Early Immune Function and Duration of Organ Dysfunction in Critically III Children with Sepsis

Muszynski, Jennifer A.; Nofziger, Ryan A; Moore‐Clingenpeel, Melissa; Greathouse, Kristin; Anglim, Larissa; Steele, Lisa; Hensley, Josey; Hanson-Huber, Lisa; Nateri, Jyotsna; Ramilo, Octavio; Hall, Mark W.

doi:10.1164/rccm.201710-2006oc

Cited by 61 publications

(77 citation statements)

References 37 publications

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“…[48][49][50] In clinical studies, low whole blood TNF-a production in response to LPS is a reproducible marker of immune suppression in critically ill patients, associated with risks of nosocomial infection, prolonged organ dysfunction, and death. [51][52][53] Our findings are in agreement with previous studies reporting similar immunosuppressive activity of WBD RCC products. 39,54 In our exploratory analyses relating immunomodulatory activity to cell-derived EV, a statistically significant correlation was identified in this study between platelet-derived EV and the suppressed LPS-induced TNF-a production in RCC at expiry.…”

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confidence: 93%

Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity

et al. 2018

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Transfusion of red cell concentrates (RCCs) is associated with increased risk of adverse outcomes that may be affected by different blood manufacturing methods and the presence of extracellular vesicles (EVs). We investigated the effect of different manufacturing methods on hemolysis, residual cells, cell-derived EVs, and immunomodulatory effects on monocyte activity. Thirty-two RCC units produced using whole blood filtration (WBF), red cell filtration (RCF), apheresis-derived (AD), and whole blood-derived (WBD) methods were examined (n = 8 per method). Residual platelet and white blood cells (WBCs) and the concentration, cell of origin, and characterization of EVs in RCC supernatants were assessed in fresh and stored supernatants. Immunomodulatory activity of RCC supernatants was assessed by quantifying monocyte cytokine production capacity in an in vitro transfusion model. RCF units yielded the lowest number of platelet and WBC-derived EVs, whereas the highest number of platelet EVs was in AD (day 5) and in WBD (day 42). The number of small EVs (<200 nm) was greater than large EVs (≥200 nm) in all tested supernatants, and the highest level of small EVs were in AD units. Immunomodulatory activity was mixed, with evidence of both inflammatory and immunosuppressive effects. Monocytes produced more inflammatory interleukin-8 after exposure to fresh WBF or expired WBD supernatants. Exposure to supernatants from AD and WBD RCC suppressed monocyte lipopolysaccharide-induced cytokine production. Manufacturing methods significantly affect RCC unit EV characteristics and are associated with an immunomodulatory effect of RCC supernatants, which may affect the quality and safety of RCCs.

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confidence: 93%

Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity

et al. 2018

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“…Simultaneous to the proinflammatory response, a systemic inhibition of the immune system occurs to restore homeostasis. 13 The result is that monocytes and macrophages have diminished capacity to release proinflammatory cytokines on stimulation and blood monocytes are reprogrammed with reduced expression of HLA-DR. 14,15 Additionally, there is an increase in T-cell apoptosis and release of antiinflammatory mediators to counteract continual inflammation. Thus, the innate and adaptive immune system contribute to sepsis-induced immunosuppression.…”

Section: Inflammatory Response In Sepsismentioning

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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“…Immunosuppression was associated with increased mortality and secondary infection, prolonged length of ICU stay and aggravated organ dysfunction in adult and children with sepsis [18,19,25,26].…”

Section: Discussionmentioning

confidence: 99%

“…According to China Country Assessment Report on Ageing and Health from World Health Organization in 2015, elderly was defined as aged 60 years or over [21]. According to previous study, early immune status was defined as the immune status within 48 hours after onset of sepsis [19]. Immune status was measured by the expression of mHLA-DR because of its proven value in septic patients [22].…”

Section: Methodsmentioning

confidence: 99%

“…Although immunosuppression is associated with poor outcome in elderly septic patients, the timing of immunosuppression remains unclear. Recently, Muszynski et al revealed that critically ill children with sepsis had immunosuppression from early stage (within 48 hours after onset of sepsis) [19]. However, early immune status of elderly patients with sepsis remains unclear.…”

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Early immunosuppression was associated with poor prognosis in elderly patients with sepsis: secondary analysis of the ETASS study

Pei

Zhang

Zhou

et al. 2020

Preprint

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Background: Although immunosuppression has been investigated in adult septic patients, early immune status remains unclear. In this study, we aimed to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality. Methods: From post hoc analysis of a multicenter, randomized controlled trial, 273 patients whose levels of monocyte human leukocyte antigen-DR (mHLA-DR) were obtained within 48 hours after onset of sepsis were enrolled. All patients were divided into elderly (≥60yrs) group and non-elderly (<60yrs) group. Early immune status was evaluated by the percentage of mHLA-DR in total monocytes within 48 hours after onset of sepsis and it was classified as immunosuppression (mHLA-DR≤30%) or non-immunosuppression (>30%). Changes in immune status were assessed by the value change in mHLA-DR on day 3 compared with the first measurement. Three logistic regression models were conducted to test the associations between early immunosuppression and hospital mortality. We also did a sensitivity analysis to find out if the definition of early immune status (24 vs. 48 hours after onset of sepsis) affects the outcomes. Results: Of the 181 elderly and 92 non-elderly septic patients, 71 (39.2%) elderly and 25 (27.2%) non-elderly died in hospital. The percentage of early immunosuppression in the elderly was twice of that of the non-elderly patients (32% vs. 16%, p=0.006). Immunosuppressed elderly had higher hospital mortality than the non-immunosuppressed elderly (53.4% vs. 32.5%, p=0.009), but there was no significant difference in mortality between immunosuppresed non-elderly patients and non-immunosuppressed non-elderly patients (33.5% vs. 26.0%, p=0.541). In all of the three logistic regression models, we found that early immunosuppression was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status did not affect the outcomes. In addition, immune status improvement on day 3 was associated with reduced hospital mortality in both elderly and non-elderly patients. Conclusion: In adult patients with sepsis, the elderly were more susceptible to early immunosuppression after onset of sepsis. Early immunosuppression was independently associated with poor prognosis in elderly patients. Trial registration: ClinicalTrials.gov NCT00711620 , 9 July 2008, https://clinicaltrials.gov/ct2/show/NCT00711620

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Early Immune Function and Duration of Organ Dysfunction in Critically III Children with Sepsis

Cited by 61 publications

References 37 publications

Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity

Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia

Early immunosuppression was associated with poor prognosis in elderly patients with sepsis: secondary analysis of the ETASS study

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