Direct oral anticoagulant drug level testing in clinical practice: A single institution experience

We performed a review of all direct oral anticoagulant (DOAC) levels – ecarin times for dabigatran and anti-Xa levels for rivaroxaban and apixaban – ordered at our institution with the purpose of evaluating DOAC levels from “real-world” (non-clinical trial) patients taking DOACs long-term, in order to assess levels obtained, reasons for checking levels, and actions taken based on the testing result. A total of 28 patients had 48 levels sent over a 36-month period. The majority of outpatient levels were within or close to the range of published values. The setting in which levels were sent influenced how results affected management decisions: in the outpatient setting, the majority of levels served to reassure clinicians that DOAC levels were within expected ranges resulting in continuation of chosen management, whereas in the inpatient setting, DOAC levels were used most frequently to detect DOAC presence in urgent clinical situations and influenced clinical decision-making in the peri-procedural and pre-operative periods. Our results demonstrate that while testing may be useful if immediately available in urgent clinical situations where assessment of drug presence is needed, DOAC level monitoring is infrequently used overall, and the lack of use combined with the paucity of available evidence to guide clinical decision-making based on the results suggests there is little urgency to make the tests widely available for routine use outside of acute settings in the emergency department and urgent surgical setting

Initiating and Managing Patients with Venous Thromboembolism on Anticoagulant Drugs: A Practical Overview

Several new oral anticoagulants have recently been approved for the treatment of venous thromboembolism (VTE). In this review, we discuss the currently approved drugs and the factors that influence the choice of anticoagulant in a given patient. Once anticoagulation is initiated, periodic monitoring of adequacy of anticoagulation may be necessary depending on the choice of anticoagulant and patient-related factors, such as renal function. Situations that may warrant need for monitoring and the tests available for this purpose are discussed. We review reversal of anticoagulation in urgent/emergent situations as well as perioperative anticoagulation interruption in the elective setting. The data on use of direct oral anticoagulants in patients with compromised renal function, obesity and bariatric surgery, and in the treatment of cancer-associated thrombosis are discussed. The review aims to provide the clinician with the essential information to allow effective and safe use of anticoagulants for the treatment of VTE

Interleukin-1 beta - a friend or foe in malignancies?

Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development

Charakterisierung von Hepatozyten in einem miniaturisierten 3D-Durchflussbioreaktor

Medikamentenentwicklung ist ein ressourcen- und zeitintensiver Prozess mit einem hohen Risiko, zu scheitern10. Um möglichst schnell und kostengünstig82 festzustellen, ob ein Medikament zulassungsfähig ist oder nicht, ist es notwendig, über möglichst gute präklinische Systeme zur Medikamententestung zu verfügen, insbesondere für pHH, da die Leber für den Großteil des Scheiterns von Medikamenten verantwortlich ist14. Da dies mit dem momentanen Goldstandard, der 2D-Kultur, aufgrund der raschen Dedifferenzierung der pHH15,16,19,20 nur eingeschränkt möglich ist, gilt es, Systeme zu entwickeln, die der 3D in vivo Situation, wie z.B. der Leber, möglichst nahe zu kommen. So sollen rasch ungeeignete Medikamente identifiziert und von der weiteren Entwicklung ausgeschlossen werden können. Im Rahmen der Dissertation wurde das System des r3D-KITChip Bioreaktors beschrieben, wobei Huh7 und pHH kultiviert wurden. Dabei konnte gezeigt werden, dass die in 3D kultivierten Huh7 eine gegenüber den in 2D kultivierten Huh7 in gesteigertem Maß Glucose und Urea freisetzen und über eine gesteigerte MDR1-Aktivität verfügen. Im Gegensatz dazu zeigten die in 3D kultivierten pHH eine geringere oder ähnliche Freisetzung von Glucose, Urea, Albumin, APAP-Metaboliten und Diclofenac-Metaboliten sowie eine geringere MDR1-Aktivität. Zusammenfassend konnten die in der Literatur beschriebenen Vorteile einer 3D-Kultivierung für pHH15,16,19,20 mit dem hier verwendeten System nicht reproduziert werden. Mögliche problematische Aspekte, wie das Gehäuse, die Perfusion und die Handhabung des Bioreaktors wurden beschrieben und können als mögliche Ansatzpunkte für eine Verbesserung des Systems dienen

Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance

Abstract Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery

Komiks w czasach niekoniecznie normalnych

Artykuł przedstawia zarys dziejów komiksu w Polsce od 1956 roku po współczesność, stawia tezy dotyczące przyczyn zachodzących wówczas zmian, odnosi się krytycznie do ocen ówczesnego dorobku komiksowegoSzyłak outlines the history of the comic book in Poland since 1956 and tries to account for the shifts that marked the development of this form of cultural production. He also presents a critical perspective on the evaluation of comic books in the past

Guidance for the treatment of deep vein thrombosis and pulmonary embolism

This guidance document focuses on the diagnosis and treatment of venous thromboembolism (VTE). Efficient, cost effective diagnosis of VTE is facilitated by combining medical history and physical examination with pre-test probability models, D dimer testing and selective use of confirmatory imaging. Clinical prediction rules, biomarkers and imaging can be used to tailor therapy to disease severity. Anticoagulation options for acute VTE include unfractionated heparin, low molecular weight heparin, fondaparinux and the direct oral anticoagulants (DOACs). DOACs are as effective as conventional therapy with LMWH and vitamin K antagonists. Thrombolytic therapy is reserved for massive pulmonary embolism (PE) or extensive deep vein thrombosis (DVT). Inferior vena cava filters are reserved for patients with acute VTE and contraindications to anticoagulation. Retrievable filters are strongly preferred. The possibility of thoracic outlet syndrome and May-Thurner syndrome should be considered in patients with subclavian/axillary and left common iliac vein DVT, respectively in absence of identifiable triggers. The optimal duration of therapy is dictated by the presence of modifiable thrombotic risk factors. Long term anticoagulation should be considered in patients with unprovoked VTE as well as persistent prothrombotic risk factors such as cancer. Short-term therapy is sufficient for most patients with VTE associated with transient situational triggers such as major surgery. Biomarkers such as D dimer and risk assessment models such the Vienna risk prediction model offer the potential to customize VTE therapy for the individual patient. Insufficient data exist to support the integration of bleeding risk models into duration of therapy planning

Symmetric tensor powers of graphs

The symmetric tensor power of graphs is introduced and its fundamental properties are explored. A wide range of intriguing phenomena occur when one considers symmetric tensor powers of familiar graphs. A host of open questions are presented, hoping to spur future research

Multi-Parameter Analysis of Biobanked Human Bone Marrow Stromal Cells Shows Little Influence for Donor Age and Mild Comorbidities on Phenotypic and Functional Properties

Heterogeneous populations of human bone marrow-derived stromal cells (BMSC) are among the most frequently tested cellular therapeutics for treating degenerative and immune disorders, which occur predominantly in the aging population. Currently, it is unclear whether advanced donor age and commonly associated comorbidities affect the properties of ex vivo-expanded BMSCs. Thus, we stratified cells from adult and elderly donors from our biobank (n = 10 and n = 13, mean age 38 and 72 years, respectively) and compared their phenotypic and functional performance, using multiple assays typically employed as minimal criteria for defining multipotent mesenchymal stromal cells (MSCs). We found that BMSCs from both cohorts meet the standard criteria for MSC, exhibiting similar morphology, growth kinetics, gene expression profiles, and pro-angiogenic and immunosuppressive potential and the capacity to differentiate toward adipogenic, chondrogenic, and osteogenic lineages. We found no substantial differences between cells from the adult and elderly cohorts. As positive controls, we studied the impact of in vitro aging and inflammatory cytokine stimulation. Both conditions clearly affected the cellular properties, independent of donor age. We conclude that in vitro aging rather than in vivo donor aging influences BMSC characteristics