Soluble receptor for advanced glycation end products is a known plasma marker of alveolar epithelial injury. However, RAGE is also expressed on cell types beyond the lung, and its activation leads to ...up-regulation of pro-inflammatory mediators. We sought to examine the relationship between plasma soluble receptor for advanced glycation end products and primary pulmonary dysfunction, extrapulmonary organ dysfunction, and mortality in pediatric acute respiratory distress syndrome patients at two early time points following acute respiratory distress syndrome diagnosis and compare these results to plasma surfactant protein-D, a marker of pure alveolar epithelial injury.
Prospective observational study.
Five academic PICUs.
Two hundred fifty-eight pediatric patients 30 days to 18 years old meeting Berlin Criteria for acute respiratory distress syndrome.
None.
Plasma was collected for soluble receptor for advanced glycation end products and surfactant protein-D measurements within 24 hours (day 1) and 48 to 72 hours (day 3) after acute respiratory distress syndrome diagnosis. Similar to surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with a higher oxygenation index (p < 0.01) and worse lung injury score (p < 0.001) at the time of acute respiratory distress syndrome diagnosis. However, unlike surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with worse extrapulmonary Pediatric Logistic Organ Dysfunction score during ICU stay (day 3; p < 0.01) and positively correlated with plasma levels of interleukin-6 (p < 0.01), tumor necrosis factor-α (p < 0.01), and angiopoietin-2 (p < 0.01). Among children with indirect lung injury, plasma soluble receptor for advanced glycation end products was associated with mortality independent of age, sex, race, cancer/bone marrow transplant, and Pediatric Risk of Mortality score (day 3; odds ratio, 3.14; 95% CI, 1.46-6.75; p < 0.01).
Unlike surfactant protein-D, which is primarily localized to the alveolar epithelium plasma soluble receptor for advanced glycation end products is systemically expressed and correlates with markers of inflammation, extrapulmonary multiple organ dysfunction, and death in pediatric acute respiratory distress syndrome with indirect lung injury. This suggests that unlike surfactant protein-D, soluble receptor for advanced glycation end products is a multifaceted marker of alveolar injury and increased inflammation and that receptor for advanced glycation end products activation may contribute to the pathogenesis of multiple organ failure among children with indirect acute respiratory distress syndrome.
Despite lower overall hospitalization rates for asthma in recent years, there has been an increase in the number of pediatric patients receiving intensive care management in the United States.
To ...investigate how the use of invasive and noninvasive mechanical ventilation for asthma has changed in the context of an evolving cohort of critically ill pediatric patients with asthma.
We analyzed children admitted to intensive care units for asthma from 2009 through 2019 in the Virtual Pediatric Systems database. Regression analyses were used to evaluate how respiratory support interventions, mortality, and patient characteristics have changed over time. Odds ratios were calculated to determine how patient characteristics were associated with respiratory support needs. Stratified analyses were performed to determine how changing practice patterns may have differed between patient subgroups.
There were 67,614 admissions for 56,727 patients analyzed. Intubation occurred in 4.6% of admissions and decreased from 6.9% to 3.4% over time (
< 0.001), whereas noninvasive ventilation as the maximal respiratory support increased from 8.9% to 20.0% (
< 0.001). Over time, the cohort shifted to include more 2- to 6-year-olds and patients of Asian/Pacific Islander or Hispanic race/ethnicity. Although intubation decreased and noninvasive ventilation increased in all subgroups, the changes were most pronounced in the youngest patients and slightly less pronounced for obese patients.
In pediatric asthma, use of intubation has halved, whereas use of noninvasive ventilation has more than doubled. This change in practice appears partially related to a younger patient cohort, although other factors merit exploration.
Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. ...Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood.
In a multicenter, case-control, public health investigation of children ages 5-18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression.
We compared 304 MIS-C case-patients (280 92% unvaccinated) with 502 controls (346 69% unvaccinated). MIS-C was associated with decreased likelihood of vaccination (adjusted OR aOR: .16; 95% CI: .10-.26), including among children ages 5-11 years (aOR: .22; 95% CI: .10-.52), ages 12-18 years (aOR: .10; 95% CI: .05-.19), and during the Delta (aOR: .06; 95% CI: .02-.15) and Omicron (aOR: .22; 95% CI: .11-.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR: .08; 95% CI: .03-.22) in 12-18-year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible case-patients were unvaccinated.
Vaccination with 2 doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5-18 years. Most vaccine-eligible hospitalized patients with MIS-C were unvaccinated.
Objective To determine the incidence, risk factors, and outcomes of pulmonary hypertension (PH) in the pediatric intensive care unit (PICU) after pediatric hematopoietic stem cell transplant (HCT). ...Methods This was a retrospective study of pediatric patients who underwent allogeneic HCT between January 2008-December 2014 at a center contributing to the Center for International Blood and Marrow Transplant Research data registry. Incidence of PH was assessed from PICU diagnostic codes from records merged from the Virtual Pediatric Systems database. Regression and survival analyses identified factors associated with post-HCT PH. Additional post-HCT morbidities and survival after PH were also assessed. Results Among 6,995 HCT recipients, there were 29 cases of PH, a cumulative incidence of 0.42% (95% CI 0.27%-0.57%) at 60 months post-HCT. In the sub-cohort of 1,067 patients requiring intensive care after HCT, this accounted for a PH prevalence of 2.72% (95% CI 1.74–3.69%). There was an increased risk of developing PH associated with Black/African American race, metabolic disorders, partially HLA-matched or cord blood allografts, graft-versus-host prophylaxis regimen, and lower pre-HCT functional status. Patients who developed PH had significant PICU comorbidities including heart failure, pulmonary hemorrhage, respiratory failure, renal failure, and infections. Survival at 6 months after diagnosis of post-HCT PH was 51.7% (95% CI 32.5%-67.9%). Conclusions PH is a rare but serious complication in the pediatric post-HCT population. A significant burden of additional comorbidities, procedural interventions, and risk of mortality is associated with its development. Close monitoring and prompt intervention for this severe complication are necessary in this vulnerable population.
In pediatric acute respiratory distress syndrome, lung injury is mediated by immune activation and severe inflammation. Therefore, we hypothesized that patients with elevated pro- and ...anti-inflammatory cytokines would have higher mortality rates and that these biomarkers could improve risk stratification of poor outcomes.
Multicenter prospective observational study.
We enrolled patients from five academic PICUs between 2008 and 2015.
Patients were 1 month to 18 years old, used noninvasive or invasive ventilation, and met the American European Consensus Conference definition of acute respiratory distress syndrome.
Eight proinflammatory and anti-inflammatory cytokines were measured on acute respiratory distress syndrome day 1 and correlated with mortality, ICU morbidity as measured by survivor Pediatric Logistic Organ Dysfunction score, and biomarkers of endothelial injury, including angiopoietin-2, von Willebrand Factor, and soluble thrombomodulin.
We measured biomarker levels in 194 patients, including 38 acute respiratory distress syndrome nonsurvivors. Interleukin-6, interleukin-8, interleukin-10, interleukin-18, and tumor necrosis factor-R2 were each strongly associated with all-cause mortality, multiple markers of ICU morbidity, and endothelial injury. A multiple logistic regression model incorporating oxygenation index, interleukin-8, and tumor necrosis factor-R2 was superior to a model of oxygenation index alone in predicting the composite outcome of mortality or severe morbidity (area under the receiver operating characteristic, 0.77 0.70-0.83 vs 0.70 0.62-0.77; p = 0.042).
In pediatric acute respiratory distress syndrome, pro- and anti-inflammatory cytokines are strongly associated with mortality, ICU morbidity, and biochemical evidence of endothelial injury. These cytokines significantly improve the ability of the oxygenation index to discriminate risk of mortality or severe morbidity and may allow for identification and enrollment of high-risk subgroups for future studies.
Abstract
Background
Transfusion-related sepsis remains an important hospital infection control challenge. Investigation of septic transfusion events is often restricted by the limitations of ...bacterial culture in terms of time requirements and low yield in the setting of prior antibiotic administration.
Methods
In 3 gram-negative septic transfusion cases, we performed metagenomic next-generation sequencing (mNGS) of direct clinical blood specimens in addition to standard culture-based approaches utilized for infection control investigations. Pathogen detection leveraged IDSeq, a new open-access microbial bioinformatics portal. Phylogenetic analysis was performed to assess microbial genetic relatedness and understand transmission events.
Results
mNGS of direct clinical blood specimens afforded precision detection of pathogens responsible for each case of transfusion-related sepsis and enabled discovery of a novel Acinetobacter species in a platelet product that had become contaminated despite photochemical pathogen reduction. In each case, longitudinal assessment of pathogen burden elucidated the temporal sequence of events associated with each transfusion-transmitted infection. We found that informative data could be obtained from culture-independent mNGS of residual platelet products and leftover blood specimens that were either unsuitable or unavailable for culture or that failed to grow due to prior antibiotic administration. We additionally developed methods to enhance accuracy for detecting transfusion-associated pathogens that share taxonomic similarity to contaminants commonly found in mNGS library preparations.
Conclusions
Culture-independent mNGS of blood products afforded rapid and precise assessment of pathogen identity, abundance, and genetic relatedness. Together, these challenging cases demonstrated the potential for metagenomics to advance existing methods for investigating transfusion-transmitted infections.
Transfusion-transmitted infections cause significant morbidity and are challenging to prevent and diagnose. We found that culture-independent metagenomic sequencing of blood products afforded rapid and precise assessment of pathogen identity, abundance, and genetic relatedness, enhancing traditional hospital infection control strategies.
Endothelial dysfunction underlies many of the major complications following hematopoietic cell transplantation (HCT), including transplant-associated thrombotic microangiopathy (TA-TMA), ...veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), and engraftment syndrome (ES). Emerging evidence similarly implicates endothelitis and microangiopathy in severe COVID-19-related multi-system organ dysfunction. Given the overlap in these two illness states, we hypothesize that prior COVID-19 infection may increase risk for HCT-related endotheliopathies. This retrospective, multicenter study included patients aged 0-25 years who underwent autologous or allogeneic HCT for any indication between January 1, 2020 and September 21, 2021, with close attention to those infected with COVID-19 in either the six months prior to transplant or twelve months following transplant. Incidences of TA-TMA, VOD/SOS, and ES were compared among patients with COVID-19 infection pre-HCT and post-HCT, as well as with historical controls who were never infected with SARS-CoV-2. Those who underwent HCT following COVID-19 infection displayed significantly increased rates of TA-TMA compared to those who were never infected. Additionally, our data suggests a similar trend for increased VOD/SOS and ES rates, although this did not reach statistical significance. Therefore, a history of COVID-19 infection prior to undergoing HCT may be a nonmodifiable risk factor for endothelial-related complications following HCT. Further studies are warranted to better clarify this relationship among larger cohorts and in the era of the Omicron SARS-CoV-2 variants.
Little is known on the use of noninvasive ventilation (NIPPV) in pediatric hematopoietic cell transplant (HCT) patients.
We sought to describe the landscape of NIPPV use and to identify risk factors ...for failure to inform future investigation or quality improvement.
This is a multicenter, retrospective observational cohort of 153 consecutive children post-HCT requiring NIPPV from 2010-2016.
97 (63%) failed NIPPV. Factors associated with failure on univariate analysis included: longer oxygen use prior to NIPPV (p=0.04), vasoactive agent use (p<0.001), and higher respiratory rate at multiple hours of NIPPV use (1hr p=0.02, 2hr p=0.04, 4hr p=0.008, 8hr p=0.002). Using respiratory rate at 4 hours a multivariable model was constructed. This model demonstrated high ability to discriminate NIPPV failure (AUC=0.794) with the following results: respiratory rate >40 at 4 hours aOR=6.3 9(95% CI: 2.4, 16.4), p<0.001 and vasoactive use aOR=4.9 (95% CI: 1.9, 13.1), p=0.001. Of note, 11 patients had a cardiac arrest during intubation (11%) and 3 others arrested prior to intubation. These 14 patients were closer to HCT 14 days (IQR:4, 73) vs 54 (IQR:21,117), p<0.01 and there was a trend toward beginning NIPPV outside of the PICU and arrest during/prior to intubation (p=0.056).
In this cohort respiratory rate at 4 hours and vasoactive use are independent risk factors of NIPPV failure. An objective model to predict which children may benefit from a trial of NIPPV, may also inform the timing of both NIPPV initiation and uncomplicated intubation.
Data on outcomes of children with cystic fibrosis admitted to PICUs are limited and outdated. Prior studies cite PICU mortality rates ranging from 37.5% to 100%. Given the advances made in cystic ...fibrosis care, we expect outcomes for these patients to have changed significantly since last studied. We provide an updated report on PICU mortality and the factors associated with death among critically ill children with cystic fibrosis.
Retrospective multicenter cohort analysis utilizing data from the Virtual Pediatric Systems database.
Data were collected from 135 PICUs from January 1, 2009, to June 20, 2018.
One-thousand six-hundred thirty-three children with cystic fibrosis accounting for 2,893 PICU admissions were studied.
None.
The primary outcome was mortality during PICU admission. Predictors included demographics, anthropometrics, diagnoses, clinical characteristics, and critical care interventions. Odds ratios of mortality were calculated in univariate and multivariable analyses to assess differences in mortality associated with predictor variables. Generalized estimating equation models were used to account for multiple admissions per patient. The overall PICU mortality rate was 6.6%. Factors associated with increased odds of mortality included hemoptysis/pulmonary hemorrhage, pneumothorax, gastrointestinal bleeding, bacterial/fungal infections, lower body mass index/malnutrition, and need for noninvasive or invasive respiratory support. Intubation/mechanical ventilation occurred in 26.4% of the 2,893 admissions and was associated with a 19.1% mortality rate. Of the nonsurvivors, 20.7% died without receiving mechanical ventilation.
The mortality rate during PICU admissions for patients with cystic fibrosis is lower than has been reported in prior studies, both in the overall cohort and in the subset requiring invasive mechanical ventilation. These data provide updated insight into the prognosis for cystic fibrosis patients requiring critical care.
To evaluate risk factors for postdischarge sequelae in children and adolescents hospitalized for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C).
...Multicenter prospective cohort study conducted in 25 United States pediatric hospitals. Patients <21-years-old, hospitalized May 2020 to May 2021 for acute COVID-19 or MIS-C with follow-up 2 to 4 months after admission. We assessed readmissions, persistent symptoms or activity impairment, and new morbidities. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI).
Of 358 eligible patients, 2 to 4 month survey data were available for 119 of 155 (76.8%) with acute COVID-19 and 160 of 203 (78.8%) with MIS-C. Thirteen (11%) patients with acute COVID-19 and 12 (8%) with MIS-C had a readmission. Thirty-two (26.9%) patients with acute COVID-19 had persistent symptoms (22.7%) or activity impairment (14.3%) and 48 (30.0%) with MIS-C had persistent symptoms (20.0%) or activity impairment (21.3%). For patients with acute COVID-19, persistent symptoms (aRR, 1.29 95% CI, 1.04-1.59) and activity impairment (aRR, 1.37 95% CI, 1.06-1.78) were associated with more organ systems involved. Patients with MIS-C and pre-existing respiratory conditions more frequently had persistent symptoms (aRR, 3.09 95% CI, 1.55-6.14) and those with obesity more frequently had activity impairment (aRR, 2.52 95% CI, 1.35-4.69). New morbidities were infrequent (9% COVID-19, 1% MIS-C).
Over 1 in 4 children hospitalized with acute COVID-19 or MIS-C experienced persistent symptoms or activity impairment for at least 2 months. Patients with MIS-C and respiratory conditions or obesity are at higher risk of prolonged recovery.
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