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Most cardiac surgery patients, with or without diabetes, develop perioperative hyperglycaemia, for which intravenous insulin is the only therapeutic option. This is labour-intensive and carries a risk of hypoglycaemia. We hypothesised that preoperative administration of the glucagon-like peptide-1 receptor agonist liraglutide reduces the number of patients requiring insulin for glycaemic control during cardiac surgery. In this randomised, blinded, placebo-controlled, parallel-group, balanced (1:1), multicentre randomised, superiority trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomised to receive 0·6 mg subcutaneous liraglutide on the evening before surgery and 1·2 mg after induction of anaesthesia or matching placebo. Blood glucose was measured hourly and controlled using an insulin-bolus-algorithm. The primary outcome was insulin administration for blood glucose above 8·0 mmol/L in the operating theatre. Research pharmacists used centralised, stratified, variable-block, randomisation software. Patients, care providers, and study personnel were blinded to treatment allocation. Between June 2017 and August 2018, 278 patients were randomised to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention-to-treat analyses (129 in the liraglutide group, 132 in the placebo group). In the liraglutide group 55 (43%) patients required additional insulin compared to 80 (61%) patients in the placebo group, absolute difference: 18% (95% CI 5·9–30·0, p = 0·003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group, see figure. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality, or postoperative complications. Preoperative liraglutide, compared to placebo, reduces insulin requirements while improving peri-operative glycaemic control during cardiac surgery. [ABSTRACT FROM AUTHOR]

Abstract: A new type of particle-loaded membrane adsorber module was prepared by coiling adsorptive fibers. In order to characterize the material and predict the module performance, the protein accessibility and mass flux of single fibers were tested in incubation experiments. The coil''s layout spacing and winding tension are useful parameters for tailoring the module for stabilization, polishing, or pharmaceutical applications. Decreasing the distance between two adjacent fibers during the coiling process affects the flow resistance and the dynamic adsorption capacity of the module. Higher flow resistance creates a higher convective flow through the fibers resulting in faster adsorption processes. Exerting a high winding tension causes fiber deformation, resulting in modules with high packing density. The feed flow is then forced through the fibers to a greater extent, thereby reducing the diffusive distance to the active sites located in the interior of the fiber, which results in steeper breakthrough curves and better ligand utilization. [Copyright &y& Elsevier]

Checkpoint inhibitor (CI) therapy has revolutionized treatment for non-small cell lung cancer (NSCLC). However, a proportion of patients do not respond to CI therapy for unknown reasons. Although the current paradigm in anti-tumor immunity evolves around T cells, the presence of tertiary lymphoid structures and memory B cells has been positively correlated with response to CI therapy in NSCLC. In addition, double negative (DN) (CD27- IgD-) B cells have been shown to be abundant in NSCLC compared to healthy lung tissue and inversely correlate with the intratumoral presence of memory B cells. Nonetheless, no study has correlated DN B cells to survival in NSCLC. In this study, we evaluated the presence and phenotype of B cells in peripheral blood with flow cytometry of patients with NSCLC and mesothelioma before receiving CI therapy and correlated these with clinical outcome. Non-responding patients showed decreased frequencies of B cells, yet increased frequencies of antigen-experienced CD21- DN (Atypical) B cells compared to responding patients and HC, which was confirmed in patients with mesothelioma treated with CI therapy. These data show that the frequency of CD21- DN B cells correlates with lack of response to CI therapy in thoracic malignancies. The mechanism by which CD21- DN B cells hamper CI therapy remains unknown. Our findings support the hypothesis that CD21- DN B cells resemble phenotypically identical exhausted B cells that are seen in chronic infection or function as antigen presenting cells that induce regulatory T cells. • Low number of B cells are correlated with lack of response to CI therapy in NSCLC. • An abundance of Atypical B cells is associated with lack of response to CIs. • These results are validated in patients with Pleural Mesothelioma. • Phenotypically these cells resemble exhausted B cells seen in chronic infection. • Chronic antigen exposure could potentially induce Atypical B cells as seen in chronic infection. [ABSTRACT FROM AUTHOR]

Background Paroxysmal Nocturnal Hemoglobinuria is characterized by complement-mediated hemolysis and an increased thrombosis risk. Eculizumab, an antibody to complement factor C5, reduces thrombotic risk via unknown mechanisms. Clinical observations suggest that eculizumab has an immediate effect. Objectives A better understanding of the mechanism via which eculizumab reduces thrombotic risk by studying its pharmacodynamic effect on coagulation and fibrinolysis. Methods We measured microparticles (MP), tissue factor (TF) activity, prothrombin fragment 1 + 2 (F1 + 2), D-dimer and simultaneously thrombin and plasmin generation in 55 PNH patients. In 20 patients, parameters were compared before and during eculizumab treatment (at 1 and 2 hours, 1, 4 and ≥ 12 weeks after commencement). Results Patients with a history of thrombosis had elevated D-dimers (p = 0.02) but not MP. Among patients on anticoagulants, those with thrombosis had higher F1 + 2 concentrations (p = 0.003). TF activity was undetectable in plasma MP. Unexpectedly, thrombin peak height and thrombin potential were significantly lower in PNH patients than in healthy controls. Fibrinolysis parameters were normal. During eculizumab treatment D-dimer levels significantly decreased after 1 hour (p = 0.008) and remained decreased at ≥ 12 weeks (p = 0.03). F1 + 2 (p = 0.03) and thrombin peak height (p = 0.02) in patients not on anticoagulants significantly decreased at ≥ week 12. MP remained unchanged. Conclusions Eculizumab induces an immediate decrease of D-dimer levels but not of other markers. The decrease in thrombin peak height and F1 + 2 suggests that eculizumab reduces thrombin generation. Elevated D-dimer levels in untreated PNH patients with a history of thrombosis suggest possible value in predicting thrombotic risk. [ABSTRACT FROM AUTHOR]