Early high-dose vasopressors in refractory septic shock: A cohort study.

Purpose: Septic shock refractory to high-dose vasopressors confers unacceptably high mortality, however, the impact of timing of peak vasopressor dose exposure on outcomes is unknown.

Methods: This retrospective cohort study included adults who required a vasopressor dose ≥0.5 μg/kg/min norepinephrine-equivalents in the first 24 h of septic shock.

Impact of therapeutic plasma exchange on intact protein S, apolipoproteins, and thrombin generation.

Introduction: Therapeutic plasma exchange (TPE), with solvent/detergent (S/D)-treated plasma as replacement fluid, is an extracorporeal blood purification technique with major impact on both coagulation and lipids. Our previous in vitro study showed that S/D-plasma enhances thrombin generation by lowering intact protein S (PS) levels.

Aims: To evaluate the impact of altered lipid balance on coagulation phenotype during heparin-anticoagulated TPE with S/D-plasma, and to investigate whether the lowered intact PS levels with concomitant procoagulant phenotype, are recapitulated in vivo.

Optimized biomimetic minerals maintain activity of mRNA complexes after long term storage.

mRNA therapeutics can be readily designed, manufactured, and brought to scale, as demonstrated by widespread global vaccination against COVID-19. However, mRNA therapies require cold chain shipment and storage from manufacturing to administration, which may limit them to affluent communities. This problem could be addressed by mimicking the known ability of mineralized fossils to durably stabilize nucleic acids under extreme conditions.

Thrombin generation, bleeding and hemostasis in humans: Protocol for a scoping review of the literature.

Introduction: Hemostasis and bleeding are difficult to measure. Thrombin generation assays (TGAs) can measure both procoagulant and anticoagulant contributions to coagulation. TGAs might prove useful for the study of bleeding disorders.

Cardiac Vagal Control Among Community Cigarette Smokers with Low to Moderate Depressive Symptoms.

Impairments in cardiac vagal control (CVC) have been independently linked to smoking status and depression and are implicated in self-regulatory processes that may exacerbate depressive symptoms and maintain smoking behavior. Yet, few studies have examined how depressive symptoms, even at low levels, influence CVC reactivity among individuals who smoke. Investigating these relationships may provide novel insights into how depressive symptoms exacerbate existing regulatory vulnerabilities among smokers.

Nucleoside analogs in ADAR guide strands targeting 5'-UA̲ sites.

Adenosine deaminases that act on RNA (ADARs) can be directed to predetermined sites in transcriptomes by forming duplex structures with exogenously delivered guide RNAs (gRNAs). They can then catalyze the hydrolytic deamination of adenosine to inosine in double stranded RNA, which is read as guanosine during translation. High resolution structures of ADAR2-RNA complexes revealed a unique conformation for the nucleotide in the guide strand base paired to the editing site's 5' nearest neighbor (-1 position).

Difficulties in emotion regulation and ad libitum smoking topography: A secondary analysis.

Introduction: Despite the well-known linkages between poor emotion regulation and subjective smoking motives, little is known about the role of emotion regulation in predicting smoking reinforcement behavior. This study examined the relation between difficulties in emotion regulation and puff velocity data, a behavioral index of smoking reinforcement, in adult daily cigarette smokers.

Method: The current study was a secondary analysis of data collected from non-treatment seeking daily smokers (N = 124).

An Examination of Cardiac Vagal Control Indices and Cognitive Stress Appraisal in Cigarette Smokers.

Identifying factors that influence how individuals who smoke cigarettes respond to stress is important as stress is a risk factor for smoking and its maintenance. This study examined the modulatory role of cardiac vagal control (CVC), a physiological correlate of self-regulation, on cognitive stress appraisal processes of adults who smoke. Sixty daily cigarette smokers were randomized to receive positive or negative feedback during a modified Trier Social Stress Test.

In vitro reversal of direct factor Xa inhibitors: Direct comparison of andexanet alfa and prothrombin complex concentrates Cofact and Beriplex/Kcentra.

Background: Both andexanet alfa and four-factor prothrombin complex concentrate (4F-PCC) are clinically applied reversal agents for direct factor Xa inhibitors (FXaIs) in emergency situations. Controversy exists whether 4F-PCC is as effective as andexanet alfa in correcting FXaI anticoagulation.

Objective: This in vitro study was designed to directly compare andexanet alfa with two different 4F-PCCs (Cofact and Beriplex/Kcentra) in their ability to correct FXaI anticoagulation.

Reversing direct factor Xa or thrombin inhibitors: Factor V addition to prothrombin complex concentrate is beneficial in vitro.

Background: Prothrombin complex concentrate (PCC) is a human plasma-derived mixture of partially purified vitamin K-dependent coagulation factors (VKCF). Current therapeutic indication is treatment and perioperative prophylaxis of bleeding in acquired VKCF deficiency. Off-label uses include treatment of direct factor Xa- or thrombin inhibitor-associated bleeds, treatment of trauma-induced coagulopathy, and hemorrhagic complications in patients with liver disease.

A pilot randomized controlled trial of smartphone-assisted mindfulness-based intervention with contingency management for smokers with mood disorders.

Unlabelled: Cigarette smoking disproportionately affects individuals with mood disorders, but smoking cessation interventions have modest effects in this population. Home mindfulness practice during abstinence incentivized via contingency management (CM) may help those in affective distress quit smoking.

Method: Adult smokers receiving outpatient psychiatric treatment for mood disorders were randomized to receive a smartphone-assisted mindfulness-based smoking cessation intervention with contingency management (SMI-CM, = 25) or enhanced standard treatment (EST, = 24) with noncontingent rewards.

Respiratory therapy for the treatment of anxiety: Meta-analytic review and regression.

Objective: Respiratory abnormalities are a hallmark of anxiety symptomatology and may serve as clinically useful modifiers for alleviating anxiety symptoms. However, gold-standard anxiety treatments (e.g.

Pleiotropic anticoagulant functions of protein S, consequences for the clinical laboratory. Communication from the SSC of the ISTH.

Hereditary deficiencies of protein S (PS) increase the risk of thrombosis. However, assessing the plasma levels of PS is complicated by its manifold physiological interactions, while the large inter-individual variability makes it problematic to establish reliable cut-off values. PS has multiple physiological functions, with only two appearing to have significant anticoagulant properties: the activated protein C (APC) and tissue factor pathway inhibitor alpha (TFPIα) cofactor activities.

Recommendations for clinical laboratory testing for protein S deficiency: Communication from the SSC committee plasma coagulation inhibitors of the ISTH.

Hereditary deficiencies of protein S (PS) increase the risk of venous thrombosis; however, assessing the plasma levels of PS can be difficult because of its complex physiological interactions in plasma, sample-related preanalytical variables, and numerous acquired disease processes. Reliable laboratory assays are essential for accurate evaluation of PS when diagnosing a congenital deficiency based on the plasma phenotype alone. This report presents the current evidence-based recommendations for clinical PS assays as well as when to test for PS abnormalities.

Emergencies on direct oral anticoagulants: Management, outcomes, and laboratory effects of prothrombin complex concentrate.

Background: In the initial absence of specific reversal agents for factor Xa inhibitors (FXa-Is), prothrombin complex concentrate (PCC) as a hemostatic agent has been recommended by guidelines. Since 2017, idarucizumab has been registered for dabigatran reversal. Still, data on the clinical outcome of direct oral anticoagulant (DOAC)-related emergencies (major bleeding or urgent interventions) is scarce.

Platelets compensate for poor thrombin generation in type 3 von Willebrand disease.

In type 3 von Willebrand disease (VWD3), the most severe form with absent von Willebrand factor (VWF), the bleeding phenotype is variable. Platelet contribution to the hemostatic defect in VWD3 calls upon further studies. We investigated the contribution of platelets to thrombin generation (TG) and platelet procoagulant activity in VWD3.

Hemostatic profile under fluid resuscitation during rivaroxaban anticoagulation: an in vitro survey.

Background: Uncontrollable bleeding is the leading cause of death in traumatically injured patients. The extent to which direct factor Xa inhibitors interfere with the applied resuscitation measures is presently unknown.

Study Design And Methods: In this study, we investigated the effect of the resuscitation fluids saline, albumin, fresh frozen plasma (FFP) and solvent/detergent (S/D)-treated plasma, fibrinogen concentrate, prothrombin complex concentrate (PCC), and combinations thereof on the hemostatic profile of rivaroxaban-anticoagulated whole blood and plasma.

Use of DOAC Stop for elimination of anticoagulants in the thrombin generation assay.

Calibrated automated thrombography (CAT) is useful in monitoring the anticoagulant status of patients treated with direct oral anticoagulants (DOACs). This as well as other applications of the CAT are hampered by the wide inter-individual variation, making the diagnosis of the anticoagulant status of a patient on DOAC difficult when using normal pooled plasma as a reference. With dabigatran, the CAT is further hampered, as this direct thrombin inhibitor also inhibits the calibrator that is used in CAT.

Abnormal coagulation and enhanced fibrinolysis due to lysinuric protein intolerance associates with bleeds and renal impairment.

Introduction: Lysinuric protein intolerance (LPI), a rare autosomal recessive transport disorder of cationic amino acids lysine, arginine and ornithine, affects intestines, lungs, liver and kidneys. LPI patients may display potentially life-threatening bleeding events, which are poorly understood.

Aims: To characterize alterations in haemostatic and fibrinolytic variables associated with LPI.

Factors related to cigarette smoking and intent to quit among adolescent inpatients with psychiatric and substance use disorders.

Purpose: Smoking behaviors and intent to quit have not been well studied among adolescent psychiatric patients. The current study examined the relationships between smoking-related variables (smoking status/heaviness and intent to quit), psychiatric diagnoses and symptomatology, and substance use among adolescents receiving psychiatric inpatient care.

Methods: Baseline data from a randomized controlled trial, testing the effect of a brief intervention on substance use, with 151 psychiatrically hospitalized adolescents with comorbid psychiatric and substance use disorders (diagnosed using semi-structured interviews) were examined for this study.

Rationale, design and pilot feasibility results of a smartphone-assisted, mindfulness-based intervention for smokers with mood disorders: Project mSMART MIND.

Background: Although individuals with psychiatric disorders are disproportionately affected by cigarette smoking, few outpatient mental health treatment facilities offer smoking cessation services. In this paper, we describe the development of a smartphone-assisted mindfulness smoking cessation intervention with contingency management (SMI-CM), as well as the design and methods of an ongoing pilot randomized controlled trial (RCT) targeting smokers receiving outpatient psychiatric treatment. We also report the results of an open-label pilot feasibility study.

Effect of solvent/detergent-treated pooled plasma on fibrinolysis in reconstituted whole blood.

Background: Hyperfibrinolysis has been observed in patients heavily transfused with solvent/detergent-treated pooled plasma (S/D plasma). We compared coagulation and fibrinolytic variables in blood containing S/D plasma with blood containing fresh-frozen plasma (FFP), with and without α2-antiplasmin or tranexamic acid (TXA) supplementation.

Study Design And Methods: Whole blood samples were reconstituted from red blood cells, platelet (PLT) concentrates, and varying mixtures of FFP and S/D plasma.