Blood and urine multi-omics analysis of the impact of e-vaping, smoking, and cessation: from exposome to molecular responses.

Cigarette smoking is a major preventable cause of morbidity and mortality. While quitting smoking is the best option, switching from cigarettes to non-combustible alternatives (NCAs) such as e-vapor products is a viable harm reduction approach for smokers who would otherwise continue to smoke. A key challenge for the clinical assessment of NCAs is that self-reported product use can be unreliable, compromising the proper evaluation of their risk reduction potential.

Evaluation of the procoagulant properties of a newly developed platelet modified lysate product.

Background: Platelet transfusion is associated with logistical problems with the national storage guidelines of platelets. This results in decreased function in vivo as a result of the platelet storage lesion, and complications such as allergic or hemolytic reactions and thrombosis. We evaluated a new, freshly prepared platelet modified lysate (PML) product designed to be more procoagulant than fresh and stored platelets.

Placental Chorionic Cyst Fluid Has Prothrombotic Properties and Differs From Amniotic Fluid.

Introduction: Chorionic cysts of the chorion laeve, fetal chorionic plate, septum, and free membranes have been associated with placental hypoxia, but they have no clear clinical significance. Although immunohistochemistry has identified fibronectin and collagen IV in cyst fluid, the contents have yet to be fully characterized.

Methods: Placental chorionic cysts (N = 10) were sampled by fluid extraction and hemotoxylin and eosin-stained sections.

Sickle red blood cells are more susceptible to in vitro haemolysis when exposed to normal saline versus Plasma-Lyte A.

Background: Normal saline has been the fluid of choice for resuscitation, rehydration and fluid replacement during plasma or red cell exchange/cytapheresis. There are increased concerns about its clinical effects and data showing it causes more haemolysis in vitro than buffered solutions such as Plasma-Lyte A.

Methods: We investigated whether normal saline or Plasma-Lyte A was associated with greater haemolysis during hours of in vitro incubation with both normal red cells and samples from patients with sickle cell anaemia.

Total plasma heme concentration increases after red blood cell transfusion and predicts mortality in critically ill medical patients.

Background: Relationships between red blood cell (RBC) transfusion, circulating cell-free heme, and clinical outcomes in critically ill transfusion recipients are incompletely understood. The goal of this study was to determine whether total plasma heme increases after RBC transfusion and predicts mortality in critically ill patients.

Study Design And Methods: This was a prospective cohort study of 111 consecutive medical intensive care patients requiring RBC transfusion.

In Vitro Methods to Characterize the Effects of Tobacco and Nontobacco Products on Human Platelet Function.

In this document, we describe methods for the isolation, treatment, and functional testing of human blood platelets in vitro. Functional assays for inflammatory function include flow cytometry and immunoassays for platelet release of platelet factor 4, soluble CD40L, prostaglandin E , and thromboxane. Assays for platelet hemostatic function described here examine platelet spreading, aggregation using platelet-rich plasma, and thromboelastography.

The HIV protease inhibitor, ritonavir, dysregulates human platelet function in vitro.

There are 37 million people globally infected with the Human Immunodeficiency Virus (HIV). People living with HIV can achieve nearly normal lifespans due to the use of antiretroviral drugs (ARVs). However, people living with HIV experience chronic inflammation and increased risk for cardiovascular diseases (CVD) relative to uninfected people.

Decreased Hemolysis and Improved Platelet Function in Blood Components Washed With Plasma-Lyte A Compared to 0.9% Sodium Chloride.

Objectives: Washing cellular blood products is accepted to ameliorate repeated severe allergic reactions but is associated with RBC hemolysis and suboptimal platelet function. We compared in vitro hemolysis and platelet function in blood components after washing with Plasma-Lyte A (PL-A) vs normal saline (NS).

Methods: RBC (n = 14) were washed/resuspended in NS or PL-A.

Elevated free hemoglobin and decreased haptoglobin levels are associated with adverse clinical outcomes, unfavorable physiologic measures, and altered inflammatory markers in pediatric cardiac surgery patients.

Background: There are data suggesting that free hemoglobin (Hb), heme, and iron contribute to infection, thrombosis, multiorgan failure, and death in critically ill patients. These outcomes may be mitigated by haptoglobin.

Study Design And Methods: 164 consecutively treated children undergoing surgery for congenital heart disease were evaluated for associations between free Hb and haptoglobin and clinical outcomes, physiologic metrics, and biomarkers of inflammation RESULTS: Higher perioperative free Hb levels (and lower haptoglobin levels) were associated with mortality, nosocomial infection, thrombosis, hours of intubation and inotropes, increased interleukin-6, peak serum lactate levels, and lower nadir mean arterial pressures.

0.9% NaCl (Normal Saline) - Perhaps not so normal after all?

Crystalloid infusion is widely employed in patient care for volume replacement and resuscitation. In the United States the crystalloid of choice is often normal saline. Surgeons and anesthesiologists have long preferred buffered solutions such as Ringer's Lactate and Plasma-Lyte A.

Management of Platelet Disorders and Platelet Transfusions in ICU Patients.

Thrombocytopenia or receipt of antiplatelet drugs, with or without bleeding, is a common indication for platelet transfusions in the ICU. However, there is almost no evidence base for these practices other than expert opinion. Also common is use of platelet transfusions prior to invasive procedures or surgery in patients with thrombocytopenia.

NF-κB Links TLR2 and PAR1 to Soluble Immunomodulator Factor Secretion in Human Platelets.

The primary toll-like receptor (TLR)-mediated immune cell response pathway common for all TLRs is MyD88-dependent activation of NF-κB, a seminal transcription factor for many chemokines and cytokines. Remarkably, anucleate platelets express the NF-κB machinery, whose role in platelets remains poorly understood. Here, we investigated the contribution of NF-κB in the release of cytokines and serotonin by human platelets, following selective stimulation of TLR2 and protease activated receptor 1 (PAR1), a classical and non-classical pattern-recognition receptor, respectively, able to participate to the innate immune system.

Resveratrol preserves the function of human platelets stored for transfusion.

Stored platelets undergo biochemical, structural and functional changes that lead to decreased efficacy and safety of platelet transfusions. Not only do platelets acquire markers of activation during storage, but they also fail to respond normally to agonists post-storage. We hypothesized that resveratrol, a cardioprotective antioxidant, could act as a novel platelet storage additive to safely prevent unwanted platelet activation during storage, while simultaneously preserving normal haemostatic function.

Breaking the mold: transcription factors in the anucleate platelet and platelet-derived microparticles.

Platelets are small anucleate blood cells derived from megakaryocytes. In addition to their pivotal roles in hemostasis, platelets are the smallest, yet most abundant, immune cells and regulate inflammation, immunity, and disease progression. Although platelets lack DNA, and thus no functional transcriptional activities, they are nonetheless rich sources of RNAs, possess an intact spliceosome, and are thus capable of synthesizing proteins.

Platelet transfusion - the new immunology of an old therapy.

Platelet transfusion has been a vital therapeutic approach in patients with hematologic malignancies for close to half a century. Randomized trials show that prophylactic platelet transfusions mitigate bleeding in patients with acute myeloid leukemia. However, even with prophylactic transfusions, as many as 75% of patients, experience hemorrhage.

Longer RBC storage duration is associated with increased postoperative infections in pediatric cardiac surgery.

Objectives: Infants and children undergoing open heart surgery routinely require multiple RBC transfusions. Children receiving greater numbers of RBC transfusions have increased postoperative complications and mortality. Longer RBC storage age is also associated with increased morbidity and mortality in critically ill children.

Mapracorat, a selective glucocorticoid receptor agonist, upregulates RelB, an anti-inflammatory nuclear factor-kappaB protein, in human ocular cells.

Selective glucocorticoid receptor agonists (SEGRAs) are a new class of compounds under clinical evaluation for treatment of ocular inflammation. Widely prescribed therapeutics, such as glucocorticoids, are effective at reducing ocular inflammation, but their long term use predisposes to undesirable side effects. The purpose of this study was to investigate a novel SEGRA, mapracorat (BOL-303242-X), and the differences in mapracorat's mechanism of action compared with traditional steroids (i.

Isoprostane and isofuran lipid mediators accumulate in stored red blood cells and influence platelet function in vitro.

Background: Stored red blood cells (RBCs) release hemoglobin (Hb) that leads to oxidative damage, which may contribute to thrombosis in susceptible transfusion recipients. Oxidative stress stimulates the generation of a new class of lipid mediators called F2 -isoprostanes (F2 -IsoPs) and isofurans (IsoFs) that influence cellular behavior. This study investigated RBC-derived F2 -IsoPs and IsoFs during storage and their influence on human platelets (PLTs).

Attenuation of inflammatory mediator production by the NF-κB member RelB is mediated by microRNA-146a in lung fibroblasts.

Lung inflammation can result from exposure to multiple types of inflammatory stimuli. Fibroblasts, key structural cells in the lung that are integral to inflammation and wound healing, produce inflammatory mediators after exposure to stimuli such as IL-1β. We and others have shown that the NF-κB member RelB has anti-inflammatory properties in mice.

Transfusion immunomodulation--the case for leukoreduced and (perhaps) washed transfusions.

During the last three decades, a growing body of clinical, basic science and animal model data has demonstrated that blood transfusions have important effects on the immune system. These effects include: dysregulation of inflammation and innate immunity leading to susceptibility to microbial infection, down-regulation of cellular (T and NK cell) host defenses against tumors, and enhanced B cell function that leads to alloimmunization to blood group, histocompatibility and other transfused antigens. Furthermore, transfusions alter the balance between hemostasis and thrombosis through inflammation, nitric oxide scavenging, altered rheologic properties of the blood, immune complex formation and, no doubt, several mechanisms not yet elucidated.

Platelet storage and transfusions: new concerns associated with an old therapy.

Platelet transfusion has long been practiced with rudimentary knowledge about optimal storage conditions and their implications for efficacy and, particularly, safety. Recent concerns about complications such as inflammation, thrombosis and altered recipient immunity have been raised about platelet transfusion. This review will discuss recent important findings that have raised these issues about platelet transfusion associated morbidity, mortality and the possible role of platelet storage in these associations.

Alterations of platelet function and clot formation kinetics after in vitro exposure to anti-A and -B.

Background: ABO-mismatched platelets (PLTs) are commonly transfused despite reported complications. We hypothesized that because PLTs possess A and B antigens on their surface, ABO-mismatched transfused or recipient PLTs could become activated and/or dysfunctional after exposure to anti-A or -B in the transfused or recipient plasma. We present here in vitro modeling data on the functional effects of exposure of PLTs to ABO antibodies.