Refining the Pediatric Multiple Organ Dysfunction Syndrome.
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SUBMITTER: Weiss SL
PROVIDER: S-EPMC9084565 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015).Data sourcesLiterature review, research data, and expert opinion.Study selectionNot applicable.Data extractionModerated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities.Data synthesisSummary of presentations and discussion supported and supplemented by relevant literature.ConclusionsAmong critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.
| S-EPMC5333132 | biostudies-literature
Project description:ObjectiveTo summarize the epidemiology and outcomes of children with multiple organ dysfunction syndrome as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development multiple organ dysfunction syndrome workshop (March 26-27, 2015).Data sourcesLiterature review, research data, and expert opinion.Study selectionNot applicable.Data extractionModerated by an experienced expert from the field, issues relevant to the epidemiology and outcomes of children with multiple organ dysfunction syndrome were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities.Data synthesisSummary of presentations and discussion supported and supplemented by the relevant literature.ConclusionsA full understanding the epidemiology and outcome of multiple organ dysfunction syndrome in children is limited by inconsistent definitions and populations studied. Nonetheless, pediatric multiple organ dysfunction syndrome is common among PICU patients, occurring in up to 57% depending on the population studied; sepsis remains its leading cause. Pediatric multiple organ dysfunction syndrome leads to considerable short-term morbidity and mortality. Long-term outcomes of multiple organ dysfunction syndrome in children have not been well studied; however, studies of adults and children with other critical illnesses suggest that the risk of long-term adverse sequelae is high. Characterization of the long-term outcomes of pediatric multiple organ dysfunction syndrome is crucial to identify opportunities for improved treatment and recovery strategies that will improve the quality of life of critically ill children and their families. The workshop identified important knowledge gaps and research priorities intended to promote the development of standard definitions and the identification of modifiable factors related to its occurrence and outcome.
| S-EPMC5334773 | biostudies-literature
Project description:Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection. We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05). Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week. Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.
2023-07-07 | GSE236877 | GEO
Project description:MotivationSepsis is a leading cause of death and disability in children globally, accounting for ∼3 million childhood deaths per year. In pediatric sepsis patients, the multiple organ dysfunction syndrome (MODS) is considered a significant risk factor for adverse clinical outcomes characterized by high mortality and morbidity in the pediatric intensive care unit. The recent rapidly growing availability of electronic health records (EHRs) has allowed researchers to vastly develop data-driven approaches like machine learning in healthcare and achieved great successes. However, effective machine learning models which could make the accurate early prediction of the recovery in pediatric sepsis patients from MODS to a mild state and thus assist the clinicians in the decision-making process is still lacking.ResultsThis study develops a machine learning-based approach to predict the recovery from MODS to zero or single organ dysfunction by 1 week in advance in the Swiss Pediatric Sepsis Study cohort of children with blood-culture confirmed bacteremia. Our model achieves internal validation performance on the SPSS cohort with an area under the receiver operating characteristic (AUROC) of 79.1% and area under the precision-recall curve (AUPRC) of 73.6%, and it was also externally validated on another pediatric sepsis patients cohort collected in the USA, yielding an AUROC of 76.4% and AUPRC of 72.4%. These results indicate that our model has the potential to be included into the EHRs system and contribute to patient assessment and triage in pediatric sepsis patient care.Availability and implementationCode available at https://github.com/BorgwardtLab/MODS-recovery. The data underlying this article is not publicly available for the privacy of individuals that participated in the study.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9236580 | biostudies-literature
Project description:BackgroundInfluenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.MethodsWe measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05).ResultsComparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week.ConclusionThus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.
| S-EPMC10390830 | biostudies-literature
Project description:BACKGROUND AND PURPOSE: Melanocortins reverse circulatory shock and improve survival by counteracting the systemic inflammatory response, and through the activation of the vagus nerve-mediated cholinergic anti-inflammatory pathway. To gain insight into the potential therapeutic value of melanocortins against multiple organ damage following systemic inflammatory response, here we investigated the effects of the melanocortin analogue [Nle? D-Phe?]?-MSH (NDP-?-MSH) in a widely used murine model of multiple organ dysfunction syndrome (MODS). EXPERIMENTAL APPROACH: MODS was induced in mice by a single intraperitoneal injection of lipopolysaccharide followed, 6 days later (= day 0), by zymosan. After MODS or sham MODS induction, animals were randomized to receive intraperitoneally NDP-?-MSH (340 µg·kg?¹ day) or saline for up to 16 days. Additional groups of MODS mice were concomitantly treated with the melanocortin MC? receptor antagonist HS024, or the nicotinic acetylcholine receptor antagonist chlorisondamine, and NDP-?-MSH. KEY RESULTS: At day 7, in the liver and lung NDP-?-MSH, significantly reduced mRNA expression of tumour necrosis factor-? (TNF-?), increased mRNA expression of interleukin-10 and improved the histological picture, as well as reduced TNF-? plasma levels; furthermore, NDP-?-MSH dose-dependently increased survival rate, as assessed throughout the 16 day observation period. HS024 and chlorisondamine prevented all the beneficial effects of NDP-?-MSH in MODS mice. CONCLUSIONS AND IMPLICATIONS: These data indicate that NDP-?-MSH protects against experimental MODS by counteracting the systemic inflammatory response, probably through brain MC? receptor-triggered activation of the cholinergic anti-inflammatory pathway. These findings reveal previously undescribed effects of melanocortins and could have clinical relevance in the MODS setting.
| S-EPMC3042202 | biostudies-literature
Project description:IntroductionSepsis is a devastating condition that is generally treated as a single disease. Identification of meaningfully distinct clusters may improve research, treatment and prognostication among septic patients. We therefore sought to identify clusters among patients with severe sepsis or septic shock.MethodsWe retrospectively studied all patients with severe sepsis or septic shock admitted directly from the emergency department to the intensive care units (ICUs) of three hospitals, 2006-2013. Using age and Sequential Organ Failure Assessment (SOFA) subscores, we defined clusters utilizing self-organizing maps, a method for representing multidimensional data in intuitive two-dimensional grids to facilitate cluster identification.ResultsWe identified 2533 patients with severe sepsis or septic shock. Overall mortality was 17 %, with a mean APACHE II score of 24, mean SOFA score of 8 and a mean ICU stay of 5.4 days. Four distinct clusters were identified; (1) shock with elevated creatinine, (2) minimal multi-organ dysfunction syndrome (MODS), (3) shock with hypoxemia and altered mental status, and (4) hepatic disease. Mortality (95 % confidence intervals) for these clusters was 11 (8-14), 12 (11-14), 28 (25-32), and 21 (16-26) %, respectively (p < 0.0001). Regression modeling demonstrated that the clusters differed in the association between clinical outcomes and predictors, including APACHE II score.ConclusionsWe identified four distinct clusters of MODS among patients with severe sepsis or septic shock. These clusters may reflect underlying pathophysiological differences and could potentially facilitate tailored treatments or directed research.
| S-EPMC4607311 | biostudies-literature
Project description:Sepsis-induced multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in critically ill patients and remains impervious to most therapeutic interventions. We utilized a clinically relevant murine model of MODS induced by ventilator-associated pneumonia to systematically delineate pathways dysregulated in lung, liver, and kidney. We focused on processes commonly activated across injured organs and constructed a MODS-associated network based on connectivity among the gene members of these functionally coherent pathways. Our analyses led to the identification of several putative drivers of MODS whose expression was regulated by epidermal growth factor receptor. Our unbiased, integrative method is a promising approach to unravel mechanisms in system-wide disorders afflicting multiple compartments such as sepsis-induced MODS, and guide the discovery of novel putative therapeutic targets.
2014-12-31 | GSE60088 | GEO
Project description:Objective: The objective of the study is to build models for early prediction of risk for developing multiple organ dysfunction (MOD) in pediatric intensive care unit (PICU) patients. Design: The design of the study is a retrospective observational cohort study. Setting: The setting of the study is at a single academic PICU at the Johns Hopkins Hospital, Baltimore, MD. Patients: The patients included in the study were <18 years of age admitted to the PICU between July 2014 and October 2015. Measurements and main results: Organ dysfunction labels were generated every minute from preceding 24-h time windows using the International Pediatric Sepsis Consensus Conference (IPSCC) and Proulx et al. MOD criteria. Early MOD prediction models were built using four machine learning methods: random forest, XGBoost, GLMBoost, and Lasso-GLM. An optimal threshold learned from training data was used to detect high-risk alert events (HRAs). The early prediction models from all methods achieved an area under the receiver operating characteristics curve ≥0.91 for both IPSCC and Proulx criteria. The best performance in terms of maximum F1-score was achieved with random forest (sensitivity: 0.72, positive predictive value: 0.70, F1-score: 0.71) and XGBoost (sensitivity: 0.8, positive predictive value: 0.81, F1-score: 0.81) for IPSCC and Proulx criteria, respectively. The median early warning time was 22.7 h for random forest and 37 h for XGBoost models for IPSCC and Proulx criteria, respectively. Applying spectral clustering on risk-score trajectories over 24 h following early warning provided a high-risk group with ≥0.93 positive predictive value. Conclusions: Early predictions from risk-based patient monitoring could provide more than 22 h of lead time for MOD onset, with ≥0.93 positive predictive value for a high-risk group identified pre-MOD.
| S-EPMC8415553 | biostudies-literature
Project description:OBJECTIVES:To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. DESIGN:Secondary analysis of a prospective, cross-sectional, point prevalence study. SETTING:International, multicenter PICUs. PATIENTS:Pediatric patients with severe sepsis identified on five separate days over a 1-year period. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). CONCLUSIONS:Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.
| S-EPMC7261134 | biostudies-literature