HFE and ALK3 act in the same signaling pathway.

Hepcidin deficiency leads to iron overload by increased dietary iron uptake and iron release from storage cells. The most frequent mutation in Hfe leads to reduced hepcidin expression and thereby causes iron overload. Recent findings suggested that HFE activates hepcidin expression predominantly via the BMP type I receptor ALK3. Here, we investigated whether HFE exclusively utilizes ALK3 or other signaling mechanisms also. We generated mice with double deficiency of Hfe and hepatocyte-specific Alk3 and compared the iron overload phenotypes of these double knockout mice to single hepatocyte-specific Alk3 deficient or Hfe knockout mice. Double Hfe-/-/hepatic Alk3fl/fl;Alb-Cre knockouts develop a similar iron overload phenotype compared to single hepatocyte-specific Alk3 deficient mice hallmarked by serum iron levels, tissue iron content and hepcidin levels of similar grades. HFE protein levels were increased in Alk3fl/fl;Alb-Cre mice compared to Alk3fl/fl mice, which was caused by iron overload - and not by Alk3 deficiency. The data provide evidence by genetic means that 1. HFE exclusively uses the BMP type I receptor ALK3 to induce hepcidin expression and 2. HFE protein expression is induced by iron overload, which further emphasizes the iron sensing function of HFE.

[Safety of cell salvage in tumor surgery : Systematic review with meta-analysis]. / Sicherheit der maschinellen Autotransfusion in der Tumorchirurgie : Systematisches Review mit Metaanalyse.

BACKGROUND: Allogeneic blood transfusion is avoidable in many oncological interventions by the use of cell salvage or mechanical autotransfusion (MAT). As irradiation is elaborate and expensive, the safety of leucocyte depletion filters (LDF) for autologous blood from the surgical field might be a more acceptable alternative for the prevention of cancer recurrences. A previous meta-analysis could not identify an increased risk of cancer recurrence. The aim of this review article is to provide an update of a previous meta-analysis from 2012 as well as a safety analysis of cell salvage with LDF due to the improved data situation. MATERIAL AND METHODS: This systematic review included all studies in PubMed, Cochrane, Cochrane Reviews and Web of Science on cell salvage or autotransfusion combined with outcomes, e.g. cancer recurrence, mortality, survival, blood transfusion, length of hospital stay (LOS) after the use of MAT without irradiation and with or without LDF. The grades of recommendations (GRADE) assessment of underlying evidence was applied. RESULTS: A total of seven new observational studies and seven meta-analyses were found that compared unfiltered or filtered cell salvage with autologous predeposition, allogeneic transfusion or without any transfusion. No randomized controlled trials have been completed. A total of 27 observational and cohort studies were included in a meta-analysis. The evidence level was low. The risk of cancer recurrence in recipients of autologous salvaged blood with or without LDF was reduced (odds ratio, OR 0.71, 95% confidence interval, CI 0.58-0.86) as compared to non-transfused subjects, allogeneic or predeposited autologous transfusion. The transfusion rate could not be assessed due to the substantial selection bias and large heterogeneity. Cell salvage does not change mortality and LOS. Leucocyte depletion studies reported a removal rate of cancer cells in the range of 99.6-99.9%. CONCLUSION: Randomized controlled trials on a comparison of MAT and allogeneic blood transfusion as well as LDF and irradiation would be desirable but are not available. From observational trials and more than 6300 subjects and various tumors, cell salvage in cancer surgery with or without LDF appears to be sufficiently safe. The efficacy of leucocyte depletion of autologous salvaged blood is equivalent to irradiation. Unavailability of radiation is not a contraindication for cell salvage use in cancer surgery. By usage of leucocyte depleted salvaged autologous blood, the risks of allogeneic transfusion can be avoided.

[Patient blood management : Medical concept for increasing patient safety]. / Patient Blood Management : Medizinisches Konzept zur Steigerung der Patientensicherheit.

Patient blood management (PBM) is a multidisciplinary evidence-based treatment model. Aims are to provide treatment of pre-existing or recently occureed deficits in blood volume and of substances that are important for erythropoiesis in patients, as well as the targeted administration of cellular and non-cellular blood products within reasonable and scientifically proven limits. The overall goal is therefore a safe therapy and complication-free course of the disease. PBM follows a strategy based on three pillars, which encompasses the aspects of optimization of anemia and hemoglobin, the handling of bleeding and the use of patient-related resources.