Circadian Variation of Plasminogen-Activator-Inhibitor-1 Levels in Children with Meningococcal Sepsis

Boeddha, Navin P.; Cnossen, Marjon H.; Hazelzet, Jan A.; Emonts, Marieke

doi:10.1371/journal.pone.0167004

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…1,2 Complex interplays among host, pathogen, and environment determine the severity of disease. [3][4][5][6] The severity of infection ranges from harmless nasopharyngeal colonization to bacteremia, meningitis, sepsis, and lethal disease.…”

Section: Introductionmentioning

confidence: 99%

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia

Boeddha

Bycroft

Nadel

et al. 2020

Critical Care Clinics

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Complex interplays among host, pathogen, and environment determine the severity of infection ranging from harmless nasopharyngeal colonization to bacteremia, meningitis, sepsis, and lethal disease. The inflammatory response includes proinflammatory and anti-inflammatory responses in innate and adaptive immunity. The net proinflammatory state causes endothelial dysfunction and activation of the hemostatic response. Within the wide range of illness severity, deposition of fibrin throughout the microcirculation could result in multiple organ dysfunction, skin grafts/amputation, and death. Meningococci hold unique properties to promote adhesion, colonization, and invasion into the bloodstream.

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Section: Introductionmentioning

confidence: 99%

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia

Boeddha

Bycroft

Nadel

et al. 2020

Critical Care Clinics

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“…Although extensive research has been performed in describing hemostasis proteins in meningococcal sepsis or sepsis in general (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), the variation of hemostasis protein levels in infections across specific pathogen groups has not yet been described. Therefore, we aimed: 1) to study the variation of hemostasis protein levels in children with invasive bacterial infections due to either Neisseria meningitidis, S. pneumoniae, S. aureus, or GAS, and 2) to describe hemostasis protein levels and their relation with mortality and disease severity.…”

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confidence: 99%

Hemostasis Proteins in Invasive Meningococcal and Nonmeningococcal Infections: A Prospective Multicenter Study

Hagedoorn

Boeddha

Kohlfürst

et al. 2022

Pediatric Critical Care Medicine

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OBJECTIVES: We aimed to describe the variation of hemostasis proteins in children with bacterial infections due to different pathogens ( Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus aureus , and group A streptococcus [GAS]) and to study hemostasis proteins in relation to mortality. DESIGN: Preplanned analysis in prospective cohort study. SETTING: Hospitals in five European countries (Austria, The Netherlands, Spain, Switzerland, and the United Kingdom). PATIENTS: Admitted children (2012–2016) with community-acquired infections due to meningococci ( n = 83), pneumococci ( n = 64), S. aureus (n = 50), and GAS ( n = 44) with available serum samples collected less than 48 hours after admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fibronectin, plasminogen activator inhibitor type 1 (PAI-1), thrombomodulin, and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) were measured in serum in 2019–2020. Additionally, von Willebrand factor, protein C, protein S, and factor IX were measured in citrate plasma available from a subset of patients. Outcome measures included in-hospital mortality and disease severity (need for ventilation/inotropes, Pediatric Index of Mortality score). Of 241 children, 21 (8.7%) died and 177 (73.5%) were admitted to PICU. Mortality rate was similar for the pathogen groups. Levels of fibronectin and thrombomodulin differed for the different pathogens ( p < 0.05). Fibronectin levels were lower in GAS infections than in S. pneumoniae and S. aureus infections but did not differ from meningococcal infections. Thrombomodulin levels in meningococcal infections were higher than in S. aureus and pneumococcal infections. Overall, the area under the curve for mortality was 0.81 (95% CI, 0.70–0.92) for thrombomodulin and 0.78 (95% CI, 0.69–0.88) for ADAMTS-13. The association of each hemostasis protein did not vary across pathogens for any of the outcome measures. CONCLUSIONS: Hemostatic disturbances in childhood bacterial infections are not limited to meningococcal sepsis but occur with a comparable severity across nonmeningococcal infections. High thrombomodulin and high ADAMTS-13 had good discriminative ability for mortality. Our results emphasize the importance of hemostatic disturbances in meningococcal and nonmeningococcal pediatric bacterial infections.

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Diurnal Variations in Immunity

Zhao

Chen

2019

Encyclopedia of Life Sciences

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Many aspects of immune systems show diurnal variations depending on environmental and physical conditions, which are driven by internal circadian biological clocks and have been widely observed. Diurnal oscillations of immune mediators coordinate with the activity of the immune system, possibly allowing the host to anticipate and handle microbial threats more efficiently. These oscillations may also contribute to stimulation of organ proliferation, recovery and the clearance of potentially harmful cellular elements from the circulation. In addition, abnormal diurnal oscillations in immune system are associated with inflammation response induced by disorders or dysregulation of behaviour, physiology, metabolism, disease symptoms or response to drugs treatment. The overview of diurnal variations perspective of human immune system may provide novel strategies in clinical treatment. Key Concepts Diurnal variations in immunity exist widely in nature. Diurnal variations in immunity show differences between species, for example mouse and human. Diurnal variations in immunity are regulated by clock genes. Disruptions of circadian oscillations of immune system are closely associated with human diseases. Chrono‐immunotherapeutics should be attracting more attention in clinical treatment.

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Circadian Variation of Plasminogen-Activator-Inhibitor-1 Levels in Children with Meningococcal Sepsis

Cited by 6 publications

References 20 publications

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia

Hemostasis Proteins in Invasive Meningococcal and Nonmeningococcal Infections: A Prospective Multicenter Study

Diurnal Variations in Immunity

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