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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...
April 13, 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
Cyriac Abby Philips, Shiv Kumar Sarin
Infections and sepsis are more common in cirrhotic than in the general population and constitute the commonest cause of sudden worsening and death. The diagnosis of systemic inflammatory syndrome and sepsis are challenging in cirrhotics due to an underlying a state of hyperdynamic circulation. Further, poor nutritional and bone marrow reserves lead to modest host immune response, the so called immunoparalysis state and the outcome of antibiotic therapy is suboptimal. In this review, a comprehensive description of current and emerging concepts in the pathogenesis and diagnosis of sepsis with importance to current and novel biomarkers for diagnosis of sepsis in cirrhosis is presented...
November 2016: Hepatology International
Roeland F Stolk, Tom van der Poll, Derek C Angus, Johannes G van der Hoeven, Peter Pickkers, Matthijs Kox
Septic shock is a major cause of death worldwide and a considerable healthcare burden in the twenty-first century. Attention has shifted from damaging effects of the proinflammatory response to the detrimental role of antiinflammation, a phenomenon known as sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis may render patients vulnerable to secondary infections and is associated with impaired outcome. The immunoparalysis hypothesis compels us to reevaluate the current management of septic shock and to assess whether we are inadvertently compromising or altering the host immune response...
September 1, 2016: American Journal of Respiratory and Critical Care Medicine
Tomoharu Miyashita, Ali Karim Ahmed, Shinichi Nakanuma, Koichi Okamoto, Seisho Sakai, Jun Kinoshita, Isamu Makino, Keishi Nakamura, Hironori Hayashi, Katsunobu Oyama, Hidehiro Tajima, Hiroyuki Takamura, Itasu Ninomiya, Sachio Fushida, John W Harmon, Tetsuo Ohta
A number of studies have reported that acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are independent risk factors for organ dysfunction and mortality in patients with sepsis. Although ALI/ARDS might be an essential therapeutic target during the management of sepsis, severe sepsis should be treated effectively and as soon as identified. We have classified three phases, ranging from sepsis to organ dysfunction, characterizing the interaction between neutrophils and platelets. The first phase is neutrophil extracellular trap (NET) formation and intravasated platelet aggregation...
July 2016: In Vivo
Christelle Rouget, Thibaut Girardot, Julien Textoris, Guillaume Monneret, Thomas RIMMELé, Fabienne Venet
Severe injuries such as severe sepsis, burn, trauma and major surgery lead to an overlapping development of pro- and anti- inflammatory responses. It is now well established that these injuries are associated with the secondary development of immune suppression, which results in significant morbidity and mortality. Recent data suggest that immunostimulatory drugs might prevent these complications. However, intensive care patients are heterogeneous, making patient stratification essential for a targeted treatment...
June 17, 2016: Minerva Anestesiologica
Norman Galbraith, Samuel Walker, Jane Carter, Hiram C Polk
BACKGROUND: Patients who survive the early phases of major sepsis and trauma can have greater susceptibility to nosocomial infection later. One cause may be impaired monocyte function, which can leave the patient at risk of overwhelming sepsis and multi-organ dysfunction. Efforts to target this immune defect have been fraught with challenges, with many questions unanswered. We summarized the past and current and likely future therapeutic approaches to augmentation of monocyte function in the surgical patient...
October 2016: Surgical Infections
M Raja, Hdt Torrance, E R Longbottom, A J Stroud, M E Vivian, P S Zolfaghari, R M Pearse, C J Hinds, M J O'Dwyer
No abstract text is available yet for this article.
December 2015: Intensive Care Medicine Experimental
E Villarreal, P Ramirez, L Cordon, P Geffner, A Cortes, M Gordon, E Gonzalez, P Kot, J Ruis, A Sampere
No abstract text is available yet for this article.
December 2015: Intensive Care Medicine Experimental
Yingying Chen, Huixian Li, Shuai Ma, Bo Deng, Jianxin Lu, Feng Ding
OBJECTIVE: To reproduce a clinically relevant "two-hit" model of sepsis complicated by pneumonia and to explore the correlation between "two-hit" and immune state. METHODS: Eighty-one male Sprague-Dawley (SD) rats were divided into groups according to the random number table. Forty-five male rats were assigned respectively to sepsis-alone group, pneumonia 4 days and 7 days after sepsis groups, respectively. Survival rate of each group was observed. Another group of 36 male rats were divided into normal control group, sepsis-alone for 1, 4 and 7 days groups, and sepsis complicated by pneumonia for 4 days and 7 days after sepsis groups, each group consisted of 6 rats...
October 2015: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Lesley Doughty
PURPOSE OF REVIEW: This review is being published to update the literature on the function of the adaptive immune system in critical illness, specifically sepsis and acute lung injury. We have focused on the role of T cells in these syndromes. RECENT FINDINGS: The adaptive immune response becomes dysfunctional during sepsis and acute lung injury in very similar ways. Many of the abnormalities contribute to morbidity and mortality. Immunoparalysis captures the breadth of the dysfunction in that T-cell functions are broadly suppressed after the early proinflammatory stages of illness...
June 2016: Current Opinion in Pediatrics
Jennifer A Muszynski, Rajan Thakkar, Mark W Hall
PURPOSE OF REVIEW: The purpose of review is to highlight the inflammatory response in critical illness and the importance of immune monitoring and modulation in the diagnosis and treatment of critical illness-induced innate immune suppression. RECENT FINDINGS: The pro and anti-inflammatory responses are known to be concurrently activated in many patients requiring intensive care, with innate immune suppression emerging as an important, and potentially reversible, complication of critical illness...
June 2016: Current Opinion in Pediatrics
Verena van der Heide, Patrick Möhnle, Jessica Rink, Josef Briegel, Simone Kreth
BACKGROUND: Immunosuppression has been recognized as a major cause of sepsis-related mortality. Currently, there is much interest in identifying central hubs controlling septic immunoparalysis. In this context, in this study, the authors investigate the role of microRNA-31 (miR-31) as a regulator of T cell functions. METHODS: Primary human T cells were separated from healthy volunteers (n = 16) and from sepsis patients by magnetic beads (n = 23). Expression of mRNA/microRNA (miRNA) was determined by real-time polymerase chain reaction...
April 2016: Anesthesiology
Norman Galbraith, Samuel Walker, Susan Galandiuk, Sarah Gardner, Hiram C Polk
BACKGROUND: Trauma, major elective surgery, and overt sepsis can lead to a cascade of immunological change. A subset of these patients will have a degree of immune suppression that leads to hyporesponsive innate defenses, increasing the risk of infective co-morbidity and death. This article is an overview of monocyte impairment in the high-risk surgical patient. Specifically, our primary focus is on observations made pertaining to monocyte function and pathophysiological mechanisms underpinning this impairment...
June 2016: Surgical Infections
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