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Praxis Aug 2018Hemophagocytic Lymphohistiocytosis Abstract. Hemophagocytic lymphohistiocytosis (HLH) is a group of rare diseases characterized by over-activation of the immune system.... (Review)
Review
Hemophagocytic Lymphohistiocytosis Abstract. Hemophagocytic lymphohistiocytosis (HLH) is a group of rare diseases characterized by over-activation of the immune system. They form two groups: primary and secondary HLH. Primary HLH are linked to mutations impairing lymphocyte cytotoxicity. Secondary HLH are triggered by infections, autoimmune diseases or neoplasia, the remaining cases being labeled idiopathic. HLH manifest as febrile states, cytopenias and hepatosplenomegaly. In the absence of treatment, they quickly lead to multiple organ failure. The diagnosis is currently based on the presence of several clinical and biological markers. Treatment consists of suppression of the triggering factor, organ support and immunosuppression. Primary forms, affecting a pediatric population, have been the subject of intense research, and are nowadays treated with established therapeutic protocols. Several recent retrospective studies have improved our knowledge of secondary HLH, which affects mostly adults and whose incidence seems to be increasing. Thus, new diagnostic criteria are currently being studied for secondary HLH, and several treatment protocols have just been published or are being evaluated.
Topics: Adult; Child; Diagnosis, Differential; Disease Progression; Humans; Interdisciplinary Communication; Intersectoral Collaboration; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation; Multiple Organ Failure; Prognosis; Rare Diseases
PubMed: 30086687
DOI: 10.1024/1661-8157/a003045 -
The Nursing Clinics of North America Sep 2018Diabetes mellitus and its complications are among the leading causes of organ failure around the world. It is imperative that timely, patient-centered care is provided... (Review)
Review
Diabetes mellitus and its complications are among the leading causes of organ failure around the world. It is imperative that timely, patient-centered care is provided to avoid microvascular and macrovascular damage. People with well-controlled diabetes can live long and healthy lives through interprofessional management, emphasizing optimal, individualized care.
Topics: Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Hyperglycemia; Multiple Organ Failure
PubMed: 30099998
DOI: 10.1016/j.cnur.2018.04.001 -
Contributions To Nephrology 2023Sepsis is a life-threatening syndrome initiated by a dysregulated host response to infection. Maladaptive inflammatory burst damages host tissues and causes organ... (Review)
Review
Sepsis is a life-threatening syndrome initiated by a dysregulated host response to infection. Maladaptive inflammatory burst damages host tissues and causes organ dysfunction, the burden of which has been demonstrated as the paramount predictor of worse clinical outcomes. In this setting, septic shock represents the most lethal complication of sepsis and implies profound alterations of both the cardiovascular system and cellular metabolism with consequent high mortality rate. Although an increasing amount of evidence attempts to characterize this clinical condition, the complexity of multiple interconnections between underlying pathophysiological pathways requires further investigations. Accordingly, most therapeutic interventions remain purely supportive and should be integrated in light of the continuous organ cross-talk, in order to match a patient's specific needs. In this context, different organ supports may be combined to replace multiple organ dysfunctions through the application of sequential extracorporeal therapy in sepsis (SETS). In this chapter, we provide an overview of sepsis-induced organ dysfunction, focusing on the pathophysiological pathways that are triggered by endotoxin. Based on the need to apply specific blood purification techniques in specific time windows with different targets, we suggest a sequence of extracorporeal therapies. Accordingly, we reported the hypothesis that sepsis-induced organ dysfunction may benefit the most from SETS. Finally, we point out basic principles of this innovative approach and describe a multifunctional platform that allows SETS, in order to make clinicians aware of this new therapeutic frontier for critically ill patients.
Topics: Humans; Multiple Organ Failure; Sepsis; Shock, Septic; Critical Illness; Syndrome
PubMed: 37290408
DOI: 10.1159/000527573 -
Shock (Augusta, Ga.) May 2016There is currently no effective treatment for multiorgan failure following shock other than supportive care. A better understanding of the pathogenesis of these sequelae... (Review)
Review
There is currently no effective treatment for multiorgan failure following shock other than supportive care. A better understanding of the pathogenesis of these sequelae to shock is required. The intestine plays a central role in multiorgan failure. It was previously suggested that bacteria and their toxins are responsible for the organ failure seen in circulatory shock, but clinical trials in septic patients have not confirmed this hypothesis. Instead, we review here evidence that the digestive enzymes, synthesized in the pancreas and discharged into the small intestine as requirement for normal digestion, may play a role in multiorgan failure. These powerful enzymes are nonspecific, highly concentrated, and fully activated in the lumen of the intestine. During normal digestion they are compartmentalized in the lumen of the intestine by the mucosal epithelial barrier. However, if this barrier becomes permeable, e.g. in an ischemic state, the digestive enzymes escape into the wall of the intestine. They digest tissues in the mucosa and generate small molecular weight cytotoxic fragments such as unbound free fatty acids. Digestive enzymes may also escape into the systemic circulation and activate other degrading proteases. These proteases have the ability to clip the ectodomain of surface receptors and compromise their function, for example cleaving the insulin receptor causing insulin resistance. The combination of digestive enzymes and cytotoxic fragments leaking into the central circulation causes cell and organ dysfunction, and ultimately may lead to complete organ failure and death. We summarize current evidence suggesting that enteral blockade of digestive enzymes inside the lumen of the intestine may serve to reduce acute cell and organ damage and improve survival in experimental shock.
Topics: Animals; Enzymes; Humans; Insulin Resistance; Multiple Organ Failure; Pancreas; Peptide Hydrolases; Shock
PubMed: 26717111
DOI: 10.1097/SHK.0000000000000544 -
Critical Care Clinics Jan 2017The development of organ dysfunction (OD) is related to the intensity and balance between trauma-induced simultaneous, opposite inflammatory responses. Early... (Review)
Review
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. However, single OD, especially acute lung injury, remains frequent. Treatment is limited, and prevention remains the mainstay strategy.
Topics: Humans; Inflammation; Multiple Organ Failure; Risk Factors; Wounds and Injuries
PubMed: 27894496
DOI: 10.1016/j.ccc.2016.08.006 -
Biochimica Et Biophysica Acta.... Oct 2017The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is... (Review)
Review
The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients.
Topics: Animals; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Lymphocytes; Multiple Organ Failure; Sepsis
PubMed: 28286161
DOI: 10.1016/j.bbadis.2017.03.005 -
Anesthesia and Analgesia Dec 2020Despite substantial advances in anesthesia safety within the past decades, perioperative mortality remains a prevalent problem and can be considered among the top causes... (Review)
Review
Despite substantial advances in anesthesia safety within the past decades, perioperative mortality remains a prevalent problem and can be considered among the top causes of death worldwide. Acute organ failure is a major risk factor of morbidity and mortality in surgical patients and develops primarily as a consequence of a dysregulated inflammatory response and insufficient tissue perfusion. Neurological dysfunction, myocardial ischemia, acute kidney injury, respiratory failure, intestinal dysfunction, and hepatic impairment are among the most serious complications impacting patient outcome and recovery. Pre-, intra-, and postoperative arrangements, such as enhanced recovery after surgery programs, can contribute to lowering the occurrence of organ dysfunction, and mortality rates have improved with the advent of specialized intensive care units and advances in procedures relating to extracorporeal organ support. However, no specific pharmacological therapies have proven effective in the prevention or reversal of perioperative organ injury. Therefore, understanding the underlying mechanisms of organ dysfunction is essential to identify novel treatment strategies to improve perioperative care and outcomes for surgical patients. This review focuses on recent knowledge of pathophysiological and molecular pathways leading to perioperative organ injury. Additionally, we highlight potential therapeutic targets relevant to the network of events that occur in clinical settings with organ failure.
Topics: Acute Kidney Injury; Heart Diseases; Humans; Liver Diseases; Multiple Organ Failure; Perioperative Care; Postoperative Complications; Risk Factors
PubMed: 33186161
DOI: 10.1213/ANE.0000000000005191 -
Frontiers in Immunology 2023Sepsis is one of the major complications of surgery resulting in high morbidity and mortality, but there are no specific therapies for sepsis-induced organ dysfunction....
Sepsis is one of the major complications of surgery resulting in high morbidity and mortality, but there are no specific therapies for sepsis-induced organ dysfunction. Data obtained under Gene Expression Omnibus accession GSE131761 were re-analyzed and showed an increased gene expression of Janus Kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3) in the whole blood of post-operative septic patients. Based on these results, we hypothesized that JAK/STAT activation may contribute to the pathophysiology of septic shock and, hence, investigated the effects of baricitinib (JAK1/JAK2 inhibitor) on sepsis-induced cardiac dysfunction and multiple-organ failure (MOF). In a mouse model of post-trauma sepsis induced by midline laparotomy and cecal ligation and puncture (CLP), 10-week-old male (n=32) and female (n=32) C57BL/6 mice received baricitinib (1mg/kg; i.p.) or vehicle at 1h or 3h post-surgery. Cardiac function was assessed at 24h post-CLP by echocardiography , and the degree of MOF was analyzed by determination of biomarkers in the serum. The potential mechanism underlying both the cardiac dysfunction and the effect of baricitinib was analyzed by western blot analysis in the heart. Trauma and subsequent sepsis significantly depressed the cardiac function and induced multiple-organ failure, associated with an increase in the activation of JAK2/STAT3, NLRP3 inflammasome and NF- κβ pathways in the heart of both male and female animals. These pathways were inhibited by the administration of baricitinib post the onset of sepsis. Moreover, treatment with baricitinib at 1h or 3h post-CLP protected mice from sepsis-induced cardiac injury and multiple-organ failure. Thus, baricitinib may be repurposed for trauma-associated sepsis.
Topics: Humans; Mice; Male; Female; Animals; Multiple Organ Failure; Mice, Inbred C57BL; Heart Diseases; Sepsis
PubMed: 37781388
DOI: 10.3389/fimmu.2023.1223014 -
Deutsche Medizinische Wochenschrift... Jul 2016Current evidence suggests that a dysregulated, i.e. systemic and extensive, immune response causes sepsis-induced multiple organ failure. Notably, this does not only... (Review)
Review
Current evidence suggests that a dysregulated, i.e. systemic and extensive, immune response causes sepsis-induced multiple organ failure. Notably, this does not only imply the initial inflammatory reaction but also the delayed sepsis-associated depression of the immune system. Endothelial dysfunction and sepsis-induced coagulopathy represent additional major pathomechanisms. Based on multiple interactions between mediators und receptors all of these mechanisms can be discussed individually only for didactical purposes. Clinically, there are charateristic microcirculatory disorders and macrocirclatory changes resulting in an impaired oxygen transport capacity. Due to an additional cytopathic hypoxia, organ function might be impaired even if physiological partial pressures of oxygen are restored. Although these changes are often functional and potentially reversible, mortality increases up to 70% in case of multiple organ failure.
Topics: Cardiovascular Diseases; Endothelium, Vascular; Germany; Humans; Immune System Diseases; Immunity, Innate; Models, Immunological; Multiple Organ Failure; Sepsis
PubMed: 27464278
DOI: 10.1055/s-0042-110742 -
FEBS Letters Aug 2020Sepsis as life-threatening organ dysfunction caused by microorganisms represents a dreadful challenge for the immune system. The role of the complement system as major... (Review)
Review
Sepsis as life-threatening organ dysfunction caused by microorganisms represents a dreadful challenge for the immune system. The role of the complement system as major column of innate immunity has been extensively studied in various sepsis models, but its translational value remains in the dark. Complement activation products, such as C3a and C5a, and their corresponding receptors provide useful diagnostic tools and promising targets to improve organ function and outcome. However, a monotherapeutic complement intervention irrespective of the current immune function seems insufficient to reverse the complex sepsis mechanisms. Indeed, sepsis-induced disturbances of cross talking complement, coagulation, and fibrinolytic cascades lead to systemic 'thromboinflammation', ultimately followed by multiple-organ failure. We propose to reliably monitor the complement function in the patient and to re-establish the immune balance by patient-tailored combined therapies, such as complement and Toll-like receptor inhibition. Our working hypothesis aims at blocking the 'explosive' innate immune recognition systems early on before downstream mediators are released and the inflammatory response becomes irreversible, a strategy that we name 'upstream approach'.
Topics: Animals; Complement Activation; Complement C3a; Complement C5a; Humans; Multiple Organ Failure; Sepsis
PubMed: 32621378
DOI: 10.1002/1873-3468.13881