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Expert Review of Anti-infective Therapy Jun 2012Sepsis has been around since the dawn of time, having been described for more than 2000 years, although clinical definitions are recent. The consensus sepsis definitions... (Review)
Review
Sepsis has been around since the dawn of time, having been described for more than 2000 years, although clinical definitions are recent. The consensus sepsis definitions have permitted worldwide epidemiological studies of sepsis to be conducted. We now recognize the common nature of sepsis and the consistency of its disease - particularly severe sepsis and septic shock. The incidence of sepsis, severe sepsis and septic shock continues to increase, and although Gram-positive bacterial pathogens remain the most common cause of sepsis, fungal organisms are increasing rapidly. We have made progress over the past half-century in identifying and treating patients with sepsis, and decreasing fatality rates reflect this progress. However, owing to the increasing incidence of sepsis, the number of people who die each year continues to increase. The mortality with sepsis, particularly related to treating organ dysfunction, remains a priority to clinicians worldwide and is deserving of greater public health attention.
Topics: Fungi; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Incidence; Mycoses; Sepsis; Severity of Illness Index; Shock, Septic
PubMed: 22734959
DOI: 10.1586/eri.12.50 -
Annals of the Academy of Medicine,... Oct 2021The use of drugs that modulate the immune system during paediatric severe sepsis and septic shock may alter the course of disease and is poorly studied. This study aims...
INTRODUCTION
The use of drugs that modulate the immune system during paediatric severe sepsis and septic shock may alter the course of disease and is poorly studied. This study aims to characterise these children who received immunomodulators and describe their clinical outcomes.
METHODS
This is a retrospective chart review of patients with severe sepsis and septic shock admitted into the paediatric intensive care unit (PICU). Clinical, haematological and outcome characteristics of patients with or without exposure to immune-modulating drugs were compared. Primary outcome was PICU mortality; secondary outcomes were 28-day ventilator-free days (VFD) and intensive care unit-free days (IFD). Univariate and multivariable analyses were performed for these outcomes.
RESULTS
A total of 109 patients with paediatric severe sepsis or septic shock were identified. Of this number, 47 (43.1%), 16 (14.7%) and 3 (2.8%) patients received systemic corticosteroids, intravenous immunoglobulins and granulocyte colony stimulating factor, respectively. Patients who received immune-modulating drugs were more likely to require invasive ventilation (38/54 [70.4%] versus 26/55 [47.3%], =0.019) compared to those who did not. PICU mortality was indifferent between the 2 groups (20/54 [37.0%] vs 11/55 [20.0%], =0.058) even after accounting for chronic complex conditions and admission organ dysfunction (PELOD score) (adjusted odds ratio 1.90, confidence interval [0.72-5.01], =0.193). However, VFD (19.5 [0-28] vs 25 [12-28] days, =0.038) and IFD (15 [0-24] vs 22 [9-26] days, =0.024) were decreased in the immunomodulator group compared to the non-immunomodulator group.
CONCLUSION
Immune-modulating drugs were frequently used in paediatric severe sepsis and septic shock. Patients who received these drugs seemed to require more PICU support. Further studies are required to examine this association thoroughly.
Topics: Child; Humans; Immunologic Factors; Intensive Care Units, Pediatric; Retrospective Studies; Sepsis; Shock, Septic
PubMed: 34755170
DOI: 10.47102/annals-acadmedsg.2021178 -
Pediatric Critical Care Medicine : a... Aug 2016In this review, we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, in monitoring therapeutic efficacy, in... (Review)
Review
OBJECTIVES
In this review, we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, in monitoring therapeutic efficacy, in stratification, and for the identification of sepsis endotypes; and the pathophysiology and management of severe sepsis and septic shock, with an emphasis on the impact of sepsis on cardiovascular function.
DATA SOURCE
MEDLINE and PubMed.
CONCLUSIONS
There is a lot of excitement in the field of sepsis research today. Scientific advances in the diagnosis and clinical staging of sepsis, as well as a personalized approach to the treatment of sepsis, offer tremendous promise for the future. However, at the same time, it is also evident that sepsis mortality has not improved enough, even with progress in our understanding of the molecular pathophysiology of sepsis.
Topics: Biomarkers; Child; Coronary Care Units; Humans; Pediatrics; Risk Factors; Sepsis
PubMed: 27490609
DOI: 10.1097/PCC.0000000000000796 -
Minerva Anestesiologica May 2008An early diagnosis of sepsis prior to the onset of clinical decline is of particular interest to health practitioners because this information increases the... (Review)
Review
An early diagnosis of sepsis prior to the onset of clinical decline is of particular interest to health practitioners because this information increases the possibilities for early and specific treatment of this life threatening condition. In comparison to acute myocardial infarction or ischemic stroke, the time to initiate therapy is thought to be crucial and the major determining factor for surviving sepsis. The treatment of severe sepsis and septic shock consists of source control, early antimicrobial therapy, and supportive and adjunctive therapies. For supportive therapy, an adequate volume loading is the most important step in the treatment of patients with sepsis. This step is performed in order to restore and maintain oxygen transport and tissue oxygenation. Therefore, the supportive treatment should focus on adequate volume resuscitation and appropriate use of inotropes and vasopressors. Within the first 24 h after the initial sepsis-induced organ failure, adjunctive therapies can help to decrease mortality in patients suffering from severe sepsis and septic shock. Ongoing research continues to provide new information on the management of sepsis. However, implementing new medical advances in the management of sepsis into daily clinical intensive care remains a major hurdle. High quality management tools are necessary to bring evidence-based therapy to the bedside. With respect to recently published studies, the importance of the time taken to improve the outcome of sepsis can not be overemphasized.
Topics: Combined Modality Therapy; Fluid Therapy; Hemodynamics; Humans; Oxygen Inhalation Therapy; Quality Control; Sepsis
PubMed: 18414361
DOI: No ID Found -
Critical Care (London, England) Sep 2013Sepsis involves a wide array of sources and microorganisms, only a fraction of which are microbiologically documented. Culture-negative sepsis poses special diagnostic... (Review)
Review
Sepsis involves a wide array of sources and microorganisms, only a fraction of which are microbiologically documented. Culture-negative sepsis poses special diagnostic challenges to both clinicians and microbiologists and further questions the validity of sepsis definitions.
Topics: Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Sepsis
PubMed: 24074289
DOI: 10.1186/cc13022 -
Science Advances May 2020Severe sepsis represents a common, expensive, and deadly health care issue with limited therapeutic options. Gaining insights into the inflammatory dysregulation that...
Severe sepsis represents a common, expensive, and deadly health care issue with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis would help develop new therapeutic strategies against severe sepsis. In this study, we identified the crucial role of cell-free DNA (cfDNA) in the regulation of the Toll-like receptor 9-mediated proinflammatory pathway in severe sepsis progression. Hypothesizing that removing cfDNA would be beneficial for sepsis treatment, we used polyethylenimine (PEI) and synthesized PEI-functionalized, biodegradable mesoporous silica nanoparticles with different charge densities as cfDNA scavengers. These nucleic acid-binding nanoparticles (NABNs) showed superior performance compared with their nucleic acid-binding polymer counterparts on inhibition of cfDNA-induced inflammation and subsequent multiple organ injury caused by severe sepsis. Furthermore, NABNs exhibited enhanced accumulation and retention in the inflamed cecum, along with a more desirable in vivo safety profile. Together, our results revealed a key contribution of cfDNA in severe sepsis and shed a light on the development of NABN-based therapeutics for sepsis therapy, which currently remains intractable.
Topics: Cell-Free Nucleic Acids; DNA; Humans; Nanoparticles; Polyethyleneimine; Sepsis
PubMed: 32523983
DOI: 10.1126/sciadv.aay7148 -
The American Journal of Pathology May 2007Sepsis remains a critical problem with significant morbidity and mortality even in the modern era of critical care management. Multiple derangements exist in sepsis... (Review)
Review
Sepsis remains a critical problem with significant morbidity and mortality even in the modern era of critical care management. Multiple derangements exist in sepsis involving several different organs and systems, although controversies exist over their individual contribution to the disease process. Septic patients have substantial, life-threatening alterations in their coagulation system, and currently, there is an approved therapy with a component of the coagulation system (activated protein C) to treat patients with severe sepsis. Previously, it was believed that sepsis merely represented an exaggerated, hyperinflammatory response with patients dying from inflammation-induced organ injury. More recent data indicate that substantial heterogeneity exists in septic patients' inflammatory response, with some appearing immuno-stimulated, whereas others appear suppressed. Cellular changes continue the theme of heterogeneity. Some cells work too well such as neutrophils that remain activated for an extended time. Other cellular changes become accelerated in a detrimental fashion including lymphocyte apoptosis. Metabolic changes are clearly present, requiring close and individualized monitoring. At this point in time, the literature richly illustrates that no single mediator/system/pathway/pathogen drives the pathophysiology of sepsis. This review will briefly discuss many of the important alterations that account for the pathophysiology of sepsis.
Topics: Anti-Inflammatory Agents; Clinical Trials as Topic; Humans; Sepsis; Signal Transduction
PubMed: 17456750
DOI: 10.2353/ajpath.2007.060872 -
JAMA Network Open Mar 2024Children undergoing treatment for leukemia are at increased risk of severe sepsis, a dysregulated immune response to infection leading to acute organ dysfunction. As...
IMPORTANCE
Children undergoing treatment for leukemia are at increased risk of severe sepsis, a dysregulated immune response to infection leading to acute organ dysfunction. As cancer survivors, they face a high burden of long-term adverse effects. The association between sepsis during anticancer therapy and long-term organ dysfunction in adult survivors of childhood cancer has not been examined.
OBJECTIVE
To determine whether severe sepsis during therapy for leukemia in childhood is associated with subsequent chronic health conditions in adult survivors.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included 644 adult survivors of childhood leukemia who were diagnosed between January 1, 1985, and July 19, 2010, and participated in the St Jude Lifetime Cohort Study. Participants were excluded if they received hematopoietic cell transplant or had relapsed leukemia. Data collection ended June 30, 2017. Data were analyzed from July 1, 2020, to January 5, 2024.
EXPOSURES
Severe sepsis episodes, defined according to consensus criteria as septic shock, acute respiratory distress syndrome, or multiorgan dysfunction associated with infection occurring during anticancer therapy, were abstracted by medical record review for all participants.
MAIN OUTCOMES AND MEASURES
Common Terminology Criteria for Adverse Events-defined chronic health condition outcomes were independently abstracted. Associations between sepsis and cumulative incidence of chronic health conditions (eg, cardiovascular, pulmonary, kidney, neurological, and neurocognitive outcomes) were compared by adjusted hazard ratios from Cox proportional hazards logistic regression. Inverse propensity score weighting was used to adjust for potential confounders, including age, year of diagnosis, and leukemia type.
RESULTS
The study sample consisted of 644 adult survivors of pediatric leukemia (329 women [51.1%] and 315 men [48.9%]; including 56 with a history of acute myeloid leukemia and 585 with a history of acute lymphoblastic leukemia) who were most recently evaluated at a median age of 24.7 (IQR, 21.2-28.3) years at a median time after leukemia diagnosis of 17.3 (IQR, 13.7-21.9) years. Severe sepsis during treatment of acute childhood leukemia occurred in 46 participants (7.1%). Participants who experienced severe sepsis during treatment were more likely to develop moderate to severe neurocognitive impairment (29 of 46 [63.0%] vs 310 of 598 [51.8%]; adjusted hazard ratio, 1.86 [95% CI, 1.61-2.16]; Pā<ā.001) significantly affecting attention, executive function, memory and visuospatial domains. Sepsis was not associated with long-term risk of cardiovascular, pulmonary, kidney, or neurological chronic health conditions.
CONCLUSIONS AND RELEVANCE
In this cohort study of long-term outcomes in survivors of pediatric leukemia, severe sepsis during anticancer therapy for leukemia was associated with a selectively increased risk for development of serious neurocognitive sequelae. Efforts to reduce the effects of anticancer therapy on long-term function and quality of life in survivors might include prevention of severe sepsis during therapy and early detection or amelioration of neurocognitive deficits in survivors of sepsis.
Topics: Adult; Male; Female; Humans; Child; Young Adult; Cohort Studies; Hematopoietic Stem Cell Transplantation; Multiple Organ Failure; Quality of Life; Disease Progression; Leukemia; Sepsis; Survivors
PubMed: 38497960
DOI: 10.1001/jamanetworkopen.2024.2727 -
Drug Design, Development and Therapy 2015The complexity of treating severe sepsis and septic shock has been elucidated in myriad studies, particularly in the past 10 years. The development of clinical... (Review)
Review
The complexity of treating severe sepsis and septic shock has been elucidated in myriad studies, particularly in the past 10 years. The development of clinical guidelines, insight into the effect of bundle elements, and results of clinical trials have brought to light further opportunities and questions in the approach to pharmaceutical interventions for the global challenge to save lives and reduce healthcare costs. Therapeutic interventions including fluid resuscitation, hemodynamic monitoring, glycemic control, corticosteroids, and antimicrobial therapy and stewardship inform outcomes. Research on biomarkers, use of mesenchymal stem cells, blood purification, immunoglobulins, and antioxidative treatments apropos the immune response may soon yield viable therapies.
Topics: Anti-Bacterial Agents; Biomarkers; Guidelines as Topic; Humans; Sepsis; Shock, Septic
PubMed: 25926718
DOI: 10.2147/DDDT.S78757 -
BioMed Research International 2014Sepsis is a systemic, deleterious host response to widespread infection. Patients with sepsis will have documented or suspected infection which can progress to a state... (Review)
Review
Sepsis is a systemic, deleterious host response to widespread infection. Patients with sepsis will have documented or suspected infection which can progress to a state of septic shock or acute organ dysfunction. Since sepsis is responsible for nearly 3 million cases per year in China and severe sepsis is a common, expensive fatal condition in America, developing new therapies becomes a significant and worthwhile challenge. Clinical research has shown that sepsis-associated immunosuppression plays a central role in patient mortality, and targeted immune-enhancing therapy may be an effective treatment approach in these patients. As part of the inflammatory response during sepsis, there are elevations in the number of myeloid-derived suppressor cells (MDSCs). MDSCs are a heterogeneous population of immature myeloid cells that possess immunosuppressive activities via suppressing T-cell proliferation and activation. The role of MDSCs in sepsis remains uncertain. Some believe activated MDSCs are beneficial to the sepsis host by increasing innate immune responses and antimicrobial activities, while others think expansion of MDSCs leads to adaptive immune suppression and secondary infection. Herein, we discuss the complex role of MDSCs in immune regulation during sepsis, as well as the potential to target these cells for therapeutic benefit.
Topics: Cell Proliferation; Cell- and Tissue-Based Therapy; China; Humans; Immunity, Innate; Immunosuppression Therapy; Lymphocyte Activation; Myeloid Cells; Sepsis
PubMed: 24995313
DOI: 10.1155/2014/598654