Extracorporeal Liver Support Therapy With Prometheus in Patients With Liver Failure in the Intensive Care Unit

Acute liver failure (ALF) and acute‐on‐chronic liver failure (AoCLF) are associated with a high mortality. In these patients an accumulation of both water‐soluble and water‐insoluble, protein‐bound, metabolic waste products occurs. Conventional extracorporeal blood purification techniques based on diffusion and/or convection such as hemodialysis or hemofiltration may only eliminate small molecular weight, water‐soluble compounds. In recent years, fractionated plasma separation and adsorption (FPSA) with the Prometheus system has been introduced for extracorporeal liver support therapy. To date, however, only limited data is available regarding the effect of this treatment on mortality and outcome of patients with advanced liver disease. Here we report on our experience with 23 patients with severe liver failure who were treated with Prometheus in our medical intensive care unit. Fourteen patients had AoCLF, and nine patients experienced ALF. The median bilirubin level at the start of Prometheus therapy was 30.5 mg/dL and the median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 26. During 40 individual treatment sessions lasting 5–6 h, Prometheus therapy reduced serum bilirubin levels from 23.7 mg/dL to 15.0 mg/dL (median values) (P < 0.001), and the overall survival was 26%. ALF patients had a better survival compared to AoCLF patients (44% vs. 22%; P = 0.022). Apart from one patient who developed hemodynamic instability during a treatment session, Prometheus therapy was well tolerated without relevant side‐effects. In conclusion, extracorporeal liver support therapy with Prometheus is a novel and safe treatment option in patients with severe liver failure. In this series, patients with ALF showed a significantly better outcome with Prometheus therapy compared to AoCLF patients.     

Serum concentrations of DKK‐1 decrease in patients with multiple myeloma responding to anti‐myeloma treatment

Lytic bone destruction is a hallmark of multiple myeloma (MM) and is because of an uncoupling of bone remodeling. Secretion of Dickkopf (DKK)‐1 by myeloma cells is a major factor which causes inhibition of osteoblast precursors. In this study, the effect of different treatment regimens for MM on serum DKK‐1 was evaluated and correlated with the response to treatment in 101 myeloma patients receiving bortezomib, thalidomide, lenalidomide, adriamycin and dexamethasone (AD) or high‐dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT). At baseline, myeloma patients had increased serum DKK‐1 as compared with patients with MGUS (mean 3786 pg/mL vs. 1993 pg/mL). There was no difference between previously untreated MM patients and patients at relapse. A significant decrease of DKK‐1 after therapy was seen in the following groups: Bortezomib (4059 pg/mL vs. 1862 pg/mL, P = 0.016), lenalidomide (11837 pg/mL vs. 4374 pg/mL, P = 0.039), AD (1668 pg/mL vs. 1241 pg/mL, P = 0.016), and AD + HDCT + ASCT (2446 pg/mL vs. 1082 pg/mL, P = 0.001). Thalidomide led to a non‐significant decrease in DKK‐1 (1705 pg/mL vs. 1269 pg/mL, P = 0.081). Within all groups, a significant decrease of DKK‐1 was only seen in responders (i.e. patients achieving complete remission or partial remission), but not in non‐responders. We show for the first time that serum DKK‐1 levels decrease in myeloma patients responding to treatment, irrespective of the regimen chosen. These data suggest that myeloma cells are the main source of circulating DKK‐1 protein and provide a framework for clinical trials on anti‐DKK‐1 treatment in MM.     

Skin microbiota analysis in human 3D skin models—“Free your mice”

In the May issue of Experimental Dermatology 2018, we published a review article focusing on human 3D skin models in the context of microbiota research. The principal intention was to provide an overview of present and future concepts to use skin models in microbiota analyses. With the present viewpoint, we would like to draw the reader's attention again to the use of human skin models in microbiota research with the aim to highlight the benefits and necessity of human skin models to analyse the human skin-microbiota interaction. This is accompanied by a critical view on mice models that often are not suitable to analyse the functional impact of the human skin microbiota. In addition, we present novel and future concepts highlighting the benefits of human 3D skin models in microbiota research.     

Abnormalities in the glycosylation of IgG in spouses of patients with rheumatoid arthritis. A family study.

Forty-seven members of eight families with a rheumatoid proband were analysed for abnormal glycosylation of IgG. The results (%G(o) which is the percentage of oligosaccharide chains lacking galactose) were corrected for age and expressed as SD units about the mean for the normal population. Seven of 8 probands, 3/8 spouses, 3/5 RA relatives and 4/26 non-RA relatives had %G(o) values greater than 1SD above the age corrected mean for the normal control population (P less than 0.001, less than 0.01, less than 0.005 and greater than 0.5 respectively). A further 13 spouse pairs were studied. Ten of 13 probands and 8/13 spouses had %G(o) values greater than 1SD above the mean (P less than 0.001 and less than 0.001 respectively). Thus in total, a strikingly high number of unaffected spouses had high %G(o) values (11/21). IgM, IgA and IgG rheumatoid factors were studied. While RA patients' sera showed a correlation between IgM and IgA rheumatoid factors and %G(o), (IgM, r = 0.41 0.05 greater than P greater than 0.02, IgA, r = 0.36, P = 0.05), no correlation between IgG RF and %G(o) was noted in the RA patients. No correlation was found between any of the RF classes and %G(o) in spouses and non-RA relatives.     

Malaria: a tumour necrosis factor inhibitor from parasitized erythrocytes.

The excessive production of tumour necrosis factor (TNF) is associated with the pathology of blood-stage malaria and phosphatidylinositol-containing phospholipid antigens from parasitized erythrocytes stimulate its secretion by macrophages, thus acting as toxins. This brief report describes some properties of an inhibitor present in lysates from erythrocytes infected with malarial parasites that blocked the detection of recombinant TNF in an enzyme-linked immunosorbent assay and diminished or abolished the cytotoxicity of TNF. It was not found in control lysates of normal erythrocytes. Its addition to macrophage cultures stimulated by toxic malarial preparations or by bacterial lipopolysaccharide also blocked the detection of TNF. These findings may explain the contradictory results obtained from different assays for TNF, and emphasize the need for caution when interpreting the results of a single assay system. If released when parasitized erythrocytes rupture in vivo, the inhibitor could help protect both parasite and host from the damaging effects of TNF.     

Infection transmission among lung transplant couples

The risk of transmission of infections in partnerships between 2 transplant recipients is unknown. The aim of this study was to evaluate transmission in such couples. In this single‐center study, lung transplant (LTx) couples were identified among outpatients between 1988 and 2016. Infection rates per year and survival were compared to matched LTx‐recipients not living in a transplant partnership. Twelve transplant couples were analyzed with cumulative 65 years of relationship. Overall infections were similar between LTx‐couples and matched LTx‐patients. No significant differences were noted in bacterial infections (.12 vs .27 per year), community‐acquired viral (CARV) infections (.26 vs .22 per year), rejection treatments (.22 vs .12 per year), or hospitalizations (.26 vs .46 per year) in transplant couples and matched controls, respectively. There was no transmission of any microbial colonization from 1 partner to the other. Five cases of simultaneously detected CARV infections occurred (metapneumovirus [3], H1N1 [1], and respiratory syncytial virus [RSV; 1]). Three couples exhibited cytomegalovirus (CMV) reactivation in both partners at the same time with confirmed seronegativity before transplantation. In this case series of 12 lung transplant couples, the partnerships between 2 transplant recipients have no greater risk of bacterial infection and colonization transmission in comparison with recipients not living in a transplant relationship. However, transplant couples should be informed about the risk for transmission of viral infections, which could impact the development of chronic lung allograft dysfunction (CLAD).