraction and purification techniques, as well as normalization procedures, are important for comparisons of miRNA levels in populations and over time. Recent advances in bioinformatics provide tools to identify putative miRNAs targets that can then be validated with dedicated assays. In vitro and in vivo approaches aim to functionally validate candidate miRNAs from correlations and to understand their impact on cellular processes. This review describes the advantages and pitfalls of the available techniques for translational research to study miRNAs with a focus on their role in regulating platelet reactivity.
Coagulopathy is a common serious complication of sepsis and septic shock; thus, its early detection and prompt management are important. For this purpose, recently the sepsis-induced coagulopathy (SIC) score was proposed.
We modified the SIC score for critically ill children with septic shock and evaluated its performance in comparison to several coagulopathy diagnostic scoring systems.
Among 135 included patients, a significant number of patients were diagnosed with coagulopathy using different coagulopathy diagnostic criteria (up to 84.4% using the SIC score). Cinchocaine molecular weight The modified SIC score, comprising the pediatric sequential organ failure assessment (pSOFA) score, prothrombin time, and D-dimer, was used to diagnose SIC in 68 (50.4%) patients. It was well correlated with the pSOFA score and the International Society on Thrombosis and Haemostasis disseminated intravascular coagulation (DIC) score, as well as the SIC score (
< 0.001). The overall 28-day mortality rate was 18.7%. Patients with coagulopathy had worse clinical outcomes compared to those without coagulopathy. The modified SIC score was identified as an independent prognostic factor for 28-day mortality. The area under the receiver operating characteristic curve for performance of the modified SIC score to predict 28-day mortality evaluated was 0.771 (95% confidence interval 0.658-0.883), better than those of the SIC and ISTH DIC scores (
< 0.05).
Critically ill pediatric patients with septic shock frequently had concomitant coagulopathy. The modified SIC score showed good ability to predict 28-day mortality, suggesting its potential as a prognostic factor in these critically ill pediatric patients.
Critically ill pediatric patients with septic shock frequently had concomitant coagulopathy. The modified SIC score showed good ability to predict 28-day mortality, suggesting its potential as a prognostic factor in these critically ill pediatric patients.Platelet transfusion is the standard treatment to control or prevent bleeding in patients with Glanzmann's thrombasthenia (GT), but platelets are often unavailable. Recombinant activated factor VII (rFVIIa) is an effective alternative to platelets in patients with GT with past/present refractoriness to platelet transfusions and antibodies to platelets. However, there is an unmet need for an alternative to platelets in patients without antibodies. This report summarizes evidence of efficacy and safety of rFVIIa in patients with GT without refractoriness or antibodies to platelets from three different sources the Glanzmann's Thrombasthenia Registry (GTR), published literature (January 01, 1999 to December 01, 2017), and the Novo Nordisk safety surveillance database. In the GTR, 133 patients received rFVIIa for the treatment of 333 bleeding episodes and prevention of bleeding in 157 surgical procedures. Overall efficacy rates were 79 and 88%, respectively, in patients treated for bleeding episodes or for the prevention of bleeding during surgery; effectiveness was generally similar across refractoriness/antibody status categories. Median dose per infusion of rFVIIa was close to that recommended for patients with GT (90 µg/kg). Data from 14 published case reports also demonstrated that rFVIIa is effective with an acceptable safety profile in patients with GT without antibodies to platelets. Analysis of adverse events reported in GTR and in Novo Nordisk safety surveillance database did not raise any new safety concerns. These data supported the label extension of rFVIIa to include cases where platelets are not readily available, which was approved by the European Medicines Agency in December 2018.Reduced megakaryocyte (MK) apoptosis and insufficient platelet production play important roles in the pathogenesis of immune thrombocytopenia (ITP). The contribution of plasma-derived exosomes to the decreased platelet count in ITP has not been entirely understood. Here, we found the percentage of apoptotic MKs in patients with ITP was significantly lower than those in healthy volunteers. In the presence of ITP plasma-derived exosomes (ITP-Exo), the apoptosis of MKs was reduced during the process of MK differentiation in vitro, which contributed to the reduced platelet production by Bcl-xL/caspase signaling. Furthermore, in vivo study demonstrated that ITP-Exo administration led to significantly delayed platelet recovery in mice after 3.5 Gy of irradiation. All these findings indicated that ITP-Exo, as a regulator of platelet production, impaired MK apoptosis and platelet production through Bcl-xL/caspase signaling, unveiling new mechanisms for reduced platelet count in ITP.
Reports describing coronavirus disease 2019 (Covid-19) in children are fewer than adult studies due to milder clinical picture. We aimed to share our experience at a single center with an emphasis on collective decision making.
A suspected case was defined as the presence of symptoms suggestive of COVID-19 and/or positive contact history. SARS-CoV-2 PCR positive patients were defined as confirmed COVID-19. Between March 12, 2020, and May 15, 2020, all children presenting with fever, cough, or respiratory difficulty were investigated for COVID-19. A total of 719 children were examined at outpatient clinics, and 495 were tested with polymerase chain reaction (PCR) for suspicion of COVID-19. A team was organized for monitoring and treating patients either as outpatients or hospitalization. Patients were evaluated in terms of age, gender, travel history, epidemiological history, clinical symptoms and signs, laboratory and radiological findings, treatment, and outcome.
Sixty patients were hospitalized for suspicion of COVID-19.
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