Université catholique de Louvain

About: Université catholique de Louvain is a education organization based out in Louvain-la-Neuve, Belgium. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 25319 authors who have published 57360 publications receiving 2172080 citations. The organization is also known as: University of Louvain & UCLouvain.

p55 Tumor Necrosis Factor Receptor Fusion Protein in the Treatment of Patients With Severe Sepsis and Septic Shock: A Randomized Controlled Multicenter Trial

Abstract: Objective. —To evaluate the safety and efficacy of p55 tumor necrosis factor receptor fusion protein, a recombinant chimeric protein of human p55 (type I) tumor necrosis factor receptor (CD120a) extracellular domain and lgG1 sequences (referred to as p55-lgG), in the treatment of patients with severe sepsis or septic shock. Design. —Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. Setting. —Forty-four community and university-affiliated hospitals in the United States and Europe. patients. —There were 498 patients enrolled in this clinical trial. Intervention. —Patients prospectively stratified within each site into refractory shock or severe sepsis groups were randomized to receive a single infusion of p55IgG, 0.083 mg/kg, 0.042 mg/kg, or 0.008 mg/kg, or placebo. Patients received standard aggressive medical/surgical care during the 28-day postinfusion period. Outcome Measure. —Twenty-eight—day all-cause mortality. Results. —The distribution of variables describing demographics, organ system dysfunction or failure, infecting microorganisms, predicted mortality, plasma interleukin 6 levels, and plasma tumor necrosis factor α (TNF-α) levels were similar among patients in the p55-lgG and placebo treatment arms. A planned interim analysis was performed after 201 patients were enrolled. Because a statistically nonsignificant trend toward increased mortality was present in patients who had received 0.008 mg/kg, this treatment arm was discontinued, and the study continued with 3 arms. Among all infused patients, there was a statistically nonsignificant trend toward reduced 28-day all-cause mortality in those who received p55-lgG compared with placebo-treated patients (5% reduction, 0.042 mg/kg vs placebo; 15% reduction, 0.083 mg/kg vs placebo;P=.30). However, in patients with severe sepsis and early septic shock (n=247), therapy with p55-lgG, 0.083 mg/kg, was associated with a 36% reduction in 28-day all-cause mortality compared with placebo (P=.07): 20 (23%) of 87 patients died among those treated with p55-lgG, 0.083 mg/kg; 30 (37%) of 82 among those treated with p55-lgG, 0.042 mg/kg; and 28 (36%) of 78 in the placebo group. A prospectively planned logistic regression analysis to assess treatment effect on 28-day all-cause mortality by means of predicted mortality and serum interleukin 6 levels as continuous covariates demonstrated a significant improvement in outcome for the patients with severe sepsis treated with p55-lgG, 0.083 mg/kg, compared with placebo (P=.01). Serious adverse events, including death and the development of new organ system dysfunction, were reported in 65% of patients infused with placebo, with no increased frequency (56%) present in the 2 p55-lgG treatment arms. There were no reports of immediate hypersensitivity reactions caused by p55-lgG. Conclusions. —In this dose-finding study, there was no decrease in mortality between placebo and p55-lgG in all infused patients. In the prospectively defined population of patients with severe sepsis who received p55-lgG, 0.083 mg/kg, there was a trend toward reduced mortality at day 28 that became significant when predicted mortality and plasma interleukin 6 levels were included in a logistic regression analysis.

Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections.

Abstract: Virus-infected cells secrete a broad range of interferons (IFN) which confer resistance to yet uninfected cells by triggering the synthesis of antiviral factors. The relative contribution of the various IFN subtypes to innate immunity against virus infections remains elusive. IFN-alpha, IFN-beta and other type I IFN molecules signal through a common universally expressed cell surface receptor, whereas type III IFN (IFN-lambda) uses a distinct cell type-specific receptor complex for signaling. Using mice lacking functional receptors for type I IFN, type III IFN, or both, we found that IFN-lambda plays an important role in the defense against several human pathogens that infect the respiratory tract such as influenza A virus, influenza B virus, respiratory syncytial virus, human metapneumovirus and SARS coronavirus. These viruses were more pathogenic and replicated to higher titers in the lung of mice lacking both IFN receptors than in mice with single IFN receptor defects. By contrast, Lassa fever virus, which infects via the respiratory tract but primarily replicates in the liver, was not influenced by the IFN-lambda receptor defect. Careful analysis revealed that expression of functional IFN-lambda receptor complexes in lung and intestinal tract is restricted to epithelial cells and few other undefined cell types. Interestingly, we found that SARS coronavirus was present in feces from infected mice lacking receptors for both type I and type III IFN but not from mice lacking single receptors, supporting the view that IFN-lambda contributes to the control of viral infections in epithelial cells of both respiratory and gastrointestinal tract.

Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy.

Abstract: Luigi Bartalena, Lelio Baldeschi, Alison J. Dickinson, Anja Eckstein, Pat Kendall-Taylor, Claudio Marcocci, Maarten P. Mourits, Petros Perros, Kostas Boboridis, Antonella Boschi, Nicola Curro, Chantal Daumerie, George J. Kahaly, Gerasimos Krassas, Carol M. Lane, John H. Lazarus, Michele Marino, Marco Nardi, Christopher Neoh, Jacques Orgiazzi, Simon Pearce, Aldo Pinchera, Susanne Pitz, Mario Salvi, Paolo Sivelli, Matthias Stahl, Georg von Arx, and Wilmar M. Wiersinga

Classification of current anticancer immunotherapies

Abstract: During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.