Association between Age and Mortality in Pediatric and Adult Acute Respiratory Distress Syndrome.

Rationale: The epidemiology, management, and outcomes of acute respiratory distress syndrome (ARDS) differ between children and adults, with lower mortality rates in children despite comparable severity of hypoxemia. However, the relationship between age and mortality is unclear.Objective: We aimed to define the association between age and mortality in ARDS, hypothesizing that it would be nonlinear.Methods: We performed a retrospective cohort study using data from two pediatric ARDS observational cohorts (n = 1,236), multiple adult ARDS trials (n = 5,547), and an adult observational ARDS cohort (n = 1,079). We aligned all datasets to meet Berlin criteria. We performed unadjusted and adjusted logistic regression using fractional polynomials to assess the potentially nonlinear relationship between age and 90-day mortality, adjusting for sex, PaO2/FiO2, immunosuppressed status, year of study, and observational versus randomized controlled trial, treating each individual study as a fixed effect.Measurements and Main Results: There were 7,862 subjects with median ages of 4 years in the pediatric cohorts, 52 years in the adult trials, and 61 years in the adult observational cohort. Most subjects (43%) had moderate ARDS by Berlin criteria. Ninety-day mortality was 19% in the pediatric cohorts, 33% in the adult trials, and 67% in the adult observational cohort. We found a nonlinear relationship between age and mortality, with mortality risk increasing at an accelerating rate between 11 and 65 years of age, after which mortality risk increased more slowly.Conclusions: There was a nonlinear relationship between age and mortality in pediatric and adult ARDS.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: 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. DESIGN: 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. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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%. CONCLUSIONS: 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.

Zimbabwe's emergency response to COVID-19: Enhancing access and accelerating COVID-19 testing as the first line of defense against the COVID-19 pandemic.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spreads rapidly, causing outbreaks that grow exponentially within a short period before interventions are sought and effectively implemented. Testing is part of the first line of defense against Corona Virus Disease of 2019 (COVID-19), playing a critical role in the early identification and isolation of cases to slow transmission, provision of targeted care to those affected, and protection of health system operations. Laboratory tests for COVID-19 based on nucleic acid amplification techniques were rapidly developed in the early days of the pandemic, but such tests typically require sophisticated laboratory infrastructure and skilled staff. In March 2020, Zimbabwe confirmed its first case of COVID-19; this was followed by an increase in infection rates as the pandemic spread across the country, thus increasing the demand for testing. One national laboratory was set to test all the country's COVID-19 suspect cases, building pressure on human and financial resources. Staff burnout and longer turnaround times of more than 48 h were experienced, and results were released late for clinical relevance. Leveraging on existing PCR testing platforms, including GeneXpert machines, eased the pressure for a short period before facing the stockout of SARs-CoV-2 cartridges for a long time, leading to work overload at a few testing sites contributing to long turnaround times. On September 11, WHO released the interim guidance to use antigen rapid diagnostic test as a diagnostic tool. The Zimbabwe laboratory pillar quickly adopted it and made plans for its implementation. The National Microbiology Reference Laboratory verified the two emergency-listed kits, the Panbio Abbott and the Standard Q, Biosensor, and they met the WHO minimum performance of ≥97% specificity and ≥80% sensitivity. Decentralizing diagnostic testing leveraging existing human resources became a game-changer in improving COVID-19 containment measures. Task shifting through training on Antigen rapid diagnostic tests (Ag-RDT) commenced, and testing was decentralized to all the ten provinces, from 1 central testing laboratory to more than 1,000 testing centers. WhatsApp platforms made it easier for data to be reported from remote areas. Result turnaround times were improved to the same day, and accessibility to testing was enhanced.

Noninvasive Ventilation Exposure Prior to Intubation in Pediatric Hematopoietic Cell Transplant Recipients.

BACKGROUND: Noninvasive ventilation (NIV) has become more studied in immunocompromised patients. However, it has not been studied in hematopoietic cell transplantation (HCT) recipients, who have higher mortality and higher pulmonary complication rates than other immunocompromised patients. This population may be prone to negative effects from this treatment modality. The aim of this study was to determine whether NIV use is associated with worse outcomes in this vulnerable patient population. METHODS: A secondary analysis of a retrospective multi-center database was performed. Twelve pediatric ICUs across the United States enrolled HCT subjects from 2009-2014 that were admitted to the pediatric ICU (PICU) with the diagnosis of acute respiratory failure. Subjects exposed to NIV prior to intubation were compared against those not exposed to NIV. Our primary outcome was all-cause mortality at 90 d; secondary outcomes included ventilator-free days (VFD) at 28 d and development of pediatric ARDS. Multivariable logistic and linear regression models were constructed using variables significant on univariable analysis. RESULTS: Two-hundred eleven subjects were included. Of these, 82 (39%) received NIV prior to intubation. Those that received NIV prior to intubation were older (13 vs 6 y, P < .001) and more commonly diagnosed with respiratory distress (90% vs 74%, P = .004). On multivariable analysis, NIV use prior to intubation was associated with a higher PICU mortality (hazard ratio 1.51 [95% CI 1.18-2.28], P = .02) and fewer VFD at 28 d (ß -3.50 [95% CI -6.09 to 0.91], P = .008). Those with NIV exposure prior to intubation also had higher rates of development of pediatric ARDS (95% vs 78%, P = .001). CONCLUSIONS: In this cohort of children post-HCT, NIV use prior to intubation was associated with worse outcomes. The benefits and risks of NIV in this patient population should be carefully evaluated prior to its use, and careful patient selection is crucial for its optimal utilization.

Pulmonary and Critical Care Considerations for e-Cigarette, or Vaping, Product Use-Associated Lung Injury.

BACKGROUND: In 2019, the United States experienced a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). More than one-half of these patients required admission to an ICU. RESEARCH QUESTION: What are the recent literature and expert opinions which inform the diagnosis and management of patients with critical illness with EVALI? STUDY DESIGN AND METHODS: To synthesize information critical to pulmonary/critical care specialists in the care of patients with EVALI, this study examined data available from patients hospitalized with EVALI between August 2019 and January 2020; reviewed the clinical course and critical care experience with those patients admitted to the ICU; and compiled opinion of national experts. RESULTS: Of the 2,708 patients with confirmed or probable EVALI requiring hospitalization as of January 21, 2020, a total of 1,604 (59.2%) had data available on ICU admission; of these, 705 (44.0%) were admitted to the ICU and are included in this analysis. The majority of ICU patients required respiratory support (88.5%) and in severe cases required intubation (36.1%) or extracorporeal membrane oxygenation (6.7%). The majority (93.0%) of these ICU patients survived to discharge. Review of the clinical course and expert opinion provided insight into: imaging; considerations for bronchoscopy; medical treatment, including use of empiric antibiotics, antiviral agents, and corticosteroids; respiratory support, including considerations for intubation, positioning maneuvers, and extracorporeal membrane oxygenation; and patient outcomes. INTERPRETATION: Review of the clinical course of patients with EVALI requiring ICU admission and compilation of expert opinion provided critical insight into pulmonary/critical care-specific considerations for this patient population. Because a large proportion of patients hospitalized with EVALI required ICU admission, it is important to remain prepared to care for patients with EVALI.

AVONET: morphological, ecological and geographical data for all birds.

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species-level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity.

Respiratory Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Respiratory dysfunction is a component of every organ failure scoring system developed, reflecting the significance of the lung in multiple organ dysfunction syndrome. However, existing systems do not reflect current practice and are not consistently evidence based. OBJECTIVE: We aimed to review the literature to identify the components of respiratory failure associated with outcomes in children, with the purpose of developing an operational and evidence-based definition of respiratory dysfunction. DATA SOURCES: Electronic searches of PubMed and Embase were conducted from 1992 to January 2020 by using a combination of medical subject heading terms and text words to define respiratory dysfunction, critical illness, and outcomes. STUDY SELECTION: We included studies of critically ill children with respiratory dysfunction that evaluated the performance of metrics of respiratory dysfunction and their association with patient-centered outcomes. Studies in adults, studies in premature infants (≤36 weeks' gestational age), animal studies, reviews and commentaries, case series with sample sizes ≤10, and studies not published in English in which we were unable to determine eligibility criteria were excluded. DATA EXTRACTION: Data were abstracted into a standard data extraction form. RESULTS: We provided binary (no or yes) and graded (no, nonsevere, or severe) definitions of respiratory dysfunction, prioritizing oxygenation and respiratory support. The proposed criteria were approved by 82% of members in the first round, with a score of 8 of 9 (interquartile range 7-8). LIMITATIONS: Exclusion of non-English publications, heterogeneity across the pediatric age range, small sample sizes, and incomplete handling of confounders are limitations. CONCLUSIONS: We propose definitions for respiratory dysfunction in critically ill children after an exhaustive literature review.

A Novel Classification of the Inframammary Fold for Use in Primary Breast Augmentation.

BACKGROUND: Previous aesthetic breast surgery algorithms have not addressed the importance of evaluating the native inframammary fold before primary breast augmentation. In the authors' experience, assessment of native inframammary fold anatomy significantly impacts surgical planning and technique. Failure to adequately evaluate and manage the inframammary fold leads to many of the common problems of the lower pole, including double-bubble deformity. METHODS: The authors assessed the inframammary fold preoperatively in 2192 consecutive patients undergoing primary breast augmentation between June of 2014 and December of 2018. A novel classification of inframammary fold morphology was devised based on review of standardized preoperative photographs. Outcome assessment was performed postoperatively at 3-month intervals. RESULTS: The authors identified four clear inframammary fold subtypes based on their clinical appearance, ranging from the nonexistent type F0 to the well-formed and fixed type F3. The key outcome measure examined was the presence of double-bubble deformity postoperatively. There were three total cases of double-bubble deformity identified in our cohort (<1 percent of patients). All cases of double-bubble deformity occurred in patients with a type 3 fold. CONCLUSIONS: The inframammary fold defines the inferior boundary of the lower pole of the breast and is a critical landmark to the aesthetic breast surgeon. The authors describe a unique and simple inframammary fold classification system that assists in selection of the appropriate approach to the inframammary fold in addition to implant dimensional planning. The authors have found that this system-in particular, the identification of the type F3 inframammary fold-has minimized the risk of inframammary fold-associated complications in over 2000 cases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Variation in winter site fidelity within and among individuals influences movement behavior in a partially migratory ungulate.

Many animals migrate to take advantage of temporal and spatial variability in resources. These benefits are offset with costs like increased energetic expenditure and travel through unfamiliar areas. Differences in the cost-benefit ratio for individuals may lead to partial migration with one portion of a population migrating while another does not. We investigated migration dynamics and winter site fidelity for a long-distance partial migrant, barren ground caribou (Rangifer tarandus granti) of the Teshekpuk Caribou Herd in northern Alaska. We used GPS telemetry for 76 female caribou over 164 annual movement trajectories to identify timing and location of migration and winter use, proportion of migrants, and fidelity to different herd wintering areas. We found within-individual variation in movement behavior and wintering area use by the Teshekpuk Caribou Herd, adding caribou to the growing list of ungulates that can exhibit migratory plasticity. Using a first passage time-net squared displacement approach, we classified 78.7% of annual movement paths as migration, 11.6% as residency, and 9.8% as another strategy. Timing and distance of migration varied by season and wintering area. Duration of migration was longer for fall migration than for spring, which may relate to the latter featuring more directed movement. Caribou utilized four wintering areas, with multiple areas used each year. This variation occurred not just among different individuals, but state sequence analyses indicated low fidelity of individuals to wintering areas among years. Variability in movement behavior can have fitness consequences. As caribou face the pressures of a rapidly warming Arctic and ongoing human development and activities, further research is needed to investigate what factors influence this diversity of behaviors in Alaska and across the circumpolar Arctic.

Early Cumulative Fluid Balance and Outcomes in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients With Acute Respiratory Failure: A Multicenter Study.

OBJECTIVES: To evaluate the associations between early cumulative fluid balance (CFB) and outcomes among critically ill pediatric allogeneic hematopoietic cell transplant (HCT) recipients with acute respiratory failure, and determine if these associations vary by treatment with renal replacement therapy (RRT). METHODS: We performed a secondary analysis of a multicenter retrospective cohort of patients (1mo - 21yrs) post-allogeneic HCT with acute respiratory failure treated with invasive mechanical ventilation (IMV) from 2009 to 2014. Fluid intake and output were measured daily for the first week of IMV (day 0 = day of intubation). The exposure, day 3 CFB (CFB from day 0 through day 3 of IMV), was calculated using the equation [Fluid in - Fluid out] (liters)/[PICU admission weight](kg)*100. We measured the association between day 3 CFB and PICU mortality with logistic regression, and the rate of extubation at 28 and 60 days with competing risk regression (PICU mortality = competing risk). RESULTS: 198 patients were included in the study. Mean % CFB for the cohort was positive on day 0 of IMV, and increased further on days 1-7 of IMV. For each 1% increase in day 3 CFB, the odds of PICU mortality were 3% higher (adjusted odds ratio (aOR) 1.03, 95% CI 1.00-1.07), and the rate of extubation was 3% lower at 28 days (adjusted subdistribution hazard ratio (aSHR) 0.97, 95% CI 0.95-0.98) and 3% lower at 60 days (aSHR 0.97, 95% CI 0.95-0.98). When day 3 CFB was dichotomized, 161 (81%) had positive and 37 (19%) had negative day 3 CFB. Positive day 3 CFB was associated with higher PICU mortality (aOR 3.42, 95% CI 1.48-7.87) and a lower rate of extubation at 28 days (aSHR 0.30, 95% CI 0.18-0.48) and 60 days (aSHR 0.30, 95% 0.19-0.48). On stratified analysis, the association between positive day 3 CFB and PICU mortality was significantly stronger in those not treated with RRT (no RRT: aOR 9.11, 95% CI 2.29-36.22; RRT: aOR 1.40, 95% CI 0.42-4.74). CONCLUSIONS: Among critically ill pediatric allogeneic HCT recipients with acute respiratory failure, positive and increasing early CFB were independently associated with adverse outcomes.

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.

BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).

Tracheal pressure generated by high-flow nasal cannula in 3D-Printed pediatric airway models.

OBJECTIVE: Heated and humidified high flow nasal cannula (HFNC) is an increasingly used form of noninvasive respiratory support with the potential to generate significant tracheal pressure. The aim of this study was to quantify the pressure generated by HFNC within the trachea in anatomically correct, pediatric airway models. METHODS: 3D-printed upper airway models of a preterm neonate, term neonate, toddler, and small child were connected to a spontaneous breathing computerized lung model at age-appropriate ventilation settings. Two commercially available HFNC systems were applied to each airway model at increasing flows and the positive end-expiratory pressure (PEEP) was recorded at the level of the trachea. RESULTS: Increasing HFNC flow produced a quadratically curved increase in tracheal pressure in closed-mouth models. The maximum flow tested in each model generated a tracheal pressure of 7 cm H2O in the preterm neonate, 10 cm H2O in the term neonate, 9 cm H2O in the toddler, and 24 cm H2O in the small child. Tracheal pressure decreased by at least 50% in open-mouth models. CONCLUSIONS: HFNC was found to demonstrate a predictable flow-pressure relationship that achieved sufficient distending pressure to consider treatment of pediatric obstructive sleep apnea and tracheomalacia in the closed-mouth models tested.

Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19.

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.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).

Prognostic relevance and inter-observer reliability of chest-imaging in pediatric ARDS: a pediatric acute respiratory distress incidence and epidemiology (PARDIE) study.

PURPOSE: Definitions of acute respiratory distress syndrome (ARDS) include radiographic criteria, but there are concerns about reliability and prognostic relevance. This study aimed to evaluate the independent relationship between chest imaging and mortality and examine the inter-rater variability of interpretations of chest radiographs (CXR) in pediatric ARDS (PARDS). METHODS: Prospective, international observational study in children meeting Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria for PARDS, which requires new infiltrate(s) consistent with pulmonary parenchymal disease, without mandating bilateral infiltrates. Mortality analysis focused on the entire cohort, whereas inter-observer variability used a subset of patients with blinded, simultaneous interpretation of CXRs by intensivists and radiologists. RESULTS: Bilateral infiltrates and four quadrants of alveolar consolidation were associated with mortality on a univariable basis, using CXRs from 708 patients with PARDS. For patients on either invasive (IMV) or non-invasive ventilation (NIV) with PaO2/FiO2 (PF) ratios (or SpO2/FiO2 (SF) ratio equivalent) > 100, neither bilateral infiltrates (OR 1.3 (95% CI 0.68, 2.5), p = 0.43), nor 4 quadrants of alveolar consolidation (OR 1.6 (0.85, 3), p = 0.14) were associated with mortality. For patients with PF ≤ 100, bilateral infiltrates (OR 3.6 (1.4, 9.4), p = 0.01) and four quadrants of consolidation (OR 2.0 (1.14, 3.5), p = 0.02) were associated with higher mortality. A subset of 702 CXRs from 233 patients had simultaneous interpretations. Interobserver agreement for bilateral infiltrates and quadrants was "slight" (kappa 0.31 and 0.33). Subgroup analysis showed agreement did not differ when stratified by PARDS severity but was slightly higher for children with chronic respiratory support (kappa 0.62), NIV at PARDS diagnosis (kappa 0.53), age > 10 years (kappa 0.43) and fluid balance > 40 ml/kg (kappa 0.48). CONCLUSION: Bilateral infiltrates and quadrants of alveolar consolidation are associated with mortality only for those with PF ratio ≤ 100, although there is high- inter-rater variability in these chest-x ray parameters.

Respiratory pathogens associated with intubated pediatric patients following hematopoietic cell transplant.

BACKGROUND: We describe organisms found in the respiratory tracts of a multicenter cohort of pediatric hematopoietic cell transplant (HCT) recipients with respiratory failure. METHODS: Twelve centers contributed up to 25 pediatric allogeneic HCT recipients requiring mechanical ventilation for respiratory failure to a retrospective database. Positive respiratory pathogens and method of obtaining sample were recorded. Outcomes were assessed using Mann-Whitney U test or chi-squared analysis. RESULTS: Of the 222 patients in the database, ages 1 month through 21 years, 34.6% had a positive respiratory culture. 105 pathogens were identified in 77 patients; of those, 48.6% were viral, 34.3% bacterial, 16.2% fungal, and 1% parasitic. PICU mortality with a respiratory pathogen was 68.8% compared to 54.9% for those without a respiratory pathogen (P = .045). Those with a positive respiratory pathogen had longer PICU length of stay, 20 days (IQR 14.0, 36.8) vs 15 (IQR 6.5, 32.0), P = .002, and a longer course of mechanical ventilation, 17 days (IQR 10, 29.5) vs 8 (3, 17), P < .0001. Method of pathogen identification, type of pathogen, and the presence of multiple pathogens were not associated with changes in PICU outcomes. CONCLUSIONS: In this multicenter retrospective cohort of intubated pediatric post-HCT patients, there was high variability in the respiratory pathogens identified. Type of pathogen and method of detection did not affect PICU mortality. The presence of any organism leads to increased PICU mortality, longer PICU stay, and increased duration of mechanical ventilation suggesting that early detection and treatment of pathogens may be beneficial in this population.

Predicting Mortality in Children With Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

OBJECTIVES: Pediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome. DESIGN: Leveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia. SETTING: The derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia. PATIENTS: There were 624 and 640 subjects in the derivation and validation cohorts, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve ≥ 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve ≥ 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts. CONCLUSIONS: We describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.

Early Use of Adjunctive Therapies for Pediatric Acute Respiratory Distress Syndrome: A PARDIE Study.

Rationale: Few data exist to guide early adjunctive therapy use in pediatric acute respiratory distress syndrome (PARDS).Objectives: To describe contemporary use of adjunctive therapies for early PARDS as a framework for future investigations.Methods: This was a preplanned substudy of a prospective, international, cross-sectional observational study of children with PARDS from 100 centers over 10 study weeks.Measurements and Main Results: We investigated six adjunctive therapies for PARDS: continuous neuromuscular blockade, corticosteroids, inhaled nitric oxide (iNO), prone positioning, high-frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation. Almost half (45%) of children with PARDS received at least one therapy. Variability was noted in the median starting oxygenation index of each therapy; corticosteroids started at the lowest oxygenation index (13.0; interquartile range, 7.6-22.0) and HFOV at the highest (25.7; interquartile range, 16.7-37.3). Continuous neuromuscular blockade was the most common, used in 31%, followed by iNO (13%), corticosteroids (10%), prone positioning (10%), HFOV (9%), and extracorporeal membrane oxygenation (3%). Steroids, iNO, and HFOV were associated with comorbidities. Prone positioning and HFOV were more common in middle-income countries and less frequently used in North America. The use of multiple ancillary therapies increased over the first 3 days of PARDS, but there was not an easily identifiable pattern of combination or order of use.Conclusions: The contemporary description of prevalence, combinations of therapies, and oxygenation threshold for which the therapies are applied is important for design of future studies. Region of the world, income, and comorbidities influence adjunctive therapy use and are important variables to include in PARDS investigations.

Acute Respiratory Distress Syndrome Following Pediatric Trauma: Application of Pediatric Acute Lung Injury Consensus Conference Criteria.

OBJECTIVES: To assess the incidence, severity, and outcomes of pediatric acute respiratory distress syndrome following trauma using Pediatric Acute Lung Injury Consensus Conference criteria. DESIGN: Retrospective cohort study. SETTING: Level 1 pediatric trauma center. PATIENTS: Trauma patients less than or equal to 17 years admitted to the ICU from 2009 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We queried electronic health records to identify patients meeting pediatric acute respiratory distress syndrome oxygenation criteria for greater than or equal to 6 hours and determined whether patients met complete pediatric acute respiratory distress syndrome criteria via chart review. We estimated associations between pediatric acute respiratory distress syndrome and outcome using generalized linear Poisson regression adjusted for age, injury mechanism, Injury Severity Score, and serious brain and chest injuries. Of 2,470 critically injured children, 103 (4.2%) met pediatric acute respiratory distress syndrome criteria. Mortality was 34.0% among pediatric acute respiratory distress syndrome patients versus 1.7% among patients without pediatric acute respiratory distress syndrome (adjusted relative risk, 3.7; 95% CI, 2.0-6.9). Mortality was 50.0% for severe pediatric acute respiratory distress syndrome at onset, 33.3% for moderate, and 30.5% for mild. Cause of death was neurologic in 60.0% and multiple organ failure in 34.3% of pediatric acute respiratory distress syndrome nonsurvivors versus neurologic in 85.4% of nonsurvivors without pediatric acute respiratory distress syndrome (p = 0.001). Among survivors, 77.1% of pediatric acute respiratory distress syndrome patients had functional disability at discharge versus 30.7% of patients without pediatric acute respiratory distress syndrome patients (p < 0.001), and only 17.5% of pediatric acute respiratory distress syndrome patients discharged home without ongoing care versus 86.4% of patients without pediatric acute respiratory distress syndrome (adjusted relative risk, 1.5; 1.1-2.1). CONCLUSIONS: Incidence and mortality associated with pediatric acute respiratory distress syndrome following traumatic injury are substantially higher than previously recognized, and pediatric acute respiratory distress syndrome development is associated with high risk of poor outcome even after adjustment for underlying injury type and severity.