Plasma from septic shock patients induces loss of muscle protein

Introduction  

ICU-acquired muscle weakness commonly occurs in patients with septic shock and is associated with poor outcome. Although atrophy is known to be involved, it is unclear whether ligands in plasma from these patients are responsible for initiating degradation of muscle proteins. The aim of the present study was to investigate if plasma from septic shock patients induces skeletal muscle atrophy and to examine the time course of plasma-induced muscle atrophy during ICU stay.     

Post-Transplant Cyclophosphamide as Sole Graft-versus-Host Disease Prophylaxis Is Feasible in Patients Undergoing Peripheral Blood Stem Cell Transplantation for Severe Aplastic Anemia Using Matched Sibling Donors

High-dose cyclophosphamide (PTCY) after allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) after HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50?mg/kg i.v. on days 3 and 4 as the sole GVHD prophylaxis after HSCT for severe aplastic anemia (SAA) in patients receiving granulocyte colony-stimulating factor–mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors after conditioning with fludarabine, CY, and single-dose total body irradiation. Thirty patients with a median age of 29 years (range, 16 to 49) were enrolled in this study. Engraftment was seen in 27 patients (90%) at a median of 16 days (range, 12 to 21) post-HSCT. None of the patients developed veno-occlusive disease of the liver or hemorrhagic cystitis. Grades II to IV acute GVHD was seen in 22% of patients with grades III to IV GVHD in 11.1%. The 2-year cumulative incidence of chronic GVHD was 22.7%. Fourteen patients (46.6%) did not require any further immunosuppression after receiving PTCY. Comparing with 2 historical cohorts of 30 patients each who received cyclosporine and methotrexate (MTX; at 15?mg/m² [MTX15] and 10?mg/m² [MTX10]), the incidence of grades II to IV acute GVHD was lower, albeit not significantly, with the use of PTCY (PTCY, 22.2%, vs MTX15, 37.1%, vs MTX10, 53.8%; P?=?.056), whereas rates of chronic GVHD were significantly reduced (PTCY, 22.7%, vs MTX15, 63.6%, vs MTX10, 76.2%; P?=?.013). Viral infections including cytomegalovirus were significantly higher with the use of PTCY (60%) compared with cyclosporine and MTX (MTX15, 23.3%, vs MTX10, 33.3%; P?=?.008). Overall survival was similar between the 3 groups. We conclude that PTCY as the sole GVHD prophylaxis is associated with low rates of acute and chronic GVHD in patients undergoing PBSC transplant for SAA using HLA-matched donors. This trial is registered at CTRI/2010/091/001480.     

Reversible Assembly of Conductive Supragel Building Blocks by Metallo-Complexes

The design of multicomponent, building block-based assemblies of polymer materials has gained tremendous interest due to the ability to combine functional variety and materials inside one integrated object. One such type of building blocks are polymer hydrogels that assemble into so-called supragels. For that, it is necessary to implement reliable intra- and innerparticle cross-linking methods that ensure mechanical stability and the supragels' adaptiveness over its life cycle, e.g., via selective assembly and disassembly. Here, a facile method for reversible interparticle cross-linking of vinylimidazole-based polymer hydrogel particles is presented. The method is based on supramolecular cross-linking via transition metal complexation. Supragels consisting of four to 27 individual 3 × 3 × 3 mm particles are successfully obtained. By swelling the preassembled hydrogels inside aqueous solutions of Zn²⁺, Cu²⁺, and Fe²⁺ ions, stable interparticle linkage is achieved within 15 min. These supragels resist mechanical forces, but can be quantitatively disassembled into their corresponding building blocks by simple ligand exchange with ethylenediaminetetraacetic acid (EDTA). With this method, it is possible to quickly build hydrogel macrostructures of any shape and complexity, which exemplarily also exhibit electrical conductivity due to the introduction of metal ions for cross-linking.