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      Dialyzable Leukocyte Extract (Transferon™) Administration in Sepsis: Experience from a Single Referral Pediatric Intensive Care Unit

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          Abstract

          Immunomodulatory agents have been proposed as therapeutic candidates to improve outcomes in sepsis. Transferon™, a dialyzable leukocyte extract (DLE), has been supported in Mexico as an immunomodulatory adjuvant in anti-infectious therapy. Here we present a retrospective study describing the experience of a referral pediatric intensive care unit (PICU) with Transferon™ in sepsis. We studied clinical and laboratory data from 123 patients with sepsis (15 in the DLE group and 108 in the control group) that were admitted to PICU during the period between January 2010 and December 2016. Transferon™ DLE use was associated with lower C reactive protein (CRP), increase in total lymphocyte counts (TLC), and decrease in total neutrophil count (TNC) 72 hours after Transferon™ DLE administration. The control group did not present any significant difference in CRP values and had lower TLC after 72 hours of admission. There was no difference in PICU length of stay between control and Transferon™ DLE group. Transferon™ DLE administration was associated with a higher survival rate at the end of PICU stay. This study shows a possible immunomodulatory effect of Transferon™ on pediatric sepsis patients.

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          Advances in the understanding and treatment of sepsis-induced immunosuppression

          Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis can induce acute kidney injury and multiple organ failures and represents the most common cause of death in the intensive care unit. Sepsis initiates a complex immune response that varies over time, with the concomitant occurrence of both pro-inflammatory and anti-inflammatory mechanisms. As a result, most patients with sepsis rapidly display signs of profound immunosuppression, which is associated with deleterious consequences. Scientific advances have highlighted the role of metabolic failure, epigenetic reprogramming, myeloid-derived suppressor cells, immature suppressive neutrophils and immune alterations in primary lymphoid organs (the thymus and bone marrow) in sepsis. An improved understanding of the mechanisms underlying this immunosuppression as well as of the similarities between sepsis-induced immunosuppression and immune defects in cancer or immunosenescence has led to novel therapeutic strategies aimed at stimulating immune function in patients with sepsis. Trials assessing the therapeutic benefit of IL-7, granulocyte-macrophage colony-stimulating factor (GM-CSF) and antibodies against programmed cell death protein 1 (PD1) and programmed cell death 1 ligand 1 (PDL1) for the treatment of sepsis are in progress. The reappraisal of sepsis pathophysiology has also resulted in a novel approach to the design of clinical trials evaluating sepsis treatments, based on an evaluation of the immune status and biomarker-based stratification of patients.
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            Persistent lymphopenia after diagnosis of sepsis predicts mortality.

            The objective of this study was to determine whether persistent lymphopenia on the fourth day following the diagnosis of sepsis predicts mortality.
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              The changing immune system in sepsis

              Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. Currently in clinical trial for sepsis are granulocyte macrophage colony stimulating factor and interferon gamma, immune-therapeutic agents that boost patient immunity. Immuno-adjuvants with promise in clinically relevant animal models of sepsis include anti-programmed cell death-1 and interleukin-7. The future of immune therapy in sepsis will necessitate identification of the immunologic phase using clinical and laboratory parameters as well as biomarkers of innate and adaptive immunity.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2019
                23 June 2019
                : 2019
                : 8980506
                Affiliations
                1Department of Clinical Immunology and Allergy, Centro Médico Nacional “20 de Noviembre,” Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City, Mexico
                2Laboratorio de Inmunidad de Mucosas, Sección de Investigación y Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
                3Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
                4Department of Pediatric Intensive Care Medicine, Centro Médico Nacional “20 de Noviembre,” Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City, Mexico
                Author notes

                Academic Editor: Marija Mostarica-Stojković

                Author information
                https://orcid.org/0000-0002-7556-5810
                https://orcid.org/0000-0002-8586-3993
                https://orcid.org/0000-0001-5250-7952
                Article
                10.1155/2019/8980506
                6612374
                31341910
                6aabd4cd-5879-48b9-9759-b72c8b6643ce
                Copyright © 2019 Maria Isabel Castrejón Vázquez et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 February 2019
                : 2 May 2019
                : 27 May 2019
                Categories
                Research Article

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