scholarly journals CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15-deficient mice protects against abdominal sepsis

2019 ◽  
Author(s):  
Isa Santos ◽  
Henrique G. Colaço ◽  
Ana Neves-Costa ◽  
Elsa Seixas ◽  
Tiago R. Velho ◽  
...  
Keyword(s):  
Septic Shock ◽  
Organ Dysfunction ◽  
Peritoneal Cavity ◽  
Host Response ◽  
Abdominal Sepsis ◽  
Growth Differentiation Factor 15 ◽  
Life Threatening ◽  
Pathogen Control ◽  
Circulating Levels ◽  
Deficient Mice

AbstractSepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to an infection. Here we report that the circulating levels of growth-differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, we find that peptidoglycan is a potent ligand that signals through the TLR2-Myd88 axis for the secretion of GDF15 and that Gdf15-deficient animals are protected against abdominal sepsis due to increased chemokine CXC ligand 5 (CXCL5)-mediated recruitment of neutrophils into the peritoneum leading to better local bacterial control. Our results identify GDF15 as a potential target to improve sepsis treatment. Its inhibition should increase neutrophil recruitment to the site of infection and consequently lead to better pathogen control and clearance.

scholarly journals CXCL5-mediated recruitment of neutrophils into the peritoneal cavity ofGdf15-deficient mice protects against abdominal sepsis

2020 ◽  
Vol 117 (22) ◽  
pp. 12281-12287 ◽  
Author(s):  
Isa Santos ◽  
Henrique G. Colaço ◽  
Ana Neves-Costa ◽  
Elsa Seixas ◽  
Tiago R. Velho ◽  
...  
Keyword(s):  
Septic Shock ◽  
Organ Dysfunction ◽  
Peritoneal Cavity ◽  
Host Response ◽  
Abdominal Sepsis ◽  
Neutrophil Recruitment ◽  
Life Threatening ◽  
Pathogen Control ◽  
Circulating Levels ◽  
Deficient Mice

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to an infection. Here we report that the circulating levels of growth and differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, we find that peptidoglycan is a potent ligand that signals through the TLR2-Myd88 axis for the secretion of GDF15, and thatGdf15-deficient mice are protected against abdominal sepsis due to increased chemokine CXC ligand 5 (CXCL5)-mediated recruitment of neutrophils into the peritoneum, leading to better local bacterial control. Our results identify GDF15 as a potential target to improve sepsis treatment. Its inhibition should increase neutrophil recruitment to the site of infection and consequently lead to better pathogen control and clearance.

scholarly journals diagnosis and trEatmEnt of patiEnts in sEptiC shoCK

New Medicine ◽  
2017 ◽  
Vol 21 (1) ◽  
pp. 31-36
Author(s):  
Jacek wadełek
Keyword(s):  
Septic Shock ◽  
Organ Dysfunction ◽  
Host Response ◽  
Signs And Symptoms ◽  
Intravenous Fluids ◽  
Failure Assessment ◽  
Acute Change ◽  
Life Threatening ◽  
Sepsis And Septic Shock ◽  
Clinical Emergency

sepsis and septic shock are a clinical emergency. sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection, and organ dysfunction is defined as an acute change in sequential organ failure assessment (sofa) score greater than 2 points secondary to an infectious cause. septic shock is defined as sepsis with persisting hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mm hg or higher, and blood lactate level greater than 2 mmol/l (18 mg/dl) despite adequate volume resuscitation. the diagnosis of septic shock begins with medical history and physical examination focused on the signs and symptoms of infection, with the aim of recognizing complex physiologic manifestations of shock. Clinicians should understand the importance of prompt administration of antibiotics, vasopressors and intravenous fluids aimed at restoring adequate circulation. they should also be aware of the limitations of the protocol-based therapy.

scholarly journals Renal Replacement Techniques in Septic Shock

2021 ◽  
Vol 22 (19) ◽  
pp. 10238
Author(s):  
Tapio Hellman ◽  
Panu Uusalo ◽  
Mikko J. Järvisalo
Keyword(s):  
Septic Shock ◽  
Organ Dysfunction ◽  
Patient Outcomes ◽  
Host Response ◽  
Kidney Injury ◽  
Polymyxin B ◽  
Critically Ill Patient ◽  
Proinflammatory Mediators ◽  
Actual Outcome ◽  
Life Threatening

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral proinflammatory mediators that evoke cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, RRT techniques can be employed for extracorporeal adsorption of inflammatory mediators using specifically developed adsorption membranes, hemoperfusion sorbent cartridges or columns; these techniques are intended to decrease the level and early deleterious effects of circulating proinflammatory cytokines and endotoxins during the first hours and days of septic shock treatment, in order to improve patient outcomes. Several methods and devices, such as high cut-off membranes, the Oxiris®-AN69 membrane, CytoSorb® and HA380 cytokine hemoadsorption, polymyxin B endotoxin adsorption, and plasmapheresis have been examined in small study series or are under evaluation as ways of improving patient outcomes in septic shock. However, to date, the data on actual outcome benefits have remained controversial, as discussed in this review.

scholarly journals The Role and Mechanism of Pyroptosis and Potential Therapeutic Targets in Sepsis: A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangtao Zheng ◽  
Weiwei Chen ◽  
Fangchen Gong ◽  
Ying Chen ◽  
Erzhen Chen
Keyword(s):  
Immune Response ◽  
Organ Dysfunction ◽  
Host Response ◽  
Therapeutic Targets ◽  
Host Immune Response ◽  
Unique Form ◽  
Pathogen Infection ◽  
Programmed Death ◽  
Life Threatening ◽  
Future Direction

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Recently was been found that pyroptosis is a unique form of proinflammatory programmed death, that is different from apoptosis. A growing number of studies have investigated pyroptosis and its relationship with sepsis, including the mechanisms, role, and relevant targets of pyroptosis in sepsis. While moderate pyroptosis in sepsis can control pathogen infection, excessive pyroptosis can lead to a dysregulated host immune response and even organ dysfunction. This review provides an overview of the mechanisms and potential therapeutic targets underlying pyroptosis in sepsis identified in recent decades, looking forward to the future direction of treatment for sepsis.

scholarly journals Parallels in Sepsis and COVID-19 Conditions: Implications for Managing Severe COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Charles Ochieng’ Olwal ◽  
Nora Nghuchuzie Nganyewo ◽  
Kesego Tapela ◽  
Alexandra Lindsey Djomkam Zune ◽  
Oloche Owoicho ◽  
...  
Keyword(s):  
Septic Shock ◽  
Respiratory Failure ◽  
Host Response ◽  
Cytokine Production ◽  
Opportunistic Infections ◽  
Global Burden ◽  
Life Threatening ◽  
Patients Experience ◽  
Sepsis Care ◽  
Multi Organ Dysfunction Syndrome

Sepsis is a life-threatening systemic illness attributed to a dysregulated host response to infection. Sepsis is a global burden killing ~11 million persons annually. In December 2019, a novel pneumonia condition termed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged and has resulted in more than 1,535,982 deaths globally as of 8th December 2020. These two conditions share many pathophysiological and clinical features. Notably, both sepsis and COVID-19 patients experience consumptive thrombocytopenia, haemolytic anaemia, vascular microthrombosis, multi-organ dysfunction syndrome, coagulopathy, septic shock, respiratory failure, fever, leukopenia, hypotension, leukocytosis, high cytokine production and high predisposition to opportunistic infections. Considering the parallels in the immunopathogenesis and pathophysiological manifestations of sepsis and COVID-19, it is highly likely that sepsis care, which has a well-established history in most health systems, could inform on COVID-19 management. In view of this, the present perspective compares the immunopathogenesis and pathophysiology of COVID-19 and non-SARS-CoV-2 induced sepsis, and lessons from sepsis that can be applicable to COVID-19 management.

scholarly journals An assessment of knowledge and education about sepsis among medical students: a multi-university survey

2021 ◽  
Vol 23 (1) ◽  
pp. 117-118
Author(s):  
Rachit Datta ◽  
◽  
Gian Luca Di Tanna ◽  
Amanda Harley ◽  
Luregn J Schlapbach ◽  
...  
Keyword(s):  
Critical Illness ◽  
Medical Students ◽  
Organ Dysfunction ◽  
Host Response ◽  
Medical Schools ◽  
Junior Doctors ◽  
Life Threatening ◽  
Time Critical ◽  
Australian Universities

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection; it affects 55 000 Australians and results in around 8700 deaths annually.1 Studies have shown that junior doctors have reduced awareness of the importance of sepsis as a time-critical illness.2 Whether this deficiency is a consequence of insufficient training on sepsis in medical schools is unknown. This study evaluated the knowledge of sepsis among medical students in two Australian universities

scholarly journals Recent application of metabolomics in the diagnosis, pathogenesis, treatment, and prognosis of sepsis

2021 ◽  
Keyword(s):  
Early Diagnosis ◽  
Organ Dysfunction ◽  
Host Response ◽  
Clinical Manifestations ◽  
Rapid Diagnosis ◽  
Pathophysiological Mechanism ◽  
Recent Application ◽  
Biochemical Pathways ◽  
Diagnosis And Prognosis ◽  
Life Threatening

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infections. It is a leading cause of morbidity and mortality in hospitalized patients. Patients with sepsis often require care in the intensive care unit (ICU) which is costly to the patients and their families. Sepsis has no specific clinical manifestations, and its pathophysiological mechanism is complex. The disease progresses rapidly which makes early diagnosis difficult. Severe forms of the disease, such as septic shock, may lead to organ dysfunction, organ failure, and death. As an emerging “-omics” technology, metabolomics has revolutionized the clinical and research landscape of sepsis. Metabolomics has been applied in the prognosis, diagnosis, and risk stratification in patients with sepsis. This technology provides details on the metabolites and biochemical pathways commonly associated with the pathophysiology of sepsis. At present, it is mostly used to identify metabolites in various diseases. Using this technology, metabolites in body fluids such as blood and urine are detected and analyzed in relation to disease progresssion. The technology therefore helps to understand the pathogenesis of diseases and promote early diagnosis and treatment of the disease. So far, the applicaition of metabolomics in patients with sepsis has not been well defined. This article briefly reviews the application of metabolomics technology in patients with sepsis in recent years, to generate ideas for improving rapid diagnosis and prognosis evaluation of patients with sepsis.

scholarly journals Pathologic Difference between Sepsis and Bloodstream Infections

2019 ◽  
Vol 3 (4) ◽  
pp. 654-663 ◽  
Author(s):  
Luis E Huerta ◽  
Todd W Rice
Keyword(s):  
Mitochondrial Dysfunction ◽  
Organ Dysfunction ◽  
Host Response ◽  
Laboratory Tests ◽  
Bloodstream Infections ◽  
Therapeutic Interventions ◽  
Coagulation Cascade ◽  
Sepsis Diagnosis ◽  
Reactive Protein ◽  
Life Threatening

Abstract Background Sepsis, defined as life-threatening organ failure caused by a dysregulated host response to infection, is a major cause of morbidity and mortality in hospitalized patients. Understanding the features that distinguish sepsis from bloodstream infections (and other types of infection) can help clinicians appropriately and efficiently target their diagnostic workup and therapeutic interventions, especially early in the disease course. Content In this review, sepsis and bloodstream infections are both defined, with a focus on recent changes in the sepsis definition. The molecular and cellular pathways involved in sepsis pathogenesis are described, including cytokines, the coagulation cascade, apoptosis, and mitochondrial dysfunction. Laboratory tests that have been evaluated for their utility in sepsis diagnosis are discussed. Summary Sepsis is defined not only by the presence of an infection, but also by organ dysfunction from a dysregulated host response to that infection. Numerous pathways, including proinflammatory and antiinflammatory cytokines, the coagulation cascade, apoptosis, and mitochondrial dysfunction, help determine if a bloodstream infection (or any other infection) progresses to sepsis. Many biomarkers, including C-reactive protein, procalcitonin, and lactic acid have been evaluated for use in sepsis diagnosis, although none are routinely recommended for that purpose in current clinical practice. While some laboratory tests can help distinguish the 2, the presence of organ dysfunction is what separates sepsis from routine infections.

scholarly journals Extracellular Vesicles: A Double-Edged Sword in Sepsis

2021 ◽  
Vol 14 (8) ◽  
pp. 829
Author(s):  
Marlies Burgelman ◽  
Charysse Vandendriessche ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Clinical Outcome ◽  
Organ Dysfunction ◽  
Extracellular Vesicles ◽  
Host Response ◽  
Current Knowledge ◽  
Healthy Controls ◽  
Lymphocyte Apoptosis ◽  
Cellular Source ◽  
Life Threatening

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Several studies on mouse and patient sepsis samples have revealed that the level of extracellular vesicles (EVs) in the blood is altered compared to healthy controls, but the different functions of EVs during sepsis pathology are not yet completely understood. Sepsis EVs are described as modulators of inflammation, lymphocyte apoptosis, coagulation and organ dysfunction. Furthermore, EVs can influence clinical outcome and it is suggested that EVs can predict survival. Both detrimental and beneficial roles for EVs have been described in sepsis, depending on the EV cellular source and the disease phase during which the EVs are studied. In this review, we summarize the current knowledge of EV sources and functions during sepsis pathology based on in vitro and mouse models, as well as patient samples.

scholarly journals Sepsis: an update in 2018

2019 ◽  
pp. S99-S101
Author(s):  
Muhammad Fuad Bangash
Keyword(s):  
Organ Dysfunction ◽  
Host Response ◽  
The United States ◽  
Review Article ◽  
Source Control ◽  
Metabolic Dysfunction ◽  
Vasoactive Agents ◽  
Sepsis Management ◽  
Failure Assessment ◽  
Life Threatening

Sepsis remains a major source of morbidity and mortality not only in the United States but worldwide. The key to save lives of these patients is to have a multi-pronged approach to the management of sepsis. In this review article we shall go through the specifics of this approach. Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The septic shock is a subset of sepsis with circulatory and cellular/metabolic dysfunction. Patients with sepsis (formerly severe sepsis) should still be identified by the same organ dysfunction criteria (including lactate level > 2 mmol/L). Organ dysfunction may also be identified using the ‘quick Sepsis-Related Organ Failure Assessment’ (qSOFA). Appropriate source control and immediate treatment with IV antibiotics is a cornerstone of sepsis management. The next step is to resuscitate patients with sepsis-induced hypoperfusion with at least 30 ml/kg of intravenous crystalloid fluid. If the patient is hypotensive despite adequate fluid resuscitation, then use of vasoactive agents like norepinephrine and vasopressin is indicated.Citation: Bangash MF. Sepsis: an update in 2018. Anaesth Pain & Intensive Care 2018;22 Suppl 1:S99-S101

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