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Modern medical care for critically ill children meets the definition of a Volatile, Uncertain, Complex, and Ambiguous (VUCA) situation with an additional “R” factor of high risk (suffering and potential death of a child). The circumstances of care for a critically ill child create a unique psychological, social, and technical crucible for all involved, one primed for conflict. This article will trace the evolution of our study of inter-group conflict between physicians in the care of critically ill children from initial observations to broad, systematic surveys and qualitative analysis of practitioner focus groups. Our findings indicated that unconscious inter-group dynamics, shaped by setting variables, can significantly impair collective work towards the best interests of patients in these fraught circumstances, making “integrative deci-sion-making” difficult to achieve. Patterns in inter-group relations clearly suggested the use of splitting as a social defence. The findings and related hypotheses pro-vided clues for strategies to mitigate the impact of these dynamics. This article con-cludes with a description of the design and pilot testing of a structured method of case review designed to provide containing structures tuned to the specific context with the ultimate aim of facilitating integrative decision-making and optimising co-ordination of care for complex cases.

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.

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.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05177-7.

Objectives Acute respiratory failure is a common reason for admission to PICUs. Short- and long-term effects on pulmonary health in previously healthy children after acute respiratory failure requiring mechanical ventilation are unknown. The aim was to determine if clinical course or characteristics of mechanical ventilation predict persistent respiratory morbidity at follow-up. Design Prospective cohort study with follow-up questionnaires at 6 and 12 months. Setting Ten U.S. PICUs. Patients Two-hundred fifty-five children were included in analysis after exclusion for underlying chronic disease or incomplete data. One-hundred fifty-eight and 130 children had follow-up data at 6 and 12 months, respectively. Interventions None. Measurements and main results Pulmonary dysfunction at discharge a priori defined as one of: mechanical ventilation, supplemental oxygen, bronchodilators or steroids at 28 days or discharge. Persistent respiratory morbidity a priori defined as a respiratory PedsQL, a pediatric quality of life measure, greater than or equal to 5 or asthma diagnosis, bronchodilator or inhaled steroids, or unscheduled clinical evaluation for respiratory symptoms. Multivariate backward stepwise regression using Akaike information criterion minimization determined independent predictors of these outcomes. Pulmonary dysfunction at discharge was present in 34% of patients. Positive bacterial respiratory culture predicted pulmonary dysfunction at discharge (odds ratio, 4.38; 95% CI, 1.66-11.56). At 6- and 12-month follow-up 42% and 44% of responders, respectively, had persistent respiratory morbidity. Pulmonary dysfunction at discharge was associated with persistent respiratory morbidity at 6 months, and persistent respiratory morbidity at 6 months was strongly predictive of 12-month persistent respiratory morbidity (odds ratio, 18.58; 95% CI, 6.68-52.67). Positive bacterial respiratory culture remained predictive of persistent respiratory morbidity in patients at both follow-up points. Conclusions Persistent respiratory morbidity develops in up to potentially 44% of previously healthy children less than or equal to 24 months old at follow-up after acute respiratory failure requiring mechanical ventilation. This is the first study, to our knowledge, to suggest a prevalence of persistent respiratory morbidity and the association between positive bacterial respiratory culture and pulmonary morbidity in a population of only previously healthy children with acute respiratory failure.

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.

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.

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)

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.

PURPOSE: Health-related quality of life (HRQL) has been identified as one of the core outcomes most important to assess following pediatric critical care, yet there are no data on the use of HRQL in pediatric critical care research. We aimed to determine the HRQL instruments most commonly used to assess children surviving critical care and describe study methodology, patient populations, and instrument characteristics to identify areas of deficiency and guide investigators conducting HRQL research. METHODS: We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Registry for studies evaluating pediatric critical care survivors published 1970-2017. We used dual review for article selection and data extraction. RESULTS: Of 60,349 citations, 66 articles met inclusion criteria. The majority of studies were observational (89.4%) and assessed HRQL at one post-discharge time-point (86.4%), and only 10.6% of studies included a baseline assessment. Time to the first follow-up assessment ranged from 1 month to 10 years post-hospitalization (median 3 years, IQR 0.5-6). For 26 prospective studies, the median follow-up time was 0.5 years [IQR 0.25-1]. Parent/guardian proxy-reporting was used in 83.3% of studies. Fifteen HRQL instruments were employed, with four used in >5% of articles: the Health Utility Index (n=22 articles), the Pediatric Quality of Life Inventory (n=17), the Child Health Questionnaire (n=16), and the 36-Item Short Form Survey (n=9). CONCLUSION: HRQL assessment in pediatric critical care research has been centered around four instruments, though existing literature is limited by minimal longitudinal follow-up and infrequent assessment of baseline HRQL.

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 Pediatric acute kidney injury (AKI) is associated with long-term morbidity and mortality; however, outcomes improve when AKI is detected earlier. Current definitions of AKI use baseline creatinine; community-acquired AKI (CA-AKI) is difficult to define and detect in the pediatric emergency department (ED) when no baseline creatinine is available. Our objective was to compare age- and gender-based creatinine norms to the traditional baseline (lowest creatinine in previous 3 months) to diagnose CA-AKI. Methods This was a retrospective cross-sectional study conducted in children 1 month-18 years of age seen in the pediatric ED in whom a creatinine was obtained. Results Per the Kidney Disease Improving Global Outcomes AKI definition in encounters with baseline creatinine available, 343/2338 (14.7%) had CA-AKI. When the upper limit of the age- and gender-based creatinine norm was applied as a surrogate baseline creatinine, CA-AKI was diagnosed in 1.5% of encounters (239/15,486). Additionally, CA-AKI was diagnosed in 178 cases using the upper limit of age- and gender-based creatinine norms only, as these cases did not have a baseline creatinine. Conclusions Age- and gender-based creatinine norms can be applied as a surrogate baseline to detect CA-AKI in all children regardless of whether baseline creatinine is available, potentially detecting it earlier.

OBJECTIVES High Vasoactive-Inotropic Scores have demonstrated association with poor outcomes in pediatric cardiac ICUs and are being calculated more frequently in studies of critically ill noncardiac patients. Available studies differ in their approach to assigning Vasoactive-Inotropic Scores, making direct comparisons difficult. The goal of this investigation is to compare multiple approaches to Vasoactive-Inotropic Score assignment to determine their strength of association with mortality in a general pediatric intensive care population. In doing so, we aim to help validate the use of the Vasoactive-Inotropic Score in noncardiac patients and to help inform future studies of the relative strength of available approaches in assigning this score. DESIGN Retrospective chart review. SETTING PICU at an academic freestanding children's hospital. PATIENTS Two-thousand seven-hundred fifty-two consecutive patients admitted over a 17-month time period were screened for receiving inotrope or vasopressor therapies regardless of disease process. Four-hundred seventy-four patients met inclusion criteria. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS For each patient treated with continuous infusions of vasoactive medications, a Vasoactive-Inotropic Score was calculated (and then recalculated) every time they had a documented dose change. Multiple strategies were evaluated to generate receiver operating characteristic curves in relation to mortality. Area under the curve was greatest when evaluating the maximum Vasoactive-Inotropic Score (Max Any) during the initial treatment course (0.788) with an increasing relative risk as the score increased. The Vasoactive-Inotropic Score at 48 hours after treatment initiation had next highest area under the curve (0.736). Primary diagnosis categories were also analyzed, and area under the curve was greatest for the cardiovascular group (0.879). CONCLUSIONS Increasing Vasoactive-Inotropic Scores for patients in the PICU are associated with mortality risk. The scoring strategy used can influence the strength of the association, as can the primary diagnosis category.

Patients with respiratory failure requiring inotropes or vasopressors are often placed on venoarterial (VA) extracorporeal membrane oxygenation (ECMO), as venovenous (VV) ECMO does not provide direct circulatory support. This retrospective multicenter study compared outcomes for 103 pediatric patients, with hemodynamic compromise, placed on VV ECMO for respiratory failure to those placed on VA ECMO. The primary outcome was survival to hospital discharge. Fifty-seven (55%) study participants were supported on VV ECMO. The two groups had similar PRISM III scores at pediatric intensive care unit (PICU) admission, and vasoactive-inotropic scores at ECMO cannulation. More VV ECMO patients received inhaled nitric oxide (iNO) (54.4 vs. 34.8%; p = 0.04) and had a higher oxygenation index (median 41.5 vs. 19.5; p = 0.04) pre-ECMO. More VA ECMO patients had cardiac dysfunction and cardiac arrest pre-ECMO (50 vs. 14%; p < 0.0001). In univariable analysis, survival to hospital discharge was higher in the VV vs. VA ECMO group (72 vs. 44%; p = 0.005), however, in multivariable models, cannulation type was confounded by cardiopulmonary resuscitation and was not independently associated with survival. VV survivors had longer ECMO duration compared with VA survivors (median, 7 vs. 4.5 days; p = 0.036) but similar PICU and hospital days. No significant difference was noted in functional outcomes or comorbidities at discharge. Cannulation type is not independently associated with survival to hospital discharge in pediatric patients on vasoactive infusions at the time of ECMO cannulation for respiratory indications.

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

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.

As pediatric intensivists who perform brain death exams routinely, it was with great concern that we read the recent Ethics Rounds article by Lee et al, “Can a Parent Refuse a Brain Death Examination?”.1 We fundamentally disagree with the authors’ conclusions and the conclusions of Drs Truog and Tasker in their 2017 Chest Counterpoint,2 upon which Lee et al base their argument. We support the analysis of Lewis and Greer in their rebuttal3 of Truog and Tasker, namely that “just as consent is not needed to diagnose cardiopulmonary failure, consent should not be needed to evaluate for total brain failure.”3 There … E-mail: nicholas.ettinger{at}bcm.edu

BACKGROUND Outcomes for patients with oncologic disease and/or after hematopoietic stem cell transplant (HSCT) requiring intensive care unit admission have improved, but indications for and outcomes after extracorporeal membrane oxygenation (ECMO) support in this population are poorly characterized. PROCEDURE We analyzed data from consecutive patients

The medical care of children with life-threatening and life-limiting illness is a crucible containing many volatile issues and complicated circumstances that predictably provoke conflict between well-meaning people. This chapter will review the prototypical types of conflicts that occur in the practice of pediatric hematology/oncology and propose methods of managing these conflicts that hinge on established ethical principles and disciplined reasoning. We draw on the broader field of conflict management for an empirically grounded understanding of conflict and conflict resolution strategies.

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.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. OBJECTIVE: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. SETTING, DESIGN, AND PARTICIPANTS: Case series of patients (age

Multiplex rapid viral tests and nasopharyngeal flocked swabs are increasingly used for viral testing in PICUs. This study aimed at evaluating how the sampling site and the type of diagnostic test influence test results in children with suspected severe viral infection.Prospective cohort study.PICUs at 21 tertiary pediatric referral centers in the United States.During the 2010-2011 and 2011-2012 influenza seasons, we enrolled children (6 mo to 17 yr old) who were suspected to have severe viral infection.We collected samples by using a standardized protocol for nasopharyngeal aspirate and nasopharyngeal flocked swabs in nonintubated patients and for endotracheal tube aspirate and nasopharyngeal flocked swabs in intubated patients.Viral testing included a single reverse transcription-polymerase chain reaction influenza test and the GenMark Respiratory Viral Panel (20 viruses). We enrolled 90 endotracheally intubated and 133 nonintubated children. We identified influenza in 45 patients with reverse transcription-polymerase chain reaction testing; the multiplex panel was falsely negative for influenza in two patients (4.4%). Six patients (13.3%) had not been diagnosed with influenza in the PICU. Non-influenza viruses were identified in 172 of 223 children (77.1%). In nonintubated children, the same virus was identified by nasopharyngeal flocked swabs and nasopharyngeal aspirate in 133 of 183 paired samples (72.7%), with +nasopharyngeal aspirate/-nasopharyngeal flocked swabs in 32 of 183 paired samples (17.4%). In intubated children, the same virus was identified by nasopharyngeal flocked swabs and endotracheal tube aspirate in 67 of 94 paired samples (71.3%), with +nasopharyngeal flocked swabs/- endotracheal tube aspirate in 22 of 94 paired samples (23.4%). Most discrepancies were either adenovirus or rhinovirus in both groups.Standardized specimen collection and sensitive diagnostic testing with a reverse transcription-polymerase chain reaction increased the identification of influenza in critically ill children. For most pathogenic viruses identified, results from nasopharyngeal flocked swabs agreed with those from nasopharyngeal or endotracheal aspirates.

Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined. 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. 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. 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.

Objectives Acute kidney injury (AKI) is a significant risk factor for morbidity and mortality in children. Little is known about community-acquired AKI (CA-AKI) in the pediatric emergency department (PED). Early recognition of AKI allows for nephroprotective measures. The goal of this investigation was to determine the incidence of CA-AKI and the frequency of clinician identified CA-AKI to better inform future nephroprotective interventions. Methods This was a retrospective cross-sectional study in the PED of a children's hospital. Children 1 month to 18 years of age seen in the PED from January 1 to December 31, 2015, and in whom at least one creatinine level was obtained were included. Patients with chronic kidney disease or end-stage renal disease or who died in the PED were excluded. Patients had CA-AKI based on modified Kidney Disease-Improving Global Outcomes criteria using the creatinine obtained in the PED compared to age-specific norms. Patients were considered identified if the PED clinician diagnosed AKI. The primary outcome was the incidence of CA-AKI. Secondary outcomes included frequency of AKI identification, nephrotoxic medication use, hospital length of stay, renal replacement therapy, and death. Fisher exact test or Pearson's chi-square test was used to calculate odds ratio (OR) with 95% confidence intervals (CIs); multivariable analyses were performed using logistic regression. Results In 2015 there were 119,151 PED visits; 15,486 met inclusion criteria. CA-AKI was present in 239 of 15,486 (1.5%) encounters. AKI was identified by PED clinicians in 46 of 239 (19%) of encounters and by the inpatient team in 123 of 199 (62%) of the encounters admitted. AKI was never recognized by a PED or inpatient clinician in 74 of 199 (37%) encounters. Encounters with AKI correctly diagnosed were older (13 years old vs. 10 years old, p = 0.0114), had more severe (stage 2 or 3) AKI (OR = 5.5, 95% CI = 2.6-11.8), and were more likely to be admitted (OR = 10.3, 95% CI = 1.38-77.4) than encounters with missed AKI. Conclusions CA-AKI remains an underrecognized entity in the PED. Better tools for early recognition of AKI in the busy PED environment are needed.

Objective Interruptive acute kidney injury alerts are reported to decrease acute kidney injury-related mortality in adults. Critically ill children have multiple acute kidney injury risk factors; although recognition has improved due to standardized definitions, subtle changes in serum creatinine make acute kidney injury recognition challenging. Age and body habitus variability prevent a uniform maximum threshold of creatinine. Exposure of nephrotoxic medications is common but not accounted for in kidney injury scores. Current severity of illness measures do not include fluid overload, a well-described mortality risk factor. We hypothesized that a multidimensional measure of renal status would better characterize renal severity of illness while maintaining or improving on correlation measures with adverse outcomes, when compared with traditional acute kidney injury staging. Design A novel, real-time, multidimensional, renal status measure, combining acute kidney injury, fluid overload greater than or equal to 15%, and nephrotoxin exposure, was developed (Fluid Overload Kidney Injury Score) and prospectively applied to all patient encounters. Peak Fluid Overload Kidney Injury Score values prior to discharge or death were used to measure correlation with outcomes. Setting Quarternary PICU of a freestanding children's hospital. Patients All patients admitted over 18 months. Intervention None. Results Peak Fluid Overload Kidney Injury Score ranged between 0 and 14 in 2,830 PICU patients (median age, 5.5 yr; interquartile range, 1.3-12.9; 55% male), 66% of patients had Fluid Overload Kidney Injury Score greater than or equal to 1. Fluid Overload Kidney Injury Score was independently associated with PICU mortality and PICU and hospital length of stay when controlled for age, Pediatric Risk of Mortality-3, ventilator, pressor, and renal replacement therapy use (p = 0.047). Mortality increased from 1.5% in Fluid Overload Kidney Injury Score 0 to 40% in Fluid Overload Kidney Injury Score 8+. When urine output points were excluded, Fluid Overload Kidney Injury Score was more strongly correlated with mortality than fluid overload or acute kidney injury definitions alone. Conclusion A multidimensional score of renal disease burden was significantly associated with adverse PICU outcomes. Further studies will evaluate Fluid Overload Kidney Injury Score as a warning and decision support tool to impact patient-centered outcomes.

Background Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. Methods The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA. Results In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified. Conclusions rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.

To describe the differences in goals for their usual practice for various medical therapies from a number of international centers for children with severe traumatic brain injury.A survey of the goals from representatives of the international centers.Thirty-two pediatric traumatic brain injury centers in the United States, United Kingdom, France, and Spain.None.None.A survey instrument was developed that required free-form responses from the centers regarding their usual practice goals for topics of intracranial hypertension therapies, hypoxia/ischemia prevention and detection, and metabolic support. Cerebrospinal fluid diversion strategies varied both across centers and within centers, with roughly equal proportion of centers adopting a strategy of continuous cerebrospinal fluid diversion and a strategy of no cerebrospinal fluid diversion. Use of mannitol and hypertonic saline for hyperosmolar therapies was widespread among centers (90.1% and 96.9%, respectively). Of centers using hypertonic saline, 3% saline preparations were the most common but many other concentrations were in common use. Routine hyperventilation was not reported as a standard goal and 31.3% of centers currently use PbO(2) monitoring for cerebral hypoxia. The time to start nutritional support and glucose administration varied widely, with nutritional support beginning before 96 hours and glucose administration being started earlier in most centers.There were marked differences in medical goals for children with severe traumatic brain injury across our international consortium, and these differences seemed to be greatest in areas with the weakest evidence in the literature. Future studies that determine the superiority of the various medical therapies outlined within our survey would be a significant advance for the pediatric neurotrauma field and may lead to new standards of care and improved study designs for clinical trials.

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.

Rationale: Fluid overload is common in the critically ill and is thought to contribute to oxygenation failure and mortality. Since increasing disease severity often requires more fluid for resuscitation, it is unclear whether fluid overload is a causative factor in morbidity or is simply an indicator of disease severity. Objective: Investigate the association between fluid overload and oxygenation while controlling for severity of illness by daily Pediatric Logistic Organ Dysfunction scores. Design and Setting: Retrospective chart review, tertiary children’s hospital. Patients and Methods: The oxygenation index, fluid overload percent, and daily Pediatric Logistic Organ Dysfunction scores were obtained in a retrospective chart review of 80 patients (mean age 58.7 ± 73.0 months) with respiratory failure. Univariate and multivariate approaches were used to assess the independent relation between fluid overload percent and duration of stay and ventilation. Interventions: None. Main Results: Higher peak fluid overload percent predicted higher peak oxygenation index, independent of age, gender, and Pediatric Logistic Organ Dysfunction (p = .009). Fluid overload percent 15% on any given day was also independently associated with that day’s oxygenation index, controlled for age, gender, and Pediatric Logistic Organ Dysfunction (p < .05). Peak fluid overload percent and severe fluid overload percent ( 15%) were both independently associated with longer duration of ventilation (p = .004, p = .01), and pediatric intensive care unit (p = .008, p = .01) and hospital length of stay (p = .02, p = .04), controlled for age, gender, Pediatric Logistic Organ Dysfunction, and in the case of ventilation, respiratory admission. Conclusion: This is the first study to report that positive fluid balance adversely affected the pediatric intensive care unit course in children who did not receive renal replacement therapy. While timely administration of fluids is lifesaving, positive fluid balance after hemodynamic stabilization may impact organ function and negatively influence important outcomes in critically ill patients. (Pediatr Crit Care Med 2012; 13:253–258)

Background This is a multisite study of cases of acute flaccid myelitis (AFM) in Texas during the year 2016 among 6 children’s hospitals. AFM is a newly recognized and poorly understood disease. Information related particularly to pathogenesis, treatment, and recovery are lacking. Methods Children age 0–18 years admitted with AFM defined as acute onset limb weakness with spinal cord lesions on MRI primarily involving gray matter during January 1–December 31, 2016, were reviewed. Abstracted information included demographics, presentation, laboratory findings, treatments, and long-term outcomes up to 18 months after onset of weakness (range 3.5–18 months; median 15 months). Results 22 patients from 5 hospitals were included. Median age was 4.9 years. Upper extremity involvement was common (77%), with all extremities being involved in 36%. Enterovirus D68 was identified in 3 cases. Other pathogens identified included human parechovirus (n = 2), human herpesvirus 6 (n = 1), non-D68 enterovirus (n = 2), rhinovirus (n = 1), Mycoplasma pneumoniae (n = 1), Bartonella henselae (n = 1), and influenza B (n = 1). In total, 32% recovered fully in strength and function, and 45% had full recovery of function. 18% remain completely dependent on caregivers. All extremities were involved in 8 patients. 6 had significant residual weakness, ranging from flaccidity in one extremity to complete caregiver dependence. One was lost to follow-up after discharge. None of the three patients with Enterovirus D-68 made a full recovery, and all three remain largely dependent on caregivers. Treatments varied, but most commonly included methylprednisolone (n = 14) or intravenous immunoglobulin (IVIG) (n = 13). All cases of full recovery were treated with steroids, IVIG, or both. 4 patients were not treated; 2 with eventual recovery of function (Figure 1). Response to IVIG and steroids was variable; no harm was noted in response to IVIG (Figure 2). Conclusion Our findings overall show more promising outcomes than those seen in the 2014 nationwide outbreak of AFM. Specific treatments were not associated with better outcomes. IVIG appeared to be helpful in several cases and, at the very least, was not harmful. Patients with all extremities involved and/or enterovirus D68 appear to have poorer outcomes. Disclosures All authors: No reported disclosures.

Background. Urinary interleukin-18 (uIL-18) is an earlier acute kidney injury (AKI) biomarker than serum creatinine (SCr) in specific populations. In the present study, the relationship between uIL-18 and AKI was determined in a heterogeneous group of critically ill children. Methods. We studied critically ill children to determine whether uIL-18 was an early predictor of AKI. SCr was determined daily for up to 14 days from mechanical ventilation initiation and up to four serial urine specimens were collected for the uIL-18 measurement. AKI was graded by paediatric modified risk, injury, failure, loss, end-stage kidneydisease(pRIFLE)criteria.Day0wasdefinedastheday of attaining pRIFLE AKI. Results. One hundred thirty-seven children aged 6.5 ± 6.4 years (53% male) were studied. The peak levels of IL-18 correlated with the severity of AKI by pRIFLE classification (P < 0.05). In non-septic AKI patients, uIL-18 rose to a level higher than control levels 2 days prior to a significant rise in SCr. Urinary IL-18 concentration from the first urine specimen was associated with AKI development within 48 h (odds ratio = 3.5, P < 0.05) independent of the paediatric risk of mortality (PRISM II) score. Urinary IL18concentration ≥100pg/mlhadaspecificityandnegative predictive value of 81 and 83% to predict AKI development within 24 h. Urinary IL-18 ≥200 pg/ml collected within 24 h of Day 0 had a specificity and positive predictive value of 93 and 88% respectively to predict the AKI duration ≥48 h. Urinary IL-18 was associated with mortality (odds ratio =1.29,P

Transactivation of the DNA-binding proteins nuclear factor-κB (NF-κB) and activator protein (AP)-1 by de novo oxyradical generation is a stereotypic redox-sensitive process during hypoxic stress of the liver. Systemic trauma is associated with splanchnic hypoxia-reoxygenation (H/R) followed by intraportal gram-negative bacteremia, which collectively have been implicated in posttraumatic liver dysfunction and multiple organ damage. We hypothesized that hypoxic stress of the liver before stimulation by Escherichia coli serotype O55:B5 (EC) amplifies oxyradical-mediated transactivation of NF-κB and AP-1 as well as cytokine production compared with noninfectious H/R or gram-negative sepsis without prior hypoxia. Livers from Sprague-Dawley rats underwent perfusion for 180 min with or without 0.5 h of hypoxia (perfusate Po2, 40 ± 5 mmHg) followed by reoxygenation and infection with 109EC or 0.9% NaCl infusion. In H/R + EC livers, nuclear translocation of NF-κB and AP-1 was unexpectedly reduced in gel shift assays vs. normoxic EC controls, as were perfusate TNF-α and IL-1β levels. Preceding hypoxic stress paradoxically increased postbacteremic reduced-to-oxidized glutathione ratios plus nuclear localization of IκBα and phospho-IκBα, but not JunB/FosB profiles. Notably, xanthine oxidase inhibition increased transactivation as well as cytokine production in H/R + EC livers. Thus brief hypoxic stress of the liver before intraportal gram-negative bacteremia potently suppresses activation of canonical redox-sensitive transcription factors and production of inflammatory cytokines by mechanisms including xanthine oxidase-induced oxyradicals functioning in an anti-inflammatory signaling role. These results suggest a novel multifunctionality of oxyradicals in decoupling hepatic transcriptional activity and cytokine biosynthesis early in the posttraumatic milieu.

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.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.Single-center pediatric intensive care unit.Sixty-six consecutive patients with 2009 H1N1 and influenza A infection.None.: 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 score10 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).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.

Objective To estimate nursing workload from the patient acuity level (PAL) assigned to patients in a pediatric intensive care unit (PICU) and to determine its influence on unplanned extubations. Design Prospective cohort study. Setting The 19-bed PICU of an urban, university-affiliated, tertiary children's hospital. Patients All patients admitted to the PICU. Interventions None. Measurements and main results The study encompassed 2,193 nursing shifts and 1,919 admissions to the PICU over 24 months. The shift census averaged 12.0 patients (range 5-18) and was staffed by 9.4 nurses (range 4-16) for an average patient/nurse ratio of 1.3 +/- 0.2. Patients were assigned a PAL of 1-7 based on a classification system derived from time studies of 12 general nursing tasks. The total PALs per shift divided by the number of nursing staff yielded an average assignment of 5.8 +/- 0.7 PALs. Forty unplanned extubations (0.76 unplanned extubations/100 ventilator days) were observed during the study period. Logistic regression revealed positive associations between unplanned extubations and patient/nurse ratio (p = .03) and the shift PAL/nurse ratio (p = .01). The likelihood of an unplanned extubation when nurses covered >6.3 PALs was 3.8 times higher than during those shifts when they covered Conclusions The likelihood of an unplanned extubation increased with higher patient/nurse and patient acuity/nurse ratios. Successful interventions to reduce the frequency of this medical error may need to address both nurse demand methodology and workload.