IMPORTANCE: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. OBJECTIVE: To compare clinical characteristics and outcomes ...of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). SETTING, DESIGN, AND PARTICIPANTS: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase–polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. EXPOSURE: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. RESULTS: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference RD, 21.4% 95% CI, 16.1%-26.7%; aRR, 1.51 95% CI, 1.33-1.72 vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% 95% CI, 5.6%-16.0%; aRR, 1.43 95% CI, 1.17-1.76 vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% 95% CI, 42.4%-52.0%; aRR, 2.99 95% CI, 2.55-3.50 vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% 95% CI, 4.7%-10.6%; aRR, 2.49 95% CI, 2.05-3.02 vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% 95% CI, 2.3%-7.3%; aRR, 2.29 95% CI, 1.84-2.85 vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL 212/523 {41%} vs 84/486 {17%}, P < .001). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. CONCLUSIONS AND RELEVANCE: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.
Abstract
Background
Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a ...highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children.
Methods
We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children’s hospitals from 2014–2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort.
Results
We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range IQR, 0.33–0.72 vs median, 0.96; IQR, 0.94–0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001).
Conclusions
An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.
Pulmonary infections in immunocompromised children frequently evade detection by current clinical diagnostics. We optimized metagenomic sequencing of pulmonary pathogens in immunocompromised children and show that metagenomic RNA sequencing identified pulmonary pathogens in approximately half of patients with negative clinical diagnostics.
An analysis of surveillance data on inpatients younger than 21 years of age who had multisystem inflammatory syndrome in children and were hospitalized between March 15 and October 31, 2020, showed ...that initial treatment with IVIG plus glucocorticoids was associated with a lower risk of cardiovascular dysfunction and a lower incidence of adjunctive therapy use than IVIG alone.
Background
The utility of bronchoscopy with bronchoalveolar lavage (BAL) in immunocompromised children is not well understood. We aim to describe the bronchoscopy diagnostic yield and complications ...and to investigate factors associated with diagnostic yield.
Methods
This is a single‐center, retrospective cohort study of 60 children with leukemia or post‐hematopoietic stem cell transplant who had a bronchoscopy with BAL between 2017 and 2021. Comparisons were done with regression analysis.
Results
Of the 60 bronchoscopies performed, 46 (77%) revealed diagnostic information: 39 (65%) identified a pathogen, 14 (23.3%) found secretions/mucus plugging, and 6 (10%) found pulmonary hemorrhage. BAL results changed antimicrobial therapy in 27 (45%) cases. Bronchoscopies were performed in the intensive care unit (27/60) or operating room (33/60), with the former having a higher diagnostic yield (96% vs. 60%, p = 0.001). Half (50%) of bronchoscopies found a new infectious diagnosis. Respiratory symptoms (n = 58, 97%), supplemental oxygen use (n = 39, 65%), and antibiotic use (n = 56, 93%) before bronchoscopy were all common. The median volume of fluid instilled during bronchoscopy was 1.3 mL/kg (interquatile range IQR: 0.7, 2.6). None of these factors were associated with the diagnostic yield. Complications were rare and minor with only one child having self‐resolved bleeding and four children, previously in room air requiring a nasal cannula. For the 27 (45%) children on mechanical ventilation when the bronchoscopy was performed, there was no difference in ventilator settings pre‐ and post‐bronchoscopy.
Conclusion
Bronchoscopies with BAL are useful, safe, and important in the diagnostic management of pulmonary complications in this cohort of children.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To determine changes in pediatric oncology hospitalizations requiring intensive care over the period 2012-2021.
Retrospective study of hospital admission.
Registry data from 36 children's hospitals ...in the U.S. Pediatric Health Information Systems database.
Children 18 years or younger admitted to any of 36 hospitals with an oncology diagnosis.
None.
There were a total of 55,827 unique patients accounted for 281,221 pediatric oncology hospitalizations over the 10-year period, and 16.6% of hospitalizations included admission to the PICU. Hospitalizations and PICU admissions steadily increased over this decade. Between 2012 and 2016, 15.1% of oncology hospitalizations were admitted to the PICU compared with 18.0% from 2017 to 2021 (difference 2.9% 95% CI, 2.6-3.2% p ≤ 0.0001). Support with invasive mechanical ventilation also increased over time with 3.7% during 2012-2016 compared with 4.1% from 2017 to 2021 (difference 0.4% 95% CI, 0.2-0.5% p ≤ 0.0001). Similar results were seen with cardiorespiratory life support using extracorporeal membrane oxygenation (difference 0.05% 95% CI, 0.02-0.07% p = 0.0002), multiple vasoactive agent use (difference 0.3% 95% CI, 0.2-0.4% p < 0.0001), central line placement (difference 5.3% 95% CI, 5.1-5.6%, p < 0.001), and arterial line placement (difference 0.4% 95% CI, 0.3-0.4%, p < 0.001). Year-on-year case fatality rate was unchanged over time (1.3%), but admission to the PICU during the second 5 years, compared with the first 5 years, was associated with lower odds of mortality (difference 0.7% 95% CI, 0.3-1.1%) (odds ratio 0.82 95% CI, 0.75-0.90% p < 0.001).
The percentage of pediatric oncology hospitalizations resulting in PICU admission has increased over the past 10 years. Despite the increasing use of PICU admission and markers of acuity, and on comparing 2017-2021 with 2012-2016, there are lower odds of mortality.
Understanding interventions preceding death in children with immunocompromised conditions is important to ensure a peaceful and dignified perideath experience. The aim of this study was to describe ...the number of interventions performed in the pediatric intensive care unit (PICU) within the 48 hours before death in this population.
This was a single-center, retrospective cohort study of all children with an underlying oncologic, hematologic, or immunologic diagnosis admitted to the PICU for at least 72 hours between 2014 and 2021. Medical records were reviewed for interventions within 48 hours preceding death and for palliative care involvement. Interventions were defined as new or escalations in respiratory support, cardiopulmonary resuscitation (CPR), vascular access, drains, and radiographic studies. Associations were evaluated using simple logistic regression.
A total of 55 patients were included in this study. The predominant PICU admission diagnoses were respiratory (51%), followed by shock (25%), and neurologic diagnoses (9%). These predominant diagnoses were similar perideath. At PICU admission, only 1 patient had a do-not-resuscitate (DNR) order. Forty-six percent had a DNR order 48 hours preceding death, and 91% had DNR orders in place at time of death. During the 48-hour period preceding death, 80% of children received at least one intervention. Radiographic studies were the most common, used in 78% of children, followed by respiratory (20%), vascular (16%), CPR (13%), and drain placement (7%). Palliative care was involved in 38% of cases and was associated with a decrease in the number of radiologic interventions (
= 0.028) and CPR (
= 0.026).
Children in the PICU with underlying immunocompromised conditions frequently receive interventions within the 48-hour period preceding death. Palliative care involvement was associated with fewer radiographic studies and fewer occurrences of CPR. The impact of interventions on the dying experience warrants further investigation.
We sought to describe the presentation, course, and outcomes of hospitalized pediatric coronavirus disease 2019 patients, with detailed description of those requiring mechanical ventilation, and ...comparisons between critically ill and noncritical hospitalized pediatric patients.
Observational cohort study.
Riley Hospital for Children at Indiana University Health in Indianapolis in the early weeks of the coronavirus disease 2019 pandemic.
All hospitalized pediatric patients with confirmed coronavirus disease 2019 as of May 4, 2020, were included.
Patients received therapies including hydroxychloroquine, remdesivir, tocilizumab, and convalescent serum and were managed according to an institutional algorithm based on evidence available at the time of presentation.
Of 407 children tested for severe acute respiratory syndrome-coronavirus 2 at our hospital, 24 were positive, and 19 required hospitalization. Seven (36.8%) were critically ill in ICU, and four (21%) required mechanical ventilation. Hospitalized children were predominantly male (14, 74%) and African-American or Hispanic (14, 74%), with a bimodal distribution of ages among young children less than or equal to 2 years old (8, 42%) and older adolescents ages 15-18 (6, 32%). Five of seven (71.4%) of critically ill patients were African-American (n = 3) or Hispanic (n = 2). Critical illness was associated with older age (p = 0.017), longer duration of symptoms (p = 0.036), and lower oxygen saturation on presentation (p = 0.016); with more thrombocytopenia (p = 0.015); higher C-reactive protein (p = 0.031); and lower WBC count (p = 0.039). Duration of mechanical ventilation averaged 14.1 days. One patient died.
Severe, protracted coronavirus disease 2019 is seen in pediatric patients, including those without significant comorbidities. We observed a greater proportion of hospitalized children requiring mechanical ventilation than has been reported to date. Older children, African-American or Hispanic children, and males may be at risk for severe coronavirus disease 2019 requiring hospitalization. Hypoxia, thrombocytopenia, and elevated C-reactive protein may be useful markers of critical illness. Data regarding optimal management and therapies for pediatric coronavirus disease 2019 are urgently needed.
We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress ...syndrome (PARDS), considering new evidence and topic areas that were not previously addressed.
International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science.
Not applicable.
Patients with or at risk for PARDS.
None.
Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%.
PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.
The etiology and outcomes of posterior reversible encephalopathy syndrome (PRES) in children with cancer are not well understood. We aim to determine the incidence of PRES, describe associated ...morbidity and mortality, and better understand risk factors in this patient population. A total of 473 children with a hematologic malignancy or postallogeneic hematopoietic cell transplantation between June 2015 and June 2020 were screened for PRES to determine incidence and whether age or underlying diagnosis are associated with development of PRES. We conducted a case-control study to evaluate whether comorbidities or chemotherapeutic agents are associated with PRES. Children with PRES were matched with 2 controls based on age and underlying diagnosis to identify additional risk factors. Fourteen patients developed PRES, with an incidence of 5.9/1000 people/year. Those diagnosed with PRES had commonly described PRES symptoms: hypertension, seizures, nausea/vomiting, altered mental status, and headaches. All patients received an magnetic resonance imaging, and most had findings consistent with PRES. Hematopoietic cell transplantation was associated with the development of PRES. The use of Etoposide was associated with PRES but comorbidities, steroids and calcineurin inhibitors were not. While PRES was infrequent in this population, it is associated with high morbidity and mortality, with ICU admissions and an overall hospital mortality, because of secondary causes, of 29%.
Background
Early-onset ventilator-associated pneumonia (VAP) is associated with poor outcomes in patients with severe traumatic brain injury (TBI). The primary aim of this study was to describe VAP, ...including the microbiology of VAP and differences in frequency of VAP when various definitions are applied. The secondary aim was to determine the clinical variables associated with the development of VAP in children with severe TBI.
Methods
This is a retrospective cohort study at a quaternary referral children’s hospital with a level I trauma center designation. Inclusion criteria were patients aged 0–18 years admitted to the pediatric intensive care unit between 2015 and 2020 with severe TBI requiring at least 2 days of invasive ventilation. VAP was defined by using Center of Disease Control (CDC) definition or clinical VAP, based on physician diagnosis. We compared general demographics, reviewed trauma and injury data, and outcomes to assess any differences between patients with VAP and non-VAP patients. Associations were tested with regression models.
Results
After applying all inclusion and exclusion criteria, 90 patients were included in the analysis. Patients with VAP were older (8.5 vs. 5.6 years,
P
= 0.03). Patients with VAP were less likely to have suffered from abusive head trauma (
P
= 0.01). Patients who received continuous neuromuscular blockade or targeted temperature management did not have different frequencies of VAP. CDC-defined VAP was diagnosed in 27% of patients. Number of patients with VAP increased to 41% for physician-diagnosed or clinical VAP. Methicillin-sensitive
Staphylococcus aureus
was the most common isolate grown, followed by
Hemophilus influenza
, with most VAP occurring on days 2–5 of intubation. VAP was not associated with mortality but was associated with worse functional status scale in patients who survived to discharge (8 vs. 7.5,
P
= 0.048). Over a cumulative period of days, nebulized 3% and albuterol were associated with decreased incidence of VAP.
Conclusions
Ventilator-associated pneumonia occurs commonly in children with severe TBI, with rates of 27–41%, depending on CDC-defined VAP or clinical VAP. The discrepancy between clinical VAP and CDC-defined VAP further illustrates the need for a standardized definition for VAP. Although most interventions were not associated with VAP, nebulized 3% saline and albuterol were associated with reduced incidence of VAP; future investigation is needed to determine whether mucolytic agents can decrease the rate of VAP in children with severe TBI.
Full text
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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