New tool improves treatment of atrial fibrillation

sperm, brain tumours, Common drugs, diabetes, chronic wounds, magnetism, intestinal tumours, molecular scissors, disease, genetic, immune cells, drug development, Diabetes, Antibiotic, hydrogen generation, chronic obstructive pulmonary disease, malaria, photosynthesis, kidney failure, Brain tumours, mental health, blood cancer, cancer, dementia, cancer treatment, antibiotic resistance, blood vessel leakage, quantum simulations, atrial fibrillation, batteries, goiter treatment, terahertz radiation, organic materials , Guild of European Research Intensive Universities, gene copies, social anxiety, blue light screens, ‘Our hope is that these findings will make it possible to discover a way to selectively inhibit the TGF-beta signals that stimulate tumour development without knocking out the signals that inhibit tumour development, and that this can eventually be used in the fight against cancer,’ says Eleftheria Vasilaki, postdoctoral researcher at Ludwig Institute for Cancer Research at Uppsala University and lead author of the study. TGF-beta regulates cell growth and specialisation, in particular during foetal development. In the context of tumour development, TGF-beta has a complicated role. Initially, it inhibits tumour formation because it inhibits cell division and stimulates cell death. At a late stage of tumour development, however, TGF-beta stimulates proliferation and metastasis of tumour cells and thereby accelerates tumour formation. TGF-beta’s signalling mechanisms and role in tumour development have been studied at the Ludwig Institute for Cancer Research at Uppsala University for the past 30 years. Recent discoveries at the Institute, now published in the current study in Science Signaling, explain part of the mechanism by which TGF-beta switches from suppressing to enhancing tumour development. Uppsala researchers, in collaboration with a Japanese research team, discovered that TGF-beta along with the oncoprotein Ras, which is often activated in tumours, affects members of the p53 family. The p53 protein plays a key role in regulating tumour development and is often altered – mutated – in tumours. TGF-beta and Ras suppress the effect of mutated p53, thereby enhancing the effect of another member of the p53 family, namely delta-Np63, which in turn stimulates tumour development and metastasis.

Atrial fibrillation increases the risk of stroke. Treatment with oral anticoagulation reduces this risk but instead increases the risk of bleeding. Today, a new blood test based tool enabling better and more individualized stroke prevention treatment is presented at a congress in Chicago, and simultaneously published in the top-ranked medical journal The Lancet.

‘We present results where we developed and thoroughly evaluated a new and simple concept for evaluation of risk and guidance of treatment decisions in patients with atrial fibrillation. The biomarker-based tool will allow personalized treatment to prevent strokes with the least risk of bleeding complications,’ says Doctor Ziad Hijazi, cardiologist and investigator, who presents the results in collaboration with his colleagues Jonas Oldgren and Lars Wallentin, from the Uppsala Clinical Research Center at Uppsala University in Uppsala, Sweden.

Atrial fibrillation is a common arrhythmia affecting approximately 3 percent of the adult population. The occurrence increases by age. In an aging population, the condition is an important public health issue and socioeconomic burden on society. Atrial fibrillation is also a major risk factor for stroke but the risk is variable between different patients and also in the same patient over time. Stroke prevention treatment with oral anticoagulation decreases the risk of stroke but confers an increased risk of bleeding.

Currently, the evaluation of the risk of stroke and bleeding is based solely on clinical characteristics, which may be associated with a considerable uncertainty. In addition, it is difficult to separate the patients’ risks for stroke and bleeding during anticoagulant treatment. In recent years, the Uppsala group has demonstrated that blood biomarkers contain more prognostic information than the currently used clinical characteristics concerning both bleeding and stroke during anticoagulation treatment in patients with atrial fibrillation. The results presented today show that the combination of the information from several biomarkers and a small amount of clinical data substantially improves the prognostication of the risk of stroke and bleeding in the individual patients. The use of biomarkers also makes the new risk scores dynamic with an opportunity to reflect both improvement and deterioration in the patient’s cardiovascular condition over time, which changes the risk of complications.

All these new findings are presented in the new article in The Lancet and in a recent manuscript in the European Heart Journal. They are also presented today at the American College of Cardiology Congress in Chicago. These reports document the development, internal and external validation and calibration of the biomarker-based tools ’ABC risk score‘ (Age, Biomarkers, Clinical history of stroke/bleeding) for prognostication of stroke and bleeding which is now also available as a web-based instrument. The results are based on the development of the instruments in one large study of 14 537 patients with atrial fibrillation randomized to two different anticoagulant medication in the ARISTOTLE-trial and their verification in another similar material of 8152 patients with atrial fibrillation randomized to three different treatment alternatives in the RE-LY trial. In both studies, blood plasma was obtained from the majority of patients at the start of the study. The levels of the biomarkers were later measured at Uppsala Clinical Research Center. The biomarkers included in the ABC-risk scores are; haemoglobin, NT-proBNP, troponin and GDF-15 or cystatin C, all of which already are or shortly will be (GDF-15) available for routine use.

‘The option to calculate the ABC-risk scores is already available today as an internet based tool and will shortly also be available as an app to facilitate its implementation in routine health care,’ says Jonas Oldgren, head of the Uppsala Clinical Research Center.

‘We think that biomarker-based risk evaluation in the near future will be the preferred tool for decision support at the selection of the optimal stroke prevention treatment for the individual patient with atrial fibrillation,’ says Professor Lars Wallentin, who has led the research and development project for many years.