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ObjectiveTo identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic.MethodsAcross 25 U.S. Overcoming COVID-19 Network hospitals, we conducted a prospective cohort study of patients

BackgroundInfluenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.MethodsWe measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q

The antibody response to the SARS-CoV-2 Omicron variant is not well studied in children. Here, the authors provide an age-stratified analysis of SARS-CoV-2 neutralizing capacity of sera from children with acute or convalescent COVID-19 as well as children with multisystem inflammatory syndrome.

Background Cardiac complications related to COVID‐19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID‐19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged 1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 [range, 10.4–17.4] versus 10.0 [range, 5.4–14.8] years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID‐19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.

Background: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. Methods: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians)

Background:. Influenza virus is a major cause of acute hypoxemic respiratory failure. Early identification of patients who will suffer severe complications can help stratify patients for clinical trials and plan for resource use in case of pandemic. Objective:. We aimed to identify which clinical variables best predict prolonged acute hypoxemic respiratory failure in influenza-infected critically ill children. Acute hypoxemic respiratory failure was defined using hypoxemia cutoffs from international consensus definitions of acute respiratory distress syndrome in patients with ventilatory support. Prolonged acute hypoxemic respiratory failure was defined by acute hypoxemic respiratory failure criteria still present at PICU day 7. Derivation Cohort:. In this prospective multicenter study across 34 PICUs from November 2009 to April 2018, we included children (< 18 yr) without comorbid risk factors for severe disease. Validation Cohort:. We used a Monte Carlo cross validation method with N2 random train-test splits at a 70–30% proportion per model. Prediction Model:. Using clinical data at admission (day 1) and closest to 8 am on PICU day 2, we calculated the area under the receiver operating characteristic curve using random forests machine learning algorithms and logistic regression. Results:. We included 258 children (median age = 6.5 yr) and 11 (4.2%) died. By day 2, 65% (n = 165) had acute hypoxemic respiratory failure dropping to 26% (n = 67) with prolonged acute hypoxemic respiratory failure by day 7. Those with prolonged acute hypoxemic respiratory failure had a longer ICU stay (16.5 vs 4.0 d; p < 0.001) and higher mortality (13.4% vs 1.0%). A multivariable model using random forests with 10 admission and eight day 2 variables performed best (0.93 area under the receiver operating characteristic curve; 95 CI%: 0.90–0.95) where respiratory rate, Fio2, and pH on day 2 were the most important factors. Conclusions:. In this prospective multicentric study, most children with influenza virus–related respiratory failure with prolonged acute hypoxemic respiratory failure can be identified early in their hospital course applying machine learning onto routine clinical data. Further validation is needed prior to bedside implementation.

Mucosal immunity plays an important role in the control of viral respiratory infections like SARS-CoV-2. While systemic immune responses against the SARS-2-CoV-2 have been studied in children, there is no information on mucosal antibody response, especially in the lower respiratory tract of children coronavirus disease 2019 (COVID-19) and post-infectious multisystem inflammatory syndrome in children (MIS-C) against emerging SARS-CoV-2 variants. Therefore, we evaluated neutralizing antibody responses in paired plasma and endotracheal aspirates of pediatric severe, acute COVID-19 or MIS-C patients against SARS-CoV-2 WA1/2020, as well as against variants of concern (VOCs). Neutralizing antibody responses against the SARS-CoV-2 WA1/2020 strain in pediatric plasma were 2-fold or 35-fold higher compared with the matched endotracheal aspirate in COVID-19 or MIS-C patients, respectively. In contrast to plasma, neutralizing antibody responses against the VOCs and variants of interest (VOIs) in endotracheal aspirates were lower, with only one endotracheal aspirate demonstrating neutralizing titers against the Iota, Kappa, Beta, Gamma, and Omicron variants. In conclusion, our findings suggest that children and adolescents with severe COVID-19 or MIS-C have weak mucosal neutralizing antibodies in the trachea against circulating SARS-CoV-2 Omicron and other VOCs, which may have implications for recovery and for re-infection with emerging SARS-CoV-2 variants.

Background: Mannose-binding lectin (MBL) is an innate immune protein with strong biologic plausibility for protecting against influenza virus-related sepsis and bacterial co-infection. In an autopsy cohort of 105 influenza-infected young people, carriage of the deleterious MBL gene MBL2_Gly54Asp(“B”) mutation was identified in 5 of 8 individuals that died from influenza-methicillin-resistant Staphylococcus aureus (MRSA) co-infection. We evaluated MBL2 variants known to influence MBL levels with pediatric influenza-related critical illness susceptibility and/or severity including with bacterial co-infections.Methods: We enrolled children and adolescents with laboratory-confirmed influenza infection across 38 pediatric intensive care units from November 2008 to June 2016. We sequenced MBL2 “low-producer” variants rs11003125(“H/L”), rs7096206(“Y/X”), rs1800450Gly54Asp(“B”), rs1800451Gly57Glu(“C”), rs5030737Arg52Cys(“D”) in patients and biologic parents. We measured serum levels and compared complement activity in low-producing homozygotes (“B/B,” “C/C”) to HYA/HYA controls. We used a population control of 1,142 healthy children and also analyzed family trios (PBAT/HBAT) to evaluate disease susceptibility, and nested case-control analyses to evaluate severity.Results: We genotyped 420 patients with confirmed influenza-related sepsis: 159 (38%) had acute lung injury (ALI), 165 (39%) septic shock, and 30 (7%) died. Although bacterial co-infection was diagnosed in 133 patients (32%), only MRSA co-infection (n = 33, 8% overall) was associated with death (p < 0.0001), present in 11 of 30 children that died (37%). MBL2 variants predicted serum levels and complement activation as expected. We found no association between influenza-related critical illness susceptibility and MBL2 variants using family trios (633 biologic parents) or compared to population controls. MBL2 variants were not associated with admission illness severity, septic shock, ALI, or bacterial co-infection diagnosis. Carriage of low-MBL producing MBL2 variants was not a risk factor for mortality, but children that died did have higher carriage of one or more B alleles (OR 2.3; p = 0.007), including 7 of 11 with influenza MRSA-related death (vs. 2 of 22 survivors: OR 14.5, p = 0.0002).Conclusions:MBL2 variants that decrease MBL levels were not associated with susceptibility to pediatric influenza-related critical illness or with multiple measures of critical illness severity. We confirmed a prior report of higher B allele carriage in a relatively small number of young individuals with influenza-MRSA associated death.

RationaleEffective immunomodulatory therapies for children with life-threatening “cytokine storm” triggered by acute influenza infection are lacking. Understanding the immune profiles of children progressing to severe lung injury and/or septic shock could provide insight into pathogenesis.ObjectivesTo compare the endotracheal and serum cytokine profiles of children with influenza-related critical illness and to identify their associations with severe influenza-associated complications.MethodsChildren with influenza-related critical illness were enrolled across 32 hospitals in development (N = 171) and validation (N = 73) cohorts (December 2008 through May 2016). Concentrations of 42 cytokines were measured in serum and endotracheal samples and clustered into modules of covarying cytokines. Relative concentrations of cytokines and cytokine modules were tested for associations with acute lung injury (ALI), shock requiring vasopressors, and death/ECMO.Measurements and main resultsModules of covarying cytokines were more significantly associated with disease severity than individual cytokines. In the development cohort, increased levels of a serum module containing IL6, IL8, IL10, IP10, GCSF, MCP1, and MIP1α [shock odds ratio (OR) = 3.37, family-wise error rate (FWER) p

Background: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI., Methods: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.S. PICUs from October through December 2022. We assigned CPS-Ped (0=discharged home at respiratory baseline to 8=death) at admission, days 2-7,10, and 14. We identified predictors of clinical improvement (CPS-Ped≤2 or 3-point decrease) by day 7 using multivariable log-binomial regression models and estimated the sample size (80% power) to detect 15% between-group clinical improvement with CPS-Ped versus hospital length of stay (LOS)., Results: Of 585 hospitalized infants, 138 (23.6%) received invasive mechanical ventilation (IMV). Of the 49 (8.4%) infants whose CPS-Ped score worsened by 2 points after admission, one died. Failure to clinically improve by day 7 occurred in 205 (35%) infants and was associated with age <3 months, prematurity, underlying respiratory condition, and IMV in the first 24 hours in the multivariable analysis. The estimated sample size per arm required for detecting a 15% clinical improvement in a potential study was 584 using CPS-Ped clinical improvement versus 2,031 for hospital LOS., Conclusions: CPS-Ped can be used to capture a range of disease severity and track clinical improvement in infants who develop RSV-related critical illness and could be useful for evaluating therapeutic interventions for RSV., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference., Data Sources: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children., Study Selection: The management of ECMO anticoagulation for critically ill children., Data Extraction: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts., Data Synthesis: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements., Conclusions: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials., Competing Interests: Drs. Alexander’s and Muszynski’s institutions received funding from the National Institutes of Health (NIH). Drs. Alexander, Bembea, Himebauch, Barbaro, and Muszynski received support for article research from the NIH. Drs. Alexander’s and Bembea’s institutions received funding from the Extracorporeal Life Support Organization (ELSO). Dr. Alexander’s institution received funding from Novartis (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF [PANORAMA-HF]). Dr. Alexander disclosed that she is Treasurer of the Board of Directors of ELSO, past Co-Chair of Pediatric Extracorporeal Membrane Oxygenation (Pedi-ECMO). Dr. Bembea’s institution received funding from the National Institute of Neurologic Disorders and Stroke and a Grifols Investigator Sponsored Research Grant. Dr. Cheifetz received funding from UptoDate. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation (ECMO) Concepts, Medtronic, Entegrion, and Hemocue. Drs. Dalton, Ozment, Barbaro, Almond, Brandão, Baumann Kreuziger, Paden, and Ryerson disclosed the off-label product use of pediatric ECMO-related medications for anticoagulation. Dr. Himebauch’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI) (K23HL153759). Drs. Karam’s and Nellis’s institutions received funding from the NHBLI (R34HL159119). Dr. Ozment received funding from Kaufman & Canoles, Social Cascade, and Wiseman Ashworth Law Group. Dr. Steiner’s institution received funding from the Department of Defense (DoD); she received funding from Medtronic and Octapharma; she disclosed that she is a Pumps for Kids, Infantsand Neonates (PumpKIN) trial Data Safety and Monitoring Board member. Dr. Alexander’s and Thiagarajan’s institution received funding from the DoD Clinical Trial Award for Trial of Indication-Based Transfusion of RBCs in ECMO trial (W81XWH2210301). Dr. Thiagarajan received funding from Society of Critical Care Medicine and ELSO. Dr. Zantek disclosed that she is a Board Member and Vice President of the North American Specialized Coagulation Laboratory Association and Board Member of the American Society for Apheresis, the External Quality Assurance in Thrombosis and Hemostasis, and Blood Network subgroup of Pediatric Acute Lung Injury and Sepsis Investigators groups; she disclosed that her spouse is an employee of Boston Scientific and owns stock in Endo International PLC. Dr. Barbaro’s institution received funding from the NHLBI (R01 HL153519 and K12 HL138039); he disclosed that he is ELSO Board of Directors and Pedi-ECMO Co-Chair. Dr. Emani received funding from Chiesi Pharma. Dr. Hyslop disclosed he is Co-Chair of ELSO Registry Database Development Committee and Coordinator Liaison to ELSO Steering Committee. Dr. Baumann Kreuziger received funding from the Health Resources and Services Administration Vaccine Injury Compensation Program. Dr. Paden disclosed that he is past president and board member of ELSO. Dr. Ryerson received an honorarium from Instrumentation Laboratory for consultation work. Dr. Sloan commenced employment with CSL Behring after the consensus process was complete. Dr. Patregnani received funding from Mallinckrodt; he discloses consultation payments from MNK pharmaceuticals and Pfizer. The Executive Committee (Drs. Alexander, Muszynski, Bembea, Cheifetz, Steiner, and Barbaro) served as arbitrators for conflict-of-interest management. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Importance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide., Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission., Design, Setting, and Participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection., Exposure: Respiratory syncytial virus., Main Outcomes and Measures: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity., Results: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days., Conclusions and Relevance: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

Background: In a 2020 pilot case-control study using medical records, we reported that non-Hispanic Black children were more likely to develop multisystem inflammatory syndrome in children (MIS-C) after adjustment for sociodemographic factors and underlying medical conditions. Using structured interviews, we investigated patient, household, and community factors underlying MIS-C likelihood., Methods: MIS-C case patients hospitalized in 2021 across 14 US pediatric hospitals were matched by age and site to outpatient controls testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 3 months of the admission date. Caregiver interviews queried race/ethnicity, medical history, and household and potential community exposures 1 month before MIS-C hospitalization (case-patients) or after SARS-CoV-2 infection (controls). We calculated adjusted odds ratios (aOR) using mixed-effects multivariable logistic regression., Results: Among 275 case patients and 496 controls, race/ethnicity, social vulnerability and patient or family history of autoimmune/rheumatologic disease were not associated with MIS-C. In previously healthy children, MIS-C was associated with a history of hospitalization for an infection [aOR: 4.8; 95% confidence interval (CI): 2.1-11.0]. Household crowding (aOR: 1.7; 95% CI: 1.2-2.6), large event attendance (aOR: 1.7; 95% CI: 1.3-2.1), school attendance with limited masking (aOR: 2.6; 95% CI: 1.1-6.6), public transit use (aOR: 1.8; 95% CI: 1.4-2.4) and co-resident testing positive for SARS-CoV-2 (aOR: 2.2; 95% CI: 1.3-3.7) were associated with increased MIS-C likelihood, with risk increasing with the number of these factors., Conclusions: From caregiver interviews, we clarify household and community exposures associated with MIS-C; however, we did not confirm prior associations between sociodemographic factors and MIS-C., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Plasma biomarkers associated with respiratory failure (RF) following hematopoietic cell transplantation (HCT) have not been identified. Therefore, we aimed to validate early (7 and 14 days post-HCT) risk biomarkers for RF. Using tandem mass spectrometry, we compared plasma obtained at day 14 post-HCT from 15 patients with RF and 15 patients without RF. Six candidate proteins, from this discovery cohort or identified in the literature, were measured by enzyme-linked immunosorbent assay in day-7 and day-14 post-HCT samples from the training (n = 213) and validation (n = 119) cohorts. Cox proportional-hazard analyses with biomarkers dichotomized by Youden's index, as well as landmark analyses to determine the association between biomarkers and RF, were performed. Of the 6 markers, Stimulation-2 (ST2), WAP 4-disulfide core domain protein 2 (WFDC2), interleukin-6 (IL-6), and tumor necrosis factor receptor 1 (TNFR1), measured at day 14 post-HCT, had the most significant association with an increased risk for RF in the training cohort (ST2: hazard ratio [HR], 4.5, P = .004; WFDC2: HR, 4.2, P = .010; IL-6: HR, 6.9, P < .001; and TFNR1: HR, 6.1, P < .001) and in the validation cohort (ST2: HR, 23.2, P = .013; WFDC2: HR, 18.2, P = .019; IL-6: HR, 12.2, P = .014; and TFNR1: HR, 16.1, P = .001) after adjusting for the conditioning regimen. Using cause-specific landmark analyses, including days 7 and 14, high plasma levels of ST2, WFDC2, IL-6, and TNFR1 were associated with an increased HR for RF in the training and validation cohorts. These biomarkers were also predictive of mortality from RF. ST2, WFDC2, IL-6 and TNFR1 levels measured early posttransplantation improve risk stratification for RF and its related mortality., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Ongoing measures to improve pediatric continuous kidney replacement therapy (CKRT) have lowered mortality rates, shifting the focus to survivor functional status. While septic acute kidney injury generates new morbidity in pediatric critically ill patients, acquired morbidities and functional status of CKRT population are unknown. We predicted that CKRT survivors are at risk for new morbidity and would have worse functional status at PICU discharge compared to baseline, and aimed to describe associated factors., Methods: Retrospective cohort study over 24 months of CKRT patients surviving to PICU discharge in a quaternary children's hospital. Functional outcome was determined by Functional Status Scale (FSS)., Results: FSS scores were higher at PICU and hospital discharge compared to baseline. Of 45 CKRT survivors, 31 (69%) had worse FSS score at PICU discharge and 51% had new morbidity (≥3 increase in FSS); majority qualified as moderate to severe disability (FSS ≥10). Four patients (9%) had new tracheostomy, 3 (7%) were ventilator dependent, and 10 (22%) were dialysis dependent. Most (23/45, 51%) required outpatient rehabilitation. Cumulative days on sedation, controlled for illness severity, were independently associated with worse FSS at PICU discharge (aOR 25.18 (3.73, 169.92)). In adjusted analyses, duration of sedation was associated with new morbidity, while neurologic comorbidity, percent fluid overload at CKRT start, and nonrenal comorbidity were associated with moderate to severe disability at PICU discharge when controlled for baseline FSS., Conclusions: CKRT survivors, with new morbidity and worse functional outcomes at PICU discharge, are a newly described vulnerable population requiring targeted follow-up. Deliberate decrease of sedation exposure in patients with decreased clearance due to organ dysfunction needs to be studied as a modifiable risk factor., (© 2021. IPNA.)

Though commonly used for adjustment of risk, severity of illness and mortality risk prediction scores, based on the first 24 h of intensive care unit (ICU) admission, have not been validated in the pediatric extracorporeal membrane oxygenation (ECMO) population. We aimed to determine the association of Pediatric Index of Mortality 2 (PIM2), Pediatric Risk of Mortality Score III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores with mortality in pediatric patients on ECMO. This was a retrospective cohort study of children ≤18 years of age included in the Pediatric ECMO Outcomes Registry (PEDECOR) from 2014 to 2018. Logistic regression and Receiver Operating Characteristics (ROC) curves were used to calculate the area under the curve (AUC) to evaluate association of mortality with the scores. Of the 655 cases, 289 (44.1%) did not survive until hospital discharge. AUCs for PIM2, PRISM III, and PELOD predicting mortality were 0.52, 0.52, and 0.51 respectively. PIM2, PRISM III, and PELOD scores are not associated with odds of mortality for pediatric patients receiving ECMO. These scores for a general pediatric ICU population should not be used for prognostication or risk stratification of a select population such as ECMO patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pinto, Guffey, Loftis, Bembea, Spinella and Hanson.)

Background: It is important to document the domains surrounding end-of-life (EOL) care in the electronic health record (EHR). No pediatric navigator exists for these purposes., Measures: Medical charts were reviewed for documentation surrounding code status and care at the time of death from January 2017 to June 2019., Intervention: Creation of a navigator in the EHR to consolidate advance care planning documents, code status orders and notes and EOL flowsheets., Outcomes: After implementing the navigator, 96% code status changes had supporting documentation, an increase of 35%. The percentage of deaths supported by a psychosocial team (social worker, chaplain and certified child life specialist) increased by 25%. Post-mortem documentation became electronic. Patient level metrics began to be electronically collected., Conclusions/lessons Learned: Little has been published regarding use of the EHR to consolidate EOL documentation in pediatrics. Development of a systematic approach to documentation is critical to providing EOL care and standardizing care delivered., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Assessing outcomes after pediatric critical illness is imperative to evaluate practice and improve recovery of patients and their families. We conducted a scoping review of the literature to identify domains and instruments previously used to evaluate these outcomes., Design: Scoping review., Setting: We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials Registry for studies evaluating pediatric critical care survivors or their families published between 1970 and 2017. We identified articles using key words related to pediatric critical illness and outcome domains. We excluded articles if the majority of patients were greater than 18 years old or less than 1 month old, mortality was the sole outcome, or only instrument psychometrics or procedural outcomes were reported. We used dual review for article selection and data extraction and categorized outcomes by domain (overall health, emotional, physical, cognitive, health-related quality of life, social, family)., Subjects: Manuscripts evaluating outcomes after pediatric critical illness., Interventions: None., Measurements and Main Results: Of 60,349 citations, 407 articles met inclusion criteria; 87% were published after 2000. Study designs included observational (85%), interventional (7%), qualitative (5%), and mixed methods (3%). Populations most frequently evaluated were traumatic brain injury (n = 96), general pediatric critical illness (n = 87), and congenital heart disease (n = 72). Family members were evaluated in 74 studies (18%). Studies used a median of 2 instruments (interquartile range 1-4 instruments) and evaluated a median of 2 domains (interquartile range 2-3 domains). Social (n = 223), cognitive (n = 183), and overall health (n = 161) domains were most frequently studied. Across studies, 366 unique instruments were used, most frequently the Wechsler and Glasgow Outcome Scales. Individual domains were evaluated using a median of 77 instruments (interquartile range 39-87 instruments)., Conclusions: A comprehensive, generalizable understanding of outcomes after pediatric critical illness is limited by heterogeneity in methodology, populations, domains, and instruments. Developing assessment standards may improve understanding of postdischarge outcomes and support development of interventions after pediatric critical illness.

Background: Acute flaccid myelitis is characterized by acute-onset flaccid limb weakness with predominantly gray matter lesions in the spinal cord spanning one or more segments. Rates of full recovery are poor, and there is no standard treatment or definitive cause., Methods: This is a retrospective review of children diagnosed with acute flaccid myelitis in Texas during 2016. Patients were identified through a Texas collaborative of six hospitals in four major metropolitan areas. Data abstraction included health history, illness presentation, medical treatments, laboratory studies, imaging data, recovery, and ability to perform activities of daily living up to approximately two years from illness onset., Results: Among all sites, 21 patients met inclusion criteria. Treatments varied with the most common being intravenous immunoglobulin, high-dose methylprednisolone, and plasmapheresis. No differences were seen in response to medical treatments. A potential etiology was found in 12 (57%) cases, including four with enterovirus D68. Five cases recovered fully. Of the 16 patients without full recovery, abilities ranged from (1) able to perform all activities of daily living for age independently (n = 5), (2) mild deficits (n = 5), and (3) substantial reliance on caregivers for activities of daily living (n = 6)., Conclusion: Many reports describe symptoms and outcomes of acute flaccid myelitis, but limited data are available on long-term functional outcomes. We were unable to make a strong case for any single cause or treatment modality. Fortunately, the majority of patients (15, 71%) were able to perform activities of daily living with complete independence or only mild deficits., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The number of children receiving extracorporeal membrane oxygenation (ECMO) has increased substantially, and includes a growing population of children with complex underlying conditions who previously may not have been considered ECMO candidates. However, it remains unclear to what extent the underlying disease impacts the risk of death in these patients, particularly related to malignancy, bone marrow transplantation, complex congenital heart disease (CHD), or chromosomal abnormalities. A retrospective study was performed using the Pediatric Health Information System database of all children placed on ECMO more than a 10 year period between 2004 and 2013. Patients with diagnoses of bone marrow transplant, leukemia, lymphoma, neutropenia, immune system abnormalities, genetic abnormalities, neoplastic disorders, and complex CHD were selected as "high risk" and their outcomes were compared with overall outcomes. Extracorporeal membrane oxygenation was used in 9,194 children. Two thousand two hundred (24%) were identified as high risk. Bone marrow transplant (81% mortality; odds ratio [OR] 3.49), leukemia (66% mortality; OR 1.88), and neutropenia (58% mortality; OR 1.62) were associated with higher odds of mortality. Complex CHD (52% mortality) and genetic syndromes (48%) were not associated with higher mortality. These findings are pertinent for clinicians and families when considering ECMO candidacy in these children.

Objectives: 1) Describe the prevalence of acquired von Willebrand syndrome in pediatric patients undergoing extracorporeal membrane oxygenation deemed to be at increased risk for the disease in our institution, 2) discuss the challenges of testing for acquired von Willebrand syndrome diagnosis, 3) describe the characteristics of the patient population found to have acquired von Willebrand syndrome and their outcomes, and 4) discuss the potential implications of acquired von Willebrand syndrome on bleeding complications., Design: Retrospective chart review., Setting: PICU and cardiovascular ICU in a single institution., Patients: All PICU and cardiovascular ICU extracorporeal membrane oxygenation patients 0-18 years old who underwent screening for acquired von Willebrand syndrome between January 2014 and December 2016., Interventions: Humate P administration to a small subset of acquired von Willebrand syndrome positive subjects., Measurements and Main Results: Laboratory data of identified patients were analyzed. The diagnosis of acquired von Willebrand syndrome was made based on decreased ristocetin cofactor activity to von Willebrand factor antigen ratio and/or abnormal multimer analysis. Clinical data were extracted from the chart and through the Pediatric Extracorporeal Membrane Oxygenation Outcome Registry to describe the demographics, comorbidities, and outcomes of this patient population. In the 2 years, 29 patients had laboratory testing performed for surveillance and in cases of clinical bleeding. Of these, 23 (79%) were positive by criteria. No significant difference in mortality rate was found between patients with acquired von Willebrand syndrome versus without. We also did not find a significant difference in the blood product utilization or bleeding complications between patients with acquired von Willebrand syndrome versus without. Humate P was administered in 39% of patients (9/23) who were positive for acquired von Willebrand syndrome, but no significant difference was seen in blood product utilization or bleeding complications between acquired von Willebrand syndrome patients receiving Humate P versus those who did not., Conclusions: Acquired von Willebrand syndrome is a common but under recognized disorder in pediatric extracorporeal membrane oxygenation patients. The clinical implications of this disorder on bleeding and its potential treatments are still unclear.

Background: Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined., Methods: Retrospective chart review including children age 0-17 years who received pentobarbital infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms of mortality, need for new medical technology assistance at hospital discharge and functional neurologic outcome determined by pediatric cerebral performance category score (PCPC). Potential patient characteristics associated with functional neurologic outcome including age, sex, ethnicity, etiology of the status epilepticus, and duration of pentobarbital infusion were evaluated., Results: Forty children met inclusion criteria. In-hospital mortality was 30% (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28) declined in function ≥ 2 PCPC categories at hospital discharge. 25% (7/28) of survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures persisted at discharge for most patients with new onset status epilepticus while the majority of patients with known epilepsy returned to baseline seizure frequency. Etiology (p = 0.015), PCPC at admission (p = 0.0006), new tracheostomy (p = 0.012), and new gastrostomy tube (p = 0.012) were associated with increase in PCPC score ≥ 2 categories in univariable analysis. Duration of pentobarbital infusion (p = 0.005) and length of hospital stay (p = 0.056) were longer in patients who demonstrated significant decline in neurologic function. None of these variables maintained statistical significance when multiple logistic regression model adjusting for PCPC score at admission was applied. At long-term follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to discharge and 23% (5/22) showed deterioration including three additional deaths., Conclusions: Mortality in this population was high. The majority of children experienced some degree of disability at discharge. Despite prolonged pentobarbital infusion, there were cases of survival with good neurologic outcome.

An infant has a massive intracranial hemorrhage. She is neurologically devastated and ventilator-dependent. The prognosis for pulmonary or neurologic recovery is bleak. The physicians and parents face a choice: withdraw the ventilator and allow her to die or perform a tracheotomy? The parents cling to hope for recovery. The physician must decide how blunt to be in communicating his own opinions and recommendations. Should the physician try to give just the facts? Or should he also make a recommendation based on his own values? In this article, experts in neonatology, decision-making, and bioethics discuss this situation and the choice that the physician faces., (Copyright © 2016 by the American Academy of Pediatrics.)

Objectives: H1N1 influenza with coinfections has been implicated to have high morbidity and mortality. We hypothesized that critically ill children with 2009 H1N1 and coinfections are at a higher risk of developing disseminated intravascular coagulation., Design: The chart review included demographics, length-of-stay, severity of illness score (Pediatric Risk of Mortality III acute physiology score), clinical laboratories, and outcomes at hospital day 90 data. Patients were classified as having methicillin-sensitive or -resistant Staphylococcus aureus, other, or no coinfections., Setting: Single-center pediatric intensive care unit., Patients: Sixty-six consecutive patients with 2009 H1N1 and influenza A infection., Interventions: None., Main Results: : There were 12, 22, and 32 patients with methicillin-sensitive or -resistant Staphylococcus aureus, other, and no coinfections, respectively. Pediatric critical care unit length-of-stay was 11, 10, and 5.5 days (median), and survival at day 90 was 83%, 96%, and 91% in patients with methicillin-sensitive or -resistant Staphylococcus aureus, other, and no coinfections. Patients with methicillin-sensitive or -resistant Staphylococcus aureus coinfections compared to patients with other, and no coinfections had higher Pediatric Risk of Mortality III acute physiology scores (14 [6-25] vs. 7 [2-10], p = .052 and 6 [2.5-10], p = .008; median [interquartile range]), higher D-dimer (16.1 [7.9-19.3] vs. 1.6 [1.1-4], p = .02 and 2.3 [0.8-8.7] µg/mL, p = .05), longer prothrombin time (19.3 [15.4-25.9] vs. 15.3 [14.8-17.1], p = .04 and 16.6 [14.7-20.4] secs, p < .39) at admission, and lower day-7 platelet counts (90K [26-161K] vs. 277K [98-314], p = .03 and 256K [152-339]/mm, p < .07). Patients with methicillin-sensitive or -resistant Staphylococcus aureus coinfections compared to patients without coinfections were more likely to be sicker with Pediatric Risk of Mortality III acute physiology score >10 vs. <10 (relative risk 2.4; 95% confidence interval 1.2-4.7; p = .035) and have overt disseminated intravascular coagulation (relative risk 4.4; 95% confidence interval 1.3-15.8, p = .025)., Conclusions: During the 2009-2010 H1N1 pandemic, pediatric patients with influenza A and methicillin-sensitive or -resistant Staphylococcus aureus coinfections were sicker and more likely to develop disseminated intravascular coagulation than patients with other or no coinfections.

We aim to present the case of a 5-week-old girl with severe respiratory failure placed on veno-venous extracorporeal membrane oxygenation (ECMO) that was then switched to veno-arterial ECMO. She required up to 60 units/kg/hr of heparin to keep her heparin level within the target range at .3-.7 units/mL. During the ECMO course, substantial thrombus formation was observed within the venous site of the ECMO cannula, which led to two circuit changes on ECMO day 9 and day 20. On ECMO day 15, she was noticed to have purpuric lesions on her chest and her right hand with no obvious arterial or venous clot detected by Doppler ultrasound. She was also noted to have remarkable hemolysis as the plasma free hemoglobin levels were substantially elevated up to 700 mg/dL. She was noted to have continuous oozing from the catheter insertion sites despite adequate underlying coagulation status. Her subsequent platelet function analysis, the thromboelastography, and thromboelastography platelet mapping suggested substantial platelet dysfunction. Her von Willebrand panel revealed absence of high molecular weight multimers. Further coagulation workup was prompted which revealed heterozygosity for factor V Leiden. The patient developed severe pulmonary hemorrhages and ECMO was discontinued on day 40.