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Isaac J Jensen, Frances V Sjaastad, Thomas S Griffith, Vladimir P Badovinac
Sepsis results in a deluge of pro- and anti-inflammatory cytokines, leading to lymphopenia and chronic immunoparalysis. Sepsis-induced long-lasting immunoparalysis is defined, in part, by impaired CD4 and CD8 αβ T cell responses in the postseptic environment. The dysfunction in T cell immunity affects naive, effector, and memory T cells and is not restricted to classical αβ T cells. Although sepsis-induced severe and transient lymphopenia is a contributory factor to diminished T cell immunity, T cell-intrinsic and -extrinsic factors/mechanisms also contribute to impaired T cell function...
March 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Katrin Schmoeckel, Daniel M Mrochen, Jochen Hühn, Christian Pötschke, Barbara M Bröker
Sepsis is frequently complicated by a state of profound immunosuppression, in its extreme form known as immunoparalysis. We have studied the role of the adaptive immune system in the murine acute peritonitis model. To read out adaptive immunosuppression, we primed post-septic and control animals by immunization with the model antigen TNP-ovalbumin in alum, and measured the specific antibody-responses via ELISA and ELISpot assay as well as T-cell responses in a proliferation assay after restimulation. Specific antibody titers, antibody affinity and plasma cell counts in the bone marrow were reduced in post-septic animals...
2018: PloS One
M Feuerecker, L Sudhoff, B Crucian, J-I Pagel, C Sams, C Strewe, A Guo, G Schelling, J Briegel, I Kaufmann, A Choukèr
The pathology of sepsis is typically characterized by an infection and excessive initial inflammation including a cytokine storm, followed by a state of immune suppression or paralysis. This classical view of a two peak kinetic immune response is currently controversially discussed. This study was a sub-study of the randomized clinical Trial SISPCT registered with (NCT00832039, Registration date: 29/01/2009). Blood samples from 76 patients with severe sepsis and septic shock were incubated for 48 h at 37 °C in vitro with bacterial or fungal recall-antigens or specific mitogen antigens within 24 hours of sepsis onset...
January 29, 2018: Scientific Reports
Asaad G Beshish, Jeffrey D Bradley, Kelli L McDonough, Nadine L N Halligan, Walker M McHugh, Julie Sturza, Mark W Hall, Timothy T Cornell, Mary K Dahmer
Extracorporeal life support (ECLS) is a widely used lifesaving technology. Whether ECLS results in immune dysregulation is unclear. This study's aim was to examine whether ECLS affected innate immune response. All patients placed on ECLS were eligible. Blood was obtained before, during, and after ECLS. Function of the innate immune system was measured by ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) and plasma cytokine levels (interleukin [IL]-6, IL-8, IL-10, and TNF-α). Immunoparalysis was defined as ex vivo TNF-α levels less than 200 pg/ml...
January 10, 2018: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Shaoyang Zhang, Qinghui Fu, Qi Chen, Ting-Bo Liang
RATIONALE: Cerebral aspergillosis (CA) is a rare manifestation of invasive aspergillosis. It usually affects seriously immunocompromised hosts. Pancreatic bacterial or/and fungal infection is common in patients with severe acute pancreatitis. PATIENT CONCERNS: We report the first case of an immunocompetent woman with infected necrotizing pancreatitis due to multidrug resistant Acinetobacter baumannii who, in the course of treatment, developed isolated CA. DIAGNOSES: Magnetic resonance imaging, rather than computed tomography, revealed latent homolateral sinus disease-the possible source of the Aspergillus infection...
December 2017: Medicine (Baltimore)
Joaquín Amores-Iniesta, Maria Barberà-Cremades, Carlos M Martínez, José A Pons, Beatriz Revilla-Nuin, Laura Martínez-Alarcón, Francesco Di Virgilio, Pascual Parrilla, Alberto Baroja-Mazo, Pablo Pelegrín
Immune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18. This process is a necessary stage in the deleterious Th1 response against allotransplantation via interferon-γ production. Lack of IL-18 resulted in a decrease in graft-infiltrating CD8 cells but an increase in regulatory T cells...
December 19, 2017: Cell Reports
Wen-Feng Fang, Ivor S Douglas, Yu-Mu Chen, Chiung-Yu Lin, Hsu-Ching Kao, Ying-Tang Fang, Chi-Han Huang, Ya-Ting Chang, Kuo-Tung Huang, Yi-His Wang, Chin-Chou Wang, Meng-Chih Lin
BACKGROUND: Sepsis-induced immune dysfunction ranging from cytokines storm to immunoparalysis impacts outcomes. Monitoring immune dysfunction enables better risk stratification and mortality prediction and is mandatory before widely application of immunoadjuvant therapies. We aimed to develop and validate a scoring system according to patients' immune dysfunction status for 28-day mortality prediction. METHODS: A prospective observational study from a cohort of adult sepsis patients admitted to ICU between August 2013 and June 2016 at Kaohsiung Chang Gung Memorial Hospital in Taiwan...
2017: PloS One
Mark W Hall, Kristin C Greathouse, Rajan K Thakkar, Eric A Sribnick, Jennifer A Muszynski
Although many forms of critical illness are initiated by a proinflammatory stimulus, a compensatory anti-inflammatory response can occur with systemic inflammation. Immunoparalysis, an important form of acquired immunodeficiency, affects the innate and adaptive arms of the immune system. Immunoparalysis has been associated with increased risks for nosocomial infection and death in a variety of pediatric critical illnesses. Evidence suggests that immunoparalysis is reversible with immunostimulants. Highly standardized, prospective immune monitoring regimens are needed to better understand the immunologic effects of critical care treatment regimens and to enrich clinical trials with subjects most likely to benefit from immunostimulatory therapies...
October 2017: Pediatric Clinics of North America
Derek B Danahy, Scott M Anthony, Isaac J Jensen, Stacey M Hartwig, Qiang Shan, Hai-Hui Xue, John T Harty, Thomas S Griffith, Vladimir P Badovinac
Sepsis is a systemic infection that enhances host vulnerability to secondary infections normally controlled by T cells. Using CLP sepsis model, we observed that sepsis induces apoptosis of circulating memory CD8 T-cells (TCIRCM) and diminishes their effector functions, leading to impaired CD8 T-cell mediated protection to systemic pathogen re-infection. In the context of localized re-infections, tissue resident memory CD8 T-cells (TRM) provide robust protection in a variety of infectious models. TRM rapidly 'sense' infection in non-lymphoid tissues and 'alarm' the host by enhancing immune cell recruitment to the site of the infection to accelerate pathogen clearance...
September 2017: PLoS Pathogens
Kim Timmermans, Guus P Leijte, Matthijs Kox, Gert Jan Scheffer, Nicole M A Blijlevens, Peter P Pickkers
Chemotherapy may result in the release of danger-associated molecular patterns (DAMPs), which can cause immunoparalysis (deactivation of the immune system). We investigated DAMPs following chemotherapy and their relationship with markers of immunoparalysis in leukemia patients. In 6 patients with acute myeloid leukemia or myelodysplastic syndrome and 12 healthy subjects, DAMPs, cytokines, and markers of immunoparalysis were determined before and during the first week after chemotherapy initiation. In the patients, plasma levels of nuclear DNA (a marker of general DAMP release) were profoundly increased before chemotherapy and further increased 4-6 h afterwards, while the specific DAMP mitochondrial DNA showed only a trend towards increase...
2017: Acta Haematologica
Wen-Feng Fang, Yu-Mu Chen, Chiung-Yu Lin, Kuo-Tung Huang, Hsu-Ching Kao, Ying-Tang Fang, Chi-Han Huang, Ya-Ting Chang, Yi-His Wang, Chin-Chou Wang, Meng-Chih Lin
BACKGROUND: Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis...
2017: PloS One
Quentin Maestraggi, Benjamin Lebas, Raphaël Clere-Jehl, Pierre-Olivier Ludes, Thiên-Nga Chamaraux-Tran, Francis Schneider, Pierre Diemunsch, Bernard Geny, Julien Pottecher
Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called "cytopathic hypoxia," perpetuates cellular dysfunction...
2017: BioMed Research International
Joseph A Carcillo, E Scott Halstead, Mark W Hall, Trung C Nguyen, Ron Reeder, Rajesh Aneja, Bita Shakoory, Dennis Simon
OBJECTIVES: We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. DESIGN: Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes...
June 2017: Pediatric Critical Care Medicine
Joseph A Carcillo, Bradley Podd, Rajesh Aneja, Scott L Weiss, Mark W Hall, Timothy T Cornell, Thomas P Shanley, Lesley A Doughty, Trung C Nguyen
OBJECTIVE: To describe the pathophysiology associated with multiple organ dysfunction syndrome in children. DATA SOURCES: Literature review, research data, and expert opinion. STUDY SELECTION: Not applicable. DATA EXTRACTION: Moderated by an experienced expert from the field, pathophysiologic processes associated with multiple organ dysfunction syndrome in children were described, discussed, and debated with a focus on identifying knowledge gaps and research priorities...
March 2017: Pediatric Critical Care Medicine
Panagiotis Papadopoulos, Aikaterini Pistiki, Maria Theodorakopoulou, Theodora Christodoulopoulou, Georgia Damoraki, Dimitris Goukos, Efrossini Briassouli, Ioanna Dimopoulou, Apostolos Armaganidis, Serafim Nanas, George Briassoulis, Sotirios Tsiodras
INTRODUCTION: This study was designed to identify changes in the monocytic membrane marker HLA-DR and heat shock proteins (HSPs) in relation to T-regulatory cells (T-regs) and other immunological marker changes in patients with systemic inflammatory response syndrome (SIRS) or sepsis/septic shock. METHODS: Healthy volunteers, intensive care unit (ICU) patients with SIRS due to head injury and ICU patients with severe sepsis/septic shock were enrolled in the current study...
April 2017: Cytokine
Talita Freitas Manzoli, Artur Figueiredo Delgado, Eduardo Juan Troster, Werther Brunow de Carvalho, Ana Caroline Barreto Antunes, Desirée Mayara Marques, Patrícia Zamberlan
OBJECTIVES: Developing malnutrition during hospitalization is well recognized worldwide, and children are at a relatively higher risk for malnutrition than adults. Malnutrition can lead to immune dysfunction, which is associated with a higher mortality rate due to sepsis, the most frequent cause of death in pediatric intensive care units (PICUs). The aim of this study was to investigate whether malnourished patients are more likely to have relative or absolute lymphopenia and, consequently, worse prognoses...
November 1, 2016: Clinics
Joseph A Carcillo, Katherine Sward, E Scott Halstead, Russell Telford, Adria Jimenez-Bacardi, Bita Shakoory, Dennis Simon, Mark Hall
OBJECTIVES: We tested the hypothesis that a C-reactive protein and ferritin-based systemic inflammation contingency table can track mortality risk in pediatric severe sepsis. DESIGN: Prospective cohort study. SETTING: Tertiary PICU. PATIENTS: Children with 100 separate admission episodes of severe sepsis were enrolled. INTERVENTIONS: Blood samples were attained on day 2 of sepsis and bi-weekly for biomarker batch analysis...
February 2017: Pediatric Critical Care Medicine
Angela Sauaia, Frederick A Moore, Ernest E Moore
The development of organ dysfunction (OD) is related to the intensity and balance between trauma-induced simultaneous, opposite inflammatory responses. Early proinflammation via innate immune system activation may cause early OD, whereas antiinflammation, via inhibition of the adaptive immune system and apoptosis, may induce immunoparalysis, impaired healing, infections, and late OD. Patients discharged with low-level OD may develop the persistent inflammation-immunosuppression catabolism syndrome. Although the incidence of multiple organ failure has decreased over time, it remains morbid, lethal, and resource intensive...
January 2017: Critical Care Clinics
Shiv Kumar Sarin, Ashok Choudhury
Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame...
December 2016: Current Gastroenterology Reports
Damien Restagno, Fabienne Venet, Christian Paquet, Ludovic Freyburger, Bernard Allaouchiche, Guillaume Monneret, Jeanne-Marie Bonnet, Vanessa Louzier
Sepsis is characterized by pro- and anti-inflammatory responses following infection. While inflammation is responsible for widespread organ damage, anti-inflammatory mediators lead to immunoparalysis increasing susceptibility to secondary infections (nosocomial pneumonia). We aimed to investigate the impact of bacterial load on survival and cytokine release in a two-hit murine (C57BL/6J) model of CLP followed by P. aeruginosa pneumonia. Plasmatic TNFα, IL-6, IL-10, sTNFr I and II were quantified until 13 days...
2016: PloS One
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