Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes

A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD65. Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD65 autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD65, but not with control antigens, compared with placebo subjects. GAD65-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD65 enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD65-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD65 immunity

International registry on the use of the CytoSorb® adsorber in ICU patients

INTRODUCTION: The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. METHODS: The registry records all relevant information in the course of product use, e. g., diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome (ClinicalTrials.gov Identifier: NCT02312024). Primary endpoint is in-hospital mortality as compared to the mortality predicted by the APACHE II and SAPS II score, respectively. RESULTS: As of January 30, 2017, 130 centers from 22 countries were participating. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 ± 15.1 years, 135 men [68.2%]). In all, 192 (97.0%) had 1 to 5 Cytosorb® adsorber applications. Sepsis was the most common indication for CytoSorb® treatment (135 patients). Mean APACHE II score in this group was 33.1 ± 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment (17.2 ± 4.8 [3-24]). However interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). CONCLUSIONS: This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. The results must be interpreted with caution, since the numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as an ultimate treatment in life-threatening situations. There were no device-associated side effects

Demonstration-based training (DBT) in the design of a video tutorial for software training

This study investigates the design and effectiveness of a video tutorial for software training. In accordance with demonstration-based training, the tutorial consisted of a series of task demonstrations, with instructional features added to enhance learning. An experiment is reported in which a demonstration-only control condition was compared with a demonstration-with-review condition. The review videos provided a recap to support retention of the procedure. Strict viewing conditions were imposed during training. Both learning and motivation were assessed. Participants were 55 students from primary and secondary schools in Germany. The outcomes showed that both tutorials significantly contributed to development of procedural knowledge and to motivation, and that the review tutorial surpassed the control. The discussion addresses the role of user control. In addition, with the effectiveness of reviews apparently becoming better established, the need arises for measures that can reveal the effects of reviews on observational learning processes

Chronic wound infections: The role of Pseudomonas aeruginosa and Staphylococcus aureus

Chronic leg ulcers affect 1-2% of the general population and are related to increased morbidity and health costs. Staphylococcus aureus and Pseudomonas aeruginosa are the most common bacteria isolated from chronic wounds. They can express virulence factors and surface proteins affecting wound healing. The co-infection of S. aureus and P. aeruginosa is more virulent than single infection. In particular, S. aureus and P. aeruginosa have both intrinsic and acquired antibiotic resistance, making clinical management of infection a real challenge, particularly in patients with comorbidity. Therefore, a correct and prompt diagnosis of chronic wound infection requires a detailed knowledge of skin bacterial flora. This is a necessary prerequisite for tailored pharmacological treatment, improving symptoms, and reducing side effects and antibiotic resistance