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Innate immune function and mortality in critically ill children with influenza: a multicenter study.

ABSTRACT: To prospectively evaluate relationships among serum cytokine levels, innate immune responsiveness, and mortality in a multicenter cohort of critically ill children with influenza infection.Prospective, multicenter, observational study.Fifteen pediatric ICUs among members of the Pediatric Acute Lung Injury and Sepsis Investigators network.Patients ?18 yrs old admitted to a PICU with community-acquired influenza infection. A control group of outpatient children was also evaluated.ICU patients underwent sampling within 72 hrs of ICU admission for measurement of a panel of 31 serum cytokine levels and quantification of whole blood ex vivo lipopolysaccharide-stimulated tumor necrosis factor-? production capacity using a standardized stimulation protocol. Outpatient control subjects also underwent measurement of tumor necrosis factor-? production capacity.Fifty-two patients (44 survivors, eight deaths) were sampled. High levels of serum cytokines (granulocyte macrophage colony-stimulating factor, interleukin-6, interleukin-8, interferon-inducible protein-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1?) were associated with mortality (p < 0.0016 for each comparison) as was the presence of secondary infection with Staphylococcus aureus (p = 0.007), particularly methicillin-resistant S. aureus (p < 0.0001). Nonsurvivors were immunosuppressed with leukopenia and markedly reduced tumor necrosis factor-? production capacity compared with outpatient control subjects (n = 21, p < 0.0001) and to ICU survivors (p < 0.0001). This association remained after controlling for multiple covariables. A tumor necrosis factor-? response <250 pg/mL was highly predictive of death and longer duration of ICU stay (p < 0.0001). Patients with S. aureus coinfection demonstrated the greatest degree of immunosuppression (p < 0.0001).High serum levels of cytokines can coexist with marked innate immune suppression in children with critical influenza. Severe, early innate immune suppression is highly associated with both S. aureus coinfection and mortality in this population. Multicenter innate immune function testing is feasible and can identify these high-risk children.

SUBMITTER: Hall MW

PROVIDER: S-EPMC3705720 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Innate immune function and mortality in critically ill children with influenza: a multicenter study.

Hall Mark W MW Geyer Susan M SM Guo Chao-Yu CY Panoskaltsis-Mortari Angela A Jouvet Philippe P Ferdinands Jill J Shay David K DK Nateri Jyotsna J Greathouse Kristin K Sullivan Ryan R Tran Tram T Keisling Shannon S Randolph Adrienne G AG

Critical care medicine 20130101 1

<h4>Objective</h4>To prospectively evaluate relationships among serum cytokine levels, innate immune responsiveness, and mortality in a multicenter cohort of critically ill children with influenza infection.<h4>Design</h4>Prospective, multicenter, observational study.<h4>Setting</h4>Fifteen pediatric ICUs among members of the Pediatric Acute Lung Injury and Sepsis Investigators network.<h4>Patients</h4>Patients ≤18 yrs old admitted to a PICU with community-acquired influenza infection. A control ...[more]

PMID: 23222256

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Project description:The impact of protein intake on outcomes in pediatric critical illness is unclear.We examined the association between protein intake and 60-d mortality in mechanically ventilated children.In a prospective, multicenter, cohort study that included 59 pediatric intensive care units (PICUs) from 15 countries, we enrolled consecutive children (age: 1 mo to 18 y) who were mechanically ventilated for ?48 h. We recorded the daily and cumulative mean adequacies of energy and protein delivery as a percentage of the prescribed daily goal during the PICU stay ?10 d. We examined the association of the adequacy of protein delivery with 60-d mortality and determined variables that predicted protein intake adequacy.We enrolled 1245 subjects (44% female) with a median age of 1.7 y (IQR: 0.4, 7.0 y). A total of 985 subjects received enteral nutrition, 354 (36%) of whom received enteral nutrition via the postpyloric route. Mean ± SD prescribed energy and protein goals were 69 ± 28 kcal/kg per day and 1.9 ± 0.7 g/kg per day, respectively. The mean delivery of enteral energy and protein was 36 ± 35% and 37 ± 38%, respectively, of the prescribed goal. The adequacy of enteral protein intake was significantly associated with 60-d mortality (P < 0.001) after adjustment for disease severity, site, PICU days, and energy intake. In relation to mean enteral protein intake <20%, intake ?60% of the prescribed goal was associated with an OR of 0.14 (95% CI: 0.04, 0.52; P = 0.003) for 60-d mortality. Early initiation, postpyloric route, shorter interruptions, larger PICU size, and a dedicated dietitian in the PICU were associated with higher enteral protein delivery.Delivery of >60% of the prescribed protein intake is associated with lower odds of mortality in mechanically ventilated children. Optimal prescription and modifiable practices at the bedside might enhance enteral protein delivery in the PICU with a potential for improved outcomes. This trial was registered at clinicaltrials.gov as NCT02354521.

Project description:Critical injury has been associated with reduction in innate immune function in adults, with infection risk being related to degree of immune suppression. This relationship has not been reported in critically injured children.Innate immune function will be reduced in critically injured children, and the degree of reduction will predict the subsequent development of nosocomial infection.Children (?18 years old) were enrolled in this longitudinal, prospective, observational, single-center study after admission to the pediatric intensive care unit following critical injury, along with a cohort of outpatient controls. Serial blood sampling was performed to evaluate plasma cytokine levels and innate immune function as measured by ex vivo lipopolysaccharide-induced tumor necrosis factor ? (TNF-?) production capacity.Seventy-six critically injured children (and 21 outpatient controls) were enrolled. Sixteen critically injured subjects developed nosocomial infection. Those subjects had higher plasma interleukin 6 and interleukin 10 levels on posttrauma days 1-2 compared with those who recovered without infection and outpatient controls. Ex vivo lipopolysaccharide-induced TNF-? production capacity was lower on posttrauma days 1-2 (P = 0.006) and over the first week following injury (P = 0.04) in those who went on to develop infection. A TNF-? response of less than 520 pg/mL at any time in the first week after injury was highly associated with infection risk by univariate and multivariate analysis. Among transfused children, longer red blood cell storage age, not transfusion volume, was associated with lower innate immune function (P < 0.0001). Trauma-induced innate immune suppression was reversible ex vivo via coculture of whole blood with granulocyte-macrophage colony-stimulating factor.Trauma-induced innate immune suppression is common in critically injured children and is associated with increased risks for the development of nosocomial infection. Potential exacerbating factors, including red blood cell transfusion, and potential therapies for pediatric trauma-induced innate immune suppression are deserving of further study.

Project description:BackgroundBoth sepsis and acute respiratory distress syndrome (ARDS) are common severe diseases in the intensive care unit (ICU). There is no large-scale multicenter study to clarify the attributable mortality of ARDS among septic patients. This study aimed to evaluate the excess mortality of ARDS in critically ill patients with sepsis.MethodsThe data were obtained from a multicenter, prospective cohort study in 18 Chinese ICUs between January 2014 and August 2015. The study population was septic patients after ICU admission. The patients were categorized into two groups: those who developed ARDS (ARDS group) within seven days following a sepsis diagnosis and those who did not develop ARDS (non-ARDS group). Applying propensity score matching (PSM), patients were matched 1:1 as ARDS and non-ARDS groups. Mortality attributed to ARDS was calculated. Subsequently, we conducted a survival analysis to estimate the impact of ARDS on mortality. The primary endpoint was 30-day mortality after sepsis diagnosis.Results2323 septic patients were eligible, 67.8% developed ARDS. After PSM, 737 patients with ARDS were matched 1:1 with 737 non-ARDS patients. ARDS's overall 30-day attributable mortality was 11.9% (95% CI 7.5-16.3%, p < 0.001). Subgroup analysis showed that the 30-day attributable mortality of mild, moderate, and severe ARDS was 10.5% (95% CI 4.0-16.8%, p < 0.001), 11.6% (95% CI 4.7-18.4%, p < 0.001) and 18.1% (95% CI 4.5-30.9%, p = 0.006), respectively. ARDS was an independent risk factor for 30-day mortality, with adjusted hazard ratios of 1.30 (95% CI 1.03-1.64, p = 0.027), 1.49 (95% CI 1.20-1.85, p < 0.001), and 1.95 (95% CI 1.51-2.52, p < 0.001) for mild, moderate, and severe ARDS, respectively.ConclusionsThe overall 30-day attributable mortality of ARDS among critically ill patients with sepsis was 11.9%. Compared with mild and moderate ARDS, severe ARDS contributed more to death. ARDS was significantly associated with an increase in the 30-day mortality.

Project description:ObjectivesWith decreasing mortality in PICUs, a growing number of survivors experience long-lasting physical impairments. Early physical rehabilitation and mobilization during critical illness are safe and feasible, but little is known about the prevalence in PICUs. We aimed to evaluate the prevalence of rehabilitation for critically ill children and associated barriers.DesignNational 2-day point prevalence study.SettingEighty-two PICUs in 65 hospitals across the United States.PatientsAll patients admitted to a participating PICU for greater than or equal to 72 hours on each point prevalence day.InterventionsNone.Measurements and main resultsThe primary outcome was prevalence of physical therapy- or occupational therapy-provided mobility on the study days. PICUs also prospectively collected timing of initial rehabilitation team consultation, clinical and patient mobility data, potential mobility-associated safety events, and barriers to mobility. The point prevalence of physical therapy- or occupational therapy-provided mobility during 1,769 patient-days was 35% and associated with older age (adjusted odds ratio for 13-17 vs < 3 yr, 2.1; 95% CI, 1.5-3.1) and male gender (adjusted odds ratio for females, 0.76; 95% CI, 0.61-0.95). Patients with higher baseline function (Pediatric Cerebral Performance Category, ≤ 2 vs > 2) less often had rehabilitation consultation within the first 72 hours (27% vs 38%; p < 0.001). Patients were completely immobile on 19% of patient-days. A potential safety event occurred in only 4% of 4,700 mobility sessions, most commonly a transient change in vital signs. Out-of-bed mobility was negatively associated with the presence of an endotracheal tube (adjusted odds ratio, 0.13; 95% CI, 0.1-0.2) and urinary catheter (adjusted odds ratio, 0.28; 95% CI, 0.1-0.6). Positive associations included family presence in children less than 3 years old (adjusted odds ratio, 4.55; 95% CI, 3.1-6.6).ConclusionsYounger children, females, and patients with higher baseline function less commonly receive rehabilitation in U.S. PICUs, and early rehabilitation consultation is infrequent. These findings highlight the need for systematic design of rehabilitation interventions for all critically ill children at risk of functional impairments.

Project description:Background: It remains unclear whether the mean vancomycin trough concentration (VTC) derived from the entire course of therapy is of potential benefit for critically ill patients. This study was conducted to explore the association between mean serum VTC and mortality in intensive care units (ICUs). Methods: 3,603 adult patients with two or more VTC records after receiving vancomycin treatment in the eICU Collaborative Research Database were included in this multicenter retrospective cohort study. Mean VTC was estimated using all measured VTCs and investigated as a continuous and categorical variable. Patients were categorised into four groups according to mean VTC: <10, 10-15, 15-20, and >20 mg/L. Multivariable logistic regression and subgroup analyses were performed to investigate the relationship of mean VTC with mortality. Results: After adjusting for a series of covariates, logistic regression analyses indicated that mean VTC, as a continuous variable, was positively correlated with ICU (odds ratio, 1.038, 95% confidence interval, [1.014-1.063]) and hospital (1.025 [1.005-1.046]) mortalities. As a categorical variable, mean VTC of 10-15 mg/L was not associated with reduced ICU (1.705 [0.975-2.981]) and hospital (1.235 [0.829-1.841]) mortalities. Mean VTC of 15-20 mg/L was not correlated with a lower risk of hospital mortality (1.370 [0.924-2.029]). Moreover, mean VTCs of 15-20 and >20 mg/L were significantly associated with higher ICU mortality (1.924 [1.111-3.332]; 2.428 [1.385-4.258]), and mean VTC of >20 mg/L with higher hospital mortality (1.585 [1.053-2.387]) than mean VTC of <10 mg/L. Similar results were observed in patients with different Acute Physiology and Chronic Health Evaluation IV score, creatinine clearance, age, and body mass index subgroups. Conclusion: Mean VTC was not associated with reduced ICU/hospital related mortality. Our results suggested that VTC monitoring might not guarantee vancomycin efficacy for ICU patients.

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Innate immune function and mortality in critically ill children with influenza: a multicenter study.

Publications

Innate immune function and mortality in critically ill children with influenza: a multicenter study.

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