Deutsche medizinische Wochenschrift
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Dtsch. Med. Wochenschr. · Oct 2012
Review[Novel therapeutic options in the treatment of BCR/ABL-negative myeloproliferative neoplasms].
Since the discovery of the JAK2V617F mutation in essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in 2005, the field of myeloproliferative neoplasms (MPN) experiences a significant gain of knowledge. Based on the novel insights in the molecular pathomechanisms of MPN many innovative drugs have been developed that are currently under investigation in clinical trials. Most data are available on the JAK inhibitors, the so called "ATP mimetics" for the treatment of MF. ⋯ In addition, other kinase inhibitors as well as histone deacetylase (HDAC) inhibitors and inhibitors of the mTOR signalling pathway are currently evaluated in clinical trials. Based on their potential synergistic action combination therapy of these substances represents another option for MPN therapy. In this review the most recently published studies using innovative treatment strategies in MPN patients are reported, and some future aspects for MPN treatment are adressed.
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Dtsch. Med. Wochenschr. · Oct 2012
Review[Current aspects of diagnostics of hepatic dysfunction in critically ill].
Hepatic dysfunction may develop in critically ill patients in the course of extrahepatic diseases such as sepsis and is frequently limiting prognosis. Conventional "static" laboratory parameters assess hepatocellular damage, synthetic function or cholestasis, providing informations about (differential) diagnostic aspects, while their significance to assess rapid changes in flow and function in the critical care setting is limited. In contrast, quantitative (or "dynamic") liver function tests, such as measurement of plasma disappearance rate of indocyanine green (PDRICG) or 13C-methacetin metabolism, assess specific metabolic and/or excretory function of the liver together with sinusoidal perfusion at the time of measurement and can detect liver dysfunction early in the course of critical illness. ⋯ For chronic liver disease, scoring systems, such as the Child-Turcotte-Pugh-score or the MELD, were developed to assess severity of disease and probability of survival. Scoring systems are also used for graft allocation. Combining scoring systems with dynamic tests holds the potential to improve predictive value, e.g. in the transplant setting.